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.

ObjectiveTo investigate the possible mechanism of Pibai Yucuo Formula （枇柏愈痤方， PYF） in treating acne from the perspective of skin barrier damage. MethodsThirty-two mice were randomly divided into blank group， model group， minocycline group， and PYF group， with 8 mice in each group. Except for the blank group， mice were induced by intradermal injection of Cutibacterium acnes （C.acnes） combined with topical application of artificial sebum to establish acne model. The blank group and model group received intragastric administration of 0.2 ml of distilled water， while the PYF group received intragastric administration of 22.75 g/（kg·d）of PYF， and the minocycline group received 0.013 g/（kg·d）of minocycline suspension， all once daily for 5 consecutive days. On day 0 and day 6 of the experiment， the body weight of mice in each group was recorded， and the absolute value of the body weight difference during the experiment was calculated. Skin conditions were assessed with multifunctional skin imaging system on the 2nd， 4th and 6th day of the experiment. Skin barrier function indicators including transepidermal water loss （TEWL）， and the water content of the stratum corneum and epidermis on day 0， 2， 4 and 6 of the experiment. Optical coherence tomography （OCT） was used to observe stratum corneum and skin thickness on the 1st， 3rd and 5th day of the experiment. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes， while ELISA was used to detect interleukin-17A （IL-17A） levels， and immunofluorescence staining was used to assess skin barrier-related proteins filaggrin （FLG） and loricrin （LOR） levels of skin lesions on day 6 of the experiment. ResultsCompared to the blank group， the model group showed a decrease in body weight on day 6， and an increase in the absolute value of the difference in body weight before and after the experiment （P＜0.05）. On day 4 and 6， TEWL values increased， while water content in the skin stratum corneum and epidermis decreased （P＜0.05）， accompanied by elevated IL-17A level and reduced immunofluorescence intensity of FLG and LOR proteins （P＜0.05）. The model group mice showed papules or pustules at the skin modeling site with progressively worsening desquamation under multifunctional skin imaging system. OCT revealed focal epidermal protrusions， blurred epidermal-dermal boundaries， and disorganized structural layers. HE staining showed significant epidermal hyperkeratosis and incomplete keratinization in the skin， with keratin plug formation in hair follicles and glandular lumens， thickened stratum corneum， hyperplasia of the stratum spinosum， as well as dense dermal inflammatory cell infiltration， and capillary dilation. Compared to the model group， both the minocycline group and the PYF group showed a reduced difference in body weight before and after experiment （P＜0.05）. On day 4 and 6， the TEWL value decreased， and water content of the skin stratum corneum increased （P＜0.05）； on day 6， the IL-17A level in the skin lesions decreased and immunofluorescence intensity of FLG and LOR proteins increased （P＜0.05）. On day 4 and 6， the severity of the skin lesions and range of redness and swelling were lighter than those in the model group， with reverted epidermal thickness， smoother surface and clearer epidermis-dermis boundary. HE staining showed that the degree of skin keratinization was reduced， and the inflammatory infiltration and vascular dilation in the dermis were improved compared to the model group. The PYF group showed better results than the minocycline group in reducing TEWL value on day 4 （P＜0.05）. ConclusionPYF may improve inflammation and skin barrier damage by downregulating IL-17A levels in lesion tissue and increasing skin barrier-related proteins， which could be one of the potential mechanism of action on acne.

