Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China.

AIM: This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients. METHODS: Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies-vaccination without screening, screening-based vaccination, and no vaccination-among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties. RESULTS: It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. CONCLUSIONS: The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.

Spatiotemporal heterogeneity and long-term impact of meteorological, environmental, and socio-economic factors on scrub typhus in China from 2006 to 2018.

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.

Impact of outdoor air pollution on the incidence of pertussis in China: a time-series study.

BACKGROUND: The increasing number of pertussis cases worldwide over the past two decades has challenged healthcare workers, and the role of environmental factors and climate change cannot be ignored. The incidence of pertussis has increased dramatically in mainland China since 2015, developing into a serious public health problem. The association of meteorological factors on pertussis has attracted attention, but few studies have examined the impact of air pollutants on this respiratory disease. METHODS: In this study, we analyzed the relationship between outdoor air pollution and the pertussis incidence. The study period was from January 2013 to December 2018, and monthly air pollutant data and the monthly incidence of patients in 31 provinces of China were collected. Distributed lag nonlinear model (DLNM) analysis was used to estimate the associations between six air pollutants and monthly pertussis incidence in China. RESULTS: We found a correlation between elevated pertussis incidence and short-term high monthly CO2 and O3 exposure, with a 10 µg/m3 increase in NO2 and O3 being significantly associated with increased pertussis incidence, with RR values of 1.78 (95% CI: 1.29-2.46) and 1.51 (95% CI: 1.16-1.97) at a lag of 0 months, respectively. Moreover, PM2.5 and SO2 also played key roles in the risk of pertussis surged. These associations remain significant after adjusting for long-term trend, seasonality and collinearity. CONCLUSIONS: Overall, these data reinforce the evidence of a link between incidence and climate identified in regional and local studies. These findings also further support the hypothesis that air pollution is responsible for the global resurgence of pertussis. Based on this we suggest that public health workers should be encouraged to consider the risks of the environment when focusing on pertussis prevention and control.

Development and Validation of a Novel Model for Predicting Coronary Heart Disease in Snoring Hypertensive Patients with Hyperhomocysteinemia.

Hypertensive patients with snoring and elevated plasma homocysteine levels are common. When these factors are combined, the risk of coronary heart disease (CHD) is high. Herein, we developed and validated an easy-to-use nomogram to predict high-risk CHD in snoring hypertensive patients with elevated plasma homocysteine.Snoring patients (n = 1,962) with hyperhomocysteinemia and hypertension were divided into training (n = 1,373, 70%) and validation (n = 589, 30%) sets. We extracted CHD predictors using multivariate Cox regression analysis, then constructed a nomogram model. Internal validation using 1,000 bootstrap resampling was performed to assess the consistency and discrimination of the predictive model using the area under the receiver operating characteristic curve (AUC) and calibration plots.We constructed a nomogram model with the extracted predictors, including age, waist-height ratio, smoking, and low-density lipoprotein cholesterol levels. The AUCs of the training and validation cohorts at 80 months were 0.735 (95% CI: 0.678-0.792) and 0.646 (95% CI: 0.547-0.746), respectively. The consistency between the observed CHD survival and the probability of CHD survival in the training and validation sets was acceptable based on the calibration plots. A total of more than 151 points in the nomogram can be used in the identification of high-risk patients for CHD among snoring hypertensive patients with elevated plasma homocysteine.We developed a CHD risk prediction model for snoring hypertension patients with hyperhomocysteinemia. Our findings provide a useful clinical tool for the rapid identification of high-risk CHD at an early stage.

Screening rate and influential factors of lung cancer with low-dose computed tomography in Asian population: a systematic review and meta-analysis.

