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Table of Content

    05 September 2021, Volume 41 Issue 9
    Reduction of carotid perfusion promotes inflammation of vascular endothelial cells in rabbits
    2021, 41(9):  1247-1252. 
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    Objective To study how does reduction of blood flow perfusion regulates cytoskeleton rearrangement and its relationship with inflammation during atherosclerosis (AS). Methods The carotid artery stenosis model was established by carotid cannula in New Zealand rabbits. The normal animals were set as control group, and animals fed with high fat diet were set as high fat group. The localization and expression of vascular inflammatory response-related proteins MCP-1, planar cell polarity signaling pathway-related proteins DVL2 and VANGL2, and cytoskeletal proteins BBS8 and γ-tubulin were determined by immunohistochemistry staining, qPCR and Western blot. Results The cannula group and high fat group have showed intimal hyperplasia, while the control group hasn’t. The localizations of DVL2 and VANGL2 have been observed mainly at the endovascular hyperplasia in the cannula group, while the positive localizations of them have been hardly observed in the other two groups. Moreover, the expressions of these proteins have been significantly upregulated in the cannula group compared to that in the control or high fat group. Conclusion The results show that reduction of blood flow perfusion was involved in the early inflammation of AS by increasing expression of MCP-1, and regulating the BBS8 and γ-tubulin during the rearrangement of microtubule cytoskeleton.
    PTTG and p21 as prognostic biomarker in radiotherapy for non-functional pituitary adenomas
    Yang Fang LI HUI MINHU
    2021, 41(9):  1253-1259. 
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    Objective To evaluate the predictive value of pituitary tumor transforming gene (PTTG) and cycle-dependent kinase inhibitor1A (p21) in the prognosis of pituitary adenomas underwent radiotherapy. Methods A total of 89 postoperative patients with nonfunctioning pituitary adenomas treated by Gamma knife radiosurgery (GKRS) between 2003 and 2013 were collected, and divided into study and validation cohorts based on the radiosurgery operation time. According to the follow-up MRI, a tumor volume decrease of more than 20% was considered radiosensitive; Expression of sixteen protein markers in pituitary adenomas was determined using a tissue microarray. Results Univariate analysis revealed that nucleus positive PTTG (HR, 1.355; P<0.05 or HR, 1.637; P<0.01) and cytoplasm high expression of p21(HR, 1.174; P<0.01 or HR, 1.378; P<0.01) were significantly correlated with radiation resistance in both study and validation group. In the study group, Kaplan Meyer (KM) curve analysis showed patients with nucleus negative PTTG (P<0.01) and cytoplasm low expression of p21(P<0.01) had a higher radiosensitivity, and the same results were obtained in the validation group(PTTG,P<0.05;P21,P<0.01). Conclusion Patients with nucleus positive PTTG and cytoplasm high expression of p21 tend to be resistant to radiotherapy in pituitary adenomas; PTTG and p21 are prognostic protein markers associated with radiation resistance.
    Probiotics improve lipid metabolism of obese mice induced by high-fat and high-sucrose diet
    2021, 41(9):  1260-1265. 
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    Objective To study the effect of probiotics on lipid metabolism disorder in obese mice induced by high-fat and high-sucrose diet. Methods C57BL/6J mice were randomly divided into control group, model group (high-fat and high-sucrose feed), probiotics group (2×109 CFU probiotics), inhibitor group (AMPK inhibitor Dorsomerphin, 10 mg/kg) and probiotics+inhibitor group, with 10 mice in each group. The liver histopathological characteristics, lipid metabolism-related indicators, autophagy and related pathway protein expression level were detected by Automatic biochemical analyzer, hematoxylin-eosin (HE) and oil red O staining method, transmission electron microscope and Western blot method. Results Compared with control group, obvious lipid vacuoles appeared in the liver tissue, the nuclear staining was deepened, a large amount of fat accumulation and autophagy bodies were reduced, lipid metabolism indexes (TC, TAG, LDL), lipid metabolism protein SREBP-1c expression level and mTOR phosphorylation level were higher (P < 0.05), lipid metabolism indexes HDL, autophagy related proteins LC3 and Beclin1 protein expression levels and AMPK phosphorylation level of model group were lower (P < 0.05). Compared with model group, the lipid vacuoles and fat accumulation in probiotics group were alleviated, and more autophagosomes were observed, TC, TAG, LDL, SREBP-1c expression level and mTOR phosphorylation level were lower (P < 0.05), HDL, LC3 and Beclin1 expression levels and AMPK phosphorylation level of probiotics group were higher (P < 0.05); the number of lipid vacuoles increased and became larger, the accumulation of fat increased, and the autophagy decreased, TC, TAG, LDL, SREBP-1c expression level and mTOR phosphorylation level were higher (P < 0.05), HDL, LC3 and Beclin1 protein expression levels and AMPK phosphorylation level of inhibitor group were lower (P < 0.05). The inhibitor group was compared with the model group, the probiotic+inhibitor group was compared with the probiotic group, the lipid vacuoles and fat accumulation in the liver tissue were higher, and the autophagy bodies were reduced, TC, TAG, LDL, SREBP-1c expression level and mTOR phosphorylation level were higher (P < 0.05), HDL, LC3 and Beclin1 protein expression levels and AMPK phosphorylation level were lower (P < 0.05). Conclusions Probiotics may activate AMPK pathway and then negatively regulate mTOR pathway, promote hepatocyte autophagy and improve lipid metabolism disorder of obese mice induced by high-fat and high-sucrose diet.
