1.Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism.
Jifeng LI ; Haolin GUO ; Ying DONG ; Shuo YUAN ; Xiaotong WEI ; Yuxin ZHANG ; Lu DONG ; Fei WANG ; Ting BAI ; Yong YANG
Chinese Journal of Natural Medicines (English Ed.) 2024;22(1):4-14
		                        		
		                        			
		                        			Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			Drugs, Chinese Herbal/pharmacology*
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		                        			Liver Diseases/drug therapy*
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		                        			Antioxidants
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		                        			Polysaccharides/therapeutic use*
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		                        			Medicine, Chinese Traditional
		                        			
		                        		
		                        	
2.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
		                        		
		                        			
		                        			Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
		                        		
		                        		
		                        		
		                        	
3.Effects of glenosphere offsets on impingement-free range of motion in reverse total shoulder arthroplasty: a standardized computer simulation study
Xiaopei XU ; Qingnan SUN ; Maoqi GONG ; Xieyuan JIANG ; Yang LIU ; Dong WANG ; Hanzhou WANG ; Shuo DIAO ; Junlin ZHOU
Chinese Journal of Orthopaedic Trauma 2024;26(2):156-162
		                        		
		                        			
		                        			Objective:To compare the effects of glenosphere offset positions on the impingement-free range of motion (ROM) in reverse total shoulder arthroplasty (RTSA).Methods:Shoulder joint models were reconstructed using shoulder CT scans of 6 patients with primary osteoarthritis. RTSA was performed virtually according to standard surgical procedures, and shoulder movements were simulated. Reverse shoulder models were constructed with 2 lateral offsets (0 and 4 mm) and 6 positional offsets (center, inferior, posterior, anterior, anterior-inferior, and posterior-inferior). The impingement-free ROM and impingement sites for abduction-adduction, flexion-extension, total rotation (sum of internal and external rotation), and total ROM (sum of ROM in all movement modes) were evaluated.Results:All the 12 combinations of different glenosphere offsets achieved 50% of the original shoulder ROM in all movements. In the abduction-adduction motion with 0 and 4 mm lateral offsets, the anterior-inferior offset provided the largest ROM (94.4°±8.7° and 105.3°±6.9°, respectively), but there was no significant difference between the positions ( P>0.05). In the flexion-extension motion with 0 and 4 mm lateral offsets, the posterior-inferior offset showed the largest ROM (194.1°±6.9° and 196.9°±9.7°, respectively), but there was no significant difference between the positions ( P>0.05). In the total rotation motion with 0 and 4 mm lateral offsets, the anterior-inferior offset had the largest ROM (141.5°±5.9° and 160.6°±8.5°, respectively), showing significant advantages over the center, anterior, and posterior offsets ( P<0.05), but insignificant advantages over the inferior and posterior-inferior offsets ( P>0.05). In total ROM, the anterior-inferior offset provided the largest ROM. When the lateral offset was 0 mm, the anterior-inferior offset provided a ROM of 421.8°±16.4°, showing significant advantages over the center and posterior offsets ( P<0.05). Compared with the lateral glenosphere offset of 0 mm, the lateral glenosphere offset of 4 mm significantly improved total shoulder ROM (122.8°±10.6° versus 145.8°±4.8°) and total ROM (390.9°±11.6° versus 428.4°±19.8°) ( P<0.05). Conclusions:The anterior-inferior, inferior, and posterior-inferior glenosphere offsets can improve ROM in all movement patterns. The position and lateral offset of the glenosphere significantly affect the total rotation and total ROM of the shoulder joint. Specifically, the anterior-inferior and inferior offsets show significant advantages over the center position in total rotation and total ROM of the shoulder joint.
		                        		
		                        		
		                        		
		                        	
4.Clinical characteristics and risk analysis of novel coronavirus repeated infection
Jing DONG ; Fang LIU ; Shouang QIAO ; Shuo WANG
Journal of Chinese Physician 2024;26(2):180-184
		                        		
