Table of Content

05 January 2025, Volume 45 Issue 1

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Original Articles

Heat-induced denaturation of cataract-related human γD-crystallin

ZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan

2025, 45(1):  1-6.  doi:10.16352/j.issn.1001-6325.2025.01.0001

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Objective To reveal the thermally induced denaturation of wild-type human γD-crystallin(HGD) and congenital cataract-related mutant (HGD P23T), and compare the differences in the structural changes between wild-type and mutants during a heating process. Methods HGD and HGD P23T were expressed and purified. The temperature-dependent intrinsic fluorescence intensity and static light scattering intensity of the protein samples were measured to reveal the temperature-dependent folding and aggregation structural changes of HGD and HGD P23T. Results When the temperature was below 70 ℃, the barycentric mean of the intrinsic fluorescence of HGD and HGD P23T shifted towards a longer wavelength with increasing temperature and the fluorescence intensity decreased indicating the unfolded protein conformations. The conformational stability of HGD P23T was weaker than that of HGD. When temperature was higher than 70 ℃, the static light scattering intensity increased significantly with temperature, indicating protein aggregation upon heating. Relative to the wild-type,HGD P23T showed a stronger aggregation potency. Conclusions Heating disrupts the folding conformation of γD-crystallin, induces the unfolded protein to aggregate. The disease-associated P23T mutation significantly reduces the conformational stability of γD-crystallin.

Melatonin promotes anoikis of mouse melanoma cell line B16-F10

GAN Yuling, LI Tingdong, LIU Libing, ZHOU Yingfen, PAN Dongsheng

2025, 45(1):  7-11.  doi:10.16352/j.issn.1001-6325.2025.01.0007

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Objective To investigate the effect and mechanism of melatonin on the anoikis of melanoma cells. Methods The drug concentration of melatonin inhibiting melanoma cell line B16-F10 was optimized based on the effect on CCK-8 assay. An anti-anoikis of melanoma cell model was developed and divided it into four groups: The blank control group, the TrkB activator group, the melatonin group and the melatonin +TrkB activator group. Calcein AM/EthD-1 fluorescence double staining was used to detect the anoikis of melanoma cells. Reactive oxygen species were detected using the fluorescent probe DCFH-DA. Western blot was used to detect the expression of Nrf2 protein and TrkB protein in each group. Results Melatonin significantly inhibited the proliferation of melanoma cells in a time-and dose-dependent manner with IC₅₀ of 1×10^-7 μmol/L. Its inhibitory effect was found to be related to induction of anoikis of melanoma cells. Melatonin could upregulate the generation of cellular reactive oxygen species(P＜0.05), while addition of TrkB activator antagonized this effect. Melatonin could reduce the expression of Nrf2 protein and TrkB protein in melanoma cells(P＜0.05), and the addition of TrkB activator could inhibite the effect of melatonin on the expression of Nrf2 protein and TrkB protein(P＜0.05). Conclusions Melatonin can inhibit the proliferation of melanoma cell line B16-F10 through the mechanism of inducing anoikis.

Impact of oxygen concentration changes on ANGPTL8 expression of human pulmonary artery endothelial cells

ZHANG Zongli, LI Tao, MA Jingwen, ZHANG Jiaxin, LI Xingchao, XI Shibing

2025, 45(1):  12-19.  doi:10.16352/j.issn.1001-6325.2025.01.0012

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Objective To explore the impact of change in oxygen concentration on the expression of angiopoietin-like protein 8 (ANGPTL8) by endothelial cells (HPAECs) of human pulmonary artery, and the role and mechanism of ANGPTL8 in pulmonary hypertension (PH). Methods HPAECs were treated under hypoxic and hyperoxic conditions, and the expression level of ANGPTL8 was detected using Western blot and PCR. The changes in endothelial-mesenchymal transition (EndMT) and ERK signaling pathway activity were analyzed. Simultaneously, newborn rats were exposed to hyperoxia to develop a bronchopulmonary dysplasia (BPD) model. The expression of ANGPTL8 protein and changes in the ERK signaling pathway in lung tissue were observed. Results Under hypoxic condition, the protein expression of ANGPTL8 in HPAECs was significantly increased accompanied by inhibition of the ERK signaling pathway. ANGPTL8 promoted the EndMT process induced by hypoxia(P＜0.05) and silencing the expression of ANGPTL8 resulted in a partial reversal of EndMT. The protein expression of ANGPTL8 was decreased in hyperoxia-exposed HPAECs and rat lung tissues accompanied by the activation of the ERK signaling pathway(P＜0.05). Conclusions ANGPTL8 is highly sensitive to the change of oxygen concentration in HPAECs and closely correlated to its expression level and to the activity of ERK signaling pathway. This result suggests that ANGPTL8 may have potential regulatory effects on the development of PH.

