Identification and verification of feature biomarkers associated with immune cells in recurrent pregnancy loss.

OBJECTIVE: The aim of this study was to investigate the causes, diagnostic markers, and treatment methods for recurrent pregnancy loss (RPL) using bioinformatics approaches. MATERIALS AND METHODS: Bioinformatics methods were utilized to analyze gene expression databases to identify key genes and modules associated with RPL. Weighted gene co-expression network analysis (WGCNA) was employed to identify gene sets related to maternal-fetal immunity. Gene set variation analysis (GSVA) and protein-protein interaction networks were used to explore signaling pathways and molecular interactions in RPL. Immune cell infiltration was assessed using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Thirteen genes were identified as potential diagnostic markers, some of which were involved in placental amino acid transport, glucose absorption, and reactive oxygen species production. Several gene sets related to protein transport, steroid synthesis, and glycosaminoglycan degradation were found to be associated with RPL. Immune cell infiltration analysis found that CD56bright NK cells and monocytes showed significantly increased infiltration in RPL and were associated with key hub genes. The validation of hub genes, including PCSK5, CCND2, SLC5A3, RASAL1, MYZAP, MFAP4, and P2RY14, as potential diagnostic markers, showed promising value. CONCLUSIONS: This study contributes to a better understanding of the etiology of RPL and potential diagnostic markers. The identified immune-related gene sets, signaling pathways, and immune cell infiltrations provide valuable insights for future research and therapeutic advancements in RPL.

[Comparison of risk factors for hemorrhagic stroke and ischemic stroke, a prospective long-term follow-up cohort study].

Objective: To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population. Methods: A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared. Result: A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio (HR)=1.56, 95%CI: 1.23-1.98], history of alcohol consumption (HR=2.46, 95%CI: 1.39-4.34), hypertension (HR=1.75, 95%CI: 1.00-3.07) and older age (HR=1.07, 95%CI: 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score (HR=1.43, 95%CI: 1.25-1.65), smoking history (HR=1.52, 95%CI: 1.13-2.05), hypertension (HR=1.51, 95%CI: 1.10-2.07), family history of stroke (HR=1.89, 95%CI: 1.13-3.15), left ventricular hypertrophy (HR=1.74, 95%CI: 1.07-2.81) and older age (HR=1.07, 95%CI: 1.05-1.08). Conclusions: Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

[Short-term efficacy and safety observation of standardized mite allergen extract rush subcutaneous immunotherapy for allergic rhinitis: a prospective study].

