Table of Content

05 September 2023, Volume 43 Issue 9

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Original Articles

Remifentanil-induced postoperative hyperalgesia is attenuated by inhibition of NMDAR-cADPR-RyRs signaling pathway in the spinal cord of rats

QIAN Yue, WANG Fang, ZHANG Jing, XIA Tianjiao, GU Xiaoping

2023, 43(9):  1335-1340.  doi:10.16352/j.issn.1001-6325.2023.09.1335

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Objective To investigate the role of NMDAR-cADPR-RyRs signaling pathway in remifentanil-induced hyperalgesia(RIH). Methods The rat model of postoperative hyperalgesia induced by remifentanil was established. SD rats were randomly divided into 6 groups as: control group, model group, RIH group, RIH+saline group, RIH+ketamine group and RIH+8-Br-cADPR group with 6 animals in each. N-methy-D-aspartic acid receptor(NMDA) antagonist ketamine or cyclic ADP-ribose(cADPR) antagonist 8-Br-cADPR was injected intrathecally 30 minutes before surgical operation in group RIH+ketamine and group RIH+8-Br-cADPR respectively. PWMT and PWTL were measured before operation and on the 1st, 2nd and 3rd days after operation. Western blotwas used to detect the protein level of p-NR2B, p-CaMKII, RyR1 and RyR3 in spinal dorsal horn neurons. The concentration of cADPR was measured by enzyme cycling assay. Results Compared with model group, PWMT and PWTL in RIH group decreased significantly on the first and the second day after remifentanil infusion, while p-NR2B, p-CaMKII, RyR1, RyR3 and cADPR in the spinal dorsal horn increased significantly (P＜0.05). After intrathecal injection of ketamine or 8-Br-cADPR, hypersensitivity to mechanical pain and thermal pain was alleviated in RIH+ketamine group and RIH+8-Br-cADPR group, and the expression level of p-NR2B, p-CaMKII, RyR1, RyR3 and cADPR decreased as compared with RIH group (P＜0.05). Conclusions Remifentanil-induced postoperative hyperalgesia of rat is attenuated by blocking NMDAR-cADPR-RyRs signaling pathway.

Influence of PTEN mutation on pathological features and prognosis of patients with mucosal melanoma

GONG Ziqi, WU Xiaowen, GUO Qian, GUO Jun, KONG Yan

2023, 43(9):  1341-1345.  doi:10.16352/j.issn.1001-6325.2023.09.1341

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Objective To investigate the effects of PTEN (phosphatase and tensin homolog)mutation on pathological characteristics and prognosis of patients with mucosal melanoma. Methods Clinical and follow-up data of 66 patients with mucosal melanoma from the Department of Melanoma and Sarcoma, Peking University Cancer Hospital from April 2019 to March 2022 were collected and the mutation of PTEN was detected by next-generation sequencing to analyze the relationship between PTEN mutation and patients′ pathological characteristics and prognosis. Results Among 66 patients with mucosal melanoma, the frequency of PTEN mutation was 19.40% and the mutation frequency was significantly associated with age at diagnosis and primary tumor site(P＜0.05); In the cohort with 42 patients receiving immunotherapy, the median progression-free survival(mPFS) of PTEN-mutant patients was 3.37 months, which was significantly lower than that of wild-type patients(9.2 months)(P＜0.05). Multivariate Cox regression analysis further confirmed that PTEN mutation was an independent prognostic factor for poor prognosis of immunotherapy(P＜0.05). Conclusions The frequency of PTEN mutation is significantly higher in patient who were diagnosed at the aged less than 60 and in patients with tumors originated from gastrointestinal mucosa. PTEN mutation is also an independent risk factor for poorer prognosis in patients receiving immunotherapy.

Hypoxic preconditioning placental mesenchymal stem cells alleviate pathological lesion in mouse models with severe acute pancreatitis

JING Guangxu, WANG Zhangpeng, LIU Zhongyu, LYU Shuang, SUN Hongyu

2023, 43(9):  1346-1352.  doi:10.16352/j.issn.1001-6325.2023.09.1346

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Objective To investigate the protective effect of hypoxia-preconditioned placental mesenchymal stem cells (HP-MSCs) on severe acute pancreatitis (SAP) of mice model and to explore its mechanisms. Methods Placental-derived mesenchymal stem cells (P-MSCs) were cultured in normoxia treatment(N-MSCs)(21% O₂) or hypoxia preconditioning(HP-MSCs)(1% O₂) for 48 h. CCK-8 and MTT assay were used to detect the viability andmigration of N-MSCs and HP-MSCs respectively. Thirty-two male C57BL/6 mice were divided into sham operation group (sham), SAP group (retrograde injection of 4% sodium taurocholate 0.1 mL/100 g into the pancreaticobiliary duct), normoxia group (N-MSCs) and hypoxia group (HP-MSCs). Six hours after the end of modeling, N-MSCs and HP-MSCs (1×10⁶/100 g) were injected to treat SAP, with 8 rats in each group. Serum and pancreatic tissue were collected at 12 h after modeling. HE staining and microscopy were used to evaluate the degree of pancreatic tissue injury and pathological score. ELISA was used to measure the activities of serum amylase and lipase and the levels of inflammatory factors. Western blot was used to detect the expression of receptor interacting protein 3 (RIP3), MLKL, phosphorylated MLKL (p-MLKL) and NLRP3 in pancreatic tissue. Results HP-MSCs showed better viability and higher capacity proliferation than N-MSCs in vitro. In vivo, compared with SAP group, the pancreatic pathological score was significantly decreased in N-MSCs group (P＜0.05). The biological activity of amylase and lipase in serum were decreased, and the level of IL-6 and TNF-α was decreased (P＜0.05). Compared with N-MSCs group, the pancreatic pathological score and the level of TNF-α and IL-6 in HP-MSCs group were significantly decreased(P＜0.05). The expression of RIP3, p-MLKL and NLRP3 in pancreatic tissue of HP-MSCs group was significantly lower than those of SAP group and N-MSCs group (P＜0.05). Conclusions HP-MSCs can significantly alleviate SAP than N-MSCs, and the mechanism is potentially related to the inhibition of RIP1/RIP3-MLKL signaling pathway.