BACKGROUND: There are currently no studies synthesizing the screening rate and influential factors of low-dose computed tomography (LDCT)-screened lung cancer in Asian population. METHODS: A systematic review was conducted, using both English and Chinese language databases on March, 2019. The pooled screening rate and estimated odds ratios (ORs) of influential factors were analyzed using random effects models. Subgroup and meta-regression analyses were also employed to explore the heterogeneity. RESULTS: The pooled LDCT lung cancer screening rate was 1.12% (95% confidence interval (CI): 0.94%, 1.32%), and increased with age. Adenocarcinoma and stage I lung cancer had higher screening rates. Analysis of influential factors in the general population showed that female and elder age (≥50 years) were significantly influencing LDCT lung cancer screening rate (for female, OR = 1.32, 95% CI: 1.15-1.52; for adults ≥ 50 years, OR = 1.94, 95% CI: 1.52-2.49). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the sample size, risk population and source of population. CONCLUSIONS: Unlike European and American populations, female and adults > 50 years rather than smoking adults were positively associated with screening rate in Asian populations. It is important to further study the benefits of lung cancer screening with LDCT in Asian populations.

Influencing factors of lung cancer in nonsmoking women: systematic review and meta-analysis.

BACKGROUND: Epidemiological studies have shown that some factors other than smoking may affect the risk of lung cancer in women, but the results are controversial. We conducted a meta-analysis to summarize the influencing factors of lung cancer in nonsmoking women. METHODS: Both English and Chinese databases were searched for publications from 1990 to 2020. All included studies were assessed according to the Newcastle-Ottawa Scale (NOS). The pooled odds ratios (ORs) and 95% confidence interval (CI) of influential factors were analyzed using the meta-analysis method, and the publication bias and sensitivity were analyzed. RESULTS: Among the five categories, the pooled OR of cooking factors category was the highest. Among 42 influencing factors, there were frequent fried food (OR = 2.42, 95% CI: 1.73-3.38) and long menstrual cycle (0.54, 95% CI: 0.39-0.75). A positive association of history of lung diseases/family lung/all cancer with lung cancer among Asian nonsmoking women (1.82, 95% CI: 1.60-2.07). Unlike other regions, cooking factors were the main risk factor for lung cancer in Asian. CONCLUSION: The meta-analysis suggests that cooking habits, diet, passive smoking, history of cancer and lung disease, and female reproduction are related to lung cancer in nonsmoking women. However, additional studies are warranted to extend this finding.

Higher prevalence of metabolic disorders in patients with bilateral primary aldosteronism than unilateral primary aldosteronism.

OBJECTIVE: Metabolic syndrome (MetS) is a frequent clinical condition in hypertension patients and is more frequently reported in primary aldosteronism (PA). This study is aimed at investigating the prevalence of MetS and its components in the two major types of patients with adrenal venous sampling (AVS)-confirmed unilateral PA and bilateral PA. DESIGN AND PATIENTS: This was a retrospective cross-section study. We analysed metabolic parameters from 169 PA patients subtyped by AVS, including 85 unilateral PA patients and 84 bilateral PA patients, and we also included 169 non-PA patients matched for age and sex. RESULTS: Patients with unilateral PA had higher concentrations of aldosterone and lower serum potassium than patients with bilateral PA. However, patients with bilateral PA had higher prevalence of MetS (79.8% vs 64.7%, P = .029), obesity (40.5% vs 24.7%, P = .029), dyslipidemia (72.6% vs 55.3%, P = .019) and hyperglycaemia (29.8% vs 16.5%, P = .040) than those with unilateral PA. Meanwhile, bilateral PA had higher BMI (27.55 ± 4.58 vs 25.57 ± 3.28 kg/m2 , P = .001), waist circumference (98.54 ± 11.44 vs 93.32 ± 10.64 cm, P = .003) and fasting plasma glucose (4.98 ± 1.16 vs 4.64 ± 0.93 mmol/L, P = .034). The logistic regression analysis also showed that bilateral PA was associated with the presence of MetS after adjustment for age, sex and duration of hypertension. CONCLUSIONS: Patients with bilateral PA have a higher prevalence of MetS than those with unilateral PA, despite unilateral PA patients exhibiting higher concentrations of aldosterone and lower serum potassium, suggesting that unilateral PA and bilateral PA may have differing mechanisms of MetS.

Distribution characteristics of circulating homocysteine and folate and related factors in agriculture, stock-raising and urban populations: a cross-sectional survey.

