BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Nonalcoholic steatohepatitis （NASH） is a chronic liver disease with the main pathological features of hepatic steatosis， inflammatory cell infiltration， and interstitial fibroplasia， and it is an important risk factor for liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. NOD-like receptor protein 3 （NLRP3） inflammasome is the core of innate immunity， and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH， which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine （TCM） and TCM compound prescriptions can improve oxidative stress， regulate lipid metabolism， and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect， while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome， in order to provide ideas for the clinical TCM treatment of NASH， as well as reference targets and research directions for the research and development of new TCM drugs.

Objective: To investigate the characteristics of temporal and spatial distribution of tuberculosis epidemics in Shache County, Kashgar Region, Xinjiang. Methods: Information on the incidence of tuberculosis in Sacha County from 2019—2021 was collected and spatiotemporally analyzed by applying the circular distribution method, local spatial autocorrelation analysis, hot and cold spot analysis, directional distribution and spatial center of gravity methods. Results : The total number of tuberculosis cases in Shache County in 2019—2021 was 8 345, of which 52.03%were male and 47.97% were female, and the patients were predominantly 60-75 years old. The number of reported incidences of TB in Tagarqi Township, Shache Township, and Chajek Township ranked among the top three in the county. Spring and summer were the disease-prone seasons for TB, and mid-March to mid-July was the period of high disease incidence. Misha Township and Ishkuli Township are the “high and high” gathering areas, while the “low and low” gathering areas are mainly concentrated in Khoshrav Township and Karasu Township. The hotspots of TB incidence in Shache county were Tagarqi township, Misha township, and Ishkuli township. During the study period, the center of gravity of TB incidence in Shache county of Kashgar area gradually shifted from the southwest to the northeast. Conclusion In Shache county, there is a certain degree of aggregation of tuberculosis outbreaks, with more men than women reporting illnesses, a larger proportion of older people, and a strong seasonal incidence of the disease, with Mixia township and Ishikuli township being the key areas of incidence. Relevant departments should continue to strengthen the disease surveillance of key populations and regions during the high incidence of tuberculosis, and take appropriate intervention measures to reduce the risk of tuberculosis transmission.

Spleen-stomach damp-heat syndrome is currently the most prevalent TCM pattern in patients with chronic atrophic gastritis (CAG), with internal damp-heat accumulation regarded as a key factor contributing to its prolonged and refractory course. This syndrome represents a critical stage in the progressive pathogenesis of CAG, characterized by a deepening pathological evolution. Modern TCM practitioners generally agree that its core pathogenesis lies in "deficiency in root and excess in superficiality, with internal damp-heat retention", and emphasize a treatment strategy that combines eliminating pathogenic factors and reinforcing the body's healthy qi through dynamic syndrome differentiation. Chinese materia medica used in treating CAG with spleen-stomach damp-heat syndrome can effectively relieve clinical symptoms, improve the internal damp-heat environment, mitigate gastric mucosal atrophy and intestinal metaplasia, and delay the inflammation-to-cancer transformation. Its mechanisms may involve eradication of Helicobacter pylori, repair of gastric mucosal injury, regulation of immune inflammatory response and other aspects, which has the advantages of multi-channel and multi-target.

Objective To observe the clinical efficacy of electroacupuncture of bilateral Yifeng(SJ17)points penetrating Lianquan(RN23)points combined with electromyographic biofeedback therapy(shortened as EMG biofeedback)in the treatment of post-stroke dysphagia.Methods A total of 94 cases of patients admitted to the wards and outpatient clinics of Handan Mingren Hospital with a definitive diagnosis of post-stroke dysphagia from April 2022 to May 2023 were selected for the study.The patients were randomly divided into observation group and control group according to the random number table method,with 47 cases in each group.Both groups of patients were given basic treatment,the control group was treated with EMG biofeedback,and the observation group was treated with electroacupuncture of bilateral Yifeng points penetrating Lianquan points on the basis of the treatment of the control group.The course of treatment covered four consecutive weeks.After one month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in traditional Chinese medicine(TCM)syndrome scores and Kubota Water Swallowing Test scores,Standardized Swallowing Assessment(SSA)scores,Functional Oral Intake Scale(FOIS)scores,and Swallowing-Quality of Life(SWAL-QOL)scores before and after treatment were observed in the patients of the two groups.The changes of tongue pressure before and after treatment were compared between the two groups.The safety and the incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate was 95.74%(45/47)in the observation group and 76.60%(36/47)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores and Kubota Water Swallowing Test scores of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,SSA and FOIS scores of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the peak tongue pressure,mean tongue pressure,duration of tongue pressure of the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the quality of life scores of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(6)No obvious adverse reactions occurred during the treatment of the two groups of patients,the difference in the incidence of adverse reactions between the two groups of patients being not statistically significant(P>0.05).Conclusion Electroacupuncture of bilateral Yifeng points penetrating Lianquan points combined with EMG biofeedback in the treatment of post-stroke dysphagia exerts certain efficacy,which can improve the swallowing function and tongue muscle strength,reduce TCM syndrome scores,and enhance patients'quality of life.