    Dihydroartemisinin reduces lung injury in rats with hemorrhagic shock
    2021, 41(9):  1266-1271. 
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    Objective To study the protective effect of dihydroartemisinin (DHA) on lung injury in rats with hemorrhagic shock (HS). Methods The rats were divided into sham operation group, model group ( The left common carotid artery was bloodletted, the blood volume was about 35% of the blood volume, the average arterial pressure dropped to 35~45 mmHg, and the Ringer's solution was resuscitated with twice the blood volume), DHA low and high-dose groups (6 and 12 mg/kg DHA per day), dexamethasone group (10 mg/kg dexamethasone per day). Intervene continuously for 7 days. The wet weight/dry weight (W/D) ratio of the lung was measured. The enzyme-linked immunosorbent assay (ELISA) method was used to determine the activity of myeloperoxidase (MPO), the levels of interleukin-12 (IL-12), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in lung tissue. The hydroxylamine method was used to determine the activity of superoxide dismutase (SOD). The thiobarbituric acid colorimetric method was used to determine the malondialdehyde (MDA) level. HE staining was used to observe lung tissue pathology. Western blot method was used to detect the relative expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB) p65, and p-NF-κB p65 protein in lung tissue. Results Compared with the sham operation group, the lung W/D, MDA, IL-12, IL-1β, and TNF-α levels, MPO activity, relative expression of TLR4, MyD88 protein, p-NF-κB p65/NF -κB p65 were significantly increased in the model group, of which the SOD activity was significantly weakened (P<0.05). Compared with the model group, lung W/D, lung tissue MDA, IL-12, IL-1β, and TNF-α levels, MPO activity, relative expression of TLR4, MyD88 protein, p-NF-κB p65/NF -κB p65 were significantly reduced in the low-dose and high-dose groups of DHA and the dexamethasone group, of which the SOD activity were significantly enhanced (P<0.05). The model group was infiltrated with a large number of inflammatory cells, the pulmonary interstitial edema was obvious, and the number of alveoli was significantly reduced. The above-mentioned pathological changes improved after intervention in DHA low and high-dose groups and dexamethasone group. Conclusions DHA can reduce lung pathological changes, pulmonary edema, oxidative damage and inflammatory response after HS, inhibit the expression of TLR4, MyD88 and NF-κB phosphorylation, and shows a protective effect on lung injury.
    Involvement of miR-125b in human pancreatic ductal epithelial barrier affected by TRAF6
    2021, 41(9):  1272-1276. 
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    Objective To investigate the effect of tumor necrosis factor receptor-associated factor 6 (TRAF6) on human pancreatic ductal epithelial barrier and targeted binding relationship between miR-125b and TRAF6. Methods HPDE6C7 cells were up-regulated TRAF6 gene expression using lentivirus infection. The protein expression of nuclear factor κB (NF-κB) pathway and tight junction was determined by Western blot, the permeability in monolayer HPDE6C7 cells was examinated with Transwell cab, to evaluate the epithelial barrier function, and the targeted binding of miR-125b and TRAF6 were identified by dual-luciferase reporter assay. Results After up-regulated expression of TRAF6 gene in HPDE6C7 cells, the protein levels of NF-κB p65, TGFβ-activated kinase 1 (TAK1) and TAK1-binding 1 (TAB1) were increased, and the protein levels of occludin and claudin-1 were decreased (P<0.05), furthermore the permeability was increased significantly (P<0.05). Dual-luciferase reporter assay confirmed that TRAF6 was the target gene of miR-125b. Conclusions TRAF6 may play a role in affecting the pancreatic ductal epithelial barrier by regulating the NF-κB signaling pathway, which may be inhibited by miR-125b targeted binding to TRAF6.
    circ_0038467 targets at miR-182 for regulating S. pneumoniae (Sp)-induced injury of human alveolar epithelial cell line HPAEpiC
    2021, 41(9):  1277-1284. 
