Mechanism of Linggui Zhugantang in Promoting Astrocyte Endocytosis and Degradation of Amyloid β / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Linggui Zhugantang （LGZGT）-containing serum on primary astrocytes （AS） induced by β amyloid 1-42 （Aβ1-42） in a rat model of Alzheimer's disease （AD） and explore the phagocytic and degradative effects of LGZGT on Aβ. MethodAn AD model was established by inducing AS with Aβ1-42. The cells were divided into normal group， model group， LGZGT low-， medium-， and high-dose （LGZGT-L， LGZGT-M， and LGZGT-H） groups， and donepezil hydrochloride group. The model group was treated with Aβ1-42 at a final concentration of 10 μmol∙L-1. The LGZGT-L， LGZGT-M， and LGZGT-H groups were treated with 10% serum containing LGZGT on the basis of the model group. Cell viability was assessed using a cell counting kit-8 （CCK-8）， lactate dehydrogenase （LDH） activity was measured using an LDH assay kit， and cell morphology was observed using an inverted microscope. The expression of Aβ-related degradation enzymes insulin-degrading enzyme （IDE） and cathepsin D （CTSD） was detected using Western blot， and the fluorescence intensity of cathepsin B （CTSB） was measured using immunofluorescence. The content of Aβ1-42 in cells was determined using an enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the normal group， the viability of AS in all groups decreased， and Aβ1-42 at different concentrations had inhibitory effects on AS proliferation. After administration， compared with the normal group， the cell survival rate of the model group decreased significantly （P<0.05）. Compared with the model group， the cell survival rates of the LGZGT-H group and donepezil hydrochloride group increased significantly （P<0.05）. The LDH activity of cells in the model group was significantly increased compared with that in the normal group （P<0.05）， and cell bodies were swollen and enlarged with increased protrusions and elongation， suggesting more obvious cell damage. Compared with the model group， the LDH activity of cells in the donepezil hydrochloride， LGZGT-L， LGZGT-M， and LGZGT-H groups decreased significantly （P<0.05）. After administration， the cell swelling in the LGZGT-M， LGZGT-H， and donepezil hydrochloride groups improved， cell protrusions shortened， and cell clustering decreased. Compared with the normal group， the expression of IDE and CTSD in the model group decreased significantly （P<0.05）. Compared with the model group， the expression of IDE increased significantly in the LGZGT-M and LGZGT-H groups （P<0.05）. Compared with the model group， the expression of CTSD increased significantly in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups （P<0.05）. The average fluorescence intensity of CTSB in the model group was significantly lower than that in the normal group （P<0.05）. Compared with the model group， the average fluorescence intensity of CTSD in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups increased significantly （P<0.05）. The intracellular content of Aβ1-42 in cells in the model group was significantly higher than that in the normal group （P<0.05）. After administration， compared with the model group， the intracellular content of Aβ1-42 in cells in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups decreased significantly （P<0.05）， and LGZGT-containing serum reduced Aβ1-42 in a dose-dependent manner （P<0.05）. ConclusionLGZGT has a protective effect on Aβ1-42-induced AS and can promote the degradation of Aβ. Its mechanism may be related to reducing Aβ toxicity， enhancing cell viability， promoting the expression of IDE， CTSD， and CTSB， and restoring lysosomal function.

Value of serum chitinase-3-like protein 1 in predicting the risk of decompensation events in patients with liver cirrhosis / 临床肝胆病杂志

