ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.

Psoriasis vulgaris is notoriously difficult to treat and prone to recurrence. Traditional Chinese medicine （TCM）， however， has shown considerable efficacy in mitigating or suppressing such recurrence. The underlying reason lies in the TCM concept of "latent pathogens"， which are prone to be reactivated by external pathogenic factors， thereby triggering relapse. At the early stage of recurrence， manifestations of "latent fire" often appear externally. If treatment is not thorough， the condition may shift into a state of "stalemate between healthy Qi and pathogenic factors"， in which the disease appears on the skin but is rooted in deeper pathological layers， remaining unresolved and accumulating internally. Over time， blood stasis arises from fire， and the fire further congeals due to stasis， leading ultimately to recurrent flare-ups. This aligns with the modern immunological concept of "immunological memory" mediated by tissue-resident memory T cells （T_RM） in the skin， which corroborates the TCM view of "latent fire inducing blood stasis". The interaction between T_RM and keratinocytes （KC） parallels the entanglement of latent fire and latent stasis， both of which are deeply entrenched and difficult to resolve. The core pathogenesis of recurrent psoriasis vulgaris lies in "latent fire causing blood stasis". The hallmark is the deep concealment and persistence of latent fire and stasis， which linger and await an opportunity to reemerge. Based on this understanding， Xijiao Dihuangtang is employed to cool the blood， resolve stasis， and eliminate latent pathogens， and treatment is tailored according to the disease stage through three-phase syndrome differentiation. In the progressive stage， both exterior and interior are treated， with emphasis on clearing latent fire. In the stationary stage， the focus shifts to dispelling latent stasis and simultaneously regulating the Zang-fu organs. In the regressive stage， efforts are made to prevent the retention of latent pathogens and to strengthen healthy Qi. Accordingly， drugs effective in dispersing wind and clearing heat， pungent-moistening and dredging the collaterals， and tonifying deficiency and moistening dryness are often employed to achieve optimal outcomes. The precise mechanisms by which Xijiao Dihuangtang treats recurrent psoriasis vulgaris remain to be fully elucidated. Current research suggests it may intervene in the recurrence process through inhibiting KC proliferation via the PI3K/Akt/mTOR signaling pathway and glycolysis， regulating the Th1/Th2 and Th17/Treg cell balances to restore immune homeostasis， suppressing inflammatory cytokine production to alleviate the inflammatory response， modulating angiogenesis-related factors， such as vascular endothelial growth factor A （VEGF-A） and matrix metalloproteinase-9 （MMP-9）， to control disease progression， and restructuring the gut microbiota to modulate systemic immunity and thereby influence the course of disease recurrence.

Objective To explore the therapeutic material basis and antitussive mechanism of Ganke Formula.Methods Ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF/MS)technology was used to analyze and identify the components of Ganke Formula in serum.30 rats were randomly divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,6 rats per group.Acute bronchitis rat model was established by smoke inhalation and cold stimulus.The experimental-L,-M,-H groups were respectively given 1.86,4.66,9.32 g·kg-1(crude drug/weight)dose of Ganke Formula per day by intragastric administration for 7 days.The control group and model group were given the equal amount of normal saline.The contents of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in rat lung tissue were determined by enzyme-linked immunosorbent assay.The expressions of phosphatidylinositol 3-kinase(PI3K)and phosphorylated protein kinase B(p-Akt)in lung were detected by Western blotting.Results Twenty-six absorbed components have been identified by UPLC-Q-TOF/MS.The contents of IL-1β in control group,model group,experimental-M,-H group were(57.80±7.67),(186.48±8.50),(166.05±9.90)and(143.19±6.31)pg·mL-1;TNF-α contents were(47.14±8.55),(316.22±9.49),(68.93±7.94)and(65.93±7.10)pg·mL-1;the relative expression levels of PI3K in lung tissues were 0.38±0.05,0.97±0.10,0.68±0.15 and 0.56±0.10;the relative expression levels of p-Akt were 0.34±0.14,0.93±0.05,0.63±0.16 and 0.49±0.14,respectively.Compared with the model group,the above indicators in the experimental-H group and control group were statistically different(P＜0.01 or P＜0.05).Conclusion Ganke Formula can intervene in the expression of inflammatory and immune regulatory factors by regulating PI3K/Akt signaling pathway,improve airway inflammation,and thus exert cough relieving effects.

