Deep Reinforcement Learning for Optimizing Restricted Access Window in IEEE 802.11ah MAC Layer.

The IEEE 802.11ah standard is introduced to address the growing scale of internet of things (IoT) applications. To reduce contention and enhance energy efficiency in the system, the restricted access window (RAW) mechanism is introduced in the medium access control (MAC) layer to manage the significant number of stations accessing the network. However, to achieve optimized network performance, it is necessary to appropriately determine the RAW parameters, including the number of RAW groups, the number of slots in each RAW, and the duration of each slot. In this paper, we optimize the configuration of RAW parameters in the uplink IEEE 802.11ah-based IoT network. To improve network throughput, we analyze and establish a RAW parameters optimization problem. To effectively cope with the complex and dynamic network conditions, we propose a deep reinforcement learning (DRL) approach to determine the preferable RAW parameters to optimize network throughput. To enhance learning efficiency and stability, we employ the proximal policy optimization (PPO) algorithm. We construct network environments with periodic and random traffic in an NS-3 simulator to validate the performance of the proposed PPO-based RAW parameters optimization algorithm. The simulation results reveal that using the PPO-based DRL algorithm, optimized RAW parameters can be obtained under different network conditions, and network throughput can be improved significantly.

Development and validation of a nomogram for individualizing fall risk in patients with hematologic malignancies.

Inpatient falls are common adverse events especially for patients with hematologic malignancies. A fall-risk prediction model for patients with hematologic malignancies are still needed. Here we conducted a multicenter study that prospectively included 516 hospitalized patients with hematologic malignancies, and developed a nomogram for fall risk prediction. Patients were divided into the modeling group (n = 389) and the validation group (n = 127). A questionnaire containing sociodemographic factors, general health factors, disease-related factors, medication factors, and physical activity factors was administered to all patients. Logistic regression analysis revealed that peripheral neuropathy, pain intensity, Morse fall scale score, chemotherapy courses, and myelosuppression days were risk factors for falls in patients with hematologic malignancies. The nomogram model had a sensitivity of 0.790 and specificity of 0.800. The calibration curves demonstrated acceptable agreement between the predicted and observed outcomes. Therefore, the nomogram model has promising accuracy in predicting fall risk in patients with hematologic malignancies.

Cr (VI) induces abnormalities in glucose and lipid metabolism through ROS/Nrf2 signaling.

The hexavalent form of chromium, Cr (VI), has been associated with various diseases in humans. In this study, we examined the mechanisms underlying the effect of Cr (VI) on glucose and lipid metabolism in vivo and in vitro. We found that Cr (VI) induced abnormal liver function, increased fasting blood glucose (FBG), as well as glucose and insulin intolerance in mice. Furthermore, Cr (VI) decreased glucose-6-phosphate (G6P) level and glucose transporter-2 (GLUT2) expression, increased the levels of triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), reduced high-density lipoprotein-cholesterol (HDL-C), and increased sterol regulatory element-binding proteins 1 (SREBP1) and fat synthase (FAS) in vitro and in vivo. Moreover, Cr (VI) promoted intracellular ROS production in vitro, and induced reduction of antioxidant enzyme level and Nrf2/HO-1 expression in vitro and in vivo. Also, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) pretreatment inhibited the production of intracellular ROS, significantly suppressed Cr (VI)-induced oxidative stress, lipid accumulation, decreased G6P and GLUT2, and improved impaired glucose tolerance and glucose and insulin intolerance caused by Cr (VI) in mice. Dh404 activated expression of Nrf2 decreased ROS level, increased HO-1 expression, ameliorated activity of the antioxidant enzyme, inhibited Cr (VI) increase of SREBP1, FAS level, and reduction of G6P and GLUT2. To sum up, these data suggest that dysregulation of ROS/Nrf2/HO-1 has an important role in Cr (VI)-induced glucose/lipid metabolic disorder.

Proteomic and Immunological Identification of Diagnostic Antigens from Spirometra erinaceieuropaei Plerocercoid.