Objective: To conduct a comparative analysis of the efficacy, safety, and cytokine changes associated with three distinct dose escalation regimens of allergen-specific immunotherapy (AIT), and to provide valuable insights into the implementation of safer and more effective accelerated immunotherapy in clinical practice. Methods: A prospective study of subcutaneous immunotherapy (SCIT) was conducted at Renmin Hospital of Wuhan University, involving patients with allergic rhinitis visited from 2019 to 2022. Participants were allocated to one of three treatment groups based on their preferences: conventional immunotherapy (CIT, 23 cases), cluster immunotherapy (CLIT, 25 cases), or rush immunotherapy (RIT, 18 cases). The RIT group received a single subcutaneous injection of 150 mg of omalizumab one week before commencing treatment. Subjective evaluation indices, including the Combined Symptom and Medication Score (CSMS), Visual Analogue Scale (VAS), and single symptom score, were recorded alongside objective evaluation indices (e.g., sIgE, tIgE, Th1/2 and Th17 cytokines) and adverse reactions. Assessments were conducted at baseline, and at 1, 7, and 15 weeks after treatment. SPSS 22.0 software was used for data processing and analysis. Results: The study included a total of 66 patients, comprising 37 males and 29 females, who completed the treatment regimen. In all three groups, CSMS and VAS scores showed significant reductions at 1, 7, and 15 weeks post-treatment (all P<0.05). Notably, the RIT group demonstrated a significantly lower VAS score (4.33±0.94) compared to the CIT (9.48±1.37) and CLIT (9.44±1.33) groups at 1 week post-treatment (P<0.05). Additionally, the RIT group (0.62±0.23) exhibited a lower CSMS score than the CIT (1.54±0.21) and CLIT (1.06±0.22) groups at 15 weeks post-treatment (P<0.05). Furthermore, at the point of reaching the maintenance dose, the RIT group (0.61±0.20) demonstrated superior improvement in nasal itching symptoms compared to the CIT (1.78±0.38) and CLIT groups (1.56±0.32), with P<0.05. The incidence of local adverse reactions in the RIT group (36/11.76%) was lower than that in the CIT (69/20.00%) and CLIT groups (62/16.53%), with P<0.05. Notably, none of the three groups reported grade 3/4 systemic adverse reactions, and there was no statistically significant difference in systemic adverse reactions among the three groups. Following treatment, IL-4, IL-5, IL-6, IL-17, sIgE, sIgE/tIgE, and Eos% exhibited varying degrees of decrease in all three groups, whereas IL-10, TNF, and IFN-γ did not show significant changes. Conclusions: All three distinct dose escalation regimens of SCIT demonstrated substantial clinical efficacy. Of note, the approach of combining a single injection of omalizumab with RIT significantly improved early-stage efficacy and exhibited the advantages of safety, effectiveness, and convenience, establishing it as a reliable immunotherapy method.

[Endovascular therapy accompanied by spontaneous portosystemic shunts for overt hepatic encephalopathy].

Objective: To preliminarily evaluate the safety and efficacy of shunt-related interventional therapy accompanied with spontaneous portosystemic shunts (SPSS) in patients with hepatic encephalopathy (HE). Methods: Case data on six patients who underwent interventional therapy accompanied by SPSS for HE from January 2017 to March 2021 were collected to evaluate the efficacy and postoperative complications. Results: All six patients underwent SPSS. Four patients had hepatitis B cirrhosis; one had alcoholic cirrhosis; and one had hepatic arterioportal fistula-induced portal hypertension. Child-Pugh liver function scores were C and B in three and three cases, respectively. The SPSS type was gastrorenal shunt in two cases; portal-thoracic-azygos venous in two cases; portal-umbilical-iliac venous in one case; and portal-splenic venous - inferior vena cava in one case. Two of them had previously had a transjugular intrahepatic portosystemic shunt (TIPS), and there were SPSS prior to TIPS. Five cases (5/6) successfully underwent shunt embolization, and one case (1/6) underwent stent implantation for flow restriction (portal-umbilical-iliac vein). The technical success rate was 100%. HE did not recur during hospitalization or the three-month follow-up period. However, one case had a recurrence of HE within a year after surgery and was treated symptomatically, while another experienced gastrointestinal bleeding a year after surgery.. Conclusion: SPSS embolization or flow restriction is effective and safe for improving HE patients' symptoms.

Paclitaxel-resistant related lncRNA DBH-AS1 promotes the proliferation and invasion of esophageal cancer.

OBJECTIVE: Chemoresistance is one of the main obstacles in the clinical treatment of cancer. However, secondary resistance to paclitaxel poses new challenges for cancer treatment. Long noncoding RNAs regulate cellular functions at different levels and mechanisms and play an important role in the biological behavior of tumors. MATERIALS AND METHODS: LncRNA microarrays were used to detect lncRNAs in Paclitaxel-resistant cells and corresponding parental cells. Cell counting kit 8 and Transwell analysis were used to test the effect of lncRNA on function. RESULTS: The expression of lncRNA DBH-AS1 in TE-4 TAX-R cells was significantly higher than that in TE-4 cells. Transwell analysis showed that the overexpression of lncRNA DBH-AS1 increased the invasion of Eca cells. Cell scratches and Transwell analysis showed that the overexpression of lncRNA DBH-AS1 in Eca cell culture supernatants promoted the migration and invasion of HUVEC. In addition, lncRNA DBH-AS1 relies on miR-21 to regulate the expression of YOD1. CONCLUSIONS: Paclitaxel-resistant lncRNA DBH-AS1 appears to promote ECa cell proliferation and invasion by acting as a ceRNA and regulating miR-21-5p /YOD1 signaling pathway.

Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes.

BACKGROUND: Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes. METHODS: Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. RESULTS: Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and < 0.01, respectively). CONCLUSION: Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes. TRIAL REGISTRATION: Not Applicable.

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

[Evaluation of the effectiveness of malaria control health education among overseas enterprise employees].

OBJECTIVE: To evaluate the effectiveness of health education on knowledge, attitude and practice (KAP) relating to malaria control among overseas enterprise employees. METHODS: In September 2019, on-site malaria control health education was conducted among all Chinese employees of a China-funded mining enterprise in the Democratic Republic of Congo. The KAP questionnaire for malaria control was generated on the Questionstar website, and the participants were subjected to two questionnaire surveys prior to and 14 months after health education. After the questionnaires were recovered, all valid questionnaires were divided into 4 groups, including the baseline group (the questionnaires filled out by respondents who received health education and participated in two questionnaire surveys before health education), the loss-to-follow-up group (the questionnaires filled out by respondents who received health education but only participated in the questionnaire survey after health education), the retest group (the questionnaires filled out by respondents who received health education and participated in two questionnaire surveys after health education) and the new group (questionnaires filled out by respondents who did not receive health education and only participated in the questionnaire survey after health education) according to subjects' receiving health education and participation in two questionnaire surveys. The correct rate of malaria control knowledge, the proportion to good attitudes towards malaria control and the proportion of good practices towards malaria control were compared between the baseline group and the loss-to-follow-up group, between the baseline group and the retest group, and between the retest group and the new group. RESULTS: A total of 110 and 142 valid questionnaires were recovered during the two surveys, and the recovery rates were 90.9% and 70.3%, respectively. There were 77, 77, 33, and 65 valid questionnaires recovered from the baseline group, the loss-to-follow-up group, the retest group, and the new group, respectively. There were no significant differences in respondents' gender, age and educational levels between the baseline group and the loss-to-follow-up group (all P values > 0.05), and there were no significant differences between the two groups in terms of the mean score of malaria control knowledge (Z = 2.011, P > 0.05), the mean score of attitudes towards malaria control (t = -0.787, P > 0.05) and the mean score of practices towards malaria control (t = -0.787, P > 0.05). There were significant differences between the retest group and the baseline group in terms of the mean score of malaria control knowledge (10.83 vs. 9.79; Z = -4.017, P < 0.05), the mean score of attitudes towards malaria control (29.48 vs. 28.61; Z = -1.981, P < 0.05) and the mean score of practices towards malaria control (6.43 vs. 5.91; Z = -2.499, P < 0.05). There were no significant differences between the retest group and the new group in terms of gender, age or education levels (all P values > 0.05), and a higher mean score of malaria control knowledge was found in the retest group than in the new group (10.83 vs. 9.81; Z = -2.962, P < 0.05), while no significant differences were seen in the mean score of attitudes towards malaria control (29.48 vs. 30.17; Z = -1.158, P > 0.05) and the mean score of practices towards malaria control (6.43 vs. 6.37; Z = -0.048, P > 0.05) between the two groups. CONCLUSIONS: Malaria control health education may significantly improve the understanding of malaria control knowledge, positive attitudes towards malaria control and the compliance of practices towards malaria control among overseas enterprise employees.

[Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics].

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.

Increased risk of temporomandibular joint disorders and craniofacial deformities in patients with juvenile idiopathic arthritis: a population-based cohort study.

