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*

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

Objective To construct an in vitro"metabolic memory"cell model of HT-22 mouse hippocampal neurons induced by high glucose,and to investigate the effect of"metabolic memory"on apoptosis and histone acetylation in HT-22 cells.Methods HT-22 cells were cultured in high glucose medium(glucose concentration was 55 mmol/L)and conventional glucose medium(glucose concentration was 25 mmol/L),and cells were divided into the control group(NG 4,6 and 8 groups,25 mmol/L glucose was cultured for 4,6 and 8 days,respectively),the high glucose group(HG 4,6 and 8 groups,respectively)and the metabolic memory group(HG2NG2,HG2NG4,HG2NG6,HG4NG2 and HG4NG4 groups,high glucose culture for 2 days to 25 mmol/L glucose culture for 2,4 or 6 days,high glucose culture for 4 days to 25 mmol/L glucose culture for 2 or 4 days).Cell viability was detected by CCK-8 method.The release of lactate dehydrogenase(LDH)in cell culture supernatant was detected,and the optimal time to establish a"metabolic memory"model was selected.Subsequently,cells were divided into the NG4 group,the NG8 group,the HG4 group,the HG4NG4 group and the HG8 group,and the cell morphology of each group was observed by optical microscope.The apoptosis rate was detected by flow cytometry.The activities of deacetylase(HDAC)and histone acetyltransferase(HAT)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot assay was used to detect expression levels of histone deacetylase 4(HDAC4),B lymphocyte tumor 2(Bcl-2),Bcl-2 related X protein(Bax)and Caspase-3 protein.Results The HG4NG4 group was the ideal cell model with high glucose metabolic memory.Cells of the NG4 group and the NG8 group were interwoven into a dense network,growing well,with spindle shaped cells and distinct synaptic structures.However,in the HG4 group and the HG8 group,the cell body became round,synaptic structure disappeared and growth was inhibited.In the HG4NG4 group,the number of cells increased but their morphology was damaged.Results of flow cytometry showed that compared with the NG8 group,the apoptosis rates were significantly increased in the HG8 group and the HG4NG4 group(P＜0.05).ELISA results showed that compared with the NG8 group,the expression levels of HDAC4,Bax,and Caspase-3 proteins increased in the HG8 group and the HG4NG4 group,while the expression level of Bcl-2 protein significantly decreased(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels of HAT and HDAC in the HG4NG4 group.Western blot reslts showed that compared with the NG8 group,the levels of HDAC4,Bax and Caspase-3 protein increased in the HG8 group and the HG4NG4 group(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels in the HG4NG4 group.Conclusion HT-22 mouse hippocampal neurons cultured with 55mmol/L high glucose for 4 days,and then cultured with 25 mmol/L glucose for 4 days are the ideal"metabolic memory"cell model.The mechanism may be related to the increased activity of HDAC,HAT and HDAC4 expression in the hyperglycemic model.

Objective: To investigate the differences and diversity changes in gut microbiota between children and adolescents with constipation and diarrhea, and healthy individuals, and to explore the correlation between changes in stool consistency and gut microbiota, in order to provide a scientific reference for the research on intestinal microecology among children and adolescents. Methods: From October 2021 to March 2022, a total of 42 children and adolescents with constipation and 37 with diarrhea from a tertiary hospital in Hangzhou City, and 43 healthy individuals from 3 primary and secondary schools were included in this study. Fecal samples of children and adolescents were collected and then stool genomic DNA was extracted for 16S rRNA gene high throughput sequencing, and the sequencing results were analyzed. In the analysis of alpha diversity, the Kruskal-Wallis rank sum test was used to compare the differences between the three groups, and the FDR multiple testing correction was used for pairwise comparisons. In the analysis of beta diversity, the Adonis test was used to compare the overall differences between the three groups, and the ANOSIM test was used for pairwise comparisons. In the LEfSe analysis, the LDA scores obtained through LDA analysis (linear regression analysis). Results: Alpha diversity analysis showed that there were statistically significant differences in the Shannon index (4.01, 3.81, 4.19) and Simpson index (0.05, 0.06, 0.04) between the diarrhea group, constipation group, and healthy group ( H=6.05, 6.35, P <0.1). Further pairwise comparison showed that the Shannon index and Simpson index of the healthy group were higher than those of the constipation group ( P <0.1). Beta diversity analysis showed that the impact of grouping factors on inter group differences was statistically significant ( R 2=0.045, P <0.1). Community composition analysis showed that there were 234 species in total among the three groups, and 36 unique species in the healthy group, 36 species in the diarrhea group, and 48 species in the constipation group. Species difference analysis showed significant differences in species composition at the genus level among the three groups ( H=0.000 05, 0.000 16, 0.000 20, 0.000 21, 0.000 53, 0.001 39, P <0.1), including Lachnospiraceae of Firmicutes phylum, Eubacterium hallii, Veillonellaceae, Qscillospiraceae, Butyricicoccaceae and Staphylococcaceae, respectively. KEGG abundance statistics and COG functional analysis showed that there were no significant differences in gene expression abundance of the same function among the three groups ( P >0.1). Conclusions The different stool consistency of children and adolescents is related to changes in gut microbiota composition. Compared to the healthy group, children with constipation or diarrhea have disrupted gut microbiota balance, with a shift in dominant bacteria and a higher abundance of opportunistic pathogens.

