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Background: China contributed 8.9% of all incident cases of tuberculosis globally in 2017, and understanding the spatiotemporal distribution of pulmonary tuberculosis (PTB) in major transmission foci in the country is critical to ongoing efforts to improve population health.Methods: We estimated annual PTB notification rates and their spatiotemporal distributions in Sichuan province, a major center of ongoing transmission, from 2005 to 2017. Time series decomposition was used to obtain trend components from the monthly incidence rate time series. Spatiotemporal cluster analyses were conducted to detect spatiotemporal clusters of PTB at the county level.Results: From 2005 to 2017, 976,873 cases of active PTB and 388,739 cases of smear-positive PTB were reported in Sichuan Province, China. During this period, the overall reported incidence rate of active PTB decreased steadily at a rate of decrease (3.77 cases per 100,000 per year, 95% confidence interval (CI): 3.28-4.31) that was slightly faster than the national average rate of decrease (3.14 cases per 100,000 per year, 95% CI: 2.61-3.67). Although reported PTB incidence decreased significantly in most regions of the province, incidence was observed to be increasing in some counties with high HIV incidence and ethnic minority populations. Active and smear-positive PTB case reports exhibited seasonality, peaking in March and April, with apparent links to social dynamics and climatological factors.Conclusions: While PTB incidence rates decreased strikingly in the study area over the past decade, improvements have not been equally distributed. Additional surveillance and control efforts should be guided by the seasonal-trend and spatiotemporal cluster analyses presented here, focusing on areas with increasing incidence rates, and updated to reflect the latest information from real-time reporting. [ABSTRACT FROM AUTHOR]

Cyrtomium adenotrichum Y. Nong & R.H. Jiang (Dryopteridaceae), a new species from Guangxi, China, is described and illustrated. This new species is similar to C. nephrolepioides (Christ) Copel., C. obliquum Ching & K. H. Shing ex K. H. Shing, C. sinningense Ching & K. H. Shing ex K. H. Shing and C. calcis Liang Zhang, N.T.Lu & Li Bing Zhang in having erect rhizomes, dense, leathery lamina and rounded sori, but it can be easily distinguishable by its stipe sparsely glandular, base obvious oblique, basiscopic base truncate, acroscopic base auriculate or ovate.

The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants (N = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0–7) and a tetracycline‐mupirocin‐β‐lactam‐dominant phase (Months 8–14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with Escherichia (25.5%) harboring the most resistance genes. In a further analysis with all available infants (N = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years (p < 0.001). Using a random‐forest approach, a set of 34 resistance genes could be used to predict age (R2 = 68.0%). Leveraging microbial host inference analyses, we inferred the age‐dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., Escherichia coli more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate‐active enzymes from Bacteroidota and a decreasing need for Pseudomonadota during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life. Highlights: We first examined the natural assembly of resistome in healthy infants' guts and identified resistance genes that were significantly impacted by age.We inferred that the age‐dependent assembly of infant resistome was a result of the shift of the gut microbiome, which was due to resistance genes being disproportionally distributed across taxa.Age‐dependent assembly of infant resistome reflected the shift in the gut microbiome, and such modifications were often a result of dietary transitions during infancy.Maturation of gut resistome was driven by infants' changing carbohydrate metabolism, which demonstrated an increasing need for carbohydrate‐active enzymes from Bacteroidota and decreasing involvements from Pseudomonadota during infancy. [ABSTRACT FROM AUTHOR]

Background: Due to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities. Methods: The Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO). Results: A total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days). Conclusions: To control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community. [ABSTRACT FROM AUTHOR]