Human sparganosis is a food-borne parasitic disease caused by the plerocercoids of Spirometra species. Clinical diagnosis of sparganosis is crucial for effective treatment, thus it is important to identify sensitive and specific antigens of plerocercoids. The aim of the current study was to identify and characterize the immunogenic proteins of Spirometra erinaceieuropaei plerocercoids that were recognized by patient sera. Crude soluble extract of the plerocercoids were separated using 2-dimensional gel electrophoresis coupled with immunoblot and mass spectrometry analysis. Based on immunoblotting patterns and mass spectrometry results, 8 antigenic proteins were identified from the plerocercoid. Among the proteins, cysteine protease protein might be developed as an antigen for diagnosis of sparganosis.

Detection of novel piroplasmid species and Babesia microti and Theileria orientalis genotypes in hard ticks from Tengchong County, Southwest China.

To reveal the genetic diversity of Babesia microti and Theileria orientalis in Southwest China, we conducted a molecular survey of piroplasms in hard ticks in a China-Myanmar border county. Host infesting and questing ticks were collected from Tengchong County in 2013 and 2014. Piroplasm infection in ticks was detected by PCR, and then, phylogenetic analysis was conducted to study the genetic diversity of the pathogens identified in ticks. All in all, six piroplasm species comprising of B. microti; B. orientalis; a novel Babesia species designated Babesia sp. Tengchong, China; T. orientalis; T. luwenshuni; and an as yet undescribed piroplasmid species referred to as Piroplasmid sp. Tengchong, China, have been identified after screening goat- and cattle-attached ticks. In addition, B. bigemina has been identified by screening questing ticks. Phylogenetic analysis based on the 18S rRNA and partial ß-tubulin gene revealed two novel potentially zoonotic genotypes designated B. microti Tengchong-Type A and B. The T. orientalis genotypes identified in the present study represent the seven known genotypes 1-5, 7, and N3 as revealed by phylogenetic analysis of 18S rRNA and MPSP genes. Importantly, an additional genotype designated N4 has also been identified in this study, which brings the number of recognized T. orientalis genotypes to a total of twelve. Thus, besides the two novel species, Babesia sp. Tengchong, China, closely related to Babesia species isolated from yak and Piroplasmid sp. Tengchong, China, our study demonstrates that additional novel B. microti and T. orientalis genotypes exist in Southwest China.

Spatial structure of the microbiome in the gut of Pomacea canaliculata.

BACKGROUND: Gut microbes can contribute to their hosts in food digestion, nutrient absorption, and inhibiting the growth of pathogens. However, only limited studies have focused on the gut microbiota of freshwater snails. Pomacea canaliculata is considered one of the worst invasive alien species in the world. Elucidating the diversity and composition of the microbiota in the gut of P. canaliculata snails may be helpful for better understanding the widespread invasion of this snail species. In this study, the buccal masses, stomachs, and intestines were isolated from seven P. canaliculata snails. The diversity and composition of the microbiota in the three gut sections were then investigated based on high-throughput Illumina sequencing targeting the V3-V4 regions of the 16S rRNA gene. RESULTS: The diversity of the microbiota was highest in the intestine but lowest in the buccal mass. A total of 29 phyla and 111 genera of bacteria were identified in all of the samples. In general, Ochrobactrum, a genus of putative cellulose-degrading bacteria, was the most abundant (overall relative abundance: 13.6%), followed by Sediminibacterium (9.7%), Desulfovibrio (7.8%), an unclassified genus in the family Aeromonadaceae (5.4%), and Cloacibacterium (5.4%). The composition of the microbiota was diverse among the different gut sections. Ochrobactrum (relative abundance: 23.15% ± 7.92%) and Sediminibacterium (16.95 ± 5.70%) were most abundant in the stomach, an unclassified genus in the family Porphyromonadaceae (14.28 ± 7.29%) and Leptotrichia (8.70 ± 4.46%) were highest in the buccal mass, and two genera in the families Aeromonadaceae (7.55 ± 4.53%) and Mollicutes (13.47 ± 13.03%) were highest in the intestine. CONCLUSIONS: The diversity and composition of the microbiome vary among different gut sections of P. canaliculata snails. Putative cellulose-degrading bacteria are enriched in the gut of P. canaliculata.

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia.

