The disruption of blood-brain barrier induced by long-term arsenic exposure is associated with the increase of MMP-9 and MMP-2: The characteristics are similar to those caused by senescence.

Accumulating evidence suggests that Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) are involved in the neuropathological processes by contributing to breaking the extracellular matrix and the tight junctions that constitute the blood-brain barrier (BBB). However, the influences of arsenic (As) on these two MMPs were inconsistent. In the cross-sectional study of 500 adults, serum MMP-2 and MMP-9 positively correlated with urine arsenic. And the positive correlation between urine tAs and serum MMP-9/2 was found in people older than 59 years. In vivo studies, we found that arsenic exposure or senescence might decrease number of neurons and neuritic density and increase serum and cortical MMP-9/2 levels. Furthermore, arsenic exposure or senescence could disrupt the tight junction of BBB and elevate MMP-9 and MMP-2 expression in the cerebral microvascular endothelium. The MMP-9 and MMP-2 are of particular interest when researching the link between arsenic exposure and nerve damage.

Environment and chronic disease in rural areas of Heilongjiang, China (ECDRAHC).

PURPOSE: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. PARTICIPANTS: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. FINDINGS TO DATE: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m2 in men and 24.65 kg/m2 in women, with >7.3% being obese (>30 kg/m2). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. FUTURE PLANS: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

MiR-140 is involved in T-2 toxin-induced matrix degradation of articular cartilage.

T-2 toxin is one of the most toxic mycotoxins contaminating various grains. It is considered an environmental risk factor for Kashin-Beck disease (KBD), an endemic degenerative osteochondrosis. Currently, the underlying molecular mechanisms of articular cartilage damage caused by T-2 toxin have not been elucidated. Studies have shown that miR-140 is essential for cartilage formation, and extracellular matrix (EMC) synthesis and degradation. The objective of this study was to investigate the mechanism of miR-140 involvement in T-2 toxin-induced articular cartilage damage. Two treatment groups, each containing wild-type mice and miR-140 knockout mice were administered with T-2 toxin (200 ng/g BW/day) or a normal diet for 1 month, 3 months, and 6 months. Results showed that T-2 toxin caused articular cartilage and growth plate damage in mice. The expression of miR-140 decreased in articular cartilage of wild-type mice treated with T-2 toxin, and miR-140 deficiency aggravated T-2 toxin-induced knee cartilage damage. T-2 toxin-caused the reduction of miR-140 expression was consistent with collagen type II (COL2A1), aggrecan (ACAN), and SRY-box containing gene 9 (SOX9) and opposite to matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS-5), and v-ral simian leukemia viral oncogene homolog A (RALA). In addition, we collected finger joints cartilage and knee joints cartilage from KBD patients and controls for paraffin embedding and sectioning. Results found that the expression of miR-140 in the articular cartilage of the KBD group was lower than that of the control group. The expression of COL2A1, ACAN, and SOX9 decreased, whereas ADAMTS-5, MMP13, and RALA increased in the articular cartilage of the KBD group. These results revealed that miR-140 might be involved in T-2 toxin-induced degradation of the ECM of articular cartilage. Moreover, the occurrence of KBD might be related to the decreased expression of miR-140 in articular cartilage.

Evaluation of Risk Factors for Chronic Obstructive Pulmonary Disease in the Middle-Aged and Elderly Rural Population of Northeast China Using Logistic Regression and Principal Component Analysis.

Purpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals. Patients and Methods: A community-based case-control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression. Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index >200 (OR, 1.42; 95% CI, 1.28-1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47-1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92-2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12-4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09-1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02-1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11-1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD. Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.

Prevalence and risk factors for depression among training physicians in China and the United States.

