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 explore the feasibility of using self-made visual throat forceps to remove hypopharyngeal foreign bodies. Methods:The throat forceps were combined with the endoscope and connected to a monitor via a data cable resulting in a visual throat forceps apparatus. This device was utilized to examine and treat the hypopharyngeal foreign bodies. Results:Among 53 patients, foreign bodies were detected in 51,with 48 cases involving hypopharyngeal foreign bodies. All were successfully extracted using the visual throat forceps. Three cases, diagnosed as esophageal foreign bodies by electronic gastroscopy, were treated using the same method. Conclusion:Visual throat forceps can be used to examine the hypopharynx and remove foreign bodies. It has the advantages of simple operation, rapid operation, and high success rate of foreign body removal from the hypopharynx. It is worthy of clinical application.
Humans ; Hypopharynx/surgery* ; Pharynx/surgery* ; Endoscopes ; Surgical Instruments ; Foreign Bodies/diagnosis*

Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis(KOA)and the potential mediating or masking effect of immune cells using Mendelian randomization(MR)systems.Methods The GWAS data on 1400 plasma metabolites,731 immune cell traits and KOA was retrieved from the genome-wide association study(GWAS)database.Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA.Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects.Results After sensitivity analysis and screening,65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA(P＜0.05).Mediation analysis found that CD45RA+CD28-CD8br％CD8br had a mediating effect in the causal relationship between three metabolites(2-hydroxyhi-ppurate,X-07765,X-23739)and the risk of KOA.2-hydroxyhippurate(salicylic acid)exerted a masking effect,and the effect ratio was 0.0412.Conclusion A variety of plasma metabolites and immune cell traits are causally related to KOA,which should not be regarded as a simple degenerative joint disease.The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells,which is worthy of more studies.

Objective:To evaluate the accuracy of an artificial intelligence (AI) model in measuring key angles on pelvic radiographs of the hip and assess its effectiveness in diagnosing developmental dysplasia of the hip (DDH) and borderline developmental dysplasia of the hip (BDDH).Methods:A retrospective analysis was conducted using anteroposterior pelvic X-ray films from 1,029 patients with suspected DDH. The data were collected from the Department of Radiology, Fourth Medical Center of the Chinese PLA General Hospital. Among the patients, 273 were male, and 756 were female, with an average age of 57.01 ± 18.16 years (range, 12-88 years). The dataset was randomly divided into a training set (720 cases), a test set (206 cases), and a validation set (103 cases). Two radiologists identified and marked key anatomical points of the hip joint to establish the training dataset, which was then used to develop a deep learning-based AI model capable of locating these key anatomical positions. Using the identified anatomical points, the AI model automatically measured and calculated the Sharp angle, center-edge (CE) angle, and T?nnis angle in the test dataset. The measurement results from the AI model were compared with those of the radiologists to evaluate the model's accuracy. The validation set was used to optimize model parameters, and the test dataset was used to evaluate the diagnostic performance of DDH. Receiver operating characteristic (ROC) curves were employed to assess the diagnostic efficacy of the AI model for DDH and BDDH.Results:The accuracy rates of the AI model in measuring the left Sharp angle, CE angle, and T?nnis angle for diagnosing DDH were 89.8%, 90.1%, and 86.8%, respectively. For the right side, the accuracy rates were 93.7%, 92.2%, and 80.5%, respectively. There were no statistically significant differences in the mean values of the Sharp, T?nnis, and CE angles between manual and AI measurements ( P>0.05). Pearson correlation tests and intraclass correlation coefficient (ICC) analyses revealed high consistency between AI and manual measurements of the Sharp angle, T?nnis angle, and CE angle, with r-values and ICC values exceeding 0.75. Additionally, the AI model performed measurements significantly faster (1.7±0.1 s) than radiologists (88.1±8.4 s and 90.3±7.4 s, P<0.001). The areas under the ROC curves (AUCs) for diagnosing DDH using the Sharp angle, CE angle, and T?nnis angle measured by the AI model were 0.883, 0.922, and 0.908 (left side) and 0.924, 0.871, and 0.922 (right side), respectively. For diagnosing BDDH, the AUCs of the left and right CE angles measured by the AI model were 0.787 and 0.676, respectively. Kappa test results indicated good agreement between the AI model and manual measurements as well as final clinical diagnoses. For the CE angle, the κ value of the AI model was 0.663, while κ values for the Sharp and T?nnis angles were all greater than 0.800. Conclusion:The convolutional neural network-based AI model effectively and automatically measures the Sharp, CE, and T?nnis angles and demonstrates high diagnostic efficacy for DDH and BDDH.

