Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.
Male ; Animals ; Humans ; Mice ; Transcription Factors/genetics* ; Mammals/metabolism* ; Cell Differentiation ; Neoplasms/genetics*

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Objective: To explore the association between weight gain during the first half of pregnancy and the risk of hypertension disorder of pregnancy (HDP). Methods: This prospective cohort study recruited singleton pregnant women in the first trimester from November 2016 to March 2019 at 19 community hospitals in Tianjin. According to pre-pregnancy body mass index (BMI), the cohort was divided into 3 groups: underweight(BMI<18.5 kg/m²), normal-weight(18.5-24.9 kg/m²), and overweight/obese(≥25.0 kg/m²). The basic information of the participants was gathered through questionnaires, and the height, weight, and blood pressure of the participants were measured along with routine pregnancy examinations. The rate of gestational weight gain (rGWG) in the 3 periods (0-13⁺⁶, 14⁺⁰-20⁺⁶, and 0-20⁺⁶ weeks) of the participants was calculated. To observe the occurrence of HDP, the participants were followed up to 42 days postpartum. Using a generalized linear model, the association between rGWG at the 3 periods during the first half of pregnancy and HDP after 20 weeks of gestation was evaluated. Results: A total of 9 805 pregnant women were finally included, with the age of (30.6±3.8) years old, 9 418 (96.1%) Han ethnicity, and 6 845 (69.8%) primipara. There were 1 184 (12.1%), 6 831 (69.7%) and 1 790 (18.3%) participants in the underweight, normal-weight, and overweight/obese groups. Five hundreds and eight pregnant women were diagnosed with HDP (5.2%). The incidences of HDP were 1.8% (21/1 184), 3.9% (269/6 831), and 12.2% (218/1 790), respectively, in underweight, normal-weight, and overweight/obese groups. Adjusted for age, pre-pregnancy BMI, primipara, and family history of hypertension, women in the entire cohort with rGWG ≥ 0.18 kg/week before 13⁺⁶ weeks of pregnancy had a 28% higher HDP risk than those with rGWG ≤ 0.00 kg/week (RR=1.28, 95%CI 1.04-1.55, P=0.015), and the risk of HDP was increased by 39% in the overweight/obese group (RR=1.39, 95%CI 1.04-1.85, P=0.026), while no correlation was found between rGWG and HDP in underweight and normal-weight pregnant women (P>0.05). Weight gain during 14⁺⁰-20⁺⁶ weeks of pregnancy in any group was not related to the risk of HDP (P>0.05).In the entire cohort, compared to rGWG ≤0.14 kg/week, rGWG≥0.28 kg/week prior to 20⁺⁶ weeks increased HDP risk by 36% (RR=1.36, 95%CI 1.11-1.67, P=0.003). Normal-weight pregnant women with rGWG≥0.29 kg/week faced a 46% higher risk of HDP than those with rGWG≤0.15 kg/week (RR=1.46, 95%CI 1.11-1.93, P=0.008).In the overweight/obese group, excessive weight gain before 20⁺⁶ weeks seemed to increased risk of HDP, but the difference was not statistically significant (RR=1.35,95%CI 0.99-1.85, P=0.059), while the connection was nonexistent in underweight women. Conclusions: Except for pre-pregnancy underweight women, excessive weight gain during the first half of pregnancy is associated with increased risk of HDP among pregnant women.
Female ; Pregnancy ; Humans ; Infant, Newborn ; Adult ; Overweight/complications* ; Thinness/epidemiology* ; Prospective Studies ; Risk Factors ; Weight Gain ; Body Mass Index ; Obesity/complications* ; Hypertension, Pregnancy-Induced/etiology* ; Cohort Studies ; Pregnancy Complications