Juvenile idiopathic arthritis (JIA) is an autoimmune disease that has been proposed to involve the temporomandibular joint (TMJ). The aim of this study was to identify the relationships between JIA, TMJ disorders, and craniofacial deformities. This cohort study included patients diagnosed with clinically active JIA between 1999 and 2013 through a nationwide longitudinal health registry. The primary outcome was the presence of a TMJ disorder. The secondary outcome was the presence of a JIA-associated craniofacial deformity. A total of 2791 patients with JIA were included in the case group; 11,164 propensity score-matched individuals without JIA were selected from the same database as controls. TMJ disorders were present in 142 individuals: 48 (1.72%) in the case group and 94 (0.84%) in the control group (relative risk 2.047, 95% confidence interval 1.446-2.898). Craniofacial deformities were present in 374 individuals: 112 (4.01%) in the case group and 262 (2.35%) in the control group (relative risk 1.722, 95% confidence interval 1.380-2.148). Patients with JIA showed a significantly greater likelihood of developing TMJ disorders and craniofacial deformities compared to matched controls.

Dementia and the Risk of Periodontitis: A Population-Based Cohort Study.

Dementia and Alzheimer's disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score-matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score-matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent (P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.

Total knee replacement in osteoarthritis patients on reducing the risk of major adverse cardiac events: a 18-year retrospective cohort study.

OBJECTIVES: Osteoarthritis (OA) is a common degenerative joint disease, and total knee replacement (TKR) is a successful surgical intervention for knee OA treatment. However, the risks of mortality and major cardiovascular events (MACEs) in patients receiving TKR remain unclear. This study investigated the risks of mortality and MACEs in knee OA patients who received TKR. METHODS: For this population-based cohort study, the Longitudinal Health Insurance Database 2000 was used. Two million individuals with knee OA defined by ICD-9-CM codes who received physical therapy between 1999 and 2017 were selected. For propensity score matching (PSM), we considered the year of knee OA diagnosis, demographics, comorbidities, co-medications, and knee OA-related hyaluronic acid or physical therapy at baseline. After PSM, regression analyses were performed to assess the association of mortality or MACEs with TKR and non-TKR individuals. RESULTS: We identified patients (n = 189,708) with a new diagnosis of knee OA between 2000 and 2017. In total, 10,314 propensity-score-paired TKR and non-TKR individuals were selected. The PSM cohort algorithm revealed that the risk of mortality or MACEs was lower in the TKR group (adjusted hazard ratio: 0.791; 95% confidence interval: 0.755-0.830) than in the non-TKR group. CONCLUSIONS: Patients with knee OA who received TKR had decreased risks of mortality and MACEs than those who did not receive TKR. Moreover, the TKR group received a reduced dosage of nonsteroidal anti-inflammatory drugs at the 1-year follow-up.

[The expression and significance of TRPM8 among chronic rhinosinusitis with nasal polyps].