Down-regulation of CD151 combined with bevacizumab inhibits the growth and microvessel density of colorectal cancer

LIU Yancai, LIU Xuegang, ZHANG Zhenya

2025, 45(1):  20-24.  doi:10.16352/j.issn.1001-6325.2025.01.0020

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Objective To investigate the effects of CD151 down-regulation combined with bevacizumab on colorectal cancer growth and microvessel density. Methods Human colorectal cancer cell line HT-29 and CD151^--HT-29 cells strain(CD151 down-regulated HT-29 cells) were treated with bevacizumab. The cells were divided into four groups: control (HT-29) group, bevacizumab-treatment group, CD151^--HT-29 group, and CD151^--HT-29 + bevacizumab-treatment group. Cell proliferation was observed in each group using the MTS assay. A subcutaneous xenograft model in nude mice was established, and the HT-29 control group and CD151^--HT-29 group were treated with either 0.9% NaCl solution or bevacizumab. The growth of subcutaneous tumors in the four groups was observed, and the volume and weight of the tumors were recorded. Tumor tissues were collected for immunohistochemical staining of endothelial cells to assess microvessel density (MVD). Results Compared with the control group, cell proliferation was significantly reduced in the bevacizumab-treated group and CD151^--HT-29 group(P＜0.001). Cell proliferation in the CD151^--HT-29 + bevacizumab-treated group was slower than that in the single treatment groups (P＜0.001). In the subcutaneous tumor model, the volume, weight, and MVD of tumors in the bevacizumab-treated and CD151^--HT-29 groups were significantly reduced compared to the control group(P＜0.01). In the CD151^--HT-29 + bevacizumab group, the tumor volume, weight, and CD34 expression were significantly lower than in the single treatment groups (P＜0.01). Conclusions CD151 protein may play a role in the regulation of angiogenesis in colorectal cancer tissues and may have a synergistic effect with bevacizumab in inhibiting microvessel formation in tumor tissues.

Total paeony glycoside alleviates brain injury of rat models developed by cerebral ischemia-reperfusion

PENG Yingjuan, LI Zhiying, SUN Linlin, YANG Huijie, WANG Tiantian, ZHOU Liping

2025, 45(1):  25-30.  doi:10.16352/j.issn.1001-6325.2025.01.0025

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Objective To investigate the effect of total paeony glycoside (TPG) on cerebral ischemia-reperfusion injury (CI/RI) of rats. Methods The rats were randomly divided into sham surgery (sham) group, CI/RI model group (simple CI/RI group), positive control group (nimodipine group, 5 mg/kg), low-dose TPG group (TPG-L group, 27 mg/kg), a high-dose TPG group (TPG-H group, 54 mg/kg)and a high-dose TPG+NOD-like receptor thermal protein domain associated protein 3 (NLRP3) activator diethyl dithiocarbamate (DDC) group (TPG-H+DDC group, 54 mg/kg TPG and 30 mg/kg DDC), with 18 rats in each, administered once a day for 7 consecutive days. After the administration, the neurological deficit score of the rats was evaluated. Nissl staining microscopy was applied to observe neuronal activity in brain tissue. 2,3,5-triphenyltetrazolium chloride (TTC) staining microscopy was applied to detect the area of cerebral infarction in rats. The level of interleukin-1β and IL-18 in brain tissue was measured by ELISA method. Western blot was applied to detect the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2X7R)/NLRP3 signaling pathway related proteins and pyroptosis related proteins such as apoptosis associated speck like protein containing a CARD (ASC) and cysteine protease 1 (caspase-1) proteins in brain tissue. Results Compared with the sham group, the neurological deficit score, infarct area, level of IL-1β and IL-18 in brain tissue and protein expression of P2X7R, NLRP3, ASC, and caspase-1 in brain tissue of rats in the simple CI/RI group were significantly increased (P＜0.05), while the proportion of Nissl body positive cells in brain tissue was significantly reduced (P＜0.05). The change in corresponding indicators of rats in the nimodipine group, TPG-L group, and TPG-H group was opposite to those in the simple CI/RI group (P＜0.05). NLRP3 activator DDC antagonized the inhibitory effect of TPG on cell pyroptosis in CI/RI rats. Conclusions TPG may inhibit brain injury in CI/RI rats by down-regulating the P2X7R/NLRP3 pathway.

Usnea acid inhibits the proliferation of human ovarian cancer cell line

SHEN Hongmei, YU Yan, FENG Xuqiang, WANG Keqiang

2025, 45(1):  31-37.  doi:10.16352/j.issn.1001-6325.2025.01.0031

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Objective To investigate the impacts of usnea acid (UA) on the proliferation of human ovarian cancer (OC) cells. Methods Ovarian adenocarcinoma cells SKOV3 were randomly divided into control group, L-UA group, M-UA group, H-UA group (with 10, 20, and 50 μmol/L UA added respectively), pcDNA3.1-NC group and pcDNA3.1-PD-1 group. RT-qPCR method was applied to detect the expression of programmed cell death 1(PD-1) and programmed cell death ligand 1(PD-L1) in SKOV3 cells. CCK-8 assay and plate method were applied to detect the effect of UA on SKOV3 cell proliferation. The effect of UA on SKOV3 cells apoptosis was examined by flow cytometry. Mouse ovarian epithelial cancer cell line ID8 cells were collected to construct an OC mouse model, and the mass and volume of OC tumors were recorded. Immuno-histochemical microscopy was applied to detect the infiltration of PD-1, PD-L1, and CD8⁺T cells. Results The PD-1 mRNA, PD-L1 mRNA, colony count, A₄₅₀ value, PCNA protein, PD-1 protein, and PD-L1 protein in the L-UA, M-UA, and H-UA groups were lower than those in the control group, the apoptosis rate and Bax protein were higher in the control group (P＜0.05). Compared with the H-UA group and the pcDNA3.1-NC group, the PD-1 mRNA, PD-L1 mRNA, colony count, A₄₅₀ value, PCNA protein, PD-1 protein, and PD-L1 protein in the pcDNA-3.1-PD-1 group increased and the apoptosis rate and Bax protein decreased (P＜0.05). The quality, volume, positivity rate of PD-1and PD-L1 of OC tumors in the UA group was lower than that in the control group, the counting number of CD8⁺T cell infiltration was higher than control group (P＜0.05). Conclusions UA may inhibit progression of OC cell line SKOV3 by regulating cell proliferation, apoptosis, and immune escape.

