In the process of maintaining the steady state of bone tissue, the transcription network and signal pathway of the body play a vital role. These complex regulatory mechanisms need precise coordination to ensure the balance between bone formation and bone absorption. Once this balance is broken, it may lead to pathological changes of bone and cartilage, and then lead to various bone diseases. Therefore, it is of great significance to understand these regulatory mechanisms for the prevention and treatment of bone diseases. In recent years, with the deepening of research, more and more lncRNA has been found to be closely related to bone health. Among them, nuclear paraspeckle assembly transcript 1 (NEAT1), as an extremely abundant RNA molecule in mammalian nuclei, has attracted extensive attention. NEAT1 is mainly transcribed from a specific site in human chromosome 11 by RNA polymerase II (RNaseP), which can form two different subtypes NEAT1_1 and NEAT1_2. These two subtypes are different in intracellular distribution and function, but they participate in many biological processes together. Studies have shown that NEAT1 plays a specific role in the process of cell growth and stress response. For example, it can regulate the development of osteoblasts (OB), osteoclasts (OC) and chondrocytes by balancing the differentiation of bone marrow mesenchymal stem cells (BMSCs), thus maintaining the steady state of bone metabolism. This discovery reveals the important role of NEAT1 in bone development and remodeling. In addition, NEAT1 is closely related to a variety of bone diseases. In patients with bone diseases such as osteoporosis (OP), osteoarthritis (OA) and osteosarcoma (OS), the expression level of NEAT1 is different. These differential expressions may be closely related to the pathogenesis and progression of bone diseases. By regulating the level of NEAT1, it can affect a variety of signal transduction pathways, and then affect the development of bone diseases. For example, some studies show that by regulating the expression level of NEAT1, the activity of osteoclasts can be inhibited, and the proliferation and differentiation of osteoblasts can be promoted, thus improving the symptoms of osteoporosis. It is worth noting that NEAT1 can also be used as a key sensor for the prevention and treatment of bone diseases. When exercising or receiving some natural products, the expression level of NEAT1 will change, thus reflecting the response of bones to external stimuli. This feature makes NEAT1 an important target for studying the prevention and treatment strategies of bone diseases. However, although the role of NEAT1 in bone biology and bone diseases has been initially recognized, its specific mechanism and regulatory relationship are still controversial. For example, the expression level, mode of action and interaction with other molecules of NEAT1 in different bone diseases still need further in-depth study. This paper reviews the role of NEAT1 in maintaining bone and cartilage metabolism, and discusses its expression and function in various bone diseases. By combing the existing research results and controversial points, this paper aims to provide new perspectives and ideas for the prevention and treatment of bone diseases, and provide useful reference and enlightenment for future research.

Aim To explore the effect of CXCL7/CX-CR2 axis on obesity-related cognitive dysfunction at both animal and cellular levels.Methods The novel object recognition test was performed to assess the cog-nition.After the preparation of the frozen sections,the activation of microglia and astrocytes in hippocampi and the level of PSD95 were determined by immunoflu-orescence staining.The content of CXCL7 in hipp-ocampi was determined by enzymelinked immunosor-bent assay.The dendritic spine density of hippocampal neurons was observed by Golgi staining.Furthermore,HT22 cells were treated with the recombinant mouse CXCL7 and/or si-RNA targeting CXCR2.After the treatment,the levels of CXCL7 and PSD95 were ob-served by immunocytochemistry staining.Results Compared with animals in the control group,there was significantly decreased discrimination index,increased activation of microglia and astrocytes,decreased con-tent of PSD95,decreased density of dendritic spine,and increased content of CXCL7 in hippocampi in the DIO group.Compared with animals in the DIO group,there were significantly increased discrimination index in the AWL group.In HT22 cells,the level of PSD95 significantly decreased in the Ctrl+CXCL7 group com-pared with the control group.This decrease was attenu-ated in the si-CXCR2+CXCL7 group compared with the Ctrl+CXCL7 group.Conclusion Chronic high-fat diet induces neuroinflammation and subsequently induces cognitive dysfunction,which may be related to the synaptic plasticity mediated by the CXCL7/CXCR2 axis.

