Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome.

BACKGROUND: Cardiovascular disease is a major complication of diabetes mellitus (DM). Type-2 DM (T2DM) is associated with an increased risk of cardiovascular events and mortality, while serum biomarkers may facilitate the prediction of these outcomes. Early differential diagnosis of T2DM complicated with acute coronary syndrome (ACS) plays an important role in controlling disease progression and improving safety. AIM: To investigate the correlation of serum bilirubin and γ-glutamyltranspeptidase (γ-GGT) with major adverse cardiovascular events (MACEs) in T2DM patients with ACS. METHODS: The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively. According to different conditions, they were divided into the T2DM complicated with ACS group (T2DM + ACS, n = 96), simple T2DM group (T2DM, n = 85), and simple ACS group (ACS, n = 90). The clinical data and laboratory indices were compared among the three groups, and the correlations of serum total bilirubin (TBIL) levels and serum γ-GGT levels with other indices were discussed. T2DM + ACS patients received a 90-day follow-up after discharge and were divided into event (n = 15) and nonevent (n = 81) groups according to the occurrence of MACEs; Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients. RESULTS: The T2DM + ACS group showed higher γ-GGT, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (HbA1c) and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups (P < 0.05). Based on univariate analysis, the event and nonevent groups were significantly different in age (t = 3.3612, P = 0.0011), TBIL level (t = 3.0742, P = 0.0028), γ-GGT level (t = 2.6887, P = 0.0085), LDL-C level (t = 2.0816, P = 0.0401), HbA1c level (t = 2.7862, P = 0.0065) and left ventricular ejection fraction (LEVF) levels (t=3.2047, P = 0.0018). Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs, and age and γ-GGT level were risk factors (P < 0.05). CONCLUSION: Serum TBIL levels are decreased and γ-GGT levels are increased in T2DM + ACS patients, and the two indices are significantly negatively correlated. TBIL and γ-GGT are independent influencing factors for MACEs in such patients.

[Health Benefit Evaluation for PM2.5 as Well as O3-8h Pollution Control in Chengdu, China from 2016 to 2020].

Both particulate matter with aerodynamics of less than 2.5 (PM2.5) and ozone are the two main air pollutants in China, which seriously endanger human health. To estimate the adverse impacts of PM2.5 and ozone on human health during the implementation of air pollution prevention and control actions in Chengdu, both the generalized additive model and the nonlinear distribution lag model of epidemiology were adopted to explore the exposure-response relationship coefficients ß of daily ozone 8h maximum concentration average (O3-8h), as well as that of PM2.5 on disease deaths in Chengdu from 2014 to 2016. On this basis, the environmental risk model and environmental value assessment model were both adopted to evaluate the health effects and health benefits in Chengdu from 2016 to 2020, respectively, with the assumption that PM2.5 and O3-8h concentration were reduced to specified air pollution control limits (35 µg·m-3 and 70 µg·m-3, respectively). The results showed 1 the annual concentration of PM2.5 presented gradually decreasing trends in Chengdu from 2016 to 2020. Specifically, ρ(PM2.5) from 63 µg·m-3 in 2016 decreased to 40.92 µg·m-3 in 2020. The average annual decline rate was approximately 9.8%. In contrast, the annual concentration of O3-8h from 155 µg·m-3 in 2016 increased to 169 µg·m-3 in 2020, and the increasing rate was approximately 2.4%. 2 Both PM2.5 and O3-8h had lag effects on three types of disease deaths. Under the maximum lag effect, the corresponding exposure-response relationship coefficients ß of PM2.5were 0.0003600, 0.0005001, and 0.0009237 for all-cause, cardiovascular, and respiratory premature deaths, respectively, whereas the corresponding ß of O3-8h were 0.0003103, 0.0006726, and 0.0007002, respectively. 3 If ρ(PM2.5) was reduced to the national secondary standard limit (35 µg·m-3), the corresponding number of health beneficiaries and economic benefits declined yearly. Specifically, the health beneficiary number of all-cause, cardiovascular, and respiratory disease deaths were reduced from 1128, 416, and 328 in 2016 to 229, 96, and 54 in 2020, respectively. There were a total number of 3314 avoidable premature deaths for all-cause diseases during the five years, resulting in a total health economic benefit of 7.66 billion yuan. 4 If we assume that ρ(O3-8h) was reduced to the concentration limit specified by the World Health Organization (70 µg·m-3), the corresponding number of health beneficiaries and economic benefits were increasing yearly. Specifically, the health beneficiaries' numbers of all-cause, cardiovascular, and respiratory disease deaths rose from 1919, 779, and 606 in 2016 to 2429, 1157, and 635 in 2020, respectively. The annual average growth rates of avoidable all-cause and cardiovascular mortality were 6.85% and 10.72%, respectively, which was higher than the annual average rise rate of ρ(O3-8h). There were 10790 total avoidable deaths from all-cause diseases during the five years, resulting in a total health economic benefit of 26.62 billion yuan. These findings indicate that PM2.5 pollution in Chengdu had been well controlled, whereas O3 pollution had become more severe and had become another key air pollutant threatening human health. Therefore, the synchronous control of PM2.5 and ozone should be implemented in the future.

