Objective To study the therapeutic effect of anisodamine on pulmonary edema after sea-water drowning(PE-SWD). Methods Rat models of PE-SWD were set up by infusing sea-water into rats lungs,and then were randomly divided into PE-SWD model group(M group) and therapeutic group with anisodamine(T group). Blood-gas indexes of arterial blood were measured at 0.5, 1, 2, 4 and 6 hours after infusion. TNF-? levels in the plasma,bronchoalveolar lavage fluid (BALF) and lung tissues were detected by ELISA. At the same time,the dry/wet weight of lung was also measured. Results The levels of blood PaO_2,SO_2 and pH in T group were obviously higher than those in M group 2h after infusion. The dry/wet weight of lung in T group was lower than that in M group. The concentration of TNF-? in plasma, BALF and lung tissues in the both M and T groups significantly higher than that in control group, and reached maximum 1h after infusion. After infusion,the TNF-? contentration in all tested specimens in T group was obviously lower than that in M group. Conclusion There was the therapeutic effect of anisodamine on the pulmonary edema after sea-water drowning possibly by decreasing TNF-? level.

BACKGROUND:In high-intensity exhaustive exercise process, the body must bear the exercise intensity decreasing splanchnic blood flow“ischemia”, at the same time, along with the movement of energy and material consumption, metabolite accumulation and oxidative stress in the body cause pathological damage, leading to a decline in exercise capacity. Thus, what is the impact on kidney filtration barrier? How to adapt to the change of renal tissue? Houttuynia cordata has the functions of heat clearing and detoxifying, dieresis for treating strangurtia, hemostatic, expel ing phlegm to arrest coughing and analgesia, if it has a protective effect on the renal injury caused by acute exhaustive exercise and its mechanism has not been reported in the literature. OBJECTIVE:To explore the effect of acute exhaustive exercise on kidney filtration barrier in rats and the intervention effect of Houttuynia cordata.METHODS:After resting and watching for 3 days, Sprague-Dawley rats received adaptive running for 15 minutes at a speed of 10 m/min on a 0° treadmil . A total of 24 rats, which can finish the running, were selected. They were divided into normal control group, exhaustive exercise group and dosed exhaustive exercise group according to the weight of layer (n=8). Rats in the exhaustive exercise group and dosed exhaustive exercise group on the 10° treadmil received once exhaustive exercise. Dosed exhaustive exercise group received intraperitoneal injection of sodium houttuyfonate 10 mL/kg at 30 minutes before exercises. The normal control group did not do any exercise. RESULTS AND CONCLUSION:Compared with the normal control group, serum urea nitrogen, serum creatinine, urine protein content, malondialdehyde concentration, renal cellapoptosis and apoptosis index were significantly increased, but nitric oxide content and nitric oxide synthase activity in the renal tissue were significantly deceased in the exhaustive exercise group (P<0.05 or 0.01). Glomerular filtration epithelial cells, the kidney filtration barrier of basement membrane and podocyte damage were obvious, showing abundant cellapoptosis, occasional y necrosis. Compared with the exhaustive exercise group, urine protein content, serum creatinine, malondialdehyde concentration, renal cellapoptosis and apoptosis index were significantly reduced, but nitric oxide content and nitric oxide synthase activity were significantly increased in the dosed exhaustive exercise group (P<0.05). No obvious pathological changes were detected, but apoptosis was visible. These findings confirmed that houttuynine made a reduction in renal cellinjury induced by exhaustive exercise and possibly significantly reduced apoptosis, increased nitric oxide synthase content, decreased malonaldehyde, and apparently increased superoxide dismutase activity, and final y protected injured renal tissue induced by exhaustive exercise.

ObjectiveTo investigate the morning blood pressure surge(MBPS) and its relationship with 24-hour blood pressure variability and anti-hypertensive drugs in middle-aged and elderly hypertensive patients.Methods A total of 521 middle-age and elderly men were surveyed with ambulatory blood pressure monitoring and ambulatory electrocardiograms recordings as well as questionnaire investigation from January 2009 to December 2010.Subjects were divided into MBPS positive group and MBPS negative group according to the level of MBPS[ ＞35 mm Hg (1 mm Hg=0.133 kPa) or ≤35 mm Hg].ResultsIn all the cases,the prevalence of MBPS was 19.4％,of which the elderly and very elderly had higher prevalences ( 18.9％ and 21.8％,respectively) than the middle-aged (5.6％,both P ＜0.01 ).Significant differences could be found in age [ ( 81.6 ± 6.4 ) years vs ( 78.7 ± 9.7 ) years ],day mean systolic blood pressure [ ( 132.8 ± 13.3) mm Hg vs ( 128.8 ±13.3) mm Hg],fasting blood glucose [ (5.96 ± 1.59) mmol/L vs (5.68 ± 1.22) mmol/L] and 24-hour blood pressure variability between the two groups ( all P ＜ 0.05 ).Significant difference could be observed in the prevalence of MBPS between the diuretics-taking group and non-taking group (27.4％ vs 17.6％,P ＜0.05 ).ConclusionsThe elderly hypertensive patients are prone to appear MBPS phenomenon.Fasting blood glucose level,24-hour blood pressure variability may be associated with MBPS.Diuretic antihypertensive treatment may not be conductive for MBPS control.

