OBJECTIVE To evaluate the cost-utility of enfortumab vedotin combined with pembrolizumab （PemEV） versus gemcitabine combined with cisplatin or carboplatin （GP） in the first-line treatment of advanced urothelial carcinoma （aUC）. METHODS From the perspective of China’s health system， a dynamic Markov model was established based on the pan-Asian subgroup data from the EV-302 trial. The study timeframe was set at 20 years， with a cycle length of 21 days and a discount rate of 5%. Using total direct medical costs and quality-adjusted life years （QALYs） as outcome measures， the incremental cost- effectiveness ratio （ICER） of the PemEV regimen compared to the GP regimen was calculated. The robustness of the model was validated through sensitivity analysis and scenario analysis， and the price thresholds for enfortumab vedotin and pembrolizumab were estimated under conditions where the PemEV regimen was more cost-effective compared to the GP regimen. RESULTS Cost- utility analysis indicated that compared to the GP regimen， PemEV regimen could generate an additional 2.602 QALYs in aUC patients， but the treatment cost increased by 3 339 703.56 yuan， with an ICER of 1 283 554.39 yuan/QALY. This figure significantly exceeded the willingness-to-pay （WTP） threshold （3 times China’s gross domestic product per capita in 2024， 287 247 yuan/QALY）. The rate parameter of the exponential distribution fitted to the overall survival curve in the PemEV regimen had the greatest impact on ICER， according to the one-way sensitivity analysis. Probabilistic sensitivity analysis suggested that the PemEV regimen had no chance of being more cost-effective than the GP regimen at the current WTP threshold. Scenario analysis revealed that the PemEV regimen consistently lacked cost-utility advantage over the GP regimen， regardless of whether the study model was changed to a partitioned survival model， the study timeframe was set to 5， 10 or 20 years， or the prices of enfortumab vedotin and/or pembrolizumab were reduced by 60%. The prices of enfortumab vedotin and pembrolizumab should be simultaneously reduced by 78.65% （55.71 yuan/mg and 38.26 yuan/mg， respectively） when the PemEV regimen had a cost-utility advantage over the GP regimen. CONCLUSIONS From the perspective of China’s healthcare system， PemEV regimen does not demonstrate a cost-utility advantage over GP regimen in the first-line treatment of aUC.

Objective: To establish a risk prediction model for diabetic peripheral neuropathy (DPN) among patients with type 2 diabetes mellitus (T2DM), so as to provide a basis for DPN prevention and control. Methods: T2DM inpatients aged 18-65 years admitted to the department of endocrinology and metabolism at Affiliated Hospital Shandong Second Medical University from April to December 2024 were selected as study subjects. Age, T2DM duration, hypertension history, 25-hydroxyvitamin D, serum C-peptide, and high density lipoprotein cholesterol (HDL-C) were collected through electronic medical records. Risk predictors of DPN among T2DM patients were screened using multivariable logistic regression model, and a nomogram was established. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: A total of 598 T2DM patients were enrolled, including 359 (60.03%) males and 239 (39.97%) females. The median age was 54.50 (interquartile range, 15.00) years, the median T2DM duration was 6.00 (interquartile range, 9.00) years. There were 262 cases of T2DM patients with DPN, accounting for 43.81%. Multivariable logistic regression identified hypertension history (OR=3.260, 95%CI: 2.220-4.790), alcohol use history (OR=2.150, 95%CI: 1.390-3.310), diabetes complications (OR=0.430, 95%CI: 0.270-0.680), T2DM duration (OR=1.040, 95%CI: 1.010-1.070), body mass index (OR=1.130, 95%CI: 1.070-1.200), 25-hydroxyvitamin D (OR=0.930, 95%CI: 0.910-0.960), and HDL-C (OR=0.400, 95%CI: 0.230-0.720) as risk predictors for DPN among T2DM patients. The area under the ROC curve of the established risk prediction model was 0.774 (95%CI: 0.737-0.812), with a sensitivity of 0.710 and a specificity of 0.723. The calibration curve after repeated sampling calibration approached the standard curve. Decision curve analysis showed that when the risk threshold probability was 0.2 to 0.4, the model demonstrates favorable clinical applicability. Conclusion The risk prediction model established in this study has favorable discrimination, calibration, and clinical utility, can effectively predict the risk of DPN among T2DM patients aged 18-65 years.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Chloropicrin is a commonly used pesticide in agricultural production. The clinical manifestations of oral poisoning patients are complex, and the lesions involve multiple organs. At present, the specific pathogenic mechanism of such poisoning is not clear, and the treatment experience is insufficient, so there are certain difficulties in clinical diagnosis, treatment and treatment. In this paper, the data of a patient with oral chloropicrin poisoning treated in Yidu Central Hospital of Weifang City in April 2023 were summarized. The patient was admitted to our hospital for treatment in time, and his condition improved after Hemopurification, methylene blue reduction, organ support, infection prevention as well as other symptomatic support. Oral chlorophenol can cause lung damage, skin and mucous membrane damage, and may have certain effects on the nervous system and kidney. Early intervention, especially blood purification, is effective.

