ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

Objective To establish a dual TaqMan probe-based qPCR method for determining the copy number of the geneti-cally modified pertussis toxin(PT) gene in detoxified pertussis vaccine strains, and to identify optimal reference genes forevaluating the genetic stability of modified strains during serial passage.MethodsSpecific primers and probes of modifiedgene PT and multiple housekeeping genes were designed. The optimal reference genes were screened by GeNorm, Norm-Finder, BestKeeper and Delta CT based on dual TaqMan probe qPCR. The copy number of PT gene of genetically detoxifiedpertussis vaccine strain was calculated by relative quantitative analysis. The specificity, linearity and repeatability of theestablished method were verified. The genomic DNA of P1, P3, P5, P10 and P15 strains used in the production of geneticallydetoxified pertussis vaccine was used as templates, and the passage stability of the strains was evaluated by using the estab-lished dual TaqMan probe qPCR method.ResultsThe stability of candidate reference genes was analyzed using GeNorm,NormFinder, BestKeeper, and Delta CT software, with Rpob identified as the most stable reference gene. Both the target PTgene and the reference Rpob gene were amplified in standard strain 58003. A good linear correlation(R~2≥ 0. 990) wasobserved between Ct values and template quantities within the concentration range of 0. 001 to 10 ng/μL. For P1 generationstrains, the 2~(-△△Ct)values from six replicate assays consistently ranged between 0. 87 and 1. 25, with an RSD of less than 20%.All tested generations exhibited single-copy PT target genes, demonstrating good genetic stability during serial passages.ConclusionThe established dual TaqMan probe qPCR assay demonstrates good primer specificity and reproducibility,making it suitable for evaluating the genetic stability of bacterial strains during serial passages in the production of geneti-cally detoxified pertussis vaccines, thereby further evaluating the quality of strains.

AIM: To investigate the relationship between the levels of serum dehydroepiandrosterone(DHEA), erythropoietin(Epo), vasohibin-1(VASH-1)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM). METHODS: Totally 185 T2DM patients(185 eyes)treated in our hospital from April 2021 to March 2024 were selected and divided into T2DM group(102 eyes)and DR group(83 eyes)based on whether retinal lesions occurred. DR patients were divided into nonproliferative DR group(NPDR, 47 cases, 47 eyes)and proliferative DR group(PDR, 36 cases, 36 eyes)based on the severity of their lesions. Fully automatic biochemical analyzer was used to detect serum biochemical indicators. ELISA was applied to detect serum levels of DHEA, Epo, and VASH-1. Pearson correlation was applied to analyze the correlation between serum DHEA, Epo, and VASH-1 levels and the severity of diabetic retinopathy. Logistic regression was applied to analyze the factors affecting the occurrence of DR. ROC curve was applied to analyze the diagnostic value of serum DHEA, Epo, and VASH-1 levels for T2DM combined with DR or PDR.RESULTS: Compared with the T2DM group, the DR group showed significantly increased DM duration, fasting blood glucose, uric acid, creatinine, and Epo, while DHEA and VASH-1 levels were significantly reduced(all P<0.05); Compared with the NPDR group, the PDR group showed a significant decrease in serum DHEA and VASH-1 levels, and a significant increase in Epo levels(all P<0.05); the levels of serum DHEA and VASH-1 were negatively correlated with the severity of DR, while the level of Epo was positively correlated with the severity of DR(all P<0.05); DHEA and VASH-1 were protective factors against DR, while Epo was a risk factor for DR(all P<0.05); the AUC of serum DHEA, Epo, and VASH-1 levels alone and in combination for the diagnosis of T2DM with DR were 0.804, 0.797, 0.805, and 0.903, respectively. The combined diagnostic value was higher than that of single diagnosis(all P<0.05); the AUC of serum DHEA, Epo, and VASH-1 levels alone and in combination for diagnosing PDR were 0.852, 0.850, 0.841, and 0.946, respectively. The value of combined diagnosis was significantly higher than that of individual diagnosis(all P<0.05).CONCLUSION:The levels of serum DHEA and VASH-1 in DR patients are clearly reduced, the level of Epo is clearly increased, and their levels are closely related to the severity of DR patients; therefore, combined detection has higher value for T2DM complicated with DR or PDR.