OBJECTIVE: To investigate homocysteine (Hcy) and folate levels, prevalence of hyperhomocysteinaemia (HHcy) and folate deficiency, which are affected by lifestyles in urban, agricultural and stock-raising populations. DESIGN: This is a cross-sectional study. SETTING: Urban, agricultural and stock-raising regions in Emin, China. PARTICIPANTS: Totally 1926 subjects - 885 (45·9 %) from urban, 861 (44·7 %) from agricultural and 180 (9·4 %) from stock-raising regions - were obtained using multistage stratified random sampling. Inclusion criteria encompassed inhabitants aged ≥15 years who resided at the current address for ≥6 months and agreed to participate in the study. Surveys on health behaviour questionnaires and physical examinations were conducted and blood samples collected. RESULTS: The folate level of subjects from the stock-raising region was the lowest, followed by those from the agricultural region, and the highest in those from the urban region (3·48 v. 6·50 v. 7·12 ng/ml, P < 0·001), whereas mean Hcy showed no significant difference across regions. The OR for HHcy in stock-raising regions was 1·90 (95 % CI 1·11, 3·27) compared with the urban region after adjusting for all possible covariates. The OR for folate deficiency in stock-raising and agriculture regions was 11·51 (95 % CI 7·09, 18·67) and 1·91 (95 % CI 1·30, 2·82), respectively, compared with the urban region after adjusting for all possible covariates. CONCLUSIONS: HHcy and folate deficiency are highly prevalent in stock-raisers, which is of important reference for HHcy control in Xinjiang, with a possibility of extension to others with approximate lifestyles.

Comparison between Whatman FTA Elute Cards and Conventional Swab for the Detection of Pathogenic Enteric Bacteria Using an RT-qPCR Assay.

The emergence of outbreaks of foodborne illness is closely associated with food contamination caused by various enteric pathogens, such as Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica serovar Enteritidis, and Staphylococcus aureus. The control of enteric pathogens poses a challenge due to the fact that these pathogens can persist for a long period of time in the environment. The rapid detection of pathogenic organisms plays a crucial role in the prevention and identification of crises related to health, safety, and well-being. Improper sample handling and processing may influence the diagnostic efficacy and accuracy. The aim of the present study was to compare the preservation capacity for enteric bacteria between Whatman Flinders Technology Associates (FTA) cards and swabs for reverse transcription-quantitative PCR (RT-qPCR) detection. It was found that Whatman FTA cards exhibited an improved preservation capacity for five types (both laboratory and environmental strains) of enteric bacteria, including Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica serovar Enteritidis, and Staphylococcus aureus for RT-qPCR detection. Hence, Whatman FTA cards may be a suitable tool for the routine isolation of foodborne bacteria for molecular diagnosis. Therefore, the use of Whatman FTA cards for sample collection and preservation may increase sensitivity and accuracy for bacteria isolation and diagnosis.

Interventions in Live Poultry Markets for the Control of Avian Influenza: A Systematic Review and Meta-analysis.

BACKGROUND: This review aimed to provide constructive suggestions for the control and management of avian influenza through quantitative and qualitative evaluation of the impact of different live poultry market (LPM) interventions. METHODS: Both English and Chinese language databases were searched for articles that were published on or before 9 November 2018. After extraction and assessment of the included literature, Stata14.0 was applied to perform a meta-analysis to explore the impacts of LPM interventions. RESULTS: A total of 19 studies were identified. In total, 224 human, 3550 poultry, and 13 773 environment samples were collected before the intervention; 181 people, 4519 poultry, and 9562 environments were sampled after LPM interventions. Avian influenza virus (AIV) detection rates in the LPM environment (odds ratio [OR], 0.393; 95% confidence interval [CI], 0.262-0.589) and the incidence of AIV infection (OR, 0.045; 95% CI, 0.025-0.079) were significantly lower after LPM interventions, while interventions were not significantly effective in reducing AIV detection in poultry samples (OR, 0.803; 95% CI, 0.403-1.597). CONCLUSIONS: LPM interventions can reduce AIV human infections and the detection rate of AIV in market environments.

[Formulation regularity and thinking of adjuvant sleep-improving Chinese medicinal health products].