Our previous genome-wide linkage analysis identified a susceptibility locus for generalized vitiligo on 22q12. To search for susceptibility genes within the locus, we investigated a biological candidate gene, X-box binding protein 1(XBP1). First, we sequenced all the exons, exon-intron boundaries as well as some 5' and 3' flanking sequences of XBP1 in 319 cases and 294 controls of Chinese Hans. Of the 8 common variants identified, the significant association was observed at rs2269577 (p_(trend) = 0.007, OR = 1.36, 95% CI = 1.09-1.71), a putative regulatory polymorphism within the promoter region of XBP1. We then sequenced the variant in an additional 365 cases and 404 controls and found supporting evidence for the association (p_(trend) = 0.008, OR = 1.31, 95% CI = 1.07-1.59). To further validate the association, we genotyped the variant in another independent sample of 1,402 cases and 1,288 controls, including 94 parent-child trios, and confirmed the association by both case-control analysis (p_(trend) = 0.003, OR = 1.18, 95% CI = 1.06-1.32) and the family-based transmission disequilibrium test (TDT, p = 0.005, OR = 1.93, 95% CI = 1.21-3.07). The analysis of the combined 2,086 cases and 1,986 controls provided highly significant evidence for the association (p_(trend) = 2.94x10(-6), OR = 1.23, 95% CI = 1.13-1.35). Furthermore, we also found suggestive epistatic effect between rs2269577 and HLA-DRB1*07 allele on the development of vitiligo (p = 0.033). Our subsequent functional study showed that the risk-associated C allele of rs2269577 had a stronger promoter activity than the non-risk G allele, and there was an elevated expression of XBP1 in the lesional skins of patients carrying the risk-associated C allele. Therefore, our study has demonstrated that the transcriptional modulation of XBP1 expression by a germ-line regulatory polymorphism has an impact on the development of vitiligo.

Walsura guangxiensis (Meliaceae), a new species from Guangxi, China, is here described and illustrated. The new species is easily distinguishable from the other two Chinese members of the genus by its petals being pale yellow, filaments being connate into tubes above the middle, the berry being oval and glabrous. An identification key of Walsura for 17 species is also provided.

Background: The integration of acupuncture with intramuscular injection of diclofenac sodium can expedite the onset of analgesia in treating acute renal colic caused by urolithiasis. However, it remains unclear whether acupuncture can accelerate pain relief constantly until complete remission. This study aimed to explore the extent to which acupuncture can expedite the onset time of response or complete pain relief in treating acute renal colic, and the predictive value of patient characteristics for treatment efficacy. Methods: This secondary analysis utilized data from a prior randomized controlled trial. Eighty patients with acute renal colic were randomly assigned 1:1 to the acupuncture group or the sham acupuncture group. After intramuscular injection of diclofenac sodium, acupuncture or sham acupuncture was delivered to patients. The outcomes included time to response (at least a 50 % reduction in pain) and complete pain relief. Between-group comparison under the 2 events was estimated by Kaplan-Meier methodology. Subgroup analysis was performed utilizing the Cox proportional hazards model. Results: The median response time and complete pain relief time in the acupuncture group were lower than those in the sham acupuncture group (5 vs 30 min, Log Rank P < 0.001; 20 min vs not observed, Log Rank P < 0.001, respectively). Hazard Ratios (HRs) for response across all subgroups favored the acupuncture group. All HRs for complete pain relief favored acupuncture, expect large stone and moderate pain at baseline. No interaction was found in either event. Conclusion: Acupuncture can accelerate the response time and complete pain relief time for patients with acute renal colic, with the efficacy universally. Trial registration: This study has been registered at Chinese Clinical Trial Registry: ChiCTR1900025202.

Different from the usual full counting statistics theoretical work that focuses on the higher order cumulants computation by using cumulant generating function in electrical structures, Monte Carlo simulation of single-barrier structure is performed to obtain time series for two types of widely applicable exclusion models, counter-flows model, and tunnel model. With high-order spectrum analysis of Matlab, the validation of Monte Carlo methods is shown through the extracted first four cumulants from the time series, which are in agreement with those from cumulant generating function. After the comparison between the counter-flows model and the tunnel model in a single barrier structure, it is found that the essential difference between them consists in the strictly holding of Pauli principle in the former and in the statistical consideration of Pauli principle in the latter. [ABSTRACT FROM AUTHOR]