Objective:To understand the status of intestinal helminth infections in Lunan area of Shandong Province (Jining City, Rizhao City, Linyi City, Heze City, and Zaozhuang City), and provide scientific basis for formulating parasitic disease prevention and control strategies.Methods:From 2016 to 2023, a stratified sampling method was used to conduct surveillance in 33 counties (cities, districts, hereinafter referred to as counties) in Lunan area of Shandong Province. Each county was divided into five areas (east, south, west, north, and center), with one administrative village (community) selected from each area. And ≥200 permanent residents (aged ≥3 years old, having lived locally for ≥6 months) were sampled from each village (community), and one stool sample was collected from each participant. The Kato-Katz method (two slides per sample) was used for parasite detection, and the results were analyzed.Results:From 2016 to 2023, a total of 49 436 people were surveyed, including 23 861 males and 25 575 females, with an age range of 3 - 105 years old. The testing identified 687 intestinal helminth infections, with an overall infection rate of 1.39%. The predominant infection was whipworm (582 cases), with an infection rate of 1.18%; followed by roundworm and hookworm, with infection rates of 0.13% (62 cases) and 0.05% (23 cases) respectively; other types of helminths ( Clonorchis sinensis and pinworm) totaled 20 cases, with an infection rate of 0.04%. From 2016 to 2023, the annual intestinal helminth infection rates were 2.76% (201/7 292), 0.90% (56/6 327), 0.84% (52/6 200), 1.70% (124/7 282), 1.23% (88/7 133), 1.45% (104/7 150), 0.34% (17/5 058), and 1.46% (45/3 084), showing an overall downward trend (χ 2trend = 42.40, P < 0.001). The ≥60 age group had the highest intestinal helminth infection rate (2.39%, 323/13 489), while the 30 - 39 age group had the lowest rate (0.68%, 48/7 016). There was statistically significant difference in infection rates among different age groups (χ 2 = 172.25, P < 0.001). There was no statistically significant difference in infection rates between genders (χ 2 = 0.03, P = 0.862). Farmers had the highest infection rate (1.69%, 560/33 118), with statistically significant differences among different occupational groups (χ 2 = 64.88, P < 0.001). Those with primary school education or below had the highest infection rate (1.82%, 445/24 469), with statistically significant differences among different education levels (χ 2 = 64.93, P < 0.001). Conclusions:In Lunan area of Shandong Province, whipworm is the predominant intestinal helminth infection, with elderly people being the high-risk group. Although the intestinal helminth infection rate in this region remains at a low level, there is still a risk of transmission. Continuous surveillance is needed, along with strengthened prevention and control measures for key populations.

Chronic lymphocytic leukemia(CLL)is a mature B-lymphocyte proliferative tumor with significant heterogeneity.Studies have demonstrated that aberrant activation of the B-cell receptor(BCR)signaling pathway repre-sents the central mechanism underlying CLL.In recent years,inhibitors targeting the BCR signaling pathway have marked-ly improved the prognosis of patients with CLL.This review summarizes the specific roles and clinical applications of the BCR and its associated signaling pathways in CLL pathogenesis,describes how BCR modulates the tumor microenviron-ment,and delineates the metabolic reprogramming mediated by BCR signaling.