Objective To analyze the spatiotemporal distribution characteristics of and trends in the disease burden of dengue fever in China from 2005 to 2024, so as to provide insights into formulation of dengue fever control strategies. Methods Data pertaining to dengue fever cases in China from 2005 to 2024 were retrieved from the Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, and city population, gross domestic product (GDP), GDP per capita, and consumer price index in China were captured from the China Statistical Yearbook, National Bureau of Statistics of China, the China City Statistical Yearbook, and bureaus of statistics in each city. The disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to dengue fever were calculated in China from 2005 to 2024. The direct and indirect economic burdens of dengue fever were estimated to calculate the total economic burden. The trends in the disease burden of dengue fever were estimated in China from 2005 to 2024 using a Joinpoint regression model with the software Joinpoint 4.9.0.0, and the average annual percent change (AAPC) and its 95% confidence interval (CI) were calculated. In addition, the DALYs rate and economic burden of dengue fever in China were subjected to global and local spatial autocorrelation analyses using the software ArcGIS 10.8. Results The gross DALYs due to dengue fever were 5 558 person-years in China from 2005 to 2024, and the DALYs of dengue fever increased from 36 person-years in 2005 to 899 person-years in 2024, with an increase of 23.97 folds. The average annual DALYs rate of dengue fever was 0.02 person-years/10⁵ in China during the 20-year study period from 2005 to 2024, and the DALYs rate peaked in 2014 (0.13 person-years/10⁵) and reduced during the COVID-19 pandemic from 2020 to 2022. YLDs were the main contributor of DALYs due to dengue fever in China from 2005 to 2024, with a total of 5 354 person-years, accounting for 96.33% (5 354 person-years/5 558 person-years) of the gross DALYs. The gross DALYs of dengue fever were 2 982 person-years among men (53.66%) and 2 575 person-years among women (46.34%) in China from 2005 to 2024, and high DALYs of dengue fever were measured among residents at ages of 15 to 30 years (1 639 person-years), 30 to 45 years (1 857 person-years), and 45 to 60 years (1 204 person-years), respectively, accounting for 84.56% (4 700 person-years/5 558 person-years) of total DALYs due to dengue fever in China. The total economic burden of dengue fever was estimated to be 612 million Yuan in China from 2005 to 2024, with an average annual economic burden of 30.584 million Yuan. The economic burden of dengue fever increased from 196 000 Yuan in 2005 to 121 million Yuan in 2024 in China, with an increase of 616.35 folds, and the per capita economic burden increased from 3 322.21 Yuan in 2005 to 4 940.01 Yuan in 2024, with an increase of 48.70%. Dengue fever cases were reported in 274 cities (counties) across 31 provinces (autonomous regions, municipalities) in China from 2005 to 2024, with relatively higher DALYs in Guangdong Province and Yunnan Province. Spatial autocorrelation analysis revealed that the disease burden of dengue fever appeared positive aggregation in Chinese cities (counties) from 2005 to 2024 (global Moran’s I = 0.045, Z = 2.24, P < 0.05), with high-high clusters mainly concentrated in the Pearl River Delta region in Guangdong Province and Xishuangbanna Dai Autonomous Prefecture and Pu’er City in Yunnan Province, and the total economic burden (global Moran’s I = 0.032, Z = 9.55, P < 0.001), per capita economic burden (global Moran’s I = 0.208, Z = 27.34, P < 0.001), and the proportion of total economic burdens in GDP in 2024 (global Moran’s I = 0.017, Z = 5.91, P < 0.001) all presented positive aggregation, with relatively higher total economic burdens mainly concentrated in Guangdong Province and Yunnan Province. Joinpoint regression analysis showed that the gross DALYs rates of dengue fever appeared an overall tendency towards a rise in China from 2005 to 2024 (AAPC = 16.24%, P = 0.029), and the DALYs rate presented an overall tendency towards a rise among both men (AAPC = 14.75%, P = 0.028) and women (AAPC = 14.93%, P = 0.037) during the study period. The per capita direct economic burden appeared an overall tendency towards a rise among dengue fever patients in China from 2005 to 2024 (AAPC = 2.16%, P = 0.012); however, there was no significant difference in the trends in the per capita indirect economic burden (AAPC = 0.46%, P = 0.470). In addition, the DALYs rate of dengue fever appeared a tendency towards a rise in 84.67% (232/274) of cities (counties) in China from 2005 to 2024, and the per capita economic burden appeared a tendency towards a rise in 85.40% (234/274) of cities (counties), while the DALYs rate and per capita economic burden of dengue fever appeared a tendency towards a rise in 77.01% (211/274) of cities (counties). Conclusions The disease burden of dengue fever significantly increased in China from 2005 to 2024. It is recommended to reinforce integrated dengue fever control in high-risk areas and among high-risk populations, and to improve the surveillance of imported dengue fever cases and vector control.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Post-stroke depression(PSD),a common stroke complication characterized by depressed mood and diminished interest,severely affects patients'recovery and quality of life.Microglial abnormal activation and polarization play key roles in PSD pathogenesis,closely associated with neuroinflammation and imbalance in neu-rotransmitter metabolism.In contrast,traditional Chinese medicine(TCM)demonstrates unique multi-target and multi-level mechanisms:regulating microglial function,ameliorating post-stroke neuroinflammatory environments,and promoting neuroplasticity,thereby potentially alleviating PSD symptoms.This review summarizes TCM's effects on microglial activation/polarization states and its therapeutic advances in PSD,providing novel perspectives and strategies for clinical management.