To summarize and analyze the current adjuvant sleep-improving Chinese medicinal health products,this study retrieved the information on health products with the sleep-improving effect published by the Department of Special Food Safety Supervision and Management,State Administration for Market Regulation( SMAR),which was statistically analyzed with Microsoft Excel and TCMISS for the characteristics of formulations. A total of 435 sleep-improving health products were collected,including 344 ones containing Chinese herbal medicines. Among them,413 health products were not suitable for adolescents,neither 194 for pregnant women. Ten Chinese herbal medicines showed a frequency of use ≥40,with 1 095 times( 73. 1%) in use. Through unsupervised hierarchical entropy-based clustering of the above Chinese herbal medicines of health products( degree of support of 45 and confidence coefficient of0. 7),12 new formulas were obtained. The composition of Chinese herbal medicines was consistent with the principles of improving sleep in traditional Chinese medicine( TCM) theories,i. e.,replenishing the heart and spleen,nourishing blood,calming the nerves,nourishing Yin,reducing internal heat,communicating the heart and kidney,replenishing Qi,relieving convulsions,clearing heat,resolving phlegm,regulating the middle warmer,soothing the liver,relieving heat,and calming the heart. According to TCM theories,syndrome differentiation was performed based on the existing sleep-improving health products,followed by data mining and analysis according to the formulation regularity,aiming to provide new ideas for the development of new Chinese medicinal health products. In particular,attention should be attached to the requirements of special populations to provide a basis for follow-up studies,exert the advantages of TCM,and lay a foundation for Chinese medicinal health products to service the public.

Novel HLA-A2 restricted antigenic peptide derivatives with high affinity for the treatment of breast cancer expressing NY-ESO-1.

Tumor immunotherapy based on specific tumor antigen has become the focus for breast cancer, and research into cancer/testes antigens (CTA) is progressing. As an important member in the CTA, NY-ESO-1 plays a crucial role in the treatment and prognosis of breast cancer. In this study, we aimed to improve the binding ability to MHC by designing and synthesizing stable NY-ESO-1-derived peptides, based on NetMHC 4.0 webserver (http://www.cbs.dtu.dk/services/NetMHC/) and HLP webserver (http://crdd.osdd.net/raghava/hlp/pep_both.htm). Moreover, after modification of the lead compound, affinity of the peptides to human leukocyte antigen-A2 (HLA-A2) was determined by a flow cytometry and an inverted fluorescence microscope in T2 cells that show high expression of HLA-A2. The results demonstrated that the affinity of peptides II-4 and II-10 to HLA-A2 was significantly better when compared to others (II-Lead, II-1 ~ II-3, II-5 ~ II-9, II-11 ~ II-15). Further studies indicated that II-4 and II-10, especially II-4, significantly promoted the maturation of HLA-A2-positive human peripheral blood-derived dendritic cells (DCs) from morphology and surface markers, the activation of CD8 + T lymphocytes, and the type-specific killing effect on HLA-A2+/NY-ESO-1+ MDA-MB-231 cells. Molecular docking studies suggested a strong interaction between peptide II-4 and HLA-A2, thereby indicating that the II-4 is a promising candidate with antigenic potential in the field of immunotherapy that needs more studies.

MiR-449b-5p targets lncRNA PSMG3-AS1 to suppress cancer cell proliferation in lung adenocarcinoma.

BACKGROUND: PSMG3-AS1 has been characterized as an oncogenic lncRNA in breast cancer, while its role in other cancers is unknown. This study investigated the role of PSMG3-AS1 in lung adenocarcinoma (LUAD). METHODS: This study included 64 LUAD patients (42 males and 22 females) who were enrolled between May 2012 and May 2014. RT-qPCR was used to evaluate the expression levels of lncRNA. Cell proliferation analysis was performed using CCK-8 kit. RESULTS: We found that upregulation of PSMG3-AS1 in LUAD predicted the poor survival of patients. MiR-449b-5p is downregulated in LUAD and the expression levels of LUAD were inversely correlated with the expression levels of PSMG3-AS1. MiR-449b-5p was predicted to target PSMG3-AS1, and overexpression of miR-449b-5p resulted in the downregulation of PSMG3-AS1 in LUAD cells. Cell proliferation analysis showed that overexpression of PSMG3-AS1 resulted in increased rate of cell proliferation. Overexpression of miR-449b-5p reduced the enhancing effects of PSMG3-AS1 on cell proliferation. CONCLUSIONS: Therefore, miR-449b-5p may target PSMG3-AS1 in LUAD to suppress cancer cell proliferation.