Effects of curcumin on the proliferation and invasiveness of pheochromocytoma cell line PC12

ZHANG Wenqian, ZHOU Yue, REN Weidong, TONG Anli

2025, 45(1):  38-43.  doi:10.16352/j.issn.1001-6325.2025.01.0038

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Objective To investigate the effects of curcumin on the proliferation, migration, invasion, and apoptosis of pheochromocytomacell line PC12. Methods PC12 cells were incubated with different concentrations of curcumin. Cell proliferation was assessed using the CCK-8 assay to determine the IC₅₀. The scratch assay was used to evaluate cell migration and Transwell chambers were employed to assess cell invasiveness. Flow cytometry was used to analyze apoptosis. qPCR was conducted to measure the mRNA expression of pro-apoptotic (Bax) and anti- apoptotic (Bcl-2) genes, and Western blot was performed to detect Bax and Bcl-2 protein expressions. Results Curcumin(10-80 μmol/L) inhibited PC12 cell proliferation in a concentration-dependent manner, with an IC₅₀ as 29 μmol/L. Curcumin also suppressed PC12 cell migration in a concentration-dependent mode; the migration rate decreased from 66% in the control group down to 51%, 5%, and 0.5% in the 10, 20, and 30 μmol/L curcumin groups, respectively. Curcumin at concentrations of 20-30 μmol/L significantly reduced PC12 cell invasiveness(P＜0.000 1). Moreover, curcumin significantly promoted PC12 cell apoptosis; the percentage of apoptotic cells increased by 2.25%, 18.53%, and 26.89% in the 10, 20, and 30 μmol/L curcumin groups as compared to those of control group, respectively. Curcumin treatment resulted in a significant up-regulation of Bax mRNA and protein expression, and a significant down-regulation of Bcl-2 mRNA and protein expression(P＜0.05). Conclusions Curcumin may significantly inhibit the proliferation, migration, and invasion of PC12 cells and arouse cell apoptosis. Its pro-apoptotic effect may be associated with alterations in the expression of Bax and Bcl-2 genes.

Injectable hydrogel loaded with bone marrow- mesenchymal stem cells promotes the repair of cartilage defect

LIU Deguo, CHEN Hong, ZHANG Jiehong, ZHENG Yuxiang, LIU Zhengang, CHEN Xuanchen, HOU Zhenhai

2025, 45(1):  44-50.  doi:10.16352/j.issn.1001-6325.2025.01.0044

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Objective To construct an injectable hydrogel (IH) entrapment system of bone marrow mesenchymal stem cells(BM-MSCs) and to explore its effect of promoting articular cartilage repair and underlying mechanism . Methods The primary BM-MSCs of mice were cultured by whole bone marrow adherent method. The differentiation potential was identified by alizarin red (ARS), oil red O (ORO) and Alcian blue (AB) staining, and the expression of CD44, CD90, CD105, CD34 and CD45 on the surface was detected by flow cytometry. BM-MSCs loaded with IH(BM-MSC-IH) was prepared, and the rheological properties of BM-MSC-IH were tested by rheological test. The model of full-thickness injury of knee cartilage in mice was established, and the mice were randomly divided into normal saline group ,BM-MSC group and BM-MSC-IH group with 8 in each. The mice were injected with BM-MSC-IH 0.2 mL, cell suspension 0.2 mL and 0.9% NaCl solidion, independently. After 6 and 12 weeks of injection, the repair of knee cartilage in mice was observed by safranin-fast green staining, and the expression of type Ⅱ collagen in knee joint was examined by immunohistochemical staining microscopy. Results The primary cultured cells showed positive expression of CD44, CD90 and CD105, but negative expression of CD34 and CD45, and had the potential of osteogenic, adipogenic and chondrogenic differentiation. The constructed BM-MSC-IH system was solid colloid, and the rheological properties were consistent with the basic characteristics of hydrogel. BM-MSC-IH effectively promoted the regeneration of mouse knee cartilage and increase the local expression of type Ⅱ collagen. Conclusions Bone marrow-mesenchymal stem cells embedded with injectable hydrogel effectively promote the repair of injured cartilage and the underlying mechanism is potentially promoting the differentiation of chondrocytes and the expression of type Ⅱ collagen. Its effect is better than application of BM-MSCs alone.

