This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

OBJECTIVES: To identify risk factors for recurrent plastic bronchitis (PB) among children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: The clinical data of children with MPP complicated by PB who underwent bronchoscopy at Gansu Province Maternity and Child Health Hospital between July 2023 and January 2025 were retrospectively analyzed. Patients were grouped into a single-episode PB group and a recurrent PB group according to the number of PB episodes. Multivariable logistic regression was used to identify risk factors for recurrent PB. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of individual and combined predictors. RESULTS: A total of 264 children were included; 188 (71.2%) had a single episode of PB and 76 (28.8%) had recurrent PB. Multivariable logistic regression analysis showed that decreased serum albumin, atelectasis, and fever persisting beyond 72 hours after the initial bronchoscopy were significantly associated with recurrent PB (all P<0.05). The combination of these predictors yielded a sensitivity of 82.9%, specificity of 61.7%, and an area under the ROC curve of 0.777 (95%CI: 0.714-0.839), outperforming any single predictor (P<0.05). CONCLUSIONS In children with MPP complicated by PB, decreased serum albumin, the presence of atelectasis, and fever persisting beyond 72 hours after the initial bronchoscopy are associated with an increased risk of PB recurrence. In such cases, early repeat or multiple bronchoscopic interventions should be considered.
Humans ; Pneumonia, Mycoplasma/complications* ; Male ; Female ; Risk Factors ; Recurrence ; Child, Preschool ; Bronchitis/etiology* ; Child ; Retrospective Studies ; Logistic Models ; Infant ; ROC Curve ; Adolescent

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Objective:To investigate the predictive value of color Doppler ultrasound combined with electrocardio-gram for right heart dys function in patients with pulmonary heart disease(PHD).Methods:A total of 100 PHD patients admitted in Dongcheng Branch of First Affiliated Hospital of Anhui Medical University between January 2020 and December 2023 were retrospectively analyzed.According to results of 6min walking test(6MWT),pa-tients were divided into good right heart function group(n=64,≥350m)and right heart dysfunction group(n=36,＜350m).The indexes of cardiac color ultrasound[isovolumic relaxation time(IVRT),isovolumetric contraction time(IVCT)and right ventricular Tei index],ECG[24h mean R-R interval standard deviation(SDNN),normal R-R interval standard deviation per 5min(SDANN)and the ratio of low frequency components to high frequency components(LF/HF)]were compared between two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of color Doppler ultrasound,ECG and their combination for right heart dys-function in PHD patients.Spearman correlation coefficient was used to analyze the association of color Doppler ul-trasound,ECG and their combination with right heart dysfunction in PHD patients.Results:Compared with those in good right heart function group,patients in right heart dysfunction group had significant higher IVRT[(120.64±14.08)ms vs.(97.87±10.93)ms],IVCT[(84.28±12.33)ms vs.(71.92±10.61)ms]and Tei index[(0.85±0.11)vs.(0.63±0.07)](P＜0.001 all),and significant lower SDNN[(75.52±12.58)ms vs.(85.58±11.75)ms],SDANN[(63.86±10.92)ms vs.(76.75±11.71)ms]and LF/HF[(1.33±0.19)vs.(1.84±0.27)](P＜0.001 all).ROC curve indicated that the AUC of color Doppler ultrasound combined ECG in diagnosing right heart dysfunction in PHD patients was 0.911(95％CI 0.838～0.959),which was significantly higher than those of color Doppler ultrasound[0.775(95％CI 0.681～0.853),Z=2.404,P=0.016]and ECG[0.688(95％CI 0.588～0.777),Z=3.968,P=0.001]alone.Spearman correlation analysis indicated that there was a significant positive correlation of color Doppler ultrasound(r=0.547),ECG(r=0.375)and their combination(r=0.810)with right heart dysfunction in PHD patients(P＜0.001 all),and the correlation between combined detection and right heart dysfunction in PHD patients was significantly higher.Conclusion:Color Doppler ultrasound combined with ECG possesses high diagnostic performance for right heart dysfunction in PHD patients.