Objective:To explore the clinical efficacy of membrane induction technique in the treatment of chronic bone infection after internal fixation of intertrochanteric fracture in adults.Methods:The data were retrospectively analyzed of the 15 adult patients who had been treated for chronic bone infection after internal fixation of intertrochanteric fracture at Department of Traumatic Orthopaedics Ⅱ, Gansu Provincial People's Hospital from May 2019 to May 2022. There were 13 males and 2 females with an age of (55.8±2.6) years. By the Cierny-Mader anatomical classification, 6 cases were type Ⅲ and 9 cases type Ⅳ; by the physiological classification, 10 cases were type A and 5 cases type B. Course of bone infection was (22.1±8.1) months. All patients were treated by membrane induction technique in 2 stages. In the first stage, antibiotic bone cement was implanted after debridement into the defects [(4.50±0.54) cm in length] followed by temporary fixation of broken ends of the fracture. After 6 to 8 weeks when infection was controlled, the second stage repair and reconstruction of bone defects was carried out. Infection control, complications, bone healing time, and Samantha X-ray bone healing score, visual analogue scale (VAS) at standing, Sanders hip score and Paley score for bone defect healing at the last follow-up were recorded.Results:The 15 patients were followed up for (27.5±2.5) months. Infection recurred after the first-stage operation in 2 cases, but was effectively controlled after debridement and follow-up observed no recurrence. Follow-up showed no such complications as donor site infection, deformation or collapse of the bone reconstructed, limb shortening, re-fracture or internal fixation failure in the 15 patients who achieved bony union after (10.3±2.1) months. At the last follow-up, the Samantha X-ray score was 6.0(5.0, 6.0) points and VAS at standing 1.0(1.0, 3.0) point for the 15 patients; by Sanders hip score, the hip function was rated as excellent in 10 cases and as fine in 5 cases; by Paley score for bone defect healing, the efficacy was rated as excellent in 7 cases, as good in 2 cases and as fair in 6 cases.Conclusion:In the treatment of chronic bone infection after internal fixation of intertrochanteric fracture in adults, membrane induction technique can effectively control infection and improve the hip function of the affected limb, leading to good clinical efficacy.

Objective:To investigate the current application status of prophylactic anti-infective drugs during the perioperative period in liver transplantation centers and provide data references for further standardizing prophylactic regimens.Methods:A questionnaire comprising 53 questions across 5 dimensions was designed and released using the WJX platform. The dimensions included basic information about medical institutions, perioperative pathogenic microorganisms, current status of empirical antibacterial prophylaxis, adjustments to prophylactic anti-infective strategies, and an overview of prophylactic measures against other pathogens. Based on the survey results, the types of common perioperative pathogens in liver transplantation, types of prophylactic antibacterial drugs, timing and duration of administration, upgraded prophylaxis strategies (such as escalation of antibiotic classes or extension of drug application duration), and prevention strategies for other pathogens were summarized.Results:A total of 13 completed questionnaires from pharmacists at liver transplantation centers were collected. The most common pathogens during the perioperative period were Gram-negative bacilli, including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. The most frequently used prophylactic antibacterial drugs were cefoperazone/sulbactam and piperacillin/tazobactam. Regarding the timing of administration, 9 centers administered drugs 0.5 to 1.0 hour before surgery, 3 within 0.5 hour, and 1 within 1 hour preoperatively. The prophylactic duration was within 7 days postoperatively for living donor liver transplantation in 10 centers, while for cadaveric donor liver transplantation, only 6 centers adhered to the 7-day duration. When donors had infections with sensitive bacteria, 9 centers upgraded prevention strategies: 2 centers escalated the antibiotic class or adjusted regimens, 5 centers extended the duration of prophylaxis, 2 centers implemented donor-specific susceptibility-guided antibacterial treatments regardless of colonization or infection, and 5 centers administered prophylaxis only in cases of colonization based on donor susceptibility results. When donors had multi-drug resistance bacterial infections, 11 centers upgraded prevention strategies: 7 escalated the antibiotic class or adjusted regimens, 4 extended prophylaxis duration, 6 implemented susceptibility-guided treatments irrespective of colonization or infection, 1 administered prophylaxis only for colonization based on donor susceptibility results, and 2 abandoned transplantations. 7 centers routinely applied antifungal prophylactic measures, including 1 for preoperative prophylaxis and 6 for postoperative prophylaxis, using caspofungin (4 centers), fluconazole (2 centers), posaconazole (1 center), and micafungin (1 center). 6 centers initiated antifungal prophylaxis in cases with donor or recipient fungal infection history or active fungal infections detected during liver procurement. Most antifungal prophylaxis was administered within 72 hours postoperative (11 centers), with durations mostly within 14 days (12 centers). For viral infections, 6 centers adopted routine postoperative prophylactic measures. Conclusions:Currently, the perioperative prophylactic anti-infective strategies in 13 liver transplantation centers are not standardized. High-quality multicenter clinical studies are needed to compare the effectiveness of different prophylactic regimens, aiming to further standardize the types and durations of prophylactic drug use.