T helper 17 (Th17) cells and regulatory T (Treg) cells, along with Th1 and Th2 cells, may contribute to the development of immune thrombocytopenia (ITP). The imbalance of Th17/Treg toward Th17 cells has been shown to play a pivotal role in the peripheral immune response. Notch signaling has been implicated in peripheral T-cell activation and effector cell differentiation. However, the role of Th17/Treg in the pathogenesis of ITP and the effect of Notch signaling on Th17/Treg imbalances remain largely elusive in ITP. In vitro, we treated peripheral blood mononuclear cells (PBMCs) from ITP and healthy controls with γ-secretase inhibitor (DAPT). Th17 cells and Treg cells were measured by flow cytometry and IL-17, IL-21, and IL-10 secretion by enzyme immunoassay technique. The mRNA expression of Ntoch1, Hes1, Hey1, RORγt, and Foxp3 was investigated by RT-PCR. Cell proliferation and apoptosis were determined by the Cell Counting Kit-8 and apoptosis detection kit. We demonstrated that DAPT was effective in inhibiting mRNA expression of Notch signaling molecules. In untreated cultured PBMCs from ITP patients, we observed elevated Th17 cell and IL-21 levels and RORγt mRNA expression, decreased Treg cells and Foxp3 mRNA expression, and an increased ratio of Th17/Treg and RORγt/Foxp3. After inactivating Notch signal by DAPT, Th17 cells and Th17/Treg ratio were dose dependently decreased and accompanied by the reduction of IL-17 in culture supernatants and RORγt mRNA expression in ITP patients. However, no significant difference was found for Treg cells and Foxp3 mRNA expression, RORγt/Foxp3 ratio, and IL-21 and IL-10 levels after DAPT treatment in ITP patients. We also present evidence that the effect of DAPT inhibition on the Th17 cell response was associated with downregulation of RORγt and IL-17 transcription using human in vitro polarization. In conclusion, our findings highlight the importance of Notch signaling in Th17/Treg imbalances in ITP. Inactivation of Notch signaling might be a potential immunoregulatory strategy in ITP patients.

Precision Prediction for Dengue Fever in Singapore: A Machine Learning Approach Incorporating Meteorological Data.

OBJECTIVE: This study aimed to improve dengue fever predictions in Singapore using a machine learning model that incorporates meteorological data, addressing the current methodological limitations by examining the intricate relationships between weather changes and dengue transmission. METHOD: Using weekly dengue case and meteorological data from 2012 to 2022, the data was preprocessed and analyzed using various machine learning algorithms, including General Linear Model (GLM), Support Vector Machine (SVM), Gradient Boosting Machine (GBM), Decision Tree (DT), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) algorithms. Performance metrics such as Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and R-squared (R2) were employed. RESULTS: From 2012 to 2022, there was a total of 164,333 cases of dengue fever. Singapore witnessed a fluctuating number of dengue cases, peaking notably in 2020 and revealing a strong seasonality between March and July. An analysis of meteorological data points highlighted connections between certain climate variables and dengue fever outbreaks. The correlation analyses suggested significant associations between dengue cases and specific weather factors such as solar radiation, solar energy, and UV index. For disease predictions, the XGBoost model showed the best performance with an MAE = 89.12, RMSE = 156.07, and R2 = 0.83, identifying time as the primary factor, while 19 key predictors showed non-linear associations with dengue transmission. This underscores the significant role of environmental conditions, including cloud cover and rainfall, in dengue propagation. CONCLUSION: In the last decade, meteorological factors have significantly influenced dengue transmission in Singapore. This research, using the XGBoost model, highlights the key predictors like time and cloud cover in understanding dengue's complex dynamics. By employing advanced algorithms, our study offers insights into dengue predictive models and the importance of careful model selection. These results can inform public health strategies, aiming to improve dengue control in Singapore and comparable regions.

Comprehensive meta-analysis of severe fever with thrombocytopenia syndrome virus infections in humans, vertebrate hosts and questing ticks.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control. METHODS: A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity. RESULTS: The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78-9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00-0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95-8.96%) and carnivores (6.34%; 95% CI 3.27-10.23%) were higher than those in rodents (0.45%; 95% CI 0.00-1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35-1.96%), followed by nymphs (0.66%; 95% CI 0.11-1.50%) and larvae (0.01%; 95% CI 0.00-0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86-3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12-0.81%). CONCLUSIONS: Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks.