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.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To explore the correlation between inflammatory markers and fibrosis of metabolic dysfunction-associated fatty liver disease(MAFLD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 769 hospitalized patients with T2DM were enrolled in this study from the Department of Endocrinology,The Second Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2023.They were divided into T2DM group(n=389)and MAFLD group(n=380)according to whether they were combined with MAFLD.According to the FIB-4 score,the MAFLD group was further divided into non-hepatic fibrosis subgroup(FIB-4＜1.3,n=267),suspected hepatic fibrosis subgroup(1.3≤FIB-4≤2.67,n=99)and advanced hepatic fibrosis subgroup(FIB-4＞2.67,n=14).The general data and biochemical indicators of each group were compared,Logistic regression analysis of influencing factors for liver fibrosis in T2DM patients with MAFLD.The diagnostic value of NLR,SIRI,PLR and PHR in predicting T2DM complicated with MAFLD liver fibrosis was evaluated by ROC curve analysis.Results BMI,lymphocytes(LY),red blood cells(RBC),hemoglobin(Hb),FPG,TG,TC,LDL-C,alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB),γ-glutamyl transpeptidase(GGT),and serum uric acid(SUA)were higher,while age,duration of DM,mean platelet volume and high-density lipoprotein cholesterol(HDL-C)were lower in MAFLD group than in T2DM group(P＜0.05).Compared with the non-hepatic fibrosis subgroup,the age,duration of DM,mean platelet volume AST and NLR were increased,while LY,PLR and PHR were decreased in the suspected hepatic fibrosis subgroup(P＜0.05).The age,AST and NLR were higher,while LY,RBC,LDL-C,PLR and PHR were lowerin the advanced hepatic fibrosis subgroup than in non-hepatic fibrosis subgroup(P＜0.05).Compared with the suspected hepatic fibrosis subgroup,FPG,HbA1c and SIRI were increased(P＜0.05),however,Hb,PLT and ALB were decreased in the advanced hepatic fibrosis subgroup(P＜0.05).Logistic regression analysis showed that NLR,SIRI,PLR and PHR were the influencing factors for liver fibrosis in T2DM combined with MAFLD.Area under ROC curve for NLR,SIRI,PLR and PHR in predicting liver fibrosis in T2DM combined with MAFLD were 0.712,0.757,0.703,0.806,respectively.The sensitivities were 0.929,0.500,0.857,0.929,and the specificities were 0.388,0.902,0.497,0.593 respectively.The optimal cut-off values were 1.573、1.465、110.819、185.379.Conclusions NLR,SIRI,PLR and PHR are the influencing factors for liver fibrosis in patients with T2DM complicated with MAFLD,which are helpful for their diagnosis.

Objective:To investigate the psychological status of the outpatients in the andrology clinic and the effect of risk warning combined with multidisciplinary team(MDT)intervention on their satisfaction.Methods:Using convenience sampling,we enrolled 600 outpatients seeking medical attention in the Department of Andrology of our hospital from July to October 2022.We ran-domized the patients into a control(n=300)and an observation group(n=300),obtained their basic information,evaluated their psychological status with the Hospital Anxiety and Depression Scale(HADS),and assessed their satisfaction with the Xijing Hospital Outpatients'Satisfaction Questionnaire(HOSQ).The controls followed the routine procedure of treatment,while the patients in the ob-servation group received early warning before intervention based on their HADS scores.We provided normal medical care for those with HADS scores≤7,employed empathetic communication for those with HADS scores of 8-10,and conducted MDT intervention for those with HADS scores≥1l,followed by comparison of the patients'satisfaction with the outpatient service between the two groups.Results:There were no statistically significant differences in general conditions between the groups of patients(P＞0.05).The mean prevalence rate of anxiety and depression was 47.83％among the male subjects,lower in the control than in the observation group(47.00％vs 48.67％,P＞0.05),but higher in the patients with the education of junior high school or below(60.99％)than in those with that of senior high school(22.34％)and university or above(16.67％),and also higher in those aged 18-40 years(67.38％)than in those aged 41-60 years(51.82％)and over 60 years old(38.33％).A significantly higher rate of satisfaction with the outpatient service was found in the observation group than in the controls(97.18％vs 90.39％,P＜0.05).Conclusion:Anxie-ty and depression are prevalent among the outpatients in the andrology clinic,with a higher prevalence rate in those with lower educa-tion and at a younger age.Early risk warning combined with MDT intervention can improve the satisfaction of the patients.

