Skeletal muscle atrophy refers to a pathological condition characterized by muscle fiber atrophy as well as decreased muscle mass and muscle strength induced by various predisposing factors. It falls under the category of “flaccidity syndrome” in traditional Chinese medicine， and its pathogenesis is mainly associated with disturbed protein homeostasis， mitochondrial dysfunction and oxidative stress injury. Active ingredients of traditional Chinese medicine exerts synergistic regulatory effects via multiple pathways， thus possessing unique advantages in the clinical prevention and treatment of skeletal muscle atrophy. This paper reviews the mechanisms by which active ingredients of traditional Chinese medicine alleviate skeletal muscle atrophy. Existing studies have demonstrated that such active ingredients can ameliorate skeletal muscle atrophy through multiple approaches： regulating protein metabolic balance （geniposide， matrine， schisandrin A， etc.） and oxidative stress （astragaloside Ⅳ， Gastrodia elata polysaccharide， Angelica sinensis polysaccharide， etc.）， improving mitochondrial function （parthenolide， berberine， curcumin， etc.）， facilitating myogenesis and myogenic differentiation （cucurbitacin Ⅱb， saikosaponin A， saikosaponin D， etc.）， suppressing inflammatory response （ursolic acid， triptolide， emodin， etc.）， ameliorating insulin resistance （akebiasaponin D， etc.）. In the future， active ingredients of traditional Chinese medicine are expected to achieve breakthroughs in clinical treatment for skeletal muscle atrophy， providing novel ideas and strategies for the prevention and treatment of degenerative disorders.

Objective:To sort out the situation,content and practical experience of the"four sinkings"in the construction of tightly-knit county medical communities,and provide references and basis for the promotion of policies in various regions.Methods:Quantitative description methods were used to analyze the development trends of the number of health technicians and medical services in primary healthcare facilities.Literature research methods were used to analyze policy content.Case analysis methods were used to summarize and analyze the implementation content and support mechanisms of the"four sinkings"in Youxi County of Fujian Province,Dongyang City of Zhejiang Province,Dongtai City of Jiangsu Province and Suixi County of Anhui Province.Results:From 2010-2022,more health technicians and medical services still flew to hospitals,indicating that personnel is an important impact factor for service sinking.The task of personnel and service sinking to the primary healthcare level is still arduous.From 2023 to 2024,China has issued multiple national policies to clarify the content of the"four sinkings",among which personnel sinking is the core,technology sinking is the means,management sinking is the support,and service sinking is the goal.Case analysis result shows that typical regions have established a long-term mechanism to promote the"four sinkings"through talent pool constrution,economic incentives,medical insurance support and informatization construction.Conclusion and Suggestions:It is needed to enhance the understanding of the"four sinkings",and promote them as important policy measures;promote the experience of typical regions,with a focus on the establishment of a long-term mechanism;and strengthen trace study and monitoring and evaluation to ensure the implementation of the"four sinkings".

Objective:To sort out the situation,content and practical experience of the"four sinkings"in the construction of tightly-knit county medical communities,and provide references and basis for the promotion of policies in various regions.Methods:Quantitative description methods were used to analyze the development trends of the number of health technicians and medical services in primary healthcare facilities.Literature research methods were used to analyze policy content.Case analysis methods were used to summarize and analyze the implementation content and support mechanisms of the"four sinkings"in Youxi County of Fujian Province,Dongyang City of Zhejiang Province,Dongtai City of Jiangsu Province and Suixi County of Anhui Province.Results:From 2010-2022,more health technicians and medical services still flew to hospitals,indicating that personnel is an important impact factor for service sinking.The task of personnel and service sinking to the primary healthcare level is still arduous.From 2023 to 2024,China has issued multiple national policies to clarify the content of the"four sinkings",among which personnel sinking is the core,technology sinking is the means,management sinking is the support,and service sinking is the goal.Case analysis result shows that typical regions have established a long-term mechanism to promote the"four sinkings"through talent pool constrution,economic incentives,medical insurance support and informatization construction.Conclusion and Suggestions:It is needed to enhance the understanding of the"four sinkings",and promote them as important policy measures;promote the experience of typical regions,with a focus on the establishment of a long-term mechanism;and strengthen trace study and monitoring and evaluation to ensure the implementation of the"four sinkings".

