Aim To investigate the effect of Toddalia asiatica(TA)on bone destruction in rheumatoid ar-thritis(RA)and its possible mechanism by network pharmacology and in vitro experiments.Methods The active components and targets of TA against RA bone damage were analyzed by network pharmacology.Mo-lecular docking was performed by using AutoDock and PyMOL software pairs.MC3T3-e1 cells were cultured in vitro,and the effect of Toddalia asiatica alcohol ex-tract(TAAE)on cell viability was detected by CCK-8,and appropriate drug concentration and intervention time were screened.The osteoblast model was induced by osteogenic induction medium,and the osteogenic differentiation was detected by ALP staining,activity detection and alizarin red staining.The expression of pathway-related proteins Wnt3a and β-catenin was de-tected by Western blot,and the pathway inhibitor DKK-1 was used to further verify whether TAAE regulated osteoblast differentiation through the Wnt/β-catenin signaling pathway.Results A total of 158 anti-RA bone destruction targets and 56 core targets were se-lected.The enrichment of KEGG signaling pathway mainly included cancer pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and cAMP signaling pathway.The results of CCK-8 showed that 1 g·L-1 TAAE could significantly improve cell survival rate.The results of ALP staining and ALP activity de-tection showed that TAAE could significantly increase the staining positive rate and ALP activity of cells in-duced by osteogenic induction medium.Western blot showed that TAAE could increase the expression of Wnt3a and β-catenin.The expression of these proteins decreased after DKK-1 inhibitors were used.Conclu-sion TAAE can regulate osteoblast differentiation through Wnt/β-catenin signaling pathway to treat os-teodestruction in rheumatoid arthritis.

Glutamate,norepinephrine,and their receptors com-prise the glutamatergic and norepinephrine systems,which mu-tually affect each other and play essential roles in mediating vari-ous neuropsychiatric diseases.This paper reviews the functions of N-methyl-D-aspartate receptor(NMDA-R)and α2-adrenergic receptor(α2-AR)and their functional crosstalk at the molecular level in brain in common neuropsychiatric diseases,which would benefit our understanding of neuropathophysiology of psychiatric diseases,drug development and optimization of clinical neuro-psychopharmacology.

Aim To explore the mechanism of modified Wuzi Yanzong pill to reduce testicular toxicity of Tripterygium wilfordii by means of network pharmacolo-gy.Methods The effective chemical composition and target of modified Wuzi Yanzong Pill to reduce testicu-lar toxicity of Tripterygium wilfordii were analyzed by using multiple databases to understand the mechanism of action.Results The first five compounds of modi-fied Wuzi Yanzong pill are quercetin,sucrose,kaempferol,galactose and ellagic acid,respectively.The first five targets were TP53,SRC,EP300,MAPK3,STAT3;KEGG pathway enrichment analysis mainly concentrated in cancer pathway,lipid and atherosclero-sis,hepatitis B,apoptosis,diabetes complications AGE-RAGE signaling pathway,PI3K-Akt signaling pathway and other signaling pathways.Conclusions The ac-tive components of modified Wuzi Yanzong pill can re-duce the testicular toxicity of Tripterygium wilfordii mainly by interfering with TP53,SRC,EP300,MAPK3,STAT3 and other targets,regulating apoptosis,PI3K-Akt signaling pathway,diabetes complications AGE-RAGE signaling pathway,lipid metabolism and other pathways.

Objective:To summarize the concept, theoretical basis, evaluation tools and mechanisms, influencing factors, and intervention measures of kinesiophobia.Methods:The literature on kinesiophobia in patients undergoing total knee replacement was electronically searched on databases such as China National Knowledge Infrastructure, China Biology Medicine disc, WanFang Data, PubMed, CINAHL, Web of Science, Embase, Scopus, PsycINFO, Cochrane Library. The search period was from database establishment to June 24, 2023. This study extracted and analyzed data from the included literature.Results:A total of 32 articles were included. The Tampa Scale for Kinesiophobia was a widely used tool for evaluating kinesiophobia. The influencing factors of kinesiophobia were demographic and disease factors, body motor function, and psychological and social factors. The intervention measures for kinesiophobia mainly included cognitive behavioral intervention, pain health education, exercise, art video or music intervention, multidisciplinary collaborative intervention, and so on.Conclusions:The concept and theoretical basis of kinesiophobia are not yet complete. It is necessary to revise and improve the theoretical model and assessment tool for kinesiophobia and construct an intervention program for kinesiophobia in combination with the concept of rapid rehabilitation.