Objective:To observe the effects of moxibustion on the levels of glucose-6-phosphate dehydrogenase(G6PD)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)in the plasma and spleen and the CD4+T-cell number in the spleen of rats with adjuvant arthritis,thus to explore the mechanism in rheumatoid arthritis(RA)treatment with moxibustion by regulating the CD4+T-cell proliferation through G6PD-mediated pentose phosphate pathway. Methods:Twenty-seven male Sprague-Dawley rats were randomly divided into a blank group,a model group,and a moxibustion group,with 9 rats in each group.Incomplete Freund's adjuvant was used to induce inflammation in the model group and the moxibustion group.The blank group and the model group were not intervened.In the moxibustion group,suspended moxibustion was performed at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 30 min,once a day for 24 times in total.Hematoxylin-eosin staining was used to evaluate the histopathological changes of rat synovial tissue;the swelling degree of the rat toes was observed by measuring the toe volume;G6PD and NADPH in the spleen and plasma were detected by Western blotting and enzyme-linked immunosorbent assay.Flow cytometry was used to detect the CD4+T-cell number in the spleen. Results:Compared with the blank group,the levels of G6PD and NADPH in the plasma and spleen and the CD4+T-cell number in the spleen were significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,the NADPH level in the spleen and plasma and the CD4+T-cell number in the spleen in the moxibustion group decreased significantly(P<0.05 or P<0.01),and the G6PD level in the plasma decreased significantly(P<0.05),but there was no significant difference in the G6PD level in the spleen(P>0.05). Conclusion:Moxibustion can regulate immunity and improve joint synovial inflammation in RA.The mechanism may be that the G6PD-mediated pentose phosphate pathway reduces the production of metabolite NAPDH in CD4+T cells,thereby inhibiting the proliferation of naive CD4+T cells.

Objective:To investigate the effect of insular involvement on the outcomes of patients with acute anterior circulation ischemic stroke.Methods:Patients with acute anterior circulation ischemic stroke admitted to the Department of Neurology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to December 2020 were retrospectively included. Demographic data, vascular risk factors, clinical and laboratory data, as well as treatment and outcomes were collected. Firstly, the correlation between the insular involvement and the outcomes was investigated, and then the bootstrap method was used to clarify the mediating role of infarct volume between the insular involvement and the poor outcomes.Results:A total of 450 patients with acute anterior circulation ischemic stroke were enrolled, among whom 79 cases (17.6%) had insular involvement and 41 (9.1%) had left insular involvement. There were 111 (24.7%) with poor outcomes, including 5 (1.1%) died. Compared to the non-insular involvement group, the insular involvement group had a higher proportion of patients with atrial fibrillation, shorter onset to door time, higher neutrophil-to-lymphocyte ratio (NLR), higher National Institutes of Health Stroke Scale (NIHSS) score at admission, larger infarct volume, and higher proportion of patients with poor outcomes (all P<0.05). In addition, patients with left insular involvement were younger than those with right insular involvement, had a higher baseline NIHSS score, a lower proportion of patients with minor stroke (NIHSS score ≤8), and had a longer onset to door time (all P<0.05). Compared to the good outcome group, the poor outcome group was older, with a higher proportion of female patients, higher systolic blood pressure, blood glucose, NLR, and NIHSS scores at admission, larger infarct volume, and a higher proportion of patients with insular involvement (all P<0.05). Mediation analysis suggested that the mediating effect of infarct volume between the insular involvement and the poor outcomes was significant (95% confidence interval 0.033-0.230; P=0.008). Conclusions:insular involvement in patients with acute anterior circulation ischemic stroke is associated with the poor outcomes, and this association may be mediated by infarct volume. Patients with left insular involvement may have more severe symptoms than those with right insular involvement, but there is no significant difference in the outcomes.

