BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

OBJECTIVE To establish a reliable mouse eosinophilic chronic rhinosinusitis model,study the histological and immunological effects of glucocorticoids on type 2 inflammatory cells and factors in nasal mucosa,and provide an animal model basis for the biological treatment of CRS and related research of resistance to glucocorticoids in vivo.METHODS The CRS model group was treated with ovalbumin and Staphylococcal enterotoxins B.The dexamethasone intervention group received an additional weekly intraperitoneal injection of dexamethasone for 8 weeks.The expression of type-2 innate lymphoid cell(ILC2)in the nasal mucosa was detected with immunofluorescence and the expression of tryptase+mast cells,eosinophil cationic protein(ECP),IL-5,IL-25,and IL-33 in the nasal mucosa was detected with immunohistochemical.RESULTS The nasal mucosa eosinophils in the dexamethasone intervention group was lower than in the CRS model group(P<0.05).Thy-1+ST2+ILC2 cells in the dexamethasone intervention group were less than those of the CRS model group,and Thy-1+ST2+ILC2 cells were rare in the control group.Tryptase+mast cells were moderately positive in the CRS model group and weakly positive in the control group and in the dexamethasone intervention group.ECP and IL-5 were strongly positive in the CRS model group and weakly positive in the control group and the dexamethasone intervention group.IL-25 was moderately positive in the control group,strongly positive in the CRS model group,and weakly positive in the dexamethasone intervention group.IL-33 was weakly positive in the control group,while the CRS model group and the dexamethasone intervention group were strongly positive.CONCLUSION Intraperitoneal injection of dexamethasone reduce the number of eosinophils,Thy-1+ST2+ILC2 cells and tryptase+mast cells in the nasal mucosa of the mouse CRS model.It can also down-regulate the expression of ECP,IL-5,and IL-25 in tissues,but it does not have a significant effect on the expression of IL-33 in tissues.

Objective:To analyze the current situation and core issues of medical escort services in Shanghai through a two-side (supply and demand) survey, so as to provide references for formulating targeted strategies for the standardized management of this industry.Methods:From June to August 2024, a questionnaire survey on awareness of escort services was conducted among patients at 16 tertiary public hospitals in Shanghai. The survey covered patients′ basic information, their needs, concerns, and expectations regarding escort services. Concurrently, a specialized questionnaire was administered to trainees enrolled in Shanghai Open University′s " elderly care escort service provider" program. This survey covered the companions′ basic profiles, types of service recipients, relevant qualifications, training programs, and standardized service procedures. Data were organized and analyzed by using SPSS 26.0 software.Results:The survey on awareness of patient escort services yielded 855 valid responses, achieving a 92.13% response rate. Among these 855 patients, the primary demand for escort services was queue management for examinations (515 cases, 71.47%), followed by assistance with registration/payment/medication pickup (528 cases, 61.74%). 587 patients (68.66%) expressed willingness to use the service. The main concerns included lack of professional expertise among attendants (538 cases, 62.92%), trust issues (494 cases, 57.78%), and fee concerns (456 cases, 53.33%). Expectations for service supervision primarily focused on service quality and safety (618 cases, 72.28%) and pricing standards (609 cases, 71.23%). The specialized survey on medical escort services yielded 194 valid questionnaires, achieving a 100.00% response rate. Among the 194 medical escort service providers, 82.5% (160 individuals) were full-time practitioners, 31.96% (62 individuals) held relevant qualification certificates, and 72.68% (144 individuals) had participated in related training programs. Regarding standardized services, 74.74% (145 individuals) of medical escorts obtained patient information prior to service delivery, 56.70% (110 individuals) signed agreements with users, and 67.01% (130 individuals) maintained records of their medical escort services.Conclusions:Shanghai′s medical escort services had achieved some success, yet faced challenges including high patient demand coupled with low trust, insufficient certification and training for escorts, and an urgent need to improve service standardization. It is recommended that medical institutions further strengthen their primary role in managing escort services. By enhancing top-level design, establishing standardized training and certification mechanisms, implementing comprehensive quality monitoring and credit evaluation systems, and other measures, they could elevate the professional competence of practitioners, reinforce patient safety safeguards, and promote the high-quality, standardized development of escort services.