Exploring value of CT coronary imaging combined with machine-learning methods to predict myocardial ischemia.

PURPOSE: To establish a machine-learning (ML) model based on coronary computed tomography angiography (CTA) images for evaluating myocardial ischemia in patients diagnosed with coronary atherosclerosis. METHODS: This retrospective analysis includes CTA images acquired from 110 patients. Among them, 58 have myocardial ischemia and 52 have normal myocardial blood supply. The patients are divided into training and test datasets with a ratio 7 : 3. Deep learning model-based CQK software is used to automatically segment myocardium on CTA images and extract texture features. Then, seven ML models are constructed to classify between myocardial ischemia and normal myocardial blood supply cases. Predictive performance and stability of the classifiers are determined by receiver operating characteristic curve with cross validation. The optimal ML model is then validated using an independent test dataset. RESULTS: Accuracy and areas under ROC curves (AUC) obtained from the support vector machine with extreme gradient boosting linear method are 0.821 and 0.777, respectively, while accuracy and AUC achieved by the neural network (NN) method are 0.818 and 0.757, respectively. The naive Bayes model yields the highest sensitivity (0.942), and the random forest model yields the highest specificity (0.85). The k-nearest neighbors model yields the lowest accuracy (0.74). Additionally, NN model demonstrates the lowest relative standard deviations (0.16 for accuracy and 0.08 for AUC) indicating the high stability of this model, and its AUC applying to the independent test dataset is 0.72. CONCLUSION: The NN model demonstrates the best performance in predicting myocardial ischemia using radiomics features computed from CTA images, which suggests that this ML model has promising potential in guiding clinical decision-making.

Reduced neutralization of SARS-CoV-2 B.1.617 variant by convalescent and vaccinated sera.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.

MicroRNA-122 as a diagnostic biomarker for hepatocellular carcinoma related to hepatitis C virus: a meta-analysis and systematic review.

OBJECTIVE: MicroRNA-122 (miR-122) has been identified as a biomarker of liver diseases. However, the miR-122 detection accuracy in patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is inconclusive. METHODS: We conducted a systematic literature search of Web of Science, Cochrane Library, PubMed, and Embase to identify studies related to the diagnostic value of miR-122 in HCV-related HCC. We analyzed the results and validated them using data from the Cancer Genome Atlas (TCGA). RESULTS: Six articles were included in this meta-analysis, comprising 354 cases and 420 controls. The pooled specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.87, 0.83, 5.1, 0.16, 32, and 0.92, respectively. Additional sub-group analyses showed that results for plasma were more sensitive than those for serum. In addition, miR-122 was better at distinguishing between HCV-associated HCC and healthy people or those with HCV than between those with HCV-associated HCC and HCV-related cirrhosis. Small samples (≤100) had better diagnostic odds ratios than larger samples (>100). Analysis of data from TCGA confirmed that miRNA-122 had a high diagnostic value. CONCLUSION: This meta-analysis demonstrates that miR-122 may be a useful diagnostic biomarker for HCV-associated HCC.