Inhibition of NRF1/ABCC1 improves chemosensitivity of human lung adenocarcinoma cell lines to cisplatin

CHEN Qingxia, LIANG Yuling, LUO Yalan, NIU Bin

2025, 45(1):  51-59.  doi:10.16352/j.issn.1001-6325.2025.01.0051

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Objective To explore the effect of nuclear respiratory factor 1(NRF1) activation of ATP binding cassette transporter C1(ABCC1) transcription on cisplatin resistance in lung adenocarcinoma cells and its potential mechanisms. Methods The expression levels of ABCC1 in lung adenocarcinoma tumor tissues were analyzed by oncogenomic datasets. Cells were grouped into: sh-NC, sh-ABCC1, sh-NC+oe-NC, sh-NRF1+oe-NC and sh-NRF1+oe-ABCC1. Real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of ABCC1 in lung adenocarcinoma cells. Cisplatin-resistant lung adenocarcinoma cell strains were constructed to detect the expression level of ABCC1. Cell proliferation, migration and invasion were assessed by colony formation and Transwell assay. The IC₅₀ values of drug-resistant lung adenocarcinoma cells treated with different doses(0, 0.001, 0.002,0.004, 0.008,0.016 and 0.032 mg/mL) of cisplatin were detected by CCK-8 assay. Western blot was used to detect the protein expression of epithelial-mesenchymal transition markers (E-cadherin, N-cadherin). Dual luciferase and ChIP assays were performed to verify the binding relationship between NRF1 and ABCC1. Results ABCC1 was highly expressed in lung adenocarcinoma tumor tissues and cells. Compared with cisplatin-sensitive lung adenocarcinoma cells, ABCC1 was highly expressed in cisplatin-resistant lung adenocarcinoma cells, and knockdown of ABCC1 significantly inhibited cell proliferation, migration and invasion, and increased the expression of E-cadherin (P＜0.05) and decreased the expression of N-cadherin (P＜0.05). Knockdown of ABCC1 significantly increased the sensitivity of lung adenocarcinoma cells to cisplatin (P＜0.05). In addition, dual luciferase and ChIP experiments confirmed the binding relationship between NRF1 and ABCC1 promoter de-binding, and NRF1 could activate the transcription of ABCC1. Knockdown of NRF1 attenuated the inhibitory effect of over-expressed ABCC1 on the proliferation, migration, invasion and cisplatin-resistance of lung adenocarcinoma cells(P＜0.05). Conclusions This study revealed the effect of the NRF1/ABCC1 axis enhancement is a potential strategy to overcome the barrier of cisplatin-resistance in chemotherapy of lung adenocarcinoma.

Small-dose esketamine combined with sufentanil reduces perioperative inflammation in elderly patients with total hip replacement

YANG Wen, LI Yong, YANG Zhuoxuan

2025, 45(1):  60-64.  doi:10.16352/j.issn.1001-6325.2025.01.0060

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Objective To analyze the impact of low-dose esketamine combined with sufentanil on peri-operative inflammation and immune function of elderly patients undergoing total hip arthroplasty (THA). Methods From January 2019 to January 2022, 120 elderly patients who underwent THA under combined spinal-epidural anesthesia and received patient-controlled intravenous analgesia (PCIA) were included. The patients were divided into a control group (analgesic drugs: sufentanil + granisetron) and an observation group (analgesic drugs: esket- amine + sufentanil+granisetron). Pain intensity was assessed using the Visual Analog Scale (VAS). Serum level of interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein (CRP) was measured by ELISA. CD4⁺ and CD8⁺ cells were detected using a CytoFLEX flow cytometer, and the CD4⁺/CD8⁺ ratio was calculated. The incidence of adverse reactions in both groups was recorded and compared. Results In resting state, the post-surgical VAS scores in the observation group patients were significantly lower than those in control group at 48 and 72 h. In the active state, the VAS scores recorded for the observation group following surgery remained notably lower than those of the control group at 24, 48, 72 h (P＜0.05). Compared with 24 h before surgery in the same group, the level of IL-6, TNF-α, and CRP in the control group significantly increased at 24, 48, and 72 h after surgery, while in the observation group, they increased at 24 and 48 h after surgery and returned to pre-operative level at 72 h (P＜0.05). The observation group exhibited significantly lower level of IL-6, TNF-αand CRP as compared to the control group over the 24, 48, 72 h following surgery(P＜0.05). Compared with 24 h before surgery in the same group, CD8⁺ (%) increased, while CD4⁺ (%) and CD4⁺/CD8⁺ decreased in the observation group at 24, 48, and 72 h after surgery. However, 72 h after surgery, these values returned to the level before operation. Twenty four, 48, and 72 h after surgery, the observation group displayed notably elevated level of CD8⁺(%), CD4⁺(%) and CD4⁺/CD8⁺ as compared to the control group(P＜0.05). No significant variation in the occurrence of adverse reactions was observed between the two groups. Conclusions Low-dose esketamine combined with sufentanil can reduce peri-operative inflammation in elderly patients undergoing THA with minimal impact on immune function.