Objective:To design two kinds of intensity modulated radiotherapy (IMRT) plans with different radiation field distributions,and to compare the dose differences of that at the dose of target region and organs at risk (OAR) for middle and lower esophageal cancer,so as to provide a reference for the design of IMRT plan. Methods:The data of 17 patients with middle and lower esophageal cancer who received IMRT at Shangluo Central Hospital from November 2022 to May 2023 were retrospectively analyzed. IMRT plans with different radiation fields for Plan 1 and Plan 2 were designed for each patient. The angles of radiation field for Plan 1 were 0°,80°,120°,160° and 200°,and those for Plan 2 were 30°,130°,180°,230° and 330°,respectively. The prescribed dose to the planning target volume (PTV) was 60 Gy/30 F. The differences in dosimetric parameters between the two plans were compared. Results:There were no statistically significant differences in the dose parameters of 2％,98％,50％ target dose (D2％,D98％,D50％),homogeneity index (HI),conformity index (CI) and monitor unit between the two groups (P>0.05). There were no significant differences in V5 of dual lungs,the mean dose (Dmean) of heart,and the maximum dose (Dmax) of spinal-cord between two groups (P>0.05). The volume percentage (V10,V20,V30) of dual lungs received radiation doses of 10,20 and 30 Gy,and the mean dose (Vmean) of lung in the Plan1 group reduced respectively 7.44％,21.16％,10.09％ and 5.31％ than those in the Plan2 group,and the differences of them were statistically significant (t=-5.845,-7.729,-2.247,-3.960,P<0.05). Heart V10 and V20 in the Plan1 group decreased respectively by 7.23％ and 5.78％,with statistical significance (t=-4.376,-3.523,P<0.01),while V30 and V40 of Plan 1 increased respectively by 2.7％ and 4.92％,without statistical significance (P>0.05). There was no significant difference in heart Dmean between the Plan1 group and the Plan2 group (P>0.05). Conclusion:Both two methods of distribution field can meet the clinical requirements,and Plan1 has more advantages in protecting organs at risk under the premise of meeting the requirements of target region.

Objective To investigate the cerebro protective effect of pre-filled sivelestat sodium during cardiopulmonary bypass(CPB)in patients with valve replacement surgery.Methods From January 2022 to December 2023,104 patients were included and randomly divided into experimental group(n=54)and control group(n=50).The sivelestat sodium 4.8mg/kg was mixed to the pre-filled solutions for CPB in experimental group,while an equal amount of physiological saline solution was mixed in control group.Internal jugular venous blood was collected 5 minutes after anesthesia induction and 10 minutes,4 hours,24 hours,and 72 hours after the aortic cross-clamp was released to detect plasma S-100 protein and interleukin(IL)-6 concentrations.Data on operation time,CPB time,mean arterial pressure,and hematocrit were also recorded.Results There were no statistical differences in operation time,CPB time,assisted circulation time,mean arterial pressure,and hematocrit between two groups(P＞0.05).After anesthesia,there were no significant differences in S-100 protein and IL-6 between two groups(P＞0.05).After,the plasma concentrations of S-100 protein and IL-6 increased in both groups,but the concentrations of S-100 protein and IL-6 in experimental group were significantly lower than those in control group at early stages(10 minutes,4 hours,24 hours)after the aortic cross-clamp was released(P＜0.05).Conclusion Sivelestat sodium,as a cerebro protective drug in CPB heart surgery,can reduce the levels of S-100 protein and IL-6,demonstrating a protective effect on central nervous cells.