Objective To compare the effects of Tripterygium wilfordii polyglycosides,cyclophosphamide,and cisplatin on the establishment of a mouse model of diminished ovarian reserve(DOR).Methods Mice were randomly divided into the following treatment groups:control(Ctrl),Tripterygium wilfordii polyglycosides(TWP),cyclophosphamide(CTX),and cisplatin(DDP).Mice in the TWP group received a 50 mg/kg suspension of Tripterygium wilfordii polyglycosides by gavage for 14 days,mice in the CTX group received a 20 mg/kg cyclophosphamide suspension by intraperitoneal injection for 14 days,and mice in the DDP group received a 1.5 mg/kg cisplatin solution by intraperitoneal injection for 14 days.The body weight,uterine index,and ovarian index were recorded,the estrous cycle was monitored using the vaginal smear method,and the levels of anti-Mullerian hormone(AMH),estradiol(E2),follicle stimulating hormone(FSH),and luteinizing hormone(LH)were detected using ELISA.Hematoxylin and eosin staining was used to detect ovarian follicle development.The rates of oocyte maturation and fertility were analyzed.Results The three treatment groups of mice all showed the following:significantly decreased body weight and ovarian index(P＜0.05);apparent disorder of the estrous cycle;significantly decreased levels of AMH and E2(P＜0.05);decreased and increased rates of developing follicles and atretic follicles,respectively(P＜0.05);and significantly decreased rates of oocyte maturation,pregnancy,and live birth(P＜0.05).Conclusions DOR mouse models were successfully constructed using Tripterygium wilfordii polyglycosides,cyclophosphamide,or cisplatin,as evidenced by decreased body weight and ovarian index,disordered estrous cycle and hormones,and DOR function,resulting in reduced rates of oocyte maturation,pregnancy,and total number of live births.These DOR effects were most appropriate in the cyclophosphamide group.

Objective To investigate the correlation between novel bone metabolism markers and the degree of aortic calcification as well as cardiovascular event risk in elderly patients treated by PD.Methods A prospective trial was conducted on 230 elderly patients receiving continuous am-bulatory PD in our department from February 2022 to February 2024.According to the occur-rence of cardiovascular events during dialysis treatment,they were divided into a cardiovascular event group(n=92)and a control group(n=138).Relevant clinical data were collected,aortic calcification was assessed using AAC scores,and serum levels of bone metabolism markers,inclu-ding osteoprotegerin,TRACP,and PINP were measured.Results The serum levels of osteoprote-gerin,TRACP and PINP were significantly higher in the cardiovascular event group than the con-trol group(P＜0.01).The cardiovascular event group had obviously severe calcification and higher AAC score than the control group(P＜0.01).The serum levels of the three bone metabolism markers were notably higher in the patients with severe calcification than those with moderate calcification,followed by mild calcification in turn(P＜0.01).Spearman correlation analysis indi-cated that the levels of the three indicators were positively correlated with the degree of aortic cal-cification in elderly PD patients(r=0.465,P=0.000;r=0.396,P=0.000;r=0.434,P=0.000).Multivariate logistic regression analysis showed that these three indicators were risk factors for cardiovascular events in elderly PD patients(P＜0.01).Conclusion The three bone metabolism markers are significantly correlated with aortic calcification severity and cardiovascular event risk in elderly PD patients.Monitoring these marker levels may be helpful for the assessment and man-agement of cardiovascular risk.

Objective To compare the effects of Tripterygium wilfordii polyglycosides,cyclophosphamide,and cisplatin on the establishment of a mouse model of diminished ovarian reserve(DOR).Methods Mice were randomly divided into the following treatment groups:control(Ctrl),Tripterygium wilfordii polyglycosides(TWP),cyclophosphamide(CTX),and cisplatin(DDP).Mice in the TWP group received a 50 mg/kg suspension of Tripterygium wilfordii polyglycosides by gavage for 14 days,mice in the CTX group received a 20 mg/kg cyclophosphamide suspension by intraperitoneal injection for 14 days,and mice in the DDP group received a 1.5 mg/kg cisplatin solution by intraperitoneal injection for 14 days.The body weight,uterine index,and ovarian index were recorded,the estrous cycle was monitored using the vaginal smear method,and the levels of anti-Mullerian hormone(AMH),estradiol(E2),follicle stimulating hormone(FSH),and luteinizing hormone(LH)were detected using ELISA.Hematoxylin and eosin staining was used to detect ovarian follicle development.The rates of oocyte maturation and fertility were analyzed.Results The three treatment groups of mice all showed the following:significantly decreased body weight and ovarian index(P＜0.05);apparent disorder of the estrous cycle;significantly decreased levels of AMH and E2(P＜0.05);decreased and increased rates of developing follicles and atretic follicles,respectively(P＜0.05);and significantly decreased rates of oocyte maturation,pregnancy,and live birth(P＜0.05).Conclusions DOR mouse models were successfully constructed using Tripterygium wilfordii polyglycosides,cyclophosphamide,or cisplatin,as evidenced by decreased body weight and ovarian index,disordered estrous cycle and hormones,and DOR function,resulting in reduced rates of oocyte maturation,pregnancy,and total number of live births.These DOR effects were most appropriate in the cyclophosphamide group.

