Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Objective:To investigate the effects of PD-1 monoclonal antibody therapy on the peripheral and local immune microenvironment of patients with microsatellite instability-high(MSI-H)rectal cancer.Methods:Samples of peripheral blood and tumor biopsy were collected from a patient with MSI-H rectal cancer before and after PD-1 monoclonal antibody treatment.The samples were dissociated into single-cell suspensions using a combination of enzymatic and mechanical methods.Immune-related marker expression on peripheral and tumor-infiltrating im-mune cells was analyzed using single-cell mass cytometry(CyTOF).Results:According to the results of CyTOF analysis,CD45+immune cells in the peripheral blood and tumor tissues were categorized into 39 and 34 cell subsets,respectively,before and after PD-1 monoclonal antibody treatment(the correlation is unclear and ambiguous).After PD-1 monoclonal antibody treatment,differences were observed in the relative abundance of immune cell subsets:B cells significantly decreased in the peripheral blood,while B cells and γδT cells significantly increased in the tumor tissue;neutrophils significantly decreased,and the proportion of CD4+TEM cells in T cell subsets significantly increased,whereas CD4+Treg cells significantly decreased.Additionally,there were differences in the expression of immune-related markers in multiple immune cell subsets in both peripheral blood and tumor tissues,with CCR6 showing a significant increase in expression across all subsets,while ICOS and PD-1 expressions in T cell subsets were significantly reduced(the specific tissues for these cells or factors are unclear).Conclusion:After PD-1 monoclonal antibody treatment in MSI-H rectal cancer,changes occurred in the composition of immune cells and the expression of immune-related markers in both peripheral blood and tumor tissues.This study reveals the dynamic adjustment of the immune microenvironment and provides important evidence for understanding the therapeutic mechanism of PD-1 monoclonal antibodies.

The sperm DNA fragmentation index (DFI) is a metric used to assess DNA fragmentation within sperm. During in vitro fertilization-embryo transfer (IVF-ET), high sperm DFI can lead to a low fertilization rate, poor embryo development, early miscarriage, etc. A kinase anchoring protein (AKAP) is a scaffold protein that can bind protein kinase A (PKA) to subcellular sites of specific substrates and protects the biophosphorylation reaction. Sperm protein antigen 17 (SPA17) can also bind to AKAP. This study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI (H-DFI) patients during IVF-ET. In addition, the study investigates the expression of AKAP, protein kinase A regulatory subunit (PKARII), and SPA17 between H-DFI and low sperm DFI (L-DFI) patients. SPA17 at the transcriptional level is abnormal, the translational level increases in H-DFI patients, and the expression of AKAP4/PKARII protein decreases. H2O2 has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm DFI. It indicates that H2O2 increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARII protein expression. These processes inhibit sperm capacitation and reduce acrosomal reactions. Embryo culture data and IVF outcomes have been documented. The H-DFI group has a lower fertilization rate. Therefore, the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARII proteins, blocked sperm capacitation, and reduced occurrence of acrosome reaction.

Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.
Humans ; Prognosis ; Intestinal Neoplasms/diagnosis* ; Duodenal Neoplasms ; Gastrointestinal Stromal Tumors ; Lymphoma ; Adenocarcinoma/surgery* ; Constipation ; Abdominal Pain ; Retrospective Studies

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans ; Fibroblast Growth Factors ; Phosphatidylinositol 3-Kinases/metabolism* ; Central Nervous System/metabolism* ; Signal Transduction/physiology* ; Alzheimer Disease

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.
Humans ; Postmortem Changes ; Artificial Intelligence ; Autopsy ; Cadaver ; Microbiota

Objective:To explore the risk factors associated with tibia fractures in children with congenital anterolateral bowing of the tibia (ALBT).Methods:A retrospective analysis was conducted on data from 87 children diagnosed with ALBT at the Children's Hospital of Hunan Province from January 2012 to January 2020. The collected data included age at initial diagnosis, affected limb side, whether there was a concomitant type I neurofibromatosis, whether there was a concomitant fibular pseudoarthrosis, whether there was concomitant ankle joint deformity, whether there was bone cystic change in the region of tibial bowing deformity, location of the apex of the bowing deformity, diameter of the tibial bowing deformity on the affected side, diameter on the healthy side in the same plane as the tibial bowing deformity, angle of lateral bending deformity of the tibia, angle of anterior bending deformity of the tibia, occurrence of tibia fracture, history of trauma before fracture, location of fracture, and age at the time of fracture. The follow-up endpoint was January 2023. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff values for the angles of lateral and anterior bending deformity of the tibia and the ratio of cross-sectional areas. The correlation between the above factors and tibial fractures in children was analyzed by single factor survival analysis, and the indicators with statistical significance were included in multivariate Cox proportional risk regression analysis to determine the risk factors for tibial fractures in children with ALBT.Results:Of the 87 children diagnosed with ALBT, the median age at initial diagnosis was 14.0 months (range, 1-93 months), with 42 males and 45 females, 44 left-sided and 43 right-sided cases. The median follow-up time for non-fracture cases was 42.0 months (range, 1-124 months). At the last follow-up, 43 children had experienced fractures, while 44 had not. The average time to fracture-free survival was 70.3 months, the median fracture-free survival time was 55.0 months, and the median survival time without fractures was 42.0 months. The ROC curve results indicated a cutoff value of 25.55° for the lateral bending angle of the tibia and 32.63° for the anterior bending angle of the tibia, with no statistically significant significance for the cross-sectional area ratio [AUC=0.54, 95% CI (0.42, 0.66), P=0.530]. Single-factor analysis of fracture-free survival suggested that there were statistically significant differences in the intergroup fracture-free survival rates of four factors: lateral bending angle of the tibia (χ 2=7.06, P=0.008), anterior bending angle of the tibia (χ 2=8.96, P=0.003), history of trauma (χ 2=18.26, P<0.001), and tibial bone cystic change (χ 2=4.30, P=0.038). The results of the multivariate Cox proportional hazards regression analysis showed that a lateral bending angle of the tibia≥25.55° ( HR=2.73, P=0.007), tibial bone cystic change ( HR=2.35, P=0.018), and history of trauma ( HR=2.65, P=0.004) were all positively correlated with fractures. Conclusion:The main risk factors for tibia fractures in children with ALBT include trauma, tibial bowing deformity with concomitant bone cystic change, and lateral bending angle of the tibia≥25.55°.