Fluorosis is widely prevalent worldwide, and China is one of the countries with a high incidence of endemic fluorosis. In recent years, study on non skeletal damage caused by fluorosis, especially cardiovascular system damage, has gradually increased. Fluoride can cause cardio vascular arteriosclerosis, hypertension and other diseases, while cardiovascular disease have hidden and acute onset, and the mortality rate has increased year by year in recent years. At present, the mechanism of cardiovascular diseases caused by fluoride is not yet clear, and further clarification is needed. This article provides an overview of the effects of fluoride on cardiovascular diseases from three aspect: epidemiological investigation, animals experiment, and in vitro cell experiment. It categorizes and analyzes the pathogenesis, providing new ideas for the study of cardiovascular system damage caused by fluorosis.

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Objective: To investigate the effects of combined exposure to black carbon and lead on the expression of cell adhesion molecules and their regulating microRNAs (miRNAs) in the rat choroid plexus epithelial Z310 cells. Methods: i) Z310 cells were randomly divided into control group, black carbon exposure group, lead exposure group and combined exposure group. The lead exposure group and black carbon exposure group were treated with 10 μmol/L lead acetate and 10 mg/L black carbon, respectively, and the combined exposure group was treated with both in the above doses. After 12.0 hours, the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) in Z310 cells was detected by Western blotting. The expression of miR-326, miR-328-3p and miR-542-3p which regulated ICAM-1 was detected by real-time fluorescent quantitative polymerase chain reaction. ii) Z310 cells or Z310 cells transfected with miRNA-326 mimic were randomly divided into control group, miRNA-326 transfection control group, combined exposure group and miRNA-326 transfection combined exposure group. Cells in the two control groups were not treated. The two combined exposure groups were treated with 10 mg/L black carbon and 10 μmol/L lead acetate for 12.0 hours. The expression of ICAM-1 was detected by Western blotting. Results: i) The relative expression of ICAM-1, VCAM-1 and MAdCAM-1 in the cells of black carbon exposure group and ICAM-1 in the lead exposure group was higher than those in the control group (all P<0.05). The relative expression of ICAM-1 and MAdCAM-1 in the combined exposure group was higher than those in the other three groups (all P<0.05). The relative expression of VCAM-1 in cells of combined exposure group was higher than those in the control group and lead exposed group (all P<0.05). The relative expression of miR-326 in cells of the lead exposure group and black carbon exposure group was lower than those in the control group (all P<0.05). The relative expression of miR-326 in the combined exposure group was lower than that in the other three groups (all P<0.05). There was no significant difference between miR-328-3p and miR-542-3p in the four groups (all P>0.05). ii) The relative expression of ICAM-1 in cells of the miR-326 transfection control group cells was lower than that in the control group (P<0.05), while in the cells in the combined exposure and miRNA-326 transfection combined exposure group, it was higher than that in the control and miRNA-326 transfection control groups (all P<0.05), and lower in the miRNA-326 transfection combined exposure group than in the combined exposure group (P<0.05). Conclusion: Black carbon or lead exposure can upregulate the expression of ICAM-1, VCAM-1 and MAdCAM-1 in Z310 cells. Black carbon and lead combined exposure lead to a synergistic effect on upregulation of ICAM-1 and MAdCAM-1 expression, particularly ICAM-1. The combined exposure of black carbon and lead may upregulate the expression of ICAM-1 by downregulating the expression of miR-326.

Objective:To investigate the current situation of informatization construction and application of operating rooms in hospitals in Sichuan Province.Methods:Stratified sampling method was used to investigate the informatization of operating rooms in 254 hospitals above the second level in 20 regions of Sichuan Province from September to October 2021. Self-designed questionnaire was used to carry out information management in 3 dimensions, including general information, patient care in operating room, medical consumables and equipment, with a total of 32 items.Results:66.5% (169/254) of hospitals used operating room information management system for management. In terms of the application of information technology in operation management, preoperative visits accounted for 15.4% (39/254) , surgical nursing documents accounted for 57.5% (146/254) , surgical pathological specimens accounted for 10.6% (27/254) , and surgical patient transportation and handover accounted for 12.2% (31/254) . 36.6% (93/254) of hospitals implemented information management of consumables, 21.3% (54/254) of hospitals implemented equipment information management, 28.7% (73/254) of hospitals used surgical instrument traceability management systems, 17.2% (44/254) of hospitals used operating room behavior management systems, 24.8% (63/254) of hospitals built a remote video education and broadcasting system and 11.8% (30/254) of hospitals built a telemedicine service system.Conclusions:In the construction of hospital informatization and intelligent promotion, the informatization construction of operating room in this investigation area has made progress, but the development and deepening degree of business informatization management needs to be further strengthened.