Tuberculosis is a serious public health problem worldwide,including China.It is a typical zoonotic disease that can be transmitted between people and animals.Effective control of zoonotic tuberculosis(ZTB)is important for achieving the END-TB goal on schedule,and markedly influences the national economy.This article reviews the pathogenic characteristics,epidemic status,history,and progress in construction of a system for global and domestic ZTB prevention and control strategies.Our goal is to help achieve complete control and eradication of ZTB and tuberculosis through departmental cooperation,and joint prevention and control measures,by improving systematic understanding of ZTB among personnel formulating ZTB prevention and control policies,high-risk professionals,and clinical workers.

AIM To study the chemical constituents from the leaves of Drynaria fortunei(Kunze)J.Sm.and their antioxidant activity.METHODS ODS-AG-HG,Sephadex LH-20 and semi-preparative HPLC were used for separation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH mothod.RESULTS Fifteen compounds were isolated and identified as kaempferol-3-O-neohesperidoside(1),dihydrodehydrodiconiferyl alcohol(2),kaempferol-3,7-di-O-α-L-rahmnoside(3),astragalin(4),loliolid(5),trichothecene analogue(6),2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane(7),maculatin(8),trichothecin(9),4-[(Z)-but-2-enoyloxy]-8-chloro-12-hydroxy-7,13-epoxytrichothec-9-ene(10),8-deoxy-trichotecin(11),β-sitosterol(12),daucosterol(13),afzelin(14),samwinol(15).The IC50 values of the leaf and rhizome extracts against DPPH free radicals were(0.072±0.005),(0.287±0.012)mg/mL,respectively.CONCLUSION Compounds 1,2,5-11,15 are isolated from this plant for the first time.The leaves of D.fortunei exhibit strong antioxidant activity.

OBJECTIVE To analyze the characteristics of 57 acquired immune deficiency syndrome(AIDS)patients complicated with cryptococcal meningitis and observe the treatment outcomes.METHODS Totally 57 AIDS pa-tients with complicated cryptococcal meningitis who were treated in Guiyang Public Health Treatment Center from Jan.2019 to Jun.2023 were continuously assigned as the cryptococcal meningitis group,meanwhile,57 patients with simple AIDS were chosen as the simple AIDS group based on a 1∶1 ratio matching case-control study.Both groups received standardized therapies on basis of the criteria.The clinical characteristics,T lymphocyte subsets,biochemical indexes and treatment outcomes were observed and compared between the two groups.RESULTS There were no significant differences in gastrointestinal reactions,fever and eye discomfort between the two groups;the incidence of neurological symptoms of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There was significant difference in the peripheral blood T lymphocyte subsets be-tween the cryptococcal meningitis group and the simple AIDS group(P＜0.05).The levels of whole blood CD4+,CD4+/CD8+and CD8+of the cryptococcal meningitis group were lower than those of the simple AIDS group;the serum glucose(GLU)level of the cryptococcal meningitis group was lower than that of the simple AIDS group;the serum adenosine deaminase(ADA)level of the cryptococcal meningitis group was higher than that of the sim-ple AIDS group;the serum immunoglobulin A(IgA)level of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There were no significant differences in the immunological failure,vir-ological failure and immunological failure plus virological failure between the two groups after the treatment for 6 months.CONCLUSIONS The incidence of neurological symptoms is higher among the patients with AIDS com-plicated with cryptococcal meningitis than among the patients with simple AIDS.The patients have poor treatment outcomes and more severe damage of T lymphocyte subset functions,and the levels of biochemical indexes vary a-mong the patients,which may provide bases for diagnosis of diseases and assessment of curative effect and prog-nosis.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:To explore the clinical characteristics and treatment methods of patients with small bowel obstruction secondary to mesenteric ischemia (MI).Methods:The clinical data of 24 patients with small intestinal obstruction secondary to MI from December 2021 to December 2024 in the Fourth Affiliated Hospital of Nanjing Medical University were retrospectively analyzed, including the clinical characteristics and surgical treatment.Results:Among the 24 patients with small intestinal obstruction secondary to MI, 19 were male and 5 were female, with ages ranging from 21 to 65 years old, and the disease course was 0.5 (1.0, 5.5) months. There were 8 cases of deep vein thrombosis, 6 cases of hypertension, 6 cases of atrial fibrillation, 5 cases of short bowel syndrome, 4 cases of abdominal trauma and 23 cases with a history of abdominal surgery. There were 4 cases of acute onset, presenting with full abdominal pain, elevated D-dimer and hematogenous intestinal obstruction. There were 20 cases of chronic onset, presenting with recurrent abdominal pain, weight loss and mechanical intestinal obstruction. The pathogenic factors were superior mesenteric vein thrombosis in 7 cases, superior mesenteric arteriosclerosis in 6 cases, mesenteric injury repair in 4 cases, superior mesenteric artery embolism in 3 cases, superior mesenteric aneurysm in 2 cases, superior mesenteric artery dissection in 1 case, and ileocolic aneurysm in 1 case. Three patients underwent surgical operations after the failure of interventional surgeries, and 20 patients were directly treated with surgery. The small intestinal obstruction was completely relieved in all cases. Another case was treated conservatively, but the small intestinal obstruction was not completely relieved.Conclusions:Small bowel obstruction secondary to MI is often atypical. CT angiography should be performed to identify the cause of obstruction due to deep vein thrombosis, atrial fibrillation, abdominal trauma or abdominal surgery. Surgery is the preferred treatment.