AIM:To explore the fundus vascular characteristics of healthy individuals based on deep learning techniques, with a view to discovering the range of normal values of the fundus arteries and veins, as well as the relationship between physiological factors, such as gender, age, body mass index(BMI), blood pressure, and fundus vasculature characteristics.METHODS:Fundus images of healthy people were taken from a professional fundus camera, and the subject's blood pressure and laboratory test was collected. Additionally, the fundus arteries and veins were segmented by the improved U-Net model, and the color, morphology and Haralick texture features of the vessels were extracted from computer vision technology.RESULTS:A total of 4 487 cases fundus images were taken and 326 cases with healthy and clear fundus images were screened, including 200 males and 126 females. There were differences in the morphology, color, and textural characteristics of the left and right eyes, as well as of the fundus arterioles and veins, with a mean vessel width(width)of 1.146 in the arteries and 1.430 in the veins, and an arteriovenous ratio about 4:5. Fundus artery and vein characteristics in healthy individuals of different ages(21-30, 31-40, 41-50): compared with the healthy population aged 21-30 and 31-40 years, arterial and venous inverse difference moment(idm), f12 and venous angular second moment(asm)values increased, and arterial and venous contrast(con), entropy(ent), difference entropy(den), and venous sum entropy(sen)values decreased in 41-50 years. Compared with the 21-30 years age group, arterial f12 values increased and venous con values decreased in 31-40 years(all P<0.05). Fundus vascular characteristics of healthy individuals of different sexes: compared with male, fundus arterial and venous sum average(sav), sum variance(sva)values, arterial curved values, and venous b mean, bsd, variance(var), sen, ent values increased in female, while venous area value of female decreased(all P<0.05). There were no statistically significant differences in fundus arteriosus and venous features in healthy subjects with different levels of BMI(all P>0.05). Fundus characteristics of healthy people with different degrees of blood pressure: there were statistically significant differences in fundus arteriosus area, width, and venous con, idm, dva, and den values between the normal blood pressure and high blood pressure groups(all P<0.05).CONCLUSION: The characteristics of the left and right eyes as well as the fundus arteries and veins differ in healthy individuals and correlate with physiological factors such as gender, age and blood pressure, which have the value of a potential microcirculation marker.

Objective:To investigate the current status of research on the construction of leadership indicator system in the medical field at home and abroad, and to analyze the characteristics of the indicator system therein.Methods:This was a bibliometric study. The group applied subject keywords to search relevant literature on the construction of leadership indicator system in the medical field at home and abroad on English websites PubMed, Web of Science, Google Scholar, CINAHL, Scopus and Chinese websites Baidu Academic, CNKI, CQVIP, Wanfang Data Knowledge Service Platform, with a time frame of 2016-2023. The basic characteristics of the literature, the theoretical framework of the research application and the research theme were extracted, and the content of the indicator system in the literature was reviewed and summarized.Results:A total of 21 literatures were included, including 7 Chinese literatures and 14 English literatures. Of these literatures, 10 focused on physician leadership, 5 on medical manager leadership, and 2 on general practitioner leadership. Among 16 research literatures, 9 informed the theoretical basis of leadership, and 4 literatures were applied research. Five main themes were identified: leadership studies of individual healthcare administrators, leadership development in healthcare, interest and attitudes of healthcare workers towards leadership learning, applications of leadership in healthcare, and the impact of leadership in healthcare on patients and healthcare organizations.Conclusions:At present, research on the construction of the leadership indicator system in the medical field presents is diverse, with differences in theoretical basis and content. The original and empirical research is still insufficient.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.

[摘 要] 目的：为解决野生型B细胞成熟抗原（BCMA）被γ分泌酶切割导致表达不稳定的问题，构建抵抗γ分泌酶切割的BCMA突变体并构建靶细胞，用于评价BCMA CAR-T细胞的杀伤功能。方法：将野生型BCMA的穿膜域替换为人CD8α穿膜域，构建抵抗γ分泌酶切割的BCMA突变体（BCMA-CD8α TM），构建过表达该突变体的U266（U266BCMA Mut）、K562（K562BCMA Mut）、SKOV3（SKOV3BCMA Mut）和CHO（CHOBCMA Mut）细胞；构建装载NFAT-EGFP报告基因的BCMA CAR Jurkat细胞（BCMA-CAR-Jurkat-Reporter）与U266BCMA Mut细胞共培养，采用FCM检测该细胞中EGFP表达水平以指示NFAT激活水平，荧光素酶法检测BCMA CAR-T细胞对Luciferase标记的K562BCMA Mut细胞的杀伤作用，实时无标记动态细胞分析技术（RTCA）检测BCMA CAR-T细胞对SKOV3BCMA Mut和CHOBCMA Mut细胞的杀伤作用。结果：应用γ分泌酶抑制剂LY411575抑制γ分泌酶活性，显著增强野生型U266细胞表面BCMA表达水平，平均荧光强度上调10倍以上；但撤除抑制剂后BCMA表达水平逐渐降低（P<0.01）；BCMA-CD8α TM突变体可抵抗γ分泌酶的切割作用，在U266细胞表面稳定表达（P>0.05）；U266细胞及过表达BCMA-CD8α TM的U266细胞与BCMA-CAR-Jurkat-Reporter细胞共培养后都可激活Reporter系统、增强EGFP表达，但该效应在BCMA-CD8α TM过表达的U266细胞中更显著（P<0.01）；BCMA-CD8α TM在BCMA表达阴性的K562、SKOV3和CHO 3种靶细胞中成功过表达，且在LY411575处理下该突变体的表达水平仅有小幅度升高；荧光素酶法检测结果显示，不同效靶比下，BCMA CAR-T细胞均可特异、高效杀伤过表达BCMA-CD8α TM的K562细胞；RTCA结果显示，不同效靶比下，BCMA CAR-T细胞均可有效识别、杀伤过表达BCMA-CD8α TM的SKOV3和CHO细胞，但同等效靶比下的Mock-T细胞无此效应。结论：本实验构建的BCMA-CD8α TM突变体能够抵抗γ分泌酶的切割，在多种靶细胞表面稳定表达，为评价BCMA CAR-T细胞体外杀伤的有效性和特异性提供多种检测手段。