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    Objective: To investigate the effect of circular RNA 0038467 (circ_0038467) targeting miR-182 on the apoptosis and endoplasmic reticulum stress of alveolar epithelial cells (HPAEpiC) induced by S. pneumoniae (Sp). Methods: HPAEpiC was divided into control (NC) group (without any treatment), SP group (SP infection), Sp+ si-NC group (Sp infection after transfection of si-NC), Sp+ si-circ_0038467 group (Sp infection after transfection of si-circ_0038467), Sp+ miR-NC group (Sp infection after transfection of miR-NC), and Sp+ miR-182 group (Sp infection after transfection of miR-182 mimics), Sp+ si-circ_0038467 + anti-miR-NC group (Sp infection after transfection of si-circ_0038467 and anti-miR-NC), Sp+ si-circ_0038467 + anti-miR-182 group (Sp infection after transfection of si-circ_0038467 and anti-miR-182). The expression of circ_0038467 and miR-182 were detected by real-time quantitative PCR. Flow cytometry detected cell apoptosis; Western blot analyzed the expression level of B-cell lymphoma (Bcl-2), heavy chain binding protein (BIP), Bcl associated X protein (Bax) and CCAAT enhancer binding protein homologous protein (CHOP), cysteine protease 3 (caspase-3), and cleaved caspase-3 proteins. The effects of circ_0038467 and miR-182 expression on HPAEpiC apoptosis and endoplasmic reticulum stress induced by S. pneumoniae were analyzed by the above methods. Results: The apoptosis rate of HPAEpiC cells, the expression of circ_0038467, Bax, caspase-3, cleaved-caspase-3, BIP and CHOP were significantly increased after SP infection (P<0.05), whereas the expression of Bcl-2 was significantly decreased (P<0.05). After circ_0038467 inhibition or miR-182 overexpression, the apoptosis rate, expression of circ_0038467, Bax, caspase-3, cleaved-caspase-3, BIP and CHOP were significantly reduced (P<0.05), whereas Bcl-2 expression was significantly increased (P<0.05). miR-182 inhibition can attenuate the effect of circ_0038467 inhibition on Sp induced HPAEpiC apoptosis and endoplasmic reticulum stress (P<0.05). Conclusion: Inhibition of circ_0038467 can attenuate Sp induced alveolar epithelial cell apoptosis and endoplasmic reticulum stress, and its mechanism is related to the targeted regulation of miR-182 expression.
    Silencing miR-26a alleviates myocardial ischemia-reperfusion injury in rats
    2021, 41(9):  1285-1290. 
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    Objective To investigate the effect of miR-26a on myocardial ischemia-reperfusion (I/R) injury in rats. Methods Rats were randomly divided into control group (n=20),I/R group (n=20) and siRNA group (n=20). Seven days before the establishment of I/R model, miR-26a siRNA was injected into tail vein to silence miR-26a gene. Ejection fraction (EF%) and shortening fraction (FS%) were measured by echocardiography.The infarct size was measured by TTC.The morphology of cardiomyocytes was detected by HE staining.TUNEL assay was used to detect the level of cardiomyocyte apoptosis.Western blot was used to detect the expression of Bcl-2 related X protein (Bax), caspase-3 and Rho/RhoA signaling pathway related proteins.Results The expression of miR-26a in I/R group was significantly higher than that in control group (P<0.05).The EF% and FS% of siRNA group were significantly improved (P<0.05).In siRNA group, the degree of myocardial infarction caused by I/R was significantly reduced, and the percentage of myocardial infarction area was increased from 43.08%±2.43% to 21.54%±1.82% (P<0.05).In siRNA group, the myofilaments were arranged orderly, the degree of myocardial necrosis was low, and the cell edema was significantly reduced compared with I/R group.The level of cardiomyocyte apoptosis in siRNA group was significantly lower than that in I/R group (P<0.05),and the expression levels of Bax and caspase-3 were also significantly decreased (P < 0.05).Inhibition of miR-26a could significantly reduce the expression of Rho/RhoA signaling pathway protein during I/R (P < 0.05).Conclusions miR-26a gene silencing may inhibit I/R-induced cardiomyocyte apoptosis by reducing expression of Rho/RhoA signaling pathway protein.
    Thalidomide alleviates renal fibrosis in nephrotic syndrome mice
    2021, 41(9):  1291-1296. 