[Study on material basis of Açaí cold drug based on neuro-endocrine-immune network].

To investigate the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling by observing the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the neurotransmitter, endocrine hormone and immune factor level in mice with deficiency-heat and deficiency-cold syndrome. KM male mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, and deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given with thyroid tablet solution(160 mg·kg~(-1)), and the mice in deficiency-cold group were given with hydrocortisone solution(25 mg·kg~(-1)) by intragastric administration every afternoon for 14 days. The mice in each administration group received corresponding drug. The neurotransmitter, endocrine hormone and immune factor levels in the mice were measured after the experiment. The Açaí alcohol extract, consistent with the Açaí powder, showed a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinna-momi Cortex, showing a regulatory effect on the deficiency-cold model mice. In this study, on the basis of proving that Açaí was was cool in property, it also revealed that alcohol extract of Açaí was cool while oil and water extract were warm in property based on the effect of Açaí on neuro-endocrine-immune network. The results suggested that the medicine property of Açaí was the result of the comprehensive action of the resolution components with different properties, and the alcohol extract of Açaí was proved as the material basis of Açaí cold medicine by using the methods of homogeneous comparison and heterogeneous disproval.

[Effect of Açaí oil, alcohol extract and water extract on temperature tendency and metabolic level of mice with deficiency-feat and deficiency-cold].

To investigate the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the temperature tendency animal behavior and intrinsic biochemical indexes, such ascyclic nucleotides and metabolic level, in mice with deficiency-heat and deficiency-cold syndrome, in order to study the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling. KM mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given thyroid tablet solution(160 mg·kg~(-1)), the mice in deficiency-cold group were given hydrocortisone solution(25 mg·kg~(-1)) through gastric perfusion every afternoon for 14 days, and each administration group was given the corresponding drug. The temperature tendency, cyclic nucleotides and metabolic level of animals were measured after the experiment. The Açaí alcohol extract was consistent with the Açaí powder, with a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinnamomi Cortex, with a regulatory effect on the deficiency-cold model mice. In this study, based on the parable theory of traditional Chinese medicine's properties and tastes, property of alcohol extract of Açaí was cool, while the property of oil and water extract were warm, the alcohol extract of Açaí was the material basis of Açaí cold medicine by the methods of homogeneous comparison and heterogeneous disproval.

[Effect of Lepidium meyenii (Maca) on neurotransmitter level and neuro-endocrine-immune network of deficiency-cold and deficiency-heat syndrome rats].

The aim of this paper was to study the effect of Lepidium meyenii(Maca) on cyclic nucleotides, neurotransmitter levels and hypothalamic-pituitary-adrenal axis and immunization of deficiency-cold and deficiency-heat syndrome rats, in order to explore the cold and hot medicinal properties of Maca. SD rats were divided into blank group, deficiency-cold syndrome group, Cinnamomi Cortex of deficiency-cold syndrome(30 g·kg~(-1)) group, high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)), deficiency-heat syndrome group, Phellodendri Chinensis Cortex(PCC) of deficiency-heat syndrome(5 g·kg~(-1)), and high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)). The rats were treated with intramuscular injection of hydrocortisone(20 mg·kg~(-1)) or dexamethasone sodium phosphate(0.35 mg·kg~(-1)) for 21 days to set up the deficiency-cold and deficiency-heat model. The levels of cAMP, cGMP, NE, DA, 5-HT, CRH, ACTH, CORT and IgM, IgG, C3, C4 were detected by radio immunoassay. Both the high-dose Maca group and the low-dose Maca group can significantly improve the overall state and body weight of rats with deficiency-cold syndrome(P<0.01, P<0.05), significantly increasing cAMP, cAMP/cGMP, NE, DA, ACTH(P<0.01, P<0.001), and significantly decreasing 5-HT(P<0.01, P<0.001). However, high-dose and low-dose Maca groups could not improve the deficiency-heat syndrome, and the levels of cAMP, cGMP, cAMP/cGMP, NE, DA, 5-HT and ACTH were not statistically significant. Maca had a significant regulatory effect on CORT, IgM, IgG and C3 content of rats with deficiency-cold and deficiency-heat syndrome(P<0.01, P<0.05, P<0.001). Maca showed the same effect with Cinnamomi Cortex in adjusting the levels of deficiency-cold rats, but in opposition to Phellodendri Chinese Cortex. This paper confirmed that Maca was slightly warm based on its effect on cyclic nucleotide levels and neuro-endocrine-immune networks by the pharmacological experimental method.