During their first year of medical residency (internship), 35% of training physicians in the United States suffer at least one depression episode. We assessed whether there is a similar increase of depression among first year residents in China, and identified predictors of depression in the two systems. 1006 residents across three cohorts (2016-2017, 2017-2018 and 2018-2019) at Shanghai Jiao Tong University and Peking Union Medical College were assessed in parallel with three cohorts of 7028 residents at 100 + US institutions. The Patient Health Questionnaire-9 (PHQ-9) depressive symptoms were measured at baseline and quarterly. Demographic, personal and residency factors were assessed as potential predictors of PHQ-9 depression scores. Similar to training interns in the US, the proportion of participants in China who met depression criteria at least once during the first year of residency increased substantially, from 9.1 to 35.1%. History of depression and symptoms at baseline were common factors significantly associated with depression during residency. By contrast, neuroticism, early family environment, female gender and not being coupled were associated with depression risk only in the US, while young age was a predictor of depression only in China. Fear of workplace violence also was a predictor in China. Long duty hours and reduced sleep duration emerged as training predictors of depression in both countries. The magnitude of depression increase and work-related drivers of depression were similar between China and the US, suggesting a need for effective system reforms in both systems.

Downregulation of lncRNA NR2F2 Antisense RNA 1 Induces G1 Arrest of Colorectal Cancer Cells by Downregulating Cyclin-Dependent Kinase 6.

AIMS: Long non-coding RNA (lncRNA) NR2F2 antisense RNA 1 (NR2F2-AS1) is an oncogenic lncRNA in lung cancer. This study aimed to investigate the role of NR2F2-AS1 in colorectal cancer (CRC). METHODS: Tissue specimens were obtained from 63 CRC patients, and gene expression was analyzed by qPCR and western blot. Overexpression was performed to analyze gene interactions. A 5-year follow-up was carried out to perform survival analysis. Cell cycle progression and proliferation were analyzed by cell cycle assay and CCK-8 assay, respectively. RESULTS: We found that NR2F2-AS1 and cyclin-dependent kinase 6 (CDK6) were both upregulated in CRC and were positively correlated. NR2F2-AS1 siRNA silencing led to downregulated CDK6 and induced Gap 1 (G1) arrest of CRC cells. CDK6 overexpression rescued G1 arrest caused by NR2F2-AS1 siRNA silencing. High expression levels of NR2F2-AS1 were closely correlated with low overall 5-year survival rate. NR2F2-AS1 siRNA silencing led to decreased rate of CRC cell proliferation. CDK6 overexpression attenuated the effects of NR2F2-AS1 siRNA silencing on cancer cell proliferation. CONCLUSIONS: Downregulation of NR2F2-AS1 induces G1 arrest of CRC cells by downregulating CDK6.

Spindle-like abdominal wall-lifting device in gasless laparoscopic surgery in animal experiments.

INTRODUCTION: CO2 pneumoperitoneum has been used to establish an operation space in laparoscopic surgery. It may have some bad consequences, such as respiratory and circulatory system changes, hypotension and hypoxia in infants and the release of free tumor cells into the abdominal cavity. Gasless laparoscopic technique can avoid these adverse effects. But present gasless laparoscopic techniques have their own disadvantages. The main shortcoming of gasless laparoscopic techniques is inadequate operative space. MATERIAL AND METHODS: We herein describe a new technique. We used a self-designed spindle-like abdominal wall-lifting device to perform gasless laparoscopic cholecystectomy in seven pigs, recording the operation time, bleeding volume and unexpected occurrences during the operation. RESULTS: Seven pigs underwent laparoscopic cholecystectomy using this technique with no conversion to open operation. The operation time was between 21 minutes and 65 minutes, with a mean operative time of 42.5 minutes. The range of bleeding volumes was 2 ml to 8 ml, with a mean operative bleeding volume of 4.3 ml. There were no massive hemorrhages, internal organ injuries or other complications during the operation. CONCLUSIONS: These preliminary outcomes indicate that the spindle-like abdominal wall-lifting device is feasible and safe in gasless laparoscopic cholecystectomy, which can provide sufficient exposure of the operative filed.