Levosimendan attenuates suspension-reperfusion injury in isolated hearts of rat models

PANG Yunting, REN Xiaoshuang, BAO Han, MENG Fanqing, SHI Feng

2025, 45(1):  65-69.  doi:10.16352/j.issn.1001-6325.2025.01.0065

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Objective To investigate the effect of levosimendan on the cyclic guanosine monophosphate-adenosin monophosphate synthase-interferon gene stimulating factor (cGAS-STING) signaling pathway during suspension-reperfusion in isolated rat myocardium. Methods The rats were divided into four groups (n=12) using random number table: continuous perfusion group (CO group),suspension-reperfusion group(SR group),suspension-reperfusion+levosimendan group (SR-L group), and suspension-reperfusion+levosimendan+STING activator: DMXAA group (SR-LD group). Heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), maximum rate of increase in left ventricular pressure (+dp/dt_max) and maximum rate of decrease in left ventricular pressure (-dp/dtmax), and Reperfusion Arrhythmia scores were recorded at the end of equilibrium perfusion (T0), 30 min of reperfusion (T1), and 60 min of reperfusion (T2) respectively. Western blot was used to detect cGAS-STING signaling pathway and autophagy-related protein expression. The size of myocardial infarction was measured by using triphenyl tetrazolium chloride (TTC). Results Compared with CO group, SR group had decreased HR, LVDP, +dp/dt_max, and -dp/dt_max at T1 and T2, increase of LVEDP,Reperfusion Arrhythmia score , percentage of myocardial infarcted area, expression of myocardial tissue cGAS and STING proteins and increased LC3 Ⅱ/Ⅰ ratio, while p62 decreased (P＜0.05); compared with SR group, SR-L group cardiac function indexes improved, myocardial tissue cGAS, STING protein expression was down-regulated, LC3 Ⅱ/Ⅰ ratio was decreased, and p62 was elevated (P＜0.05); SR-LD group reversed the improvement of myocardial injury by levosimendan compared with SR-L. Conclusions Levosimendan may protect myocardial tissue by inhibiting the cGAS-STING signaling pathway, down-regulating cardiomyocyte autophagy and reducing myocardial infarction size, so to improve cardial function.

Sevoflurane reversiblely down-regulates BMAL1 expression of myocardium clock gene of diabetes rat models

LIU Hui, HAN Chongfang, QIN Xiaoying, YU Jing, HE Jiandong, YANG Wenqu

2025, 45(1):  70-75.  doi:10.16352/j.issn.1001-6325.2025.01.0070

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Objective To observe the effect of sevoflurane(SEV) on the expression of myocardial biological clock gene aromatic hydrocarbon receptor nuclear transport-like protein 1(BMAL1) in diabetic rats and to explore its changes. Methods Sixty healthy male SD rats with a body mass of 200-250 g were divided into oxygen inhalation group (NC) and sevoflurane inhalation group (SEV). The diabetic model was routinely replicated, and the model was divided into oxygen group (DM) and sevoflurane group (DM+SEV) with an inhalation time of 5 h(n=15). Four groups of experimental animals were executed at 0, 12 and 24 h after the anesthesia was stopped and then myocardial tissue was isolated. Western blot was used to determine the expression level of biological clock gene BMAL1 protein and its activation enzyme USP9X; HE staining microspy to observe the pathological changes of myocardial tissue and immuno-fluorescence co-localization to observe the relationship between USP9X and BMAL1. Results At 0 and 12 h after stopping anesthesia, the expression of BMAL1 and USP9X in the DM+SEV group was significantly down-regulated as compared with the DM group, and the expression of BMAL1 and USP9X in the DM+SEV group was significantly down-regulated(P＜0.05) at 24 h after stopping anesthesia (P＞0.05). HE staining microscopy found changes of myocardial tissue structure in the DM+SEV group at 0 and 12 hrs after stopping anesthesia. This change was most significant at 0 h after stopping anesthesia, but the myocardial tissue structure was neatly arranged at 24 h. The results of immuno-fluorescence colocalization showed that USP9X and BMAL1 proteins were mainly distributed in the cytoplasm of cardio-myocardium with and overlapping parts between them. Under the influence of sevoflurane, there was less overlap between the two at 0 and 12 hrs after stopping anesthesia and more overlap between the two at 24 h, which was close to that of the DM group. Conclusions Sevoflurane reversibly changes the expression of myocardial circadian clock gene BMAL1 in diabetic rats and this change still existe for 12 h after stopping anesthesia, then significantly fade away 24 hrs after stopping anesthesia.

Clinical Sciences

Clinical value of serum levels of MC-CP, CCL26 and DcR3 in the diagnosis of COPD complicated with OSAS

CHEN Liping, SHI Yongxing, CHEN Yanhong, FENG Ping, ZHANG Changhong, LIN Weijia, XIANG Baoli