Objective To Investigate the efficacy of modified electroconvulsive therapy(MECT)in patients with schizophrenia across different genders.Methods From May 2018 to August 2022,481 patients with schizophrenia were recruited from three psychiatric hospitals in Luzhou,Zigong,and Yibin.According to gender grouping,both groups received adjunctive MECT treatment for two consecutive weeks for a total of six treatments.The differences in positive and negative syndrome scale(PANSS)scores before and after treatment,UKU adverse reaction rating scale(UKU),and gastrointestinal symptom rating scale(GSRS)scores were compared between the two groups.Results After quality control,463 cases were followed up for analysis including 246 males and 217 females.Compared with pre-treatment,the total PANSS score and scores on each subscale were significantly reduced in both genders after treatment(P<0.001).When comparing the reduction rates between the groups,the male patients showed a higher reduction rate in negative symptoms than the female patients(31.24%±30.24%vs.25.80%±33.96%,P<0.05).However,there were no significant differences between the two groups in the reduction rates of the total score,positive symptoms,and general psychopathology(P>0.05).The comparison of adverse reactions showed that the frequency of other types of adverse reactions was higher in female patients than in male patients(47.47%vs.37.80%,P<0.05).However,no significant differences were observed in the adverse reactions related to the mental,neurological,autonomic nervous system,and gastrointestinal systems(P>0.05).Correlation analysis revealed that the reduction rate of the PANSS total score was positively correlated with smoking history(r=0.135,P=0.034)and alcohol history(r=0.160,P=0.012)in male patients,while the reduction rate of the PANSS total score was negatively correlated with the disease duration(r=-0.210,P=0.002)and positively correlated with the age of onset(r=0.145,P=0.032)in female patients.Conclusion MECT is significantly effective for both male and female patients with schizophrenia.Compared to female patients,MECT shows a more pronounced effect on negative symptoms in male patients.Additionally,the factors related to the efficacy of MECT differ between genders,indicating that it is necessary to consider the clinical characteristics of patients comprehensively when selecting an MECT treatment plan.

Objective To Investigate the efficacy of modified electroconvulsive therapy(MECT)in patients with schizophrenia across different genders.Methods From May 2018 to August 2022,481 patients with schizophrenia were recruited from three psychiatric hospitals in Luzhou,Zigong,and Yibin.According to gender grouping,both groups received adjunctive MECT treatment for two consecutive weeks for a total of six treatments.The differences in positive and negative syndrome scale(PANSS)scores before and after treatment,UKU adverse reaction rating scale(UKU),and gastrointestinal symptom rating scale(GSRS)scores were compared between the two groups.Results After quality control,463 cases were followed up for analysis including 246 males and 217 females.Compared with pre-treatment,the total PANSS score and scores on each subscale were significantly reduced in both genders after treatment(P<0.001).When comparing the reduction rates between the groups,the male patients showed a higher reduction rate in negative symptoms than the female patients(31.24%±30.24%vs.25.80%±33.96%,P<0.05).However,there were no significant differences between the two groups in the reduction rates of the total score,positive symptoms,and general psychopathology(P>0.05).The comparison of adverse reactions showed that the frequency of other types of adverse reactions was higher in female patients than in male patients(47.47%vs.37.80%,P<0.05).However,no significant differences were observed in the adverse reactions related to the mental,neurological,autonomic nervous system,and gastrointestinal systems(P>0.05).Correlation analysis revealed that the reduction rate of the PANSS total score was positively correlated with smoking history(r=0.135,P=0.034)and alcohol history(r=0.160,P=0.012)in male patients,while the reduction rate of the PANSS total score was negatively correlated with the disease duration(r=-0.210,P=0.002)and positively correlated with the age of onset(r=0.145,P=0.032)in female patients.Conclusion MECT is significantly effective for both male and female patients with schizophrenia.Compared to female patients,MECT shows a more pronounced effect on negative symptoms in male patients.Additionally,the factors related to the efficacy of MECT differ between genders,indicating that it is necessary to consider the clinical characteristics of patients comprehensively when selecting an MECT treatment plan.