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To introduce a new fully endoscopic visualized laminar trepanning approach with a periendoscopic trephine under local anesthesia for resection of highly migrated lumbar disc herniation (LDH) and report the clinical outcomes of one year follow-up.Twenty-one patients with highly migrated LDH who underwent percutaneous endoscopic lumbar discectomy via the laminar trepanning approach from June 2019 to August 2020 were retrospectively reviewed. Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms-Pain Interference (PI) and Physical Function (PF) were selected as outcome measures. The operating duration and complication were documented.The average age of the 21 patients (15 males, 6 females) was 37.8 ± 6.0 years (29-52 years). Disc migration originated from L4/5 in 19 patients, L5/S1 in two patients. The mean operative duration was 54.1 ± 9.0 minutes (42-79 min). All patients were followed up to 12 months after the operation. PROMIS PI T-scores decreased significantly from pre-operatively mean 68.6 ± 2.4 to 54.4 ± 1.9 (P 0.001) and 47.1 ± 4.3 (P 0.001) at six weeks and 12 months, respectively. PROMIS PF T-scores improved significantly from pre-operatively mean 26.7 ± 4.7 to 44.3 ± 4.2(P 0.001) and 58.4 ± 4.0 (P 0.001) at six weeks and 12 months, respectively. No complications and disc herniation recurrences occurred.The targeted full endoscopic laminar trepanning under local anesthesia with a visualized periendoscopic trephine offers a safe, efficient and cost-effective option for the resection of highly migrated LDH.

Background Endometriosis is a benign gynecologic disease that causes chronic pelvic pain, dysmenorrhea and infertility and shares several characteristics with malignant tumors, afflicting women of reproductive age. Hexokinase 2 plays an essential role as the first rate-limiting enzyme in the metabolic glycolysis pathway, and its abnormal elevation in tumors is associated with tumor genesis and metastasis. However, the expression and role of hexokinase 2 in endometriosis remain unclear. Methods We sequenced the primary endometrial stromal cells from patients with endometrioma and utilized immunohistochemistry, quantitative real-time PCR, and western blot to determine the expression of hexokinase 2. Then wound healing assays, cell invasion assays, and cell proliferation assays were performed to explore the functions of hexokinase 2 in endometrial stromal cells. Furthermore, mice models of endometriosis were used to observe the effects of hexokinase 2 inhibitors in vivo. Lastly, glycolysis metabolism detection and transcriptome sequencing were carried out in hexokinase 2-knockdown endometrial stromal cells to analyze the mechanism of hexokinase 2 affecting cell function. Results Endometrial stromal cells of endometrioma displayed active glycolysis metabolism and elevated expression of hexokinase 2. Downregulating hexokinase 2 reduced the migration, invasion, and proliferation capacity of endometrial stromal cells. Knockdown of hexokinase 2 induced upregulation of signal transducer and activator of transcription 1 and their phosphorylation to attenuate the proliferation of endometrial stromal cells. Conclusions Hexokinase 2 is associated with the migration, invasion, and proliferation of endometrial stromal cells, which might provide new insights into the pathogenesis and treatment of endometriosis. Summary Sentence HK2 is upregulated in ovarian endometrioma and knockdown of HK2 induced upregulation of signal transducer and activator of transcription 1 (STAT1) and their phosphorylation to attenuate the proliferation of endometrial stromal cells.

The purpose of the study was to investigate whether premenopausal body mass index (BMI) and waist circumference (WC) influence age at menopause. A total of 2116 women aged 35-64 years from two communities of the CMCS Beijing cohort were recruited in 1992 and followed up to 2018. Of 1439 premenopausal women at baseline, 6 women data were missing. Finally, 1433 women were included for analysis. Overweight was defined as BMI 24-27.99 kg/m

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson’s disease (PD). To explore early alterations and underlying associations of dopamine and microstructure in PD patients utilizing the hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI). Twenty-five PD patients in early stages and twenty-four matched healthy controls underwent hybrid 18F-fluorodopa (DOPA) PET-diffusion tensor imaging (DTI) scanning. The striatal standardized uptake value ratio (SUVR), DTI maps (fractional anisotropy, FA; mean diffusivity, MD) in subcortical grey matter, and deterministic tractography of the nigrostriatal pathway were processed. Values in more affected (MA) side, less affected (LA) side and mean were analysed. Correlations and mediations among PET, DTI and clinical characteristics were further analysed. PD groups exhibited asymmetric pattern of dopaminergic dysfunction in putamen, impaired integrity in the microstructures (nigral FA, putaminal MD, and FA of nigrostriatal projection). On MA side, significant associations between DTI metrics (nigral FA, putaminal MD, and FA of nigrostriatal projection) and motor performance were significantly mediated by putaminal SUVR, respectively. Early asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. The findings further implied that molecular degeneration mediates the modulation of microstructural disorganization on motor dysfunction in the early stages of PD., To explore early alterations and underlying associations of dopamine levels and microstructure in Parkinson’s Disease (PD), Shang et al use a hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) approach in early stage patients and age-matched controls. Their data implies that molecular degeneration mediates the effects of microstructural disorganization on motor dysfunction in the early stages of PD.

To explore the dietary patterns and its relationship with abdominal obesity among the adult women in Zhejiang Province.We recruited 2915 female residents aged 18 and older by using multi-stage stratified cluster sampling method; We conducted questionnaires survey and physical examinations to understand the basic information and nutritional status of the residents. Dietary patterns were extracted with factor analysis, and the multivariate Logistic regression model was used to analyze the association between dietary patterns and abdominal obesity among the participants.The prevalence rate of abdominal obesity and general obesity among the subjects were 33.07% and 9.23%, respectively. The highest rate of abdominal obesity was among the female who were above 65 years old, living in rural areas with low education. On the other hand, the lowest rate of abdominal obesity was among females with higher education(Plt;0.0001). Four dietary patterns identified with factor analysis were grain pattern, nut-legume pattern, milk-eggs pattern and modern pattern, accounting for 38.5% of total variance. After adjusting confounding factors as age, education level, occupation, marital status, urban/rural and exercise status, the participants with the fourth quartile(Q4) score of nut-legume dietary pattern had a low risk of abdominal obesity(OR=0.720, 95% CI 0.571-0.908, P=0.0012) compared to those with the quartile(Q1) first score.The nut-legume dietary pattern is negatively associated with abdominal obesity in female adults.

Dyskalemia involves critical electrolyte abnormalities and increases mortality risk in patients with acute clinical conditions. However, the association between dyskalemia and adverse outcomes in the general population is less well established. To investigate the association of serum potassium levels with mortality and cardiovascular events in the general population and to explore the characteristics of individuals at high risk. A prospective cohort study. A total of 5220 participants aged 50–79 years in the Chinese Multi-provincial Cohort Study. Serum potassium levels were measured by the ion-selective electrode method. The outcomes were incident cardiovascular disease (CVD), CVD death, non-CVD death, and total death. Of the 5220 participants, 48.2% were men, and the mean age was 62.3 (SD 7.6) years. Hyperkalemia was found in 8.7% of the participants and was significantly associated with total death (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.18–2.23) and CVD death (HR, 2.12; 95% CI, 1.25–3.61) after adjustment. Furthermore, the HRs (95% CIs) of hyperkalemia combined with 2 and ≥ 3 risk factors were 2.37 (1.50–3.74) and 4.06 (2.37–6.95) for total death and 3.26 (1.56–6.80) and 8.42 (4.06–17.50) for CVD death, respectively. The 10-year cumulative incidence of total death was 17.4% for participants with 2 or more risk factors. Hyperkalemia is associated with an increased risk of all-cause and CVD death, and this risk is more pronounced in patients with multiple risk factors. Our findings suggest that early identification and management of hyperkalemia in the general population are warranted.

