METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

ObjectiveTo establish a population pharmacokinetic （PPK） model of teicoplanin in septic patients from Intensive Care Unit （ICU） and to explore its pharmacokinetic characteristics and related covariates. MethodsThe study included 66 septic patients hospitalized in the department of critical care medicine from November 2017 to February 2020. After intravenous dosing of teicoplanin in septic patients， the trough concentration of teicoplanin was determined by high performance liquid chromatography （HPLC） and the concentration-time data was analyzed by non-linear mixed effect model. The pharmacokinetic parameters and residual errors were evaluated. The influence of covariates on model parameters was tested by forward addition and backward elimination. The predictive performance of the final model was assessed by internal validation. ResultsA two-compartment model best described the teicoplanin concentration-time data. The PPK parameter estimates were central clearance of 0.45 L/min， peripheral clearance of 0.72 L/min， central volume of distribution of 39.74 L and peripheral volume of distribution of 152.41 L. Creatinine， total protein， and lactate were found to significantly affect central clearance of teicoplanin （P<0.05）. ConclusionThe two-compartment PPK model of teicoplanin established in this study could be used for individualized treatment in septic patients from ICU due to its good stability and high predictive accuracy.

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Breast Neoplasms/pathology* ; Drug Resistance ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Treatment Outcome

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective: To understand the harm degree of underground noise and provide basis for noise control. Methods: In November 2019, 13 typical coal mines in Sichuan Province were selected as the research objects, and a total of 1203 sites and 609 jobs of noise exposure were investigated. Results: The noise intensity P75 >80 dB (A) was measured. The noise intensity of the inspection place of the air compressor is >86 dB (A) , the noise intensity of the inspection place of the gas drainage and the operation place of the main fan is between 80-85 dB (A) . Conclusion: Besides the harm of dust, noise exposure should also be paid attention to, and the measures of sound absorption and sound insulation should be taken or personal protection should be strengthened.
Coal ; Coal Mining ; Dust/analysis* ; Noise ; Occupational Exposure

INTRODUCTION: There is paucity of data on the occurrence of cardiovascular events (CVEs) in critically ill patients with sepsis. We aimed to describe the incidence, risk factors and impact on mortality of CVEs in these patients. METHODS: This was a retrospective cohort study of critically ill patients admitted to the medical intensive care unit (ICU) between July 2015 and October 2016. The primary outcome was intra-hospital CVEs, while the secondary outcomes were in-hospital mortality, ICU and hospital length of stay. RESULTS: Patients with sepsis (n=662) had significantly more CVEs compared to those without (52.9% versus 23.0%, P<0.001). Among sepsis patients, 350 (52.9%) had 1 or more CVEs: 59 (8.9%) acute coronary syndrome; 198 (29.9%) type 2 myocardial infarction; 124 (18.7%) incident atrial fibrillation; 76 (11.5%) new or worsening heart failure; 32 (4.8%) cerebrovascular accident; and 33 (5.0%) cardiovascular death. Factors associated with an increased risk of CVEs (adjusted relative risk [95% confidence interval]) included age (1.013 [1.007-1.019]); ethnicity-Malay (1.214 [1.005-1.465]) and Indian (1.240 [1.030-1.494]) when compared to Chinese; and comorbidity of ischaemic heart disease (1.317 [1.137-1.527]). There were 278 patients (79.4%) who developed CVEs within the first week of hospitalisation. Sepsis patients with CVEs had a longer median (interquartile range [IQR]) length of stay in the ICU (6 [3-12] vs 4 [2-9] days, P<0.001), and hospital (21 [10-42] vs 15 [7-30] days, P<0.001) compared to sepsis patients without CVEs. There was no difference in in-hospital mortality between the 2 groups (46.9% vs 45.8%, P=0.792). CONCLUSION CVEs complicate half of the critically ill patients with sepsis, with 79.4% of patients developing CVEs within the first week of hospitalisation, resulting in longer ICU and hospital length of stay.
Cardiovascular Diseases/epidemiology* ; Critical Illness/epidemiology* ; Hospital Mortality ; Humans ; Intensive Care Units ; Length of Stay ; Retrospective Studies ; Risk Factors ; Sepsis/epidemiology*

Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human body networks mechanisms and the clinical applications of melatonin were summarized to provide reference for exploring the focus and direction of further clinical application research.

Objective:To explore the application effect of problem-based learning (PBL) combined with WeChat assisted teaching pattern in teaching rounds of encephalopathy department.Methods:Undergraduate interns of Batch 2018 from the encephalopathy department were enrolled in the study. The observation group ( n=36) was taught by PBL combined with WeChat teaching mode. The control group ( n=36) was taught by the conventional teaching mode. At the end of rotation, the scores of theoretical and practical skills tests of the two groups were compared, and at the same time, the results of the survey were compared according to the questionnaire. SPSS 19.0 was used for statistical analysis of the data. Results:The test scores of the observation group were significantly higher than those of the control group ( P<0.05). The recognition in nine aspects of the observation group was also significantly higher than that of the control group, such as the interaction with the teaching teachers, the effect of improving clinical learning interest and the ability of inspiring thinking and innovation ( P<0.05). There was no significant difference in recognition about improving the efficiency of clinical teaching rounds between two groups ( P>0.05). Conclusion:PBL combined with WeChat teaching rounds model has certain advantages over traditional rounds in TCM clinical teaching, which are mainly manifested in the mastery of clinical knowledge, the communication ability of interns, the ability of interaction and cooperation, the ability of innovation and thinking, and the improvement of learning initiative.

Objective: To compare the therapeutic efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This is a multicenter randomized controlled trial. From March 2017 to July 2019, moderate to severe OSAHS patients from three clinical center in Shanghai who were intolerant to continuous positive airway pressure (CPAP) and with velopharyngeal and glossopharyngeal plane obstruction were enrolled in this study. According to the surgical type, they were 1∶1 randomized to HUPPP plus radiofrequency ablation of tongue base group (Ablation group) or HUPPP plus traction of tongue base group (Traction group). All patients completed over-night standard Polysomnography (PSG), upper-airway assessment (Friedman classification, Müller test, CT and cephalometric examination), preoperative routine examination, Epworth Sleepiness Scale (ESS) and Quebec sleep questionnaire (QSQ). Six to 12 months after operation, all the above-mentioned examinations were repeatedly performed. Changes of aforementioned variables before and after operation were assessed. Results: A total of 43 patients with moderate to severe OSAHS were enrolled in this study. One patient lost to follow-up, the remaining 21 were allocated to Ablation group and 21 were allocated to Traction group. The total therapeutic efficacy of all patients was 69.05% (61.90% in Ablation group and 76.19% in Traction group), but there was no statistical significance between the two groups (P= 0.317). The value of sleep scale score (ESS and QSQ), objective sleep variables (apnea-hypopnea index, oxygen saturation, percentage of time with blood oxygen less than 90% in total sleep time, oxygen desaturation index and micro-arousals) and upper airway cross-sectional area (palatopharyngeal and retrolingual area) of the two groups were improved (P<0.05), but the differences between the two groups were not statistically significant (P>0.05). Conclusion: For moderate to severe OSAHS who had glossopharyngeal plane obstruction, both HUPPP plus radiofrequency ablation of tongue base or HUPPP plus traction of tongue base are effective treatment for OSAHS, and the curative effect is similar. The choice of surgical type could be selected according to patient's or surgical conditions.
China ; Humans ; Oxygen Saturation ; Radiofrequency Ablation ; Sleep Apnea, Obstructive/surgery* ; Tongue/surgery* ; Traction