OBJECTIVE: To observe the changes of functional connectivity of brain pain-emotion regulation region in patients with cervical spondylosis of cervical type by functional magnetic resonance imaging (fMRI). METHODS: Thirty-two subjects were selected. Of them, 16 patients with cervical spondylosis of cervical type were divided into an observation group and 16 healthy subjects into a control group. The patients in the observation group were treated with acupuncture at Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and RESULTS: In the observation group, the VAS score was (1.94±1.12) after the treatment, which was lower than (5.62±1.20) before treatment ( CONCLUSION Pain involves the formation and expression of "pain-emotion-cognition". Acupuncture can systematically regulate the brain functional connections between cognitive regions such as dorsal prefrontal lobe and anterior cingulate gyrus and emotional regions such as insula and VTA in patients with cervical spondylosis of cervical type, suggesting that acupuncture has a multi-dimensional and comprehensive regulation effect on pain.
Acupuncture Therapy ; Brain/diagnostic imaging* ; Emotions ; Humans ; Magnetic Resonance Imaging ; Pain ; Spondylosis/therapy*

Type 1 diabetes (T1D) is an autoimmune disease that resulted from the severe destruction of the insulin-producing β cells in the pancreases of individuals with a genetic predisposition. Genome-wide studies have identified HLA and other risk genes associated with T1D susceptibility in humans. However, evidence obtained from the incomplete concordance of diabetes incidence among monozygotic twins suggests that environmental factors also play critical roles in T1D pathogenesis. Epigenetics is a rapidly growing field that serves as a bridge to link T1D risk genes and environmental exposures, thereby modulating the expression of critical genes relevant to T1D development beyond the changes of DNA sequences. Indeed, there is compelling evidence that epigenetic changes induced by environmental insults are implicated in T1D pathogenesis. Herein, we sought to summarize the recent progress in terms of epigenetic mechanisms in T1D initiation and progression, and discuss their potential as biomarkers and therapeutic targets in the T1D setting.
Diabetes Mellitus, Type 1/genetics* ; Epigenesis, Genetic/genetics* ; Genetic Predisposition to Disease/genetics* ; Humans ; Incidence ; Twins, Monozygotic

Objective:To analyze the traditional Chinese medicine（TCM） syndromes of 46 patients with coronavirus disease-2019 (COVID-19) by cluster analysis method. Method:The 46 COVID-19 patients with TCM symptoms, signs, tongue and pulse were analyzed by frequency analysis and clustering analysis, and the TCM syndrome types of COVID-19 patients were classified and summarized by combining clinical expertise, and the evolution law was analyzed by combining the median days of the syndrome collection. Result:The major signs and symptoms of the 46 patients with COVID-19: fever (frequency of 39, accounted for 84.8%), poor appetite (frequency of 44, 95.7%), fatigue (frequency of 42, 91.3%), wheezing breath (frequency of 35, 76.1%), dry mouth (frequency of 21, 45.7%), lung condition short (frequency of 20, 43.5%), defecate pond (frequency of 15, 32.6%), red tongue (frequency 30, accounting for 65.2%), yellowish moss (frequency 27, accounting for 58.7%), and slimy pulse (frequency 30, accounting for 62.5%). TCM syndromes were divided into seven types, i.e. dampness and heat syndrome (13 cases), dampness and toxin syndrome (10 cases), heat stasis syndrome (7 cases), dampness and heat syndrome (5 cases), cold dampness internal invasion syndrome (4 cases), dampness poison blood stasis syndrome (2 cases).According to the time of onset, there were cold and dampness syndrome (median days 6.5 days), dampness was heavier than heat syndrome (10 days), dampness and heat syndrome (10 days), dampness and heat syndrome (11.5 days), heat stagnation of liver and gallbladder syndrome (13 days), dampness and blood stasis syndrome (15 days), and Yin injury syndrome (16 days). Conclusion:Among the 46 cases of COVID -19, damp-heat syndrome was the most common, followed by heat stagnation of liver and gallbladder syndrome, Yin injury and gas consumption syndrome, cold and damp internal invasion syndrome, and dampness and blood stasis syndrome. The pathogenesis of the disease evolved into heat and poison, and later appeared to consume Qi Yin performance.