Background and objectives This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. Methods Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. Results The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). Conclusions In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

Objective. Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes, leading to disability and decreased quality of life. In past research and clinical studies, the lower limb function of DPN patients was often the principal subject of research, with little attention given to the upper limb and hand. Our goal was to assess and compare hand function between elderly diabetic patients with DPN and without DPN. Methods. A total of 52 diabetic patients were registered and underwent hand function assessments and electrodiagnostic tests. Dynamometer, pinch meter, Semmes Weinstein monofilaments, and the Purdue Pegboard Test (PPT) were used to assess the patients’ grip strength, pinch strength, tactile sensory threshold, and hand dexterity. Results. Compared with the non-DPN group, the elderly DPN group showed worse thumb-middle fingertip pinch strength and thumb-little fingertip pinch strength in the dominant hand (3.50 (2.50, 4.25) vs. 4.50 (3.00, 5.00), p = 0.019 ; 1.50 (1.00, 2.00) vs. 2.50 (2.00, 3.00), p < 0.001 ); the elderly DPN group displayed worse thumb-middle fingertip pinch strength, thumb-ring fingertip pinch strength, and thumb-little fingertip pinch strength in the nondominant hand (3.50 (2.00, 4.50) vs. 4.00 (3.00, 5.00), p = 0.013 ; 2.50 (1.25, 3.00) vs. 3.00 (2.50, 3.50), p = 0.033 ; 1.00 (0.75, 2.25) vs. 2.50 (2.00, 2.50), p < 0.001 ). The elderly DPN group scored lower than the non-DPN group on the PPT test of assembly ( 13.96 ± 5.18 vs. 16.96 ± 4.61 , t = 2.212 , p = 0.032 ). Conclusion. Motor function limitation is the principal hand dysfunction in elderly patients with DPN, which is mainly manifested as a decline in fingertip pinch strength and a decrease in hand dexterity. This trial is registered with Clinical Trial Registry no. ChiCTR1900025358.

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in patients with chronic kidney disease (CKD) and acute coronary syndrome (ACS). This study aimed to explore the frequency and impact of AF on clinical outcomes in CKD patients with ACS. Methods CKD inpatients with ACS between November 2014 and December 2018 were included based on the improving care for cardiovascular disease in China-ACS (CCC-ACS) project. Included patients were divided into an AF group and a non-AF group according to the discharge diagnosis. Multivariable logistic regression was used to adjust for potential confounders. Results A total of 16,533 CKD patients with ACS were included. A total of 1418 (8.6%) patients had clinically recognized AF during hospitalization, 654 of whom had an eGFR of 45 to 2, and 764 had an estimated glomerular filtration rate (eGFR) 2. Compared with the non-AF group, the AF group had a higher risk of in-hospital mortality [OR 1.250; 95% CI (1.001–1.560), P = 0.049] and major adverse cardiovascular events (MACEs) [OR 1.361; 95% CI (1.197–1.547), P 2, patients with eGFR 2 had a 1.512-fold increased risk of mortality and a 1.435-fold increased risk of MACEs. Conclusions AF was a risk factor affecting the short-term prognosis of ACS patients in the CKD population. Furthermore, the lower the eGFR, the higher the risk of in-hospital mortality and MACEs in CKD patients with ACS. Trial registry: Clinicaltrial.gov, NCT02306616. Registered 29 November 2014, https://clinicaltrials.gov/ct2/show/NCT02306616?term=NCT02306616&draw=2&rank=1

Background: Little is known about variation in vitamin B12 and folate status among Chinese women 2 years postpartum. This study assessed intake of vitamin B12 and folate and biomarkers of nutrient status among Chinese women postpartum. Methods: Demographic information, multi-/single-nutrient supplementation, dietary data, serum vitamin B12 and serum folate were assessed in 982 women within 2 years postpartum, using ten investigation sites in Zhejiang Province from the National Nutritional Study 2016–2017, which is a nationally representative cross-sectional study, to form a representative provincial sample of Zhejiang Province. The dietary diversity score (DDS) was used for assessing the dietary pattern. Results: Vitamin B12 increased slightly at the early stage of postpartum and then dropped over time. Serum folate level elevated with postpartum time. The median serum vitamin B12 concentration was 494.59 (373.21–650.20) pg/mL, and folate was 7.58 (5.02–10.34) ng/mL. Correspondingly, vitamin B12 levels suggesting marginal deficiency (200–300 pg/mL) and deficiency (

Facial nerve schwannomas located at internal auditory canal and cerebellopontine angle (IAC/CPA FNS) were diagnosed intraoperatively, it poses a therapeutic dilemma to the surgeon.To report our experience in managing IAC/CPA FNS and to propose a treatment strategy.A total of 14 patients with IAC/CPA FNS who were diagnosed intraoperatively and treated by operation between 2015 and 2019 were retrospectively studied.Unilateral hearing loss was the most common symptom and all these patients had normal facial nerve function preoperatively. Surgical approaches used in these patients including translabyrinthine (2 cases), retrosigmoid (RS) (11 cases), and middle cranial fossa (MCF) approach (1 case). Eight patients underwent partial resection, three patients underwent subtotal resection and three patients had complete tumor removal with facial nerve reconstruction. All partial resection patients and two patients underwent subtotal resection achieved a long-term HB grade I facial nerve function. The long-term facial nerve function of patients underwent complete resection and nerve grafting was no better than HB grade III.1 of the eight patients underwent partial resection experienced tumor regrowth during the follow-up.Partial or subtotal resection for IAC/CPA FNS may provide an opportunity of retaining excellent facial nerve function. Regular postoperative imaging is helpful to monitor the recurrence.

Background Omega-3 polyunsaturated fatty acids (PUFAs) produce lipid mediators with both anti-inflammatory and pro-resolution properties, including resolvins. The purpose of this study was to detect serum resolvin E1 (RVE1) levels in Hashimoto’s thyroiditis (HT) patients and healthy controls (HCs) and to evaluate the relationship of RVE1 with thyroid autoimmunity. Methods A total of 57 participants were recruited, including 30 untreated HT patients and 27 age- and sex‐matched HCs. The levels of RVE1 in serum were measured via enzyme-linked immunosorbent assay (ELISA). An electrochemiluminescence immunoassay was used for the measurement of thyroid-stimulating hormone (TSH), total T4 (TT4), TT3, free T4 (FT4), FT3, anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) levels. Hemogram tests and routine biochemical analyses were performed on each sample. Results The serum level of RVE1 of HT patients (24.09, 15.76–34.38 pg/mL) was significantly lower than that of healthy controls (28.51, 20.76–51.23 pg/mL) (P = 0.027). RVE1 levels showed a downward trend with increasing TgAb levels (P for trend = 0.001). Multivariable ordinal logistic regression analysis showed that RVE1 levels were negatively correlated with increasing TgAb levels in both the unadjusted (OR = 0.9446, 95 % CI = 0.9111–0.9782, P = 0.002) and adjusted models (OR = 0.9380, 95 % CI = 0.8967–0.9811, P = 0.005). Conclusions Decreased RVE1 levels might be a sign that HT is associated with inflammatory resolution dysfunction. RVE1 may serve as a protective factor against increased TgAb levels.