Objective:To investigate the relationship of pks gene islands with virulence genes, capsular serotypes and biofilm formation in Klebsiella pneumoniae ( Kp). Methods:A total of 113 Kp clinical isolates were collected in the First Affiliated Hospital of Fujian Medical University and divided into two groups based on the presence of pks gene islands: pks+ and pks- groups. The hypermucoviscous (HM) phenotype was detected by string test. Five virulence genes ( peg-344, rmpA, rmpA2, iucA, iroB) and six common capsular serotypes (K1, K2, K5, K20, K54, K57) were detected by polymerase chain reaction (PCR). The biofilm formation ability was measured by crystal violet staining. Results:Among the 113 Kp isolates, 46 were pks+ strains and 67 were pks- strains. The detection rate of HM phenotype was higher in the pks+ group than in the pks- group [87.0% (40/46) vs 43.3% (29/67)]. The detection rates of virulence genes ( peg-344, rmpA, rmpA2, iucA, iroB) and K1 serotype in the pks+ group were also higher than those in the pks- group ( P<0.05). The biofilm formation ability of the pks+ strains was higher than the pks- strains ( P<0.05). Conclusions:Kp strains carrying pks gene islands were likely to display a HM phenotype and mainly belonged to the K1 serotype. Most of the pks+Kp strains carried the virulence genes of peg-344, rmpA, rmpA2, iucA and iroB, and had a greater ability to form biofilms.

Objective: “Food addiction” may be one of the drivers of the obesity epidemic. Bariatric surgery-induced weight loss can significantly alleviate food addiction in overweight or obese people. Appetite regulation is part of the feedback control system for energy balance. The purpose of this study was to investigate the effects of mobile application-based dietary intervention on weight-loss and food addiction in overweight and obese adults. Methods: A total of 101 overweight or obese people aged over 18 years, who were admitted to the obese multidisciplinary clinic of Ningbo First Hospital from August 2015 to January 2018 were enrolled. All subjects received health education and dietary guidance, and submitted their diet log through the weight management application of their smartphone. Over 12 weeks, a dietitian guided and corrected the subjects who did not meet the diet standards. Interviews, physical examinations, laboratory tests, and the Yale Food Addiction Scale Questionnaire survey were administered before and after the intervention (12 weeks) comparing subjects’ weight, food addiction symptom count, and the proportion of food addiction before and after intervention. Statistical analysis of body composition measurements, blood biochemical parameters, and symptom count scores was performed using paired data t-test, McNemar chi-square test, and Fisher’s exact test. Results: A total of 101 overweight and obese subjects were enrolled, including 31 males and 70 females, with an average age of (30.4±7.3) years, mean body mass index of (32.76±4.46) kg/m², and average body weight of (89.95±17.12) kg. The proportion of food addiction was 26.73%. After 12 weeks of dietary intervention with the mobile application, the number of people with food addiction decreased from 27 to 14, the proportion of food addiction decreased by 12.87%, the proportion of symptom counts ≥3 decreased from 41.58% to 19.80%.（χ²=5.17， 11.26, all P <0.01), and the symptom count decreased from 2.25 ±1.61 to 1.50±1.31 (t=3.64, P<0.001). Simultaneously, body weight, BMI, and waist circumference decreased by (6.54±1.03) kg, (2.35±0.36) kg/m², and (6.50±0.86) cm (t=6.36, 5.62 and 3.78, all P<0.001), respectively, compared with those before the intervention. Metabolic indicators such as fasting glucose, insulin resistance index, and LDL-C cholesterol also significantly improved, with a decrease of (0.38±0.10) mmol/L, 1.83±0.46, (0.22±0.75) mmol/L (t=3.67, 3.59, 2.97, all P<0.01). Conclusion The smartphone application-based dietary intervention can effectively improve blood glucose and lipid levels in overweight and obese people, reduce visceral fat accumulation and reduce insulin resistance, and improve the food addiction status of overweight and obese people.

Objective: To explore the association of the glycosylated hemoglobin (HbA1c) level at admission with 90 days functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: Patients admitted to the Department of Neurology, Tongji Hospital from January to December 2017 were prospectively and continuously enrolled in this study. Clinical data were collected at admission and functional outcomes 90 days after ICH were assessed by using the modified RANKIN scale. Univariate and multivariate conditional logistic regression models were constructed. Patients were divided into four groups according to the quartile of HbA1c values. The median value of HbA1c in each group was taken as the substitute value and P for trend was calculated. The logistic regression model was fitted by restricted cubic splines to investigate the association between HbA1c level and outcome of ICH. Results: A total of 345 patients with ICH were enrolled, including 214 with favorable outcomes and 131 with poor outcomes (99 severe disability cases and 32 deaths). The risk of poor 90 days outcomes was significantly associated with HbA1c level at admission indicated by multivariate logistic regression analysis, and the P for trend test was <0.001 (middle-level group vs. low-level group: OR=2.33, 95%CI: 1.07-5.07; high-level group vs. low-level group: OR=2.52, 95%CI: 1.12-5.64; extremely high-level group vs. low-level group: OR=6.80, 95%CI: 3.01-15.34). Results from the restricted cubic spline showed that there was a linear correlation between HbA1c level at admission and poor 90 days outcomes of ICH (χ²=14.81, P<0.001; non- linear test: P=0.118). Compared with patients with HbA1c level of 6.5%, the risk of poor outcomes in patients with HbA1c level of <6.5% decreased linearly with the decrease in HbA1c level at admission, and the risk in patients with HbA1c level >6.5% was higher but not significantly. Conclusion There was correlation between high HbA1c level at admission and 90 days poor outcome of ICH. High HbA1c level is an independent prediction indicator for ICH.