Objective To establish a rapid detection and identification method for the chemical components of Longshengzhi capsules based on UPLC-Q-TOF/MS.Method UPLC-Q/TOF-MS technology was used to analyze and identify the chemical components of Longshengzhi capsules.The chromatographic column was a Waters Acquity UPLC BEH C18 column(100mm×2.1mm,1.7 μm),and the mobile phase A was 0.1%formic acid water.The mobile phase B was a methanol acetonitrile(1∶1)solution containing 0.1%formic acid(B).The flow rate is 0.3mL/min,the column temperature is 40℃,and the injection volume is 2 μL.The ion source adopts the electric spray ion source.The data is collected in the positive and negative ion modes,and the collection range is m/z 50～1200.The identification and matching are carried out through UNIFI software combined with manual verification of chemical components.Result 87 chemical components were preliminarily and rapidly identified.Conclusion The established method can systematically and rapidly analyze the chemical components in Longsheng leeches,providing a basis for the study of medicinal substances and having important significance for the quality control of Longsheng leeches.

Chloropicrin is a commonly used pesticide in agricultural production. The clinical manifestations of oral poisoning patients are complex, and the lesions involve multiple organs. At present, the specific pathogenic mechanism of such poisoning is not clear, and the treatment experience is insufficient, so there are certain difficulties in clinical diagnosis, treatment and treatment. In this paper, the data of a patient with oral chloropicrin poisoning treated in Yidu Central Hospital of Weifang City in April 2023 were summarized. The patient was admitted to our hospital for treatment in time, and his condition improved after Hemopurification, methylene blue reduction, organ support, infection prevention as well as other symptomatic support. Oral chlorophenol can cause lung damage, skin and mucous membrane damage, and may have certain effects on the nervous system and kidney. Early intervention, especially blood purification, is effective.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Objective:To investigate the main factors that influence ALT abnormalities in workers exposed to benzene.Methods:In June 2022, data of 613 enterprises with benzene hazards and 585 enterprises with non-benzene hazards in Tianjin in 2021 were collected, and occupational health examination data of 13018 workers with benzene exposure and 13018 workers with non-benzene exposure were collected, and the region, enterprise type, industry classification and enterprise scale of the employer were analyzed. And occupational health examination data of workers with benzene exposure and non-benzene exposure. The effects of personal general situation, occupational history, enterprise information and benzene exposure on alanine aminotransferase were evaluated by additive interaction.Results:Compared with the group of non-benzene-exposed workers, the personal general conditions, occupational history, company information were higher in the benzene-exposed workers, and the differences were statistically significant ( P<0.05). The quantitative analysis of additive interaction found that gender ( RERI=2.632, 95% CI: 1.966-3.297; AP=0.383, 95% CI: 0.311-0.456; S=1.813, 95% CI: 1.530-2.149), age ( RERI=1.142, 95% CI: 0.928-1.356; AP=0.462, 95% CI: 0.371-0.552; S=4.461, 95% CI: 1.800-11.053), length of service ( RERI=-1.199, 95% CI: -1.653--0.745; AP=-0.456, 95% CI: -0.640--0.271; S=0.576, 95% CI: 0.479-0.693), region ( RERI=0.421, 95% CI: 0.148-0.694; AP=0.161, 95% CI: 0.053-0.268; S=1.350, 95% CI: 1.057-1.726), industry classification ( RERI=0.627, 95% CI: 0.345-0.910; AP=0.232, 95% CI: 0.132-0.332; S=1.584, 95% CI: 1.233-2.035) and benzene exposure had a statistically significant additive interaction with abnormal serum ALT. Conclusion:Emphasis should be placed on male workers under the age of 40 in the petrochemical industry, oil storage and transportation, and power production, so as to protect the health of workers more specifically and reduce the risk of disability due to disease.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

Objective:To investigate the main factors that influence ALT abnormalities in workers exposed to benzene.Methods:In June 2022, data of 613 enterprises with benzene hazards and 585 enterprises with non-benzene hazards in Tianjin in 2021 were collected, and occupational health examination data of 13018 workers with benzene exposure and 13018 workers with non-benzene exposure were collected, and the region, enterprise type, industry classification and enterprise scale of the employer were analyzed. And occupational health examination data of workers with benzene exposure and non-benzene exposure. The effects of personal general situation, occupational history, enterprise information and benzene exposure on alanine aminotransferase were evaluated by additive interaction.Results:Compared with the group of non-benzene-exposed workers, the personal general conditions, occupational history, company information were higher in the benzene-exposed workers, and the differences were statistically significant ( P<0.05). The quantitative analysis of additive interaction found that gender ( RERI=2.632, 95% CI: 1.966-3.297; AP=0.383, 95% CI: 0.311-0.456; S=1.813, 95% CI: 1.530-2.149), age ( RERI=1.142, 95% CI: 0.928-1.356; AP=0.462, 95% CI: 0.371-0.552; S=4.461, 95% CI: 1.800-11.053), length of service ( RERI=-1.199, 95% CI: -1.653--0.745; AP=-0.456, 95% CI: -0.640--0.271; S=0.576, 95% CI: 0.479-0.693), region ( RERI=0.421, 95% CI: 0.148-0.694; AP=0.161, 95% CI: 0.053-0.268; S=1.350, 95% CI: 1.057-1.726), industry classification ( RERI=0.627, 95% CI: 0.345-0.910; AP=0.232, 95% CI: 0.132-0.332; S=1.584, 95% CI: 1.233-2.035) and benzene exposure had a statistically significant additive interaction with abnormal serum ALT. Conclusion:Emphasis should be placed on male workers under the age of 40 in the petrochemical industry, oil storage and transportation, and power production, so as to protect the health of workers more specifically and reduce the risk of disability due to disease.