ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ²=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.

Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Objective: To characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To analyze the clinical efficacy of intelligent wireless endoscopy in transurethral resection of the prostate, so as to provide evidence for clinical application. Methods A retrospective analysis was conducted on the clinical data of 70 patients with benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate at Tongling People's Hospital during Jan. 2023 and Dec. 2024. Based on the type of endoscopes used, patients were divided into a wireless endoscopy group and a traditional endoscopy group, with 35 patients in either group. Differences between the two groups were compared in terms of surgical preparation time, operation time, postoperative hospital stay, catheter indwelling time, intraoperative blood loss, surgical complications, and operating comfort during the procedure. Results All 70 operations were successfully completed without severe urinary incontinence. The wireless laparoscopy group demonstrated significantly shorter surgical preparation time compared to the traditional laparoscopy group [(12.14±2.39)min vs. (14.89±0.80)min, P＜0.001].There was no statistically significant difference in the operation time between the two groups [(93.51±34.49)min vs. (101.71±34.87)min, P=0.326]. There were no statistically significant differences between the two groups in postoperative hospital stay, catheter indwelling time, intraoperative blood loss, and surgical complications (P＞0.05). The wireless endoscopy group demonstrated significantly higher operating comfort compared to the traditional endoscopy group [(3.94±0.77) vs. (2.57±0.61), P＜0.001]. Conclusion The use of intelligent wireless endoscopy for transurethral resection of the prostate is comparable to traditional endoscopy in surgical efficacy and patient safety, but it can shorten preoperative preparation time and improve operator comfort.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Gastric cancer remains a highly prevalent malignancy worldwide, with surgical resection currently constituting the cornerstone of treatment aimed at improving long-term patient survival. Owing to their notable advantages, including reduced surgical trauma and accelerated postoperative recovery, minimally invasive procedures are progressively supplanting conventional open surgery and have become the mainstream approach in gastric cancer management. Concurrently, the rapid advancement of artificial intelligence (AI) technologies has enabled real-time intraoperative monitoring of surgical scenes, thereby furnishing novel technical support for adjunctive decision-making, surgical navigation, and skill assessment during gastrectomy. This article provides a systematic review of the current status of AI applications in minimally invasive gastric cancer surgery, with a particular focus on research progress pertaining to instrument recognition, surgical phase identification, delineation of normal anatomical structures, detection of metastatic foci, and early warning of intraoperative adverse events. Furthermore, we discuss the potential value of AI in enhancing surgical efficiency, ensuring patient safety, and optimizing surgical education. On this basis, we further analyze the principal challenges and inherent risks confronting current AI systems, with the aim of informing future technological innovation and facilitating clinical translation.

ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.