OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Objective To investigate the correlation between hyperuricemia and the risk of type 2 diabetes mellitus, and to explore whether hyperuricemia is an independent risk factor of type 2 diabetes mellitus. Methods Using a prospective cohort study design, 300 adult volunteers who underwent physical examinations at the 3201 Hospital were recruited from January to December 2021. They were divided into a high uric acid group and a non-high uric acid group based on their uric acid levels. The incidence of diabetes in people with different uric acid levels was observed within two years through follow-up. SPSS26.0 software was used to statistically analyze the data. Results The data of this study showed that hyperuricemia significantly increased the risk of type 2 diabetes mellitus (P=0.01，OR=3.551). In addition, BMI had a significant impact on the risk of diabetes (P=0.000，OR =0.115), but the impact of age and gender was not statistically significant (both P>0.05). Conclusion Hyperuricemia is positively correlated to the incidence of type 2 diabetes. The higher the uric acid level, the higher the incidence of type 2 diabetes. The uric acid level has a good evaluation value in the incidence of type 2 diabetes mellitus. This finding provides a basis for early intervention of hyperuricemia as a potential risk factor for type 2 diabetes.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.

Objective:To compare the clinical data and peripheral blood levels of CXC chemokine ligand (CXCL) 9 and CXCL10 between patients with progressive non-segmental vitiligo who were sensitive to systemic glucocorticoid treatment and those who were resistant, and to clarify key clinical factors influencing the sensitivity to systemic glucocorticoid treatment.Methods:From May 2021 to May 2023, a cohort of patients with progressive non-segmental vitiligo receiving systemic glucocorticoid treatment was established in Huashan Hospital, Fudan University. Clinical data and peripheral blood samples were prospectively collected from all enrolled patients. Standard treatment, i.e., intramuscular injections of 1 ml of compound betamethasone once a month, was administered. After 3-month treatment, the improvement of patients′ skin lesions was estimated, and the vitiligo area and severity index (VASI) score and the Vitiligo European Task Force assessment tool (VETFa) were used to evaluate the efficacy. Patients with VASI changes ≥ 0 and VETFa progression scores ≤ 0 point were included in the glucocorticoid-sensitive group (i.e., the patients′ condition was stable or improved), otherwise those with VASI changes < 0 and VETFa progression scores of 1 point were included in the glucocorticoid-resistant group. Associations of lesion locations, specific clinical markers (trichrome lesions, confetti-like depigmentation, and Koebner phenomenon), previous medication history, family history of vitiligo, etc. with the response to systemic glucocorticoid treatment were analyzed. At baseline and after 3-month treatment, peripheral blood samples were collected from the patients, and enzyme-linked immunosorbent assay was performed to detect the plasma levels of CXCL9 and CXCL10. Statistical analysis was carried out by using the chi-square test, Fisher′s exact test, binary logistic regression analysis, Mann-Whitney U test, and Wilcoxon signed-rank test. Results:A total of 142 patients with vitiligo were enrolled, and 127 completed 3-month treatment, including 77 males and 50 females. Their age at diagnosis was 18 to 65 (36.6 ± 11.4) years, and the disease duration ranged from 2 months to 58 (13.5 ± 10.7) years; 25 (19.7%) had a family history of vitiligo; the percentage of lesion area to total body surface area before treatment ranged from 1% to 70% (11.5% ± 12.7%), and the VASI score was 1% to 70% (10.8% ± 11.6%). Multivariate logistic regression analysis showed that the absence of specific clinical markers (odds ratio [ OR] = 6.900, 95% confidence interval [ CI]: 1.228, 38.757, P = 0.028), carrying a single specific clinical marker ( OR = 2.579, 95% CI: 1.012, 6.574, P = 0.047), having a history of topical glucocorticoid treatment ( OR = 2.643, 95% CI: 1.019, 6.850, P = 0.041), the absence of family history of vitiligo ( OR = 5.090, 95% CI: 1.070, 24.215, P = 0.030), and lesions on the proximal extremities ( OR = 3.767, 95% CI: 1.315, 10.793, P = 0.037) were risk factors for the resistance to systemic glucocorticoid treatment in the patients with vitiligo. After 3-month treatment, the glucocorticoid-sensitive group showed a significant decrease in plasma CXCL10 levels compared with those before treatment ( W = 571.00, P < 0.001), while there was no significant difference between the pre- and post-treatment CXCL10 levels in the glucocorticoid-resistant group ( W = 48.00, P = 0.524). Additionally, no significant difference was observed in changes of the plasma CXCL9 level before and after treatment between the glucocorticoid-sensitive and glucocorticoid-resistant groups ( P > 0.05) . Conclusions:Carrying no or a single specific clinical marker, having a history of topical glucocorticoid treatment, the absence of family history of vitiligo, and lesions on the proximal extremities appeared to be risk factors for the resistance to systemic glucocorticoid treatment in patients with progressive non-segmental vitiligo. Changes in CXCL10 levels after treatment may be used as an important evaluation indicator for determining whether patients with progressive vitiligo were resistant to systemic glucocorticoid treatment.

ObjectiveTo understand the prevalence of respiratory syncytial virus （RSV） infections among children hospitalized with severe acute respiratory infections （SARI） in Huzhou， Zhejiang Province， and to explore the epidemiological characteristics and influencing factors of RSV. MethodsNasopharyngeal swab samples from children under 15 years of age， newly admitted to the Huzhou First People's Hospital from 2018 to 2022 and who met the SARI surveillance definition， were collected for respiratory virus nucleic acid testing. SPSS 25.0 and Excel 2016 software were used for statistical analysis of the data. ResultsA total of 1 076 samples were tested for nucleic acids， with an overall positivity rate of 11.2%. The positivity rate of infants under 5 years old was relatively high （16.7%）. RSV infection showed a seasonal distribution， mainly concentrated in autumn and winter， with the highest positivity rate in December （22.3%）. A total of 23 cases of respiratory mixed infection were detected， with a mixed infection rate of 2.13%， among which 16 were RSV-related mixed infections. Logistic regression analysis indicated that season and age were risk factors for RSV infection. ConclusionFrom 2018 to 2022， RSV showed different epidemiological characteristics across different ages and seasons in SARI cases in Huzhou， with significant differences， providing a scientific basis for future prevention of RSV infections.

With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Infantile epileptic spasm syndrome(IESS)is a new concept proposed recently.IESS is a unique and age-specific refractory epilepsy syndrome.The recent advances in molecular biology,neuroimmunol-ogy and the in-depth study of anti-epileptic mechanism in antiepileptic drugs have led to the achievements in the definition and treatment of infantile epileptic spasm.At present,the use of traditional antiepileptic drugs is de-creasing,while the use of new antiepileptic drugs is increasing.In this paper,based on the relevant literature in recent years,the authors discuss the pathogenesis,epidemiology,etiology,diagnosis,treatment,therapeutic drugs,clinical progress,efficacy,and safety of infantile epileptic spasm,hoping to introduce the latest status in research and achievements of IESS.