Maxent modeling for predicting the global potential distribution of talaromycosis marneffei / 中国热带医学

@#Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

CASA: a comprehensive database resource for the COVID-19 Alternative Splicing Atlas.

BACKGROUND: As a key process in transcriptional regulatory mechanisms, alternative splicing (AS) plays a crucial role in maintaining the diversity of RNA and protein expression, and mediates the immune response in infectious diseases, especially for the COVID-19. Therefore, urgent data gathering and more research of AS profiles in microbe-infected human cells are needed to improve understanding of COVID-19 and related infectious diseases. Herein, we have created CASA, the COVID-19 Alternative Splicing Atlas to provide a convenient computing platform for studies of AS in COVID-19 and COVID-19-related infectious diseases. METHODS: In CASA, we reanalyzed thousands of RNA-seq datasets generated from 65 different tissues, organoids and cell lines to systematically obtain quantitative data on AS events under different conditions. A total of 262,994 AS events from various infectious diseases with differing severity were detected and visualized in this database. In order to explore the potential function of dynamics AS events, we performed analysis of functional annotations and drug-target interactions affected by AS in each dataset. RNA-binding proteins (RBPs), which may regulate these dynamic AS events are also provided for users in this database. RESULTS: CASA displays microbe-induced alterations of the host cell splicing landscape across different virus families and helps users identify condition-specific splicing patterns, as well as their potential regulators. CASA may greatly facilitate the exploration of AS profiles and novel mechanisms of host cell splicing by viral manipulation. CASA is freely available at http://www.splicedb.net/casa/ .

Efficacy and safety of endothelin receptor antagonists, phosphodiesterase type 5 Inhibitors, and prostaglandins in pediatric pulmonary arterial hypertension: A network meta-analysis.

Background: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by pulmonary vascular remodeling and increased pulmonary artery pressure, leading to impaired lung oxygenation, right heart failure, and even death. Although great advances have been made in PAH-targeted medications for pediatric patients, the efficacy and safety of these treatments are controversial. Methods: We retrieved relevant articles from electronic databases including PubMed, EMBASE, Web of Science, and Cochrane Library until 12 April 2022. To compare the effectiveness and safety of endothelin receptor antagonists (ERAs), phosphodiesterase type 5 Inhibitors (PDE-5i), and prostaglandins (ProA) in the treatment of pediatric PAH, we investigated six hemodynamic parameters, four respiratory parameters, intensive care unit (ICU) stay duration, length of hospital stay, and two safety outcomes. Results: A total of 27 randomized controlled trials (RCTs) were included in the meta-analysis with 1,574 pediatric participants. The duration of mechanical ventilation was shorter for patients using bosentan, sildenafil, and ProsA, compared with that for patients using the placebo. Bosentan helped to shorten more time for mechanical ventilation than ProsA did, while ProsA was more effective than sildenafil in this respect. As for the length of stay in the ICU, patients administered by ProsA or sildenafil needed shorter ICU stay, compared to those using the placebo, while ProsA was more effective for shortening ICU stay time. In light of safety outcomes, there was a statistically significant difference between the sildenafil and the placebo group. Sildenafil surpassed ProsA in reducing the incidence of pulmonary hypertension (PH) crisis. Conclusions: ERAs were more effective than ProsA in shortening the duration of mechanical ventilation, while ProsA were better for shortening the duration of mechanical ventilation and ICU stay than PDE-5i. PDE-5i were found to generate more benefits in decreasing the occurrence of PH crisis, though further investigation is warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=351505.

Pananx notoginseng saponins attenuate CCL2-induced cognitive deficits in rats via anti-inflammation and anti-apoptosis effects that involve suppressing over-activation of NMDA receptors.