Objective To investigate the value of serum chitinase-3-like protein 1 (CHI3L1) in predicting the risk of decompensation events in patients with liver cirrhosis, since prediction of decompensation events and adoption of active preventive measures are the key to improving the survival time of patients with liver cirrhosis. Methods A case-control study was conducted for 305 patients with liver cirrhosis who were diagnosed and treated in Tianjin Second People's Hospital from January 2019 to May 2021, among whom there were 200 patients with compensated liver cirrhosis and 105 patients with decompensated liver cirrhosis at baseline. According to whether decompensation events occurred within 1 year, the 305 patients with liver cirrhosis were divided into decompensation group with 79 patients and non-decompensation group with 226 patients; according to whether decompensation events occurred for the first time within 1 year, the 200 patients with compensated liver cirrhosis were divided into first-time decompensation group with 43 patients and non-first-time decompensation group with 157 patients. The independent samples t -test or the Mann-Whitney U test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test or the chi-square test was used for comparison of categorical data between groups. The binary logistic regression analysis was used to investigate the association between each variable and decompensation events; the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to investigate the value of each variable in predicting decompensation events, and the maximum value of Youden index was used to determine the optimal cut-off value. Results The patients who experienced decompensation events within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [243.00 (136.00-372.00) ng/mL vs 117.50 (67.75-205.25) ng/mL, U =4720.500, P < 0.001], and the patients who experienced decompensation events for the first time within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [227.98 (110.00-314.00) ng/mL vs 90.00 (58.00-168.50) ng/mL, U =1 681.500, P < 0.001]. Patients with cirrhosis with higher baseline CHI3L1 levels had an increased risk of decompensation events within 1 year ( OR =1.004, 95% CI : 1.002-1.006, P < 0.001); Patients with compensated cirrhosis with higher baseline serum CHI3L1 levels had an increased risk of first decompensated event within 1 year ( OR =1.006, 95% CI : 1.003-1.008, P < 0.001). The baseline serum level of CHI3L1 had an AUC of 0.751 in predicting the risk of first-time decompensation events, with a sensitivity of 90.7% and a specificity of 55.4% at the optimal cut-off value of 95.5 ng/mL. The predictive model based on the combination of serum CHI3L1 level and Child-Pugh class had an AUC of 0.809, with a sensitivity of 72.1% and a specificity of 77.1% at the maximum value of Youden index. Conclusion Serum CHI3L1 level can be used as an effective predictive factor for the risk of first-time decompensation events in patients with compensated liver cirrhosis, and its combination with Child-Pugh class shows a higher predictive value.

The toxic effect of lithium ion on neurons (PC12 cells) and Aß42 molecules.

In this study, the neurotoxicity of Li ion and its effect on the morphologies of Aß42 molecules were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, fluorescence (FL), atomic force microscopy (AFM), and circular dichroism (CD) spectroscopy. MTT assays show that Li ion with a dosage level lower than 50 mg/l did not show detectable cytotoxicity on pheochromocytoma (PC12) cells whereas a dosage level higher than 100 mg/l resulted in significant cytotoxicity. The interaction between Aß42 and Li ion occurs, and the quenching effect of Li ion on the fluorescence emission of AΒ42 is found to be concentration dependent, suggesting that Li ion can bind to the Aß42 molecules. CD results suggest that a more incompact conformation state will be adopted upon the interaction between Aß42 and Li ion. According to AFM images, Li ion could induce the formation of the fibrils after incubation for 3 or 5 days. The formation of the oligomer and fibrils originates from the strong interactions between Aß42 and Li ion. Li ion could accelerate the random coil Aß42 monomers aggregating into the ß-sheet fibrils, which would induce the neurotoxic effect.

Changes in the Consumption of Antibiotics and Resistance Rate of Escherichia coli after Special Rectification as Well as Their Correlation Analysis in Inpaitents of Our Hospital / 中国药房