Histone demethylase inhibitor GSK-J4 reduces body weight in high-fat diet-induced obese mice

CHEN Xin, CHEN Jun, XU Xing, WANG Xu

2023, 43(9):  1353-1358.  doi:10.16352/j.issn.1001-6325.2023.09.1353

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Objective To investigate how histone demethylase inhibitor GSK-J4 could reduce body weight in obese mice fed high-fat diet(HFD). Methods After 16 weeks of feeding C57/BL6 mice with a HFD, GSK-J4 was injected intraperitoneally for 16 days, during which time the body weight and body temperature were monitored. The serum leptin expression was measured using ELISA kits. Direction of macrophage polarization in epididymis and subcutaneous adipose tissue was detected by flow cytometry. The browning degree of white fat in adipose tissue of epididymis and subcutaneous adipose tissue was evaluated by HE staining microscopy and immunohistochemistry.Quantitative PCR was used to analyze the levels of related cytokines and the expression levels of genes related to oxidative phosphorylation in macrophages. Results Compared with solvent control group, GSK-J4 reduced body weight in a time-dependent manner. Serum leptin expression was significantly decreased (P＜0.01); The surface marker CD11c⁺ decreased in epididymal and subcutaneous adipose tissue macrophages. The degree of browning of subcutaneous white fat was increased; The mRNA level of oxidative phosphorylation related genes was stimulated in brown adipose tissue, and the expression of IL-1β was decreased. Conclusions The histone demethylase inhibitor GSK-J4 can reduce M1 polarization of macrophages. After treatment with GSK-J4, the body weight of obese mice induced by HFD is significantly decreased and the energy consumption is increased.

Pemetrexed inhibits the proliferation of lung adenocarcinoma cell line A549

PAN Shan, LIN Kengqiang, CHEN Shuxing

2023, 43(9):  1359-1363.  doi:10.16352/j.issn.1001-6325.2023.09.1359

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Objective To investigate whether pemetrexed can regulate the proliferation of lung adenocarcinoma cells. Methods Human lung adenocarcinoma cell line A549 was selected for cell resuscitation, culture and passage, and was divided into control group, low-dose and high-dose pemetrexed intervention group. CCK-8 assay was used to detect proliferation inhibition rate of A549 cells. Flow cytometry was used to detect cell cycle and apoptosis; Western blot was used to detect the difference between proteins related to apoptosis and to PI3K/AKT signal pathway function. Results With the increase of drug dose and treatment time, both inhibition rate to A549 cells proliferation and apoptosis were significantly increased.The expression of cleaved caspase-3 and Bad protein was also significantly increased while the expression of Bcl-2 protein was significantly decreased (P＜0.05 or P＜0.01). At 48 h of culture, with the increase of pemetrexed concentration, the proportion of G₀/G₁ phase of A549 cells increased significantly, while the proportion of S phase and G₂/M phase decreased significantly (P＜0.05 or P＜0.01);The expression of PI3K, AKT and p-AKT wassignificantly decreased (P＜0.05 or P＜0.01). Conclusions Pemetrexed can inhibit the proliferation and promote apoptosis of lung adenocarcinoma cell line A549, potentially through a mechanism of inhibiting PI3K/AKT signaling pathway.

Comparison of acute immunological liver injury models in two different species of mice

HU Ning, HUANG Hannian, XIA Daozong

2023, 43(9):  1364-1368.  doi:10.16352/j.issn.1001-6325.2023.09.1364

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Objective To explore the dose difference on concanavalin A (Con A) induced acute immunological injury of liver in two different species of mice. Methods Thirty six male BALB/C mice and 40 male C57BL/6 mice were randomly divided into 6 groups.BALB/C mice were divided into a control group and five (5, 10, 15, 20 and 25 mg/kg ConA) experimental groups, while C57BL/6 mice were divided into a control group and five (5, 7.5, 10, 12.5 and 15 mg/kg ConA) experimental groups. The experimental groups were injected with different doses of ConA. After 16 hrs of fasting, the serum samples were collected by orbital blood sampling. Biopsy samples of liver,spleen andthymus were weighed and visceral index was calculated. The liver tissue was microscopied with histological technology. The activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was measured by colorimetric method. The release and expression of tumor necrosis factor (TNF-α) were detected using ELISA. Finally, the ConA optimum dose was determined based on animal mortality in each group. Results In BALB/C mice, two animals died at the dosage of 25 mg/kg ConA. The activity of AST, ALT and TNF-α content showed a dose-dependent increase with ConA(P＜0.05). The liver index was positively correlated with the dose of ConA (P＜0.05). The spleen index from group of 5 mg/kg was higher than that from groups of 10 and 15 mg/kg, showing a tend of increase- decrease-increase kinetic profile. In C57BL/6 mice, one animal died at the dosage of 10 mg/kg ConA, one at 12.5 mg/kg and two at 15 mg/kg ConA. The activity of AST,ALT and TNF-α content showed a dose-dependent increase with ConA (P＜0.05). The liver index was positively correlated with the dose of ConA. The spleen index at 7.5 mg/kg was higher than other dose groups, showing a trend of increase followed by decrease. In both strains of mice, thymus index decreased with the increase of dose. The extent of liver lesions in both species of mice was positively correlated with the dose of ConA,progressing from inflammatory cell infiltrates at low doses to liver tissue necrosis at high doses, and from focal necroses to patchy necrotic lesion. Conclusions C57BL/6 mice are more sensitive to ConA than BALB/C mice. The appropriate dosage for BALB/C mice to replicate animal models is 20 mg/kg, while the appropriate dosage for C57BL/6 mice is 10 mg/kg.

Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ

ZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang

2023, 43(9):  1369-1374.  doi:10.16352/j.issn.1001-6325.2023.09.1369

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Objective To explore the analgesic effect and underlying mechanisms of dexmedetomidine(DEX) with spared nerve injury(SNI) rat model. Methods Forty-eight SD rats were randomly divided into control group, SNI group, DEX group and DEX+GW9662 group, with 12 rats in each. From first day to 14th days after SNI surgery, rats in DEX group were intra-thecally injected with 2 μg/kg (10 μL) of dexmedetomidine,rats in DEX group were intrathecally injected with 2 μg/kg of dexmedetomidine+300 μg of PPAR-γ inhibitor (GW9662), while rats in control and SNI groups were intrathecally injected with equal volume of solvent. At day 1 before operation, day 3, 7, 14 after operation, paw withdrawal threshold and thermal withdrawal latency were detected to evaluate the painintensity. At post-operative day 14,immunofluorescence staining was used to detect the expression of Iba-1 in spinal dorsal horn, Western blot was used to detect the expression of Iba-1 and PPAR-γ in ipsilateral spinal dorsal horn, ELISA was used to detect the levels of IFN-γ and IL-6 in ipsilateral spinal dorsal horn. Results On postoperative day 7 and 14, compared with control group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn were enhanced in SNI group(P＜0.05). Compared with SNI group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn decreased in EDX group(P＜0.05). Compared with DEX group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal increased in DEX+GW9662 group(P＜0.05). Conclusions Dexmedetomidine obviously inhibits pain sensitization of SNI rats. The underlying analgesic mechanism may be related to the up-regulation of PPAR-γ in spinal dorsal horn.

Analysis of differentially expressed proteins in Hashimoto thyroiditis patients with obesity by serum-based proteomics

MA Guoying, Jiazireya·ZAIYINATI, LI Suli, GUO Yanying

2023, 43(9):  1375-1382.  doi:10.16352/j.issn.1001-6325.2023.09.1375

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Objective To explore the effects of obesity and normal weight on serum proteomic differences in Hashimoto thyroiditis(HT) patients, and to observe the existing differential proteins and related pathways. Methods The serum samples from 10 obese and 10 normal weight patients with Hashimoto thyroiditis patients and from 10 controls were collected. The proteins in the serum were extracted and degraded by trypsin, analyzed by liquidchromatography-mass spectrometry, compared with the control group, identified the expression changes of differential proteins in the two groups, and analyzed by bioinformatics. Results There were 180 serum differential proteins were detected between Hashimoto thyroiditis group and control group; The differential proteins were involved in relaxin signal pathway,adrenergic signaling in cardiomyocytes and cardiac muscle contraction; There were 232 differential proteins in Hashimoto thyroiditis complicated with obesity group as compared with the control group. The differential proteins related to pathways were inflammatory mediators to regulate TRP channel, C-type lectin receptor signaling pathway and Apelin signaling pathway; The results showed that there were 212 differential proteins in serum between the Hashimoto thyroiditis patients with or without obesity group, and the pathway of differential protein enrichment was estrogen signaling pathway. Conclusions Both Hashimoto thyroiditis patients with or without obesity has a changed protein expression in serum but the change may increase the risk of developing thyroid cancer only in patients combined with obesity. The results provide a theoretical basis for further research of the disease and is of great significance for clinical diagnosis and treatment.

Pterostilbene reduces paraquat-induced pulmonary fibrosis in rat model

CHEN Xinjun, WANG Qinyu, CHEN Le, GU Chunyu, WU Zhuo

2023, 43(9):  1383-1389.  doi:10.16352/j.issn.1001-6325.2023.09.1383

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Objective To investigate the effect and mechanism of pterostilbene (Pte) on paraquat (PQ)-induced pulmonary fibrosis in rats. Methods The rats were randomly divided into control group, PQ group (intragastric administration of 50 mg/kg paraquat at one time), and low, medium and high dose of Pte intervention group (after 30 minutes of intragastric administration of PQ, 25, 50 and 100 mg/kg Pte were administered respectively. Once a day for 7 days). After 7 days of treatment, the morphology of lung tissue was evaluated by hematoxylin-eosin (HE) staining microscopy and pulmonary fibrosis was evaluated by Masson trichrome staining. The level of IL-1β, IL-6 and MIP-2 in bronchoalveolar lavage fluid (BALF) was determined by ELISA. MDA and SOD contents in lung tissues were detected with commercially available kit. The protein expression of E-cadherin, α-SMA, vimentin,Nrf2, NF-κB p65, NF-κB p65, TGF-β1, Smad3 and p-Smad3 in lung tissue was detected by Western blot. Results Compared with the control group, the injury degree of lung tissue, the score of pulmonary fibrosis, the level of IL-1β, IL-6 and MIP-2 in BALF, the content of MDA in lung tissue, the protein expression of α-SMA, vimentin and TGF-β1 and the phosphorylation level of NF-κB p65 and Smad3 protein in lung tissue were all significantly increased in PQ group (P＜0.05), while the content of SOD and the protein expression of E-cadherin and Nrf2 in lung tissue were significantly decreased (P＜0.05). After Pte intervention, the injury of lung tissue, the score of pulmonary fibrosis, the level of IL-1β, IL-6 and MIP-2 in BALF, the content of MDA in lung tissue, the protein expression of α-SMA, vimentin and TGF-β1 and the phosphorylation of NF-κB p65 and Smad3 protein in lung tissue were all significantly decreased in Pte group (P＜0.05), while the content of SOD and the protein expression of E-cadherin and Nrf2 in lung tissue were significantly increased (P＜0.05). Conclusions Pterostilbene may inhibit fibrosis progression by reducing oxidative stress and decrease of inflammatory response in the lung through activation of Nrf2 and inhibition of NF-κB and TGF-β1/Smad2/3 signaling pathways.