Objective To investigate the correlation between novel bone metabolism markers and the degree of aortic calcification as well as cardiovascular event risk in elderly patients treated by PD.Methods A prospective trial was conducted on 230 elderly patients receiving continuous am-bulatory PD in our department from February 2022 to February 2024.According to the occur-rence of cardiovascular events during dialysis treatment,they were divided into a cardiovascular event group(n=92)and a control group(n=138).Relevant clinical data were collected,aortic calcification was assessed using AAC scores,and serum levels of bone metabolism markers,inclu-ding osteoprotegerin,TRACP,and PINP were measured.Results The serum levels of osteoprote-gerin,TRACP and PINP were significantly higher in the cardiovascular event group than the con-trol group(P＜0.01).The cardiovascular event group had obviously severe calcification and higher AAC score than the control group(P＜0.01).The serum levels of the three bone metabolism markers were notably higher in the patients with severe calcification than those with moderate calcification,followed by mild calcification in turn(P＜0.01).Spearman correlation analysis indi-cated that the levels of the three indicators were positively correlated with the degree of aortic cal-cification in elderly PD patients(r=0.465,P=0.000;r=0.396,P=0.000;r=0.434,P=0.000).Multivariate logistic regression analysis showed that these three indicators were risk factors for cardiovascular events in elderly PD patients(P＜0.01).Conclusion The three bone metabolism markers are significantly correlated with aortic calcification severity and cardiovascular event risk in elderly PD patients.Monitoring these marker levels may be helpful for the assessment and man-agement of cardiovascular risk.

Objective:To assess the predictive value of dosiomics in predicting the occurrence of bone marrow suppression (BMS) in patients with pelvic tumors during radiotherapy.Methods:A retrospective analysis was conducted on the clinical data and radiotherapy planning documents of 129 patients with pelvic region tumors who underwent radiotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2019 to January 2023. The region of interest (ROI) was outlined for bone marrow in the pelvic region by Accu Contour software in planning CT, and the ROI was exported together with the dose distribution file. According to a stratified randomization grouping method, the patients were divided into the training set and test set in an 8 vs. 2 ratio. The dosiomic features were extracted from the ROI, and the two independent samples t-test and the least absolute shrinkage and selection operator (LASSO) algorithm was employed to identify the best predictive characteristics. Subsequently, the dosiomic scores were calculated. Clinical predictors were identified through both univariant and multivariate logistic regression analyses. Predictive models were constructed by using clinical predictors alone and combining clinical predictors and dosiomic scores. The efficacy of predictive model was assessed by plotting the receiver operating characteristic (ROC) curve and evaluating its performance through the area under the ROC curve (AUC), the calibration curve, and decision curve analysis (DCA). Results:Fourteen dosiomic features that showed a strong correlation with the occurrence of BMS were screened and utilized to calculate the dosiomic scores. Based on both univariant and multivariate logistic regression analyses, chemotherapy, planning target volume (PTV) and V 5 Gy were identified as clinical predictors. According to the combined model, the AUC values for the training set and test set were 0.911 and 0.868, surpassing those of the clinical model (AUC=0.878 and 0.824). Furthermore, the analysis of both the calibration curve and DCA suggested that the combined model had higher calibration and net clinical benefit. Conclusion:The combined model has a high diagnostic value for predicting BMS in patients with pelvic tumors during radiotherapy.