Infection and biogeographical characteristics of Paragonimus westermani and P. skrjabini in humans and animal hosts in China: A systematic review and meta-analysis.

BACKGROUND: Paragonimiasis, primarily caused by Paragonimus westermani and P. skrjabini in China, is a common food-borne parasitic zoonosis. However, the national distribution of Paragonimus spp. infection and its associated environmental determinants remain poorly understood. In this paper, we summarize the infection of P. westermani and P. skrjabini and describe key biogeographical characteristics of the endemic areas in China. METHODS: Data on Paragonimus infection in humans and animal hosts were extracted from eight electronic databases, including CNKI, CWFD, Chongqing VIP, SinoMed, Medline, Embase, PubMed, and Web of Science. A random-effects meta-analysis model was used to estimate the pooled prevalence. All survey locations were georeferenced and plotted on China map, and scatter plots were used to illustrate the biogeographical characteristics of regions reporting Paragonimus infection. RESULTS: A total of 28,948 cases of human paragonimiasis have been documented, with 2,401 cases reported after 2010. Among the 11,443 cases with reported ages, 88.05% were children or adolescents. The pooled prevalence of P. skrjabini is 0.45% (95% CI: 0.27-0.66%) in snails, 31.10% (95% CI: 24.77-37.80%) in the second intermediate host, and 20.31% (95% CI: 9.69-33.38%) in animal reservoirs. For P. westermani, the pooled prevalence is 0.06% (95% CI: 0.01-0.13%) in snails, 52.07% (95% CI: 43.56-60.52%) in the second intermediate host, and 21.40% (95% CI: 7.82-38.99%) in animal reservoirs. Paragonimus are primarily distributed in regions with low altitude, high temperature, and high precipitation. In northeastern China, only P. westermani infections have been documented, while in more southern areas, infections of both P. westermani and P. skrjabini have been reported. CONCLUSIONS: Paragonimiasis remains prevalent in China, particularly among children and adolescents. Variations exist in the intermediate hosts and geographical distribution of P. westermani and P. skrjabini. Additionally, altitude, temperature, and precipitation may influence the distribution of Paragonimus.

Correlation of ACR and TcPO2 in diabetic kidney disease patients: A pilot study.

OBJECTIVE: Transcutaneous oxygen pressure (TcPO2) is used to assess microcirculation clinically; however, it is not widely available especially in rural hospital. The study was designed to explore potential alternatively biomarkers to assess microcirculation in diabetic kidney disease (DKD). METHODS: A total of 404 patients from Xuzhou first hospital were recruited according to the case records system. Patients were grouped via the ratio of albuminuria and creatinine (ACR; <30 mg/g, 30-300 mg/g, >300 mg/g). Biomarkers in different ACR groups were compared by analysis of variance. Correlation analysis was determined by Pearson or Spearman analysis and binary logistic regression. The receiver operating characteristics (ROC) curve was performed to elucidate the prediction effect of ACR on TcPO2. RESULTS: A total of 404 diabetic patients were recruited with 248 patients diagnosed as DKD and 156 non-DKDs. Age and cystatin C were significantly higher in the ACR3 group compared with those in the ACR1 group, whereas glomerular filtration rate, low-density lipoprotein cholesterol, and TcPO2 were markedly decreased in the ACR3 group (p < .05). Frequency of low TcPO2 (<40 mm Hg) was markedly increased as increment of ACR stages with 30.2% in the ACR3 group (p < .01). There was a negative correlation between TcPO2 and age, ACR, chronic kidney disease (CKD), fast blood glucose, diabetes mellitus (DM) duration, and diabetic neuropathy. Further, binary logistic regression showed ACR was an independent influence factor for low TcPO2. After adjusting for age, gender, hypertension, DM duration, body mass index, glycated hemoglobin, diabetic neuropathy, and CKD, ACR was still an independent influence factor for TcPO2 (odds ratio = 2.464, p < .01). The area under the ROC curve was 0.768 (95% confidence interval: 0.700-0.836, p < .001) for ACR. The analysis of ROC curves revealed a best cutoff for ACR was 75.25 mg/g and yielded a sensitivity of 71.7% and a specificity of 71.7%. CONCLUSIONS: ACR could be used as an alternative biomarker for assessing microcirculation in DKD patients.