Cordycepin inhibits proliferation of human keratinocyte cell line HaCaT induced by TNF-α

LIANG Huiyong, WEI Qiuhui, DING Ya, PENG Xiaoqing, YAO Jing, SU Qijian

2023, 43(9):  1390-1393.  doi:10.16352/j.issn.1001-6325.2023.09.1390

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Objective To study the effect of cordycepin on proliferation, apoptosis and inflammatory reaction of human keratinocyte cell line HaCaT induced by TNF-α. Methods HaCaT cells were divided into control group, model group and intervention groups including low, middle, high dose (cordycepin 25 μmol/L, 50 μmol/L and 100 μmol/L, respectively). HaCaT cells were incubated with by 40 μg/L TNF-α in model group and cordycepin intervention group for 24 hours. Then, the cordycepin intervention groups were incubated with corresponding cordycepin for 24 hours. Cell proliferation was detected by CCK-8 method. Apoptosis was detected by flow cytometry. And mRNA expression of interleukin (IL)-8, IL-1β was detected by RT-qPCR. Results After 24 hours of cordycepin incubation, cell proliferation rate decreased (P＜0.05), cell apoptosis rate increased(P＜0.05)and mRNA expression of IL-8 and IL-1β decreased (P＜0.05). Conclusions Cordycepin can inhibit TNF-α-induced proliferation and inflammatory reaction of HaCaT cells and promote apoptosis of these cells.

Effects of lidocaine on mitophagy in lung tissues of rat models with acute lung injury

XU Guiping, CHEN Xueying, ZHANG Yuxuan, Malipate·YILIAIKEBAIER

2023, 43(9):  1394-1398.  doi:10.16352/j.issn.1001-6325.2023.09.1394

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Objective To investigate the effect of lidocaine on mitophagy in model rat of acute lung injury(ALI). Methods The rats were divided into the control group, acute lung injury group (group ALI:intraperitoneal injection of 10 mg/kg of lipopolysaccharide(LPS) and lidocaine intervention group (group lidocaine:after intraperitoneal injection of LPS,receiving a loading dose of lidocaine of 10 mg/kg and continued for 3 h with dosage of 10 mg/kg per hour). The rats were sacrificed 24 hrs after LPS, blood was collected for blood gas analysis, and calculated for oxygenation index (OI).Thoracotomy was performed immediately after blood collection, the samples of left lung tissue were collected to determine the expression of mitophagy-related protein E3 ubiquitin ligase (Parkin), microtubule-associated protein 1 light chain 3 (LC3) and p62 by Western blot, and then LC3-Ⅱ/LC3-Ⅰ was calculated. After-wards, right-upper lung tissue structure was microscopy and the mitochondrial autophagy in the right lower lung tissue was examined by transmission electron microscopy. Results Compared with control group, the level of Parkin, LC3-Ⅱ/LC3-Ⅰ and PaCO₂ was increased in both group ALI and group lidocaine(P＜0.05),while PaO₂,OI,pH and p62 were decreased(P＜0.05). Compared with group ALI,the level of Parkin and LC3-Ⅱ/LC3-Ⅰ was decreased in group of lidocaine intervention (P＜0.05),while PaO₂,OI,pH and p62 were increased(P＜0.05).The results of light microscopy showed intact alveolar structure and normal cell morphology in group control, inflammatory cell infiltration, interval thickening and alveolar collapse were found in group ALI, and less degree in group lidocaine than in group ALI. Transmission electron microscopy showed that the lung tissue and mitochondrial structure were normal in group control; in group ALI, the lung tissue cell was found to be swollen and formed with physalides companying by mitochondrial autophagosomes; The degree of injury in group lidocaine was decreased as compared with group ALI. Conclusions Lidocaine attenuates acute lung injury and the mechanism may be related to inhibition of mitophagy hyperactivation.

DEPDC1 is up-regulated in uterine corpus endometrial cancer

YANG Tingting, HUANG Jie, GUO Jianxin, HAN Jian

2023, 43(9):  1399-1407.  doi:10.16352/j.issn.1001-6325.2023.09.1399

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Objective To explore the expression and function of DEP domain containing 1 (DEPDC1) in uterine corpus endometrial cancer(UCEC). Methods The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to analyze the expression of DEPDC1 mRNA in normal endometrial tissues and UCEC tissues, the relationship with patient clinicopathological parameters and prognosis. Immuno-histochemistry (IHC), Western blot and RT-qPCR were used to detect the expression of DEPDC1 in UCEC cell lines and tissue. The CCK-8 assay, colony formation assay, and tumor xenograft were used to investigate the effect of DEPDC1 on cancer proliferation. Results DEPDC1 mRNA was up-regulated in UCEC (P＜0.001) and was correlated with the clinical stages (P＜0.001), tissue differentiation (P＜0.05) and histological type(P＜0.001) of UCEC. Compared with the DEPDC1 mRNA low expression patients, the patients with high expression of DEPDC1 showed lower disease-specific survival(DSS) and progress-free interval (PFI) (P＜0.01). The IHC, Western blot, and RT-qPCR showed that DEPDC1 was up-regulated both in UCEC tissue and cell lines. Down regulation of DEPDC1 inhibited the colony formation, invasion and tumor sphere formation, cell proliferation rate, and tumourigenesis in vivo. Conclusions DEPDC1 is up-regulated in UCEC that is correlated with the malignant progression and poor prognosis of UCEC.