2025, 45(1):  76-80.  doi:10.16352/j.issn.1001-6325.2025.01.0076

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Objective To investigate the clinical value of serum mast cell carboxypeptidase (MC-CP), C-C motif chemokine 26 (CCL26), and decoy receptor 3 (DcR3) in the diagnosis of obstructive sleep apnea syndrome (OSAS) in chronic obstructive pulmonary disease (COPD). Methods Ninety COPD patients who visited the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were collected. Among them, 48 patients with simple COPD were included in the COPD group, and 42 patients with COPD combined with OSAS were included in the COPD-OSAS group. During the same period, 48 healthy volunteers who underwent physical examination in that Hospital of Hebei North collected as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to detect serum level of MC-CP, CCL26, and DcR3. Receiver operating characteristic (ROC) curve was applied to analyze the clinical value of serum level of MC-CP, CCL26, and DcR3 in the diagnosis of COPD complicated with OSAS. Multivariate Logistic regression was applied to analyze the influencing factors of COPD complicated with OSAS. Results Compared with the control group, the smoking index, C-reactive protein (CRP)and white blood cell count (WBC) in the COPD and COPD-OSAS groups increased obviously in sequence, the ratio of forced expiratory volume in first second to forced vital capacity (FEV1/FVC) decreased obviously in sequence (P＜0.05); Compared with the control group, the level of MC-CP, CCL26, and DcR3 in patients with COPD and COPD-OSAS increased significantly in sequence (P＜0.05); The combination of serum MC-CP, CCL26 and DcR3 had a higher area under the curve(AUC) for the diagnosis of COPD complicated with OSAS compared to the individual diagnosis (Z=4.066, P＜0.001; Z=2.391, P＜0.05; Z=2.353, P＜0.05). Multivariate Logistic regression analysis showed that smoking index, serum level of MC-CP, CCL26 and DcR3 were influencing factors for COPD complicated with OSAS (P＜0.05). Conclusions The simultaneously increased expression of MC-CP, CCL26 and DcR3 in the serum of COPD may support clinical diagnostic of COPD patients with OSAS.

Effect of tactile vibration feedback training combined with 1 Hz repetitive transcranial magnetic stimulation on stroke patients with hemiplegia

LI Bo, LIU Libin, LI Ying, LIU Jing, ZHAO Liuzhuang

2025, 45(1):  81-85.  doi:10.16352/j.issn.1001-6325.2025.01.0081

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Objective To analyze the effects of tactile vibration feedback training combined with 1 Hz repetitive transcranial magnetic stimulation on limb balance and walking ability of stroke patients with hemiplegia. Methods From August 2021 to August 2023, 98 patients with stroke and hemiplegia who were diagnosed and treated in Daxing District People's Hospital were selected and divided into training group and stimulation group according to different treatment schemes with 49 in each. The training group was given tactile vibration feedback training, and the stimulation group was given tactile vibration feedback training combined with 1 Hz repetitive trans-cranial magnetic stimulation. The clinical symptoms, ability of keeping balance and walk, life situation and curative effect of the two groups were analyzed. Results After 8 weeks of treatment, the scores of mouth and drooling points, language impairment points, and hemiparalysis points in the two groups were all lower than those before treatment (P＜0.05), and the above indexes in the stimulation group were even lower than those in the training group (P＜0.05). After 8 weeks of treatment, the scores of Lindmark Balance Reaction, Berg Balance scale (BBS), stride length, 10-meters maximum walking speed(10 mMWS), Barthel index(BI) and Functional Independence Measure(FIM) in both groups were higher than those before treatment (P＜0.05), and the above indexes in the stimulation group were higher than those in the training group(P＜0.05). After 8 weeks of treatment, the total effective rate in the stimulation group (91.84%) was higher than that in the training group (69.39%)(P＜0.05). Conclusions Tactile vibration feedback training plus 1 Hz repetitive trans-cranial magnetic stimulation can significantly alleviate the clinical symptoms of stroke patients with hemiplegia and can improve their ability of keeping balance, walking and management of daily life.

Elevated levels of serum PKM2, Gal-3 and CitH3 could predict pulmonary infection complicated by mechanical ventilation

HUANG Hangdong, LI Danyu, ZHU Xiaofeng

2025, 45(1):  86-90.  doi:10.16352/j.issn.1001-6325.2025.01.0086

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Objective To investigate the relationship between serum level of pyruvate kinase M2 (PKM2), galectin-3(Gal-3) and citrolinated histone H3 (CitH3) and pulmonary infection in patients with mechanical ventilation (MV). Methods A total of 120 patients with MV admitted to Jinhua Central Hospital from October 2022 to March 2024 were included in the study. They were divided into pulmonary infection group (n=50) and non-pulmonary infection group (n=70). Serum level of PKM2, Gal-3 and CitH3 was detected by ELISA. The patients were divided into good prognosis group (n=79) and bad prognosis group (n=41). Multivariate Logistic regression analysis was performed to analyze the factors affecting the adverse prognosis of MV patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum PKM2, Gal-3 and CitH3 for poor prognosis in patients undergoing MV. Results Compared with non-pulmonary infection group, serum level of PKM2, Gal-3 and CitH3 in pulmonary infection group was increased (P＜0.05). The level of serum PKM2, Gal-3 and CitH3 in the poor prognosis group was increased (P＜0.05). The Clinical Pulmonary Infection score (CPIS) of the poor prognosis group was higher than that of the good prognosis group (P＜0.05). PKM2, Gal-3 and CitH3 were all risk factors for poor prognosis in MV patients (P＜0.05). The area under the curve (AUC) of PKM2, Gal-3, CitH3 and combined prediction of poor prognosis were 0.712, 0.839, 0.779 and 0.925, respectively. AUC of combined diagnosis of PKM2, GAL-3, CITH3 and combined diagnosis was better than that of single detection (Z=4.261, 2.521, 3.676, P＜0.001, 0.05, 0.001). Conclusions The serum level of PKM2, Gal-3, and CitH3 in MV patients with concurrent pulmonary infections is found to be higher than those in those without pulmonary infections, so these three factors have potential predictive value for poor prognosis of MV patients.