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    Objective To investigate the effects of thalidomide on epidermal growth factor receptor (EGFR)/extracellular signal regulated kinase (ERK) signaling pathway and renal fibrosis in nephrotic syndrome mice. Methods The mice were randomly divided into control group, model group to prepare membranous nephropathy model, thalidomide group was given thalidomide solution 100mg / kg, leflunomide group was given leflunomide solution 5mg / kg, 15 mice in each group. 10 times 10 day for 4 weeks. The 24-hour urine protein (24h-Upro) was measured before, after and 4 weeks after treatment; after 4 weeks of treatment, the biochemical indexes of mice in each group were detected by automatic biochemical analyzer; the levels of serum interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF - α) were detected by enzyme-linked immunosorbent assay (ELISA); hematoxylin eosin (HE) staining, Masson staining and periodic acid schiff (PAS) staining were used to observe the renal pathological changes in each group; and the expressions of EGFR and ERK mRNAs and proteins were detected by real-time fluorescence quantification (RT-qPCR) and Western blot. Results Compared with the control group, the 24h Upro in the model group was significantly increased (P < 0.05). After 4 weeks of treatment, compared with those in the control group, the glomerulus volume of the model group was larger, there were vacuolar lesions in the renal tubules, and the epithelial cells of the renal tubules had the deposition of eosinophilic protein, and the 24h-Upro, the contents of TC, TG, BUN and Scr in serum, the expressions of IL-6, IL-8 and TNF - α in serum, the mRNA levels of EGFR and ERK in renal tissue, the protein expressions of p-EGFR/EGFR and p-ERK/ERK were significantly higher (P < 0.05); compared with those in the model group, the above pathological symptoms of leflunomide group and thalidomide group were significantly reduced, and the 24h-Upro, the contents of TC, TG, BUN and Scr in serum, the expressions of IL-6, IL-8 and TNF - α in serum, the mRNA levels of EGFR and ERK in renal tissue, the protein expressions of p-EGFR/EGFR and p-ERK/ERK were significantly lower (P < 0.05). Conclusions Thalidomide may reduce renal damage and inhibit renal fibrosis by inhibiting EGFR/ERK signaling pathway.
    miR-141-3p inhibits the migration and invasion of gastric cancer cell line AGS through targeting PDCD1
    2021, 41(9):  1297-1302. 
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    Objective To investigate the role of miR-141-3p on the migration and invasion of gastric cancer cells, and to reveal its potential molecular mechanism. Methods The expression of miR-141-3p in clinical tissue samples, normal gastric mucosal epithelial cell line (GES-1) and gastric cancer cell line (AGS) was detected by RT-qPCR. miR-141-3p mimic was transfected into AGS cells, and then the migration and invasion of cells were detected by Transwell assay. The luciferase reporter experiment detects whether miR-141-3p exerts its biological effects by targeting programmed cell death protein 1 (PDCD1). AGS cells that had over-expressed miR-141-3p were then infected with lentivirus PDCD1, and cell migration and invasion were subsequently detected. Results Compared with adjacent tissues and GES-1 cells, the expression of miR-141-3p in gastric cancer tissues and AGS cells was significantly decreased. Over-expression of miR-141-3p could significantly inhibit the migration and invasion of AGS cells. miR-141-3p negatively regulates PDCD1 expression by directly binding to the 3'-UTR of PDCD1 mRNA. Over-expression of PDCD1 could reverses the inhibitory effect of miR-141-3p over-expression on the migration and invasion of GAS cells. Conclusions miR-141-3p inhibits the migration and invasion of gastric cancer cells by down-regulating the target gene PDCD1.
    Lactobacillus rhamnoides alleviates liver graft-versus-host disease after transplantation of hematopoietic stem cell through regulating intestinal microbiota
    2021, 41(9):  1303-1308. 
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    Objective To investigate the effect and mechanism of Lactobacillus rhamnosus GG (LGG) on liver graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Methods Mice were randomly divided into three groups, including control, GVHD (the donor-derived bone marrow and spleen cell suspension were reinfused through the tail vein), and LGG groups (LGG gavage after modeling, 200 μL/mouse, twice a week for 5 weeks). The pathological changes of liver tissues were observed by HE staining, the liver function and the levels of plasma cytokines IL-6, IL-18 and TNF-α were detected by ELISA, and the changes of intestinal microbiota were detected by PCR. Results Compared with mice in the control group, mice in GVHD group showed shorter survival time, obvious liver function damage and pathological changes, increased levels of plasma cytokines IL-6, IL-18 and TNF-α (P<0.01), and decreased intestinal microbiota diversity (P<0.05). LGG treatment significantly alleviated the above-mentioned pathological changes induced by GVHD in the liver (P<0.05). Conclusions LGG can reduce the levels of inflammatory factors in liver by regulating the intestinal microbiota, thereby alleviating GVHD in mice after HSCT, suggesting that LGG may be useful in the treatment of GVHD.
    Identifying of important sites of the conducting pore of nicotinic acetycholine receptor through two-electrode voltage-clamp
    2021, 41(9):  1309-1312. 