HIV-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain, ultimately leading to progressive decline of cognitive abilities and memory. Chemokine CC motif ligand 2 (CCL2) is elevated in cerebrospinal fluid (CSF), and has been believed to contribute to HAND. Previous studies by our research team have shown that CCL2 enhances N-Methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) and causes nerve cell damage. However, there are few drugs currently available to treat nerve damage that is caused by CCL2. Panax notoginseng saponins (PNS) are isolated from Panax notoginseng and benefit the human body in various ways, including the neuroprotective effect. However, the protective effect of PNS on CCL2-induced neurotoxicity remains unknown. In this study, we found that PNS improved CCL2-induced learning and memory impairment, and inhibited CCL2-induced cell death. These effects may be due to inhibiting over-activation of NMDA receptors by alleviating the dysfunction of glutamate metabolism. Furthermore, PNS-modulated CCL2-inducd intracellular oxidative stress was found to attenuate cell inflammation. Additionally, PNS pretreatment evidently inhibited apoptotic pathways by reducing the Bax/BCL-2 ratio and caspase-3, 8, 9 expressions. In conclusion, this study demonstrates that PNS provides substantial neuroprotection against CCL2-induced neurotoxicity, and may be a novel therapeutic agent in CCL2-induced HAND or other neurodegenerative diseases.

Characterizing the HIV/AIDS Epidemic in the United States and China.

The HIV/AIDS data from the national surveillance systems of China and the United States from 1985 to 2014 were compared to characterize the HIV/AIDS epidemic in both countries. The current estimated national HIV prevalence rate in China and the United States are 0.0598% and 0.348%, respectively. In the United States, the annual number of new HIV infections has remained relatively stable (~50,000 each year) and has shown a downward trend in recent years. The Chinese national HIV prevalence is still low, and new HIV infections have been contained at a low level (50,000-100,000 each year). However, the epidemic has showed an increasing trend since 2012. By risk group, in both countries, men who have sex with men (MSM), heterosexual sex, and injection drug use (IDU) are the most common modes of transmission of new HIV infections. However, in the United States, MSM is the dominant transmission route, accounting for >60% of new infections; whereas in China, heterosexual sex has now become the dominant route, also accounting for >60% of new infections. A rapid increase in the proportion of HIV cases that were attributed to MSM and an obvious decrease in the proportion of HIV cases attributed to IDU in China in recent years imply that the China's epidemic is still evolving, to some extent, copying what was experienced in the United States. By age group, the proportions of HIV cases that were attributed to the age group 25-59 were comparable between the two countries. However, the United States had a higher proportion of cases that were attributed to age groups 15-19 and 20-24 than China, indicating that youth account for more infections in the United States. One other fact worth noting: in China there is a significant increase in the number of HIV new infections in individuals over 50 years of age, which results in much higher proportion of cases that were attributed to age groups 60-64 and over 65 in China than those in the United States. By race/ethnicity, in the United States, Blacks/African Americans continue to experience the most severe HIV burden, followed by Hispanics/Latinos. In China, no official data on race/ethnicity disparities are currently available. Thus, region, risk group, age are important factors in the HIV epidemics in both countries.

[Relationship between pre-exposure prophylaxis and HIV infection: a meta-analysis].

OBJECTIVE: To evaluate the effect on pre-exposure prophylaxis (PrEP) to prevent HIV infection in high risk populations. METHODS: A computerized literature searching had been carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wanfang, Tsinghua Tongfang database and related websites to collect relevant papers (from establishment to June 2012) with the key words of pre-exposure prophylaxis, HIV, AIDS, high risk populations, relative risk, reduction. All randomized controlled trials (RCT) papers about using single or compound antiretroviral drugs (ARVs) orally or topically before HIV exposure or during HIV exposure in high risk populations were enrolled. Meta-analysis was conducted using Stata 10.0 to calculate the pooled RR value (95%CI). Consistency test was performed and publication bias was evaluated. RESULTS: Finally 5 RCT papers were enrolled, including 10 271 persons who were at high risk of HIV infection. The number of the experimental group was 5929, among which 116(1.96%) became infected. The number of the control group was 4342, among which 201(4.63%) became infected. Meta-analysis showed that the pooled relative risk (RR) and 95%CI was 0.49 (0.39 - 0.61), P < 0.05, indicating that the persons in experimental group had a 0.49 times lower risk of HIV infected, as compared with the control group. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 825. CONCLUSION: PrEP was an effective and safe protection measure to reduce HIV infection in high risk populations.