In-hospital cardiac arrest (IHCA) is one of the most deleterious complications of ST-segment elevation myocardial infarction (STEMI).We systematically analyzed the clinical characteristics of STEMI patients with IHCA, as well as predictors and treatments associated with risk of IHCA, using a nationwide database.In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we stratified patients presenting with STEMI within 24 hours after symptom onset according to IHCA or no IHCA during the index hospitalization. We analyzed patients' clinical characteristics, mortality, and independent correlates of IHCA.Of 40,670 STEMI patients, 2.2% (95% CI: 2.1%-2.4%) experienced IHCA. Among IHCA patients, the in-hospital mortality was 53.0% (95% CI: 49.7%-56.3%). IHCA represents 55.0% (95% CI: 51.6%-58.4%) of inpatient deaths. Age ≥75 years, female, nonsmoker, prior diabetes mellitus, prior renal failure, out-of-hospital cardiac arrest, heart rate100 beats/min, systolic blood pressure 90 mm Hg, and Killip IV were identified as predictors of IHCA. IHCA patients were less likely to receive β-blockers and ticagrelor during the first 24 hours after first medical contact and were less likely to undergo primary percutaneous coronary intervention. After adjustment, primary percutaneous coronary intervention (adjusted HR: 0.82; 95% CI: 0.71-0.95), β-blockers (adjusted HR: 0.63; 95% CI: 0.47-0.86), and ticagrelor (adjusted HR: 0.57; 95% CI: 0.42-0.76) were associated with a reduced risk of IHCA.IHCA is rare in STEMI but is associated with high mortality. Multiple modifiable and unmodifiable factors are associated with its occurrence, suggesting that early intervention and rational drug treatment may improve its prognosis. (CCC Project- Acute Coronary Syndrome; NCT02306616).

Premature delivery is one of the direct factors that affect the early development and safety of infants. Its direct clinical manifestation is the change of uterine contraction intensity and frequency. Uterine Electrohysterography(EHG) signal collected from the abdomen of pregnant women can accurately and effectively reflect the uterine contraction, which has higher clinical application value than invasive monitoring technology such as intrauterine pressure catheter. Therefore, the research of fetal preterm birth recognition algorithm based on EHG is particularly important for perinatal fetal monitoring. We proposed a convolution neural network(CNN) based on EHG fetal preterm birth recognition algorithm, and a deep CNN model was constructed by combining the Gramian angular difference field(GADF) with the transfer learning technology. The structure of the model was optimized using the clinical measured term-preterm EHG database. The classification accuracy of 94.38% and

Background The aim of this study was to examine the possible association between serum micronutrients (vitamin D, retinol, zinc), C-reactive protein (CRP), and obesity among children and adolescents. Methods Weight and height were measured and serum 25-hydroxy vitamin D, serum retinol, serum zinc, and CRP were measured in 2818 children and adolescents (6–17 years of age), and the data of 10 investigation sites in Zhejiang Province were used. The difference of micronutrients (vitamin D, retinol, zinc) and CRP among different nutritional status were explored by ANOVA and Chi-square test. The associated factors of micronutrients and CRP of overweight and obesity were explored by multifactor analysis. Results There were significant differences between male students and female students on BMI, 25(OH)D3, and CRP, and there were significant differences between children and adolescents and between students living in urban area and rural area on BMI, 25(OH)D3, retinol, and zinc(t > 1.96, p F = 2.612, 15.022, p Conclusion Gender, living area, age, CRP concentration, and vitamin A status were associated with children and adolescents with overweight and obesity compared to low/normal BMI. More attention in the intervention of overweight and obesity should be paid to boys living in urban areas, and high serum concentration of CRP should also be concerned.

Objective This study investigated changes of plasma cytokines and aimed to build a dynamic nomogram for diabetic macular edema (DME) in type 2 diabetes mellitus (T2DM). Methods In a pilot cohort, plasma samples were selected from 9 T2DM patients and 9 DME patients to screen for cytokine differences. The screening cytokines were then validated by enzyme-linked immunoassay in a cohort, which contained 100 DME (DME group) and 100 T2DM patients without DME (T2DM group). A dynamic nomogram for predicting DME was developed, based on the plasma cytokines. Results In the pilot cohort, 11 plasma cytokines were significantly increased in the DME group. In the validation cohort, platelet-derived growth factor (PDGF)-BB, tissue inhibitors of metalloproteinase (TIMP)-1, angiopoietin (ANG-1), and vascular endothelial cell growth factor receptor (VEGFR)-2 were confirmed to be significantly elevated in the DME group. The dynamic nomogram demonstrated good calibration and discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.88. In the test set, sensitivity, specificity, and AUC were 73.3%, 80.0%, and 0.84, respectively. Conclusion Plasma cytokines were closely associated with DME. A novel dynamic monogram including ANG-1, PDGF-BB, TIMP-1, and VEGFR2 was a novel tool for predicting DME.

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25–0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11–0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19–induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

Background The incidence and the risk factors of in-hospitalized acute kidney injury (AKI) in patients hospitalized for atrial fibrillation (AF) were unclear. Methods The Improving Care for Cardiovascular Disease in China-AF (CCC-AF) project is an ongoing registry and quality improvement project, with 240 hospitals recruited across China. We selected 4527 patients hospitalized for AF registered in the CCC-AF from January 2015 to January 2019. Patients were divided into the AKI and non-AKI groups according to the changes in serum creatinine levels during hospitalization. Results Among the 4527 patients, the incidence of AKI was 8.0% (361/4527). Multivariate logistic analysis results indicated that the incidence of in-hospital AKI in patients with AF on admission was 2.6 times higher than that in patients with sinus rhythm (OR 2.60, 95% CI 1.77–3.81). Age (per 10-year increase, OR 1.22, 95% CI 1.07–1.38), atrial flutter/atrial tachycardia on admission (OR 2.16, 95% CI 1.12–4.15), diuretics therapy before admission (OR 1.48, 95% CI 1.07–2.04) and baseline hemoglobin (per 20 g/L decrease, OR 1.21, 95% CI 1.10–1.32) were independent risk factors for in-hospital AKI. β blockers therapy given before admission (OR 0.67, 95% CI 0.51–0.87) and non-warfarin therapy during hospitalization (OR 0.71, 95% CI 0.53–0.96) were associated with a decreased risk of in-hospital AKI. After adjustment for confounders, in-hospital AKI was associated with a 34% increase in risk of major adverse cardiovascular (OR 1.34, 95% CI 1.02–1.90, p = 0.023). Conclusions Clinicians should pay attention to the monitoring and prevention of in-hospital AKI to improve the prognosis of patients with AF.