Objective: To compare the expression and difference of melastatin-related transient receptor potential 8(TRPM8) among chronic rhinosinusitis, nasal polyps and normal mucosa tissues. And to explore the significant expression of TRPM8 among CRSwNP. Methods: Fifty-one patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from February 2019 to January 2020 were recruited, including 33 males and 18 females, aged from 14 to 65 years old (34.55±1.689).Immunohistochemistry was used to detected the expression of TRPM8 protein among CRSsNP(17),CRSwNP (17) and control tissuses(17). In addition, the correlation between the expression of TRPM8 protein in CRSwNP patients and preoperative CT Lund-Mackay scores and preoperative VAS scores and sinonasal outcome test-20 scores was analyzed, respectively. The primary human nasal epithelial cells were cultured in vitro and the expression of TRPM8 was detected by quantitative real-time PCR and western blotting. The tissue in control group, chronic rhinosinusitis without nasal polyps (CRSsNP) group and the CRSwNP group were collected and grinded into tissue homogenized. The expression of TRPM8 protein was detected by western blotting after 24 h stimulation after homogenate was added into the medium of RPMI 2650 and primary nasal epithelial cells. Results: Compared with the control, the expression of TRPM8 was significantly up-regulated in nasal polyps (t=6.852, P<0.05). TRPM8 was mainly expressed in epithelial cells. The expression of TRPM8 in the epithelial cells of CRSsNP had no difference with the control group (t=1.980, P>0.05). In addition, the expression of TRPM8 in CRSwNP patients was positively correlated with the preoperative CT Lund-Mackay scores and VAS scores and SNOT-20 scores (r=0.512, P<0.05;r=0.853, P<0.01;r=0.814, P<0.01). After cultured primary epithelial cells in vitro, the expression level of TRPM8 in epithelial cells derived from nasal polyp was significantly higher than that in control group (t=8.845, P<0.05). By adding the homogenization of control and CRSsNP and CRSwNP tissues, the expression of TRPM8 in RPMI 2650 cells and primary nasal epithelial cells was changed and that was significantly increased after adding the homogenization of the group of CRSwNP. Conclusion: TRPM8 is highly expressed in nasal polyps epithelial cells, suggesting that TRPM8 may be involved in the pathogenesis of nasal polyps regulated by nasal epithelial cells.

[Analysis of bacterial pathogens and clinical characteristics of children with respiratory tract infections in Tianjin].

Objective: To analyze the pathogenic bacteria and epidemiological characteristics in children with respiratory tract infection in Tianjin area. Methods: Retrospective case analysis was performed on 2 392 hospitalized children in the wards of respiratory diseases, intensive care unit and special care ward of Tianjin Children's Hospital from June 2018 to May 2019. Thirteen pathogenic bacteria in deep sputum and bronchoalveolar lavage fluid samples were detected by loop-mediated isothermal amplification. The laboratory data and clinical characteristics of the infected children were analyzed, and the comparison between groups was performed by t test or χ2 test. Results: Among 2 392 cases, 1 407 were males and 985 females. There was no significant difference in the detection rate between males and females (72.5% (1 020/1 407) vs.74.2% (731/985), χ2=0.87, P=0.35). A total of 1 751 strains and 12 kinds of positive respiratory pathogens were detected, with a detection rate of 73.2%. Among them, 913 (38.2%) strains were Mycoplasma pneumoniae (MP), 514 (21.5%) were Streptococcus pneumoniae (Sp), 381 (15.9%) were Methicillin-resistant Staphylococcus aureus (MRSA) and 279 (11.7%) were Hemophilus influenzae (Hi). There was significant difference in the detection rate of pathogens among different age groups (χ²=83.67, P<0.01). The positive rate of alveolar lavage fluid group was higher than that of deep sputum fluid group [81.6% (614/752) vs. 69.3% (1 137/1 640), χ2=39.89, P<0.01]. The length of hospital stay of children infected with different pathogens was significantly different (all P<0.01). There was significant difference in duration of fever among children infected with different pathogens (χ²=228.69,103.56, 3.96, 27.38,24.50,41.66, all P<0.05). There were 63 (7.7%) cases of atelectasis, 260 (31.9%) cases of pleurisy and 120 (14.7%) cases of pleural effusion in MP children. Children with Sma were most likely to involve the heart system (2/9), and children with Eco infection had a higher incidence of complications such as those of blood (3/19), urinary (2/19), digestive systems(4/19), systemic inflammatory response syndrome and sepsis (1/19). Conclusions: The main bacterial pathogens of respiratory tract infection in children in Tianjin were MP, Sp, MRSA and Hi. It is suggested that clinicians should not only pay attention to the respiratory symptoms of children, but also pay attention to the complications caused by bacterial pathogen infection, so as to prevent the deterioration of the disease and improve the prognosis.

[Relationship between emotional apathy and motor symptoms, sleep and cognitive function in patients with early Parkinson's disease].