Synthesis and evaluation of redox-sensitive gonadotropin-releasing hormone receptor-targeting peptide conjugates.

Lytic peptides have been demonstrated to exhibit obvious advantages in cancer therapy with binding ability toward tumor cells via electrostatic attractions, which are lack of active targeting and aggregation to tumor tissue. In the present study, five conjugated lytic peptides were redesigned and constructed to target gonadotropin releasing hormone receptors (GnRHr), meanwhile, the disulfide bridge was introduced to achieve redox sensitive delivery based on the experience from the preliminary work of lytic peptides P3 and P7. YX-1, was considered to be the most promising for in-depth study. YX-1 possessed high potency (IC50 = 3.16 ±â€¯0.3 µM), low hemolytic effect, and cell membrane permeability in human A2780 ovarian cancer cells. Moreover, YX-1 had prominent pro-apoptotic activity by activating the mitochondria-cytochrome c-caspase apoptotic pathway. The study yielded the conjugate YX-1 with superior properties for antineoplastic activity, which makes it a promising potential candidate for targeting cancer therapy.

Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors.

BACKGROUND: In recent years, proinflammatory cytokine interleukin-1ß (IL-1ß) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1ß. Here, we investigated the role of P2X7R in the pathogenesis of depression. METHODS: Male Sprague-Dawley rats were subjected to chronic unpredictable stressors (CUS) for 3 weeks. At the end of week 1, 2, and 3, extracellular ATP, caspase 1, IL-1ß, and components and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) were evaluated as biomarker of neuroinflammation. In separate experiments, the rats were microinjected with P2X7R agonists ATP, BzATP, and saline into the hippocampus, respectively, or exposed to CUS combined with hippocampal microinjection with P2X7R antagonist, BBG and A438079, and saline, respectively, for 3 weeks, followed by exposed to forced swimming test and open-field test. Moreover, we also evaluated the depressive and anxiety-like behavior of P2X7-null mice in forced swimming test, open-field test, and elevated plus maze. RESULTS: Along with stress accumulation, extracellular ATP, cleaved-caspase 1, IL-1ß, and ASC were significantly enhanced in the hippocampus, but P2X7R and NLRP3 were not. Immunoprecipitation assay indicated that along with the accumulation of stress, assembly of NLRP3 inflammasome and cleaved caspase 1 in NLRP3 inflammasome were significantly increased. Moreover, antagonists of P2X7R, either BBG or A438079, prevented the development of depressive-like behaviors induced by chronic unpredictable stress in rats. Meanwhile, we could not observe any depressive-like or anxiety-like behaviors of P2X7-null mice after they had been exposed to CUS. The results implied that P2X7 knockout could impede the development of depressive-like and anxiety-like behaviors induced by CUS. In contrast, chronic administration of agonists of P2X7R, either ATP or BzATP, could induce depressive-like behaviors. CONCLUSIONS: The activation of P2X7R and subsequent NLRP3 inflammasome in hippocampal microglial cells could mediate depressive-like behaviors, which suggests a new therapeutic target for the prevention and treatment of depression.

Clinical Characteristics, Laboratory Identification, and In Vitro Antifungal Susceptibility of Yarrowia (Candida) lipolytica Isolates Causing Fungemia: a Multicenter, Prospective Surveillance Study.

Our case series showed that uncomplicated Yarrowia lipolytica fungemia might be treated with catheter removal alone. The Vitek 2 YST identification (ID) card system, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and internal transcribed spacer and 25S nuclear ribosomal DNA (nrDNA) gene sequencing provided reliable identification. All isolates had low MICs to voriconazole, echinocandins, and amphotericin B.