ObjectiveTo investigate the therapeutic mechanism of artemether in diabetic sarcopenia（DS）using network pharmacology and animal experiments. MethodsPotential active components and therapeutic targets were screened using artemisinin as the parent compound. The predicted targets were intersected with DS-related targets， followed by construction of a protein-protein interaction （PPI） network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed to identify the key biological processes and signaling pathways. Molecular docking was further used to evaluate the binding affinity between artemether and core targets. The DS mouse model was established using db/db mice， followed by artemether intervention. Fasting blood glucose， body weight， diabetes-related symptoms， body composition， grip strength， serum and skeletal muscle triglyceride levels， and muscle fiber cross-sectional area （CSA） were assessed. The expression levels of forkhead box O1 （FoxO1）， Atrogin-1， muscle RING finger protein 1 （MuRF1）， acyl-CoA synthetase short-chain family member 2 （ACSS2）， carnitine palmitoyltransferase 2 （CPT2）， and fatty acid-binding protein 3 （FABP3） in skeletal muscle were detected by qRT-PCR， Western blot， immunofluorescence， and immunohistochemistry. In addition， metabolomics was performed to analyze changes in acylcarnitine metabolites in skeletal muscle. ResultsA total of 68 overlapping targets between artemether and diabetic sarcopenia （DS） were identified. The core targets included AKT1， FoxO1， NFKB1， FBXO32， and TRIM63， which were mainly enriched in the phosphoinositide 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， forkhead box O （FoxO） signWaling pathway， tumor necrosis factor （TNF） signaling pathway， and insulin resistance-related pathways. Molecular docking analysis showed that artemether exhibited favorable binding affinity with the core targets. Animal experiments demonstrated that artemether reduced fasting blood glucose， ameliorated metabolic symptoms， increased lean mass and grip strength， decreased serum and skeletal muscle triglyceride levels， and increased muscle fiber cross-sectional area （CSA） in DS mice. In addition， artemether downregulated the mRNA and protein expression levels of FoxO1， FBXO32/Atrogin-1， TRIM63/MuRF1， ACSS2， CPT2， and FABP3， and improved the disturbance of acylcarnitine metabolism in skeletal muscle. ConclusionArtemether improves metabolic and skeletal muscle phenotypes in DS mice. Its effects may be associated with the amelioration of lipid metabolic disorders and the downregulation of FoxO1 and its downstream ubiquitin-proteasome pathway-related factors Atrogin-1 and MuRF1 in skeletal muscle.

Liuhetang is one of the classic prescriptions included in the Catalogue of Ancient Classic Prescriptions （the Second Batch）. This study adopts the method of literature review to systematically sort out the ancient literature about Liuhetang and obtained a total of 127 effective data records， involving 82 ancient books （including 2 Japanese books）. The origin， medicinal composition， compatibility， original plants and their processing methods， dosage， decocting method， usage， and indications of Liuhetang were analyzed. Liuhetang is first recorded in the Formulary of the Bureau of Taiping People's Welfare Pharmacy in the Song Dynasty， consisting of Amomi Fructus， Pinelliae Rhizoma， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， red Poria， Pogostemonis Herba， Lablab Semen Album， Chaenomelis Fructus， Moslae Herba， Magnoliae Officinalis Cortex， Zingiberis Rhizoma Recens， and Jujubae Fructus. The original plants of these herbal medicines follow those in the 2020 edition of the Pharmacopoeia of the People's Republic of China. The raw materials of Amomi Fructus， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， red Poria， Pogostemonis Herba， Chaenomelis Fructus， Moslae Herba， Magnoliae Officinalis Cortex， Zingiberis Rhizoma Recens， and Jujubae Fructus are used in this prescription. Pinelliae Rhizoma， Glycyrrhizae Radix et Rhizoma， Lablab Semen Album， and Magnoliae Officinalis Cortex are processed with alum， stir-fried， processed with Zingiberis Rhizoma Recens， and processed with Zingiberis Rhizoma Recens， respectively. The recommended formula is composed of 0.79 g Amomi Fructus， 0.79 g Pinelliae Rhizoma， 0.79 g Armeniacae Semen Amarum， 0.79 g Ginseng Radix et Rhizoma， 0.79 g Glycyrrhizae Radix et Rhizoma， 1.57 g red Poria， 1.57 g Pogostemonis Herba， 