Low-dielectric-constant (low-k) materials are an indispensable part of microprocessors as they can alleviate electronic crosstalk, charge build-up, and signal propagation delay. However, existing low-k materials usually have k values higher than 2 and inferior thermo-mechanical properties, which restrict the development of microelectronic devices. Although we have recently discovered that larger polyhedral oligomeric silsesquioxanes (POSS) are useful building blocks for fabricating advanced ultra-low-k materials, it remains to be seen whether a POSS cage and linker could be leveraged to tune the structure-property of the materials and create ultra-low-k materials with improved comprehensive properties. Herein, we propose a series of POSS-based hybrid materials (i.e., c-TnPBn and c-TnFn, n = 8, 10, and 12) that consist of distinct POSS cages and linkers. When the linker is kept identical, the gradual enlargement of the POSS cage enhances the porosity/free volume fraction of materials, resulting in quasi-linearly reduced k values for the resulting materials (k = 1.93 for c-T12PB12, 2.14 for c-T12F12). Meanwhile, the materials’ comprehensive properties can be significantly improved by increasing the POSS cage size or varying the linker’s length and type. As a result, ultra-low-k materials with good processability, low surface roughness (< 0.40 nm), excellent thermostability (> 480 °C), mechanical properties (elastic modulus > 2.5 GPa), and hydrophobicity have been obtained, and the low-k values can be maintained under high temperature (e.g., 300 °C) and wet condition. This work reveals the critical contribution of POSS cage size and linker to the structure and properties of POSS-based low-k materials and offers promising materials for the future of the microelectronic industry.

Existing model synchronization mechanisms of federated learning (FL) are mostly based on single-layer parameter server architecture,which are difficult to adapt to current heterogeneous wireless network scenarios.There are some problems such as excessive communication load on single-point and poor scalability of FL.In response to these problems,this paper proposes an efficient model synchronization scheme for FL in hybrid wireless edge networks.In a hybrid edge wireless network,edge devices transmit local models to nearby small base stations.After receiving local models from edge devices,small base stations exe-cute the aggregation algorithm and send the aggregated models to the macro base station to update the global model.Considering the heterogeneity of channel performance and the competitive relationship of data transmission on the wireless channel,this paper proposes a new type of grouping asynchronous model synchronization scheme and designs a transmission rate aware channel allocation algorithm.Experiments are carried out on real data sets.Experimental results show that the proposed transmission rate aware channel allocation algorithm in grouping asynchronous model synchronization scheme can reduce communication time by 25%～60% and greatly improve the training efficiency of FL.

The fall armyworm (FAW) Spodoptera frugiperda is a major polyphagous pest that feeds mainly on food crops, such as corn and rice, posing a serious threat to the safety of food crops worldwide. Trehalase, can degrade trehalose and the resulting products participate in the synthesis of chitin, one of the main components of outer epidermis in insects. Therefore, trehalase inhibitors have been identified as novel agents for pest control. We report the insecticidal potential of a trehalase inhibitor validamycin against FAW. Validamycin (1 µg/µL) when injected in FAW using microinjection could significantly reduce trehalase activity 48 h later, especially, the activity of soluble trehalase, then the glucose content and glycogen content also decrease. In addition, the deaths of larvae in validamycin treated group at each instar stage were higher than those in the control group, moreover, validamycin treatment increased the pupal weight and prolonged pest development. Similarly, validamycin also significantly inhibited the chitinase activity and caused the accumulation of chitin in FAW. Results of qRT-PCR showed that the expression levels of two trehalose genes (SfTRE1 and SfTRE2), which encode key enzymes in chitin biosynthesis pathway, were significantly reduced, while the expression levels of fructose-6-phosphate transaminase, glucosamine-phosphate N-acetyltransferase and chitinase genes were significantly increased. It is obvious that validamycin has an influence on physiological metabolism and development of FAW, the results obtained will be conducive to the prevention and control of FAW in the future. [ABSTRACT FROM AUTHOR]

