ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

Objective To analyze the clinical distribution,drug resistance characteristics,molecular prevalence,and impact of immunocompromised status on the infection rate of carbapenem-resistant Enterobacteriaceae(CRE)isolated from pediatric respiratory tract samples(sputum,bronchoalveolar lavage fluid).Methods A retrospective analysis was conducted on clinical data of hospitalized children from 2019 to 2023.A total of 1 235 non-repetitive strains of Enterobacteriaceae bacteria were obtained from pediactric respiratory tract samples.Drug susceptibility testing,multilocus sequencing typing(MLST),and resistance-related gene sequencing were performed on 100 isolated CRE strains,to study the clinical distribution,drug resistance characteristics,and molecular prevalence of CRE,and to further analyze the impact of immunocompromised status on the respiratory CRE infection rate in children.Results From 2019 to 2023,the detection rate of CRE in 1 235 strains of Enterobacteriaceae bacteria was 8.10%(100/1 235).Among them,51.0%(51/100)of CRE were isolated from the intensive care unit(ICU),of which 33.0%(33/100)were isolated from the Surgical ICU,18.0%(18/100)of CRE was isolated from the Medical ICU;32.0%(32/100)of CRE were isolated from Department of Neonatology,with the majority(74.0%)isolated from infants under 6 months of age.Of all pediatric patients,85.0%recovered and were discharged after treatment.Immunocompromised status was identified as an independent risk factor for CRE infection.Among 100 strains of CRE,Carbapenem-resistant Klebsiella pneumoniae(CRKP)was the most commonly detected strain,accounting for 88.0%(88/100),followed by Escherichia coli at 6.0%(6/100)and Enterobacter cloacae at 4.0%(4/100).CRE strains were highly resistant to carbapenems and cephalosporins,with prevalent resistance to amikacin,ciprofloxacin,and levofloxacin.However,their resistance rates were relatively low to tigecycline,colistin,minocycline,ceftazidime/avibactam,meropenem/vaborbactam,and imipenem/relebactam.The screening results of carbapenem resistance genes showed that blaKPC-2 was the most prevalent gene(74.0%),followed by blaNDM-1(14.0%)and blaNDM-5(11.0%).Molecular typing showed that ST11 type CRE was the dominant type,comprising 72.0%(72/100)and was the primary epidemic clone.Conclusions CRKP is the most prevalent CRE strain isolated from pediatric respiratory tract samples,primarily identified in the ICU,Department of Neonatology,and among infants under 6 months of age.Immunocompromised status is an independent risk factor for respiratory CRE infection in children.CRE generally has high resistance to antibacterial drugs,with blaKPC-2 being the dominant resistance genotype,and ST11 as the predominant multilocus sequence type.Clinical management should account for these characteristics to implement timely interventions and rational therapeutic strategies.

Objective To investigate the antimicrobial resistance patterns of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from children for better prevention,treatment,and control of CRKP infections in children.Methods A total of 182 clinical CRKP strains were collected between January 2018 and December 2020 in Hebei Children's Hospital.All CRKP strains were identified by matrix-assisted laser desorption ionization-time of flight(MALDI-TOF)mass spectrometry.The common carbapenemase genes(blaKPC,blaNDM,blaIMP,blaVIM,blaOXA-48)of CRKP isolates were studied by PCR.Multilocus sequence typing(MLST)was performed for homology analysis.Results The 182 children infected with CRKP were mainly infants(＞28 days to＜1 years),accounting for 49.45％(90/182),followed by newborns(≤28 days),accounting for 36.26％(66/182).The main source of the 182 CRKP isolates was sputum(50.55％,92/182),blood(15.93％,29/182),and urine(13.19％,24/182).The strains were mainly isolated from patients in neonatology(30.22％,55/182),general surgery(21.43％,39/182),cardiac surgery(13.19％,24/182),and intensive care unit(11.54％,21/182).Antimicrobial susceptibility testing showed that all of the 182 CRKP strains were resistant to cefepime,ceftazidime,piperacillin-tazobactam,and cefoperazone-sulbactam(100％).Overall,97.8％,71.4％,81.9％,75.8％,69.2％,and 2.7％of the strains were resistant to aztreonam,amikacin,ciprofloxacin,levofloxacin,doxycycline,and tigecycline,respectively.The prevalence of carbapenemase gene blaKPC-2 was the highest(73.63％,134/182),followed by blaNDM-5(15.38％,28/182),and blaNDM-1(11.54％,21/182).A total of 15 different sequence types(ST)were identified by MLST,of which ST11 was the most common type(72.53％,132/182),followed by ST17(11.54％,21/182).Conclusions CRKP isolates in Hebei Children's Hospital showed high level resistance to antimicrobial agents.Antimicrobial therapy should be prescribed cautiously according to the results of antimicrobial susceptibility testing to avoid the emergence of resistant strains.KPC-2-producing ST1 1 type CRKP strains may be prevalent in this hospital.Effective control measures should be taken to avoid further spread of such CRKP strains.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To investigate the features of peripheral blood lymphocyte subsets in children with sepsis and evaluate the value of these cells in combination with multiple indicators in the diagnosis of pediatric sepsis.Methods:A retrospective study was conducted on 86 sepsis children and 83 children with local infection admitted to Hebei Children′s Hospital from October 2022 to October 2024. Baseline clinical data, peripheral blood lymphocyte subsets, and other laboratory indicators were compared between the two groups. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to evaluate the independent risk factors correlated with the initiation of sepsis. The receiver operating characteristic (ROC) curve was plotted to evaluate the value of each independent risk factor for diagnosing sepsis.Results:The thrombin time, the absolute counts of NK, CD3 + T, CD4 + T, and CD8 + T cells, the levels of IgG and IgM, and the counts of lymphocytes and platelets were lower in the sepsis children than in the children with local infection. However, the prothrombin time (PT), activated partial thromboplastin time, the levels of fibrinogen, direct bilirubin, and C-reactive protein (CRP) were higher in the sepsis group (all P<0.05). The variables screened by LASSO regression were analyzed by the multivariate logistic regression, and the results showed that PT, absolute CD4 + T cell count, and the levels of IgM and CRP were independent risk factors for sepsis. The ROC analysis indicated that the area under the ROC curve (AUC) for PT, absolute CD4 + T cell count, and IgM and CRP levels when used individually in diagnosing sepsis was 0.729, 0.593, 0.605, and 0.795, respectively. The AUC for the four indexes when used in combination for diagnosing sepsis reached 0.822, showing greater superiority over that of the single index. Conclusions:The combined measurement of PT, absolute CD4 + T cell count, and the levels of IgM and CRP can improve the diagnostic efficacy for sepsis in children. Early monitoring of these indexes facilitates the assessment of the condition in children suffering from sepsis.