AIM To study the chemical constituents form the leaves of Castanopsis orthacantha Fance and their α-glucosidase inhibitory activities.METHODS The methanol extract form the leaves of C.orthacanth was isolated and purified by various column chromatography methods,such as MCI gel CHP 20P,Sephadex LH-20,Diaion HP20SS,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were determined by PNPG method.RESULTS Eighteen compounds were isolated and identified as protocatechuic acid(1),gallic acid(2),3-O-α-L-arabininopyranosyl-4-hydroxybenzoic acid(3),3-O-galloyl shikimic acid(4),methyl 4-epi-shikimate-3-O-gallate(5),5-O-galloyl shikimic acid(6),5-O-caffeoylshikimic acid(7),6-O-galloyl-glucoside(8),1,6-di-O-galloyl-β-D-pyranogluloside(9),1,3-di-O-galloyl-α-D-glucoside(10),2,3-di-O-galloyl-D-glucoside(11),β-O-methylgluco-2,3-digalloyl esters(12),(3R,1'S)-[1'-(6"-O-galloyl-β-D-gluco-pyranosyl)oxyethyl]-3-hydroxy-dihydrofuran-2(3H)-one(13),4-O-D-(6'-O-galloyl)glucopyranyl-(E)-p-coumaryl acid(14),chestanin(15),1-desgalloyl eugeniin(16),picrorhiza acid(17),11-methyl chebulate(18).The IC50 values of compounds 2 and 16 were(0.12±0.059),(0.00089±0.00025)mmol/L,respectively.CONCLUSION All compounds are isolated from the leaves of C.orthacantha for the first time.Compounds 2 and 16 have strong α-glucosidase inhibitory activities.

AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.

Objective To investigate the efficacy and safety of intensity-modulated radiation therapy combined with camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods A total of 84 patients with advanced HCC admitted to our hospital from January to December 2020 were selected as the study objects,and were randomly divided into the observation group and the control group,with 42 cases in each group.Patients in the observation group received intensity-modulated radiation therapy combined with carrelli-zumab,and patients in the control group received intensity-modulated radiation therapy.The short-term efficacy,immune function and long-term survival rate of patietns in the two groups were compared,and the incidence of adverse reactions was recorded.Results The total effec-tive rates of the observation group 1 month and 3 months after treatment were significantly higher than those of the control group(P<0.05).The levels of CD3+,CD4+ and CD4+/CD8+ 1 month and 3 months after treatment were all increased in the two groups,while the levels of CD8+ in both two groups were decreased(P<0.05),and the levels of CD3+,CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group(P<0.05),and the levels of CD8+ in the observation group were lower than those in the control group(P<0.05).The median survival time of patients in the observation group was significantly longer than that of patients in the control group(P<0.05).The incidence of cutaneous capillary hyperplasia in the observation group was higher than that in the control group(P<0.001),and there was no significant difference in the incidence of other adverse reactions between the two groups(P>0.05),and all of adverse reactions were grades 1 to 2.Conclusion Intensity-modulated radiation therapy combined with camrelizumab has a good effect on HCC,it can improve the immune function of the body,and control the development of the disease,with good safety.

CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.