Objective To analyze the epidemiological characteristics and immunization history of pertussis cases in Yichang City, Hubei Province from 2018 to 2023. Methods Data on the incidence and immunization history of pertussis cases were collected in Yichang City from 2018 to 2023, and the epidemiological characteristics was analyzed and described. Results A total of 109 cases of pertussis were reported in Yichang from 2018 to 2023, and the annual average reported incidence rate was 0.45/100,000. The incidence rate reported in each year was between 0～1.58/100,000. The area with the highest annual reported incidence rate was Xiling District (1.19/100,000). There was a statistically significant difference in the incidence rate between different years (χ²=208.26, P < 0.001). The annual reported incidence rate showed a significant increasing trend (χ² trend =125.71, P < 0.001). The ratio of male to female cases was 1.22. There was no significant difference in the annual reported incidence rates between males and females (χ²=0.85, P=0.36). Children aged 3-9 years accounted for 60.55%. Students and scattered children accounted for 45.87% and 36.70%, respectively. Before the onset of the disease, 72.48% had a history of immunization with pertussis-containing vaccine, and 27.52% had no history of immunization. The shortest interval between the last dose of pertussis-containing vaccine and the onset of the disease was 8 days, the longest was 4057 days, and the median was 1882 days. Conclusion From 2018 to 2023, the reported incidence of pertussis in Yichang City has been on the rise, with the majority of cases occurring in children and students under the age of 9. It is recommended to strengthen pertussis disease monitoring.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective To investigate the role of homologous genes absent from the wings of drosophila melanogaster(Notch)signaling pathway in the imbalance of helper T cells 1(Th1)and helper T cells 2(Th2)and the intervention mechanism of Qizhi Zhoufei Granule in chronic obstructive pulmonary disease(COPD).Methods Ten of seventy Wistar rats were selected as the blank control group,and the other rats were established by cigarette smoking combined(CS)with tracheal infusion of lipopolysaccharide(LPS).The COPD model was established by randomly selecting 3 rats in the control group and the model group to verify the success of the model.At the end of modeling,gavage administration was performed.The rats in the model group were randomly divided into model control group,positive control group(67.5 μg·kg-1)and Qizhi Zhoufei Granule high,medium and low treatment group(3.24,1.62,0.81 g·kg-1).Each group was treated with normal saline,dexamethasone acetate suspension and Qizhi Zhoufei Granule suspension at high,medium and low doses.The rats in the blank control group were given the same volume of normal saline as the model control group.After modeling with 28 days and treatment with 28 days,peak inspiratory flow(PIF)and peak expiratory flow(PEF)were detected by the animal lung function test system.Rats were killed to extract lungs,spleen,serum and bronchoalveolar lavage fluid(BALF),hematoxylin-eosin(HE)staining was used to evaluate the pathological changes of lung tissues.The level of tumor necrosis factor-α(TNF-α)in serum and BALF was determined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect Th1/Th2 cells in spleen.Immunohistochemistry(IHC)and western blot were used to detect Notch1,Hes1 and Hey1 protein levels in lung tissues.Real-time fluorescence quantitative polymerase chain reaction(Real-Time PCR)was used to detect Notch1,Hes1 and Hey1 gene expression levels in lung tissues.Result Compared with the blank control group,the lung function of the model control group was significantly decreased(P<0.05),inflammatory cell infiltration and bronchial structure destruction occurred in the lung tissue,TNF-α content in serum and BALF increased significantly(P<0.05),the percentage of spleen Th1 cells was significantly decreased(P<0.05),and the percentage of Th2 cells was significantly increased(P<0.05),the protein and mRNA expressions of Notch1,Hes1 and Hey1 in lung tissues were significantly increased(P<0.05),the differences were statistically significant;Compared with the model control group,the lung function of rats in each administration group was significantly increased(P<0.05),the pathological injury of lung tissue was alleviated,TNF-α content in serum and BALF decreased significantly(P<0.05),the percentage of spleen Th1 cells was significantly increased(P<0.05),the percentage of Th2 cells was significantly decreased(P<0.05),the lung tissue of Notch1,Hes1,Hey1 protein and mRNA expression were significantly decreased(P<0.05),the differences were statistically significant.Conclusion Qizhi Zhoufei Granule regulate Th1/Th2 balance by inhibiting Notch signaling pathway,thereby improving pulmonary function and pathological injury,and affecting immune function in COPD rats.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective:To observe the effect of epigallocatechin gallate (EGCG) on intestinal injury in sepsis, and to investigate the effect on endoplasmic reticulum stress (ERS) apoptotic pathway.Methods:Sixty male SD rats were selected and divided into five groups according to the randomized numeric table method: the sham operation group (Sham group), the cecal ligation and puncture sepsis group (CLP group), the sepsis+EGCG low-dose group (postoperative intraperitoneal injection of EGCG 25 mg/kg, EL group), the sepsis+EGCG medium-dose group (postoperative intraperitoneal injection of EGCG 50 mg/kg, EM group), and sepsis+EGCG high-dose group (postoperative intraperitoneal injection of EGCG 75 mg/kg, EH group), each group with 12 rats. The rats in each group were executed 24 h after modeling and specimens were collected. Inflammatory factors in serum were detected by enzyme-linked immunosorbent assay. Pathological changes of ileum were observed under light microscope after hematoxylin eosin staining and evaluated according to the Chiu's score. The intestinal tissues were stained for tight junction protein-1 (CLDN1, Claudin-1), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), protein kinase RNA-like endoplasmic reticulum kinase (PERK), cysteinyl aspartate specific protein-12 (Caspase-12), and CCAAT enhancer-binding protein homologous protein (C/EBP-homologous protein antibody, CHOP) protein expression was detected by protein immunoblotting assay. The positive areas of Claudin-1, p-PERK, CHOP, and Caspase-12 in intestinal tissue were detected by immunohistochemistry.Results:Compared with the Sham group, the serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and the Chiu's score of rats in the CLP group were increased (all P<0.05). The ileal mucosal tissues showed reduced expression of Claudin-1, ERS apoptosis-associated protein p-PERK, CHOP, and Caspase-12 expression were increased (all P<0.05). Compared with the CLP group, the intestinal injury in rats was alleviated after the administration of low, medium and high dose EGCG intervention (all P<0.05). The serum inflammatory factor level, Chiu's score and the protein expression level and positive area of ERS apoptosis-related proteins, p-PERK, CHOP, and Caspase-12 in the small intestinal tissues of EL group were further reduced compared with that of the CLP group were further decreased, and EM group was further decreased than EL group, and EH group was further decreased than EM group (all P<0.05). The protein expression level and positive area of Claudin-1 in small intestinal tissues of EL group were further increased compared with that of CLP group (both P<0.05), and EM group was further increased compared with that of EL group and EH group was further increased compared with EM group (all P<0.05). Conclusions:EGCG may have a protective effect on intestinal injury in septic rats by inhibiting the activation of ERS-induced apoptotic pathway, and the efficacy of high-dose EGCG has a better effect.

