OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture （消肿止痛合剂） combined with antibiotic bone cement in the treatment of diabetic foot ulcer （DFU） with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group （36 cases） and the control group （36 cases）. Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds， while the treatment group received oral Xiaozhong Zhitong Mixture （50 ml per time， three times daily） in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate， serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， malondialdehyde （MDA）， superoxide dismutase （SOD）， C-reactive protein （CRP）， and white blood cell （WBC） count were observed before and after treatment， and visual analog scale （VAS） scores for wound pain， traditional Chinese medicine （TCM） syndrome scores， and the DFU Healing Scale （DMIST scale） were also compared. Liver and kidney function were evaluated before and after treatment， and adverse events such as allergic reactions， worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was （87.93±9.34）%， significantly higher than （81.82±12.02）% in the control group （P = 0.035）. Compared to pre-treatment levels， both groups showed significant reductions in serum CRP， WBC， MDA， IL-1β， and TNF-α levels， with an increase in SOD level （P＜0.05）. TCM syndrome scores， VAS， and DMIST scores also significantly decreased in both groups （P＜0.05）， with greater improvements in the treatment group （P＜0.05）. No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing， reducing inflammatory response， and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome， with good safety for DFU patients with damp-heat obstructing syndrome.

[Objective] To compare next generation sequencing (NGS) library construction technology between probe hybridization capture and amplicon methods, and analyze the influencing factors of HLA genotyping resolution level and its prospects in clinical applications. [Methods] A total of 207 clinical samples with known typing results and samples from the proficiency testing plan were selected. The conformity rate of HLA genotyping results, allele coverage and typing data analysis indicators were confirmed, and the effects of two library construction methods on the level of HLA genotyping discrimination were compared. [Results] The concordance rate of 207 samples with the feedback results of PT or prior well-characterized HLA genotypes was 100%. Among them, 91 samples were captured using hybridization probe capture method. Compared with the original amplicon method, the hybridization probe capture method can distinguish the alleles of DRB1 and DPB1 that cannot be determined in 13 samples. The allelic imbalance of DRB1, DPA1, and DQB1 loci in 6 samples was resolved. Three samples were found to have missed detection of alleles at the DQA1 and DQB1 loci. [Conclusion] The performance indicators of hybridization probe capture and amplicon performance confirmation meet the requirements of clinical detection of HLA genotyping, which provides an experimental method and basis for clinical application.

Objective To investigate the population density and seasonal fluctuations of Aedes albopictus in Guangzhou City, Guangdong Province, from 2021 to 2023, so as to provide insights into A. albopictus control and management of dengue fever. Methods The surveillance of A. albopictus density was performed in all surveillance sites assigned across all streets (townships) in Guangzhou City during the period from January to December from 2021 to 2023. The surveillance frequency was twice every half month from May to September, and once every month for the rest of a year. In each surveillance period, A. albopictus mosquito larvae were captured from indoor and outdoor small water containers in residential areas, parks, medical facilities, schools, other government sectors and social organizations, construction sites, special industries and others for mosquito species identification. Adult mosquitoes were captured using electric mosquito suction apparatus for species identification and gender classification. Adult mosquitoes and mosquito eggs were collected with mosquito and egg traps at the breeding and dwelling places of Aedes mosquitoes for identification. The mosquito oviposition index (MOI), Breteau index (BI), adult mosquito density index (ADI) and standard space index (SSI) were calculated. The A. albopictus density was classified into grades 0, 1, 2 and 3 in each surveillance site, with Grade 0 density defined eligible, and the eligible rate of A. albopictus density was calculated at all surveillance sites each year from 2021 to 2023. In addition, the changing trends in MOI, SSI, BI and ADI of A. albopictus were analyzed in Guangzhou City from 2021 to 2023. Results The eligible rates of A. albopictus density were 61.69%, 68.75% and 55.15% in surveillance sites of Guangzhou City from 2021 to 2023 (χ² = 297.712, P < 0.001), and appeared a tendency towards a reduction followed by a rise each year, which gradually reduced since January, maintained at a low level during the period between May and October, and gradually increased from November to December. The MOI, SSI, BI and ADI of A. albopictus all appeared a tendency towards a rise followed by a reduction in Guangzhou City during the period between January and December from 2021 to 2023. The BI of A. albopictus peaked in the first half of June in 2021 (4.03), the first half of July in 2022 (3.89) and the last half of August in 2023 (5.02), and the SSI of A. albopictus peaked in the last half of June in 2021 (0.93), the last half of May in 2022 (0.59), and the last half of June (0.94) and the first half of September in 2023 (1.12). In addition, the MOI of A. albopictus peaked in the first half of May in 2021 (8.64), the first half of June in 2022 (8.96), and the last half of May (10.21) and the last half of June in 2023 (10.89), and the ADI of A. albopictus peaked in the first half of June in 2021 (3.41), the last half of June in 2022 (4.06), and the first half of July in 2023 (3.61). Conclusions The density of A. albopictus is high in Guangzhou City during the period from May to October, and the risk of local outbreak caused by imported dengue fever is high. Persistent intensified surveillance of the density and seasonal fluctuation of A. albopictus is recommended and timely mosquito prevention and control is required according to the fluctuation in the A. albopictus density.

