OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease （CKD）. METHODS Fifty male SD rats were randomly divided into a sham surgery group （10 rats） and a modeling group （40 rats）. The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling， the rats were randomly divided into model group， esaxerenone group （positive control）， and TCM low- and high-dose groups， with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone， while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively， the sham surgery group and model group were given an equal volume of physiological saline， all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea （SUr）， serum creatinine （SCr）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels； enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α（TNF-α）； immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α） ， mitochondrial transcription factor A （TFAM）， absent in melanoma 2（AIM2）， caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in renal tissue； real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group， the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction， severe tubular dilation， and increased deposition of blue fibrin； the levels of SUr， SCr， MDA， IL-1β， IL-6， TNF-α，the protein expression of AIM2， GSDMD， caspase-1， IL-1β， IL-18 ， and the mRNA expression of AIM2 were significantly increased or up-regulated （P＜0.01）； the levels of SOD， the protein expression of PGC-1α， TFAM were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function， alleviate renal inflammatory damage and pyroptosis， and exert renal protective effects by regulating the AIM2 pyroptosis pathway.

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia， and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different， while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms， prepulse inhibition （PPI）， cognitive functioning and neurotrophic factors in patients with chronic schizophrenia， so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） were enrolled and grouped using random number table method， each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment， Patients were required to complete Positive and Negative Symptom Scale （PANSS）， detection of both strong and weak PPIs in a startle modification passive attention paradigm， Wisconsin Card Sorting Test （WCST） and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score， PPI， WCST and neurotrophic factor levels of the groups， with the pretest used as the covariate. Results3 months after treatment， no statistical difference was found in the scores of PANSS general psychopathology subscale， positive symptom subscale， negative symptom subscale and total score between two groups after treatment （F=0.621， 0.815， 0.743， 0.752， P>0.05）. There were no statistically significant differences between the two groups in PPI inhibition rate， single intense stimulus amplitude， single intense stimulus latency， prepulse inhibition amplitude， or prepulse inhibition latency （F=0.174， 0.001， 0.183， 0.171， 0.001， P>0.05）. There was no statistically significant difference in the total number of WCST tests between two groups （F=0.512， P>0.05）， whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group （F=3.737， 4.621， 4.892， 5.130， P<0.05）. A significant increase in brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） along with a reduction in glial fibrillary acidic protein （GFAP） were documented in risperidone group when compared to risperidone group （F=4.414， 3.781， 6.319， P<0.05）. No significant difference was demonstrated in the incidence of adverse reactions between the two groups （χ²=0.261， P>0.05）. ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 （number， FY2021-147）］

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate left ventricular function and myocardial ischemia in patients with different degrees of left anterior descending（LAD）coronary artery stenosis by using post-stress regional myocardial work（MW）and coronary flow reserve（CFR），and to analyze the diagnostic efficacy of each parameter for different degrees of stenosis in the LAD.Methods:A retrospective analysis was conducted on 76 patients with suspected coronary artery disease who underwent coronary angiography and attended the Fourth Affliiated Hospital of Harbin Medical University from January 2023 to June 2024. According to the degree of LAD stenosis，30 cases were categorized into the mild stenosis group（stenosis < 50%），25 cases in the moderate stenosis group（50%≤stenosis < 70%），and 21 cases in the severe stenosis group（70% ≤ stenosis ≤ 90%）. Transthoracic Doppler echocardiography was applied to obtain CFR LAD. Longitudinal strain in the left anterior descending region（LS LAD），peak strain dispersion（PSD），left anterior descending region work index（WI LAD）and left anterior descending region work efficiency（WE LAD）were obtained at rest and under stress，respectively. The LAD regional MW indexes were compared between the groups in two pairs. The correlation between CFR LAD and the degree of LAD stenosis was analyzed. ROC curves were plotted to compare the diagnostic efficacy of LAD regional MW parameters and CFR LAD for moderate and severe LAD stenosis. Results:①At rest：compared with the mild stenosis group，the absolute value of LS LAD，WI LAD，and WE LAD were reduced in the severe stenosis group，and the differences were statistically significant（all P < 0.05）. Compared with the moderate stenosis group，WE LAD was reduced in the severe stenosis group，and the difference was statistically significant（ P < 0.05）. Differences in two-by-two comparisons between groups in the resting state for the remaining parameters were not statistically significant（all P > 0.05）. Under stress：compared with the mild stenosis group，the absolute values of LS LAD，WI LAD，and WE LAD were reduced in the moderate and severe stenosis groups，and the PSD was increased in the severe stenosis group，and the differences were statistically significant（all P < 0.05）. Compared with the moderate stenosis group，the absolute values of LS LAD，WI LAD，and WE LAD were reduced in the severe stenosis group，and the differences were statistically significant（all P < 0.05）. Differences between two-by-two comparisons between groups in the remaining parameters at loading state were not statistically significant（all P > 0.05）. ②CFR LAD was negatively correlated with the degree of LAD stenosis（ r = -0.809， P < 0.05）. ③The ROC curves showed that the peak WE LAD of the regional MW parameters predicated the largest area under the ROC curve（AUC）for moderate and severe stenosis in LAD，0.803 and 0.897，respectively，with cutoff values of 92.5% and 91.5%. The cutoffs of CFR LAD ≤ 2.5 and CFR LAD ≤ 2.0 predicted the greatest AUC for moderate and severe stenosis in LAD at 0.743 and 0.901，respectively. Peak WE LAD combined with CFR LAD predicted the greatest AUC for moderate and severe stenosis in LAD at 0.826 and 0.967，respectively. Conclusions:Regional MW parameters and CFR LAD can sensitively detect left ventricular hypo-function in patients with different degrees of stenosis in LAD. Peak WE LAD and CFR LAD are reliable predictors of moderate and severe stenosis in LAD. A combination of the two techniques can significantly improve diagnostic efficacy.