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    Objective To detect the main amino acid sites in the ion-conducting pore of the human ???nicotinic receptor by two-electrode voltage-clamp. Methods The amino acids in the transmembrane region M2 of nAChR ?? subunit (from Leu248 to Ala258) were mutated to hydrophilic serine one by one by site-directed mutagenesis. The cRNA was synthesized in vitro and microinjected into Xenopus oocytes. After 1~3 days, the function of wild type nAChR ?? and its mutants were detected by two-electrode voltage-clamp. Results After the hydrophilic mutation on the second transmembrane domain , it was indicated that the mutations of the hydrophobic residues (L248、V252、L256和L255) to hydrophilic ones significantly decrease the EC50 values of the receptor to agonist acetylcholine. The hydrophilic mutations of these four M2 residues resulted in a dramatic leftward shift of the dose-response curve and decrease desensitization. Moreover, the desensitization rate was positively correlated to the EC50 values in log scale. Conclusions The residues L248, V252, L256 and L255 in the transmembrane M2 of nAChR ?? are the main sites which are lining the ion-conducting pore.
    Erastin induces cell apoptosis in human non-small cell lung cancer cell line A549
    2021, 41(9):  1313-1317. 
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    Objective In this study, we aimed to figure out whether Erastin induces apoptosis and tried to investigate the molecular mechanism in A549 cells. Methods A549 cells were treated with Erastin at different concentrations, with or without ROS scavenging agent N-acetyl-L-cysteine (NAC) and with or without apoptosis inhibitor (Z-VAD-FMK). Then we measured iron content with Iron Assay Kit, cell injure and apoptosis with CCK-8 and flow cytometry in A549 cells. Results Erastin induced the increase of iron content and induced the injury in A549 cells. Erastin further induced apoptosis of A549 cells (p<0.05), which was inhibited by apoptosis inhibitor Z-VAD-FMK. And Erastin induced an increase in peroxides (ROS) and subsequently induced apoptosis(p<0.05), which was attenuated by the ROS scavenging agent NAC(p<0.05). Conclusion Erastin has an inhibitory effect on NSCLC A549 by inducing intracellular ROS production, which provides evidences for the pathogenesis, diagnosis and treatment of NSCLC.
    Evaluation of inflammation of perirenal adipose tissue in C57BL/6J mice with high-fat diet
    2021, 41(9):  1318-1322. 
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    Objective To evaluate the inflammatory response of perirenal adipose tissue induced by high-fat diet in C57BL/6J mice. Methods Mice were randomly divided into normal diet group (control group, n=6) and high-fat diet group (HFD group, n=6). The mRNA expressions of TNF-α, CD11c, IL-1β, IL-10, TGF-β1, CD206 in perirenal adipocytes were detected by RT-qPCR. The expressions of F4/80, CD68 and LCA in perirenal adipose tissue and renal parenchyma were detected by immunohistochemistry. Results Compared with the control group, the mRNA relative expression levels of TNF-α and IL-1β in perirenal adipose tissue of mice in HFD group were increased(P<0.05); The expression of F4/80, CD68 and LCA in perirenal fat increased in HFD group(P<0.05). Conclusions High-fat diet induced inflammation in perirenal adipose tissue of C57BL/6J mice.
    Expression, activity measurement and structure prediction of spermatogenic regulator: recombinant human HSF5
    2021, 41(9):  1323-1328. 
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    Objective To obtain soluble expression of recombinant human HSF5 protein and predict the structure of HSF5 bound to heat shock element. Methods The nucleotide sequence encoding the target gene was subcloned into expression vector pET-22b(+), followed by transformation into Escherichia coli strain BL21(DE3) and expression induction with IPTG. The recombinant protein was purified using an Ni-NTA affinity column and gel filtration chromatography. A gel shift assay was carried out after the incubation of the purified HSF5 protein and an oligonucleotide containing a heat shock element. Structure prediction was done by means of homology modeling and molecular dynamics simulation. Results Soluble expression of human HSF5 protein was achieved with high purity production. The purified protein showed good binding activity with the heat shock element. A reasonable protein-DNA binding model was obtained. Conclusion The recombinant HSF5 protein was produced in soluble form with good yield and activity, which lays a solid foundation for mechanistic studies of this novel spermatogenic regulator in the future.
    Application of the consciousness index (IoC1) combined with injury sensitive index (IoC2) in cesarean section under general anesthesia
    2021, 41(9):  1329-1332. 