Objective To compare the safety of laparoscopic pancreatoduodenectomy(LPD)and open pancreatoduodenectomy(OPD)and analyze the learning curve and safety at different stages of LPD.Methods A retrospective analysis was conducted on the clinical data of 50 LPD patients and 54 OPD patients in the Department of Hepatopancreatobiliary Surgery of Suzhou Hospital Affiliated to Nanjing Medical University from January 2020 to June 2024,and intraoperative and postoperative conditions were compared.The Cumulative Sum(CUSUM)analysis method was used to analyze the technical nodes of the LPD learning curve.Results There were no significant differences in operation time and intraoperative blood loss between the LPD group and the OPD group(P＞0.05).There was also no significant difference in the incidence rates of pancreatic fistula(grade B and C),delayed gastric emptying,postoperative bleeding,biliary fistula and intra-abdominal infection between the LPD group and the OPD group(P＞0.05).A time series plot of operation time was drawn based on the patient's operation time and surgical sequence,yielding a fitted curve.Curve analysis showed initial stage and stable stage were finished at the 17th and 24th cases.The LPD learning curve could be divided into three stages:stage Ⅰ characterized as the initial stage(cases 1 to 17),stage Ⅱ characterized as the stable stage(cases 18 to 24),and stage Ⅲ characterized as the proficient stage(cases 25 to 50).The operation time in stages Ⅱ and Ⅲ was significantly shorter than that in stage Ⅰ,and the intraoperative blood loss in stage Ⅰ was significantly higher than that in stage Ⅲ(P＜0.05).There was no significant difference in the incidence of complications among the three stages(P＞0.05).Conclusion LPD and OPD show no significant differences in indications and safety.The LPD learning curve can be divided into three stages.As the number of surgeries completed increa-ses,the operation time of physicians gradually shortens,and the incidence of complications of patients gradually decreases.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

OBJECTIVE To study the intervention effects of Wenshen Tongluo Zhitong Recipe(WTZR)on macrophage senes-cence and senile osteoporosis.METHODS The senescent macrophage model was established using hydrogen peroxide(H2 O2)and subsequently divided into four groups:control,model,low-dose drug-treated serum,and high-dose drug-treated serum.β-galactosidase staining,Western blot and qPCR were employed to evaluate the mRNA expression of senescence markers p21 and p53.ROS staining and JC-1 staining were applied to assess mitochondrial function in macrophages.The mRNA levels of Interleukin(IL)-6,IL-10,CD206,and inducible nitric oxide synthase(iNOS)were determined by qPCR analysis.Immunofluorescence was used to evaluate argi-nase(ARG1)and iNOS protein expressions for assessing the impact of drug-containing serum on macrophage polarization.qPCR analy-sis was conducted to measure osteocalcin(OCN),collagen type Ⅰ alpha 1(Col1a1),runt-related transcription factor 2(Runx2)mRNA levels as osteoblast-related markers;ALP staining along with alizarin red staining were performed to evaluate the effect of macrophage conditioned medium treated with drug-containing serum on bone marrow mesenchymal stromal cell(BMSC)osteogenic differentiation.C57BL/6J mice were randomly allocated into four groups:control group,model group,WTZR low-dose group,and WTZR high-dose group.The senile osteoporosis(SOP)mouse model was established by D-galactose.Micro-CT scanning analyzed fe-mur microstructure while HE staining detected pathological changes in femur bone tissue samples collected from each experimental con-dition.Furthermore,Western blot was used to detect the senescence-related molecules p21 and p53 and the osteogenesis-related mark-ers OCN and Runx2,qPCR analysis measured tibial expression levels of senescence-related molecules(p21,p53)as well as macro-phage polarisation-related molecules(IL-6,iNOS,CD206,and IL-10)to assess the effect of this compound on a mouse model simula-ting SOP.RESULTS Following intervention with serum containing WTZR,there was a significant decrease in the number of senes-cent positive cells compared to the model group.Additionally,there was a notable decrease in p21 and p53 mRNA and proteins expres-sion(P＜0.05,P＜0.01,P＜0.001).Furthermore,drug-containing WTZR effectively inhibited ROS production induced by H2 O2 and mitigated mitochondrial membrane potential reduction in macrophages(P＜0.05,P＜0.001).Treatment with drug-containing WTZR re-sulted in down-regulated mRNA expression of M1-related gene iNOS(P＜0.05)while up-regulating mRNA expression of M2-related genes CD163 and CD206(P＜0.05).The drug-containing WTZR significantly reduced fluorescence intensity for iNOS(P＜0.01)while increasing ARG1(P＜0.05)fluorescence intensity.Moreover,conditioned medium from macrophages treated with drug-containing ser-um increased ALP positive cell count(P＜0.01,P＜0.001),alizarin red positive area(P＜0.05),as well as Col1a1,Runx2 and OCN mRNA expression levels(P＜0.05,P＜0.01).The Tb.N,BMD,and BV/TV were significantly higher in the WTZR group compared to the model group(P＜0.05,P＜0.01,P＜0.001);meanwhile,Tb.Sp was notably lower than that observed in the model group(P＜0.05,P＜0.01);bone trabeculae were significantly improved,increased in number and widened.Additionally,the compound could significantly inhibit the D-galactose induced up-regulation of tibial senescence-related genes and proteins p21 and p53(P＜0.05,P＜0.001,P＜0.0001),promote the expression of osteogenesis-related markers OCN and Runx2 protein(P＜0.01,P＜0.0001),promote the down-regulation of M1 related genes IL-6 and iNOS(P＜0.05),and promote the expression of M2 related genes IL-10 and CD206(P＜0.05,P＜0.01).CONCLUSION Wenshen Tongluo Zhitong Recipe may play an anti-osteoporosis effect by inhibiting macrophage senescence and promoting the osteogenic differentiation of BMSC.