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 investigate the correlation between color parameters (L^*, a^*, b^*, Eab^*) and the contents of reducing sugars, total polysaccharides, total oligosaccharides, as well as four saccharides (fructose, glucose, sucrose, and kestose) during the nine cycles of steaming and sun-drying processing of Polygonatum kingianum, and to preliminarily explore the optimal processing duration.
Methods: The color changes were objectively evaluated using a colorimeter. The anthrone-sulfuric acid method was employed to determine total polysaccharides and oligosaccharides. The 3,5-dinitrosalicylic acid (DNS) colorimetric method was used to measure total reducing sugar content. High-performance liquid chromatography coupled with charged aerosol detection (HPLC-CAD) was applied for quantitative analysis of fructose, glucose, sucrose, and kestose. Multivariate statistical analysis was conducted to assess samples from different processing stages.
Results: Significant variations in color and component contents were observed across processing stages. The herbal pieces progressively darkened with increased processing cycles: brightness (L^*) and total color difference (Eab^*) initially decreased then stabilized, while a^* (red-green) and b^* (yellow-blue) values first increased then declined. Total polysaccharides and oligosaccharides showed overall decreasing trends, whereas reducing sugars initially increased before stabilizing. Fructose and glucose levels rose continuously, while sucrose and kestose decreased progressively, becoming undetectable after five cycles.
Conclusion: The chromatic alteration and saccharide composition of P. kingianum showed significant correlation with processing duration. Both total color difference (Eab^*) and reducing sugar content stabilized after four processing cycles (12 hours), suggesting that four cycles of steaming and sun-drying may represent the optimal processing duration.

Objective: To investigate the correlation between the color parameters (L^*, a^*, b^*, Eab^* values) of Polygoni Multiflori Radix Praeparata powder prepared by different processing techniques and the contents of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucopyranoside, emodin, physcion, emodin-8-O-β-D-glucopyranoside, physcion-8-O-β-D-glucopyranoside.
Methods: The L^*, a^*, b^* and Eab^* values of Polygoni Multiflori Radix Praeparata powder prepared by different processing techniques were determined by spectrophotometer, and the contents of the five components were determined by high performance liquid chromatography. Secondly, SPSS 26.0 software and Simca 14.1 software were used to analyze the correlation.
Results: Through the hierarchical cluster analysis (HCA), it was found that the steamed samples and black bean steamed samples could be obviously divided into two categories: raw products and processed products. The processed products could be further divided into 2-8 h and 12-48 h. Pearson correlation analysis showed that the content of stilbene glycoside was significantly positively correlated with L^*, a^* and b^* values (P<0.01). The a^* value was significantly positively correlated with the content of emodin and physcion (P<0.01). Emodin-8-O-β-D-glucoside was positively correlated with L^* value and b^* value, while physcion-8-O-β-D-glucoside was negatively correlated with a^* value. Partial least squares discriminant analysis (PLS) showed that 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside (VIP=1.69) and emodin-8-O-β-D-glucoside (VIP=1.06) were the key variables affecting chromaticity characteristics (P<0.01).
Conclusion: The three processes of steaming, black bean steaming and black bean stewing are consistent in composition transformation and chromaticity variation, and stilbene glycoside can be used as a specific index component to characterize the processed color. Chromatic parameters can effectively reflect the processing progression and serve as quality monitoring indicators during production.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective To analyze the relationship between obesity indicators,muscle mass indices and hypertension in Dongxiang adults,and establish and evaluate a Nomogram model based on these indicators used to predict the risk of hypertension in this population.Methods A total of 1209 Dongxiang adults from Linxia Prefecture,Gansu Province were selected,11 obesity indicators and 5 muscle mass indicators,including neck circumference(NC),waist-to-hip ratio(WHR),BMI,ponderal index(PI),conicity index(CI),a body shape index(ABSI),body roundness index(BRI),abdominal volume index(AVI),hip index(HI),body adiposity index(BAI),and the ratio of limb fat mass to body weight(LFWR),appendicular skeletal muscle mass(ASM),appendicular skeletal muscle mass index(ASMI),appendicular skeletal muscle mass to BMI ratio(ASMBMI),skeletal muscle index(SMI),and trunk muscle mass to body weight ratio(TMWR)were measured.Logistic regression analysis was used to explore the relationship between each indicator and hypertension.Nomogram prediction model was constructed and validated by using R language.Results Among Dongxiang males,the NC,BMI,PI,WHR,CI,AVI,BRI,BAI,ASM,ASMI,and LFWR were lower in the normal and high-normal blood pressure groups compared to the hypertensive group,while SMI,ASMBMI,and TMWR were higher.Among females,similar trends were observed,with lower NC,BMI,PI,WHR,CI,AVI,BRI,BAI,and LFWR in the normal blood pressure and high-normal blood pressure groups compared to the hypertensive group,but SMI,ASMBMI,and TMWR higher than the hypertensive group(P＜0.05).Results of multivariate Logistic regression analysis indicated that age,NC,and WHR were risk factors for hypertension in Dongxiang adults,while was protective factor(P＜0.05).The area under curve(AUC)of the Nomogram model constructed based on these factors was 0.796,and the Bootstrap internal validation C-index was 0.7957,indicating good calibration of the model.Conclusion The Nomogram model constructed based on obesity and muscle mass indicators has good predictive efficiency for predicting the risk of hypertension in Dongxiang adults.