Serum levels of homocysteine and leptin in Tibet Tibetans at Shannan area

LI Jun, Pemawangza

2023, 43(9):  1408-1411.  doi:10.16352/j.issn.1001-6325.2023.09.1408

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Objective To investigate the serum level of homocysteine (HCY) and leptin in Tibetans at Shannan area of Tibet. Methods A total of 880 Tibetan individuals who underwent routine physical examination from February 2018 to January 2021 in Shannan area of Tibet were enrolled as study subjects. Chemiluminescence method was used to compare the HCY and leptin levels among different age groups, genders, and seasons, and to study the distribution of serum HCY and leptin levels in Tibetans at Shannan area. Results With increasing age, the serum level of HCY and leptin significantly increased. The serum level of HCY and leptin in males was significantly higher than that in females (P＜0.05). Season had no significant effect on serum HCY and leptin levels (P＞0.05). The upper limits of serum HCY and leptin levels from males were 22.18 μmol/L and 7.85 μg/L respectively, while those for females were 18.01 μmol/L and 7.01 μg/L respectively. Conclusions The serum levels of HCY and leptin are significantly elevated in Tibetans at Shannan area. The risk factors found in local residents at Shannan area should be targeted in health education of local people.

Clinical Sciences

Expression and significance of CST4 in Kazakh esophageal squamous cell carcinoma

Yierxiati·TUERHONG, ZHANG Haiping, Kawuli·JUMAI, LI Ziyao, ZHANG Liwei, Yidilisi·AWUTI

2023, 43(9):  1412-1416.  doi:10.16352/j.issn.1001-6325.2023.09.1412

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Objective To explore the expression and clinical significance of cystatin S(CST4) in patients with esophageal squamous cell carcinoma(ESCC)in Kazakhs. Methods Totally 49 specimens from Kazakh ESCC patients who received surgical treatment were collected. RT-qPCR and immunohistochemical methods were used to detect CST4 expression in cancer tissues and adjacent tissues. Chi-square(χ²) test was used to analyze the relationshipbetween CST4 expression and the clinicopathological parameters. Kaplan-Meier method and Cox regression model were used to estimate the correlation between CST4 expression and overall survival. Results CST4 mRNA expression in ESCC tissues was higher than that in adjacent tissues (P＜0.05). CST4 protein expression in ESCC tissues (53.1%, 26/49) was higher than that in adjacent tissues (28.2%, 11/39) (χ²=5.506, P＜0.05). The expression of CST4 was significantly associated with lymph node metastasis (P＜0.05) and TNM stage (P＜0.01). Those with high CST4 expression had higher lymph node metastasis rate and later TNM stage. Univariate survival analysis showed that CST4 expression level(P＜0.01), invasion depth (P＜0.05) and TNM stage (P＜0.01) were associated with overall survival. Multivariate survival analysis showed that the CST4 expression (P＜0.05) and the invasion depth (P＜0.05) were independent prognostic factors for survival of ESCC patients. Conclusions CST4 expression is related to the occurrence, progression and prognosis of ESCC so it can be a potential prognostic marker for ESCC in Kazakhs.

Clinical value of plasma hsa_circ_005230 in the diagnosis and prognosis evaluation of primary hepatocellular carcinoma

Yimamaimaitijiang·ABRA, Pakhardin·BAIKERE, YI Chao, TONG Qing

2023, 43(9):  1417-1422.  doi:10.16352/j.issn.1001-6325.2023.09.1417

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Objective To detect the expression level of circular RNA (circRNA) hsa_circ_005230 in the plasma of primary hepatocellular carcinoma (HCC), and to explore its clinical value in the diagnosis and prognosis of HCC. Methods The non-coding RNA high-throughput sequencing data in the GEO database was used to screen the circRNA expression in HCC (cancer tissue/paracancerous tissue). RT-qPCR was used to detect hsa_circ_005230 in the plasma of 60 HCC patients, 30 hepatitis B patients and 30 healthy people. Expression levels and their relationship with clinicopathological characteristics of HCC patients were evaluated. The receiver operating characteristic(ROC) curve to evaluate the clinical value of hsa_circ_005230 in the diagnosis of HCC. Survival analysis was performed by Kaplan-Meier method, and multivariate prognostic analysis was performed by Cox regression. Results The most significant up-regulated expression was found in hsa_circ_005230 from the GEO database. The expression level of hsa_circ_005230 in plasma of HCC patients was significantly higher than that of hepatitis B group and healthy control group (P＜0.01); The increase of hsa_circ_005230 expression was related to tumor size (P＜0.05) and to the stage of tumor lymph node metastasis(P＜0.01); ROC analysis showed that the area under the ROC curve (AUC) of plasma hsa_circ_005230 in differentiating HCC from healthy people was 0.69, the sensitivity was 70%,and the specificity was 82 %.The overall survival rate of patients with high hsa_circ_005230 level was significantly lower than that of patients with low hsa_circ_005230 level. Univariate analysis showed that alpa-fetoprotein(AFP)(P＜0.01) and hsa_circ_005230 (P＜0.01) were related factors affecting the prognosis of HCC. Cox multivariate analysis revealed that hsa_circ_005230 was an independent prognostic indicator in HCC patients. Conclusions The hsa_circ_005230 may be used as a new biological marker for the diagnosis and prognostic evaluation of HCC.