Gold nanoparticles(AuNPs)present unique physicochemical characteristics,excellent biocom-patibility and ease of surface functionalization,which have become the research hotspots in the field of biosens-ing.This article reviews the synthesis methods,main properties and surface functionalization of AuNPs,as well as the research progress of application in various sensing platforms.

Background::Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC) in China. The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen (HBsAg). However, current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking. We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China.Methods::Questionnaires including information of sex, age, ethnicity, marital status, educational level, source of drinking water, as well as smoking and alcohol consumption history and serum samples were collected from females aged 45–64 years and males aged 35–64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023. Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg.Results::A total of 603,082 individuals were enrolled, and serum samples were collected for analysis from January 1, 2015 to December 31, 2023. The prevalence of HBsAg positive in the study population was 5.23% (31,528/603,082). The prevalence of HBsAg positive was greater in males than in females (5.60% [17,660/315,183] vs 4.82% [13,868/287,899], χ 2 = 187.52, P <0.0001). The elderly participants exhibited a greater prevalence of HBV infection than younger participants (χ 2 = 41.73, P <0.0001). Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females. Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier. Conclusions::The current prevalence of HBV infection remains above 5% in populations eligible for HCC screening in China.

Objective To compare the image quality of half-fourier acquisition single-shot turbo spin-echo(HASTE)sequence based on deep learning(DL)reconstruction algorithm(HASTE-DL)sequence with conventional BLADE turbo spin echo(TSE)(BLADE-TSE)sequence in liver T2WI scanning,and to explore the application value of HASTE-DL sequence.Methods Forty-four patients underwent liver BLADE-TSE and HASTE-DL sequences scanning and the image quality was subjectively and objectively evalua-ted.The image overall quality,detail sharpness,liver anatomical sharpness,bile duct clarity and artifacts of the two sequences were qualitatively scored by the quadripartite method for subjective evaluation.The objective evaluation included quantitative analysis of the signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and scanning time of the two sequences.Results There were no sig-nificant differences in image overall quality,liver anatomical sharpness and artifacts scores between the two sequences(P＞0.05).Compared to the BLADE-TSE sequence,the score of the image bile duct clarity of the HASTE-DL sequence was higher(P＜0.001),how-ever the detail clarity of the HASTE-DL sequence was lower(P＜0.001).In addition,both the SNRliver and CNRliver/erector spinal muscle of the HASTE-DL sequence were better(P＜0.001).The scanning time of the HASTE-DL sequence was much shorter.Conclusion Compared with BLADE-TSE sequence images,the overall quality of HASTE-DL sequence images meets the diagnostic requirements,with higher bile duct clarity,better SNRliver and CNRliver/erector spinal muscle,and shorter scanning time.Thus,HASTE-DL sequence can be used as a supplement to conventional BLADE-TSE sequences for liver MRI scanning.

Objective:To study the safety and efficiency of endovascular treatment in pediatric severe cerebral venous sinus thrombosis(CVST).Methods:This was a case series study.Data of pediatric severe CVST patients who received endovascular treatment in the Department of Neurointerventional, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023 were retrospectively analyzed.The technical success rate, periprocedural complications, neurologic and radiologic outcomes were collected to study the safety and efficacy of endovascular treatment in pediatric severe CVST.Results:A total of 15 patients were included in this study, including 6 males(40.0%) and 9 females(60.0%) with a mean age of(14.60±2.26) years.The modified Rankin Scale score(mRS) before endovascular treatment was(3.47±1.06) points, and the time from onset to endovascular treatment was 17(12-26) days.Thirteen patients(86.7%) received mechanical thrombectomy through catheter aspiration and/or stent-retriever thrombectomy followed or not followed by intrasinus thrombolysis(IST), and 2 patients(13.3%) received IST only.The technical success rate was 100%.Three patients(20.0%) had periprocedural complications.Ten patients(66.7%) had mRS≤2 points at discharge.Twelve patients(80.0%) had valuable neurologic and radiologic follow-ups with a duration of 9.5(3.5-19.0) months, and they all had mRS≤2 points.Among the 12 patients, 8(66.7%) had good cerebral venous recanalization.Conclusions:Endovascular treatment is technically feasible in pediatric severe CVST patients, with acceptable safety and efficacy.