Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

With the widespread adoption of lung cancer screening, an increasing number of patients are being diagnosed with early-stage lung adenocarcinoma. For stage ⅠA lung adenocarcinoma, sublobar resection is the primary treatment approach. However, in patients with concomitant spread through air space (STAS), numerous studies advocate for lobectomy as the mainstay of treatment. Due to the limitations in preoperative prediction and intraoperative frozen section evaluation for assessing STAS, current research is largely restricted to using clinical and imaging features to predict STAS occurrence, with results that are inconsistent and unsatisfactory. Furthermore, most studies focus on individual clinical or imaging characteristics, and there is a lack of large-sample investigations. The rise of artificial intelligence in recent years has provided new insights into solving this problem, and existing studies have shown that artificial intelligence demonstrates better performance in STAS prediction compared to conventional methods. This article reviews the value of artificial intelligence in predicting STAS.

Gastrointestinal polyposis syndromes are primarily characterized by multiple polyps in the gastrointestinal tract, with their pathogenic mechanisms largely related to genetic factors and involving multiple signaling pathways. Adenomatous polyposis syndromes are mainly associated with APC gene variants, while some cases may arise from MUTYH gene variants. Peutz-Jeghers syndrome is primarily linked to STK11 gene variants. Juvenile polyposis syndrome is mainly associated with variants in the SMAD4 and BMPR1A genes. PTEN hamartoma tumor syndrome is predominantly caused by PTEN gene variants. Hereditary mixed polyposis syndrome is primarily related to variants of the GREM1 and BMPR1A genes. This article systematically summarizes the advances in genetic research on Gastrointestinal polyposis syndromes to enhance clinicians' understanding of these diseases and improve their diagnostic and therapeutic approaches.
Humans ; Adenomatous Polyposis Coli/genetics* ; Smad4 Protein/genetics* ; Peutz-Jeghers Syndrome/genetics* ; PTEN Phosphohydrolase/genetics* ; Bone Morphogenetic Protein Receptors, Type I/genetics* ; Intestinal Polyposis/congenital* ; Intercellular Signaling Peptides and Proteins/genetics* ; Adenomatous Polyposis Coli Protein/genetics* ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinase Kinases ; Neoplastic Syndromes, Hereditary

OBJECTIVE: To explore the implementation effect of hour-1 bundle for sepsis patients based on crisis resource management (CRM) system. METHODS: A historical control study was conducted. The hour-1 bundle for sepsis based on CRM was used to train 24 nurses in the emergency department from October 2022 to March 2023. Clinical data of sepsis patients admitted to the emergency department of the First People's Hospital of Zunyi from April 2022 to September 2023 were collected. The patients were divided into three groups based on different stages of CRM system construction: control group (before construction, from April to September in 2022), improvement group (during construction, from October 2022 to March 2023) and observation group (after construction, from April to September in 2023). The baseline data, implementation rate of hour-1 bundle [including blood culture, antibiotic usage, blood lactic acid (Lac) detection, fluid resuscitation, hypertensors usage], identification and diagnosis time, and prognosis parameters [including correction rate of hypoxemia, intensive care unit (ICU) occupancy rate, and 28-day survival rate]. Sepsis cognition survey and non-technical skill (NTS) evaluation of nurses in emergency department were conducted before and after training. RESULTS: Finally 43 cases were enrolled in the control group, improvement group and observation group, respectively. There was no statistically significant difference in baseline data including the gender, age, primary site, heart rate, systolic blood pressure, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mechanical ventilation ratio among the three groups with comparability. With the gradual improvement of the CRM system, the implementation rate of 1-hour bundle was gradually increased, and the implementation rate in the control group, improvement group and observation group were 65.12% (28/43), 74.42% (32/43) and 88.37% (38/43), respectively, with statistically significant difference (P < 0.05). It was mainly reflected in the completion rate of blood culture, antibiotic usage rate, Lac detection rate and hypertensors usage rate within 1 hour, which were significantly higher in the observation group than those in the control group [completion rate of blood culture: 90.70% (39/43) vs. 62.79% (27/43), antibiotic usage rate: 88.37% (38/43) vs. 60.47% (26/43), Lac detection rate: 93.02% (40/43) vs. 72.09% (31/43), hypertensors usage rate: 88.37% (38/43) vs. 60.47% (26/43), all P < 0.05]. The fluid resuscitation rates within 1 hour in the three groups were all over 90%, with no statistically significant difference among the three groups. The recognition and diagnosis time in the observation group was significantly shorter than that in the control group and the improvement group (hours: 0.41±0.15 vs. 0.61±0.21, 0.51±0.18, both P < 0.05), the correction rate of hypoxemia and 28-day survival rate were significantly higher than those in the control group [correction rate of hypoxemia: 95.35% (41/43) vs. 74.42% (32/43), 28-day survival rate: 83.72% (36/43) vs. 60.47% (26/43), both P < 0.05], and ICU occupancy rate was significantly lower than that in the control group [72.09% (31/43) vs. 93.02% (40/43), P < 0.05]. After training in the CRM system, the score of the sepsis awareness survey questionnaire for emergency department nurses was significantly increased as compared with before training (60.42±5.29 vs. 44.17±9.21, P < 0.01), and NTS also showed significant improvement. CONCLUSION CRM plays a significant role in promoting the implementation of sepsis hour-1 bundle, which can improve the implementation rate of hour-1 bundle and NTS of medical staff, effectively improve patients' hypoxemia, reduce patients' ICU occupancy rate and 28-day risk of death.
Humans ; Sepsis/therapy* ; Emergency Service, Hospital ; Patient Care Bundles ; Intensive Care Units ; Female ; Male ; Middle Aged