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    Objective To investigate the application of the consciousness index IoCl combined the injury sensitive index IoC2 in cesarean section under general anesthesia. Methods Sixty patients undergoing cesarean section under general anesthesia, ASA grade I~II, aged 18~42, were randomized into control group (C group) depth of anesthesia and intensity of analgesia were evaluated by traditional monitoring; the consciousness index IoCl combined the injury sensitive index IoC2 group (IoC group) IoC1 and IoC2 were used to guide by the depth of sedation and the intensity of analgesia. Mean arterial pressure (MAP) and heart rate (HR) were recorded. The incidence of the HR and MAP fluctuations≥ ±20% of the baseline, the dosage of propofol, the dosage of remifentanyl and neonatal apgar score, anesthesia time, wake up time of the two groups were compared. Postoperative pain scores, nausea, vomiting, and intraoperative awareness were compared. Results Compared with the T0 time point, HR and MAP were significantly decreased in the two groups at time point T1, HR and MAP in the C group were significantly increased at the time points T2 and T3, and significantly decreased at the end of the operation (T4) (P < 0.05). HR and MAP in IoC group increased significantly only at the time point T2. Compared with C group, propofol dosage, remifentanil dosage and the recovery time in the IoC group were significantly reduced, and the incidence of HR and MAP fluctuations beyond 20% of the baseline, postoperative nausea and vomiting were significantly reduced (P< 0.05). Conclusions During the general anesthesia for cesarean section, the IoCl and IoC2 can reflect the level of consciousness and degree of analgesia well. It can monitor the depth of anesthesia and guide the perioperative anesthesia better, shorten the recovery time of anesthesia, make hemodynamics more stable, reduce postoperative complications, and improve the quality of obstetric anesthesia.
    A congenital generalized lipodystrophy patient complicated with critical central neurological involvement due BSCL2 mutations
    2021, 41(9):  1333-1337. 
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    Objective To retrospectively analyze the clinical data of a patient with congenital generalized lipodystrophy (CGL) type 2 caused by BSCL2 mutation. Methods The clinical data of a patient with CGL was analyzed, including clinical features, laboratory data. The next generation sequencing was adopted to inspect gene mutations associated with CGL. Sanger sequencing was used to verify the pathogenic mutations. Treatment and follow-up were given to the patient. Results A 5-year-8-month old boy diagnosed with CGL manifested as lacking of subcutaneous fat,hepatomegaly,acanthosis nigricans,developmental retardation, epilepsy, ataxia and neurodegeneration. The levels of serum liver enzyme, triglyceride and fasting insulin increased. Multiple types of seizures were detected by EEG. The second generation gene sequencing revealed homozygous mutations of BSCL2 gene, c.782dupG inherited from his parents respectively. Treatment including diet control, metformin and lamotrigine did not work well, and neurologic function deteriorated gradually. Conclusions CGL2 may have serious nervous degeneration besides typical lipodystrophy, which may be lethal.
    Discussion on development strategy and progress of mesenchymal stem cell products from pharmaceutical perspective
    2021, 41(9):  1338-1341. 
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    The management of stem cell products have been transformed into the drug mode, whose research and development will benefit from traditional pharmaceutical ideas. Taking mesenchymal stem cell products as an example, this paper discusses the problems restricting the development of stem cell products from the perspectives of various pharmaceutical disciplines, such as medicinal chemistry, pharmaceutics, pharmaceutical analysis and pharmacokinetics, so as to provide a new perspective for the development of stem cell products in the future.
    Research progress on molecular mechanism of the interaction between autophagy and apoptosis
    2021, 41(9):  1342-1346. 
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    Autophagy and apoptosis are two different physiological phenomena, but they are closely related in function and this paper mainly introduces the classification and process of autophagy and apoptosis, and discusses the influence of some key regulatory proteins in the formation of autophagosome and the dual role of apoptosis and anti apoptosis proteins on autophagy and apoptosis, so as to explore the relationship between autophagy and apoptosis, and to provide theoretical basis for further study of autophagy and apoptosis related diseases.
    Research progress on the role of N6-methyladenosine (m6A) RNA modification in reproductive system diseases
    2021, 41(9):  1347-1351. 
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    N6-methyladenosine (m6A) RNA modification is a post-transcriptional modification occurring on the 6th N atom of RNA adenine (A), regulating the structure, stability, splicing, output, translation and decay of mRNA, and thus extensively affecting the life processes of various organisms.This paper summarized the role and mechanism of various m6A methylase in the occurrence and development of reproductive system diseases, aiming to provide new basis for early diagnosis, treatment and prognosis of reproductive system diseases.
    Research progress on the role of TRIB3 in obesity pathogenesis
    2021, 41(9):  1352-1355. 
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    Tribbles homolog 3 (TRIB3,TRB3) is a kind of protein kinase inhibitors involved in a variety of biological processes including apoptosis, stress response, transcription and transcriptional regulation. Obesity is a chronic metabolic disease caused by many factors, including lifestyle, endocrine and drug factors. Abnormal expression of TRIB3 in vivo may be involved in the development of obesity, with expansion of adipose tissue and visceral fat leading to metabolic disorders, organ dysfunction, male infertility, various chronic diseases, and increased mortality. Therefore, exploring the mechanism of Trib3 in obesity is beneficial to provide new ideas for the diagnosis and treatment of obesity.
