ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 （Fas）/cysteine protease-8 （Caspase-8）/cysteine protease-3 （Caspase-3） signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury （CLI）. MethodsAmong 48 Wistar rats，12 rats were randomly selected as the blank group，and the other rats were administered alpha-naphthalene isothiocyanate （ANIT） by gavage to induce a CLI model. The modeling rats were randomly divided into the model group， the ursodeoxycholic acid group（0.1 g·kg^-1） and the Yinchenhao Tang group（9.23 g·kg^-1），with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），gamma-glutamyl transpeptidase （γ-GT），total bilirubin （TBil） and total bile acid （TBA） in serum were detected. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3，B-cell lymphoma-2 （Bcl-2） associated X protein （Bax） and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with those in the blank group，the levels of ALT，AST，ALP，γ-GT，TBA and TBil in serum of the model group were significantly increased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased （P<0.01）. The arrangement of hepatocytes was disordered，and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly increased（P<0.05，P<0.01），while the protein and mRNA expressions of Bcl-2 were significantly decreased （P<0.05，P<0.01）. Compared with those in the model group，the levels of ALP，γ-GT，TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased（P<0.05，P<0.01）. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the mRNA expression of Bcl-2 was significantly increased （P<0.05，）. The levels of ALT，AST，γ-GT，TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased （P<0.05，P<0.01）. The protein expression of Fas and Bax and the mRNA expression of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the protein and mRNA expression of Bcl-2 were significantly increased （P<0.05，P<0.01）. Hepatocyte injury，inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI，and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

Plasminogen activator is a kind of enzyme that plays a key role in the process of physiological hemostasis and thrombolysis. Its main function is to convert plasminogen into active plasmin, thereby initiating the dissolution of fibrin and maintaining blood mobility. This article discusses the safety of plasminogen activator in the intraocular application, elaborates on the types, structure, physiological function and mechanism of action of plasminogen activator in the eye. The analysis addresses the ocular tissue damage and systemic adverse reactions that may be caused by the application of plasminogen activator in the eye, and the risks and countermeasures combined with relevant research examples, aiming to provide reference for the safe application of plasminogen activator in clinical practice.

ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

Tuberculosis is still the second leading cause of death from a single source of infection in the world.There is a two-way relationship between tuberculosis and the nutritional status of the body,which affects and causes each other.Vitamin D is an essential micronutrient,most research results show that vitamin D deficiency is common in tuberculosis patients,which is related to lack of sunlight,decreased dietary intake of vitamin D and anti-tuberculosis drug treatment.Low level vitamin D can increase tuberculosis susceptibility to some extent,but the research results are not completely consistent.This paper reviews the nutritional status of vitamin D in tuberculosis patients in recent years,the causes of vitamin D deficiency in tuberculosis patients and the relationship between vitamin D deficiency and susceptibility of tuberculosis,so as to provide references for further study on the role of vitamin D in tuberculosis prevention and treatment.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

(Peri)Menopausal insomnia is one of the most common symptoms experienced by women in(peri)menopausale,and can cause varying degrees of damage to both the physical and mental health of individuals.Modern medicine believes that the decline in estrogen levels and the imbalance in estrogen receptor expression are closely related to the occurrence of(peri)menopausale insomnia in women.Traditional Chinese Medicine believes that the imbalance of yin and yang in the body,caused by the disharmony between the heart and kidney,is an important factor in the onset of this disease.Professor Xiao Chengcong,a renowned master of traditional Chinese medicine,has summarized years of clinical experience and has developed a unique therapeutic approach for this disease using the harmonizing method.Her self-designed empirical formula,Gengxin Decoction,has been proven to have a good therapeutic effect in clinical trials.The team has further confirmed in animal studies that Gengxin Decoction can increase estrogen levels,promote estrogen receptor expression in the hypothalamus,influence the regulation of monoamine neurotransmitters,enhance the negative gene expression of the biological clock,reduce brain excitability,and restore the circadian rhythm of the biological clock.This article discusses the decline in estrogen levels and the imbalance in estrogen receptor expression which promote the occurrence and development of(peri)menopausal insomnia,the role of Gengxin Decoction and the harmonizing method in the etiology and pathogenesis of(peri)menopausal insomnia,and the alignment between the physiological effects of Gengxin Decoction and the balance of estrogen levels and estrogen receptor expression,aiming to reveal the scientific connotation of Professor Xiao Chengcong's use of the harmonizing method to treat(peri)menopausal insomnia,to provide a reference for clinical treatment,and to promote the dissemination and inheritance of the academic thoughts of traditional Chinese medicine master Professor.

