Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m² group (P_interaction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans ; Male ; Arsenic/urine* ; Creatinine ; East Asian People ; Testosterone/blood* ; Urinalysis ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

【Objective】 To investigate the characteristics of chronic obstructive pulmonary disease related pulmonary hypertension (COPD-PH) patients and determine the correlation between pulmonary hypertension severity and impaired lung function severity. 【Methods】 A total of 565 patients with COPD who underwent echocardiography and estimated pulmonary artery pressure (sPAP) were recruited. According to whether sPAP was greater than 35 mmHg, the patients were divided into non-COPD-PH group (243 cases) and COPD-PH group (322 cases). According to the level of sPAP, COPD-PH patients were subdivided into mild group, moderate group, and severe group. The degree of airflow limitation in patients with COPD was divided into GOLD 1 to 4. We analyzed the general clinical data characteristics of the patients, pulmonary function indexes differences among patients with different severity of COPD-PH, and the correlation between pulmonary artery pressure and pulmonary function indexes. 【Results】 Compared with patients in the non-COPD-PH group, those in the COPD-PH group were older (P=0.001), had a higher brain natriuretic peptide(BNP) level (P<0.001) and D-dimer level (P=0.020), and a lower diffusing capacity of the lung for carbon monoxide (DLco)% predicted (P=0.001). There were significant differences in the artery partial pressure of oxygen (PaO2) (P=0.017) and DLco% predicted (P=0.004) among patients with mild PH, moderate PH, and severe PH. Severe COPD-PH group had lower PaO2 compared with mild-moderate COPD-PH group, and the higher the PH severity classification, the lower the patients’ DLco% predicted. No significant differences were found in lung ventilation function indexes. There was no significant difference in sPAP among GOLD 1 to 4 groups, and distribution of PH severity and COPD airflow limitation severity was not matched. There was a significant negative correlation between sPAP and DLco% predicted, but no significant correlation between sPAP and lung ventilation indexes. 【Conclusion】 Advanced age, BNP and D-dimer can be used as important predictors for PH occurrence in COPD patients. The degree of hemodynamic impairment does not match the degree of airflow limitation, but it is significantly negatively correlated with diffusion function impairment.

The direct acting substances of Cuscuta chinensis in vivo were preliminarily identified through the correlation analysis of "metabolites-effect identification" model. The ovariectomized female rats were i.g administered with 95% ethanol extract part, 40% ethanol elution part and n-butanol extract part of Cuscuta chinensis. The serum fingerprints of different parts and times of administration were established by UPLC/Q-TOF-MS. At the same time, serum estradiol (E₂), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected. Bivariate correlation analysis and grey correlation analysis were used to screen estrogenic components. The results showed that nine direct acting substances in vivo highly related to estrogen effect were found in the drug containing serum, which were hyperoside, astragalin, methyl quercetin glucuronide, quercetin-diglucuronide, quercetin, apigenin, isoquercitrin, kaempferol glucuronide and kaempferol. We can preliminarily screen out the direct acting substance of estrogen effect of Cuscuta chinensis in vivo based on the research idea of serum spectrum effect correlation. It provides a reliable basis for revealing the estrogeneffective substances of Cuscuta chinensis and confirming the quality markers. This experiment was approved by Harbin University of Commerce Ethics Committees (Approval No. HSDU2020-065).