Abstract Background Acute renal colic caused by urinary calculi (ARCUC) has a considerable impact on the quality of life. Acupuncture might be a potential treatment option. However, the evidence is limited. We will conduct this trial to evaluate the efficacy and safety of acupuncture as adjunctive treatment to diclofenac for ARCUC. Methods/design A total of 80 eligible patients who are diagnosed with urinary stone renal colic will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture. The primary outcome will be the response rate of patients achieving a reduction of > 50% on visual analog score (VAS) from baseline to 10 min after treatment. Secondary outcomes will include the VAS, remedial analgesia, re-visit and admission rate, blinding assessment, credibility and expectancy, and adverse event. All patients who receive randomization will be included in the intent-to-treat analysis. Discussion The finding of this trial will provide evidence on the efficacy and safety of acupuncture for the treatment of ARCUC. The results of this study will be published in peer-reviewed journals. Trial registration ClinicalTrials.gov ChiCTR 1900025202 . Registered on August 16, 2019.

Objective To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) and gonadotropin-releasing analogues (GnRH-a) as pretreatments for the hysteroscopic transcervical resection of myoma (TCRM) for type 2 submucosal fibroids greater than 4 centimeters in diameter. Materials and methods Seventy-nine patients were assigned into two groups according patient preference: 42 in HIFU and 37 in GnRHa. TCRM was performed after 3 months of pretreatment with HIFU or GnRHa. Results Following pretreatment with HIFU or GnRHa, uterine-fibroid symptom (UFS) scores and hemoglobin levels (HGB) showed improvement. The fibroid maximum diameter, size of fibroids, and volume of the uterus were decreased. Following HIFU pretreatment, one case reported complete vaginal fibroid expulsion, and four reported partial fibroid expulsion. No similar cases were found in the GnRHa group. Eighteen patients were lost to follow-up prior to TCRM. Among the 31 patients in HIFU, the fibroids were downgraded to type 0 in 10 cases and type 1 in 5 cases. Of the 30 patients in GnRHa, the treated fibroids were downgraded to type 1 in 9 cases. The mean operation time and intraoperative blood loss of the HIFU group were significantly lower than those in the GnRHa group. No significant differences were observed in the incidence of intraoperative complications and the one-time resection rate of fibroids between the two groups (p>.05). Conclusions HIFU seems to be superior to GnRHa as a pretreatment method prior to TCRM for type 2 submucosal fibroids greater than 4 centimeters in diameter

Background Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), associated with severe manifestations of the disease. Pediatric immunization with inactivated EV71 vaccine was initiated in 2016 in the Asia-Pacific region, including China. We analyzed a time series of HFMD cases attributable to EV71, coxsackievirus A16 (CA16), and other enteroviruses in Chengdu, a major transmission center in China, to assess early impacts of immunization. Methods Reported HFMD cases were obtained from China's notifiable disease surveillance system. We compared observed postvaccination incidence rates during 2017–2018 with counterfactual predictions made from a negative binomial regression and a random forest model fitted to prevaccine years (2011–2015). We fit a change point model to the full time series to evaluate whether the trend of EV71 HFMD changed following vaccination. Results Between 2011 and 2018, 279 352 HFMD cases were reported in the study region. The average incidence rate of EV71 HFMD in 2017–2018 was 60% (95% prediction interval [PI], 41%–72%) lower than predicted in the absence of immunization, corresponding to an estimated 6911 (95% PI, 3246–11 542) EV71 cases averted over 2 years. There were 52% (95% PI, 42%–60%) fewer severe HFMD cases than predicted. However, the incidence rate of non-CA16 and non-EV71 HFMD was elevated in 2018. We identified a significant decline in the trend of EV71 HFMD 4 months into the postvaccine period. Conclusions We provide the first real-world evidence that programmatic vaccination against EV71 is effective against childhood HFMD and present an approach to detect early vaccine impact or intended consequences from surveillance data. [ABSTRACT FROM AUTHOR]

According to the requirements of interconnection of all things,background of development of establishing IoT using the LEO satellite communication network is researched.The development status of LEO IoT at home and abroad is analyzed,and the technical challenges and research content of LEO IoT are discussed.