Objective: To study the relationship between emotional apathy and motor symptoms, sleep, and cognitive function in patients with early Parkinson's disease (PD). Methods: One hundred and twenty-nine early PD patients who were treated in the Second Affiliated Hospital of Soochow University from June to October 2020 were included, including 82 male and 47 female patients. The emotional apathy was assessed by modified apathy rating scale (MAES). The above 129 patients were divided into 67 patients in the PD with emotional apathy group (MAES>14 points) and 62 patients in the PD without emotional apathy group (MAES≤ 14 points). Age, gender, course of disease and levodopa equivalent dose were also collected. Hoehn-Yahr stage and unified Parkinson's disease rating scale PartⅢ(UPDRS-Ⅲ), Pittsburgh Sleep Quality Index (PSQI), polysomnography, and Montreal Cognitive Assessment Scale (MoCA) were used to evaluate the motor symptoms, sleep and cognitive functions of patients with early PD, and the clinical characteristics of patients with early PD with apathywere determined. Results: Compared with PD patients without apathy, those with apathy had longer disease duration [M(Q1,Q3)][5.0 (3.0, 7.0) years vs 3.0 (2.0, 5.0) years, P=0.006] and severer motor symptoms [20.0 (10.0, 28.0) vs 14.0 (8.5, 23.0), P=0.047]. There was no significant difference in PSQI score between the two groups. Among the 33 patients who completed polysomnography, compared with PD patients without apathy (n=16), those with apathy (n=17) had a longer rapid eye movement (REM) sleep latency [150 (124, 184) min vs 87 (57, 133) min, P=0.035)] and more frequent periodic limb movements in the REM phase(P=0.042).The REM sleep ratio (r=0.373, P=0.042), apnea-hypopena index (AHI)(r=0.374, P=0.046) and oxygen deficit index (r=0.409, P=0.025) were positively correlated with the degree of apathy in PD patients. PD patients with apathy had relatively poorer performance in cognition assessment than those without apathy and total MoCA score was inversely correlated with the degree of apathy (r=-0.231, P=0.017). Conclusion: Early PD patients with apathy have objective sleep disorders dominated by REM sleep disorders, which can have a negative impact on cognitive function.

Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

The relationship between famine exposure in early life and left atrial enlargement in adulthood.

BACKGROUND: Increased left atrium diameter (LAD) is associated with an elevated risk of cardiovascular diseases. The relationship between nutrition status and left atrial enlargement (LAE) is still unclear. The present study aimed to investigate the association of famine exposure in early life with LAE in adulthood. METHODS: Participants were divided into non-exposed, fetal, early, middle and late childhood exposed groups according to birth data. LAE was defined when LAD was ≥3.9 cm in women and ≥4.1 cm in men, or ≥2.3 cm m-2 by a sex-independent cut-off normalised for body surface area. Multivariate logistic regression was performed to calculate the odds ratio (OR) and confidence interval (CI) between famine exposure and LAE. RESULTS: In total, 2522 [905 male, mean (SD) age 59.1 (3.65) years] subjects were enrolled, including 392 (15.5%) LAE subjects. The prevalence of LAE in non-exposed, fetal, early, middle and late childhood exposed groups was 55 (10.8%), 38 (11.2%), 88 (18.1%), 102 (16.7%) and 109 (19.0%), respectively. Compared to the non-exposed group, the ORs for LAE were in fetal (OR = 0.956, 95% CI = 0.605-1.500, P = 0.847), late (OR = 1.748, 95% CI = 1.208-2.555, P = 0.003), middle (OR = 1.647, 95% CI = 1.140-2.403, P = 0.008) and early (OR = 1.630, 95% CI = 1.116-2.399, P = 0.012) childhood exposed groups after adjusting potential cofounders. When stratified by gender, smoking, body mass index, hypertension and diabetes, we found that the effect of famine exposure on LAE was only modified by diabetes (Pinteraction  = 0.007). CONCLUSIONS: Famine exposure during childhood stage might increase the risk of LAE in adults, and this effect interacts with diabetes.

