Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective:To evaluate the effect of esketamine on caspase-11-mediated non-canonical pathway pyroptosis in sepsis-induced acute lung injury in rats.Methods:Eighteen SPF healthy Sprague-Dawley rats, aged 8-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+ esketamine group (CLP+ ES group). Sepsis was induced by CLP in anesthetized animals. Esketamine 10 mg/kg was injected via the tail vein immediately after development of the model, and the equal volume of normal saline was injected via the tail vein in the other two groups. At 24 h after development of the model, the rats were sacrificed under anesthesia, and the lung tissues and blood samples were taken. The wet to dry lung weight ratio (W/D ratio) was calculated, and the pathological changes were observed and the lung injury was scored. The expression of caspase-11, gasdermin D-N (GSDMD-N), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) was detected by Western blot. The expression of caspase-11 and GSDMD-N mRNA was detected by quantitative real-time polymerase chain reaction. The serum concentration of interleukin-1β (IL-1β) was determined by enzyme-linked immunosorbent assay. Results:Compared with Sham group, the lung injury score and W/D ratio were significantly increased, the expression of caspase-11 and GSDMD-N protein and mRNA was up-regulated, the expression of p-PI3K and p-AKT was down-regulated, and the concentration of IL-1β was increased in CLP group ( P<0.05). Compared with CLP group, the lung injury score and W/D ratio were significantly decreased, the expression of caspase-11 and GSDMD-N protein and mRNA was down-regulated, the expression of p-PI3K and p-AKT was up-regulated, and the concentration of IL-1β was decreased in CLP+ ES group ( P<0.05). Conclusions:The mechanism by which esketamine alleviates sepsis-induced acute lung injury may be related to the inhibition of caspase-11-mediated non-canonical pathway pyroptosis in rats.

BACKGROUND:Patients with chronic ankle instability tend to overpronate when walking,which increases the risk of ankle sprain during the stance phase of the walking cycle.Clinicians often use Kinesio taping or athletic taping for ankle taping.Since Kinesio taping is elastic and athletic taping cannot be stretched,there are differences in technical applications and physiological mechanisms between them,which may result in different rehabilitation effects.OBJECTIVE:To compare the effects of Kinesio taping and athletic taping on the frontal plane of the foot motion and the horizontal plane of the tibia motion in patients with chronic ankle instability during the stance phase of walking.METHODS:Forty patients with chronic ankle instability were randomly divided into Kinesio taping group and athletic taping group.In the Kinesio taping group,two patches were pasted from the inside to the outside of the hind foot to generate pulling tension that facilitates foot eversion;in the athletic taping group,ankle locking basket taping was used.Walking tests were conducted on an electric treadmill before and after taping.A three-dimensional motion analysis system was used to obtain the kinematic parameters of the subjects'foot and tibia.RESULTS AND CONCLUSION:After taping,in the Kinesio taping group,the foot valgus angle increased in the early stance phase(P<0.05),but there was no effect on foot position in the late stance phase(P>0.05).After taping,in the athletic taping group,internal rotation of the tibia increased in the late stance phase(P<0.05);however,there was no significant change in tibial position in the early stance phase(P>0.05).To conclude,compared with athletic taping,Kinesio taping can provide a flexible pulling force that is beneficial for foot eversion in the early stance phase of the gait cycle,while not restricting normal foot inversion in the late stance phase.Therefore,Kinesio taping may be a practical rehabilitation therapy for patients with chronic ankle instability,correcting abnormal motion of the ankle joint without restricting its natural motion.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

This report evaluates the preliminary outcomes of a "six-in-one" integrated cough and asthma center developed under a dual-contract physician model at the Changfeng Community Health Service Center in Putuo District, Shanghai. By combining the efforts of family doctors and medical specialists, the center integrated six core functions-clinical treatment, prevention, nursing, rehabilitation, pharmacy, and nutrition-into a seamless management system covering screening, diagnosis, therapy, and follow-up. Supported by specialist guidance and teaching clinics, the model significantly enhanced comprehensive respiratory disease management capabilities within the community setting. The initiative not only improved patient health outcomes but also strengthened multidisciplinary collaboration and resource efficiency, offering a replicable example for improving chronic disease management in primary care through integrated and coordinated service delivery.

Objective:To evaluate the effect of esketamine on caspase-11-mediated non-canonical pathway pyroptosis in sepsis-induced acute lung injury in rats.Methods:Eighteen SPF healthy Sprague-Dawley rats, aged 8-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+ esketamine group (CLP+ ES group). Sepsis was induced by CLP in anesthetized animals. Esketamine 10 mg/kg was injected via the tail vein immediately after development of the model, and the equal volume of normal saline was injected via the tail vein in the other two groups. At 24 h after development of the model, the rats were sacrificed under anesthesia, and the lung tissues and blood samples were taken. The wet to dry lung weight ratio (W/D ratio) was calculated, and the pathological changes were observed and the lung injury was scored. The expression of caspase-11, gasdermin D-N (GSDMD-N), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) was detected by Western blot. The expression of caspase-11 and GSDMD-N mRNA was detected by quantitative real-time polymerase chain reaction. The serum concentration of interleukin-1β (IL-1β) was determined by enzyme-linked immunosorbent assay. Results:Compared with Sham group, the lung injury score and W/D ratio were significantly increased, the expression of caspase-11 and GSDMD-N protein and mRNA was up-regulated, the expression of p-PI3K and p-AKT was down-regulated, and the concentration of IL-1β was increased in CLP group ( P<0.05). Compared with CLP group, the lung injury score and W/D ratio were significantly decreased, the expression of caspase-11 and GSDMD-N protein and mRNA was down-regulated, the expression of p-PI3K and p-AKT was up-regulated, and the concentration of IL-1β was decreased in CLP+ ES group ( P<0.05). Conclusions:The mechanism by which esketamine alleviates sepsis-induced acute lung injury may be related to the inhibition of caspase-11-mediated non-canonical pathway pyroptosis in rats.

Objective:This study systematically summarized the construction experience of the immunology platform at the Institute of Basic Medical Sciences, Peking University Third Hospital, aiming to provide theoretical references and practical guidance for research-oriented hospitals in building high-quality research platforms.Methods:This study employed case study analysis to elaborate on the platform development initiatives, integrating literature analysis and in-depth interviews to conduct a horizontal comparison of management models among peer research platforms.Results:Through five years of development, the platform had achieved remarkable outcomes via a model integrating ″Talent cultivation-Technological innovation-Equipment procurement″ Research talents had demonstrated breakthroughs in securing national-level research grants, publishing high-impact papers, and obtaining scientific awards. The technical service system had achieved enhancement in both service scope and professional depth, fostering robust interdisciplinary synergy. The platform had effectively expanded its societal engagement capacity.Conclusions:The sustainable advancement of research-oriented hospital immunology platform necessitates establishing standardized flow cytometry databases and implementing high-dimensional data integration. Building upon multidisciplinary convergence, it is imperative to pioneer innovative operational mechanisms characterized by efficiency, open-access, and shared frameworks.