OBJECTIVE:To provide reference for rational use of antibiotics in clinic.METHODS:The quarterly information about the consumption of antibiotics in inpatients of our hospital during Jan.2012-Dec.2016 were collected from Center for Antibacterial Surveillance.DDDs of various antibiotics and Escherichia coli were analyzed statistically;the detection of E.coli,producing ESBLs and drug resistance during the same period were also analyzed statistically.The correlation between DDDs of antibiotics and resistance rate was investigated by Pearson test.RESULTS:During 2012-2016,DDDs of cephalosporins was the highest in inpatients of our hospital,followed by cephamicins and macrolides.Total DDDs of antibiotics showed a decreasing trend and a slight rebound in 2016.After 2013,DDDs of most antibiotics were basically same to the change of total DDDs.However,DDDs of compound preparations of penicillin and β-lactamase inhibitors,cephalomycm,carbapenems and glycopeptides showed an upward trend.In 2012,DDDs of second-generation cephalosporin was the highest among cephalosporins;since 2013,DDDs of first-generation cephalosporin was the highest in this category.Anti-E.coli drugs included piperacillin sodium and tazobactam sodium,ceftazidime,ceftriaxone,cefepime,cefoxitin,aztreonam,meropenem,gentamicin,levofloxacin.Among anti-E.coli drugs,DDDs of cefatriaxone was the highest in 2012,while that of cefoxitin was the highest in 2016;the consumption of aztreonam decreased most obviously.During 2012-2016,110,132,104,131,243 strains of E.coli were detected in our hospital respectively.The rate of producing ESBLs decreased to 56.6％,57.0％,50.6％,48.4％,45.0％.E.coli was highly resistant to ampicillin,cefazolin,ceftriaxone and compound sulfamethoxazole,while poorly resistant to piperacillin sodium and tazobactam sodium,cefoxitin,imipenem and amikacin.Resistance rate of piperacillin sodium and tazobactam sodium was positively correlated with DDDs of ceftriaxone,aztreonam,gentamicin,levofloxacin,cephalosporins (fast-,third-generation cephalosporins),tetracyclines,quinolones and total DDDs (r were 0.880 to 0.929,P＜0.05).Resistance rate of ceftazidime was positively correlated with DDDs of ceftriaxone,aztreonam,gentamicin,levofloxacin,cephalosporins (fast-,second-,third-generation cephalosporins),tetracyclines,quinolones and total DDDs (r were 0.888 to 0.991,P＜0.05).Resistance rate of cefepime was positively correlated with DDDs of aminoglycosides(r was 0.901,P＜0.05).Resistance rate of gentamicin was negatively correlated with DDDs of compound preparations of penicillin and β-lactamase inhibitors,cefepime (r were-0.914,-0.921,P＜0.05).Resistance rate of imipenem was negatively correlated with DDDs of ceftriaxone,aztreonam,gentamicin,levofloxacin,cephalosporins (fast-,second-,third-generation cephalosporins),aminoglycosides,tetracyclines,quinolones and total DDDs (r were-0.994 to-0.878,P＜0.05).Resistance rates of anti-E.coli drugs were all independent from their DDDs (P＞0.05).The rate of E.coli producing enzyme was positively correlated with resistance rate of gentamicin(r was 0.955,P＜0.05),while was independent from resistance rate or DDDs of other drugs (P＞0.05).CONCLUSIONS:After antibiotics special rectification,total consumption of antibiotics in inpatients of our hospital show a downward trend,and the varieties also change greatly.Although drug resistance is serious,the rate of producing enzyme is decreasing.Antibiotics should be selected carefully according to the monitoring data of bacterial resistance,drug sensitivity test results,the correlation between the consumption of antibiotics and resistance rate so as to reduce the occurrence of bacterial resistance.

Diagnostic value of FibroTest for liver fibrosis in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the diagnostic value of FibroTest (FT) for liver fibrosis in patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>One hundred and forty-two patients with CHB were tested for the following five indicators: alpha2-microglobulin (a2-MG), haptoglobin (Hp), gamma-glutarnyl peptidase (GGT), total bilirubin (TBIL), and apolipoprotein A1 (ApoA1). The resultant data, along with the age and sex of the patients, were put into an algorithm to compute the final results of the FT. During the same period of FT, all of the CHB patients underwent liver stiffness measurement by FibroScan (FS) as well as liver biopsy. Considering the liver biopsy as the gold standard, we determined receiver operating characteristic (ROC) curves at different endpoints. Calculation of the area under the ROC curves (AUROC) was performed to evaluate the diagnostic importance of FT, FS towards the treatment of liver fibrosis in patients with CHB.</p><p><b>RESULTS</b>Significant fibrosis (Scheuer score (S) more than or equal to 2) was predicted with an AUROC for FS, FT of 0.827 (0.753-0.900), 0.897 (0.844-0.949). Significant fibrosis (S more than or equal to 3) was predicted with an AUROC for FS, FT of 0.883 (0.818-0.949), 0.968 (0.932-1.00). Significant fibrosis (S=4) was predicted with an AUROC for FS, FT of 0.943 (0.893-0.993), 0.991 (0.973-1.00).</p><p><b>CONCLUSION</b>s FT is a novel tool that can be used to assess the degree of fibrosis in patients with CHB.</p>

Accumulation of intravenously injected carboxylated single-walled carbon nanotubes in rat axillary lymph nodes / 中国组织工程研究