Objective:To investigate the factors influencing the delayed onset of intrapartum fever following epidural labor analgesia and their impact on maternal and neonatal outcomes.Methods:Select parturients who experienced intrapartum fever following labor analgesia(T≥38.0℃,age≥18 years,singleton pregnancy,ASA classification Ⅱ)between January 1,2021,and December 31,2023.Group them based on the median time of intra-partum fever onset after labor analgesia:those with onset times less than the median were classified as the ear-ly-onset fever group,and those with onset times greater than the median were classified as the late-onset fever group.Using univariate and multivariate Logistic regression analysis to explore factors influencing the delay in in-trapartum fever onset and the pregnancy outcomes of the mothers and newborns in both groups.Results:A total of 253 parturients were included,and the time range of onset of intrapartum fever following epidural labor analgesi-a was 1.83-28.42 hours,with a median fever onset time of 8.00 hours.There were 126 cases in the early-onset group and 127 in the late-onset group.Multivariate Logistic regression analysis indicated that primiparous women,artificial membrane rupture,and neonatal birth weight were independent risk factors for delayed fever onset(OR＞1,P＜0.05),whereas the administration of oxytocin prior to labor analgesia was found to be a protective factor(OR＜1,P＜0.05).The late-onset group exhibited higher levels of white blood cells(WBC),C-reactive pro-tein,longer hospital stays,higher hospitalization costs,greater diagnosis rates of chorioamnionitis,higher NICU ad-mission rates,as well as a higher incidence of neonatal pneumonia,for newborns compared to the early-onset group(P＜0.05).Conclusions:Primiparous women,artificial membrane rupture,and higher neonatal birth weight may be associated with delayed onset of intrapartum fever,while oxytocin administration prior to labor analgesia may offer some protective benefit.The later the onset of intrapartum fever,the worse the clinical outcomes for both mother and infants.

Cancer is a group of chronic diseases caused by a combination of genetic and environmental factors.Immune cells play a vital role in the regulation of tumor diseases.Recently,innate lymphoid cells(ILCs)have been found to have an important regu-latory role in the tumor microenvironment.ILCs are tissue resident immune cells located mainly in the mucosa and first barrier organs and have been extensively studied for defense against pathogenic invasion,lymphatic development and tissue repair.The role of ILCs in tumor immunity has received increasing attention in recent years.Among the various subpopulations of ILCs cells,the regulation of ILC3s in tumor immunity is the most controversial.Therefore,we summarized the role of ILC3s in tumor immunity by combining rele-vant studies on the involvement of ILC3s in tumor immune regulation in recent years.

Autophagy is a conserved physiological phenomenon commonly found in all eukaryotic cells,which promotes cell survival by degrading intracellular proteins and organelles during starvation or nutrient deficiency.Dysfunc-tion autophagy is closely related to various diseases.Soluble N-elthylmaleimide-sensitive factor attachment protein recep-tor(SNARE)complex is a protein complex that mediates membrane fusion and plays a key role in the fusion process of au-tophagosomes and lysosomes.The aberrant assembly of the SNARE complex results in the arrest of autophagic flow,there-by leading to cellular dysfunction and the occurrence of diseases.In this review,we summarized the roles of SNARE pro-teins in the autophagosome-lysosome fusion and the latest research in related diseases,providing a reference for studying the mechanism of autophagy and diseases targeting the SNARE complex.