Objective: To determine the prevalence and determinants of folic acid (FA) supplementation in Chinese couples planning for pregnancy and in women during early pregnancy. Methods: This was a cross-sectional study based on the Shanghai PreConception Cohort (SPCC) study. Data on FA supplementation and socio-demographic features were collected using questionnaires. Couples visiting clinics for pre-pregnancy examination and pregnant women at < 14 gestational weeks were recruited in Shanghai, China, between March 2016 and September 2018. Results: Among the pregnancy planners, 42.4% (4,710/11,099) women and 17.1% (1,377/8,045) men used FA supplements, while 93.4% (14,585/15,615) of the pregnant women used FA supplements. FA supplement use was higher in female pregnancy planners who were older ( : 1.13, 95% : 1.08-1.18), had higher education ( : 1.71, 95% : 1.53-1.92), and were residing in urban districts ( : 1.06, 95% : 1.01-1.11) of FA supplementation; female pregnancy planners with alcohol consumption ( : 0.95, 95% : 0.90-0.99) had lower odds of FA supplementation. In early pregnancy, women with higher educational level ( : 1.04, 95% : 1.03-1.06), who underwent pre-pregnancy examination ( : 1.02, 95% : 1.01-1.03) had higher odds of using an FA supplement; older aged ( : 0.99, 95% : 0.98-0.99), and multigravida ( : 0.97, 95% : 0.96-0.98) had lower odds of FA supplementation. Conclusion Although the majority of pregnant women took FA supplements, more than half of the women planning for pregnancy did not. Urgent strategies are needed to improve pre-conception FA supplementation.
Adult ; China ; Cohort Studies ; Cross-Sectional Studies ; Diet ; Dietary Supplements ; analysis ; Female ; Folic Acid ; administration & dosage ; Humans ; Male ; Pregnancy ; Surveys and Questionnaires ; Vitamin B Complex ; administration & dosage ; Young Adult

Objective:To investigate the rehabilitation resources of community health centers in Shanghai. Methods:December, 2018, all 247 community health centers in 16 districts of Shanghai were investigated with Health Institution Questionnaires, including the number of rehabilitation personnel (physiatrician, physical therapists) and the number of rehabilitation beds, etc. Results:There were 152 physiatrician and 597 physical therapists in community health centers in Shanghai. The numbers of physiatrician and physical therapists per 1000 registered population were 0.01 and 0.04, and were 0.03 and 0.12 for per 1000 registered elderly population. There were 17 484 beds in community health centers, in which the rehabilitation beds were 1425, accounting for 8.15%. Besides, the numbers of rehabilitation beds per 1000 registered population and registered elderly population in Shanghai were 0.10 and 0.30. Conclusion:The development of community-based rehabilitation in Shanghai is unbalanced. There is lack of community-based rehabilitation resources, the supply of service is insufficient, and there is gap between supply and demand. It is suggested to strengthen the support to community-based rehabilitation, and improve the supply of community-based rehabilitation resources.

Objective: To investigate the clinico-pathological characteristics, outcomes and their predictors in malignant hypertension related kidney injury with and without primary glomerular diseases. Methods: Patients with clinical diagnosis of malignant hypertension, biopsy-proven kidney injury caused by malignant hypertension and complete clinical data from January 2010 to December 2018 were retrospectively analyzed. According to clinical and renal pathology, patients were divided into malignant hypertension related kidney injury without primary nephropathy group and with primary nephropathy group. Clinico-pathological characteristics and outcomes were evaluated and compared between malignant hypertension related kidney injury with and without primary glomerular diseases. Results: Totally 31 biopsy-proven kidney injury patients were analyzed. Among them, there were 18 cases with primary glomerular diseases and 13 cases without primary glomerular diseases, with age of (32.5±6.5) years old and (34.7±8.1) years old, respectively. There were 12 males in both group. The proportion of primary IgA nephropathy was higher (16/18) in the group of malignant hypertension related kidney injury with primary glomerular diseases. Malignant hypertension with primary glomerular diseases patients had lower plasma albunin level [(32.7±6.4) g/L vs (38.5±7.3) g/L, P=0.027], higher 24-hour proteinuria level [(4.03±2.71) g vs (1.45±0.98) g, P=0.002] and higher incidence rates of dysmorphic hematuria (14/18 vs 0, P=0.001) than those without primary glomerular diseases patients. Glomerular sclerosis, mesangial proliferation, tubular atrophy and interstitial fibrosis were more severe in malignant hypertension with primary glomerular diseases patients (all P<0.05), but the ischemic wrinkling of glomerular capillary was more severe in malignant hypertension without primary glomerular diseases (P<0.01). There were no differences of acute or chronic malignant hypertensive injury in small artery and in afferent arterioles between the two groups. Cox regression analysis showed that loss of brush-border with flattening of tubular epithelium was the predictor for renal partial recovery (HR=5.956, 95% CI 1.198-29.614, P=0.029). Kaplan-Meier analysis showed that malignant hypertension patients with primary glomerular diseases had shorter renal survival time than those without primary glomerular diseases [(24.1±9.3) months vs (56.6±12.4) months], and accumulative renal survival rate of malignant hypertension patients with primary glomerular diseases was lower than that without primary glomerular diseases (11.6% vs 53.3%, Log-rank χ²=5.022, P=0.025). Multivariate Cox regression analysis showed that severe tubular atrophy and interstitial fibrosis were independent risk factors for end-stage renal disease in malignant hypertension patients (HR=5.870, 95% CI 1.372-25.112, P=0.017). Conclusions Malignant hypertension with primary glomerular diseases patients have more severe clinico-pathological renal impairment and poorer prognosis of long-term renal survival than those without primary glomerular diseases. Acute renal tubular injury (loss of brush-border with flattening of tubular epithelium) is the only predictor of renal function improvement in patients with malignant hypertension and renal impairment within one year. Tubular atrophy/interstitial fibrosis is a risk factor for end-stage renal disease in patients with malignant hypertension. Renal biopsy is an indispensable tool for predicting short-term and long-term renal outcomes.