Characteristics of in peripheral blood of 70 hospitalized patients and 8 diarrhea patients with COVID-19.

Objective: To analyze the blood test indicators of patients after infection of COVID-19 in Chongqing and analyze the clinical indicators of 8 patients with diarrhea. Materials and Methods: From January 26, 2019 to February 13, 2020, 70 patients diagnosed with 2019-nCoV according to the World Health Organization interim guidance for NCP and divided into diarrhea and non-diarrhea groups. The laboratory tests liver and kidney function, blood routine, coagulation function, and immune status. Results: The study population included 70 hospitalized patients with confirmed CONV-2019. NCP patients (43males and 27 females) with a mean age of 48.57±17.80 (9~82) years and only 4.3% of patients have lung-related diseases. The positive rate of ESR, CRP, PT, IL6, lymphocyte count, GGT, Prealbumin and CD4 was more than 50%. We further analyzed the differences between 8 diarrhea patients and 62 non-diarrhea patients. Among these indicators, only Lymphocyte, CRP, Prealbumin and Cystatin C positive rate is more than 50%. Although there is no statistical difference in GGT, 100% of the 7 patients tested decreased. Conclusion: Our data recommended that the ESR, CRP, PT, IL6, lymphocyte count, GGT, prealbumin and CD4 have important value in the diagnosis of COVID-19, and the decrease of GGT may be an important indicator for judging the intestinal dysfunction of patients.

Characterization of trehalose-6-phosphate phosphatase in trehalose biosynthesis, asexual development, stress resistance and virulence of an insect mycopathogen.

Biological control potential of entomopathogenic fungi depending on conidiation capacity, conidial stress tolerance and virulence can be improved through genetic engineering. To explore a possible role of trehalose biosynthesis pathway in improving fungal pest-control potential, we characterized biological functions of trehalose-6-phosphate phosphatase (BbTPP) in Beauveria bassiana, an insect mycopathogen that serves as a main source of fungal insecticides. Deletion of BbTPP resulted in abolished trehalose biosynthesis, reduced conidiation capacity, decreases in conidial thermotolerance and UV-B resistance, increased hyphal sensitivities to chemical stresses, and attenuated virulence. By contrast, over-expression of BbTPP led to increased trehalose accumulation, decreased T6P accumulation, and enhanced stress tolerance and virulence despite little impact on growth and conidiation under normal conditions. These results indicate that BbTPP serves as not only a key player in control of trehalose biosynthesis required for multiple cellular functions but also a potential candidate to be exploited for genetic improvement of fungal potential against insect pests.

[Study of the Role and Mechanism of Asprosin/Spartin Pathway in Cardiac Microvascular Endothelial Injury Induced by Diabete Mellitus].