As the "main force" for providing health services, there has been a constant increase in the number of health service and management graduates in recent years, but with a lack of satisfactory quality. The concept of outcome-based education (OBE) takes the needs of all parties as the starting point and foothold for practice, which can ensure the consistency between the goal of talent training and the learning achievements of students to the greatest extent. This article proposes to integrate the educational concept of OBE into the training path of health service and management talents, clarify talent training objectives by understanding the needs of all parties, optimize the curriculum system according to training objectives, and construct a diversified evaluation system with the organic combination of process evaluation and summative assessment, in order to continuously optimize the training path of health service and management talents and cultivate applied health management talents with knowledge, ability, and quality.

AIM:To exploring the mechanism of Xin Mai Jia(XMJ)in inhibiting hypertensive cardiac hypertrophy through network pharmacology and animal experiments.METHODS:Retrieving the ac-tive ingredients and target points of XMJ by search-ing the TCMSP database and related literature re-ports;using the Gene Cards,OMIM,and Drug Bank databases to screen targets for hypertensive cardi-ac hypertrophy;constructing a network of tradi-tional Chinese medicine-active ingredients-poten-tial targets and a protein-protein interaction(PPI)network;using DAVID software for target gene on-tology(GO)functional enrichment analysis and Kyo-to Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis;using Auto Dock soft-ware for molecular docking.A spontaneously hy-pertensive rat(SHR)model was established,and hematoxylin-eosin(HE)staining was used to detect the morphology of cardiac tissue and cellular hy-pertrophy,Masson staining was used to detect col-lagen deposition in cardiac tissue,and Western blot to detect the expression of heat shock protein(HSP90AA1),mammalian target of rapamycin(mTOR),peroxisome proliferator-activated receptor y(PPARG),and tumor necrosis factor(TNF-α)in car-diac tissue.RESULTS:A total of 56 potential active ingredients were identified in XMJ,and 5,492 tar-gets related to hypertensive cardiac hypertrophy were obtained.The targets in the core network were ranked according to their Degree values,and four main targets were selected:HSP90AA1,mTOR,PPARG,and TNF-α.The results of HE staining showed that compared with the normal group,the average area of cardiomyocytes in the SHR group increased significantly(P＜0.05),while there was no significant change in the XMJ group.The hypertro-phy in the SHR+XMJ group was significantly alleviat-ed(P＜0.05).The results of Masson staining showed that compared with the normal group,the levels of interstitial fibrosis and perivascular fibrosis in the SHR group rats increased significantly(P＜0.01),and XMJ could significantly reduce the fibrosis levels in the SHR group rats(P＜0.01).The results of Western blot showed that compared with the normal group rats,the expression of HSP90AA1 and PPARG in the myocardial tissue of SHR group rats was downregu-lated,mTOR phosphorylation was downregulated,and TNF-α was significantly upregulated(P＜0.01).In the SHR+XMJ group,the expression of HSP90AA1,PPARG,and TNF-α in the myocardial tis-sue of rats returned to normal levels,and mTOR phosphorylation returned to normal levels.In the XMJ group,there were no significant changes in the above indicators compared with the normal group rats.CONCLUSION:The mechanism underly-ing the inhibitory effect of XMJ on myocardial cell hypertrophy in hypertension involves a comprehen-sive action through multiple components,multiple targets,and multiple pathways.

Objective:To investigate transition pattern of health status among middle-aged and elderly population in China based on frailty index.Methods:In this retrospective cohort study, middle-aged and elderly people were selected from the China Health and Retirement Longitudinal Study (CHARLS) in 2011; and 1 434 subjects were followed up to 2015. The frailty index was calculated from the prevalence of chronic diseases, daily activity ability and blood biomarkers, and the frailty state was divided by quartiles of the frailty index. Markov models were constructed to determine the transition probabilities of different frailty states.Results:The mean age of the 1 434 subjects was (59.0±9.4) years and the mean frailty index was 0.11±0.05. In the healthy individuals, 63.0% remained healthy after a four-year follow-up; during the same follow-up period, 40.9% of the mildly frail individuals and 23.0% of the moderately frail individuals remained in their baseline frailty status. Increasing age leaded to a gradual increase in the probability of the population shifting to a severely frailty state. Women were more likely to shift to severe frailty status than men (0.029 vs 0.019, Z=3.03, P=0.002). Conclusion:Among middle-aged and elderly population in China, the transition of health states follows a pattern where higher frailty levels are associated with lower stability. Advanced age and female gender are identified as risk factors for progression to severe frailty.