Objective To finding out the characters of vascular remolding after the establishment of native arteriovenous fistula on the wrist,and exploring the influential factors.Methods Doppler ultrasound was used to monitor the diameter of cephalic vein,brachial artery,radial artery and ulnar artery at the time before the surgery and one day,one week,two weeks,four weeks and eight weeks after the surgery respectively.The tendency of the diameter change was analyzed.Results Twenty eight patients completed the whole monitor session,in which eleven were female.The average age of those patients was (53.68 ± 2.61) years old.Twelve of them were diabetic nephropathy.The diameters of all vessel were increased more rapidly at the first day than any other days after surgery(all P ＜ 0.01).The patients were divided into two groups depending on whether diabetic nephropathy.No significant difference was found between the two groups on the tendency of diameter change in cephalic vein and brachial artery (all P ＞ 0.05).However,the tendency of diameter change in radial artery and ulnar artery was statistically significant difference between the two groups (all P ＜ 0.05).Conclusions Cephalic vein,brachial artery,radial artery and ulnar artery are all apparently dilated on the first day after the surgery.The vascular dilation and diameter increasing become much slower after the period,the diameter tend to be stable.The primary diseases may affect the tendency of the diameter change in radial artery as well as ulnar artery.

Objective To study the value and effectiveness of surgical management and mapping in supratentorial tumoral complicated with epilepsy and to study the correlations between tumor and the epileptogenic focus.Methods The clinical data of 121 patients with supratentorial cerebral tumor but epilepsy as initial symptom were retrospectively analyzed for the incidence of pre-and postoperative epileptic seizures,including grade Ⅰ glioma in 1 5 cases and grade Ⅱ glioma in 35 cases,grade Ⅲ-Ⅳglioma in 12 cases,menigoma in 32 cases,metastases in 10 cases,cavernous angiomas in 15 cases,and ependymomas in 2 cases.Results Surgery based on CT/MRI,seizure type and EEG changes was conducted.There was no death in operation.The highest incidence was in frontal lobe and the lowest in occipital lobe.Correlations between localization of tumor and the epileptogenic focus:there were 50 cases in the same location,near or beside tumors in 28 cases,far separate apart(＞2 cm)from tumors in 25 cases,no relationship was found in 18 cases.103 patients were followed up for one to nine years.31 patients had a few seizures in the early postoperative period.Epileptic seizures were cured without anti-epilepsy drugs in 83 cases.Conclusion There are some differences between tumors'location and epileptogenic focus in supratentorial tumoral epilepsy.The location and size of epileptogenic zone should be detected before and during operation.The resection of the tumor combined with the resection of the epileptogenic zone"epilepsy surgery"can provide good results.

Objective:To investigate the role of LncRNA-TUG1 in the injury of intestinal epithelial cells induced by lipopolysaccharide (LPS).Methods:LPS was used to treat HIEC-6 human intestinal epithelial cells for 24 h to construct a sepsis injury model. Whole transcriptome RNA sequencing was used to analyze the expression changes of mRNA, microRNA and lncRNA in HIEC-6 cells after LPS treatment. Real-time fluorescence quantitative (qRT-PCR) and Western blot was performed to detect the expression changes of lncRNA-TUG1, microRNA-132-3p (miR-132-3p), SIRT1 mRNA and SIRT1 protein in HIEC-6 cells after LPS treatment. The expression levels of LncRNA-TUG1, miR-132-3p and SIRT1 were artificially changed by in vitro transfection. qRT-PCR and Western blot were used to confirm the regulatory effect of lncRNA-TUG1 on microRNA-132-3p and SIRT1. CCK-8 and flow cytometry were used to analyze the effects of LncRNA-TUG1, miR-132-3p and SIRT1 on the proliferation and apoptosis of HIEC-6 cells. The dual luciferase report analysis was used to verify the targeting relationship between LncRNA-TUG1, miR-132-3p and SIRT1. Statistical analysis was performed using SPSS 17.0, and differences between the two groups were compared using independent sample t test. Results:RNA sequencing results showed that the expressions of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells after LPS treatment ( t=3.26, P<0.05 and t=2.55, P<0.05), but the expression of miR-132-3p was increased ( t=4.12, P<0.05). In vitro cell experiments, the expression of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells treated with LPS ( t=5.69, P<0.05 and t=5.712, P<0.05), while the expression of miR-132-3p was increased ( t=3.88, P<0.05). Overexpression of lncRNA-TUG1 increased the proliferation rate ( t=6.55, P<0.05) and decreased the apoptosis rate ( t=3.94, P<0.05) of LPS-treated cells. Upregulation of lncRNA-TUG1 decreased the expression of miR-132-3p ( t=4.66, P<0.05), and increased the mRNA and protein levels of SIRT1 ( t=3.91, P<0.05). Transfection of miR-132-3P mimic could inhibit the mRNA ( t=4.08, P<0.05) and protein levels of SIRT1. In LPS-treated cells, the cells co-transfected with miR-132-3pmimic and siRNA-SIRT1 had a lower proliferation rate ( t=4.55, P<0.05 and t=5.67, P<0.05) and a higher apoptosis rate ( t=3.90, P<0.05 and t=4.22, P<0.05) than those transfected with only pcDNA3.1-lncRNA-TUG. Conclusions:lncRNA-TUG1 may act as a ceRNA to regulate miR-132-3p/SIRT1, therefore alleviating HIEC-6 cell injury caused by LPS. Intervention of lncRNA-TUG1/miR-132-3p/SIRT1 regulatory pathway may become a potential strategy to prevent sepsis-induced intestinal mucosal damage.