		                        			
		                        			Objective:To understand the clinical characteristics of novel coronavirus reinfection and explore the risk factors of novel coronavirus reinfection.Methods:The clinical data of 340 patients with novel coronavirus infection who were admitted to the Fever Clinic of Beijing Traditional Chinese Medicine, Capital Medical University from December 2022 to January 2023 were included. The general characteristics, basic diseases, clinical symptoms, and examination results of the first and second infections in the non repeated infection group, the repeated infection group, and the repeated infection group were compared. Binary logistic multivariate analysis was used to explore the risk factors of novel coronavirus reinfection.Results:In this study, 340 patients with novel coronavirus infection were included, 180 of whom were repeatedly infected. There was no statistically significant difference (all P>0.05) in terms of gender, age, body mass index (BMI), exercise, smoking, daily routine, and underlying disease between the recurrent infection group and the non recurrent infection group. However, the vaccination rate of the recurrent infection group was lower than that of the non recurrent infection group [80.0%(144/180) vs 88.0%(142/169), P<0.05]; In the repeated infection group, 157 cases (87.2%) were accompanied by overall discomfort (including headache, fatigue, muscle and joint pain), which was significantly higher than 122 cases (76.2%) in the non repeated infection group. The proportion of pneumonia occurring during the first infection was higher than that in the non repeated infection group [15.6%(28/180)], and the difference was statistically significant ( P<0.05). The interval between the first and second infections in the repeated infection group was (166.2±8.3)days. Cough and phlegm were the main clinical manifestations of two infections; The duration of re infection was shorter than that of the first infection [(7.03±2.30)days vs (8.94±3.02)days, t=6.739, P<0.001]; Secondary infections had less incidence of pneumonia [5.0%(9/180) vs 15.6%(28/180), χ 2=10.874, P=0.001]; 153 patients (85.0%) reported milder secondary infections. The results of binary logistic regression showed that cough, expectoration, body discomfort and pneumonia during the first infection were risk factors for repeated infection of novel coronavirus ( OR=2.710, 2.293, 2.808, P<0.05), and vaccination was a protective factor to avoid repeated infection ( OR=0.470, P=0.019). Conclusions:The symptoms of novel coronavirus reinfection are generally mild and the course of disease is relatively short. For vulnerable people, novel coronavirus vaccine should be actively inoculated to strengthen protection.
		                        		
		                        		
		                        		
		                        	
5.The expression and significance of serum HO-1 and NQO-1 in children with different severity of mycoplasma pneumoniae infection
Chao JIN ; Yanxiang BAI ; Li XU ; Shuo SHI ; Bin ZHANG ; Haixin DONG
Journal of Chinese Physician 2024;26(3):408-412
		                        		
		                        			
		                        			Objective:To explore the expression and clinical significance of heme oxygenase-1 (HO-1) and quinone oxidoreductase (NQO-1) in children with different severity levels of mycoplasma pneumoniae (MP) infection.Methods:A total of 140 children with MP infection who were treated at the Affiliated Hospital of Jining Medical University from January to June 2022 were selected as the observation group, while 100 healthy children who underwent physical examination were selected as the control group. The serum levels of interleukin-2 (IL-2), IL-6, IL-10, IL-1β, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), HO-1, and relative expression of NQO-1 protein were compared between the control group and the observation group, as well as between children with different degrees of MP infection, Forced vital capacity (FVC), maximum expiratory volume in the first second (FEV 1), peak expiratory flow rate (PEF), 50% forced expiratory flow rate and maximum mid expiratory flow rate (MEF 25-70), 50% forced expiratory flow rate (MEF 50), and 25% forced expiratory flow rate (MEF 25). Pearson correlation method was used to analyze the correlation between the expression of HO-1 and NQO-1 with inflammatory factors and lung function indicators. The receiver operating characteristic (ROC) curve was used to analyze the value of HO-1 and NQO-1 expression in predicting severe MP. Results:The serum levels of IL-2, IL-6, IL-10, IL-1β, TNF-α, IFN-γ, and HO-1 in the observation group were significantly higher than those in the control group (all P<0.05), while the relative expression level of NQO-1 protein was significantly lower than that in the control group ( P<0.05). The FVC, FEV 1, PEF, MEF 25-70, MEF 50, and MEF 25 in the observation group were significantly lower than those in the control group (all P<0.05). The serum levels of IL-2, IL-6, IL-10, IL-1β, TNF-α, IFN-γ, and HO-1 in the observation group of severe children were significantly higher than those in mild children (all P<0.05), while the relative expression of NQO-1 protein, FVC, FEV 1, PEF, MEF 25-70, MEF 50, and MEF 25 were significantly lower than those in mild children (all P<0.05). HO-1 in children with MP infection is positively correlated with IL-6, IL-1β, and IFN-γ, while the relative expression level of NQO-1 protein is negatively correlated with IL-6, IL-1β, and IFN-γ (all P<0.05); HO-1 was negatively correlated with MEF 50 and MEF 25, while the relative expression level of NQO-1 protein was positively correlated with MEF 50 (all P<0.05). The area under the ROC curve for predicting the relative expression levels of HO-1 and NQO-1 proteins in severe MP was 0.871 and 0.934, respectively (all P<0.05). Conclusions:The expression of serum HO-1 and NQO-1 in children with MP infection is correlated with cytokines and lung function indicators, and has certain application value in predicting severe illness.
		                        		