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective To explore the impact of obstructive sleep apnea(OSA)on cognitive impairment in post-stroke patients,to explore its underlying mechanism and to evaluate potential diagnostic value by dynamically moni-toring the level of brain-derived neurotrophic factor(BDNF)and Tau protein in serum.Methods Totally 96 stroke patients admitted to Mianyang third People's Hospital from February 2022 to June 2024 were selected.They were divided into the groups complicated with OSA and control one without OSA following up of neuropsychological scales for 1 week,1 month,3 months,and 6 months after stroke for evaluating cognitive function.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the level of BDNF and Tau protein in serum.The correlation of test results and the degree of cognitive impairment as well as their diagnostic value were analyzed.Results The AHI in the OSA group was significantly higher than that of control group,while LSaO2 and MSaO2 were significantly lower in the OSA group(P＜0.05).One week and 1,3,6 month months after the onset of the disease,the MMSE and MoCA scores in the OSA group were significantly lower than those in the control group,BDNF level was signifi-cantly lower while Tau protein level was significantly higher as compare to those in control group(P＜0.05).Pear-son correlation analysis showed that the serum BDNF level was positively correlated with both MMSE score(r=0.654,P＜0.001)and MoCA score(r=0.689,P＜0.001).However,the serum Tau protein level was nega-tively correlated with both MMSE score(r=-0.623,P＜0.001)and MoCA score(r=-0.667,P＜0.001).The ar-ea under the curve(AUC)of the combined detection of BDNF and Tau protein was greater than that of the individ-ual detection.The diagnostic value of the combined detection of BDNF and Tau protein for cognitive impairment in post-stroke patients was greater than that of the individual detection(P＜0.05).Conclusions OSA significantly exacerbates patients'cognitive impairment after stroke.Elevated serum BDNF level and decreased Tau protein level may be the underlying mechanisms of cognitive impairment.Serum BDNF and Tau protein may function as potential biomarkers for diagnosis of cognitive impairment after stroke.

Objective:To explore and evaluate the effectiveness of integrating standardized patient cases with simulation-based teaching in internship teaching in the department of obstetrics and gynecology.Methods:This study enrolled 60 interns from the Department of Obstetrics and Gynecology at Hangzhou First People's Hospital between January 2022 and December 2023. Participants were randomly assigned using a random number table into a control group (simulator training) and an experimental group (simulated standardized patient consultation integrated with simulation training). Simulation-based teaching was performed for seven skill modules. After training, participants underwent both skill assessments and questionnaire surveys. Skill assessment scores, professional competencies, and self-evaluation outcomes were compared between the two groups.Results:In skill assessments for delivery [(90.50±5.51) vs. (84.90±5.30)], I° perineal laceration repair [(91.98±6.87) vs. (84.18±10.24)], abortion[(90.43±6.79) vs. (84.10±5.36)], and diagnostic curettage [(92.57±8.19) vs. (85.80±8.61)], the experimental group scored significantly higher than the control group ( P<0.05). The experimental group showed higher scores in demonstrating empathy [53.33% (16/30) vs. 23.33% (7/30), P<0.05] and prioritizing doctor-patient communication [96.67% (29/30) vs. 46.67% (14/30), P<0.01]. Additionally, the experimental group reported higher scores in course satisfaction [(9.48±0.50) vs. (9.02±0.45)], performance self-assessment [(9.17±0.35) vs. (8.65±0.27)], engagement during simulation-based training [(9.62±0.43) vs. (8.43±1.21)], and learning gains [(9.53±0.87) vs. (8.88±1.02)]. Conclusions:Compared to simulation-based teaching alone, the integration of standardized patient cases can improve learning outcomes for complex and comprehensive skill modules and contribute to the development of professional competencies.