Objective:To investigate the impact of exogenous lactate on the replication of dengue virus type 2 (DENV-2) in Raw264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and THP-1 cells and explore its association with cell activation.Methods:BMDMs from BALB/c mouse bone marrow were prepared and evaluated by flow cytometry to detect the proportion of F4/80 + CD11b + cells. Glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), and monocarboxylate transporters 4 (MCT4) expression at mRNA level in BMDMs at different time points after DENV-2 infection were measured by qRT-PCR. The content of lactate in the culture supernatants was quantified via colorimetric assay. CCK-8 assay was used to evaluate the impacts of different concentrations of lactate on the viability of Raw264.7 cells, BMDMs, and THP-1 cells. qRT-PCR was used to detect the expression of DENV-2 E gene, TGF-β, CD86, retinoic acid-inducible gene Ⅰ (RIG-Ⅰ), IFN-β, interferon-stimulated gene 15 (ISG15), and ISG56 at mRNA level in cells infected with DENV-2 at different MOIs in the presence of different concentrations of lactate. Meanwhile, flow cytometry was used to analyze the expression of CD86 and CD206. Results:The percentage of BMDMs was (87.53±1.66)%. GLUT1 expression at mRNA level exhibited a decrease in BMDMs at 24 h after DENV-2 (MOI=3) infection following a transient increase at 12 h ( P<0.05), while HK2 expression at mRNA level was higher that than in blank control and inactivated DENV-2 infection groups at 12, 24, and 36 h ( P<0.01). Besides, there was an increase in both MCT4 mRNA level and the content of lactate in culture supernatants at 24 h after DENV-2 (MOI=1.5) infection ( P<0.05). The viability of the three types of cells remained above 80% when the concentration of lactate was 31.25 mmol/L. Lactate at the concentration of 35 mmol/L increased the expression of the DENV E gene at mRNA level in DENV-2-infected BMDMs at MOI=1 or MOI=2 ( P<0.05). Besides, it promoted the expression of DENV E gene at mRNA level in Raw264.7 and THP-1 cells ( P<0.001) as well as the expression of CD163, TGF-β, RIG-Ⅰ, IFN-β, ISG15 and ISG56 at mRNA level in BMDMs at MOI=1.5, but inhibited the expression of CD86 at mRNA level in BMDMs ( P<0.05). It also up-regulated CD206 protein expression ( P<0.01) and down-regulated CD86 protein expression ( P>0.05) in BMDMs. Conclusions:Exogenous lactate enhances DENV-2 replication in both human- and murine-derived macrophages and that might correlate with M2 macrophage polarization.

Abstract: Objective　To investigate the effect of Aedes albopictus salivary protein rAlb-34k2-1-induced mouse splenocytes immune response on dengue virus type 2 (DENV-2)-infected bone marrow-derived macrophages (BMDM) in vitro. Methods　The specific cell proliferation response of splenic cells from immunized/non-immunized mice to Alb34k2-1 protein was analyzed using the CCK-8 assay. The antigen-presenting cells (APCs) loaded with mosquito saliva proteins rAlb-34k2-1 protein/rAalb_CTL1 protein were prepared and co-cultured with lymphocytes from spleens of immunized/non-immunized mice. On the one hand, the levels of DENV-2 nucleic acids in BMDM treated with cell supernatants from mixed lymphocyte co-cultures were analyzed by qRT-PCR, and the effect of specific T cell response induced by rAlb-34k2-1 on DENV-2 replication in BMDM was analyzed. On the other hand, the expression of the DENV-2 E gene in BMDM pretreated with rAlb-34k2-1 protein was also evaluated to determine the direct effect of immunized mouse spleen lymphocytes co-cultured at 48 h and 72 h and the effect of spleen lymphocytes from immunized or non-immunized mice on DENV-2 replication in pretreated BMDMs was analyzed. Results　Compared to the non-immunized group, the rAlb-34k2-1 protein in vitro caused a specific proliferation of immunized-splenocytes, with a proliferation index (SI) >2 (P<0.000 1).Mixed lymphocyte culture supernatants loaded with rAlb-34k2-1 protein inhibited DENV-2 replication in BMDM, while the mixed lymphocyte culture supernatants loaded with rAalb_CTL1 protein had no such effect (2-ΔΔCT<0.5, P<0.05). There was no difference in DENV-2 intracellular replication in rAlb-34k2-1 pretreated BMDM after co-culture with either immunized-lymphocytes or non-immunized-lymphocytes. Conclusions　The supernatant induced by the mouse T cell response to the rAlb-34k2-1 protein can inhibit DENV-2 replication in BMDM cells, providing preliminary experimental evidence to explore the role of mosquito salivary protein-induced immune responses in the pathogenesis of mosquito-borne viruses.