		                        		
		                        		
		                        	
6.Challenges Faced by "Young" Ethics Committees under the Mode of Collaborative Review
Xiaoyan DONG ; Shuo YIN ; Xubin ZHANG ; Quan XIAO
Chinese Medical Ethics 2024;35(5):508-512
		                        		
		                        			
		                        			In the process of exploring standardized and efficient ethical review models for multi-center drug clinical trials, the ethical review alliance emerged as the times require. Compared with mature ethics committees, higher requirements have been put forward for the "young" ethics committees. By analyzing problems existing in review work of "young" ethics committees in the ethics review alliance, this paper discussed the measures to improve the review quality of "young" ethics committees and promote the standardized and efficient operation of the alliance, and put forward countermeasures and suggestions for improving the homogenization of ethics review and accelerating the clinical research process of innovative drugs.
		                        		
		                        		
		                        		
		                        	
7.Surgical treatment for mitral valve regurgitation in children by artificial chords
Shun LIU ; Shuo DONG ; Mengxuan ZOU ; Yangxue SUN ; Chuhao DU ; Jie DONG ; Shoujun LI ; Jun YAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1855-1858
		                        		
		                        			
		                        			Artificial chord is a mature mitral valve repair technique, especially in adult mitral valve repair. It is still challenging to repair mitral valve in children with artificial chords because the quality of mitral valve is soft and immature. There are some differences in the methods of suture, the choice of suture size and the number of artificial chords. Although the artificial chords could not grow naturally, we found through the long-term research that most children did not have mitral valve restriction or even chords rupture due to itself can compensate through the growth of the flap and papillary muscle. This article summarizes the recent research progress on the treatment of mitral valve insufficiency in children with artificial chords, providing reference for clinical treatment.
		                        		
		                        		
		                        		
		                        	
8.Bioinformatics analysis and experimental validation of ferroptosis in peri-implantitis
Zhewei ZHANG ; Jiaohong WANG ; Wei WU ; Shuo DONG ; Guoqing LI ; Chunbo TANG
STOMATOLOGY 2024;44(7):527-535
		                        		
		                        			
		                        			Objective To investigate the key genes associated with ferroptosis in peri-implantitis and explore the potential mecha-nisms regulating peri-implantitis.Methods Several datasets were obtained from the GEO database.Differential expressed genes were screened,and GO and KEGG analyses were performed.A PPI network was constructed using the STRING website.Key genes were val-idated using a test set,and the diagnostic value of key genes was determined.The content and proportion of 22 immune cells in peri-im-plantitis tissues were obtained through immune infiltration analysis.Key genes were validated by qRT-PCR and Western Blot(WB).Results There were 1 138 differential genes between peri-implantitis tissues and normal gingival tissues,of which 29 were related to ferroptosis.The gene expression in peri-implantitis tissues mainly involved processes such as immune response activation.Five key genes in the ferroptosis-related differential genes,namely SOX2,GJA1,IL1B,GPX2 and CHAC1,were differentially expressed in peri-implantitis tissues and had high diagnostic value.Immune infiltration analysis showed significant changes in immune cells such as memory B cells and plasma cells in peri-implantitis tissues.qRT-PCR and WB confirmed significant differential expression of mRNA and the protein transcribed by key genes.Conclusion Differential genes between peri-implantitis and ferroptosis are screened using bioinformatics analysis and biological validation,providing new insights into the study on peri-implantitis.
		                        		
		                        		
		                        		
		                        	
9.ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor,exerts antidepressant effect via dual mechanism of monoamine enhancement and inflammation suppression
Jingwen ZHANG ; Qiongyin FAN ; Susu ZHANG ; Yang ZHANG ; Ya LUO ; Xinming SHEN ; Luyao LUO ; Beilei DONG ; Jincao LI ; Shuo LI ; Huajin DONG ; Xingzhou LI ; Yupeng HE ; Rui XUE ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(5):321-334
		                        		
		                        			
		                        			OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.
		                        		
		                        		
		                        		
		                        	
10.Improvement of sleep by Jiawei Tianwang Buxin Dan and its mechanisms in simulated model of plateau exposure in rats
Jiaying HUANG ; Jingcao LI ; Yongfang GU ; Yumeng LIU ; Renhong QIU ; Yang ZHANG ; Rui XUE ; Shuo LI ; Huajin DONG ; Yanxin WANG ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(6):401-409
		                        		
		                        			
		                        			OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.
		                        		
		                        		
		                        		
		                        	
            
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