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.

Acute respiratory distress syndrome(ARDS)is a common clinical syndrome in intensive care unit(ICU)with high morbidity and mortality.Recently,the new global definition of ARDS has redefined the diagnosis of ARDS,which is divided into non-intubated ARDS,intubated ARDS and ARDS with limited resources.Hypoxia is the main clinical manifestation of ARDS,and respiratory support therapy is the first-line treatment for ARDS.With respect to non-intubated ARDS,current guidelines do not provide a clear preference between high flow nasal cannula(HFNC)and non-invasive mechanical ventilation(NIV).In order to improve clinical managmet of non-intubated ARDS,we review the role of HFNC and NIV in non-intubated ARDS in this paper.

Objective:To compare the effect of transcranial magnetic stimulation (rTMS) of the contralesional hemisphere at different frequencies on the recovery of upper limb motor function after a moderate-to-severe ischemic stroke.Methods:The inter-hemisphere compensation model was applied along with electroencephalogram (EEG) power spectrum density measurements. Thirty stroke survivors were randomly assigned to a sham stimulation group ( n=9), a high-frequency stimulation group ( n=11) or a low-frequency stimulation group ( n=10). In addition to physical and pharmacological therapy, the low-frequency and high-frequency groups received 1Hz or 5Hz rTMS, while the sham group received sham stimulation. The rTMS was delivered over the contralesional (unaffected) hemisphere once daily for 20 minutes over 15 consecutive days. Before, as well as 7 and 15 days after the treatment, all of the subjects′ motor functioning was assessed using the Fugl-Meyer Assessment for the upper extremity (FMA-UE) and their ability in the activities of daily living was assessed using the modified Barthel Index (MBI). Resting-state EEGs with the eyes closed were also recorded, and absolute alpha power across the whole brain was calculated. Changes from baseline FMA-UE and MBI scores and absolute alpha power were analyzed using one-way and repeated-measures analysis of variance. Results:After the treatment, significant within-group improvements from baseline were observed in the FMA-UE scores, MBIs and absolute alpha power, except for absolute alpha power in the low-frequency and sham groups. The repeated-measures analysis of variance revealed significant time × group interactions for FMA-UE ( F=9.926, P≤0.001), MBI ( F=8.789, P≤0.001) and absolute alpha power ( F=4.511, P≤0.05). So the treatment effects varied among the groups. Post hoc Bonferroni-corrected comparisons showed that the high-frequency group exhibited significantly greater improvements from baseline in terms of all three indicators compared with the other two groups. Conclusions:High-frequency (5Hz) rTMS applied to the contralesional hemisphere produced greater improvement than low-frequency (1Hz) stimulation in the upper limb motor function of patients with moderate-to-severe stroke. These findings support the use of the interhemispheric compensation model to guide rTMS therapy, particularly for patients with FMA-UE scores below 43.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objective To investigate the clinical characteristics of lower respiratory tract infections oc-currence and respiratory system prognosis in infantile stage of children patients with bronchopulmonary dys-plasia(BPD).Methods Fifty premature infants with lower respiratory tract infection and BPD treated in this hospital from March 2017 to December 2020 were selected as the BPD group and 50 preterm infants with low-er respiratory tract infection without BPD during the same period were selected as the non-BPD group.The clinical data and occurrence situation of respiratory system diseases within 3 years after birth in the two groups were collected and analyzed.Results Compared with the non-BPD group,the incidence rates of tachy-pnoea(48.0%vs.12.0%),wheeze(44.0%vs.10.0%),wheezing rale(44.0%vs.10.0%),three concave sign(28.0%vs.8.0%),cyanosis(20.0%vs.4.0%),severe pneumonia(48.0%vs.12.0%)and respirato-ry failure(20.0%vs.4.0%)in the BPD group were higher,the hospitalization duration[7.5(7.0,10.0)d vs.7.0(6.0,7.0)d]was longer,the reaching peak time ratio[18.20%(14.65%,22.25%)vs.24.85%(19.55%,32.78%)],the reaching peak volume ratio[22.15%(19.43%,23.83%)vs.25.65%(22.40%,34.90%)]and the inspiratory/expiratory ratio(0.70±0.12 vs.0.76±0.11)were lower,the 3-year total lower respiratory tract infection times[5.0(4.0,10.0)times vs.3.0(2.0,5.0)times],wheeze times[2.0(1.0,4.0)times vs.0.5(0,1.0)times],the hospitalization times[3.00(2.00,5.00)times vs.2.00(1.00,2.00)times],severe pneumonia times[2.0(1.0,2.0)times vs.1.0(0,1.0)times]and wheeze times in differ-ent ages were more,total hospitalization duration[29.50(19.50,38.25)d vs.13.00(7.00,17.75)d]was lon-ger,the differences were statistically significant(P<0.05).Conclusion The children patients with BPD are prone to lower respiratory tract infections,especially 0-<1 years old,the proportion of severe pneumonia af-ter infection is higher and wheezing is easily to develop.

Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS)on the sleep disorder and examination results of recruits.Methods At a training base,the Pittsburgh Sleep Quality Index(PSQI)was used to screen the recruits with sleep disorders(total score of PSQI>7).The recruits were randomly assigned to rTMS group or sham rTMS group.Both groups received cognitive and behavioral intervention therapy,including sleep health education and relaxation training.Moreover,the rTMS group was treated with rTMS at the right posterior parietal lobe by continuous theta burst stimulation(cTBS)twice a day at an interval of at least 50 min for 5 consecutive days as a course of treatment with an interval of 2 days for a total of 2 courses of treatment.The coil position and stimulus intensity of sham rTMS group were consistent with the rTMS group,but the head of subjects was perpendicular to the coil plane and there was no effective stimulation.Before and after treatment,PSQI,self-rating depression scale,generalized anxiety disorder-7 and health questionnaire-15 were used to evaluate the sleep,mood and physical state of the recruits.The training result was assessed one month after treatment.The total effective rate of PSQI improvement and examination results were compared between the two groups.The independent influencing factors of excellent examination result were analyzed.Results Among 351 recruits,83 with sleep disorders completed treatment and follow-up.There were 40 patients in the rTMS group and 43 patients in the sham rTMS group.There was no significant difference between the two groups at baseline.After treatment,the total effective rate of PSQI improvement in the rTMS group was higher than that in the sham rTMS group(77.50%vs 53.49%,P=0.022).The average examination score and excellent rate of the rTMS group were higher than those of the sham rTMS group(91.58±3.19 vs 89.47±4.67,P=0.020;85%vs 65.12%,P=0.037).Logistic regression analysis showed that the treatment mode(rTMS group)was the independent influencing factor of excellent examination results(P=0.032).Conclusion rTMS can effectively and safely improve the sleep disorders and examination results of recruits.rTMS may play a positive role in improving the learning and training effect of recruits,which needs to be further proved.