Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To analyze the epidemiological characteristics of active pulmonary tuberculosis (pulmonary tuberculosis) in Xi'an from 2013 to 2023 and predict the incidence trend of pulmonary tuberculosis in Xi'an by using autoregressive integrated moving average (ARIMA) product seasonal models to provide a decision-making basis for tuberculosis prevention and control.Methods:The incidence data of pulmonary tuberculosis reported in Xi'an from 2013 to 2023 were collected through the Tuberculosis Information Management System of the Chinese Center for Disease Control and Prevention. The Excel 2016 software was used for descriptive statistical analysis of pulmonary tuberculosis incidence data reported in Xi'an from 2013 to 2023. The SPSS 20.0 software was used to establish an ARIMA product seasonal model to predict the incidence of pulmonary tuberculosis in Xi'an.Results:A total of 49 860 cases of pulmonary tuberculosis were reported in Xi'an from 2013 to 2023, with an annual average incidence of 45.60/100 000. The incidence showed a downward trend in the past decade. The incidence was high in spring, with a peak from March to May, a small peak from November to January, and a low incidence in February and October. The annual average incidence of pulmonary tuberculosis in 2 suburban counties (52.80/100 000) was higher than that in 14 urban areas (43.21/100 000) ( χ2=20.19, P<0.001). With the increase of age, the incidence of pulmonary tuberculosis was higher, and the incidence of the males was higher than that of female ( χ2=378.34, P<0.001), the ratio of male to female incidence was 1.73∶1. The most occupation of the population was farmers, accounting for 46.54%. The established ARIMA (0, 1, 1) (1, 1, 1) 12 product seasonal model exhibited a good prediction effect, with the Bayesian Information Criterion being -1.567, the root mean square error being 0.42, and the mean absolute percentage error being 9.62. The average relative error between the actual value and the predicted value was 6.63%, and the 95% CI of the predicted value included the actual value. Conclusions:2013-2023, the incidence of pulmonary tuberculosis in Xi'an has been on the decline as a whole. Special attention should be paid to the prevention and control of tuberculosis in districts (counties) adjacent to mountainous areas in the south, people aged 60 years and above, and farmers and other vulnerable groups. The established ARIMA (0, 1, 1) (1, 1, 1) 12 product seasonal model exhibited a good predictive effect and can be applied to the short-term prediction of tuberculosis incidence.

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.

Chronic heart failure(CHF)is a common end-stage manifestation of cardiovascular disease,and the"spleen-small intestine-heart"axis is its important mechanism.Current studies have shown that the"spleen"in TCM and mitochondria function are similar,and the physiological dysfunction of the"small intestine"is also closely related to intestinal bacterial dysbiosis,and the pathology of the spleen and the small intestine will be transmitted to the heart to accelerate the occurrence and development of CHF.Based on the relevant theory of spleen-small intestine-heart,this article described the correlation between abnormal mitochondrial energy metabolism and imbalance of intestinal flora and CHF from the aspects of the spleen,small intestine and heart,and believed that the essence of CHF is a pathological condition formed by mitochondrial energy metabolism crisis and intestinal microecological disorders,which could provide theoretical references for the TCM prevention and treatment of CHF.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

BACKGROUND: Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear. METHODS: Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low. RESULTS: In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM_2.5 concentrations coexisted with low precipitation. CONCLUSIONS Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology* ; Humans ; Female ; Male ; Aged ; Middle Aged ; Cross-Over Studies ; Hospitalization/statistics & numerical data* ; Adult ; Hemorrhagic Stroke/etiology* ; Meteorological Concepts ; Weather ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Aged, 80 and over ; Young Adult

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

Objective : To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs. Methods: Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results: Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased. Conclusion Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.