1.57 g Lablab Semen Album， 1.57 g Chaenomelis Fructus， 3.15 g Moslae Herba， and 3.15 g Magnoliae Officinalis Cortex. The above medicines should be pulverized to reach 10 meshes， mixed with 450 mL water， 3 g Zingiberis Rhizoma Recens， and 3 g Jujubae Fructus， and decocted to reach a volume of 240 mL. The filtrate should be taken three times a day. In ancient times， Liuhetang was mainly used to treat cholera， vomiting， diarrhea， phlegm， dyspnea， cough， chest distension， dizziness and pain in the head， swelling in the limbs， lethargy， loss of appetite， difficult urination and dark urine caused by heat and dampness damage to the spleen and disharmony between spleen and stomach. In modern times， Liuhetang is mainly used to treat the digestive system diseases such as gastroenteritis， hepatitis， stomach pain， and diarrhea. The above research confirmed the key information of Liuhetang， providing a basis for the clinical application of this prescription.

Acute Gelsemium poisoning is a systemic disease primarily affecting the central nervous system and respiratory symptoms caused by the ingestion of a substantial amount of Gelsemium within a short period. It manifests as sudden onset and rapid progression, primarily caused by accidental ingestion due to misidentification, and posing significant health risks. The compilation of the Technical Plan for Emergency Health Response to Acute Gelsemium Poisoning describes in detail the specialized practice and technical requirements in the process of handling acute Gelsemium poisoning, including accident investigation and management, laboratory testing and identification, in-hospital treatment, and health monitoring. The guidelines clarify key procedures and requirements such as personal protection, investigation elements, etiology determination, medical rescue, and health education. The key to acute Gelsemium poisoning investigation lies in promptly identifying the toxin through exposure history, clinical manifestations, and sample testing. Because there is no specific antidote for Gelsemium poisoning, immediate removal from exposure, rapid elimination of the toxin, and respiratory monitoring are critical on-site rescue measures. Visual identification of food or herbal materials, followed by laboratory testing to determine Gelsemium alkaloids in samples is a rapid effective screening method. These guidelines offer a scientific, objective, and practical framework to support effective emergency responses to acute Gelsemium poisoning incidences.

Objective To analyze the characteristic influencing factors for enlarged perivascular spaces(EPVS)in different regions of acute ischemic stroke(AIS)patients and explore their un-derlying pathogenesis.Methods A total of 172 AIS patients admitted to our department from September 2020 to September 2023 were consecutively enrolled.According to the distribution of EPVS,they were divided into basal ganglia EPVS group(n=103)and non-basal ganglia EPVS group(n=69),as well as centrum semiovale EPVS group(n=77)and non-centrum semiovale EPVS group(n=95).General information,NIHSS score at onset,TOAST classification,fasting blood glucose,liver function,coagulation function,and homocysteine(Hcy)level were collected in all the patients.Multivariate logistic regression analysis was used to identify independent influen-cing factors for EPVS in different regions.Results The basal ganglia EPVS group had significant-ly advanced age and larger proportion of hypertension than the non-basal ganglia EPVS group,while the centrum semiovale EPVS group had smaller proportion of hyperhomocysteinemia,and larger ratios of smoking and alcohol consumption,higher alanine aminotransferase(ALT)level,and longer thrombin time than the non-centrum semiovale EPVS group(P＜0.05,P＜0.01).Mul-tivariate logistic regression analysis showed that hypertension(OR=2.093,95％CI:1.045-4.192,P=0.037)and age(OR=1.071,95％CI:1.016-1.130,P=0.011)were independent influ-encing factors for basal ganglia EPVS,while alcohol consumption(OR=2.418,95％CI:1.097-5.330,P=0.029)and thrombin time(OR=1.593,95％CI:1.129-2.249,P=0.008)were inde-pendent influencing factors for centrum semiovale EPVS.Conclusion EPVS in different regions of AIS patients are associated with distinct risk factors.Age and hypertension are primary influen-cing factors for basal ganglia EPVS,while alcohol consumption and prolonged thrombin time are significant factors for centrum semiovale EPVS.

AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

Objective:To investigate the changes in hepatic phase II detoxification enzymes and their mechanism in metabolic associated steatohepatitis (MASH) induced by a methionine-choline-deficient (MCD) diet in mice.Methods:Ten C57BL/6J mice were randomly divided into two groups, with five mice in each group, and fed with a control diet (NCD group) and a methionine-choline-deficient diet (MCD group) for four consecutive weeks to establish the MASH model in mice. Mice body weight was recorded weekly. Mice peripheral blood and liver tissue samples were collected after four weeks. The liver histopathological changes were observed by hematoxylin-eosin staining and Sirius red staining in liver tissue. The levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides were measured by an automatic biochemical analyzer. Triglyceride and total cholesterol were used to evaluate the lipid accumulation condition in the liver of mice with Oil red O staining. Real-time fluorescence quantitative PCR was used to detect the expression of liver inflammatory factors interleukin (IL)-1β and monocyte chemoattractant protein-1 (MCP-1) condition. Transcriptome sequencing and bioinformatics were used to analyze the changes in gene expression profiles in the liver of mice and screen differentially expressed genes. The expression conditions of phase Ⅱ detoxification enzymes glutathione S-transferase mu 4 (GSTM4), dihydronicotinamide riboside:quinone oxidoreductases (NQO-2), sulfotransferase 1β1 (SULT1β1), and uridine diphosphate glucuronosyltransferase 2 family, polypeptide A3(UGT2A3) were verified by real-time fluorescent quantitative PCR. Plasma malondialdehyde content, total antioxidant capacity (T-AOC), plasma and liver glutathione content were determined using commercial kits. The expression of nuclear factor E2-related factor 2 (Nrf2), GSTM4, and UGT1A6 was examined by Western blotting. The independent sample t-test was used for comparison between the groups. Results:The body weight of mice in the MCD group showed a gradual downward trend, while the body weight of mice in the NCD group did not change significantly following four weeks of different dietary feeding. The MCD group mice liver had yellow-white appearance with round edges. The liver/body mass index was significantly lower in the NCD group ( t=3.216, P<0.01). Hematoxylin-eosin staining showed that hepatocytes in the MCD group had an occurrence of fatty degeneration accompanied by inflammatory cell infiltration, with a higher NAFLD activity score (NAS) compared to the NCD group ( t=7.155, P<0.001). Sirius red staining showed that the the liver of the MCD group had mildly increased periportal fibers. Plasma biochemical tests indicated that plasma ALT, AST, and triglyceride levels were significantly higher in the MCD group than those in the NCD group ( t=8.920, P<0.001; t=6.696, P<0.001; t=3.904, P<0.01). Oil red O staining showed that a large number of lipid droplets accumulated in the liver tissue of the MCD group and were more severe than those in the NCD group ( t=7.405, P<0.001). The triglyceride content was significantly higher in the liver of the mice in the MCD group than that in the NCD group ( t=3.559, P<0.01), and the expression of inflammatory factors IL-1β and MCP-1 was significantly increased ( t=2.562 and 2.391, respectively, P<0.05). Transcriptome sequencing analysis showed that the expression profile of genes related to lipid metabolism was changed in the liver tissue of the mice in the MCD group. The expression of multiple phase Ⅱ detoxification enzymes was significantly