OBJECTIVE: To detect the effects and mechanism of asprosin (Asp) and spartin on the injury of mice cardiac microvascular endothelial cells (CMECs) induced by high glucose. METHODS: The cultured CMECs were divided into 2 groups, one group is normal group (5.5 mmol/L glucose in the medium) and another is HG group (30 mmol/L glucose in the medium). Real-time PCR (qRT-PCR) and Western blot were respectively used to detect the mRNA level of spastic paraplegia 20 (SPG20) and protein expression of spartin in CMECs. Upregulation or downregulation of the expression of spartin was achieved via transfection with adenovirus (Ad) or small interfering RNA (siRNA) respectively. CMECs with downregulation of spartin expression were firstly treated with anti-oxidant N-acetylcysteine (NAC) or Asp respectively for 48 h, and then were interfered with 30 mmol/L glucose for 24 h afterward. The apoptosis of cell was detected by flow cytometry. Nitric oxide (NO) production was detected by NO probe and ELISA kit. The intracellular reactive oxygen species (ROS) levels were tested by DHE staining and ELISA kit. Type 2 diabetic model mice were established and then divided into T2DM group and T2DM+Asp group. After the model mice were established successfully (random blood glucose was more than 16.7 mmol/L), Asp (1 µg/g) was intraperitoneally injected once a day. After 2 weeks, mice echocardiography was performed to test cardiac diastolic function. The integrity of the microvascular endothelium was observed by scanning electron microscopy. RESULTS: Compared with the normal group, the mRNA level of SPG20 and protein expression of spartin in mice CMECs of HG group were significantly reduced (P < 0.05). Under the condition of high glucose, Ad transfection induced significant decrease of the intracellular ROS level and the apoptosis level of the CMECs (P < 0.05), while NO increased after Ad transfection. In contrast, siRNA intervention resulted in opposite effect. In addition, the antioxidant NAC partly reversed the above changes caused by downregulating spartin. Asp upregulated the level of SPG20 mRNA and spartin protein expression in CMECs, reduced ROS production, reduced apoptosis and increased NO production. However, intervention effects of Asp, such as decreasing of ROS production, inhibiting apoptosis of CMECs and increasing of NO production, were partly reversed in spartin downregulated cells. In vivo, we found that Asp can improve cardiac function and increase the integrity and smoothness of cardiac microvascular endothelium in type 2 diabetic mice. CONCLUSION: Asp can inhibit oxidative stress in mice CMECs through upregulating spartin signaling pathway, thereby alleviating the damage of microvascular endothelium in diabetic heart.

Low-voltage electrical cell lysis using a microfluidic device.

Cell lysis, where cellular material is released, is the basis for the separation and purification of cell contents, biochemical analysis, and other related experiments. It is also a key step in molecular, real-time, and cancer diagnoses as well as in the drug screening of pathogens. The current methods of lysing cells have several limitations, such as damage to the activity of cellular components, the need for a large number of cell samples, time-consuming processes, and the danger of high voltage. Therefore, a simple, fast, and efficient method for the manipulation of micro-volume cells or for single cell lysis is significant for further scientific research and practical application. In this study, a new low-voltage controllable method for cell lysis was established, and a corresponding microfluidic chip was developed. Simple, efficient and rapid micro-volume cells and single cell lysis were successfully achieved under a low-voltage alternating current with a voltage of 16 Vp-p and frequency of 10 kHz. The lysis process was investigated in detail by separately labelling the whole cell, cytoplasm, and nucleus using fluorescent proteins, which indicated that the whole cell was completely lysed. Analysis of voltage and frequency effects revealed that a higher voltage and optimized frequency enhanced the cell lysis efficiency. The presented study provides a new strategy for the lysis of micro-volume cells or a single cell, which is valuable for on-chip real-time diagnostics and point of care (POC) applications.

Efficacy of single-stage and two-stage Fowler-Stephens laparoscopic orchidopexy in the treatment of intraabdominal high testis.

BACKGROUND/OBJECTIVE: To compare the curative effect of single-stage and two-stage Fowler-Stephens (F-S) laparoscopic orchidopexy for intraabdominal high testis and explore the appropriate surgical approach. METHODS: We performed a prospective analysis of the clinical data of 28 patients who underwent F-S laparoscopic orchidopexy for intraabdominal high testis in our department from May 2012 to April 2015, including 15 cases of the single-stage F-S operation and 13 cases of the two-stage F-S operation. By comparing the two groups preoperative and postoperative (6 months) clinical data of testicular position, testicular volume, and sex hormone levels [testosterone (T), follicle stimulating hormone (FSH), and estradiol (E2)], we analyzed the difference in efficacy between the two procedures. RESULTS: Twenty-eight patients completed laparoscopic surgery, no case was converted, and no testis was excised. All patients were followed up for 9-25 months after the operation, with an average follow-up of 16.2 months. The postoperative testicular volume of the single-stage and two-stage F-S groups was not significantly reduced (p>0.05). In both groups, the postoperative T levels were significantly increased compared to the preoperative levels (p<0.05), while the FSH and E2 levels were significantly decreased (p<0.05). The differences in testicular volume and T, FSH, and E2 levels between the two surgical procedures were not significant (p>0.05). In the single-stage F-S group, the testes were located in the scrotum in 13 cases and retracted to the lower groin in two cases. In the two-stage F-S group, the testes were located in the scrotum in 12 cases and retracted to the lower groin in one case. The difference in postoperative testicular position between the two groups was not significant (p>0.05). CONCLUSION: In the case of testis with good collateral circulation, single-stage F-S laparoscopic orchidopexy had the same safety and efficacy as the two-stage F-S procedure. Surgical options should be based on comprehensive consideration of intraoperative testicular location, testicular ischemia test, and collateral circumstances surrounding the testes. Under the appropriate conditions, we propose single-stage F-S laparoscopic orchidopexy be preferred. It may be appropriate to avoid unnecessary application of the two-stage procedure that has a higher cost and causes more pain for patients.