Objective:To investigate the predictive value of color Doppler ultrasound combined with electrocardio-gram for right heart dys function in patients with pulmonary heart disease(PHD).Methods:A total of 100 PHD patients admitted in Dongcheng Branch of First Affiliated Hospital of Anhui Medical University between January 2020 and December 2023 were retrospectively analyzed.According to results of 6min walking test(6MWT),pa-tients were divided into good right heart function group(n=64,≥350m)and right heart dysfunction group(n=36,＜350m).The indexes of cardiac color ultrasound[isovolumic relaxation time(IVRT),isovolumetric contraction time(IVCT)and right ventricular Tei index],ECG[24h mean R-R interval standard deviation(SDNN),normal R-R interval standard deviation per 5min(SDANN)and the ratio of low frequency components to high frequency components(LF/HF)]were compared between two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of color Doppler ultrasound,ECG and their combination for right heart dys-function in PHD patients.Spearman correlation coefficient was used to analyze the association of color Doppler ul-trasound,ECG and their combination with right heart dysfunction in PHD patients.Results:Compared with those in good right heart function group,patients in right heart dysfunction group had significant higher IVRT[(120.64±14.08)ms vs.(97.87±10.93)ms],IVCT[(84.28±12.33)ms vs.(71.92±10.61)ms]and Tei index[(0.85±0.11)vs.(0.63±0.07)](P＜0.001 all),and significant lower SDNN[(75.52±12.58)ms vs.(85.58±11.75)ms],SDANN[(63.86±10.92)ms vs.(76.75±11.71)ms]and LF/HF[(1.33±0.19)vs.(1.84±0.27)](P＜0.001 all).ROC curve indicated that the AUC of color Doppler ultrasound combined ECG in diagnosing right heart dysfunction in PHD patients was 0.911(95％CI 0.838～0.959),which was significantly higher than those of color Doppler ultrasound[0.775(95％CI 0.681～0.853),Z=2.404,P=0.016]and ECG[0.688(95％CI 0.588～0.777),Z=3.968,P=0.001]alone.Spearman correlation analysis indicated that there was a significant positive correlation of color Doppler ultrasound(r=0.547),ECG(r=0.375)and their combination(r=0.810)with right heart dysfunction in PHD patients(P＜0.001 all),and the correlation between combined detection and right heart dysfunction in PHD patients was significantly higher.Conclusion:Color Doppler ultrasound combined with ECG possesses high diagnostic performance for right heart dysfunction in PHD patients.