This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

Objective To investigate the expression of pepsin in vocal cord polyps and vocal cord cancer,and to compare the difference of pepsin expression.Methods From May 2020 to December 2021,27 patients with vocal cord polyp,27 patients with vocal cord cancer and 23 healthy volunteers were selected.RSI and RFS scoring scales were used for scoring,pepsin detection kit was used for saliva pepsin detection,and immunohistochemical methods were used to detect the expression of pepsin in vocal cord tissues of patients with vocal cord polyps and vocal cord cancer.Results The RSI score,RFS score and pepsin test kit results of vocal cord polyp group and vocal cord canc-er group were higher than those of non-vocal cord disease group,and the differences of the three indexes were statis-tically significant(P＜0.05).RSI score,pepsin detection kit results and pepsin immunohistochemistry results of vocal cord polyp group showed no significant difference compared with vocal cord cancer group(P＞0.05).The RFS score of vocal cord polyp group was significantly different from that of vocal cord cancer group(P＜0.05).Conclusion Pepsin may be an important pathogenic factor of vocal cord polyp and vocal cord cancer,and play an im-portant role in the occurrence of these two diseases.The difference of pepsin expression in vocal cord polyp and vo-cal cord cancer suggests that pepsin may have different pathogenesis.

BACKGROUND:Natural bone morphogenetic protein 2 disperses and degrades rapidly in vivo,reducing local concentration and therapeutic efficacy.Simply combining bone morphogenetic protein 2 with tissue engineering scaffolds could not stay in vivo for a long time,making it difficult to achieve good sustained and controlled release effects.OBJECTIVE:To prepare and test the biological properties and chondrogenic induction effect of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold.METHODS:SD rat tail collagen was extracted and a collagen cartilage scaffold was prepared using a vacuum freeze-drying machine chemical crosslinking method.The plasmid expressing collagen-binding domain-bone morphogenetic protein 2 was constructed by rapid cloning C112 homologous recombination,constructed by genetic engineering,and introduced into E.coli,and then collagen-binding domain-bone morphogenetic protein 2 was isolated and purified.Natural bone morphogenetic protein 2 and collagen-binding domain-bone morphogenetic protein 2 were combined with collagen cartilage scaffolds,respectively,to detect the release level of bone morphogenetic protein 2 in the scaffolds.The biocompatibility of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold was detected by CCK-8 assay and F-Actin staining.Bone marrow mesenchymal stem cells were implanted on two kinds of collagen cartilage scaffolds for chondrogenic induction,and their chondrogenic induction activity was tested.RESULTS AND CONCLUSION:(1)The binding rate of collagen-binding domain-bone morphogenetic protein 2 to collagen cartilage scaffolds was higher than that of natural bone morphogenetic protein 2(P<0.05).After being immersed in PBS for 7 days in vitro,the release of bone morphogenetic protein 2 in the collagen-binding domain bone morphogenetic protein 2-collagen cartilage scaffold was smaller than that in the natural bone morphogenetic protein 2-collagen cartilage scaffold(P<0.05).The results of the CCK-8 assay and F-Actin staining showed that the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold had no obvious cytotoxicity and had good biocompatibility.(2)After 14 days of chondrogenic induction,ELISA detection demonstrated that the expressions of agglutincan and type Ⅱ collagen A1 in the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold group were higher than those in the natural bone morphogenetic protein 2-collagen cartilage scaffold group(P<0.05).Under scanning electron microscopy,more bone marrow mesenchymal stem cells were observed on the inner wall of the pores of the two groups of scaffolds,and the cell morphology and size were the same,and the cells were closely arranged,without cell fragmentation or abnormal morphology.(3)The results indicate that the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold has good biological properties and chondrogenic induction activity.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