BACKGROUND:Lymph-targeted tracing and therapy based on carbon nanotubes have been one of the hottest researches on targeting tumor diagnosis and treatment. To evaluate the accumulation of carbon nanotubes in axil ary lymph node can provide experimental evidences for developing nano-tracers and drug carriers which are more lymph-specific and more biocompatible. OBJECTIVE:To study the accumulation of the intravenously injected carboxylated single-wal ed carbon nanotubes in axil ary lymph nodes of Sprague-Dawley rats, and to evaluate their effect on blood cel s. METHODS:Sixty-four Sprague-Dawley rats were randomly divided into two groups. Rats in testing group were injected with carboxylated single-wal ed carbon nanotubes suspension (2 mg/kg), while those in control group were injected with 5%glucose solution (1 mL/kg), both through the tail vein, three times per week. Four periods of 7, 60, 90 and 120 days were set (the 120-day period referred to 90 days of administration fol owed by 30 days of drug withdrawal). At the end of each period, eight rats from each group were randomly picked out, to col ect blood samples via the abdominal aorta for blood routine test. Final y the axil ary lymph nodes were observed, and the lymph node samples of rats in the testing group were col ected and analyzed at 120 days by transmission electron microscope. RESULTS AND CONCLUSION:Compared with the control group, black staining of axil ary lymph nodes of rats in testing group was not obvious at the end of the 7-day period. However, with the increase of the dosing periods, the lymph nodes of the rats in the testing group became enlarged, firm and black stained, coupled with a significant rising in the percentage of blood neutrophils. After 30 days of drug withdrawal, the size of the rat axil ary lymph nodes was reduced and black staining partly faded, with the decreasing of blood neutrophil percentage. Under the transmission electron microscope, abundant carboxylated single-wal ed carbon nanotubes were uptaken by lymphocytes to form a large number of phagocytic vacuoles after drug withdrawal for 30 days. It indicates that the short-term tracing of rat axil ary lymph nodes by carboxylated single-wal ed carbon nanotubes injected through the tail vein is relatively weak, while the long-term intravenous injection can cause their accumulation in rat axil ary lymph nodes, coupled with the increase of neutrophils;after drug withdrawal, the carboxylated single-wal ed carbon nanotubes can be slowly cleared by the lymph nodes.

Mediating effect of hopelessness between depression and suicide risk in junior middle school students / 中华行为医学与脑科学杂志

Objective To explore the relation among depression,hopelessness and suicide risk,as well as the mediating effect of hopelessness between depression and suicide risk.Methods 1 381 students were recruited from five junior middle schools in Linyi by using cluster random sampling.They were investigated with General Situation Questionnaire,Scale for Suicide Ideation(SSI),Beck Hopelessness Scale (BHS) and Beck Depression Iventory (BDI).Results Suicide risk in junior middle school was significant positively correlated with depression and hopelessness (r=0.43 and 0.64 respectively,P＜0.01).Hopelessness partly mediated the relationship between depression and suicide risk (55.8％).Furthermore,hopelessness showed partial mediating effect on the relationship between depression and suicide risk in boys (42.7％) and in 7th Grade students (29.9％),and also complete mediating effect in girls (74.1％) and in 8th Grade students (95.3％).Conclusion The suicide risk in middle school students increase with the increasing of the severity of depression and hopelessness.The hopelessness plays different mediating effects on relation between depression and suicide risk in students with different gender and grade.

Detection of serum endothelial cell specific molecule 1 in gastric cancer patients and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of serum endothelial cell specific molecule 1 (ESM-1) in gastric cancer and to evaluate the effect of serum ESM-1 as a potential serum biomarker.</p><p><b>METHODS</b>Serum ESM-1 was detected by enzyme-linked immunosorbent assay (ELISA) and CEA, CA19.9, CA72.4 were detected by electrochemiluminescence immunoassay (ECLIA) in 102 patients with gastric cancer preoperatively. At the same time, serum ESM-1, CEA, CA19-9, CA72-4 in 41 healthy adults volunteers were detected with the same method. In addition, the follow-up data of all the patients were collected.</p><p><b>RESULTS</b>Compared to healthy volunteers, the serum ESM-1 level in gastric cancer patients increased (P<0.01). The sensitivity and specificity of serum ESM-1 were 73.9% and 51.2% respectively. In contrast, the sensitivities of CEA, CA19-9 and CA72-4 were only 16.1%, 18.3% and 23.2% respectively. High level of serum ESM-1 indicated poor outcomes (P<0.05).</p><p><b>CONCLUSIONS</b>Serum ESM-1 increases in the peripheral blood of the gastric cancer patients. It may be a potential serum marker to help diagnosis and prediction of prognosis of gastric cancer patients.</p>