Evaluating the difference in clinical efficacy for t(11;14) multiple myeloma patients with CD20^- or CD20⁺

ZHAO Weihong, HUANG Bintao, LIU Rui, XIANG Caixia

2023, 43(9):  1423-1427.  doi:10.16352/j.issn.1001-6325.2023.09.1423

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Objective To examine the differences in therapy response and confirm the effective regimen for multiple myeloma (MM) patients with t (11; 14)/CD20^- or CD20⁺, for the selection of transplantation as early treatment. Methods To find the differences in therapy response and to confirm the effective regimen for multiple myeloma (MM) patients with t (11; 14)/CD20^- or CD20⁺, for the selection of transplantation as the early treatment. There were three cytogenetics groups: t(11; 14)/CD20^- or CD20⁺ and low-risk profile including normal or cytogenetics other than t (11; 14). Eligible patients received the bortezomib-based induction and lenalidomide-based consolidation/maintenance regimen. Results Patients with t(11;14) gained adverse therapy response for bortezomib induction regimen than other low-risk arm (OR rate: 11.1% versus 84.0% versus 85.2%, P＜0.01). A prospective found that although the patients with t(11;14)/CD20^- showed the poor overall response for the bortezomib-based regimen, lenalidomide-based treatment schedule makes them gain a similar therapy advantage comparing with t(11;14)/ CD20⁺ and other low-risk group in the study The subgroup analyses of progression-free survival(PFS) and overall survival(OS) by continued lenalidomide-based consolidation/maintenance treatment also showed a benefit for lenalidomide therapy compared with observation regardless of cytogenetic risk profile and response at baseline (PFS at 4 years reached 75.0% versus 77.1% versus 84.2%, OS at 4 years was 75.0% versus 88.5% versus 90.4%, respectively). Moreover, the lenalidomide regimen little induced the incidence of fatal complications and was tolerated. There were only 3.2%, 8.4% and 15.8% patients had agranulocytosis, peripheral neuropathy and infection of 3-4 grade. Conclusions Lenalidomide regimen is more effective for t (11, 14)/ CD20^- risk MM and t(11;14)/CD20⁺ and other cytogenetically low-risk MM are consistent in PFS and OS. In addition, the initial response rate of MM patients with unsatisfactory bortezomib treatment can also be improved.

Chemical composition of gallstone in Tibetans from Tibet Autonomous Region

CHEN Biao, Dawa, Basangdunzhu, Rensang, Suolangduojie

2023, 43(9):  1428-1431.  doi:10.16352/j.issn.1001-6325.2023.09.1428

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Objective To study the characteristics of gallstone composition in Tibetans. Methods Gallstone/gallbladder stone(GS) specimens were collected from 106 Tibetan patients in the Department of General Surgery of Tibet Autonomous Region People′s Hospital from January to June 2021. The contents of cholesterol, bilirubin, cholic acid and calcium, sulfur, iron and zinc in gallstone were determined by ultraviolet spectrophotometer and by inductively coupled plasma spectrometer. Results Among 106 cases of cholecystolithiasis, 8.49% (9 cases) were cholesterol gallstones with cholesterol content of 534(528,725)μg/mg; 19.81% (21 cases) were pigment stones, and the content of bile pigment was 320(311,413)μg/mg; 71.69% (76 cases) were other types of stones; At the same time, bile acid with different contents was detected in three types of stones, and the content of bile acid in other types of stones was 22(12,33)μg/mg; The content of calcium, zinc and sulfur in pigment stone was relatively high(P＜0.05), but the content of iron didn′t show had significant difference. Conclusions Gallstone ofTibetan people is mainlycomposed of other stones and pigment stones. Cholesterol stones only account for a small proportion, which is quite different from the composition profile from other parts of China. The content of calcium, sulfur and zinc in pigment stone is relatively high, and the content of calcium is the highest element.

Establishment of a predictive model for benign and malignant prostatic peripheral lesions by combined TRUS and CEUS

SUN Ya, SHI Yanping, LI Huarong, WANG Jiajun, XU Jingxu, LIANG Lei

2023, 43(9):  1432-1438.  doi:10.16352/j.issn.1001-6325.2023.09.1432

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Objective To construct a machine learning model based on radiomics features by combing conventional B-mode transrectal ultrasound (TRUS) and contrast-enhanced ultrasound (CEUS)in order to improve prostate cancer (PCa) detection in the peripheral zone, and to explore its clinical application value. Methods A retrospective study of 109 cases (45 benign, 64 malignant lesions) with targeted biopsy-confirmed pathology who underwent B-mode and CEUS examinations was performed. Time-intensity curves were obtained using Sonoliver software forall lesions in regions of interest. The following parameters were collected: the maximum intensity (IMAX), the rise time (RT), the time to peak (TTP), and the mean transit time (MTT). Clinical risk factors, including age, serum total prostate-specific antigen (tPSA), free PSA(fPSA), f/t PSA, prostate volume and prostate-specific antigen density (PSAD), were collected. Feature selection and model construction were carried out by feature correlation analysis and multivariable Logistic regression analysis, respectively. Results Finally, 32 features were screened out by the radiomics models. Three radiomics models (B model, CEUS model and B-CEUS combined model) were established by logistic regression, and radiomics scores were obtained at the same time. The risk factors like age, PSAD, and RT were significant independent predictors (P＜0.05). The diagnostic accuracy of B model, CEUS model, B-CEUS combined model, risk factor model and risk factor-radiomics combined model were 0.75, 0.71, 0.73, 0.70 and 0.84, respectively, and the area under the curves(AUC) were 0.79, 0.75, 0.84, 0.79 and 0.91, respectively. The risk factor-radiomics combined model had a significant significance in the validation cohort (P＜0.05). Conclusions The machine learning model combined with conventional B-mode TRUS, CEUS, and relevant clinical factors can better predict the benign and malignant prostate peripheral lesions, which may significantly support clinical decision-making.