Purpose: To investigate the protective effect of the acetone extract of Rumex japonicas Houtt. (AER) on rat myocardial cells. Methods: R. japonicas was extracted with 75 % aqueous ethanol by reflux to afford total extract (TER). TER was suspended in water and then extracted with acetone to afford acetone fraction of R. japonicas (AER). High performance liquid chromatography (HPLC) combined with standard substances was carried out to analyze the major constituents of AER. Apoptosis in myocardial H9c2 cell line was induced by H2O2 (100 µmol/L). The cells were treated with AER (50, 100 and 200 µg/mL, and cell viability was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, while oxidative stress level in H9c2 cells was evaluated by determining levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatinine kinase (CK), superoxide dismutase (SOD), and catalase (CAT). Furthermore, apoptotic proteins (caspase-3, Bax and Bcl-2) in H9c2 cells were analyzed by using western blot assay. Results: Results revealed that the main components of AER are aloe-emodin, rhein, emodin, chrysophanol and physcion. AER (50, 100 and 200 µg/mL) inhibited the cell viability reduction of the H9c2 cells induced by H2O2 (p < 0.05, p < 0.01, p < 0.01, respectively). AER (50, 100 and 200 µg/mL) decreased LDH and CK contents of H9c2 cells (p < 0.01). The levels of SOD (p<0.01) and CAT (p < 0.01) were increased by AER treatments (100 and 200 µg/mL); in addition, AER (50, 100 and 200 µg/mL) decreased MDA levels (p < 0.01). Besides, the present results also revealed that AER could down-regulate caspase-3 and Bax, but up-regulated Bcl-2. Conclusion: AER alleviates apoptosis induced by H2O2 in myocardial H9c2 cells via inhibition of oxidative stress and mitochondria-mediated apoptosis. This finding suggests that AER can potentially be developed for the treatment of myocardial apoptosis. [ABSTRACT FROM AUTHOR]

A small-target detection approach was proposed,which is based on the modified local reverse entropy operator and the improved region growing technology.The approa adopted the fact that the emergence of small target could lead to the large change of local reverse entropy.The proposed approach made use of the local reverse entropy map to suppress the small-target image background,and then adopted the improved region growing technique to effectively detect small targets.Experimental results show that the proposed approach can detect small targets accurately and quickly.

Many studies have illustrated adverse effects of short-term exposure to air pollution on human health, which usually assumes a linear exposure-response (E-R) function in the delineation of health effects due to air pollution. However, nonlinearity may exist in the association between air pollutant concentrations and health outcomes such as adult pneumonia hospital visits, and there is a research gap in understanding the nonlinearity. Here, we utilized both the distributed lag model (DLM) and nonlinear model (DLNM) to compare the linear and nonlinear impacts of air pollution on adult pneumonia hospital visits in the coastal city of Qingdao, China. While both models show adverse effects of air pollutants on adult pneumonia hospital visits, the DLNM shows an attenuation of E-R curves at high concentrations. Moreover, the DLNM may reveal delayed health effects that may be missed in the DLM, e.g., ozone exposure and pneumonia hospital visits. With the stratified analysis of air pollutants on adult pneumonia hospital visits, both models consistently reveal that the influence of air pollutants is higher during the cold season than during the warm season. Nevertheless, they may behave differently in terms of other subgroups, such as age, gender and visit types. For instance, while no significant impact due to PM 2.5 in any of the subgroups abovementioned emerges based on DLM, the results from DLNM indicate statistically significant impacts for the subgroups of elderly, female and emergency department (ED) visits. With respect to adjustment by two-pollutants, PM 10 effect estimates for pneumonia hospital visits were the most robust in both DLM and DLNM, followed by NO 2 and SO 2 based on the DLNM. Considering the estimated health effects of air pollution relying on the assumed E-R functions, our results demonstrate that the traditional linear association assumptions may overlook some potential health risks. • The effect of air pollution on adult pneumonia hospital visits were investigated. •Air pollution exhibits adverse health effects on adult pneumonia hospital visits. •The exposure-response of air pollution exhibits a significant nonlinear feature. •The linear model may overlook some potential health risks of air pollution. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) and bipolar disorder (BD) are serious chronic disabling mental and emotional disorders, with symptoms that often manifest atypically in children and adolescents, making diagnosis difficult without objective physiological indicators. Therefore, we aimed to objectively identify MDD and BD in children and adolescents by exploring their voiceprint features., Methods: This study included a total of 150 participants, with 50 MDD patients, 50 BD patients, and 50 healthy controls aged between 6 and 16 years. After collecting voiceprint data, chi-square test was used to screen and extract voiceprint features specific to emotional disorders in children and adolescents. Then, selected characteristic voiceprint features were used to establish training and testing datasets with the ratio of 7:3. The performances of various machine learning and deep learning algorithms were compared using the training dataset, and the optimal algorithm was selected to classify the testing dataset and calculate the sensitivity, specificity, accuracy, and ROC curve., Results: The three groups showed differences in clustering centers for various voice features such as root mean square energy, power spectral slope, low-frequency percentile energy level, high-frequency spectral slope, spectral harmonic gain, and audio signal energy level. The model of linear SVM showed the best performance in the training dataset, achieving a total accuracy of 95.6% in classifying the three groups in the testing dataset, with sensitivity of 93.3% for MDD, 100% for BD, specificity of 93.3%, AUC of 1 for BD, and AUC of 0.967 for MDD., Conclusion: By exploring the characteristics of voice features in children and adolescents, machine learning can effectively differentiate between MDD and BD in a population, and voice features hold promise as an objective physiological indicator for the auxiliary diagnosis of mood disorder in clinical practice., (© 2024. The Author(s).)