downregulated. Real-time fluorescence quantitative PCR verification demonstrated that the expression of four phase Ⅱ detoxification enzymes GSTM4, NQO2, SUIL1β1, and UGT2A3 were significantly lower in the liver of the mice in the MCD group than those in the NCD group ( t=2.498, 3.570, 3.768, and 4.166, respectively, P<0.05). The detection kit showed that compared with the NCD group, the malondialdehyde content in the liver of mice in the MCD group increased ( t=3.601, P<0.01), while the plasma total glutathione ( t=11.93, P<0.001) and reduced glutathione levels were significantly reduced ( t=3.635, P<0.01). The total antioxidant capacity of the liver decreased ( t=2.872, P<0.05), and the total glutathione and reduced glutathione levels in the liver were significantly increased ( t=3.175 and 3.064, P<0.05). Western blotting showed that the expression of Nrf2, GSTM4, and UGT1A6 proteins was significantly lower in the MCD group than that in the NCD group ( t=3.385, 2.990, 2.168, P<0.05). Conclusions:The expressions of multiple phase Ⅱ detoxification enzymes and antioxidant capacity are reduced in the liver of MASH mice induced by the MCD diet, and its mechanism is related to the down-regulation of the expression of the upstream regulatory factor Nrf2 protein.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective: To explore the association between physical activity, anxiety symptoms and academic performance among junior high school students, so as to provide data support for optimizing school physical education and health work and formulating physical activity guidelines. Methods: From September to December 2022, a convenience cluster sampling method was used to survey 2 800 junior high school students in a middle school from Anqing City, Anhui Province. Data were collected on the students anxiety symptoms, academic performance, 24 hour physical activity [moderate to vigorous intensity physical activity(MVPA), light intensity physical activity(LPA), sedentary behavior(SB), and sleep(SLP) duration] as well as demographic characteristics. Compositional data analysis was used to explore the associations between 24 hour physical activity, anxiety symptoms and academic performance among junior high school students, and to predict the optimal time use combination pattern. Results: Among the junior high school students, 16.0% (447 students) reported anxiety symptoms, and 42.0% (1 175 students) achieved excellent or good academic performance. Compositional data analysis showed that increased SLP duration was associated with both reduced anxiety symptoms ( β =-0.18) and decreased academic performance ( β =-0.03) among junior high school students; increased MVPA duration was correlated with fewer anxiety symptoms ( β =-0.02) and lower academic performance ( β =-0.13); in contrast, increased SB duration was linked to more anxiety symptoms ( β =0.09) and higher academic performance ( β =0.09) (all P <0.01). LPA duration exhibited a non linear relationship with anxiety symptoms and academic performance in junior high school students (all P >0.05). The time use combination pattern corresponding to the lowest anxiety symptoms and highest academic performance (top 5%) in adolescents was 611 (520-640) minutes of SLP, 258 (230-320) minutes of SB, 454 (280-610) minutes of LPA, and 117 (20-200) minutes of MVPA per day. Conclusions The 24 hour physical activity of junior high school students is associated with anxiety symptoms and academic performance. Therefore, it is recommended to increase the time spent on SB, MVPA, and LPA for junior high school students, while reducing SB.