Expression and clinical significance of miR-483-3p in serum of gestational diabetes mellitus patients

ZHANG Lina, JIA Mengtao, SUN Zeyun, ZHANG Jianjun

2025, 45(1):  91-97.  doi:10.16352/j.issn.1001-6325.2025.01.0091

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Objective To investigate the expression and clinical significance of miR-483-3p in patients with gestational diabetes mellitus (GDM). Methods A total of 100 GDM patients with 24-32 weeks of gestation who underwent routine obstetric examination in Anqiu People′s Hospital were selected as the normal glucose tolerance (NGT) group, and a total of 98 healthy pregnant women of the same age of 24-32 gestational weeks were selected as the NGT group. The expression level of miR-483-3p was detected by RT-qPCR, the diagnostic value of miR-483-3p in GDM was analyzed by receiver operating characteristic (ROC) curve, the correlation between the expression levels of miR-483-3p and clinical indicators in the GDM group was analyzed by chi-square test, and the risk factors of GDM were analyzed by Logistic regression. Dual luciferase reporter gene assay was used to verify the targeting relationship between miR-483-3p and autophagy-related protein 7(ATG7). CCK8, flow cytometry and Transwell assays were used to detect the proliferation, apoptosis, and migration and invasion ability of cells, respectively. Results The expression level of miR-483-3p in the serum of patients in the GDM group was significantly higher than that in the NGT group. The expression of miR-483-3p had diagnostic value for GDM. Pre-pregnancy BMI, FBG, FINS, HOMA-IR and TG were significantly correlated with serum miR-483-3p expression. In addition, BMI and TG before pregnancy were risk factors leading to GDM. miR-483-3p regulated HG-treated HTR-8/SVneo cell proliferation, apoptosis, migration and invasion by targeting at ATG7. Conclusions miR-483-3p is involved in the disease progression of GDM and is a potential biomarker of GDM diagnosis.

Case Reports

Sellar multiple myeloma in an elderly patient: a case report

CHEN Xiaoxue, DUAN Lian, KE Xiaoan, YANG Hongbo, PAN Hui, ZHU Huijuan, WANG Linjie

2025, 45(1):  98-101.  doi:10.16352/j.issn.1001-6325.2025.01.0098

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Objective To investigate the clinical characteristics in an elderly patient with sellar multiple myeloma. Methods Clinical features, laboratory data and radiologic profile of an elderly patient with sellar multiple myeloma were collected. Results The patient was an 85-year-old male. The main clinical manifestations were fatigue, poor appetite and polyuria. Laboratory examinations showed a significant decrease in blood sodium, several anterior pituitary hormones and an increase in total protein, mass of pituitary lesion and concentration of prolactin. During etiological screening, it was found that the blood immunoglobulin G (IgG) level was significantly increased, the blood M protein was positive and the bone marrow smear showed myeloma cells accompanied by multiple osteolytic lesions in the bones of the whole body. Considering the diagnosis of multiple myeloma, the pituitary lesion was likely to be the extra-medullary involvement. Conclusions The intrasellar plasmacytoma is not common. The disease onset is insidious with clinical features and imaging findings lacking specificity. Therefore, diagnosis relies on biopsy which poses risks for elderly patients and increases diagnostic challenges leading to misdiagnosis.

Mini Reviews

Role of collapsin response mediator proteins in optic nerve injury

ZHU Yuchun, XI Xinyuan, YANG Zhen, FENG Dongfu

2025, 45(1):  102-106.  doi:10.16352/j.issn.1001-6325.2025.01.0102

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Collapsin response mediator proteins (CRMPs), also known as dihydropyrimidine-like proteins, contain five isoforms (CRMP1, CRMP2, CRMP3, CRMP4, CRMP5). In central nervous system, CRMPs are mainly involved in a variety of physiological processes such as neuronal differentiation and migration, synaptic plasticity, neurite growth and development and guiding extension. Recent studies have found that inhibiting or reducing the phosphorylation of CRMPs can affect the survival and axonal regeneration of retinal ganglion cells (RGCs) after optic nerve injury, which may provide new ideas for the treatment of optic nerve injury in the future.

Post-translational modification of Keap1 regulates oxidative stress-related diseases

QU Ying, MAO Caiyun, ZHONG Qing, ZHANG Rong, SONG Yunjia

2025, 45(1):  107-111.  doi:10.16352/j.issn.1001-6325.2025.01.0107

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The activation of Keap1-Nrf2 signaling pathway is an important mechanism for cells to resist oxidative stress. Under oxidative stress, Keap1 is affected by post-translational modification(PTM) such as glutathione, alkylation and S-sulfhydrylation, which weakens its binding to Nrf2, leading to Nrf2 accumulation, nuclear translocation and the expression and transcription of downstream detoxification and antioxidant defense proteins. The PTM of Keap1 is involved in the regulation of a variety of oxidative stress-related diseases such as cancer, Parkinson′s disease and atherosclerosis. For example, alkylation inhibits abdominal aortic aneurysm formation, methylation promotes innate resistance of breast cancer, and S-sulfhydrylation improves atherosclerosis, which provides a theoretical basis for finding new drug targets and biomarkers.