Introduction: Given the rapid geographic spread of dengue and the growing frequency and intensity of heavy rainfall events, it is imperative to understand the relationship between these phenomena in order to propose effective interventions. However, studies exploring the association between heavy rainfall and dengue infection risk have reached conflicting conclusions, potentially due to the neglect of prior water availability in mosquito breeding sites as an effect modifier., Methods: In this study, we addressed this research gap by considering the impact of prior water availability for the first time. We measured prior water availability as the cumulative precipitation over the preceding 8 weeks and utilized a distributed lag non-linear model stratified by the level of prior water availability to examine the association between dengue infection risk and heavy rainfall in Guangzhou, a dengue transmission hotspot in southern China., Results: Our findings suggest that the effects of heavy rainfall are likely to be modified by prior water availability. A 24-55 day lagged impact of heavy rainfall was associated with an increase in dengue risk when prior water availability was low, with the greatest incidence rate ratio (IRR) of 1.37 [95% credible interval (CI): 1.02-1.83] occurring at a lag of 27 days. In contrast, a heavy rainfall lag of 7-121 days decreased dengue risk when prior water availability was high, with the lowest IRR of 0.59 (95% CI: 0.43-0.79), occurring at a lag of 45 days., Discussion: These findings may help to reconcile the inconsistent conclusions reached by previous studies and improve our understanding of the complex relationship between heavy rainfall and dengue infection risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Cheng, Jing, Collender, Head, Li, Yu, Li, Ju, Chen, Wang, Cleary and Lai.)