BackgroundSevere mental disorders represent a major public health concern due to the high disability rates and substantial disease burden， which has garnered significant national attention and prompted their inclusion in public health project management systems. However， credible evidence regarding the current status of disease management and factors influencing disease stabilization among patients with severe mental disorders in Luzhou City， Sichuan Province， remains limited. ObjectiveTo investigate the current management status of patients with severe mental disorders in Luzhou City， Sichuan Province， and to analyze influencing factors of disease stabilization among patients under standardized care， so as to provide evidence-based insights for developing targeted management strategies to optimize clinical interventions for this patient population. MethodsIn March 2023， data were extracted from the Sichuan Mental Health Service Comprehensive Management Platform for patients with severe mental disorders in Luzhou City who received management between December 2017 and December 2022. Information on mental health service utilization and clinical status changes was collected. Trend analysis was conducted to evaluate temporal changes in key management indicators for severe mental disorders in Luzhou City. Logistic regression analysis was employed to identify factors influencing the disease stabilization or fluctuation of these patients. ResultsThis study enrolled a total of 20 232 patients. In Luzhou City， the stabilization rate and standardized management rate of severe mental disorders were 94.89% and 79.36% in 2017， respectively， which increased to 95.33% and 96.92% by 2022. The regular medication adherence rate rose from 34.42% in 2018 to 86.81% in 2022. In 2022， the regular medication adherence rate was 71.80% for schizophrenia， 55.26% for paranoid psychosis， and 51.43% for schizoaffective disorder. Multivariate analysis identified the following protective factors for disease stabilization： age of 18~39 years （OR=0.613， 95% CI： 0.409~0.918）， age of 40~65 years （OR=0.615， 95% CI： 0.407~0.931）， urban residence （OR=0.587， 95% CI： 0.478~0.720）， and regular medication adherence （OR=0.826， 95% CI： 0.702~0.973）. Risk factors for disease fluctuation included poor （OR=1.712， 95% CI： 1.436~2.040）， non-inclusion in care-support programs （OR=1.928， 95% CI： 1.694~2.193）， non-participation in community rehabilitation （OR=2.255， 95% CI： 1.930~2.634）， and intermittent medication adherence （OR=3.893， 95% CI： 2.548~5.946）. ConclusionThe stability rate， standardized management rate， and regular medication adherence rate of patients with severe mental disorders in Luzhou City have shown a year-by-year increase. Age， household registration status， economic condition， medication compliance， and community-based rehabilitation were identified as influencing factors for disease fluctuation in these patients. ［Funded by Luzhou Science and Technology Plan Project （number， 2022-ZRK-186）］

Pancreatic cancer is characterized by nerve invasion and a high mortality rate， and its pathological process depends on the complex interaction network between tumor and the nervous system. Based on the concept of “pancreatic cancer neuroecology”， this article analyzes the mechanism of action of peripheral motor nerve， sensory nerve， and central nerve in tumorigenesis， pain regulation， and cachexia formation and emphasizes the synergistic regulatory role of immune cells， Schwann cells， and extracellular matrix in the microenvironment of perineural invasion. At the same time， this article further elaborates on the metabolic interaction and chemotaxis between neuraxis and tumor， the effect on promoting chemotherapy resistance， and the dynamic relationship between neuroplasticity and tumor adaptability. In clinical practice， this article summarizes the key value of perineural invasion in prognostic evaluation， preoperative evaluation， and the selection of surgical strategy. In addition， this article reviews the basic research advances in the biomarkers and potential targets associated with perineural invasion in pancreatic cancer and points out the limitations of current model and transformation research. In the future， systematically analyzing the nerve-tumor-immune network and targeting its key nodes may provide multi-dimensional strategies and new breakthroughs for the precise intervention of pancreatic cancer， the reversal of drug resistance， and the relief of symptoms.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.