Objective:To comprehensively evaluate the ability of common resting state functional magnetic resonance imaging (rs-fMRI) indices to detect abnormal brain activity in childhood absence epilepsy (CAE).Methods:Simultaneous electroencephalography-functional magnetic resonance imaging (fMRI) data of 20 patients with CAE who were treated in the Jinling Hospital, Nanjing University School of Medicine from February 2010 to September 2021 were retrospectively collected. After excluding 2 patients with CAE with greater head movement, 44 fMRI data containing discharges from 18 patients were obtained finally. The generalized spike and slow-wave discharges (GSWD) related fMRI activation mappings were obtained by using the generalized linear model. At the same time, 94 age- and sex-matched healthy controls underwent rs-fMRI scanning. Meanwhile, 12 indices of rs-fMRI were calculated respectively [amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF), regional homogeneity (ReHo), functional connectivity density (FCD), long FCD, local FCD, granger causality density (GCD)-in, GCD-out, GCD-int, resting state functional magnetic resonance imaging lag analysis (RSLA), Hurst index and brain entropy]. Two-sample t-tests were employed to detect significant differences in 12 indices of rs-fMRI. The Dice coefficient was used to evaluate the overlap between different brain maps of 12 indices of rs-fMRI and the GSWD-related blood oxygenation level dependent (BOLD) activation. Results:Positive activation of GSWD-related BOLD in CAE was mainly in the bilateral thalamus, and negative activation was mainly in default mode network (DMN) related brain regions. There was a significant overlap between the abnormal brain regions detected by various resting-state indicators: compared with normal controls, ALFF, fALFF, ReHo, GCD-in, GCD-out and local FCD were elevated in the bilateral thalamus, while FCD, long FCD, GCD-int and RSLA were decreased in CAE; ALFF, fALFF, ReHo, local FCD, GCD-out, RSLA and brain entropy were decreased in the DMN, while FCD, long FCD, GCD-in and GCD-int were increased in CAE. The Dice coefficient of long FCD was the highest (0.365),FCD was 0.362, while the Hurst index showed the lowest (0.142).Conclusions:Rs-fMRI indices variously revealed abnormal brain activity in CAE, in which the FCD is better for detection of epileptic activity. Rs-fMRI could be helpful to understand the pathophysiological mechanism of CAE, and to find reliable imaging markers.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Background::The ideal blood pressure (BP) target for patients with atrial fibrillation (AF) is still unclear. The present study aimed to assess the effect of the baseline BP on all-cause mortality in patients with AF.Methods::This registry study included 20 emergency centers across China and consecutively enrolled patients with AF from 2008 to 2011. All participants were followed for 1 year ± 1 month. The primary endpoint was all-cause mortality.Results::During the follow-up, 276 (13.9%) all-cause deaths occurred. Kaplan-Meier curves showed that a systolic blood pressure (SBP) ≤110 mmHg or >160 mmHg was associated with a higher risk of all-cause mortality (log-rank test, P = 0.014), and a diastolic blood pressure (DBP) <70 mmHg was associated with the highest risk of all-cause mortality (log-rank test, P = 0.002). After adjusting for confounders, the multivariable Cox regression model suggested that the risk of all-cause mortality was increased in the group with SBP ≤110 mmHg (hazard ratio [HR], 1.963; 95% confidence interval [CI], 1.306-2.951), and DBP <70 mmHg (HR, 1.628; 95% CI, 1.163-2.281). In the restricted cubic splines, relations between baseline SBP or DBP and all-cause mortality showed J-shaped associations (non-linear P <0.001 and P = 0.010, respectively). The risk of all-cause mortality notably increased at a lower baseline SBP and DBP. Conclusions::Having a baseline SBP ≤110 mmHg or DBP <70 mmHg was associated with a significantly higher risk of all-cause mortality in patients with AF. An excessively low BP may not be an optimal target for patients with AF.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.