Airway microecology of children with bronchial asthma is related to serum immune factors

HE Lei, YAN Kai, DENG Yingxia

2023, 43(9):  1439-1442.  doi:10.16352/j.issn.1001-6325.2023.09.1439

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Objective To investigate the correlation between 16S rRNA gene high-throughput sequencing of induced sputum and serum immune factors in children with bronchial asthma at different stages. Methods From April 2019 to May 2021, 96 children with bronchial asthma who were treated in Chengdu Shuangliu District Maternal and Child Health Hospital were selected, which covered 46 remission cases and 50 acute cases.In addition, 40 healthy children who underwent physical examination at the same time were selected as the controls group. MiSeq high-throughput sequencing platform was used to sequence the 16S rRNA gene in induced sputum from three groups of children, and the level of IL-4, IL-10, IL-17 and IFN-γ in three groups of children was detected by enzyme-linked immunosorbent assay. Results The results correlation analysis showed that Shannon index was negatively correlated with IL-4 and IL-17 in children with bronchial asthma (P＜0.001), Shannon index was positively correlated with IL-10 and IFN-γ (P＜0.001); Ace index was positively correlated with IL-4 and IL-17 in children with bronchial asthma (P＜0.001). Ace index was negatively correlated with IL-10 and IFN-γ(P＜0.001). Conclusions The airway microecology of children with bronchial asthma is obviously dysregulated.

Mini Reviews

Research progress of endothelial lipase as a therapeutic target for coronary heart disease

SONG Xingming, Harisa·ERKENJIAN, Dilihumal·ABLAITI, GAO Ying

2023, 43(9):  1443-1447.  doi:10.16352/j.issn.1001-6325.2023.09.1443

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Endothelial lipase(EL) is mainly generated by vascular endothelial cells and is responsible for regulating liver lipid metabolism and intestinal lipid absorption. In the inflammatory state, EL can also promote the adhesion and aggregation of macrophages and platelets in the damaged vascular endothelium. EL can also promote the proliferation of damaged vascular endothelial cells, and inhibit the over-expression of EL can reduce the degree of atherosclerosis. However, in acute coronary artery disease and oxidative stress reaction, EL can enhance the antioxidant capacity of high-density lipoprotein cholesterol, reduce the damage of inflammatory reaction to vascular endothelium, enhance the energy metabolism of damaged cardiomyocytes and inhibit apoptosis of damaged cardiomyocytes. As a new therapeutic drug for dyslipidemia and atherosclerosis, endothelial lipase inhibitor needs more extensive clinical trials to clarify its true clinical efficacy, safety and specific clinical application scenarios.

Advances on the role of PTTG1 in the pathogenesis of tumors

WU Nianping, HUANG Huili, ZHOU Kuaile, ZHOU Cefan, TANG Jingfeng

2023, 43(9):  1448-1452.  doi:10.16352/j.issn.1001-6325.2023.09.1448

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Pituitary tumor transforming gene 1(PTTG1) is an oncogene which isolated from the pituitary gland. PTTG1 was previously reported to bind and inhibit separase to affect sister chromatid separation and lead to chromosome aneuploidy, activate the DNA damage response pathway to induce p53-dependent senescence, and also transactivate some oncogenes and promote cell transformation and tumorigenesis in nude mice. It can also promote tumor growth and invasion by affecting Wnt/β-catenin, epithelial-mesenchymal transition(EMT), and TGFβ/SMAD3 pathways. This article provides ideas for the development of tumor therapeutic drugs targeting PTTG1.

Progress of research on the role of exosomes in the occurrence and development of liver precancerous lesions

YANG Yaqian, PAN Yanfang, QU Mengyang, FANG Yan, YING Xiaoping, ZHANG Meiqian, WEI Jing

2023, 43(9):  1453-1456.  doi:10.16352/j.issn.1001-6325.2023.09.1453

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Increased secretion of exosomes in precancerous lesions of hepatocellular carcinoma can directly promote the disease from inflammatory response to cancer through intercellular communication. Exosomes participate in the occurrence and development of hepatocellular precancerous lesions by affecting angiogenesis, epithelial-mesenchymal transition and immunoregulation,so exomes may become a new therapeutic target for hepatocellular precancerous lesions and provide new ideas for the diagnosis and treatment of hepatocellular carcinomas.

Progress of exosomal PD-L1 in diagnosis and treatment of non-small cell lung cancer

YAN Chenhong, JIN Er

2023, 43(9):  1457-1461.  doi:10.16352/j.issn.1001-6325.2023.09.1457

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Exosomal PD-L1(exoPD-L1) is secreted by cancer cells in some patients with non-small cell lung cancer and this molecule participates in the development of tumors. As liquid biopsy detection, the detection of exosomal PD-L1 has a great deal of advantages, such as non-invasive and stable. Furthermore, exosomal PD-L1 has a bright prospect in early diagnosis in lung cancer, which also has close contact with TNM of non-small cell lung cancer. Exosomal PD-L1 is related to tumor tissue PD-L1 and can be used to select people who in deed suit immumunotherapy.Monitoring exosomal PD-L1 dynamically is meaningful for evaluating the effects of immunotherapy in patients with non-small cell lung cancer. Study has found that blocking the secretion of exosomal PD-L1 could assist immunotherapy. The application of exosomal PD-L1 is quite potential to the treatment of patients at advanced stage of non-small cell lung cancer.

Diagnostic difficulties and treatment progress of primary gastric lymphoma

DAI Di, LIU Yuqin

2023, 43(9):  1462-1466.  doi:10.16352/j.issn.1001-6325.2023.09.1462

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Primary gastric lymphoma (PGL) is the most common gastric malignant tumor except gastric cancer, most of which have no specific clinical symptoms. It is usually not accurately diagnosed. And it is prone to misdiagnosis and missed diagnosis. The main treatments include surgery, radiotherapy, chemotherapy and targeted therapy. And the immunotherapy is expected to be a potential treatment modality. Understanding the difficulties in the diagnosis process is the guarantee of accurate diagnosis and the basis for subsequent precision treatment.