Objective:To explore the impact of a comprehensive fall prevention training program on early postural con-trol disorders in elderly patients with Parkinson's disease(PD).Method:Thirty-five early PD patients were randomized into two groups:a conventional training group(n=18)and a fall prevention training group(n=17).Both groups received standard pharmacological therapy and routine functional training,which included strength training and aerobic exercise.The fall prevention training group ad-ditionally received posture control training based on central regulatory mechanisms.All the training were con-ducted 5 sessions per week over an 8-week period.Assessments were performed using a dynamic and static balance training system prior to the program and again after 8 weeks of intervention.The evaluation comprised the sensory organization test(SOT),limits of stability(LOS),and timed up and go test(TUG),as well as the unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ)and Parkinson's disease questionnaire 39(PDQ-39).Result:Within-group comparisons:the total SOT score,SOT proprioception,SOT vestibular function,and the max excursions(MXE)in forward,backward,leftward,and rightward directions in the fall prevention training group were significantly higher after treatment(P<0.05).The visual dependency and visual scores of the SOT in the fall prevention training group did not show significant differences compared to before treat-ment(P>0.05).In the conventional training group,there were no significant differences in total SOT scores,SOT proprioception,SOT visual dependence,SOT vestibular function,or visual scores before and after treat-ment(P>0.05).The leftward MXE in the conventional training group showed a significant increase after treat-ment(P<0.05),while there were no significant differences in forward,backward,and rightward MXE(P>0.05).Both groups exhibited significant decreased TUG,UPDRS-Ⅲ,and PDQ-39 scores after treatment(P<0.05).Between-group comparisons:the total SOT score and vestibular function score in the fall prevention training group was higher than in the conventional training group after treatment(P<0.05,P<0.01).The TUG score in the fall prevention training group was lower than in the conventional training group after treatment(P<0.05).Prior to treatment,there were no significant differences in all indicators between the two groups(P>0.05).There were no significant differences in SOT proprioception,SOT visual dependence,SOT visual scores,MXE in forward,backward,leftward,and rightward directions,UPDRS-Ⅲ,and PDQ-39 after treat-ment between the two groups(P>0.05).Conclusion:The fall prevention training program designed for early PD patients in this study can significantly improve the balance-related sensory integration,proprioception,and vestibular function in these patients,en-hance their MXE in LOS.However,the effects on functional mobility,motor function,and quality of life re-main unclear.Further studies are needed to explore the long-term efficacy of this training program on early postural control disorders in PD patients and its effects on PD patients with cognitive impairments.

BACKGROUND:Cellular pyroptosis is an important pathological mechanism of cerebral ischemia/reperfusion injury.Buyang Huanwu Tang is a classic formula for the clinical treatment of ischemic stroke in traditional Chinese medicine,and cellular pyroptosis may be an effective target of Buyang Huanwu Tang in the treatment of cerebral ischemia/reperfusion injury.OBJECTIVE:To observe the effect and mechanism of Buyang Huanwu Tang on pyroptosis in brain tissues of middle cerebral artery occlusion/reperfusion rats.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,model group,Astragalus membranaceus group and Buyang Huanwu Tang group.Except for the sham operation group,all groups were subjected to middle cerebral artery occlusion for ischemia for 2 hours and reperfusion for 72 hours.The rats in the Astragalus membranaceus group and Buyang Huanwu Tang group were continuously gavaged with the corresponding volume of drugs until ischemia and reperfusion for 72 hours after awakening from the modeling,once in the morning and once in the evening.Zea Longa score was used to observe the neurological deficits of rats.TTC staining was performed to observe cerebral infarct size in rats.Hematoxylin-eosin staining was used to observe the pathological changes of the brain tissue.Immunofluorescence was used to observe the co-expression of Tunel and Cleaved-Caspase-1 in the brain tissue and the expression of the junction protein ASC.Immunohistochemistry and western blot were used to detect the expression of pyroptosis-related proteins in rat brain tissues.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the neurological deficit score of rats was significantly higher in the model group(P<0.01),and compared with the model group,the neurological deficit score of rats was significantly lower in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).(2)Compared with the model group,the volume ratio of cerebral infarction was lower in the Astragalus membranaceus group and Buyang Huanwu Tang group(P<0.01).(3)In the model group,the nuclei of neuronal cells in the brain tissue were deeply stained or lysed,and arrangement of the cells was disorganized.Compared with the model group,the pathologic damage of the brain was less severe in the Buyang Huanwu Tang group and the Astragalus membranaceus group.(4)Compared with the sham operation group,the number of Tunel and Cleaved-Caspase-1 double-positive cells and immunofluorescence intensity of ASC in the brain tissue was significantly increased in the model group,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β was significantly elevated in the model group(P<0.01).Compared with the model group,the number of Cleaved-Caspase-1 and Tunel double-positive cells,immunofluorescence intensity of ASC,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β were all significantly decreased in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).The results indicate that Buyang Huanwu Tang and its monarch drug Astragalus membranaceus can effectively alleviate brain tissue injury in rats with middle cerebral artery occlusion and reperfusion,and its mechanism may be related to the inhibition of neuronal cell pyroptosis.