Biofilms of vaginal Lactobacillus in vitro test.

This paper focuses on biofilms of Lactobacillus spp. - a type of normal flora isolated from healthy human vaginas of women of childbearing age; thereupon, it broadens the research scope of investigation of vaginal normal flora. The static slide culture method was adopted to foster biofilms, marked by specific fluorescence staining. Laser scanning confocal and scanning electron microscopy were used to observe the microstructure of the biofilms. Photographs taken from the microstructure were analysed to calculate the density of the biofilms. The body of Lactobacillus spp., though red, turned yellow when interacting with the green extracellular polysaccharides. The structure of the biofilm and aquaporin within the biofilm were imaged. Lactobacillus density increases over time. This study provides convincing evidence that Lactobacillus can form biofilms and grow over time in vitro. This finding establishes an important and necessary condition for selecting proper strains for the pharmaceutics of vaginal ecology.

Ribociclib: new antitumor drug of cyclindependent kinase 4/6 inhibitor / 药物评价研究

Ribociclib is an oral small molecule cyclindependent kinase 4/6 inhibitor,which inhibits tumor progression by inhibiting the conversion of tumor cells from G1 phase to S phase.The combination ofribociclib and letrozole was approved in the United States on March 13,2017 as a treatment for HR+/HER2-advanced and metastatic breast cancer patients.Clinical results showed that the drug on advanced and metastatic tumors had a significant inhibitory effect and could extend the survival of patients without deterioration compared with using letrozole alone.The incidence of adverse drug reactions is higher,but the tolerance is better.This article focuses on pharmacodynamics,pharmacokinetic,clinical results and adverse effects of this drug.

Exposure to vanadium promotes primary cultured rat microglial inflammation and migration / 中国比较医学杂志

Objective To observe the changes of rat microglial inflammation and migration after exposure to sodium metavanadate(NaVO3·2H2O), and to analyze the possible mechanisms of vanadium neurotoxicity. Methods Primary cultured rat microglial cells were incubated with NaVO3·2H2 O. Morphological changes and the Iba1 expression of microglia were tested by immunofluorescence assay. iNOS, Cox-2, ERK and p-ERK protein expressions were determined by western blotting. The levels of TNF-α and IL-1β in the culture medium were tested by enzyme-linked immunosorbent assay. The migration of microglia was tested by immunofluorescence staining using wound-healing assay. Results Microglia changed from resting state with ramous shape to round shape in activated state after NaVO3·2H2 O exposure, and the expression of Iba1 increased obviously. The protein expressions of iNOS and COX-2 increased significantly compared with the control. The levels of TNF-αand IL-1βwere also increased significantly. NaVO3·2H2 O promotes the migration of microglia through ERK pathway. Conclusions Exposure to NaVO3·2H2 O promotes primary cultured rat microglial inflammation and migration. These results suggest that the inflammatory reaction of microglia may be one of the possible mechanisms of neurotoxicity caused by vanadium exposure.

