Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

OBJECTIVE: To investigate the predictive value of circulating free DNA (cfDNA) combined with interleukin 10 (IL-10) in predicting central nervous system infiltration (CNSI) in diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 63 patients with DLBCL in our hospital from May 2021 to April 2023 were retrospectively analyzed. The 63 patients were divided into CNSI group (15 cases) and non-CNSI group (48 cases) base on whether CNSI occurred. The age, sex, Ann Arbor stage, ECOG score, IPI risk, CNS-IPI risk, number of extranodal sites involved, bone marrow involvement, hypertrophic disease, B symptoms, source cells, glucose quantification, Pandy test, cerebrospinal fluid (CSF) chlorine, CSF nucleated cell count, CSF protein, peripheral blood cfDNA, and IL-10 status were compared between the two groups. The correlation between cfDNA, IL-10 in peripheral blood and CSF protein was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of peripheral blood cfDNA and IL-10 on secondary CNSI in DLBCL patients. The last follow-up was on November 30, 2023. Kaplan-Meier method was used to calculate the time of secondary CNSI in the non-CNSI group. RESULTS: The IPI risk, CNS-IPI risk, number of extranodal sites involved, and CSF protein in the CNSI group were significantly higher than those in the non-CNSI group (all P <0.05). The levels of cfDNA and IL-10 in peripheral blood of CNSI group were significantly higher than those of non-CNSI group (both P <0.01). cfDNA and IL-10 in peripheral blood were both positively correlated with CSF protein (r =0.402 4, 0.315 1). ROC curve analysis showed that peripheral blood cfDNA and IL-10 had certain predictive value for CNSI, and the area under the curve (AUC) was 0.829 and 0.742, respectively. The AUC of the combined detection was 0.910, with a sensitivity of 80.00% and a specificity of 93.70%. The diagnostic efficacy was significantly higher than that of the two prediction values alone. The median follow-up time was 20 (6-31) months. Non-CNSI patients were grouped based on peripheral blood cfDNA combined with IL-10 positive or negative pairs. The time of secondary CNSI in positive group was significantly shorter than that in negative group (P <0.05). CONCLUSION cfDNA and IL-10 in peripheral blood of DLBCL patients with CNSI are significantly increased, and the combined detection of cfDNA and IL-10 has good predictive value for CNSI.
Humans ; Interleukin-10/blood* ; Lymphoma, Large B-Cell, Diffuse/blood* ; Retrospective Studies ; Female ; Male ; Cell-Free Nucleic Acids/blood* ; Middle Aged ; ROC Curve ; Prognosis ; Central Nervous System Neoplasms ; Central Nervous System/pathology* ; Adult ; Predictive Value of Tests

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors

Objective To construct the animal model,and to study the expression and clinical signifi-cance of YKL-40 in the progress of chronic renal failure complicating cardiac dysfunction.Methods C57BL/6N mice were chosen as the experimental subjects and divided into the blank control(BC)group,renal failure(RF)group,heart failure(HF)group and renal combined heart failure group.The renal failure model was constructed by adenine perfusion.The heart failure model was constructed by subcutaneous injection of isopro-terenol.The renal failure and heart failure group model was established by adenine perfusion combined with subcutaneous injection of isoproterenol.The validity of constructed models was evaluated by creatinine(SCr),urea nitrogen(BUN)and BNP levels,renal ultrasound and ultrasonic cardiogram examination results.The levels of C-reactive protein(CRP)and YKL-40 were detected by ELISA,and the YKL-40 mRNA expression level in kidney and heart tissues was measure by RT-qPCR.The Image J software was used to calculate the collagen fiber area of the Masson staining results.Results Except the blank control group,the mice weights in the other 3 groups were decreased,and the differences were statistically significant(P＜0.05).SCr,BUN,average renal cross sectional area,average renal volume and renal CVF in the renal failure group and renal combined heart failure group were higher than those in the blank control group and heart failure group(P＜0.05).The levels of LVEF,LVCO,LVSV,LVFS,LVPWd and LVPWs in the heart failure group and renal combined heart failure group were lower than those in the blank control group and renal failure group(P＜0.05).LVEF and LVFS in the renal combined heart failure group were higher than those in the heart failure group(P＜0.05).Compared with the blank control group,the serum CRP and YKL-40 levels in the other three groups were higher(P＜0.05);the CRP and YKL-40 levels in the renal combined heart failure group were higher than those in the renal failure group and heart failure group(P＜0.05).In the myocardial tis-sues,the YKL-40 mRNA expression level in the heart failure group and renal combined heart failure group was higher than those in the blank control group and renal failure group(P＜0.05).YKL-40 had the correla-tion with CRP(r=0.88,P＜0.05).Serum YKL-40 had the correlation with renal tissue YKL-40 gene expres-sion(r=0.77,P＜0.05),and had the correlation with the renal tissue CVF(r=0.89,P＜0.05).Conclusion YKL-40 has the influencing effect on renal failure complicating heart dysfunction,and could serve as the biomarker to mo-nitor the renal insufficiency complicating heart function abnormality.