    Body donation in China: yesterday, today and tomorrow
    2021, 41(9):  1356-1359. 
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    Anatomical dissection course relies much on cadavers. Body donation is the primary source of cadavers used in anatomical dissection course in China. Since the 1970s, body donation programs have been gradually established, supporting the anatomical dissection courses and the cultivation of medical students. This article reviews the development of body donation programs in China and relevant researches from the following five aspects: very early stage, ethics and laws, data collection and questionnaire survey, humanistic care and humanistic education, and problems and countermeasures. This article may pave the way for further development of body donation programs in China and relevant researches in the future.
    Research progress of clinical effects of anti-Ro52/TRIM21 antibody in connective tissue diseases
    Tingting YAN Jing XUE
    2021, 41(9):  1360-1365. 
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    Anti-Ro52 autoantibody, also known as Anti-TRIM21 autoantibody, is one of the widespread autoantibody in connective tissue diseases. It was first detected in the patients of Sj?gren's syndrome, which has long been considered as an unknown component of anti-SS/Ro autoantibodies. With the development of molecular biology technology, antibodies against Ro52 are considered as an independent autoantibodies. However, there is still some uncertainty about the clinical applications. Recent studies have found that various connective tissue diseases can be positive for anti-Ro52 antibodies alone or in combination with other ones, leading to clinical manifestations or prognosis heterogeneity.
    Acromegaly and hypertension
    Shu-Chang WANG Hui-Juan 无ZHU, Hui PAN
    2021, 41(9):  1366-1370. 
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    Acromegaly is usually caused by pituitary adenomas that secrete growth hormone (GH). The disease is prone to complications of hypertension, which aggravates the state of the illness and increase the burden of disease. This paper aims to summarize the prevalence, clinical characteristics, pathophysiological mechanism, diagnosis and treatment of hypertension in patients with acromegaly and the influence of the disease control of acromegaly on hypertension in order to deepen the understanding of the disease and provide evidence for good prevention and control of hypertension in patients with acromegaly.
    Evaluation of precision teaching based on APP for online self-learning in joint diagnostic ultrasound
    2021, 41(9):  1371-1375. 
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    Objective To evaluate the use of online self-learning APP for precision education in joint ultrasound. Methods 12 sonographers were placed into three groups (4 per group) based on their experience in ultrasound diagnosis. At first, all of them were approached to the training courses in self-learning app to study "the joint ultrasound scoring system". After that, they were admitted to “the ultrasound images assessment platform” in-app to perform the ultrasound score on 140 small joints with inflammatory rheumatic diseases. The overall agreement rates (%) and ICC values were calculated to analyze the assessment results among the three groups (%/ICC). A questionnaire survey was also administered at the end of the study via the app to determine the ease of use of self-learning app. Results A good interobserver agreement was reached among the three groups (65.2%~67.7%/0.49~0.97). In detail, the best interobserver results were found for the detection of PDUS synovitis (74.40%~81.70%/0.91~0.94) and tenosynovitis/paratenonitis in all joints (87.50%~93.80%/0.97~0.98). Good ICC values was found for the detection of GSUS synovitis, but the agreement rates in this region were poor (45.10%~47.80%/0.58~0.74). For the presence or absence of erosions, moderate agreement rate was calculated, however, the ICC values among the three groups were poor (66.70%~77.80%/0.44~0.58). Regarding agreements in the finger joint regions, lower agreement results were found in both of MCP3 (61.1%~71.3%) and PIP2/3 joints (57.4%~63.9%), and a variable agreement rates were found for wrist joints (64%~80%). The majority of survey respondents indicated favorable receptivity to the online self-learning app (75%) including finding it helpful to improve the learning efficiency and interests (91.7%). Furthermore, a more accurate definitions about the joint ultrasound score, standardization of image acquisition and adequate dynamic ultrasonography were advised to further improve interobserver agreements. Conclusions The online self-learning APP can be used as an effective tool in joint ultrasound training. And the detailed analysis of the assessment results based on the feedback from the students can help to further optimize and improve the teaching process to realize the precision education in joint ultrasound.
    Innovation examples of electrocardiograph teaching mode in the time of big data
    2021, 41(9):  1376-1378. 
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    The development of a platform of clinical electrocardiograph (ECG) big data and diversified internet teaching resources brings opportunities to explore the innovation of electrocardiograph (ECG) teaching mode under large amount of data. By analyzing current problems of traditional ECG teaching, this article puts forward three examples of ECG teaching innovation with ECG mass data platform: sequential teaching combined with theory and practical teaching, heuristic teaching based on ECG vector theory and self-directed learning, and expounds their implementation strategies.