Aims This study aimed to investigate changes of plasma cytokines and to develop machine learning classifiers for predicting non-proliferative diabetic retinopathy among type 2 diabetes mellitus patients. Results There were 12 plasma cytokines significantly higher in the non-proliferative diabetic retinopathy group in the pilot cohort. The validation cohort showed that angiopoietin 1, platelet-derived growth factor-BB, tissue inhibitors of metalloproteinase 2 and vascular endothelial growth factor receptor 2 were significantly higher in the NPDR group. Machine learning algorithms using the random forest yielded the best performance, with sensitivity of 92.3%, specificity of 75%, PPV of 82.8%, NPV of 88.2% and area under the curve of 0.84. Conclusions Plasma angiopoietin 1, platelet-derived growth factor-BB, and vascular endothelial growth factor receptor 2 were associated with presence of non-proliferative diabetic retinopathy and may be good biomarkers that play important roles in pathophysiology of diabetic retinopathy. Materials and methods In pilot cohort, 60 plasma cytokines were simultaneously measured. In validation cohort, angiopoietin 1, CXC-chemokine ligand 16, platelet-derived growth factor-BB, tissue inhibitors of metalloproteinase 1, tissue inhibitors of metalloproteinase 2, and vascular endothelial growth factor receptor 2 were validated using ELISA kits. Machine learning algorithms were developed to build a prediction model for non-proliferative diabetic retinopathy.

Background Circulating angiopoietin-like 2 (ANGPTL2) protein levels are known to be significantly increased in numerous chronic inflammatory diseases and are associated with the diagnosis and/or prognosis of cardiovascular diseases, diabetes, chronic kidney disease, and various types of cancers. However, no data regarding the relationship between ANGPTL2 and diabetic foot ulcers (DFUs) are available. Here, we explored the potential link between ANGPTL2 and DFUs. Methods A total of 68 participants with type 2 diabetes mellitus (T2DM) were recruited, including 28 patients with DFU and 40 diabetic patients without DFUs. The clinical characteristics of T2DM patients with and without DFUs were compared. Serum concentrations of ANGPTL2 and VEGF were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANGPTL2 and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANGPTL2 and the severity and presence of DFUs. Results Serum levels of ANGPTL2 were higher in patients with DFUs than those in diabetic controls. Serum ANGPTL2 levels were higher in the advanced stages of DFUs. Spearman correlation analysis revealed strong positive associations of ANGPTL2 with CRP, VEGF and ESR in all subjects. In addition, serum ANGPTL2 was still positively correlated with DFUs stage after adjusting the risk factors. After adjusting for age, sex, HbA1C and duration of diabetes, ANGPTL2 was found to be independently associated with the presence of DFUs. Conclusions Circulating ANGPTL2 levels are an independent risk factor for DFUs. This suggests that ANGPTL2 may play important roles in the development of DFUs, a possibility that needs to investigated in prospective studies.

Current biomarkers did not overcome the limitations of clinical application due to the heterogeneity of ovarian tumors. The role of nuclear factor of activated T cells (NFAT) in the prognosis of different histological subtypes of ovarian cancer remains unclear. NFAT expression was analyzed in 302 ovarian tumors from The Cancer Genome Atlas (TCGA) dataset and was further confirmed by 88 ovarian tumor specimens, including 30 clear-cell carcinoma, 34 serous carcinoma, and 24 papillary serous cystadenocarcinoma. The correlations between NFAT expression, cancer biomarkers, and clinical characteristics in different subtypes of ovarian tumors were analyzed. ALGGEN PROMO, reporter assay, and NFAT overexpression and knockdown were used to identify chondroadherin (CHAD) as the downstream target of NFAT. NFAT was significantly upregulated only in late-stage clear-cell carcinoma, but not in other two subtypes. NFAT levels were correlated with CA72-4 levels and poor overall survival and disease-free survival (P

Gamma-aminobutyric acid (GABA) analogs are being used by an increasing number of reproductive-age women. However, there is concern regarding the teratogenic potential of GABA analogs.We performed this systematic review and meta-analysis to assess the relationship between GABA analog exposure and risk of adverse neonatal outcomes.Eight cohort studies were included in the meta-analysis. Exposure to a GABA analog during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 1.19, 95% confidence interval [CI] 0.96-1.46, P = 0.106) or a small for gestational age (SGA) infant (OR 1.99, 95% CI 0.78-5.1, P = 0.152) compared to no exposure. However, exposure to a GABA analog was associated with an increased risk of preterm birth (PB) (OR 1.56, 95% CI 1.04-2.35, P = 0.033), spontaneous abortion (SA) (OR 1.64, 95% CI 1.14-2.38, P = 0.008), or termination of pregnancy (TOP) (OR 3.02, 95% CI 2-4.56, P 0.001).Exposure to GABA analogs during pregnancy does not appear to be associated with congenital malformation, although there was some evidence of a higher risk of several other negative neonatal outcomes. Given the few studies included, larger prospective studies controlling for important confounders are needed to verify our findings.

BackgroundBK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) causes renal allograft dysfunction and graft loss. However, the mechanism of BKPyV replication after kidney transplantation is unclear. Clinical studies have demonstrated that immunosuppressants and renal ischemia–reperfusion injury (IRI) are risk factors for BKPyV infection. Studying the pathogenic mechanism of BKPyV is limited by the inability of BKPyV to infect the animal. Mouse polyomavirus (MPyV) is a close homolog of BKPyV. We used a model of MPyV infection to investigate the core genes and underlying mechanism of IRI and immunosuppressants to promote polyomavirus replication.Materials and MethodsOne-day-old male C57BL/6 mice were intraperitoneally injected with MPyV. At week 9 post-infection, all mice were randomly divided into IRI, immunosuppressant, and control groups and treated accordingly. IRI was established by clamping the left renal pedicle. Subsequently, kidney specimens were collected for detecting MPyV DNA, histopathological observation, and high-throughput RNA sequencing. Weighted gene correlation network analysis (WGCNA), protein–protein interaction network analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to screen for core genes and common signaling pathways involved in promoting MPyV replication by IRI and immunosuppressants.ResultsAfter primary infection, MPyV established persistent infection in kidneys and subsequently was significantly increased by IRI or immunosuppressant treatment individually. In the IRI group, viral loads peaked on day 3 in the left kidney, which were significantly higher than those in the right kidney and the control group. In the immunosuppressant group, viral loads in the left kidney were significantly increased on day 3, which were significantly higher than those in the control group. Protein–protein interaction network analysis and WGCNA screened complement C3, epidermal growth factor receptor (EGFR), and FN1 as core genes. Pathway enrichment analysis based on the IRI- or immunosuppressant-related genes selected by WGCNA indicated that the NF-κB signaling pathway was the main pathway involved in promoting MPyV replication. The core genes were further confirmed using published datasets GSE47199 and GSE75693 in human polyomavirus-associated nephropathy.ConclusionsOur study demonstrated that IRI and immunosuppressants promote polyomavirus replication through common molecular mechanisms. In future studies, knockdown or specific inhibition of C3, EGFR, FN1, and NF-κB signaling pathway will further validate their critical roles in promoting polyomavirus replication.

Data about the sequelae of women who infected COVID-19 while pregnant are scarce. We aimed to describe the prevalence of symptoms, pulmonary functions, and radiological changes at a follow-up of 12 months in 18 pregnant women who developed COVID-19 at different gestational ages. Our results showed that most women who infected COVID-19 while pregnant experienced a progressive improvement of their symptoms within 12 months, however, some still had little COVID-related symptoms but without a reduced quality of life. All their 18 newborns were growing up healthy.