AIM:To investigate the protective effects of Klotho protein against hypoxia/reoxygenation(H/R)-in-duced damage in rat cardiomyocytes,and to elucidate its underlying mechanisms.METHODS:Rat cardiomyocyte H9c2 cells were divided into 4 groups:control,H/R,low-concentration(1 μmol/L)Klotho+H/R,and high-concentration(10 μmol/L)Klotho+H/R groups.Cells were pretreated with Klotho at specified concentrations before induction of H/R injury.Flow cytometry was used to determine cardiomyocyte apoptosis rates,while reactive oxygen species(ROS)levels were measured using the DCFH-DA probe.Additionally,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were assessed using biochemical assay kits.Mitochondrial membrane potential was evaluated using the JC-1 as-say,and activity of caspase-3 and caspase-9 was quantified.Western blot analysis was conducted to measure the protein expression of cytochrome C(Cyt-C),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in cardio-myocytes from each group.RESULTS:Compared with the control group,the H/R group exhibited significantly increased apoptosis rates(P<0.05),elevated ROS levels and MDA content,decreased SOD activity(P<0.05),reduced mitochon-drial membrane potential(P<0.05),increased caspase-3 and caspase-9 activity(P<0.05),decreased mitochondrial Cyt-C and Bcl-2 protein expression(P<0.05),and increased cytoplasmic Cyt-C and Bax protein expression(P<0.05).In comparison with the H/R group,both low-and high-concentration Klotho treatments significantly reduced cardiomyocyte apoptosis(P<0.05),lowered ROS levels and MDA content(P<0.05),increased SOD activity(P<0.05),restored mito-chondrial membrane potential(P<0.05),decreased caspase-3 and caspase-9 activity(P<0.05),increased mitochondrial Cyt-C and Bcl-2 expression(P<0.05),and decreased cytoplasmic Cyt-C and Bax expression(P<0.05).Notably,the high-concentration Klotho group demonstrated more pronounced protective effects(P<0.05).CONCLUSION:Klotho protein exerts protective effects against H/R-induced cardiomyocyte injury,possibly by inhibiting mitochondria-mediated apoptosis.

AIM:To investigate the protective effects of Klotho protein against hypoxia/reoxygenation(H/R)-in-duced damage in rat cardiomyocytes,and to elucidate its underlying mechanisms.METHODS:Rat cardiomyocyte H9c2 cells were divided into 4 groups:control,H/R,low-concentration(1 μmol/L)Klotho+H/R,and high-concentration(10 μmol/L)Klotho+H/R groups.Cells were pretreated with Klotho at specified concentrations before induction of H/R injury.Flow cytometry was used to determine cardiomyocyte apoptosis rates,while reactive oxygen species(ROS)levels were measured using the DCFH-DA probe.Additionally,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were assessed using biochemical assay kits.Mitochondrial membrane potential was evaluated using the JC-1 as-say,and activity of caspase-3 and caspase-9 was quantified.Western blot analysis was conducted to measure the protein expression of cytochrome C(Cyt-C),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in cardio-myocytes from each group.RESULTS:Compared with the control group,the H/R group exhibited significantly increased apoptosis rates(P<0.05),elevated ROS levels and MDA content,decreased SOD activity(P<0.05),reduced mitochon-drial membrane potential(P<0.05),increased caspase-3 and caspase-9 activity(P<0.05),decreased mitochondrial Cyt-C and Bcl-2 protein expression(P<0.05),and increased cytoplasmic Cyt-C and Bax protein expression(P<0.05).In comparison with the H/R group,both low-and high-concentration Klotho treatments significantly reduced cardiomyocyte apoptosis(P<0.05),lowered ROS levels and MDA content(P<0.05),increased SOD activity(P<0.05),restored mito-chondrial membrane potential(P<0.05),decreased caspase-3 and caspase-9 activity(P<0.05),increased mitochondrial Cyt-C and Bcl-2 expression(P<0.05),and decreased cytoplasmic Cyt-C and Bax expression(P<0.05).Notably,the high-concentration Klotho group demonstrated more pronounced protective effects(P<0.05).CONCLUSION:Klotho protein exerts protective effects against H/R-induced cardiomyocyte injury,possibly by inhibiting mitochondria-mediated apoptosis.

AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target pro-teins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P＜0.01),while the number of entries into the central region increased(P＜0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P＜0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P＜0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.