    Methods innovation in courses with ideological-political elements for master postgraduates of basic medicine
    2021, 41(9):  1379-1382. 
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    This paper reporrs the organization and implementation of courses with ideological-political elements for postgraduates by means of questionnaires and interviews, and puts forward suggestions on improving the quality and efficiency of ideological and political courses, enhancing teachers' awareness of ideological and political education and capabilities, establishing a curriculum reform system of ideological and political education, and paying attention to the synergistic effect between ideological and political education and the relevant courses, so as to provide reference for the revision of syllabus , curriculum standards and curriculum remodeling of ideological-political courses.
    Application of objective structured clinical examination (OSCE) in the assessment of anesthetic residents
    2021, 41(9):  1383-1386. 
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    Objective To set up methods for objective structured clinical examination (OSCE) for its application in assessment for clinical competencies of residents in standardized training for anesthesiology. Methods Designed OSCE assessment stations, including writing-up medical records, training standardized patients, as well as working-out forms for assessment scoring. All third-year residents attended the OSCE examination in 2018 and 2019. At the end of the exams, the residents' performance was evaluated according to the preset score forms. Results Six stations were set up for OSCE, including oral examination, endotracheal intubation, spinal anesthesia, deep vein catheterization, cardiopulmonary resuscitation and preoperative interview, the OSCE exam lasted for 70 minutes. Totally 44 residents took part in OSCE and all passed examination. Compared with the results of oral exam, clinical skills and preoperative interview, the results showed that the score of clinical skills was significantly higher than that of oral exam and preoperative interview (P < 0.01), the score of oral exam was significantly lower than that of preoperative interview station (P < 0.01). There were moderate positive correlations between oral exam and clinical skill, clinical skill and preoperative interview, and between oral exam and preoperative interview. Conclusion Clinical competencies of anesthetic residents can be assessed by OSCE in multiple aspects, which provides an effective examination method for residents training in anesthesiology.
    Evaluation of Scientific Research Competencies of ultrasound residents from different grades or different education backgrounds
    2021, 41(9):  1387-1391. 
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    Objective This study analyzed the ultrasound residents’ scientific research competencies, in order to provide basis for training program of scientific research abilities, and improve their scientific research competencies. Methods This study conducted a self-reported questionnaire on the ultrasound residents in Peking union medical college hospital, in order to investigate their scientific research competencies, based on different grades or study backgrounds. Results The result showed that there are differences between the residents from different grades or study backgrounds in terms of scientific research competencies. The ranking of average scores of residents from different grades are,from high to low, the third year, the first year and second year (256 ± 48, 231 ± 28, 214±48). And the ranking of average scores of residents from different study backgrounds are, from high to low, clinical post-doctoral fellows, graduate students, and standardized training residents (294 ± 18, 236 ±33, 214 ± 42). For the results of detailed research abilities, all residents are lack of the abilities of scientific research design and fund writing, paper writing, and learning scientific research knowledge through reading. Conclusions It is suggested that hospitals need to provide hierarchical guidance to residents in order to improve their scientific research competencies to meet the requirement of model medical science.
    Comparison and enlightenment of higher medical education between China and the United States
    2021, 41(9):  1392-1395. 
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    This paper compared the curriculum systems of the Harvard Medical School, The Ohio State University School of Medicine, Peking Union Medical College and Zhejiang University School of Medicine, analyzed the characteristics of different medical education modes, and summarized the direction of medical education reformation. The author hopes that through the introducing the reform experience of each category, this paper may provide a reference for the reformation of high medical education in China.
    Human anatomy combined with physical examination: a survey on the course reform
    2021, 41(9):  1396-1402. 
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    Objective To investigate the attitude of 8-year-program clinical medical students in Peking Union Medical College (PUMC) towards current anatomy course and their perspective on introducing physical examination into anatomy course, and to raise feasible reform strategy. Methods Survey on Wechat through wjx questionnaires was performed among 4th, 5th, 6th, 7th, 8th grade students in PUMC. Results 216 qualified questionnaires were collected. 207 (95.8%) and 196 (90.7%) students identified with the importance of anatomy course and agreed to introduce physical examination into anatomy course, respectively. Two major problems were considered existing in current anatomy course, the lack of feasible ways to review in later stage (149, 69.0%) and poor connection between anatomy and clinical courses leading to poor retention of the knowledge (143, 66.2%). 65 (30.1%) preferred online course and 151 (69.9%) preferred traditional offline course to offer the new course. Conclusions Most clinical medical students in different learning stage in PUMC approved to introduce physical examination into anatomy course. Related educational reform of anatomy course is necessary. The new course should be offered mainly in traditional offline way, combined with online content.