Although sluggish cognitive tempo (SCT) symptoms are often observed in children with attention deficit hyperactivity disorder (ADHD), an increasing number of studies have highlighted its uniqueness. Nevertheless, no national survey on SCT among children and adolescents has been conducted in China. Hence, this research aims to study SCT in China and to evaluate the differences between SCT and ADHD symptoms by comparing their risk factors in terms of life events (LE) and parental rearing behaviors (PRB). This cross-sectional study used data from a survey on 71,929 children and adolescents in 5 province-level regions in China to study the incidence and demographic information of SCT in the Chinese population. Subsequently, the study investigated the comorbidity of ADHD and SCT, and conducted three logistic regressions on the LE and PRB scores to predict whether participants develop symptoms of ADHD or SCT, or neither symptom. 6658 participants were allocated into the SCT group, and the weighted point prevalence of SCT was 9.78%. 36.34% of participants with ADHD (n = 676) were found to demonstrate SCT symptoms, whereas no statistically significant difference was observed in its comorbidity to the three ADHD subtypes (χ 2  = 1.668, p > 0.05, Δ = 2). The regression results on the presence or absence of ADHD revealed paternal excessive-interference and rejection, and maternal favoring were associated with ADHD diagnosis, whereas paternal punishment and favoring and maternal emotional warmth was related to the absence of ADHD symptoms. Academic stress and maternal excessive-interference were associated with SCT symptoms, and maternal emotional warmth associated with SCT absence. Concerning the presence of ADHD-only or SCT-only symptoms, LE adaptation was found to relate to SCT-only symptoms, while PRB paternal rejection and maternal favoring were associated with ADHD-only symptoms. While evidencing the high prevalence of SCT in China, our findings supported that although ADHD and SCT were highly comorbid, they may be considered two independent disorders with different risk factors. Specifically, participants with SCT symptoms are more vulnerable to stress from LE and tend to face more maladjustment than ADHD and normally-developing participants, and maternal rearing behaviours are the key factors to SCT symptoms. SCT brings global challenges in its diagnosis and treatment, and the challenge is more severe in a mentally stressful environment. Therefore, stress management and SCT etiology studies are recommended., (© 2023. Springer Nature Limited.)

Background: Although several pathways have been proposed as the prerequisite for a safe phase-out in China, it is not clear which of them are the most important for keeping the mortality rate low, what thresholds should be achieved for these most important interventions, and how the thresholds change with the assumed key epidemiological parameters and population characteristics., Methods: We developed an individual-based model (IBM) to simulate the transmission of the Omicron variant in the synthetic population, accounting for the age-dependent probabilities of severe clinical outcomes, waning vaccine-induced immunity, increased mortality rates when hospitals are overburdened, and reduced transmission when self-isolated at home after testing positive. We applied machine learning algorithms on the simulation outputs to examine the importance of each intervention parameter and the feasible intervention parameter combinations for safe exits, which is defined as having mortality rates lower than that of influenza in China (14.3 per 100, 000 persons)., Results: We identified vaccine coverage in those above 70 years old, number of ICU beds per capita, and the availability of antiviral treatment as the most important interventions for safe exits across all studied locations, although the thresholds required for safe exits vary remarkably with the assumed vaccine effectiveness, as well as the age structure, age-specific vaccine coverage, community healthcare capacity of the studied locations., Conclusions: The analytical framework developed here can provide the basis for further policy decisions that incorporate considerations about economic costs and societal impacts. Achieving safe exits from the Zero-COVID policy is possible, but challenging for China's cities. When planning for safe exits, local realities such as the age structure and current age-specific vaccine coverage must be taken into consideration., (© 2023. The Author(s).)

Modeling the global dynamics of emerging infectious diseases (EIDs) like COVID-19 can provide important guidance in the preparation and mitigation of pandemic threats. While age-structured transmission models are widely used to simulate the evolution of EIDs, most of these studies focus on the analysis of specific countries and fail to characterize the spatial spread of EIDs across the world. Here, we developed a global pandemic simulator that integrates age-structured disease transmission models across 3,157 cities and explored its usage under several scenarios. We found that without mitigations, EIDs like COVID-19 are highly likely to cause profound global impacts. For pandemics seeded in most cities, the impacts are equally severe by the end of the first year. The result highlights the urgent need for strengthening global infectious disease monitoring capacity to provide early warnings of future outbreaks. Additionally, we found that the global mitigation efforts could be easily hampered if developed countries or countries near the seed origin take no control. The result indicates that successful pandemic mitigations require collective efforts across countries. The role of developed countries is vitally important as their passive responses may significantly impact other countries., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