AIM: To systematically evaluate the efficacy and safety of low-concentrations atropine eye drops in controlling adolescent myopia.METHODS:A computer search was conducted on Wanfang Data, CNKI, VIP, PubMed, Cochrane Library, and Embase databases from January 2010 to March 2024 on clinical studies on low-concentration atropine eye drops for controlling adolescent myopia. Two researchers independently screened trials, extracted data, evaluated risk of bias and quality, and used Review Manager5.4 software to perform Meta-analysis.RESULTS:A total of 17 articles, involving 3 764 cases and 3 952 eyes, were included. The Meta-analysis showed that compared with the control group, low concentrations of atropine could effectively slow down the growth of axial length [MD=-0.15, 95% CI(-0.20, -0.10), P<0.00001], significantly controlled the changes in spherical equivalent [MD=0.39, 95% CI(0.29, 0.48), P<0.00001], and had a significant effect on pupil diameter [MD=0.80, 95% CI(0.33,1.28), P=0.0010] and amplitude of accommodation [MD=-2.54, 95%CI(-4.49, -0.60), P=0.01].CONCLUSION:Low-concentrations atropine are effective in controlling spherical equivalent and axial length of myopia in adolescents, significantly affecting pupil diameter and amplitude of accommodation, and effectively delaying the progression of myopia.

Background Injury is a major public health issue, and studying the correlation between temperature and injury in the context of climate change is of great significance for injury prevention and control. Objective To analyze the association between temperature and the volume of emergency medical service response due to injury in Chengdu. Methods Using a retrospective ecological study design, weather data in Chengdu were collected from 1 January 2022 to 31 December 2023 from Chengdu Meteorological Office, including daily average temperature, daily average relative humidity, average wind speed, average pressure, sunshine, and rainfall. Emergency medical service data were collected from an emergency medical service center in Chengdu. A distributional lag non-linear model was conducted to calculate the association between temperature and volume of emergency medical service response due to injury, and gender- and age-stratified analyses were followed to identify susceptible groups. Results Overall 219685 incidents of emergency medical service dispatching due to injury were collected during the study period. The top three injury causes were traffic accident (90765, 41.32%), poisoning (44101, 20.07%), and falling (44046, 20.05%). When daily average temperature exceeded 17.9 ℃, as the temperature rised, the volume of emergency medical service response for injury increased. In terms of the single-day lag effect, the risk of emergency medical service response for injury elevated on lag1 and persisted until lag6, the maximum daily effectwas observed on lag2, lag3 and lag4, and their relative risks associated with every 1℃ higher above 17.9 ℃ were both 1.08 times, 95%CIs were (1.03, 1.14), (1.04, 1.12), and (1.04, 1.16) respectively. Both men and women were susceptible to temperature, but on the same lag day, the men's RR value was higher than the women's. There was no statistical difference in the lag effect of temperature on the 0-17 age group; the lag effect on the 18-44 age group appeared on lag1, and lasted to lag6; that for the 45-64 age group appeared on lag1, and lasted to lag4; that for the 65 age group and over was only on lag 3 (RR: 1.05, 95%CI: 1.00, 1.10). Conclusion As the temperature rises, the volume of emergency medical service response due to injury is increased in Chengdu. In particular, the associated impact is significant on males and people aged 18-44 years old.

The toad, known for its various medicinal properties including parotid gland secretion (toad venom), dried skin, and gallbladder (toad bile), holds considerable medicinal applications as a valuable traditional Chinese animal medicine. Currently, in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin; however, a lesser number of detailed analyses were concentrated on the toad bile. This review provides an overview of the chemical constituents in the bile of the Bufo genus, with a special focus on the cholestane and bufadienolides, and highlights the progress in their biosynthetic pathway and pharmacological activities. The analysis uncovers a distinct category of unsaturated Δ²² or Δ²³-C₂₇/C₂₈ bile acids in the toad gallbladder, potentially acting as key intermediaries in forming C-17 α-pyrone of bufadienolides. Furthermore, the high presence of 3α-OH configured bufadienolides in toad bile, in contrast to the common 3β-OH configured found in toad venom or skin, indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control. This review provides scientific basis for the development and utilization of toad bile resources, and provides useful reference for the discovery of lead compounds, analysis of the biosynthetic pathway of bufadienolides, and research on toad physiology.