Objective To investigate the effect of Yes-associated protein(YAP)on intervertebral disc nucleus pulposus cells and its possible mechanism.Methods The relatively normal and degenerative intervertebral disc tissues of patients who underwent lumbar surgery in our hospital from March 2021 to July 2022 were harvested,and then the expression of YAP in the tissues were detected by immunohistochemistry assay and Western blotting.Human primary nucleus pulposus cells were isolated and primarily cultured,and treated with IL-1β to induce degeneration.Then the cells was divided into control group,IL-1β group,IL-1β+LV-YAP group,IL-1β+YAP-siRNA group,and IL-1β+LV-YAP+3-MA group.Western blot analysis was used to detect the expression of the proteins related to extracellular matrix catabolism and autophagy in each group.Finally,a rat model of disc degeneration was established,and the expression of YAP and LC3 and disc degeneration were observed with MRI,Alcian blue staining and immunohistochemistry.Results The expression level of YAP was significantly lower in the degraded disc tissues than the relatively normal disc tissues(P＜0.05).The IL-1β+LV-YAP group had significantly increased protein levels of Collagen Ⅱ,Aggrecan,and LC3-11(P＜0.05),and decreased levels of MMP-3 and MMP-13(P＜0.05)when compared with the cells after IL-1β treatment,whereas the IL-1β+YAP-siRNA group showed the exact opposite effects.What's more,pretreatment with autophagy inhibitor 3-MA resulted in decreased number of GFP-LC3 positive particles and protein levels of Collagen Ⅱ,Aggrecan and LC3-Ⅱ(P＜0.05),and increased protein expression of MMP-3 and MMP-13(P＜0.05)in comparison with the conditions in the IL-1β+LV-YAP group.Furthermore,YAP overexpression promoted LC3 expression and inhibited disc degeneration in rat model of disc degeneration.Conclusion YAP overexpression can inhibit extracellular matrix degradation by promoting autophagy in human nucleus pulposus cells and thus delaying disc degeneration.

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

Helicobacter pylori infection is an important causative factor in a variety of gastrointestinal diseases,such as atrophic gastritis,peptic ulcer disease,and gastric cancer.Timely eradication treatment is con-ducive to maintaining the health of patients.With the increase of drug resistance in Helicobacter pylori,dual therapy with proton pump inhibitors combined with high-dose amoxicillin has gradually gained attention.Potassium-competitive acid blockers are new types of antacids that have a faster onset of action and a longer lasting acid sup-pression effect than traditional proton pump inhibitors,making it more suitable for dual therapy.In recent years,scholars have carried out a lot of exploration,improvement and verification of potassium-competitive acid blockers dual therapy,and this article reviews its research progress.

Venous thromboembolism(VTE)is a prevalent complication in orthopedics.In recent years,machine learning has been widely applied in orthopedics.The essence of machine learning lies in utilizing algorithms to analyze vast amounts of data and construct risk prediction models that can accurately forecast unknown clinical outcomes.By integrating high-risk factors,machine learning aids medical professionals in precisely identifying and screening individuals with a high risk of VTE and offering them timely individualized interventions.This article reviews the concept and classification of machine learning,the advantages of machine learning in enhancing model prediction ability,and the current application status of machine learning in constructing risk prediction models for patients with VTE.