Research progress on osteoporosis with common geriatric syndromes

LI Miao, LI Rui, CHENG Xinchun

2025, 45(1):  112-115.  doi:10.16352/j.issn.1001-6325.2025.01.0112

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Osteoporosis is common in elderly population. The risk of falls and bone fractures in elderly patients with osteoporosis are closely related to the elderly syndrome^[1]. This article introduces the coexistence of osteoporosis and geriatric syndrome, which will limit the functional independence of patients and lead to more complex medical management. Osteoporosis has some association with common geriatric syndromes, and patients with osteoporosis are more likely to suffer from more geriatric syndromes, and their quality of life and prognosis are worse. This article reviews epidemiological status, influencing factors and management strategies of osteoporosis comorbid with geriatric syndrome, aiming to provide a basis for the integrated management of osteoporosis.

Progress of researches on the differential diagnosis of Pneumocystis jiroveci infection and colonization

LI Xingchen, TONG Jin

2025, 45(1):  116-120.  doi:10.16352/j.issn.1001-6325.2025.01.0116

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Pneumocystis jiroveci(PJ) is an atypical conditional pathogenic fungus. PJ colonization is a potential risk factor for Pneumocystis jiroveci pneumonia (PJP). Active identification of PJ colonization or infection is conducive to rational use of antibiotics. Although serum G test combined with molecular detection technology, peripheral blood CD4⁺ T level and independent characterization of trophozoites and cysts by transcriptome sequencing technology may support identifying PJ colonization and diagnosis of infection, unified standards have not yet been established. Based on the pathogenic characteristics and pathogenic mechanism of PJ,clinical characteristics and diagnostic methods of PJP, this paper reviews the progress of differential diagnosis of PJ infection and colonization, so as to provide more objective and comprehensive differential strategy for clinical diagnosis and treatment.

Effects of heavy metal exposure on bronchial asthma in children

WANG Beilei, SU Xingyue, MA Xiang

2025, 45(1):  121-125.  doi:10.16352/j.issn.1001-6325.2025.01.0121

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Bronchial asthma(asthma) is a chronic respiratory disease with complex etiology. Because of increasing application of heavy metals in human society, human exposure to heavy metals is a challenge to public health. This review summarizes recent studies to evaluate the effects and mechanisms of heavy metal exposure on asthma in children. Results of researches have showed that heavy metal exposure resulted in production of reactive oxygen species (ROS) to induce oxidative stress, enhancement of the level of inflammatory cytokines, promoting airway inflammatory response and airway remodeling and thus aggravating the occurrence and development of asthma. Further study on these effects may lead to the development of clinical guidance for asthma management.

Role of mitochondrial fusion in doxorubicin-induced cardiotoxicity

WANG Yuqi, WANG Xinyu, LUO Haowen, LU Zhaoxin, ZHAO Yiwei, CHANG Pan

2025, 45(1):  126-129.  doi:10.16352/j.issn.1001-6325.2025.01.0126

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Adriamycin is a widely used anti-tumor drug. Targeting mitochondrial fusion proteins/mitofusion 1/2(MFN1/2) and nuclear factor-erythroid 2-related factor 2(NRF2) can up-regulate the expression of mitochondrial fusion protein through PKCε/Stat3/MFN2, SIRT1/MFN2, AMPK/NRF2 and other signaling pathways, promote mitochondrial fusion, maintain kinetic balance and protect mitochondrial function, reduce myocardial cell apoptosis and reduce cardiac toxicity. Understanding the regulatory role and mechanism of mitochondrial fusion in doxorubicin-induced cardio toxicity will provide new strategies for the prevention and treatment of diseases.

Mechanism of spasmolytic polypeptide-expressing metaplasia in gastric mucosa induced by Helicobacter pylori infection

WANG Hainuo, LI Yufan, WANG Yuying, SHEN Qianying, ZHU Jinxia, ZHENG Lifei

2025, 45(1):  130-134.  doi:10.16352/j.issn.1001-6325.2025.01.0130

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Helicobacter pylori(H. pylori) infection triggers gastric mucosal inflammatory responses and spasmolytic polypeptide-expressing metaplasia (SPEM). These pathological conditions can escalate the severity of chronic gastritis, gastric ulcers and even cause gastric cancer. SPEM is frequently viewed as an early sign of gastric mucosal injury and the onset of carcinogenesis. A comprehensive analysis of the genesis and molecular regulation of SPEM cells in the context of H. pylori infection further has enlightened the pathogenesis of gastric mucosal diseases and provide new ideas and targets for diagnosing and treatment of H. pylori-related gastric mucosal diseases. This paper reviews a variety of molecular biomarkers associated with SPEM, encompassing TFF2, CD44v9, and AQP5, and delineates their pivotal regulatory functions in H.pylori infection and SPEM. This paper also reviews the origination of SPEM cells and pertinent molecular regulatory mechanisms.

Pathogenesis of acute lung injury of the newborns

YANG Ruotong, ZHAO Guoying, WANG Hao

2025, 45(1):  135-139.  doi:10.16352/j.issn.1001-6325.2025.01.0135

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Due to factors such as narrow airways and incomplete development of alveoli, newborns are prone to acute lung injury (ALI), which may progress to severe condition known as acute respiratory distress syndrome (ARDS). The mechanisms underlying the occurrence and progression of ALI in newborns involve various aspects, including oxidative stress, iron death, inflammatory response and reduction of pulmonary surfactant. Further research into these mechanisms is expected to provide strategy to guide clinical management in novo pathway.