This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

OBJECTIVE To evaluate the cost-effectiveness of acalabrutinib， zanubrutinib， and ibrutinib as first-line treatments for patients with chronic lymphocytic leukemia （CLL）. METHODS A partitioned survival model was developed to simulate the 10-year disease progression of treatment-naive CLL patients. The model used a 4-week cycle length， and an annual discount rate of 4.5% was applied to both costs and health outcomes. Relevant clinical trial literature was systematically reviewed， and survival data for each treatment strategy were extracted. Using the ibrutinib arm from the RESONATE-2 trial as the anchor arm， an anchored indirect comparison approach was performed to estimate the relative treatment effects of acalabrutinib group and zanubrutinib group versus ibrutinib group. Survival curves for progression-free survival and overall survival for each treatment strategy were generated by combining the relative efficacy estimates with the survival data from the anchor arm. Quality-adjusted life year （QALY） were used as the model outcome measure. The incremental cost-effectiveness ratio and incremental net monetary benefit （INMB） were calculated to assess the economic value of the three treatment regimens. The willingness-to-pay （WTP） threshold was set at twice the 2025 per capita gross domestic product of China， corresponding to 199 330 yuan/QALY. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analyses were conducted to evaluate the robustness of the base-case results. RESULTS In the base-case analysis， compared with ibrutinib group， both acalabrutinib group and zanubrutinib group demonstrated cost-saving and health-improving advantages. The INMBs were 149 361.37 yuan for acalabrutinib group and 194 783.94 yuan for zanubrutinib group， indicating that both strategies were dominant over ibrutinib. One-way sensitivity analysis showed that drug prices， hazard ratios between treatment strategies， and utility values were the major factors influencing the results. Probabilistic sensitivity analysis demonstrated that when the WTP threshold was below 450 000 yuan/QALY， acalabrutinib group and zanubrutinib group regimens consistently had higher probabilities of being cost-effective than ibrutinib group. Scenario analyses showed that acalabrutinib group and zanubrutinib group remained cost-effective compared with ibrutinib group under alternative assumptions， including different anchor arms， high-risk patient cohorts， and an extended 20-year time horizon. CONCLUSIONS Compared with ibrutinib， zanubrutinib and acalabrutinib can provide greater economic value as first-line treatments for CLL， with zanubrutinib demonstrating a more pronounced cost-effectiveness advantage.

BACKGROUND:Endometrial receptivity is a key factor in embryo implantation in northwest Tibetan cashmere goats,and the expression of genes related to endometrial receptivity and their variable splicing are still unclear. OBJECTIVE:To analyze and explore genes and variable splicing events related to endometrial receptivity in northwest Tibetan cashmere goats. METHODS:On days 5 and 15 of pregnancy(representing pre receptive endometrium group and receptive endometrium group),three northwest Tibetan cashmere goats were randomly selected.Endometrial tissue was collected and stained with hematoxylin and eosin to observe tissue morphology.Immunohistochemical staining was used to detect the expression of endometrial receptive marker proteins leukemia inhibitory factor and vascular endothelial growth factor.After the total RNA was extracted and the quality test was qualified,transcriptome sequencing was performed to search differentially expressed mRNAs,lncRNAs,circRNAs,and miRNAs,perform functional prediction,and analyze alternative splicing mRNAs and lncRNAs related to endometrial receptivity. RESULTS AND CONCLUSION:(1)Compared with the pre receptive endometrium group,the expression levels of leukemia inhibitory factor and vascular endothelial growth factor proteins in the endometrial tissue of the receptive endometrium group were significantly increased.(2)The sequencing results showed that the differentially expressed genes were mostly mRNA and lncRNA genes,including 250 upregulated mRNAs,193 upregulated lncRNAs,135 downregulated mRNAs,and 123 downregulated lncRNAs,which were significantly enriched in the Wnt,Hedgehog,and Hippo signaling pathways.(3)Alternative splicing event analysis uncovered 8 differentially expressed variable splicing transcripts,which were all mRNA transcripts,including 2 downregulated and 6 upregulated,and were significantly associated with vascular endothelial growth factor receptor signaling,cell motility,and embryonic development.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

Acute lung injury(ALI)is a common critical illness caused by intrapulmonary or extra-pulmonary factors,which is accompanied by ex-tremely high morbidity and mortality.Its pathogen-esis is extremely complex and difficult to treat.Src homology 2 domain-containing protein tyrosine phosphatase(Shp2),a key cellular signal transduc-tion molecule,plays a pivotal role in the pathophys-iological processes of diverse diseases.Notably,in the context of pathogen infection,Shp2 regulates the functionality of cellular immunity,lung epitheli-al cells,and vascular endothelial cells.This review article highlights the significant role of Shp2 in the onset and progression of ALI,emphasizing its regu-lation of inflammatory response,apoptosis,and ox-idative stress.Shp2 could emerge as a novel thera-peutic target for ALI,offering valuable insights for the development of innovative drug candidates to treat this debilitating condition.

BACKGROUND:Magnesium and magnesium-based materials have good biocompatibility,stable osteogenic properties,and biological activities such as vascularization and immune regulation,and show a broad application prospect in stomatology.OBJECTIVE:To summarize the mechanism of magnesium-based materials in the treatment of oral diseases in terms of osteogenesis,angiogenesis,and immunomodulation,and to review the application prospects of magnesium and magnesium-based materials in the field of oral diseases in recent years.METHODS:Chinese search key words were"magnesium,magnesium alloys,magnesium-based metals,fractures,implants,restorations,endodontics,periodontitis,periodontal disease,cysts,oral cancer."English search key works were"magnesium,magnesium-based alloy,fracture,facial bone fractures,denture,dental implant,restorative dentistry,pulpitis,periodontitis,periodontal diseases,oral cancer."The articles were retrieved on CNKI,WanFang,PubMed,and Web of Science databases.By analyzing and reading literature for screening,84 articles were finally included for review.RESULTS AND CONCLUSION:Magnesium and magnesium-based materials can be used as bone internal fixation devices for jaw fracture or orthognathic surgery.Due to the special biological properties of magnesium,it can not only ensure stable osteogenesis,but also avoid the possibility of secondary surgery,which has the potential to be widely used.In the field of bone regeneration in stomatology,magnesium,relying on its superior biological properties,shows better mechanical properties and antibacterial properties than existing clinical materials,providing more options for the development and application of materials in this field.With the help of the biological activity of magnesium,magnesium-based coating materials give full play to the anti-inflammatory and antioxidant effects,further promote implant bone bonding and soft tissue integration,and have great application prospects in implant surface modification and promoting implant stability.Although magnesium has been involved in maxillofacial intraoral soft tissue regeneration and treatment,dental tissue engineering,there are still a lot of gaps.To ensure the stable biological characteristics of magnesium,it is usually necessary to add other alloys or carry out magnesium surface modification.However,the biological evaluation system of degradable metal implants is not perfect at present.The clinical application of magnesium in oral diseases still needs to be further clarified in the future.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.