Objective:To investigate the changes in the expression of toll like receptor 4 (TLR4), pentamerin-3 (PTX3) and Apelin in the blood of patients with sepsis and their relationship with the condition and prognosis.Methods:From March 2015 to March 2020, 82 patients with sepsis in the First People′s Hospital of Chenzou were retrospectively selected, including 22 patients in septic shock group, 34 patients in severe sepsis group and 26 patients in general sepsis group. 82 healthy people in the same period were selected as the control group. The expression of serum TLR4, PTX3, Apelin, Sequential Organ Dysfunction Score (SOFA), Acute Physiology and Chronic Health Score System Ⅱ (APACHE Ⅱ) were measured and compared. The relationship between the expression of serum TLR4, PTX3 and Apelin and the scores of SOFA and APACHE Ⅱ in patients with sepsis were analyzed. The general data and the expression of serum TLR4, PTX3 and Apelin in patients with sepsis with different prognosis (28 day survival and death) were counted. The influencing factors of prognosis in patients with sepsis were observed, and the predictive significance of serum TLR4, PTX3 and Apelin on the prognosis of patients with sepsis was analyzed.Results:Comparison of serum TLR4, PTX3 and Apelin level in the groups: septic shock group>severe sepsis group>general sepsis group>control group ( P<0.05); The serum level of TLR4, PTX3 and Apelin in patients with high SOFA and APACHE Ⅱ scores were higher than those in patients with low SOFA and APACHE Ⅱ scores ( P<0.05); Pearson correlation showed that serum level of TLR4, PTX3 and Apelin was positively correlated with the SOFA and APACHE Ⅱ scores of sepsis patients ( P<0.05); The levels of serum TLR4, PTX3, Apelin and the scores of SOFA and APACHE Ⅱ in the dead patients with sepsis were higher than those in survival patients ( P<0.05); Logistic regression analysis found that serum level of TLR4, PTX3, Apelin, SOFA score, and APACHE Ⅱ score were all important risk factors for 28 day death of sepsis patients ( P<0.05); The receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of combined blood indexes (TLR4, PTX3 and Apelin) in predicting the prognosis of patients with sepsis were 85.71% and 85.25%. Conclusions:The expression of serum TLR4, PTX3 and Apelin in patients with sepsis can be significantly increased, which is related to the patient′s condition and prognosis and can provide a certain basis for clinical diagnosis and treatment.

Protein aggregation is a critical issue in the production of biopharmaceuticals. During protein production, transport and storage, various factors can lead to protein aggregation. With the in-depth study, different ways of protein aggregation and various influencing factors were identified. This includes physical and chemical factors, translation modifications and protein structure. Since protein aggregation exerts major impact on the activity and homogeneity of proteins, it is of great importance to study the ways of protein aggregation and how to control it to obtain high-quality proteins. The review focuses on three ways of protein aggregation, namely 3D domain swapping, salt bridge formation, and oxidative stress, as well as methods to control protein aggregation during protein production, transport and storage. This may facilitate reducing the loss caused by the formation of protein aggregation and improving the purity and homogeneity of protein in research and commercial production.
Protein Aggregates ; Proteins/chemistry* ; Oxidative Stress

Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.

Objective: To identify the definition of heat wave based on mortality risk assessment in different regions of China. Methods: Daily mortality (from China Information System for Disease Control and Prevention) and meteorological data (from National Meteorological Information Center in China) from 66 counties with a population of over 200 000 were collected from 2006-2011. With the consideration of climate type and administrative division, China was classified as seven regions. Firstly, distributed lag non-linear model (DLNM) was used to estimate community-specific effects of temperature on non-accidental mortality. Secondly, a multivariate meta-analysis was applied to pool the estimates of community-specific effects to explore the region-specific temperature threshold and the duration for definition of heat wave. Results: We defined regional heat wave of Northeast, North, Northwest, East, Central and Southwest China as being two or more consecutive days with daily mean temperature higher than or equal to the P₆₄, P₇₁, P₈₅, P₆₇, P₇₅ and P₇₇ of warm season (May to October) temperature, respectively, while the thresholds of temperature were 21.6, 23.7, 24.3, 25.7, 28.0 and 25.3 ℃. The heat wave in South China was defined as five or more consecutive days with daily mean temperature higher than or equal to the P₉₃ (30.4 ℃) of warm season (May to October) temperature. Conclusion The region-specific definition of heat wave developed in our study may provide local government with the guidance of establishment and implementation of early heat-health response systems to address the negative health outcomes due to heat wave.