Background Renal insufficiency (RI) is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate the attributable risk associated with mild RI for the in-hospital outcomes in patients with ACS. Methods The Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 92,509 inpatients with a discharge diagnosis of ACS were included. The attributable risk was calculated to investigate the effect of mild RI (eGFR 60-89 ml / min · 1.73 m2) on major adverse cardiovascular events (MACEs) during hospitalization. Results The average age of these ACS patients was 63 years, and 73.9% were men. The proportion of patients with mild RI was 36.17%. After adjusting for other possible risk factors, mild RI was still an independent risk factor for MACEs in ACS patients. In the ACS patients, the attributable risk of eGFR 60-89ml/min·1.73m2 to MACEs was 7.78%, 4.69% of eGFR 45-59 ml/min·1.73m2, 4.46% of eGFR 30-44 ml/min·1.73m2, and 3.36% of eGFR2. Conclusion Compared with moderate to severe RI, mild RI has higher attributable risk to MACEs during hospitalization in Chinese ACS population.

To explore the sociodemographic disparity in the nutritional status including BMI, vitamin D and vitamin A status among children and adolescents in Zhejiang Province. Weight, height serum 25-hydroxyvitamin D, and serum retinol were assessed in 2818 children and adolescents (6–17 years of age), using ten investigation sites in Zhejiang Province including urban and rural areas data from the China National Nutritional Study 2016–2017, which is a nationally representative cross-sectional study, to form provincial representative sample of Zhejiang Province. Sociodemographic disparity was explored. The prevalence of low weight, eutrophic, overweight and obese were 6.7%, 70.4%, 11.6%, and 11.2%, respectively. Significant difference was observed on BMI between males and females (P

OBJECTIVES Cardiovascular dysautonomia can be present at early, late and even prodromal stages of Parkinson's disease. This study aimed to describe the characteristics of 24-h ambulatory blood pressure (BP) monitoring and investigate the frequency of cardiovascular dysautonomia in Parkinson's disease without an abnormal BP history. METHODS Parkinson's disease patients without history of abnormal BP were consecutively enrolled from three Chinese centres, on whom office BP measurement, neurological evaluations and 24-h ambulatory BP monitoring were performed. RESULTS Totally, 101 Parkinson's disease patients (42.6% women) with an average age of 66.6 ± 8.2 years were included in our cohort, and data analysis revealed that 26 (25.74%) patients suffered from orthostatic hypotension, among whom 18 (69.23%) were symptomatic. Patients with orthostatic hypotension compared with those without had significantly higher nocturnal SBP level, and more severe nonmotor symptoms, autonomic dysfunction and cognitive impairment. Further, 54 out of 101 (53.47%) individuals had a reverse dipping pattern in SBP and/or DBP. Reverse dippers had more cases of orthostatic hypotension (P

Aim A high-risk strategy has been implemented for lipid-lowering therapy in the primary prevention of cardiovascular disease. However, atherosclerosis and cardiovascular events are common among individuals with low cardiovascular risk. This study aimed to determine whether the small dense low-density lipoprotein cholesterol (sdLDLC) level can predict carotid atherosclerosis progression and identify high-risk individuals. Methods Baseline sdLDLC and low-density lipoprotein cholesterol (LDLC) were measured in 808 participants from the Chinese Multi-provincial Cohort Study, aged 45-74 years. Adjusted relative risk was calculated using a modified Poisson regression model to assess the relationship between sdLDLC and 5-year atherosclerosis progression, as indicated by the progression, incidence, and multi-territorial extent of carotid plaque. Results The 5-year atherosclerosis progression increased significantly with increased sdLDLC. Baseline sdLDLC was significantly associated with the short-term risk of plaque progression after multivariable adjustment, even in participants with low LDLC or a 10-year estimated cardiovascular risk. sdLDLC predicted plaque progression (relative risk 2.05; 95% confidence interval 1.43-2.93) in participants with LDLC ＜130 mg/dL. Furthermore, participants with the highest sdLDLC but intermediate or low cardiovascular risk (accounting for 16% of the cohort) had double the risk of plaque progression, which was comparable to those with the same sdLDLC and high cardiovascular risk, relative to those with the lowest sdLDLC levels and low cardiovascular risk. Conclusions sdLDLC is independently associated with the progression of carotid atherosclerosis, which may provide a basis for clinicians to reclassify individuals believed to be at low cardiovascular risk into the high-risk category, and those with high sdLDLC may benefit from more aggressive cholesterol-lowering treatment.

OBJECTIVE To investigate the relationship between serum vitamin D concentration and lumbar disc degeneration (LDD) in postmenopausal women and the epidemiologic factors affecting low back pain (LBP). METHODS Between July 2017 and December 2018, 232 participants were retrospectively enrolled. Serum concentrations of bone turnover markers were measured using electrochemiluminescence assays. Disc degeneration was evaluated using the Pfirrmann grading system. Other variables were assessed using relevant questionnaires. RESULTS The mean age of the women was 65.6 ± 10.1 and their serum 25(OH)D concentrations were 19.38 ± 9.21 ng/mL. The prevalences of severe vitamin D deficiency ( 30 ng/mL) were 12.9% and 12.5%, respectively. The severely deficient group had higher visual analog scale (VAS) scores for LBP (P = 0.002) and lower bone mineral density T scores (P = 0.004) than the other groups. Lower 25(OH)D concentration (

Growing evidence has suggested a possible relationship between dietary calcium intake and metabolic syndrome (MetS) risk. However, the findings of these observational studies are inconclusive, and the dose-response association between calcium intake and risk of MetS remains to be determined. Here, we identified relevant studies by searching PubMed and Web of Science databases up to December 2018, and selected observational studies reporting relative risk (RR) with 95% confidence interval (CI) for MetS based on calcium intake and estimated the summary RRs using random-effects models. Eight cross-sectional and two prospective cohort studies totaling 63,017 participants with 14,906 MetS cases were identified. A significantly reduced risk of MetS was associated with the highest levels of dietary calcium intake (RR: 0.89; 95% CI: 0.80–0.99; I2 = 75.3%), with stronger association and less heterogeneity among women (RR: 0.74, 95% CI: 0.66–0.83; I2 = 0.0%) than among men (RR: 1.06, 95% CI: 0.82–1.37; I2 = 72.6%). Our dose-response analysis revealed that for each 300 mg/day increase in calcium intake, the risk of MetS decreased by 7% (RR: 0.93; 95% CI: 0.87–0.99; I2 = 77.7%). In conclusion, our findings suggest that dietary calcium intake may be inversely associated with the risk of MetS. These findings may have important public health implications with respect to preventing the disease. Further studies, in particular longitudinal cohort studies and randomized clinical trials, will be necessary to determine whether calcium supplementation is effective to prevent MetS.