The role of mitochondrial DNA mutations in coronary heart disease.

Coronary heart disease (CHD) is a leading cause of death worldwide. It is a multifactorial disorder resulting from harmful interactions between genetic and environmental factors. Due to the central role of mitochondria in cellular energy homeostasis, there is growing evidence supporting the role of damage to mitochondrial components such as mitochondrial DNA (mtDNA) in the pathogenesis and progression of CHD. However, the molecular mechanisms linking mtDNA and CHD remains unknown. In terms of mutations, we found that mitochondrial transfer RNA (mt-tRNA) genes are hot spots for pathogenic mutations associated with CHD. These mutations cause structural and functional changes in tRNA; specifically, failure of tRNA metabolism may impair mitochondrial protein synthesis and lead to mitochondrial dysfunction responsible for CHD. This review provides a detailed summary of the mtDNA mutations that have been reported to be associated with CHD and further discusses the possible molecular mechanisms behind the involvement of these mtDNA mutations in CHD.

[Expanding the pandemic influenza preparedness framework to the epidemic of COVID-19].

On March 11, 2020, WHO officially declared that COVID-19 had become Pandemic. As of March 31, the epidemic had affected more than 178 countries and regions, with more than 780 000 confirmed cases. The Pandemic Influenza Preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits (the 'PIP Framework' or 'Framework') is an international arrangement adopted by the World Health Organization in May 2011 to improve global pandemic influenza preparedness and response. Since the transmission route and transmission capacity of COVID-19 are similar to that of influenza A (H1N1) in 2009, which conforms to the basic elements of "human pandemic", and the epidemic scale has exceeded that of influenza A (H1N1)， it is probable to incorporate COVID-19 epidemic response into PIPF, and at the same time to verify and improve PIPF in practice. It is recommended that WHO, other international organizations and relevant countries make full use of the PIPF system to respond to the epidemic and better coordinate national actions at the global level. At the same time, China should also make the planning and deploy of domestic epidemic prevention and control and international epidemic cooperation under the framework.

[The clinical significance of plasma PTX3 in patients with secondary hemophagocytic lymphohistiocytosis].

Objective: To investigate the significance of plasma pentraxin 3 (PTX3) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). Methods: Plasma PTX3 levels were tested by ELISA in 48 newly diagnosed sHLH patients, 18 healthy volunteers and 9 lymphoma controls in the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2019. Clinical parameters were collected, and the correlations with PTX3 levels were analyzed. Results: PTX3 level in newly diagnosed group was significantly higher than that of healthy control group [16.29(1.17-66.00) vs. 0.76(0.01-7.86) µg/L, P<0.01]. Patients with lymphoma-associated HLH(LHLH) had higher plasma level of PTX3 than Fhose with infection-associated HLH (IHLH) [24.29(3.36-66.00) vs. 9.56(1.17-36.50)µg/L, P<0.05]. Plasma PTX3 levels in 48 sHLH patients were positively correlated with serum ferritin (P<0.05). Receiver operating characteristic (ROC) curve for plasma PTX3 levels of sHLH and healthy controls produced a cutoff value at 3.9 µg/L, with its 86.7% sensitivity and 94.4% specificity. And ROC analysis showed that PTX3 17.5 µg/L was the critical value for diagnosis of LHLH from non-LHLH group, that the sensitivity and specificity were 63.0% and 76.2% respectively. The 1-year overall survival (OS) rate in patients with PTX3≥17.5 µg/L was significantly lower in those with PTX3<17.5 µg/L (18.5% vs. 75.8%, P<0.01). Conclusion: These results indicate the potential of PTX3 as a biomarker for diagnosis and prognosis in patients with sHLH.