Exposure to vanadium promotes primary cultured rat microglial inflammation and migration / 中国比较医学杂志

Objective To observe the changes of rat microglial inflammation and migration after exposure to sodium metavanadate(NaVO3·2H2O), and to analyze the possible mechanisms of vanadium neurotoxicity. Methods Primary cultured rat microglial cells were incubated with NaVO3·2H2 O. Morphological changes and the Iba1 expression of microglia were tested by immunofluorescence assay. iNOS, Cox-2, ERK and p-ERK protein expressions were determined by western blotting. The levels of TNF-α and IL-1β in the culture medium were tested by enzyme-linked immunosorbent assay. The migration of microglia was tested by immunofluorescence staining using wound-healing assay. Results Microglia changed from resting state with ramous shape to round shape in activated state after NaVO3·2H2 O exposure, and the expression of Iba1 increased obviously. The protein expressions of iNOS and COX-2 increased significantly compared with the control. The levels of TNF-αand IL-1βwere also increased significantly. NaVO3·2H2 O promotes the migration of microglia through ERK pathway. Conclusions Exposure to NaVO3·2H2 O promotes primary cultured rat microglial inflammation and migration. These results suggest that the inflammatory reaction of microglia may be one of the possible mechanisms of neurotoxicity caused by vanadium exposure.

[Research on genetic stability to American ginseng introduced into China for 30 years].

To study the genetic stability of Panax quinquefolium after introduced into China for 30 years, the samples of P. quinquefolium from 14 regions of China were studied. RAPD molecular marker technology was applied in this research, and POPGEN32 data analysis and NTSYS2. 10 cluster diagram were used to analyze the data. The results showed that there are abundant genetic diversity in the ginseng samples. There were 81 polymorphic bands based on the 13 random primers. The polymorphism was 83.51%, the effective number of alleles (N(e)) was 1.456 7; Nei's gene diversity index (H) was 0.274 8; Shannon's diversity index (H(o)) was 0.419 4. The clustering analyses indicated that P. quinquefolium and P. ginseng were classified into two obvious groups, especially, it was also found that the P. quinquefolium could be divided into two obvious groups based on whether the P. ginseng was cultivated in the same region or not, but it was thought that there was not genetically a qualitative difference. Thus it suggests that a good breeding field should be established in Jilin Province of China for the germplasm purification.

[Effects of PreS2 synthetic peptides on infiltrating T lymphocyte subgroups expression in hepatocellular carcinoma].

OBJECTIVES: To explore whether PreS2 can change the percentage of T lymphocyte subgroups and the ration of CD4+/CD8+ in hepatocellular carcinoma (HCC) caused by HBV. METHODS: The P120-146 region composed by the way of Merrifield, which was the most intensive antigen in PreS2 peptides, served as the antigen after dissolved in 0.01 mol/L PBS. 12 patients were chosed as the subjects, who were pathologically diagnosed as HCC after operation, were HBsAg-, HBeAg-, anti-HBc, and HBV DNA positive in serum, and expressed HBsAg in HCC tissue. The monocytes were isolated and cultured in 96 microplate with 1x 10(6) cells in every well, then the PreS2 synthetic peptides was added in at the doses of 1microg, 5microg, and 10microg, also IL-2 with 500 U was added in. Seven days later, the percentage of CD3+, CD4+, CD8+, and the ratio of CD4+/CD8+ were detected. RESULTS: It was found that the percentage of CD4+ increased significantly (t = 3.508, P < 0.01), and the ratio of CD4+/CD8+ decreasedly obviously (t = 2.235, P < 0.05) in the 5microg PreS2 synthetic peptides group, compared with those in the control group. The percentage of CD3+ rised markedly in the IL-2 group, compared with that in the control group. CONCLUSION: With proper doses, PreS2 is capable of changing the expression of T lymphocyte subgroups in HCC tissue, increasing the percentage of CD4+ obviously and changing the motionless state of CD8+, to make the carcinoma cell killed through the action of CD4+ and CD8+.