Nucleic Acid Prevalence of Zoonotic Babesia in Humans, Animals and Questing Ticks, a Systematic Review and Meta-Analysis.

Background: Zoonotic Babesia infections are an emerging public health threat globally. The geographical distribution, animal reservoirs and tick vectors vary greatly across Babesia species, and estimations of prevalence reported in works within the literature are also quite different. Better prevalence estimates and identification of moderators are needed to understand the global transmission risk of different zoonotic Babesia species, and to provide crucial background information for the diagnosis, treatment and control of zoonotic babesiosis. Methods: We conducted a systematic review and meta-analysis to determine the global nucleic acid prevalence of different zoonotic Babesia species in humans, animals and ticks. Relevant publications were obtained from several electronic databases and grey literature up to December 2021. Articles were included if they were published in English or Chinese and reported the nucleic acid prevalence of zoonotic Babesia species in humans, animals or ticks. The pooled estimates of prevalence were determined using a random effect model. Heterogeneity was investigated using subgroup analyses and random effect meta-regression models. Results: Of 3205 unique studies, 28 were included by the systematic review of zoonotic Babesia for humans, 79 for animals and 104 for ticks. The results showed overall pooled estimates of nucleic acid prevalence for the following: B. microti-1.93% (0.32-4.69%) in humans; B. microti-7.80% (5.25-10.77%), B. divergens-2.12% (0.73-4.08%) and B. venatorum-1.42% (0.30-3.16%) in animals; and B. microti-2.30% (1.59-3.13%), B. divergens-0.16% (0.05-0.32%), and B. venatorum-0.39% (0.26-0.54%) in questing ticks. The type of population, animal reservoir or tick vector, detecting method and continent were moderators possibly associated with heterogeneity, yet the remaining heterogeneity that was not explained was still substantial (all QE p values < 0.05). Conclusions:B. microti is the most prevalent and widely distributed zoonotic Babesia species globally. The wide range of suitable animal reservoirs and potential transmission vectors and high prevalence in animals and ticks may contribute to the worldwide distribution of B. microti. Other zoonotic Babesia species were relatively less prevalent and were reported in quite limited areas.

Spatio-temporal disparities of Clonorchis sinensis infection in animal hosts in China: a systematic review and meta-analysis.

BACKGROUND: Clonorchis sinensis, one of the most important food-borne zoonotic trematodes, remains prevalent in China. Understanding its infection status in animals is crucial for controlling human clonorchiasis. Here we conducted a systematic review and meta-analysis to focus on the spatio-temporal disparities of C. sinensis infection in animals in China. METHODS: Data on C. sinensis prevalence in snails, the second intermediate hosts, or animal reservoirs in China were extracted from electronic databases including PubMed, Embase, Web of Science, Chinese Wanfang database, CNKI, VIP, and China Biomedical Literature database. A random-effects meta-analysis model was utilized to estimate the pooled prevalence in each of the above animal hosts. Subgroup analysis and multivariable meta-regression were performed to explore potential sources of heterogeneity across studies and compare the temporal disparity of infection rates between high and low epidemic areas. Scatter plots were used to depict the biogeographical characteristics of regions reporting C. sinensis infection in animals. RESULTS: The overall pooled prevalence of C. sinensis was 0.9% (95% CI: 0.6-1.2%) in snails, 14.2% (12.7-15.7%) in the second intermediate host, and 14.3% (11.4-17.6%) in animal reservoirs. Prevalence in low epidemic areas (with human prevalence < 1%) decreased from 0.6% (0.2-1.2%) before 1990 to 0.0% (0.0-3.6%) after 2010 in snails (P = 0.0499), from 20.3% (15.6-25.3%) to 8.8% (5.6-12.6%) in the second intermediate hosts (P = 0.0002), and from 18.3% (12.7-24.7%) to 4.7% (1.0-10.4%) in animal reservoirs. However, no similar decrease in prevalence was observed in high epidemic areas (with human prevalence ≥ 1.0%). C. sinensis infections were predominantly reported in areas with altitudes below 2346 m and annual cumulative precipitation above 345 mm and were mostly concentrated in eastern China. CONCLUSIONS: There are spatio-temporal disparities in the animal infections of C. sinensis in different areas of China. Animal infections are primarily concentrated in regions with low altitude and high precipitation. The results suggest that implementing One Health-based comprehensive measures targeting both humans and animals, especially in high epidemic areas, is essential for successful eradication of C. sinensis in China.