[Benefits of promoting male circumcision among the general population in the high HIV prevalence areas of Guangxi Province].

OBJECTIVE: To evaluate the effect of promoting male circumcision among the general population in the high HIV prevalence areas of Guangxi Province. METHODS: We interviewed 590 male residents from Hezhou and Qinzhou areas of Guangxi Province and conducted intervention using male circumcision promotion materials and various methods. If the subjects were willing and had no contraindication, they were referred to the appointed hospitals to receive circumcision. We conducted follow-up visits at 6 and 9 months after intervention for the changes in the subjects' knowledge, attitude and practice related to male circumcision. RESULTS: The male circumcision knowledge, willingness and operation rate were significantly improved after intervention (P < 0.05), but with no significant difference between the two follow-up visits (P > 0.05). The number of those who knew that phimosis and redundant prepuce were the reasons for circumcision increased from 66.1% at baseline to 81.9% and 79.8% at the two follow-up visits; those who knew that circumcision could prevent AIDS and sexually transmitted diseases increased from 28.0% to 77.4% and 78.6%; those who knew that surgical complications could be pain, bleeding and infection increased from 29.5%, 19.3% and 39.3% to 72.5%, 58.2% and 59.4% at the first follow-up and 75.0%, 57.0% and 63.0% at the second; those who were willing to receive circumcision increased from 35.3% at baseline to 59.6% and 61.3% at the two follow-up visits; and the rate of surgery increased from zero to 12.7% and 16.1%. CONCLUSION: The promotion of male circumcision among the general population in the high HIV prevalence areas of Guangxi Province significantly improved their knowledge, attitude and practice related to AIDS prevention. And the promotion activities should focus on the publicity of AIDS knowledge, risks of phimosis and redundant prepuce, and safety of circumcision.

[Antiviral effect of lamivudine on HIV-1 targeting MT2 cells influenced by morphine].

OBJECTIVE: To determine whether morphine having the ability to influence the antiviral effect of lamivudine (3TC) in vitro study. METHODS: MT2 cells were randomly assigned into morphine + 3TC treatment group, morphine + naloxone + 3TC treatment group, naloxone + 3TC treatment group. Both 3TC and virus control groups were set up. The corresponding MT2 cells were treated with opiates antagonist (naloxone) for 0.5 hours before the 24-hours morphine treatment program was implemented while all of the groups were then infected with equal amounts of cell-free HIV-1 IIIB strain and 3TC. HIV-1 p24 antigen in culture supernatants collected at days 3, 4, 5 and 6 after infection status was tested and the inhibition of 3TC anti-HIV-1 p24 antigen of various treatment groups calculated. RESULTS: Inhibition of 3TC anti-HIV-1 p24 antigen of Morphine + 3TC treatment group was the lowest when HIV-1 infected cells at 3(rd)and 4(th) day and showed significant difference (P < 0.05) when compared to the 3TC control. However, there was no statistically significant difference among them (P > 0.05), when virus was infected the cells at 5(th)and 6(th) day. The difference of 3TC anti-HIV-1 p24 antigen inhibition between the morphine + naloxone + 3TC treatment group and the naloxone + 3TC treatment group was not significant (P > 0.05). Similar results were obtained when these two groups were compared to the 3TC control group (P > 0.05), respectively. The 3TC anti-HIV-1 p24 antigen inhibition of each treatment group reduced as the time of infection prolonged, showing a significant and time-course effect. CONCLUSION: The 3TC antiviral effect was reduced by morphine in the early stage of infection, and could be blocked by naloxone.

[Acceptability of male circumcision among male miners in Baise of Guangxi].