Objective:To analyze the genetic characteristics of the prevalent strains of Varicella-Zoster virus (VZV) in the population of Dali, Yunnan, and to understand its evolutionary status in the population of Dali.Methods:Herpes fluid and 163 sera were collected from 249 patients clinically suspected to have varicella or herpes zoster in the Department of Dermatology of the Second People′s Hospital of Dali city, Yunnan province, China, from 2023 to 2024. The levels of VZV-specific IgG and IgM antibodies in serum were detected using enzyme-linked immunoassay. Viral DNA was extracted from the herpes fluid, and the cycle threshold ( Ct) of the samples was detected using quantitative real-time polymerase chain reaction (qPCR), and some samples with Ct ≦ 22 were selected for sequencing by next-generation sequencing technology (next-generation sequencing). Next-generation sequencing (NGS) was used to obtain 90 whole genome sequences of VZV, and the sequencing result were compared with the sequences of reference strains for multiple sequence comparison and evolutionary analysis. Snapgene was used to translate the nucleotides into amino acids, and the result were compared with the amino acid sequences of the reference strain. Results:Of the 90 VZV whole-genome sequences, one whole-genome sequence was from an adult varicella patient, and the remaining 89 whole-genome sequences were from herpes zoster patients. The serum-specific IgG antibody positivity rate was 99.4%, and the IgM antibody positivity rate was 52.8%. The result of both single nucleotide polymorphism (SNPs) site typing and genome-wide phylogenetic tree analysis showed that 83 of the 90 VZV whole-genome sequences in this study were on the same branch as Clade 2, and 7 VZV whole-genome sequences were on the branch of Clade 9.Conclusions:The main endemic branch in Dali region in 2023-2024 was Clade 2, with the emergence of Clade 9 branch; there were amino acid mutations in the proteins encoded by ORF22 and ORF68 in 83 VZV whole genome sequences of Clade 2 branch, and the mutations did not cause significant changes to the protein structure.

Aim To investigate the effect and potential mechanisms of tetramethylpyrazine(TMP)on athero-sclerotic plaques.Methods 43 ApoE-/-mice were used to establish the animal model of atherosclerosis(As)by high-fat diet for 8 weeks,3 of which were used for model outcome verification,and another 40 model mice were randomly divided into model group,TMP low dose(25 mg/kg)group,TMP medium dose(50 mg/kg)group,TMP high dose(100 mg/kg)group and atorvastatin(AT,2.6 mg/kg)group,with 8 mice in each group;another 8 C57BL/6J mice were set as control group.After gavaging administration for 8 weeks,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL)in the serum were detected by biochemical methods,and the As index was calculated.The levels of oxidized low density lipoprotein(ox-LDL),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),monocyte chemoattractant protein-1(MCP-1),intercellular adhesion molecule-1(ICAM-1)in serum were detected by ELISA method.The pathological changes of aorta was evaluated by HE staining.The aortic plaque formation was evaluated by oil red O staining,and the plaque area percentage was calculated.The aortic fibrosis was evaluated by Masson staining,and the collagen area percentage was calculated.The expression of monocyte macro-phage antibody-2(MOMA-2)and α-smooth muscle actin(α-SMA)in the aorta was detected by immunohistochemistry(IHC)method,and the plaque vulnerability index was calculated.The mRNA and protein expression of peroxisome pro-liferator-activated receptor γ(PPARγ),nuclear factor-κB p65(NF-κB p65)in aorta were detected by RT-qPCR or West-ern blot method.Results Compared with control group,the levels of TC,TG,LDL,ox-LDL,TNF-α,IL-1β,MCP-1,ICAM-1 in serum and As index of the mice were significantly increased in model group,while the level of HDL was sig-nificantly decreased(P＜0.05).The aorta showed pathological changes such as uneven thickening of the intima,accu-mulation of foam cells and fat cells,formation of a large number of plaques,lumen stenosis and infiltration of inflammatory cells;the percentage of aortic plaque area,percentage of collagen area,MOMA-2 and α-SMA positive area,plaque vulner-ability index were all significantly increased(P＜0.05).The mRNA and protein expression of PPARγ in aorta were sig-nificantly decreased,and the mRNA and protein expression of NF-κB p65 were significantly increased(P＜0.05).Com-pared with model group,the levels of TC,TG,LDL,ox-LDL,TNF-α,IL-1β,MCP-1,ICAM-1 in serum and As index of the mice were significantly decreased in the TMP medium,high dose group and AT group,the level of HDL was signifi-cantly increased(P＜0.05).The pathological changes of aorta were significantly improved.The plaque area percentage,collagen area percentage,MOMA-2 positive area percentage and plaque vulnerability index were significantly decreased,and the α-SMA positive area percentage was significantly increased(P＜0.05).The mRNA and protein ex-pression of PPARγ in aorta were significantly increased,the mRNA and protein expression of NF-κB p65 were significantly decreased(P＜0.05).Moreover,TMP exhibited a certain dose-dependent effect on various detection indicators(except MCP-1)in As mice.The regulatory effect of TMP high dose group on various detection indicators(except LDL and As index)in As mice was comparable or superior to those of AT group.Conclusion TMP can reduce the area of As plaque and improve the stability of vulnerable plaque in As mice,its mechanism may be related to regulating PPARγ/NF-κB signaling pathway,improving lipid metabolism and inhibiting inflammatory response.