Background: The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up. Methods: This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME

Describe and predict the malignant tumor deaths in Xi'an so as to provide evidence for the government to formulate the prevention and treatment plans.Overall malignant tumor death in Xi'an in the past 16 years was described. The multi-decrease life table was used to calculate cumulative mortality risk by cause and life expectancy reduction years by cause of malignant tumors in 2020. The join point regression models were used to analyze the change trend of standard mortality of malignant tumors in Xi'an from 2005 to 2020. The appropriate gray models were selected to predict the death of malignant tumors in Xi'an in the next decade.The mortality of total malignant tumors in Xi'an showed that men are higher than women and the elderly are higher than other groups. As for 2020, lung cancer had the highest risk of death for both men and women, while leukemia had the highest life expectancy reduction years by cause. From 2005 to 2020, standardized mortality of majority malignant tumors showed downward trends, which were particularly obvious in recent years. The prediction results of several major malignant tumors showed that in the next decade, the mortality of most malignant tumors had downward trends, but combined with the increase of population in the future, the number of malignant tumor deaths in Xi'an will continue to increase.Malignant tumors in Xi'an have decreasing mortality trends in recent years, and effective measures to prevent and treat tumors should be strengthened in the future.

BackgroundOverweight and obesity are well-known risk factors for type 2 diabetes mellitus (T2DM). The effect of the maximum body mass index (BMImax), which indicates the highest body weight before the diagnosis of T2DM, is not fully understood. This study aimed to explore the predictive value of BMImax in the progression of diabetes.MethodsThis prospective study recruited 2018 subjects with normal glucose tolerance in Beijing, China. The subjects were followed up for eight years, and the association between BMImax and glucose outcomes was evaluated.ResultsNinety-seven of the 2,018 participants developed diabetes by the end of the study. Compared to individuals with normal glucose tolerance, those who developed diabetes were characterized by higher levels of fasting plasma glucose (FPG), 2 h postload glucose (PBG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-c), a higher prevalence of a familial history of diabetes and a lower level of high‐density lipoprotein cholesterol (HDL-c). Multivariate regression analysis of sex-stratified groups suggested that FPG, HbA1c, SBP and familial history of diabetes were independent risk factors for diabetes, but that BMImax was a unique indicator for female patients.ConclusionsBMImax might be an independent predictor of T2DM in females, but it does not seem to be associated with the risk of diabetes in males. BMImax could be regarded as an indicator in the prevention and management of diabetes.

Prostacyclin (PGI

Acute myocardial infarction (AMI) poses a serious disease burden in China, but studies on small-area characteristics of AMI incidence are lacking. We therefore examined temporal trends and geographic variations in AMI incidence at the township level in Beijing. In this cross-sectional analysis, 259,830 AMI events during 2007–2018 from the Beijing Cardiovascular Disease Surveillance System were included. We estimated AMI incidence for 307 consistent townships during consecutive 3-year periods with a Bayesian spatial model. From 2007 to 2018, the median AMI incidence in townships increased from 216.3 to 231.6 per 100,000, with a greater relative increase in young and middle-aged males (35–49 years: 54.2%; 50–64 years: 33.2%). The most pronounced increases in the relative inequalities was observed among young residents (2.1 to 2.8 for males and 2.8 to 3.4 for females). Townships with high rates and larger relative increases were primarily located in Beijing’s northeastern and southwestern peri-urban areas. However, large increases among young and middle-aged males were observed throughout peri-urban areas. AMI incidence and their changes over time varied substantially at the township level in Beijing, especially among young adults. Targeted mitigation strategies are required for high-risk populations and areas to reduce health disparities across Beijing.

Endometriosis (EMs) is characterized as an estrogen-dependent disease. Whereas, the underlying mechanism for activated estrogen biosynthesis in EMs lesions is largely unknown. We analyzed cholesterol metabolism and estrogen biosynthesis condition of EMs lesions by biological information analysis of GEO datasets, and further verified both

To explore the clinical effects of posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis.Twenty-four patients with Kümmell disease complicated with kyphosis treated by posterior short-segment pedicle screw internal fixation combined with vertebroplasty from January 2016 to December 2018 were retrospectively analyzed, including 6 males and 18 females, aged 63 to 85 (73.1±6.5) years old. The clinical effect was evaluate by visual analogue scale (VAS), Oswestry Disability Index (ODI), the anterior height of injured vertebral body, and the sagittal Cobb angle of the affected segment beforeoperation, at 3 days and final follow up after operation. And the surgical complications were observed.All 24 patients were followed up from 12 to 24 months with an average of (15.5±3.2) months. The VAS score was decreased from 5.21±1.06 preoperatively to 2.38±0.58 at 3 days postoperatively and 1.71±0.75 at final follow-up;ODI was decreased from (50.4±13.5)% preoperatively to (20.9±8.0)% at 3 days postoperatively and (16.7±9.6)% at final follow-up;the anterior height of injured vertebral body was restored from (8.0±4.2) mm before surgery to (18.1±5.0) mm at 3 days after surgery and (16.8±5.1) mm at final follow up;the sagittal Cobb angle of affected segment was decreased from (19.5±6.3)° preoperatively to (7.6±2.1)° at 3 days after surgery and(8.4±1.7)° at final follow-up. VAS, ODI, anterior height of injured vertebral body, and sagittal Cobb angle of affected segment were significantly improved at 3 days after operation and at final follow-up (Posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis has relatively small surgical trauma, excellent clinical results, good vertebral height recovery, satisfactory correction of kyphotic angle, and fewer complications, etc. It is a safe and effective surgical method to treat Kümmell disease with kyphosis.

Background The surgical management of Mayo III/IV tumor thrombi is difficult and risky, and robotic surgery is even more difficult. The purpose of this study was to introduce the step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus, which was the core technique of robot operation for Mayo III/IV tumor thrombus. Method A total of 18 patients were included in this study. The average tumor thrombus height was 2.4 cm above the level of the second porta hepatis (SPH), and 9 patients were prepared for cardiopulmonary bypass (CPB) before surgery. During the operation, the height of the tumor thrombus was lowered orderly for 2-3 times, and the blood flow blocking method was changed sequentially. The CPB was required when tumor thrombus in the atrium; After the height of the thrombus was lowered to the atrium entrance, CPB was stopped and the blood flow was blocked in the upper- and retro-hepatic inferior vena cava (IVC); After the tumor thrombus continued to descend to the lower part of the SPH, liver blood flow could be restored, and then, the blood flow was simply blocked in the retro-hepatic IVC to complete the removal of the thrombus and the repair or resection of the IVC. Finally, the diseased kidney and renal vein were removed. Results All operations were successfully completed, and 2 cases were transferred to laparotomy. Seven cases received CPB, while the other 11 did not. 15 patients underwent two times of the lowering of the tumor thrombus, 2 patients underwent one time and 1 patient underwent three times. The mean liver/IVC dissociation and vascular suspension time was 22.0 min. All patients had less than Clavien-Dindo grade III complications, no serious complications occurred during operation, and no patient died within 90 days. Conclusions The step-by-step and orderly decline of tumor thrombus height is the key to the success of robot Mayo III / IV tumor thrombus surgery. This method can shorten FPH and CPB time and improve the success rate of surgery.

Background: The association between preoperative overt hypothyroidism and early outcomes after coronary artery bypass grafting (CABG) is unclear. This study aimed to evaluate the influence of overt hypothyroidism on the outcomes of CABG. Methods: The series included 189 overt hypothyroid patients who underwent CABG at Fuwai Hospital. These patients were 1:4 matched with 737 euthyroid patients using propensity score matching. The early postoperative outcomes were compared. Results: After propensity score matching, the incidences of impaired wound healing, reintubation, and the total complications were higher in hypothyroid patients than euthyroid patients (11.8% vs. 0.9%, pConclusions: CABG in overt hypothyroid patients is associated with a higher incidence of postoperative complications, stronger postoperative inotropic support, and longer mechanical ventilation time.