[Clinical research of using optimal compliance to determine positive end-expiratory pressure].

OBJECTIVE: To observe the availability and security of optimal compliance strategy to titrate the optimal positive end-expiratory pressure (PEEP), compared with quasi-static pressure-volume curve (P-V curve) traced by low-flow method. METHODS: Fourteen patients received mechanical ventilation with acute respiratory distress syndrome (ARDS) admitted in intensive care unit (ICU) of Tianjin Third Central Hospital from November 2009 to December 2010 were divided into two groups(n = 7). The quasi-static P-V curve method and the optimal compliance titration were used to set the optimal PEEP respectively, repeated 3 times in a row. The optimal PEEP and the consistency of repeated experiments were compared between groups. The hemodynamic parameters, oxygenation index (OI), lung compliance (C), cytokines and pulmonary surfactant-associated protein D (SP-D) concentration in plasma before and 2, 4, and 6 hours after the experiment were observed in each group. RESULTS: (1) There were no significant differences in gender, age and severity of disease between two groups. (2)The optimal PEEP [cm H(2)O, 1 cm H(2)O=0.098 kPa] had no significant difference between quasi-static P-V curve method group and the optimal compliance titration group (11.53 ± 2.07 vs. 10.57 ± 0.87, P>0.05). The consistency of repeated experiments in quasi-static P-V curve method group was poor, the slope of the quasi-static P-V curve in repeated experiments showed downward tendency. The optimal PEEP was increasing in each measure. There was significant difference between the first and the third time (10.00 ± 1.58 vs. 12.80 ± 1.92, P < 0.05). And the optimal compliance titration method had good reproducibility as the optimal PEEP without significant difference in each measure. (3) After the quasi-static P-V curve traced, the heart rate (HR, bpm), temperature (centigrade), interleukin-6 (IL-6, ng/L), tumor necrosis factor-α (TNF-α, ng/L), SP-D (µg/L) showed a gradually increasing tendency, the mean artery pressure (MAP, mm Hg, 1 mm Hg = 0.133 kPa), continuous cardiac index [CCI, L×min(-1)×m(-2)], OI (mm Hg), and C [ml/cm H(2)O] showed a gradually decreased tendency, all of these parameters reached the peak or trough at 6 hours after the experiment, and there was significance compared with those before experiment (HR: 117.34 ± 8.53 vs. 93.71 ± 5.38, temperature: 38.05 ± 0.73 vs. 36.99 ± 1.02, IL-6: 144.84 ± 23.89 vs. 94.73 ± 5.91, TNF-α: 151.46 ± 46.00 vs. 89.86 ± 13.13, SP-D: 33.65 ± 8.66 vs. 16.63 ± 5.61, MAP: 85.47 ± 9.24 vs. 102.43 ± 8.38, CCI: 3.00 ± 0.48 vs. 3.81 ± 0.81, OI: 62.00 ± 21.45 vs. 103.40 ± 37.27, C: 32.10 ± 2.92 vs. 49.57 ± 7.18, all P < 0.05). The results suggested that the drawing of quasi-static P-V curve would aggravate the lung injury. And in optimal compliance titration method group, there were no significant differences in HR, MAP, temperature, CCI, OI, C, cytokines and SP-D before and after titration. CONCLUSION: Optimal compliance titration method has good reproducibility, safety and usability.

[Values of tandem mass spectrometry in etiologic diagnosis of cerebral developmental retardation].

