Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Objective To establish a fluorescent recombinase-aided amplification (RAA) assay for detection of Strongyloides stercoralis nucleic acid and to preliminarily evaluate its performance. Methods Six sets of specific primers targeting S. stercoralis 18S ribosomal RNA (18S rRNA) gene and one fluorescent probe were designed and synthesized. The optimal primer-probe set was determined through systematic screening and optimization to establish the fluorescent RAA assay. The assay was evaluated using S. stercoralis genomic DNA at concentrations of 100, 10, and 1 pg/μL, and 100, 10, and 1 fg/μL, as well as recombinant pUC57 plasmids containing the target gene fragments at 1 × 10⁵, 1 × 10⁴, 1 × 10³, 1 × 10², 1 × 10¹, 1 × 10⁰ copies/reaction, to determine the analytical sensitivity. Genomic DNA from Ascaris lumbricoides, Ancylostoma duodenale, Enterobius vermicularis, Angiostrongylus cantonensis, Trichinella spiralis, Clonorchis sinensis, Schistosoma japonicum, and Taenia saginata was used to assess assay specificity. A total of 25 stool samples from patients suspected of S. stercoralis infection were tested by the modified Baermann funnel technique, PCR, and the established fluorescent RAA assay. The sensitivity, specificity, concordance rate and their 95% confidence intervals (CI) of these three techniques were estimated, and agreement between methods was evaluated using the Kappa coefficient. Results Exo-4 was identified as the optimal primer set screened from the six primer sets, and the best amplification performance was achieved when the final concentrations of the forward and reverse primers were 0.44 μmol/L and a probe concentration was 0.20 μmol/L. The limit of detection of the fluorescent RAA assay was 100 fg/μL for genomic DNA of S. stercoralis and 1 × 10⁰ copies/reaction for recombinant plasmids. Specific fluorescence signals were detected within 5 min, with no cross-reactivity observed with A. lumbricoides, A. duodenale, E. vermicularis, A. cantonensis, T. spiralis, C. sinensis, S. japonicum, or T. saginata. Among the 25 clinical stool samples from patients suspected of S. stercoralis infections, the modified Baermann funnel technique and fluorescent RAA assay detected 19 positives and 6 negatives, whereas PCR detected 18 positives and 7 negatives. The fluorescent RAA assay showed a sensitivity of 100.00% [95% CI: (82.35%, 100.00%)], specificity of 100.00% [95% CI: (54.07%, 100.00%)], concordance rate of 100.00% [95% CI: (86.28%, 100.00%)], and a Kappa coefficient of 1.00 [95% CI: (1.00, 1.00)] (P < 0.001) relative to the modified Baermann funnel technique, and a sensitivity of 100.00% [95% CI: (81.47%, 100.00%)], specificity of 85.71% [95% CI: (42.13%, 99.64%)], concordance rate of 96.00% [95% CI: (79.65%, 99.90%)], and a Kappa coefficient of 0.90 [95% CI: (0.70, 1.00)] (P < 0.001). Positive amplification products emitted green fluorescence under a portable blue-light device, enabling visual interpretation of results. Conclusions The fluorescent RAA assay established in this study is rapid, highly sensitive, and highly specific. It enables detection of S. stercoralis nucleic acid under isothermal conditions and allows visual interpretation of results, providing a novel tool for rapid clinical diagnosis and field screening of S. stercoralis infections.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Objective To understand the clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry,and to provide references for promoting the standardized practice of psychiatric protective restraints and updating the consensus.Methods By the convenience sampling method,a questionnaire survey was conducted among nurses from 480 hospitals in 30 provinces from June 15 to July 15,2024.The survey was conducted using the instrument for evaluating clinical applicability of guide-lines(version 2.0)and a self-compiled questionnaire on the clinical implementation of the restraint consensus.Results A total of 7,844 valid questionnaires were collected,with a valid questionnaire recovery rate of 93.78％.The results of clinical applicability scoring showed that the consensus had the lowest availability score(64.72％)and the highest acceptability score(76.74％).The results showed that nurses' receiving training and the level of their hospitals were the main influencing factors for scores in various dimensions(P＜0.05).4,774 participants(87.42％)believed that the application of consensus could enhance the standardization of nurses' restraint operations.The safety rate of the restraint consensus was 79.51％,and the economic ratio was 76.87％.Among the evaluators,1,739(22.17％)believed that there were implementation obstacles in the consensus.Conclusion The clinical applicability of the consensus is relatively good,and the application of the consensus helps to improve the standardization of clinical operations.In the future,efforts should be made to strengthen the promotion and training of the consensus,develop hierarchical promotion strategies according to the characteristics of medical institutions,and improve the quality of evidence for the consensus,so as to further enhance the clinical application effect of the consensus.