Objective:To characterize the epidemiological features of hemorrhagic fever with renal syndrome (HFRS) in Jixi region, Heilongjiang Province, and to develop an autoregressive integrated moving average (ARIMA) model to predict the incidence trend of HFRS, thus to provide a scientific basis for targeted prevention and control.Methods:HFRS case data and host animals surveillance data from January 2013 to December 2024 in Jixi City were collected. Descriptive epidemiological methods were used to analyze the temporal, spatial, and population distribution characteristics of HFRS, with comparisons made using the chi-square test. ArcGIS10.8.2 software was employed for spatial clustering analysis. Moran I was used to assess the overall spatial trend of HFRS incidence. Getis-Ord Gi * analyses was used to identify the hotspots and coldspots. SaTScan v10.2 software was applied to detect spatiotemporal clusters. The Spearman correlation analysis was used to examine the relationship between rodent viral load index and HFRS incidence. ARIMA model was constructed and optimized using Bayesian information criterion (BIC) for short-term prediction of HFRS. Results:From January 2013 to December 2024, a total of 1 045 HFRS cases were reported in Jixi City, with an average annual incidence rate of 5.09/100 000. Three epidemic peaks were observed: 2014 (8.12/100 000), 2019 (7.22/100 000), and 2023 (3.86/100 000). The temporal distribution showed a bimodal pattern, with the autumn-winter peak (October to December) having more cases than the spring-summer peak (May to June). Geographically, cases were mainly concentrated in the central-eastern urban areas of Jixi City. The average annual incidence rate in males (7.89/100 000) was significantly higher than that in females (2.24/100 000), the difference was statistically significant ( χ2=322.15, P<0.001). The highest incidence rate was observed in the 50 to 59 age group (6.79/100 000), and farmers accounted for the largest proportion of cases (59.04% (617/1 045)). Spatial analysis revealed clustered distribution (Moran I=0.50, P<0.05), with hotspots in Hulin City and Mishan City. Spatiotemporal analysis identified one significant cluster (radius=89.2 km). No correlation was found between the rodent viral load index and HFRS incidence ( r=0.455, P=0.138). The optimal short-term prediction model was ARIMA (1, 0, 0) (0, 1, 1) (BIC=-3.24), which forecasted 38 HFRS cases in Jixi City in 2025. Conclusions:HFRS incidence in Jixi City exhibits periodicity, seasonality, and spatial clustering. The developed ARIMA model provides a valuable tool for predicting incidence trends, thus to optimize vaccination, rodent control, and surveillance measures in high-risk areas and populations.

Objective:To analyze the current situation and core issues of medical escort services in Shanghai through a two-side (supply and demand) survey, so as to provide references for formulating targeted strategies for the standardized management of this industry.Methods:From June to August 2024, a questionnaire survey on awareness of escort services was conducted among patients at 16 tertiary public hospitals in Shanghai. The survey covered patients′ basic information, their needs, concerns, and expectations regarding escort services. Concurrently, a specialized questionnaire was administered to trainees enrolled in Shanghai Open University′s " elderly care escort service provider" program. This survey covered the companions′ basic profiles, types of service recipients, relevant qualifications, training programs, and standardized service procedures. Data were organized and analyzed by using SPSS 26.0 software.Results:The survey on awareness of patient escort services yielded 855 valid responses, achieving a 92.13% response rate. Among these 855 patients, the primary demand for escort services was queue management for examinations (515 cases, 71.47%), followed by assistance with registration/payment/medication pickup (528 cases, 61.74%). 587 patients (68.66%) expressed willingness to use the service. The main concerns included lack of professional expertise among attendants (538 cases, 62.92%), trust issues (494 cases, 57.78%), and fee concerns (456 cases, 53.33%). Expectations for service supervision primarily focused on service quality and safety (618 cases, 72.28%) and pricing standards (609 cases, 71.23%). The specialized survey on medical escort services yielded 194 valid questionnaires, achieving a 100.00% response rate. Among the 194 medical escort service providers, 82.5% (160 individuals) were full-time practitioners, 31.96% (62 individuals) held relevant qualification certificates, and 72.68% (144 individuals) had participated in related training programs. Regarding standardized services, 74.74% (145 individuals) of medical escorts obtained patient information prior to service delivery, 56.70% (110 individuals) signed agreements with users, and 67.01% (130 individuals) maintained records of their medical escort services.Conclusions:Shanghai′s medical escort services had achieved some success, yet faced challenges including high patient demand coupled with low trust, insufficient certification and training for escorts, and an urgent need to improve service standardization. It is recommended that medical institutions further strengthen their primary role in managing escort services. By enhancing top-level design, establishing standardized training and certification mechanisms, implementing comprehensive quality monitoring and credit evaluation systems, and other measures, they could elevate the professional competence of practitioners, reinforce patient safety safeguards, and promote the high-quality, standardized development of escort services.