Systematic review of randomized controlled trials of traditional Chinese medicine treatment of non-acute bronchial asthma complicated by gastroesophageal reflux.

OBJECTIVE: To assess the effectiveness and safety of Traditional Chinese Medicine (TCM) treatment of non-acute bronchial asthma complicated by gastroesophageal reflux. METHODS: We searched databases from MEDLINE, Cochrane Library, CNKI, VIP, CBM, Wanfang Data, and TCM Database Systems. All randomized, controlled trials (RTCs) of TCM treatment of non-acute asthma complicated by gastroesophageal reflux were included. Data were independently collected by two reviewers. The standards for assessing quality described in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate articles. Meta-analyses were conducted using Rev- Man 5.0.17 software. Heterogeneity was assessed, and a corresponding effects model was used to merge and analyze results. Indexes used to evaluate curative effects were: clinical efficacy, symptom scores, pulmonary function values, and adverse incidents. Effectiveness was indicated using risk ratio (RR) or mean difference (MD), and 95% confidence intervals (CIs) were calculated. RESULTS: Six RCTs were included, involving 304 patients with non-acute asthma complicated by gastroesophageal reflux. The treatment groups received Chinese drugs alone or TCM combined with standard Western medical treatment, and the control groups received standard Western medical treatment alone. Standard Western medical treatment included anti-inflammatory drugs and bronchodilators for asthma, and drugs to promote gastric peristalsis and inhibit gastric acid production for gastroesophageal reflux. Methodological quality was low in all six RCTs. Two RCTs showed that clinical efficacy was higher in the treatment group than in the control group (RR: 1.43, 95%CI: 1.10 to 1.87 vs RR: 1.51, 95% CI: 1.09 to 2.08). One RCT showed that the asthma score was lowered more effectively in the treatment group than in the control group (MD:-1.10, 95% CI:-2.04 to-0.16). Two RCTs showed that the gastroesophageal reflux score was reduced more effectively in the treatment group than in the control group (RR:-3.70, 95% CI:-4.30 to 3.10 vs RR:-5.30, 95% CI:-6.32 to -4.28). One RCT showed that some pulmonary function values were improved more effectively in the treatment group than in the control group (P < 0.05). No differences were seen in the various indexes between groups in the other RCTs. No adverse reactions, dropout rates, or follow-up rates were reported in any of the RCTs. CONCLUSIONS: The clinical symptoms of non-acute asthma complicated by gastroesophageal reflux can be improved by some Chinese drugs. Curative effects can be increased by combining the use of TCM with Western medicine. Because of the small quantity and low quality of research reported to date, it is necessary to conduct further RCTs to confirm these results. The results of this systematic review indicate that the quality of future clinical trials should be improved by including larger patient numbers, correctly randomizing patients into study groups, using blinding methods to measure and assess outcomes, and using accepted indexes to evaluate curative effects.

Dengue Incidence Trends and Its Burden in Major Endemic Regions from 1990 to 2019.