OBJECTIVES: To investigate the values of tandem mass spectrometry (MS/MS) in etiologic diagnosis and understanding therapeutic effect in cerebral developmental retardation, and to help patients in early diagnosis, treatment and favorable prognosis. METHODS: One hundred and fifty-eight childhood patients with brain heteroplasia were tested from July 2004 to October 2006. The blood was collected on filter paper, punched and extracted into methanol solution with stable isotope labeled internal standards, then derivatized with butanolic-HCl. After preparation, the samples were analysed by tandem mass spectrometry. Eleven MS/MS-positive patients were further analyzed based on gas chromatography/mass spectrometry (GC/MS) analysis of urine, clinical course, and treatment outcome. RESULTS: Eleven of 158 patients (7.0%) with inborn metabolic error were confirmed, including five with methylmalonic acidemia, two with propionic acidemia, one with ornithine transcarbamylase deficiency, one with maple syrup urine disease, one with phenylketonuria, and one with biotinidase deficiency. Among them, five were male, six were female, aged from 4 days to 21 months. The clinical manifestations were diverse, including mental developmental retardation or degradation (11 cases), convulsion (5 cases), coma (4 cases), vomiting (4 cases), malnutrition (4 cases), lethargy (3 cases), repeated infection (3 cases), hypotonia (2 cases), etc. Laboratory findings showed metabolic acidosis, hyperammonemia, hyperlactacidemia, anemia, etc. MRI findings of the brain showed cerebral atrophy, a pattern of bilateral T(2)W high signal intensity or/and T(1)W low signal intensity in cerebral white matter and multiple encephalomalacia or vesicular change, ect. In methylmalonic acidemia patients, the early onset with severe acidosis and coma have had a poor prognosis. Improvement was observed in 8 cases after treatment with vitamin B(12), L-carnitine, special milk, low-protein diet or biotin, etc. However 3 MMA patients died. CONCLUSION: MS/MS was helpful for some patients in etiologic diagnosis and understanding therapeutic effect of cerebral developmental retardation. Early diagnosis and appropriate treatment are essential to improve the prognosis and prevent brain damage.

[Analysis of haplotype-based haplotype relative risk and transmission disequilibrium test in childhood absence epilepsy].

OBJECTIVE: Childhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 8% - 15% of all childhood epilepsies. A positive family history of epilepsy, a hereditary factor being one of the pathogeneses, is found in 15% - 44% of children with absence seizures. The phenotype of CAE is specific (including seizure forms and EEG), therefore it is suitable for genetic study. The purpose of this study was to confirm the linkage of childhood absence epilepsy to chromosome 8q24 in China. METHODS: Twenty-nine trios families (a patient and his/her parents) as patient group and 10 normal trios families as control group were investigated for chromosome 8q24 by haplotype analysis with 5 microsatellite DNA markers (D8S554, D8S534, D8S1100, D8S1783, D8S1753). Genomic DNA was isolated from 4 ml human peripheral blood by using the conventional procedure, and then was treated using the PCR method. PCR products were analyzed by gene scan. Statistical methodology included haplotype-based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT). RESULTS: In this study, the polymorphism information content (PIC) of 5 microsatellite DNA markers were: 0.519, 0.828, 0.528, 0.654 and 0.772. HHRR showed D8S554(4) (chi(2) = 5.939, P < 0.05), D8S1100(3) (chi(2) = 5.081, P < 0.05), D8S1783(6) (chi(2) = 4.308, P < 0.05). TDT showed D8S554(4) (chi(2) = 4.46, P < 0.05), D8S1783(6) (chi(2) = 4, P < 0.05). In order to exclude false association results, the authors analyzed every family in detail. Four trios families transmitted allele D8S1783(6) to their offspring, and the same allele hasn't been found in controls. The further work showed that locus D8S1783 had transmission disequilibrium with CAE, the other two loci were a false association. CONCLUSION: (1) Childhood absence epilepsy in the Chinese population may be linked to chromosome 8q24, the CAE gene is transmitted disequilibrium on locus D8S1783. Combined with other research results, we suppose that CAE gene may be in the ECA1 area on chromosome 8q24. (2) The CAE gene perhaps has a genetic heterogeneity in the population of different areas and different races. (3) HHRR and TDT seem to be the best statistical methods to do linkage disequilibrium study in the trios family.