Progress on the role of ABCG2 and SLC2A9 in the onset of hyperuricemia and gout

YANG Lijuan, DONG Qiumei, WU Hao

2023, 43(9):  1467-1471.  doi:10.16352/j.issn.1001-6325.2023.09.1467

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ABCG2 and SLC2A9 encode the uric acid transporters ABCG2 and GLUT9. ABCG2 single nucleotide polymorphism (SNP) can reduce the expression and transport function of ABCG2 protein, and then cause intestinal uric acid excretion dysfunction, resulting in the increase of blood uric acid. The regulation of blood uric acid by SLC2A9 is complicated. Loss of function of SLC2A9 may lead to decreased renal tubule uric acid reabsorption, impaired intestinal uric acid excretion and impaired hepatic uric acid uptake. ABCG2 promotes gout attacks by causing hyperuricemia(HUA) and increasing inflammatory responses. On the contray, loss of function of SLC2A9 can instead reduce oxidation and inflammatory responses. In addition, ABCG2 has a close relationship with early-onset gout and its SNP is a risk factor for early onset gout.

Progress on the role of exosomal miRNAs in organ fibrosis

FANG Lu, LIU Ruiqi, LIANG Peng, CEN Ying

2023, 43(9):  1472-1476.  doi:10.16352/j.issn.1001-6325.2023.09.1472

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Exosomes are tiny vesicles that are actively secreted by a variety of cells, which regulate various physiological and pathological processes of the body by carrying proteins, lipids, miRNAs and other biological molecules. Exocrine microRNAs(miRNAs) stably exist in the body fluid circulation and participate in many pathological processes of organs. In organ fibrosis disease, the content of the exosomal miRNAs shows significant differential expression profile as compared with normal tissues, and promotes or inhibits organ fibrosis by regulating different signal pathways. It is considered to be the latest biological indicator for diagnosing organ fibrosis and judging its degree of fibrosis, and a new therapeutic target for fibrosis disease.

Medical Education

Practice of mindfulness training to reduce anxiety in college students

WANG Zhonghui, LIAN Yiyao, LIU Junxiang

2023, 43(9):  1477-1480.  doi:10.16352/j.issn.1001-6325.2023.09.1477

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Objective To explore the effect of mindfulness training on anxiety symptom of Chinese college students with high anxiety and its internal mechanism. Methods A total of 2 416 college students from two universities in Beijing were evaluated and recruited according to their scores. They were divided into intervention group and control group with twenty in each. All students were pre-tested by State-trait Anxiety Inventory Questionnaire (STAI) and the Five-factor Mindfulness Questionnaire (FFMQ). After that, students in the intervention group received an 8-week training of mindfulness cognitive therapy. After the training, all students were post-tested with the same scales. Results Mindfulness training reduced state anxiety (F=6.21, P＜0.001) and trait anxiety scores (F=6.15, P＜0.001) in the intervention group, improved their total score of mindfulness (F=6.26, P＜0.001), observation (F=5.21, P＜0.01), description (F=6.24, P＜0.001) and non-response(F=5.80, P＜0.01). Conclusions Mindfulness training effectively reduces the anxiety symptoms of college students with high anxiety.

Application of literature case presentation and discussion in teaching of clinical epidemiology for professional Master students

HAN Huijun, LIAO Wei, WANG Li

2023, 43(9):  1481-1485.  doi:10.16352/j.issn.1001-6325.2023.09.1481

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Objective To strengthen the research capacity of professional Master students in clinical medicine,a new teaching mode of literature case presentation and discussion was tried in clinical epidemiology teaching and the teaching effectiveness was evaluated. Methods The professional Master students in clinical medicine of Peking Union Medical College who joined clinical epidemiology courses during 2019—2021 were selected as the research subjects(n=128). In 2019, the lecture-based teaching was adopted. In 2020 and 2021, a 4-hour literature case presentation and discussion class was added for the topic of “cohort study”. Feedback on the new teaching mode was collected through questionnaires from students taking the course in 2021. Results The average per-question score rate across all questions in the final examination for a student in 2020 was higher than that in 2019 (the median value was 84.7% vs 75.4%, P＜0.001). There was no statistical difference in the average per-question score rate across questions related to the cohort study topic for a student between the two years. Students′ score ratefor the case presentation and discussion in 2020 was positively correlated with the average per-question score rate for not only questions related to the cohort study topic but also all questions in the final examination(r=0.40, P＜0.01; r=0.31, P＜0.05). Among the students taking the course in 2021, 80% believed that they had achieved the knowledge-learning goal of this case discussion class. About 90% agreed that the teaching mode of literature case presentation and discussion was helpful in improving their ability in designing clinical research, reading literatures, presenting research work and carrying out team collaboration. All students were satisfied with this new teaching mode. Conclusions Conducting literature case presentation supplemented with discussion in clinical epidemiology teaching can help students better to Master clinical research methodology and enhance their comprehensive research capacity.

Medical Supervision

An empirical study on the ethical issues caused by the experiment of rhesus monkey carrying human brain gene

GUI Yixin, DU Yingjie, ZHANG Xinqing

2023, 43(9):  1486-1489.  doi:10.16352/j.issn.1001-6325.2023.09.1486

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Objective In 2019, A Chinese medical research team constructed a transgenic rhesus monkey model of human MCPH1, which is necessary to understand the cognition and behavior tendency of researchers on this new type of ethical issues. Methods The research group developed a questionnaire containing demographic information and ethical situational questions. The respondents were medical researchers who applied for the National Natural Science Foundation of China in 2019. The data obtained are analyzed by descriptive statistics. Results Overall, 70.9% of respondents (n=11 164) believed that there were ethical challenges when use the genetically modified monkeys who carrying human genes for medical research; The most prominent ethical issues were “unacceptable risk-benefit ratio” (49.1%) and “harm to rhesus monkeys” (33.7%); 31.1% of them believed that the study could be carried out when improvement from the ethics committee of their institution was availabl. Conclusions Medical researchers are cautious about such genetically modified monkeys. The 3R principle shouldbe strictly implemented in the medical research of transgenic monkeys, and the study of human-rhesus monkey chimerism should follow ethical norms and be strictly reviewed.