Objective:To characterize the epidemiological features of hemorrhagic fever with renal syndrome (HFRS) in Jixi region, Heilongjiang Province, and to develop an autoregressive integrated moving average (ARIMA) model to predict the incidence trend of HFRS, thus to provide a scientific basis for targeted prevention and control.Methods:HFRS case data and host animals surveillance data from January 2013 to December 2024 in Jixi City were collected. Descriptive epidemiological methods were used to analyze the temporal, spatial, and population distribution characteristics of HFRS, with comparisons made using the chi-square test. ArcGIS10.8.2 software was employed for spatial clustering analysis. Moran I was used to assess the overall spatial trend of HFRS incidence. Getis-Ord Gi * analyses was used to identify the hotspots and coldspots. SaTScan v10.2 software was applied to detect spatiotemporal clusters. The Spearman correlation analysis was used to examine the relationship between rodent viral load index and HFRS incidence. ARIMA model was constructed and optimized using Bayesian information criterion (BIC) for short-term prediction of HFRS. Results:From January 2013 to December 2024, a total of 1 045 HFRS cases were reported in Jixi City, with an average annual incidence rate of 5.09/100 000. Three epidemic peaks were observed: 2014 (8.12/100 000), 2019 (7.22/100 000), and 2023 (3.86/100 000). The temporal distribution showed a bimodal pattern, with the autumn-winter peak (October to December) having more cases than the spring-summer peak (May to June). Geographically, cases were mainly concentrated in the central-eastern urban areas of Jixi City. The average annual incidence rate in males (7.89/100 000) was significantly higher than that in females (2.24/100 000), the difference was statistically significant ( χ2=322.15, P<0.001). The highest incidence rate was observed in the 50 to 59 age group (6.79/100 000), and farmers accounted for the largest proportion of cases (59.04% (617/1 045)). Spatial analysis revealed clustered distribution (Moran I=0.50, P<0.05), with hotspots in Hulin City and Mishan City. Spatiotemporal analysis identified one significant cluster (radius=89.2 km). No correlation was found between the rodent viral load index and HFRS incidence ( r=0.455, P=0.138). The optimal short-term prediction model was ARIMA (1, 0, 0) (0, 1, 1) (BIC=-3.24), which forecasted 38 HFRS cases in Jixi City in 2025. Conclusions:HFRS incidence in Jixi City exhibits periodicity, seasonality, and spatial clustering. The developed ARIMA model provides a valuable tool for predicting incidence trends, thus to optimize vaccination, rodent control, and surveillance measures in high-risk areas and populations.

Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P＜0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.

Objective To construct and validate an effective prognostic nomogram for the patients with incidental gallbladder cancer(IGBC).Methods The clinical data of 161 patients with IGBC requiring radical surgery admitted to the First Affiliated Hospital of Xi'an Jiaotong University from May 2011 to October 2022 was analyzed retrospectively.COX proportional risk regression model was used to screen for influencing factors on overall survival(OS)of IGBC.Nomogram was constructed based on independent influencing factors that affected the prognosis of IGBC patients.The concordance index(C-index)and calibration curve were used to validate the performance of the model.Receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA)were used to validate the predictive accuracy and net benefit of the plotted column chart.Results Univariate COX regression analysis suggested that age,T stage,N stage,M stage,preoperative carcinoembryonic antigen(CEA),preoperative carbohydrate antigenl9-9(CA19-9),preoperative red blood cell volume distribution on width coefficient of variation(RDW-CV),treatment method,and recurrence and metastasis were risk factors which affected the long-term survival of IGBC patients after radical surgery.Multivariate COX regression analysis suggested that T stage,N stage,preoperative CA19-9,preoperative RDW-CV,preoperative AST,treatment methods,and recurrence and metastasis were independent risk factors which affected the prognosis of IGBC patients.The C-index of the constructed prognostic model was 0.872.The calibration plot demonstrated good performance of the Nomogram.ROC curve analysis showed an area under the curve of 0.869,confirming a high sensitivity and specificity.A high net benefit was proven by DCA.Conclusions The constructed Nomogram.can accurately and intuitively predict the survival probability of IGBC patients after radical surgery.