The aim of this study was to develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties and absolute bioavailability of isoschaftoside in rats. Blood sampling was performed at different time points after intragastric administration of isoschaftoside(1. 5, 3. 0, 6. 0 mg/kg)and 0. 5 mg/kg by intravenous injection. Isoschaftoside was analyzed by a validated LC-MS/MS method in plasma; the pharmacokinetic parameters and absolute bioavailability were evaluated by software DAS 3. 0. The results showed that the linear concentration ranges of isoschaftoside was 1. 0- 500. 0 ng/mL(r=0. 997 6). The precision, accuracy, matrix effect, sensitivity, dilution reliability and stability met the requirements of biological sample analysis. For ig administration of isoschaftoside(1. 5, 3. 0, 6. 0 mg/kg), the pharmacokinetic parameter cmax was(109. 34±22. 87), (259. 84±95. 35)and(499. 26±288. 09)ng/mL; AUC0-t was(310. 57±46. 18), (552. 67±207. 14)and(1 075. 03±371. 19)h ·ng/mL; t1/2 was(2. 36±0. 22), (2. 91±0. 19)and(3. 04±0. 86)h; tmax was(1. 03±0. 25), (1. 18±0. 17)and(1. 5±0. 43)h; MRT0-t was(11. 33±1. 53), (11. 27±1. 09)and(8. 29±0. 76)h, respectively. For iv administration of isoschaftoside(0. 5 mg/kg), the pharmacokinetic parameter AUC0-t was(1 536±421. 3)h ·ng/mL; t1/2 was(2. 57±0. 46)h; MRT0-t was(9. 55±2. 37)h. Furthermore, the absolute bioavailability was 6. 73%, 5. 99%, 5. 80%, respectively. The LC-MS/MS analysis method established in this study was accurate and sensitive, so it can be applied to the pharmacokinetic study of isoschaftoside.

Objective: To investigate the detection of thyroid nodules and related risk factors in nuclear power workers, and to provide scientific evidence for thyroid protection of nuclear power workers. Methods: In December 2018, select 295 workers of a nuclear power production enterprise and 238 administrative staff of it, and select 250 staff members of a thermal power generation enterprise 70 kilometers away from the nuclear power station to conduct thyroid ultrasound examination and questionnaire survey for single factor. Analysis and further multivariate logistic regression analysis were used to study the risk factors of thyroid nodules in the population. Results: Women and smoking history were independent risk factors for the increased incidence of thyroid nodules in the study population; three shifts work pattern was an independent risk factor for the increased prevalence of thyroid nodules in nuclear power workers (P<0.05) , and other factors such as the history of nuclear exposure had no significant correlation with thyroid nodules (P>0.05) . Conclusion Nuclear exposure has little effect on the prevalence of thyroid nodules in nuclear power workers.