Objective:To assess the safety of a novel domestically developed direct visualization system of peroral cholangiopancreatoscopy for the exploration of biliary tract.Methods:Clinical data from 384 patients with biliary tract diseases who underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Endoscopy Center of Shanghai Xuhui District Central Hospital from November 2017 to December 2022 were retrospectively analyzed. Patients were categorized into 2 groups based on the type of cholangioscope: the novel cholangiopancreatoscopy system group ( n=159) and the SpyGlass group ( n=225). In the novel cholangiopancreatoscopy system group, the new direct visualization system of China-made peroral cholangiopancreatoscopy was used for bile duct exploration, while the SpyGlass group utilized the SpyGlass system for bile duct inspection. Propensity score matching (PSM) was used as a nearest-neighbor method with a caliper of 0.01 to minimize confounding factors, resulting in a balanced sample of 122 patients in each group after matching. The primary outcome was the incidence of short-term complications, with secondary outcomes including technical success rates and post-treatment outcomes. Results:After PSM, there were no significant differences in baseline characteristics between the two groups ( P>0.05). Regarding short-term postoperative complications, pancreatitis occurred in 1.6% (2/122) of patients in the novel cholangiopancreatoscopy system group and 7.4% (9/122) in the SpyGlass group. The new system significantly reduced the incidence of post-procedure pancreatitis ( χ2=4.665, P=0.031). The cholecystitis was absent in the novel cholangiopancreatoscopy system group, while it occurred in 0.8% (1/122) cases in the SpyGlass group, with no significant difference between the two groups after the procedure ( P=1.000). Regarding technical success rate, the novel system group achieved a rate of 99.2% (121/122), while the SpyGlass group achieved 97.5% (119/122) ( P=0.622). A slightly higher success rate was observed in the novel system group.There were 81 cases of postoperative biliary drainage in the novel cholangiopancreatoscopy system group and 74 cases in the SpyGlass group. Conclusion:The novel direct visualization system of peroral cholangiopancreatoscopy is safer than SpyGlass in the exploration of biliary system diseases. Endoscopists are encouraged to choose the appropriate cholangioscopy system based on individual patient characteristics for the direct visualization, diagnosis, and treatment of biliary diseases.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To explore the association between psychological resilience and internet addiction among senior primary school students,so as to provide a scientific basis for formulating strategies for preventing internet addiction and enhancing psychological resilience in this group.Methods A stratified cluster sampling method was employed.In May 2021,a total of 1 618 fourth-and fifth-grade students from 5 primary schools in Jiading District,Shanghai were surveyed on psychological resilience and internet addiction through questionnaires.Independent sample t-tests,chi-square tests,and Logistic regression models were used for data analysis.Results Among the 1 618 students,the prevalence rate of internet addiction was 8.8%(142 students).The total score of psychological resilience(t=6.215,P<0.001)and the scores of three dimensions,namely family support(t=3.509,P<0.001),goal focus(t=6.965,P<0.001),and positive perception(t=5.887,P<0.001),of those reported with internet addiction were all significantly lower than those without internet addiction.Multivariate logistic regression analysis showed that compared with individuals with low psychological resilience,those with moderate(aOR=0.395,95%CI:0.267-0.584,P<0.001)and high psychological resilience(aOR=0.167,95%CI:0.077-0.365,P<0.001)had a lower probability of internet addiction.The three sub-dimensions of psychological resilience,namely goal focus,positive perception and family support,also showed a statistically significant negative association with internet addiction in these students.Conclusion Nearly one-tenth senior primary school students in Jiading District self-reported internet addiction.Higher levels of psychological resilience were associated with a lower probability of internet addiction among senior primary school students.Focusing on enhancing the goal focus,positive perception and family support dimensions in psychological resilience may be of great significance for preventing internet addiction among senior primary school students.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Perception of recurrence risk in cardiovascular disease (CVD) patients plays a significant role in aspects such as their quality of life and treatment adherence. This paper reviews the theoretical foundations of recurrence risk perception, the conceptual origins and developmental process, measurement tools, influencing factors of recurrence risk perception in CVD patients, and research progress of recurrence risk perception in CVD management. The aim is to provide a basis for developing scientifically effective intervention measures for CVD patients in the future.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

A QuEChERS cleanup-ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was established for simultaneous determination of traditional and emerging 71 kinds of per-and polyfluoroalkyl substances(PFAS)in Chinese herbal medicine Eckloniae Thallus.The extraction solvent employed here was 0.2%formic acid-acetonitrile with sodium chloride-anhydrous sodium sulfate(3:1,m/m)as salting-out agent,and the purification was carried out using graphitized carbon black and octadecyl-bonded silica as adsorbents.The sample separation was carried out on a Horizon C18 chromatographic column(150 mm×2.1 mm,1.6 μm)by gradient elution with 2.5 mmol/L ammonium acetate aqueous solution(containing 2.5 mmol/L acetic acid)and acetonitrile as the mobile phases.The flow rate was set at 0.4 mL/min,with an injection volume of 5 μL.The chromatographic separation of each target compound and internal standard substance could be achieved within 15 min.An electrospray ion source was utilized for simultaneous scanning of positive and negative ions under the scheduled multiple reaction monitoring(sMRM)mode,and the internal standard method was used for quantitative analysis.The results of method validations showed that the 71 kinds of PFAS had good linearity,with a correlation coefficient(r)greater than 0.997,spiked recoveries of 76.2%?122.0%and relative standard deviations(RSDs)of 5.5%?14.8%.The limits of detection were in the range of 0.3-60 ng/kg and the limits of quantification were in the range of 0.8-199 ng/kg.The developed method was used for detection of PFAS in 14 batches of Eckloniae Thallus samples,and a total of 19 kinds of PFAS were detected.The findings indicated that PFAS residues were commonly present in Eckloniae Thallus,with perfluorocarboxylic acids(PFCAs)exhibiting the highest concentrations.The method was simple,robust and efficient in preparation,sensitive in detection with high throughput,and suitable for monitoring residual PFAS compounds,including both ionic and neutral in food-medicine homology samples such as Eckloniae Thallus.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.