In order to understand the prevalence and genetic variation of H9N2 subtype avian influ-enza virus in Shandong,a total 492 tracheal and lung tissue samples collected from chicken farms with respiratory symptoms in partial areas in Shandong were detected by H9 subtype AIV real-time RT-PCR,and the positive samples were inoculated with chicken embryos for two generations.Whole genome sequences of the positive strains by applying Illumina Miaseq platform,and genetic evolution and mutation at positions associating with viral pathogenicity and transmissibility were analyzed.The results showed that there were 72 samples were positive for H9 subtype AIV among the 492 samples,with a positive rate of 14.63％.Thirty-four strains of H9 subtype AIV were ob-tained from the positive samples after passing through chicken embryo,meanwhile,the 34 isolates were all H9N2 subtype AIV by whole genome sequencing analysis.By analyzing the evolutionary tree of HA and NA genes,HA and NA genes of the 34 H9N2 AIV strains belonged to Y280-like branch and F/98-like branch,respectively.Meanwhile,based on above branches,there were obvious time node subbranch,which one was"isolates before 2013",another one was"isolates after 2013".The HA cleavage sites of thirty-four H9N2 strains were all 325PSRSSR↓GLF333,which met the se-quence characteristics of the lowly pathogenic avian influenza virus,and the HA receptor binding site 226 amino acid was leucine,which had the characteristics of blinding to a-2,6 mammalian sialic acid receptors.Among the internal amino acid sites that are key to mammalian adaptation,all strains had an I368V mutation in the PB1 gene that enhanced viral transmissibility in mammals and the PB2 genes of some strains were mutated to enhance the mammalian adaptation of I292 V and A588 V.The above results illustrated that the H9N2 subtype AIV gene segments in Shandong have different degrees of recombination and gene variation,so it is necessary to strengthen the monito-ring of virus variation.

The health insurance fund acts as the resource for the survival of medical institutions.However,it has shown a development trend of structural friction in the county.By analyzing the relationship between strategic purchasing and the function of health insurance system,this study clarifies the central position of payment and the roles of fund allocation and service compensation.By analyzing the reasons of the imbalance between the health insurance fund and primary services in the county,this study proposes that the strategic purchasing of health care services in the county needs to take into account both the front-end of payment-allocation,and the front-end of service--primary.On this basis,this study put forwards the strategic purchasing of primary health services,which aims to cut off the fund"competition"channel between hospitals and primary health care institutions by changing the fund distribution method;to guide the primary health care to proactively identify and satisfy the changes of the county's residents'service needs by adjusting the service compensation method;and supplemented with joint advocacy and collaborative supervision.The strategic purchasing of primary health services will gradually promote the development of primary health services in the county from sustainable to high-quality.

Objective:This study explored the designs of physicians'compensation incentives that were compatible with the reform of Diagnosis-related groups(DRG)payment,so as to provide a reference for optimizing policies related to medical insurance payment reform.Methods:We designed seven different physicians'compensation schemes that converted DRG payment incentives into salary incentives,using economic experiments.The total of 210 medical students and 65 doctors were recruited as subjects.We tested the quantity of medical services for patients that participants provided and the corresponding patient health benefits under different incentive schemes.Results:The two designs of feedback of DRG payment to physicians and linking DRG payment surplus to physicians'performance wages both could transmit the incentive of the payment methods to the service providers.On this basis,a quality-based pay-for-performance payment was introduced,and the deviation between the quantity of services provided by subjects and the optimal quantity of services decreased,and the loss ratio of patient health benefits also decreased.Conclusion:When transmitting DRG payment incentives to medical service providers,the physician compensation design combined with quality-based pay-for-performance payments is more conducive to improving patient health benefits.