BACKGROUND: Dengue has become one of the major vector-borne diseases, which has been an important public health concern. We aimed to estimate the disease burden of dengue in major endemic regions from 1990 to 2019, and explore the impact pattern of the socioeconomic factors on the burden of dengue based on the global burden of diseases, injuries, and risk factors study 2019 (GBD 2019). METHODS: Using the analytical strategies and data from the GBD 2019, we described the incidence and disability-adjusted life years (DALYs) of dengue in major endemic regions from 1990 to 2019. Furthermore, we estimated the correlation between dengue burden and socioeconomic factors, and then established an autoregressive integrated moving average (ARIMA) model to predict the epidemic trends of dengue in endemic regions. All estimates were proposed as numbers and age-standardized rates (ASR) per 100,000 population, with uncertainty intervals (UIs). The ASRs of dengue incidence were compared geographically and five regions were stratified by a sociodemographic index (SDI). RESULTS: A significant rise was observed on a global scale between 1990 and 2019, with the overall age-standardized rate (ASR) increasing from 557.15 (95% UI 243.32-1212.53) per 100,000 in 1990 to 740.4 (95% UI 478.2-1323.1) per 100,000 in 2019. In 2019, the Oceania region had the highest age-standardized incidence rates per 100,000 population (3173.48 (95% UI 762.33-6161.18)), followed by the South Asia region (1740.79 (95% UI 660.93-4287.12)), and then the Southeast Asia region (1153.57 (95% UI 1049.49-1281.59)). In Oceania, South Asia, and Southeast Asia, increase trends were found in the burden of dengue fever measured by ASRs of DALY which were consistent with ASRs of dengue incidence at the national level. Most of the countries with the heaviest burden of dengue fever occurred in areas with low and medium SDI regions. However, the burden in high-middle and high-SDI countries is relatively low, especially the Solomon Islands and Tonga in Oceania, the Maldives in South Asia and Indonesia in Southeast Asia. The age distribution results of the incidence rate and disease burden of dengue fever of major endemic regions showed that the higher risk and disease burden are mainly concentrated in people under 14 or over 70 years old. The prediction by ARIMA showed that the risk of dengue fever in South and Southeast Asia is on the rise, and further prevention and control is warranted. CONCLUSIONS: In view of the rapid population growth and urbanization in many dengue-endemic countries, our research results are of great significance for presenting the future trend in dengue fever. It is recommended to policy makers that specific attention needs to be paid to the negative impact of urbanization on dengue incidence and allocate more resources to the low-SDI areas and people under 14 or over 70 years old to reduce the burden of dengue fever.

Cross-watershed distribution pattern challenging the elimination of Oncomelania hupensis, the intermediate host of Schistosoma japonica, in Sichuan province, China.

BACKGROUND: Snail control is critical to schistosomiasis control efforts in China. However, re-emergence of Oncomelania hupensis is challenging the achievements of schistosomiasis control. The present study aimed to test whether the amphibious snails can spread across watersheds using a combination of population genetics and geographic statistics. METHODS: The digital maps and attributes of snail habitats were obtained from the national survey on O. hupensis. Snail sampling was performed in 45 counties of Sichuan Province. The cox1 gene of specimens was characterized by sequencing. Unique haplotypes were found for phylogenetic inference and mapped in a geographical information system (GIS). Barriers of gene flow were identified by Monmonier's maximum difference algorithm. The watercourses and watersheds in the study area were determined based on a digital elevation model (DEM). Plain areas were defined by a threshold of slope. The slope of snail habitats was characterized and the nearest distance to watercourses was calculated using a GIS platform. Spatial dynamics of high-density distributions were observed by density analysis of snail habitats. RESULTS: A total of 422 cox1 sequences of O. hupensis specimens from 45 sampling sites were obtained and collapsed into 128 unique haplotypes or 10 clades. Higher haplotype diversity in the north of the study area was observed. Four barriers to gene flow, leading to five sub-regions, were found across the study area. Four sub-regions ran across major watersheds, while high-density distributions were confined within watersheds. The result indicated that snails were able to disperse across low-density areas. A total of 63.48% habitats or 43.29% accumulated infested areas were distributed in the plain areas where the overall slope was < 0.94°. Approximately 90% of snail habitats were closer to smaller watercourses. Historically, high-density areas were mainly located in the plains, but now more were distributed in hilly region. CONCLUSIONS: Our study showed the cross-watershed distribution of Oncomelania snails at a large scale. Natural cross-watershed spread in plains and long-distance dispersal by humans and animals might be the main driver of the observed patterns. We recommend cross-watershed joint control strategies for snail and schistosomiasis control.

[Introduction of dynamic balancing randomization method and its application].

