Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*