Objective To investigate neurological function, volume of cerebral infarction, changes of lipid peroxidation, and the intervention effect of compound angelica injection (CAI) on rats with focal cerebral ischemia injury. Methods Models of rat with cerebral ischemia were reproduced by middle cerebral artery occlusion (MCAO). All animals were randomly divided into sham-operation group, model group, CAI group, and edaravone group. 1 hour after the models were established, rats in the sham-operation group and model group received intraperitoneal injection with normal saline, while rats in CAI group and edaravone group received intraperitoneal injection with relevant medicine for continuing 7 days. Volume of cerebral infarction was detected by Tetrazole staining method, neurologic function were detected by neuroethology, and concentration of MDA in brain tissue was also detected. Results After 7-day cerebral ischemia, compared with the model group, volume of cerebral infarction in CAI group was significantly reduced (P<0.05), and the concentration of MDA was a little lower. Conclusion CAI has significant protective effects which can significantly improve neurological function, reduce volume of cerebral infarction, and alleviate the effects of lipid peroxidation of rats with focal cerebral ischemia injury.

OBJECTIVETo investigate the effects of lead exposure on the copper concentration in the brain and serum and the expression of copper transporters in the choroid plexus among rats.

METHODSSixty specific pathogen-free Sprague-Dawley rats were randomly divided into a control group and three lead-exposed groups, with 8 mice in each group. The lead-exposed groups were orally administrated with 500 (low-dose group)), 1 000 (middle-dose group), and 2 000 mg/L (high-dose group) lead acetate in drinking water for eight weeks. And the rats in control group were given 2 000 mg/L sodium acetate in drinking water. The content of lead and copper in the serum, hippocampus, cortex, choroid plexus, bones, and cerebrospinal fluid (CSF) was determined by inductively coupled plasma-mass spectrometry (ICP-MS). Confocal and real-time PCR methods were applied to measure the expression of copper transporters including copper transporter 1 (Ctr1), antioxidant protein 1 (ATX1), and Cu ATPase (ATP7A).

RESULTSCompared with the control group, the lead-exposed groups showed significantly higher lead concentrations in the serum, cortex, hippocampus, choroid plexus, CSF, and bones (P < 0.05) and significantly higher copper concentrations in the CSF, choroid plexus, serum, and hippocampus (P < 0.05). Confocal images showed that Ctr1 protein was expressed in the cytoplasm and cell membrane of choroid plexus in control group. However, Ctr1 migrated to CSF surface microvilli after lead exposure. Ctr1 fluorescence intensity gradually increased with increasing dose of lead, except that the middle-dose group had a higher Ctr1 fluorescence intensity than the high-dose group. In addition, the middle- and high-dose groups showed a lower ATX1 fluorescence intensity compared with the control group. Real-time PCR data indicated that the three lead-exposed groups showed significantly higher mRNA levels of Ctr1 and ATP7A compared with the control group (P < 0.05).

CONCLUSIONCopper homeostasis in the choroid plexus is affected by lead exposure to induce copper homeostasis disorders in brain tissue, which may be one of the mechanisms of lead neurotoxicity.

Adenosine Triphosphatases ; Animals ; Brain ; Cation Transport Proteins ; drug effects ; Choroid Plexus ; drug effects ; metabolism ; Copper ; metabolism ; Homeostasis ; Organometallic Compounds ; toxicity ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effect of Buyang Huanwu Decoction on blood-brain barrier of focal cerebral ischemia rats, and explore the mechanism of the decoction. Methods The model of focal cerebral ischemia was made by thread embolism method. SD rats were divided randomly into sham-operated group, model group and Buyang Huanwu Decoction group. Buyang Huanwu Decoction group was given Buyang Huanwu Decoction by gavage, the sham-operated group and model group were given normal saline of the same quantity 24 h after modeling. The nervous function deficit scores was evaluated, brain tissues and serum were taken from the rats after treating for seven days, infarct volume was detected by TTC staining, and pathological changes of microvessel were observed microscopically in HE stained sections. And the protein level of MMP-9, MMP-2, VEGF in brain tissue and the serum levels of vWF in serum of every groups were measured by ELISA. Results Compared with model group, Buyang Huanwu Decoction significantly improved the neurological behavior performance, decreased the cerebral infarct volume, alleviated the pathological changes and decreased the protein level of MMP-9, MMP-2, VEGF, vWF. Conclusion Buyang Huanwu Decoction has the protective effect on blood-brain barrier in the model rats of focal cerebral ischemia. The mechanism may be related with restrainning the expression of MMP-9, MMP-2, VEGF, vWF.