Background The right posterior segment (RPS) graft was introduced to overcome graft size discrepancy in living donor liver transplantation (LDLT). However, it was very rarely used in pediatric patients. Here we presented 4 pediatric LDLT cases receiving RPS graft between January 2015 and April 2020 in our center. A total of 1868 LDLT procedures were performed in this period. Methods Recipients included 1 boy and 3 girls with a median age of 45 months (range from 40 to 93 months). They were diagnosed with progressive familial intrahepatic cholestasis, propionic academia, ornithine transcarbamylase and biliary atresia, respectively. Four donors were all mothers with a median age of 32.5 years (31–38 years). Computer tomography angiography indicated posterior right branches branched off separately from main portal veins (type III variation). Three of these donor livers had 1 orifice of right hepatic veins (RHV). In the remaining 1 donor liver, the RHV showed 3 orifices and an outflow patch plastic was performed. Inferior right hepatic veins weren’t found in four donor grafts. The median graft weight was 397.5 g (352–461 g) and the median graft-to-recipient weight ratio was 2.38% (1.44–2.80%). Results Postoperative complications occurred in neither donors nor recipients. Within the median follow-up duration of 29 months (14–64 months), four children are all alive with normal liver function. Conclusion In summary, for older children weighed more than 15 kg with donors’ variation of type III portal veins, the use of RPS grafts could be a feasible and favorable option.

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

Well-regulated maternal-fetal immune tolerance is a prerequisite for normal pregnancy. Hyperactivated immune cells and overwhelming inflammatory responses trigger adverse gestation outcome, such as recurrent spontaneous abortion (RSA). Local exacerbation of immunomodulatory cells in maternal decidua is a critical event, tightly linked with fetus acceptance. Owning to the notable immunoregulatory potentials, mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs) have been separately reported as promising therapeutic approaches for refractory RSA attributable to certain immune disorders. However, the cross-talk between MSCs and Tregs at the fetal-maternal interface remains poorly understood. Here we revealed, for the first time, that umbilical MSCs could induce expansion of decidual Foxp3+CD4+ T cells with upregulated production of IL-10 and TGF-β. Meanwhile, MSCs reinforced the immune suppressive functions of decidual Tregs (dTregs). More important, MSCs-instructed dTregs gained enhanced capacity to suppress Th1 and Th17 related inflammatory responses. In vivo data demonstrated that adoptive transfer of MSCs obviously promoted accumulation of Foxp3+ dTregs in lipopolysaccharide (LPS)-induced mice abortion model and spontaneous abortion model (DBA/2-mated female CBA/J mice). Furthermore, MSCs treatment effectively ameliorated absorption rate in both models. This study may offer a new insight for the application of MSCs and Tregs in clinical recurrent miscarriage.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can cause liver diseases in the host, including hepatitis and hepatomegaly. High mobility group box 1 (HMGB1) is the main inflammatory mediator causing cell injury or necrosis. HMGB1 binds to toll like receptor 4 (TLR4), then activates the nuclear factor-κB (NF-κB) signaling pathway, which promotes the release of inflammatory factors. Our previous studies showed that HMGB1 mediated TLR4/NF-κB signaling pathway plays an important role in liver injury induced by T. gondii infection. Resveratrol (RSV) is a small polyphenol, which has anti-inflammatory, anti-cancer, anti-T. gondii effect. However, the effect of RSV on liver injury caused by T. gondii infection is unclear. This study used the RH strain tachyzoites of T. gondii to infect murine liver line, NCTC-1469 cells to establish an in vitro model and acute infection of mice for the in vivo model to explore the protective effect of RSV on liver injury induced by T. gondii infection. The results showed that RSV inhibited the proliferation of T. gondii in the liver, reduced the alanine aminotransferase/aspartate aminotransferase levels and pathological liver damage. Additionally, RSV inhibited the production of tumor necrosis factor-α, inducible nitric oxide synthase and HMGB1 by interfering with the TLR4/NF-κB signaling pathway. These results indicate that RSV can protect liver injury caused by T. gondii infection by intervening in the HMGB1/TLR4/NF-κB signaling pathway. This study will provide a theoretical basis for RSV treatment of T. gondii infection induced liver injury.

Background The role of calcineurin/NFAT signaling in ovarian cancer has been unknown. NFAT was significantly overexpressed in ovarian cancer tissues and that overexpression of NFAT was significantly associated with metastasis and poor prognosis on clinical tissue level. To investigate whether NFAT upstream protein, calcineurin (CN), affects the prognosis in various histological subtype of ovarian cancer (OC). Methods The association between CN and clinical features was analyzed in 50 OC patients treated from 2007 to 2012. CN expression was examined using immunohistochemistry. We observed the association of CN expression with the prognosis in these patients. Results CN expression was significantly increased in later-stage tumor tissue of serous carcinoma compared with those with early-stage. The expression of CN positively correlated with the serum cancer antigen 125 (CA125) level in ovarian clear-cell carcinoma and the serum alpha-fetoprotein (AFP) level in papillary serous cystadenocarcinoma. Particularly, higher CN expression in tumor tissues significantly correlated with reduced overall survival among patients with serous carcinoma. In addition, the serum cancer antigen 72–4 (CA72–4) level, serum carcinoembryonic antigen (CEA) levels, pathological stage, lymph node metastasis, and chemotherapeutic resistance were identified as significant prognostic factors in ovarian clear-cell carcinoma, serous carcinoma, or papillary serous cystadenocarcinoma. Conclusions CN is upregulated in ovarian cancer tissues with later-stage and that the expression of CN, CA72–4, and CEA was remarkably associated with poor prognosis in unique subtype of ovarian cancer. CN levels may be investigated for use as a prognostic biomarker for risk assessment in unique subtype of OC patients. Electronic supplementary material The online version of this article (10.1186/s13048-019-0550-0) contains supplementary material, which is available to authorized users.

Purpose. Angiopoietin-like proteins (Angptls) play critical roles in biological processes, primarily in lipid metabolism. The functional state of the thyroid has a profound influence on metabolism in the human body. Therefore, the aim of this study was to investigate possible changes in serum Angptl3, 4, and 8 levels in hypothyroid patients. Methods. The study included 29 patients with clinical hypothyroidism, 30 patients with subclinical hypothyroidism, and 29 healthy subjects. Baseline clinical indices, including serum thyroid function tests, were recorded and serum Angptl3, 4, and 8 levels were measured across the three groups. Results. Serum Angptl3 and 8 levels were significantly higher in the hypothyroid groups compared to the control group (p < 0.05). There were no differences in Angptl4 levels among the three groups (p > 0.05). Positive correlations were identified between Angptl3 and high-density lipoprotein cholesterol (r = 0.431, p < 0.001), and there was a negative correlation between Angptl3 and total tri-iodothyronine (TT3) (r = -0.220, p = 0.047) and free tri-iodothyronine (r = - 0.279, p = 0.013) levels. Angptl8 was positively correlated with triglyceride (r = 0.267, p = 0.012) and cholesterol levels (r= 0.235, p = 0.028) but was negatively correlated with tri-iodothyronine (r = -0.24, p = 0.031). Furthermore, we used receiver operating characteristic curve analysis to evaluate the diagnostic performance of Angptl3 and 8 in discriminating thyroid dysfunction. The area under curve for detecting thyroid dysfunction based on Angptl3 and Angptl8 was 0.763. Conclusions. Our data show that serum Angptl3 and 8 levels are increased in clinical and subclinical hypothyroid patients and that Angptl3 and 8 may serve as possible biomarkers of hypothyroid disease.