Following the development of clinical trials, the methodology of clinical trials has developed a great deal, including randomization method and blinding method, etc. The method of randomization includes simple randomization, stratification randomization, etc. Dynamic randomization is also considered as a method of randomization. Two dynamic randomization methods are introduced in this paper, including a method considering the balance of numbers in each group and a method considering prognostic factors. This paper also demonstrates the procedure of dynamic randomization of the above two methods by simulations and actual examples.

Probe A shown in the GeneXpert MTB/RIF assay during the detection of Mycobacterium intracellular infections.

Mycobacterium tuberculosis (MTB) is commonly diagnosed via the GeneXpert MTB/RIF assay. The cycle threshold (Ct) value of probe A from this assay produced a fluorescence signal upon Mycobacterium intracellulare detection. No other nontuberculous mycobacteria (NTM) exhibited positive probe signals. Using a confirmed mycobacterial culture as a standard, probe A of the assay exhibited 84% sensitivity (95% confidence interval [CI]: 71%-97%) and 50% specificity (95% CI: 37%-63%) for clinical samples. For M. intracellulare strains, probe A exhibited 90% sensitivity (95% CI: 80%-100%) and 50% specificity (95% CI: 37%-63%). The identity of the amino acid sequence and 81-bp core region of rpoB from MTB and NTM suggested that the highly conserved property might be associated with a mismatch between the probes and the chromosomal DNA target. Probe A yielded a positive signal upon M. intracellulare detection; thus, probe A may help diagnose M. intracellular infections.

Engineering a probiotic strain of Escherichia coli to induce the regression of colorectal cancer through production of 5-aminolevulinic acid.

Bacterial vectors can be engineered to generate microscopic living therapeutics to produce and deliver anticancer agents. Escherichia coli Nissle 1917 (Nissle 1917) is a promising candidate with probiotic properties. Here, we used Nissle 1917 to develop a metabolic strategy to produce 5-aminolevulinic acid (5-ALA) from glucose as 5-ALA plays an important role in the photodynamic therapy of cancers. The coexpression of hemAM and hemL using a low copy-number plasmid led to remarkable accumulation of 5-ALA. The downstream pathway of 5-ALA biosynthesis was inhibited by levulinic acid (LA). Small-scale cultures of engineered Nissle 1917 produced 300 mg l-1 of 5-ALA. Recombinant Nissle 1917 was applied to deliver 5-ALA to colorectal cancer cells, in which it induced the accumulation of antineoplastic protoporphyrin X (PpIX) and specific cytotoxicity towards colorectal cancer cells irradiated with a 630 nm laser. Moreover, this novel combination therapy proved effective in a mouse xenograft model and was not cytotoxic to normal tissues. These findings suggest that Nissle 1917 will serve as a potential carrier to effectively deliver 5-ALA for cancer therapy.

Intestinal microbiome profiles in Oncomelania hupensis in mainland China.

Oncomelania hupensis plays a significant role in the transmission of schistosomiasis japonica, which remains a major public health concern in China. Understanding the biological characteristics of O. hupensis is a prerequisite for its control; however, there are currently no studies investigating the intestinal microbiota of the O. hupensis snail. This study aimed to profile the intestinal microbiome of O. hupensis across different ecological landscapes in mainland China. DNA was extracted from the intestines of the collected snails and the bacterial communities were detected using 454 pyrosequencing. A total of 3,799 operational taxonomic units (OTUs) were obtained, and Proteobacteria, Firmicutes, and Actinobacteria were identified as the dominant bacterial taxa at the phylum level. Bacillus and Lactococcus were the most common genera in samples obtained from the four ecological landscapes. Snail specimens were clustered into three clades according to microbial community diversity, and thirty-seven genera that contributed to differential microbiota distributions were identified. Co-occurrence network analysis indicated a symbiotic relationship for the intestinal microbiota of O. hupensis, and PICRUSt analysis predicted forty-one metabolic functions in all snail samples, including membrane transport, amino acid metabolism, carbohydrate metabolism, replication and repair, energy metabolism, as well as xenobiotics biodegradation and metabolism. These findings improve our understanding of bacterial ecology in the O. hupensis intestine; further studies will focus on the relationship between O. hupensis intestinal microbiota and the microbiota in their specific ecological environments.