Objective:To investigate the current status of application of stereotactic body radiation therapy (SBRT) in China, aiming to provide reference for promoting the development of this technology.Methods:From January to March 2024, a questionnaire was designed and distributed online, targeting member units of the Professional Committee of Stereotactic Radiosurgery Treatment, which covers 175 radiotherapy units in 30 provinces and regions nationwide. The survey focused on the current application of SBRT technology and its utilization in the treatment of early-stage non-small cell lung cancer (NSCLC). A statistical description of the survey results was presented.Results:Of 175 questionnaires distributed, a total of 130 valid responses were collected, with an effective response rate of 74.3%. A total of 81.5% (106/130) of the units had implemented SBRT technology, and 99.1% of the respondents believed it was necessary to further promote SBRT technology, yet the actual training rate was only 67.0%. SBRT equipment configuration: there were a total of 267 SBRT equipment, featuring a diverse range of types, with traditional linear accelerators as the mainstays, accounting for 76.0% ( n=203), followed by 12.0% ( n=32) for TOMO, 6.4% ( n=17) for Cyber knife, 3.7% ( n=10) for Gamma knife, and proton/heavy ion equipment at 1.5% ( n=4), respectively. The percentage of units with multi-leaf collimator leaf widths ≤0.5 cm was 93.4% (99/106). The application of SBRT: the first radiotherapy unit commenced SBRT in 2000, and this technology entered a period of rapid growth after 2015, sustaining a steady increase over the past decade; SBRT technology was mainly applied in the brain, lung, liver, bone, adrenal gland, and kidney, with application rates of 97.2%, 94.3%, 86.8%, 71.7%, 56.6%, and 27.4%, respectively, while the application rates for the pancreas, metastatic lymph nodes, and other parts were less than 5%. Current status of SBRT technology application in early-stage NSCLC: 90.6% (96/106) of units had implemented SBRT; pre-treatment multi-disciplinary diagnosis and treatment accounted for 77% (74/96); the proportion of application units for peripheral and central type lung cancer lesions both exceeded 57.3%, whereas the application rate for ultra-central type and lesions > 5 cm lung cancer was less than 30%; there was significant variability in the selection of reference guidelines, dose fractionation patterns, and the concept of central type among units. Conclusions:The development of SBRT technology in China is in a period of steady growth, but several issues such as low training rate and lack of standardization still exist. The survey results provide important reference for clinical training and promotion of SBRT technology in China.

Objective To analyze the epidemiological and pathogenic characteristics of acute respiratory in-fection in Yangpu District of Shanghai,and to provide scientific basis for the prevention and treatment of re-spiratory tract infection.Methods A total of 1 062 patients diagnosed with acute respiratory infection in the hospital from June 2023 to June 2024 were selected as the research objects.The nucleic acid of 13 pathogens in nasopharyngeal swabs of patients was detected and the positive rate was calculated.The positive rate of differ-ent age groups and seasons was analyzed.Results Among 1 062 patients,716 cases were detected positive,the total positive rate was 67.42%,of which 577 cases were single infection,the positive rate was 54.33%.The top five positive pathogens were Mycoplasma pneumoniae(MP,16.48%),human coronavirus(HCOV,9.42%),human rhinovirus(HRV,7.63%),human metapneumovirus(HMPV,5.46%)and parainfluenza vi-rus(HPIV,3.39%).A total of 139 cases were infected with multiple pathogens,with a positive rate of 13.09%.MP,HRV,and HCOV were the dominant pathogens,which were prone to multiple infections.A to-tal of 139 cases were infected with multiple pathogens,with a positive rate of 13.09%.MP,HRV,and HCOV were the dominant pathogens,which were prone to multiple infections.The total positive rate of respiratory pathogens in children was 86.38%,the positive rates of single infection and multiple infection were 65.12%and 21.26%,respectively,which were significantly higher than those in other age groups(P<0.05).Among the 577 children with single infection,MP and HRV were the main pathogens in children,MP and HCOV were the main pathogens in young and middle-aged patients,and HCOV and HRV were the main pathogens in the elderly patients.The total positive rate of pathogens was the highest in winter(69.88%),and the lowest in summer(49.54%).HRV had the highest positive rate in spring,HCOV had the highest positive rate in summer,MP had the highest positive rate in autumn,and influenza virus(including influenza A virus,influen-za A/H3N2 virus,influenza B virus)had the highest positive rate in winter(P<0.05).Conclusion MP,HCOV,HRV,HMPV and HPIV are the top five pathogens of acute respiratory tract infection in Yangpu dis-trict of Shanghai.The etiological characteristics were related to age and seasonality of patients.

Objective To evaluate the intravascular volume at different levels of edema and disease course by the fractional excretion of filtered sodium(FeNa)of children with primary nephrotic syndrome(PNS).Methods A total of 172 children with newly diagnosed PNS who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2022 to September 2024 were selected and divided into non-e-dema group(n=51),mild edema group(n=43),moderate edema group(n=46)and severe edema group(n=32)according to the degree of edema at the time of admission.A total of 40 healthy children who underwent physical examination during the same period were selected as the healthy control group.Serum creatinine,ser-um sodium were detected before and after treatment.Urine samples were collected to detect urine creatinine,urine sodium,FeNa was calculated and compared according to the results,and the degree of edema was recor-ded.24 h urine samples were collected on the same day to detect 24 h urine protein quantification and 24 h u-rine volume.Results On day 1 to 2 of the course of the disease,about 12%of the PNS children had FeNa<0.2%,indicating insufficient intravascular volume,which was mainly concentrated in the severe edema group.The moderate,severe edema group had a significantly lower FeNa level than the non-edema group,mild edema group,and healthy control group(P<0.01).The moderate edema group had a significant increase in FeNa on days 6 to 7 of the course of the disease,and the severe edema group had a significant increase in Fena on days 11 to 12 of the course of the disease(P<0.01).Conclusion Intravascular volume of PNS children with mod-erate to severe edema is often reduced,and intravascular volume may be insufficient in severe edema.PNS chil-dren with moderate to severe edema have increased intravascular volume with the extension of the course of disease and the improvement of the condition.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.