Recently, gestational diabetes mellitus (GDM) exhibits an obvious trend of increase in pregnant mothers and usually causes several abnormities or diseases for the offspring. Although several studies have been reported for potential molecular mechanisms, relevant genes or mutated sites have not been intensively investigated in China.In the present study, 218 pregnant mothers (GDM group: 103 individuals and control group: 115 individuals) in China were enrolled to conduct genome-wide association study (GWAS) and pathway analyses for the purpose of related genes associated with GDM in China.Our results identified 23 SNPs exhibiting closely association with GDM using multiple tests. Annotation of these 23 SNPs identified four genes (The identification of these potential genes associating with GDM enriched the potential molecular mechanisms of GDM in Asia and will provide abundant stocks for subsequent clinical verifications for better understanding the molecular mechanisms, diagnosis, drug development and clinical treatment of GDM.

Supplemental Digital Content is available in the text, Objective: To investigate the association of serum bilirubin level with hearing outcomes in bilateral sudden sensorineural hearing loss (BSSHL) patients. Participants: One hundred thirteen in-patient BSSHL patients were consecutively enrolled between July 2008 and December 2015 in a tertiary center. Main Outcome Measures: Multivariable linear regression, generalized estimating equations (GEE), and stratified analyses were applied to examine the association between serum bilirubin level and hearing outcome measures such as final hearing threshold and absolute and relative hearing gains in BSSHL. Results: After full adjustment for potential confounders, total bilirubin levels (TBIL) were observed to be positively and independently associated with hearing outcomes as measured by final hearing (β [95% confidence interval {CI}]: −1.5 [−2.7, −0.2] dB HL per 1 μmol/L increase in TBIL) and absolute and relative hearing gains (β [95% CI]: 1.4 [0.2, 2.7] dB and 1.6 [0.2, 3.1] dB, respectively) in the severe to profound hearing loss subpopulation. Conclusions: Higher TBIL levels, within the normal or mildly elevated ranges, were independently and significantly associated with better hearing outcome in BSSHL patients with severe to profound hearing loss. Given bilirubin elevation treatments exist, our finding suggests a novel pharmacological strategy for this specific subpopulation.

Background This study aimed to examine hospital performance on evidence-based management strategies for non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and variations across hospitals. Methods Improving Care for Cardiovascular Disease in China (CCC)-ACS project is an ongoing registry and quality improvement project, with 150 tertiary hospitals recruited across China. We examined hospital performance on nine management strategies (Class I Recommendations with A Level of Evidence) based on established guidelines. We also evaluated the proportion of patients receiving defect-free care, which was defined as the care that included all the required management strategies for which the patient was eligible. The hospital-level variations in the performance were examined. Results From 2014 to 2018, 28,170 NSTE-ACS patients were included. Overall, 16% of patients received defect-free care. Higher-performing metrics were statin at discharge (93%), cardiac troponin measurement (92%), dual antiplatelet therapy (DAPT) within 24 hours (90%), and DAPT at discharge (85%). These were followed by metrics of β-blocker at discharge (69%), angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) at discharge (59%), and risk stratification (56%). Lower-performing metrics were smoking cessation counseling (35%) and percutaneous coronary intervention (PCI) within recommended times (33%). The proportion of patients receiving defect-free care substantially varied across hospitals, ranging from 0% to 58% (Median (interquartile range):12% (7%–21%)). There were large variations across hospitals in performance on risk stratification, smoking cessation counseling, PCI within recommended times, ACEI/ARB at discharge and β-blocker at discharge. Conclusions About one in six NSTE-ACS patients received defect-free care, and the performance varied across hospitals.

Hepatocellular carcinoma (HCC) generally occurs in the presence of chronic liver injury, often as a sequela of liver fibrosis. Hepatic progenitor cells (HPCs) are known to be capable of forming both hepatocytes and cholangiocytes in chronic liver injury, which are also considered a source of myofibroblasts and tumor-initiating cells, under carcinogenic circumstances. However, the underlying mechanisms that activate HPCs to give rise to HCC are still unclear. In current study, the correlation between HPCs activation and liver fibrosis and carcinogenesis was investigated in rats and human specimens. We analyzed the role of HPCs in tumorigenesis, by transplanting exogenous HPCs in a diethylnitrosamine-induced rat HCC model. Our data indicated that HPC activation correlated with hepatic fibrosis and hepatocarcinogenesis. We further found that exogenous HPC infusion promoted liver fibrosis and hepatocarcinogenesis, while lipopolysaccharides (LPS) played an important role in this process. However, results of our study indicated that LPS did not induce HPCs to form tumor in nude mice directly. Rather, LPS induced myofibroblast-like morphology in HPCs, which enhanced the tumorigenic potential of HPCs. Further experiments showed that LPS/Toll-like receptor 4 (TLR4) signaling mediated the differentiation of HPCs into myofibroblasts and enhanced the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which led to the aberrant expression of Ras and p53 signaling pathways in HPCs, and finally, promoted the proliferation and malignant transformation of HPCs, by long non-coding RNA regulation. Besides, examination of HCC clinical samples demonstrated that IL-6 and TNF-α production correlated with HPC activation, hepatic fibrosis, and HCC recurrence. Our study indicates that both myofibroblasts and tumor cells are derived from HPCs. HPC-derived myofibroblasts create tumor microenvironment and contribute to the proliferation and malignant transformation of HPCs. Furthermore, LPS present in the chronic liver inflammation microenvironment might play an important role in hepatocarcinogenesis, by regulating the plastic potential of HPCs.

Background: Petrous bone cholesteatoma (PBC) is a rare but local aggressive lesion which can lead to severe complications. Surgery is the mainstay for its treatment. Objectives: To analyse the clinical characteristics and surgical outcomes in a series of patients with PBC, paying special attention to cochlea preservation and use of endoscope. Materials and methods: Retrospective study of 51 patients with PBC who underwent surgery at our centre. Results: Hearing loss (72.5%) and facial paralysis (58.8%) were the two most common symptoms. According to Sanna's classification, supralabyrinthine subtype (51.0%) was the most common subtype, followed by the massive subtype (33.3%). In most patients, PBC was radically removed using subtotal petrosectomy (80.4%). Endoscope was used for assistance in six cases. Various managements of facial nerve were used in different cases. Hearing rehabilitation was not emphasized (44 postoperative dead ear); however, cochlea was preserved as far as possible (45.3%). Recurrence was identified in five patients by MRI with diffusion weighted imaging (DWI) sequence. No recurrence was detected in patients underwent surgery with endoscope assistance. Conclusions and significance: radical excision and functional reconstruction constitute the framework of PBC surgery. Cochlea preservation is critical for possible cochlear implantation in the future. Use of endoscope has the potential to enhance surgical precision and reduce recurrence.