OBJECTIVE: To investigate the acceptability of male circumcision among male miners in Baise, Guangxi, China. METHODS: A questionnaire-based survey on the willingness to be circumcised (WTC) and its influential factors were conducted among Guangxi male miners recruited by random cluster sampling. RESULTS: Of 569 subjects who were surveyed, 143 (25.13%) expressed their willingness to be circumcised. Univariate analysis showed that marital status, education level, and the awareness of the hazards of phimosis and redundant prepuce and reasons for circumcision were significantly different between WTC group and the non-WTC group (all P<0.05). Furthermore, the incidence of phimosis or redundant prepuce also significantly differed between these two groups (P=0.0001). Logistic regression analysis found marital status (OR=0.498ì95%CI=0.272-0.913), history of foreskin disease (OR=8.181, 95%CI=4.252-15.741), and awareness of the risk that a redundant prepuce may cause smegma (OR=1.713ì95%CI=1.090-2.693) were significantly correlated with the male miners WTC. CONCLUSIONS: Male miners in this area have low WTC. Education on the basic knowledge of acquired immunodeficiency syndrome and circumcision may help promote the application of circumcision.

Keratinocyte growth factor (KGF) gene therapy mediated by an attenuated form of Salmonella typhimurium ameliorates radiation induced pulmonary injury in rats.

The aim of this study is to investigate the effect of KGF (Keratinocyte growth factor) gene therapy mediated by the attenuated Salmonella typhimurium Ty21a on radiation-induced pulmonary injury in rats model. Sprague-Dawley rats were divided into three groups: TPK group (treated with TPK strain, attenuated Salmonella typhimurium Ty21a-recombined human KGF gene); TP group (treated with TP strain, attenuated Salmonella typhimurium Ty21a-recombined blank plasmid); and Saline group (treated with saline). After intraperitoneal administration for 48 h, the thoraxes of the rats were exposed to X-ray (20 Gy), and the rats were administered again two weeks after radiation. On the 3rd, 5th, 7th, 14th and 28th day after radiation, the rats were sacrificed and lung tissues were harvested. Histological analysis was performed, MDA contents and SOD activity were detected, mRNA levels of KGF, TGF-ß, SP-A and SP-C were measured by Real-time RT-PCR, and their concentrations in the BALF were quantified with ELISA. Administration of TPK strain improved the pathological changes of the lung on the 28th day. In the TPK group, KGF effectively expressed since the 3rd day, MDA contents decreased and SOD activity increased significantly, on the 7th day and 14th day respectively. SP-A and SP-C expression elevated, whereas TGF-ß expression was inhibited in the TPK group. These results suggest that this novel gene therapy of KGF could ameliorate radiation-induced pulmonary injury in rats, and may be a promising therapy for the treatment of radiative pulmonary injury.

[Acceptability and influencing factors on pre-exposure prophylaxis programs among female sex workers in Guangxi, China].

OBJECTIVE: To study the acceptability of pre-exposure prophylaxis (PrEP) program on prevention of human immunodeficiency virus (HIV) infection among female sex workers (FSWs) in Guangxi of China. METHODS: A cross-sectional survey using convenience sampling was administered among 405 FSWs in Nanning, Liuzhou and Beihai cities of Guangxi, China. Self-designed questionnaire, face to face interviews were used to collect HIV-related risk behaviors, knowledge and acceptability of PrEP. RESULTS: After an introduction on PrEP, presuming that it was effective, safe and free of charge, 85.9% of the 405 FSWs said they would use it. Data from logistic regression analysis showed that significant factors of intent to use PrEP would include the followings: workplace (OR = 2.256, P = 0.009), monthly income (OR = 0.257, P = 0.004), family closeness (OR = 0.338, P = 0.012), knowledge on HIV/AIDS (OR = 2.802, P = 0.028), HIV/AIDS risk was introduced from a strange client (OR = 0.363, P = 0.049), whether the gatekeeper ordering the use of condom (OR = 0.432, P = 0.010), whether consistent using condom with clients (OR = 3.010, P = 0.002), whether ever using drugs to prevent STD infection (OR = 3.570, P = 0.049) etc. CONCLUSION: Awareness on HIV/AIDS knowledge and self-protection seemed the main influential factors while health education might promote the acceptability of PrEP.