Objective To understand the implementation status of"Diagnosis of Ascariasis"(WS/T 565-2017)and provide a scientific basis for promoting,revising,and improving the Standard.Methods Using the convenient sampling method,the investigation targeted professional and technical personnel at the provincial,city,county,and township levels engaged in parasitic disease prevention,control,or diagnosis and treatment in Anhui and Sichuan provinces.No less than 150 individuals were included in each province.The implementation survey of Diagnosis of Ascariasis(WS/T 565-2017)was conducted by the subjects completing a questionnaire by themselves.Results The response rate to the questionnaire was 91.90%(386/420).The awareness and utilization rates of the Standard were 81.87%and 49.22%,respectively and both increased with age(χ2 trend=7.977 and 19.016,respectively,P＜0.01).Respondents with college degrees(90.72%)had a higher awareness rate(χ2=8.619,P＜0.05).In terms of utilization rate,males(58.38%),those with college degrees(67.01%),staff members of provincial-level units(77.78%),and personnel in medical institutions(71.43%)had higher utilization rates(χ2=13.486,17.166,8.426,and 5.956,respectively,all P＜0.05).The survey indicated that 57.77%of the work units of respondents have conducted promotional activities,and 53.89%of the work units of respondents have sent personnel to participate in training.Moreover,this proportion tended to increase as the unit level decreased(χ2 trend=9.403 and 14.729,P＜0.01).The level of participation in publicity and training by medical institutions(89.29%)was significantly higher than that of disease control institutions(55.31%and 51.12%,respectively,χ2=12.290 and 15.225,P＜0.01).Furthermore,training participation is a crucial factor in enhancing awareness rates.A total of 368 respondents(95.34%)reported that their work units have conducted testing for ascariasis.Additionally,378 individuals(97.92%)believe that the Standard is"applicable"or"basically applicable,"while 369(95.60%)felt that no revisions were needed.Conclusions The results indicated that"Diagnosis of Ascariasis"(WS/T 565-2017)remains applicable to the diagnostic needs of ascariasis and it is recommended to strengthen its promotion and implementation.

BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

Various chromatographic methods were comprehensively applied to study the chemical composition of the ethyl acetate extract from Aucklandiae Radix. The structures of all compounds were identified by analyzing their physicochemical properties and using spectroscopic methods. Two new sesquiterpenoids, named auclappsines A and B(1 and 2) were isolated and identified. Through in vitro high content screening and with the use of a guggulsterone-induced L02 cells, the effects of 1 and 2 on farnesoid X receptor(FXR) protein expression were investigated. The results showed that 1 had a significant FXR activation effect, providing a scientific basis for the development of drugs for the treatment of liver and gallbladder diseases.
Receptors, Cytoplasmic and Nuclear/genetics* ; Humans ; Sesquiterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Cell Line ; Molecular Structure