Objective:To explore the association between thyroid function and chronic kidney disease (CKD) in adults.Methods:A cross-sectional study was conducted in adults who received health checkup in the First Affiliated Hospital of Shandong First Medical University from January to December in 2021. Clinical data were collected, including age, gender, height, weight, blood pressure, etc. And blood glucose, blood lipid, blood creatinine, blood uric acid, routine urine function, thyroid function (free triiodine, free thyroxine, thyroid stimulating hormone) were measured. Multivariate logistic regression model was used to investigate the correlation between thyroid function indicators and the onset of CKD; and receiver operator characteristic (ROC) curve was used to explore the ability of thyroid function indicators in evaluating CKD.Results:In the study, 46 342 adults with an average age of (47.6±14.3) years were enrolled, of which 56.2% were males. The prevalence of DeGFR (eGFR<60 ml·min -1·(1.73 m 2) -1), proteinuria and CKD was 1.15%, 0.53% and 1.58%, respectively. The TSH subgroup analysis showed that the prevalence of DeGFR, albuminuria and CKD in the hypothyroidism group was significantly increased to 1.07%, 2.36% and 3.20%, respectively (all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis showed that FT3 was negatively associated with CKD ( OR=0.63, 95% CI: 0.54-0.74), however FT4 ( OR=1.05, 95% CI: 1.03-1.07) and TSH ( OR=1.03, 95% CI: 1.01-1.04) were positively correlated with CKD. Similar results were obtained in the subgroup without hypertension and diabetes ( P<0.05). The ROC analysis indicated that FT3 had a better capability for evaluating CKD than FT4 and TSH, with an area under the curve of 0.63, a cut-off value of 4.18 pmol/L, and a sensitivity and specificity of 57.5% and 62.6%, respectively. Conclusions:Thyroid function status is closely associated with the onset of CKD in the adult population receiving health check-up. FT3 is a risk factor for the onset of CKD.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.

Objective:To observe the rehabilitation effect of balance training relying on tilted table on diaphragmatic function of patients with prolonged disorder of consciousness (pDoC).Methods:A prospective study was performed. Thirty patients with pDoC were enrolled from Department of Hyperbaric Oxygen Medicine and Rehabilitation, General Hospital of Southern Theater Command of PLA from May to December 2023. The pateints were divided into study group ( n=15) and control group ( n=15) according to different rehabilitation. Patients from the control group received conventional rehabilitation, while those in the study group received passive balance training relying on tilted table in addition to conventional rehabilitation. Diaphragmatic ultrasound examination was performed before treatment, and 4 and 8 weeks after treatment to measure diaphragm excursion (DE), diaphragm thickening inspiration (DTei), diaphragm thickening expiration (DTee) and diaphragm thickening fraction (DTF) so as to assess the diaphragmatic functions of patients with pDoC. Results:During treatment, 2 patients dropped out from the study group resulting from the willing of the family members, ultimately including 13 and 15 patients in the study and control groups, respectively. (1) Between-group comparison: no significant difference in DE, DTei, DTee or DTF was noted between the study group and control group 4 weeks after treatment ( P>0.05). However, 8 weeks after treatment, the study group had statistically increased DE, DTei and DTF compared with the control group ([1.65±0.32] cm vs. [1.21±0.22] cm; [2.07±0.26] cm vs. [1.83±0.26] cm; and [24.39±3.19]% vs. [18.93±2.50]%). (2) Within-group comparison: both group had significantly increased DE 4 and 8 weeks after treatment compared with those before treatment ( P<0.05); in the study group, DE 8 weeks after treatment was significantly increased compared with that 4 weeks after treatment ( P<0.05). No significant difference in DTei, DTee or DTF was noted in both groups between 4 weeks after treatment and before treatment ( P>0.05). In the study group, DTei, DTee and DTF 8 weeks after treatment were significantly higher than those before treatment and 4 weeks after treatment ( P<0.05). Conclusion:Balance training relying on tilted table is feasible and effective in improving diaphragmatic function in patients with pDoC, and the effect is positively correlated with treatment time within a certain time.