Objective:To explore the effects of Qingre Qudu Decoction for fumigation combined with three-gap drainage on wound healing and serum inflammatory factors in patients with acute perianal abscess.Methods:Randomized controlled trial was conducted. A total of 117 patients with acute perianal abscess in the hospital were enrolled as the observation objects between August 2022 and May 2024. According to random number table method, they were divided into observation group (59 cases) and control group (58 cases). Both groups received three-gap drainage therapy. On basis of three-gap drainage, control group was given potassium permanganate, while observation group was given Qingre Qudu Decoction for fumigation. All patients were treated for 14 d. The growth of granulation tissue and wound secretions before and after treatment was evaluated. VAS scale was used to evaluate the degree of incision pain, and Wexner score was used to assess incontinence; ELISA was used to detect serum activator A (ACTA), immunoturbidimetry was used to detect serum CRP, and radioimmunoassay was used to detect serum IL-6 levels. The occurrence of complications and abscess recurrence during treatment was recorded, and clinical efficacy was evaluated.Results:The total effective rate of the observation group was 96.61% (57/59), while that of the control group was 82.76% (48/58), with statistical significance ( χ2=6.10, P=0.014). After treatment, scores of granulation tissue growth and wound secretions in observation group, and scores of VAS and Wexner incontinence in observation group were lower than those in the control group ( t=9.66, 5.00, 7.98, 3.65, P<0.001), and wound healing time was shorter than that in control group ( t=8.41, P<0.001). After treatment, levels of serum ACTA, CRP and IL-6 in observation group were lower than those in control group ( t=15.30, 2.08, 19.34, P<0.01 or P<0.05). The incidence of postoperative complications in the observation group was 6.78% (4/59), while in the control group it was 27.59% (16/58), with statistical significance ( χ2=8.93, P=0.003). Conclusion:Qingre Qudu Decoction for fumigation combined with three-gap drainage can relieve postoperative incision pain, inhibit inflammatory response, accelerate the recovery of wound and promote the recovery of anal function and improve clinical efficacy.

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation(FMT)on chemotherapy-induced diarrhea(CID)in mice.Methods Fifteen C57BL/6N mice were divided into control group,CID model group and CID+FMT group according to the random number distribution and remainder grouping method,with 5 mice per group.Control group received no intervention,and their feces were used to prepare fecal bacteria suspension.CID model group was injected intraperitoneally with fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,followed by gavage with 0.1 ml of saline on alternate days.CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week,followed by intraperitoneal injection of fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,with the experiment ending on the 14th day.During the experiment,the mice's food intake and body weight were recorded.At the end of the experiment,the mice were euthanized with deep carbon dioxide anesthesia,and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin(HE)staining and histopathological examination.Fecal samples were collected for 16S rRNA gene sequencing.Shannon index,Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice.Similarity analysis(Anosim)was used to perform non-parametric on the inter-group differences of intestinal flora among the mice.Linear discriminate analysis size effect(LEfSe)and nonmetric multidimensional scaling(NMDS)were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice.Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group(P<0.05),while there was no significant difference between CID+FMT group and CID model group(P>0.05).The weight of mice in CID model group decreased by 42.04%,while control group mice gained 10.24%,with a significant difference between the two groups(P<0.05).The weight of mice in CID+FMT group decreased by 8.12%,which was significantly improved compared to CID model group(P<0.05).HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged,with atrophy and deformation,accompanied by inflammatory cell infiltration,and the pathological score was higher than that of control group(P<0.05).Compared with CID model group,the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved,with less damage,and the pathological score was lower than that of CID model group,but the difference was not statistically significant(P>0.05).The α-diversity analysis showed that there were significant differences in the Shannon,Simpson and Chao1 indices among the three groups(P<0.05).ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group.LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae,and the intestinal flora in CID+FMT group was similar to that of control group,with an enrichenment of familiy_Enterobacteriaceae.Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice,making it more similar to normal intestinal flora,thereby protecting intestinal mucosa,reducing damage and alleviating the severity of CID.

Currently, transcatheter intervention is the preferred treatment for patients with anatomically suitable atrial septal defects. However, the use of nickel-titanium alloy occluders in interventional procedures results in lifelong presence of the implant in the body, leading to complications such as metal allergies and arrhythmias in some patients. To overcome the short-term and long-term complications associated with the presence of metal, and to avoid radiation exposure and metal toxicity, this paper reports a case of successful transcatheter closure of atrial septal defect in a pediatric patient with metal allergies using fully biodegradable occluder under ultrasound guidance, achieving excellent results by interventional therapy.