With the aid of laboratory typing techniques, infectious disease surveillance networks have the opportunity to obtain powerful information on the emergence, circulation, and evolution of multiple genotypes, serotypes or other subtypes of pathogens, informing understanding of transmission dynamics and strategies for prevention and control. The volume of typing performed on clinical isolates is typically limited by its ability to inform clinical care, cost and logistical constraints, especially in comparison with the capacity to monitor clinical reports of disease occurrence, which remains the most widespread form of public health surveillance. Viewing clinical disease reports as arising from a latent mixture of pathogen subtypes, laboratory typing of a subset of clinical cases can provide inference on the proportion of clinical cases attributable to each subtype (i.e., the mixture components). Optimizing protocols for the selection of isolates for typing by weighting specific subpopulations, locations, time periods, or case characteristics (e.g., disease severity), may improve inference of the frequency and distribution of pathogen subtypes within and between populations. Here, we apply the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework to simulate and optimize hand foot and mouth disease (HFMD) surveillance in a high-burden region of western China. We identify laboratory surveillance designs that significantly outperform the existing network: the optimal network reduced mean absolute error in estimated serotype-specific incidence rates by 14.1%; similarly, the optimal network for monitoring severe cases reduced mean absolute error in serotype-specific incidence rates by 13.3%. In both cases, the optimal network designs achieved improved inference without increasing subtyping effort. We demonstrate how the DIOS framework can be used to optimize surveillance networks by augmenting clinical diagnostic data with limited laboratory typing resources, while adapting to specific, local surveillance objectives and constraints., Competing Interests: The authors have declared that no competing interests exist.

Background: With the progress of urbanization, the mobility of people has gradually increased, which has led to the further spread of dengue fever. This study evaluated the transmissibility of dengue fever within districts and between different districts in Zhanjiang City to provide corresponding advice for cross-regional prevention and control. Methods: A mathematical model of transmission dynamics was developed to explore the transmissibility of the disease and to compare that between different regions. Results: A total of 467 DF cases (6.38 per 100,000 people) were reported in Zhanjiang City in 2018. In the model, without any intervention, the number of simulated cases in this epidemic reached about 950. The dengue fever transmissions between districts varied within and between regions. When the spread of dengue fever from Chikan Districts to other districts was cut off, the number of cases in other districts dropped significantly or even to zero. When the density of mosquitoes in Xiashan District was controlled, the dengue fever epidemic in Xiashan District was found to be significantly alleviated. Conclusions: When there is a dengue outbreak, timely measures can effectively control it from developing into an epidemic. Different prevention and control measures in different districts could efficiently reduce the risk of disease transmission.

Background: Restoration of joint congruity is an important factor for the prevention of subsequent arthritis in patients with Bennett's fracture. Surgical treatment of Bennett's fracture is thus generally recommended for displaced intra-articular fractures to the proximal aspect of the thumb metacarpal. Fluoroscopic examination is used to evaluate the adequacy of closed reduction after pinning of Bennett's fracture. The purpose of this study was to determine the accuracy of fluoroscopy to determine the reduction of Bennett's fractures., Methods: A model was created, to mimic a Bennett's fracture utilizing ten fresh-frozen cadaveric hands. An oblique cut was made in the proximal aspect of the thumb metacarpal using an oscillating saw. The small oblique fragment involved 1/4-1/3 of the joint surface was then shifted in position creating a step-off or gap at the fracture site. An anatomical reduction model, gap models (1 mm, 2 mm, 3 mm), and step-off models (1 mm, 2 mm, 3 mm) were created using percutaneous fixation with two 1.0 mm Kirschner wires for each cadaveric hand. Fluoroscopic assessment then took place and was reviewed by 2 attending hand surgeons blinded to the actual position. Their estimated fluoroscopic position was then compared to the actual displacement., Results: The step-off and gap on fluoroscopic examination showed a significant difference compared to the step-off and gap from direct visualization. The frequency of underestimation for the 3 mm displacement models from the fluoroscopic examination was 60%. The frequency for overestimated was 9% for the models in which displacement was within 2 mm (0, 1, 2 mm)., Conclusions: The assessment of articular gap and step-off using PA (postero-anterior), AP (antero-posterior), and lateral view of fluoroscopic examination is not accurate as compared to the examination by direct visualization. Surgeons need to be aware that PA, AP and lateral view of fluoroscopic examination alone may not be sufficient to judge the final position of a reduced Bennett's fracture. Other methods such as live fluoroscopy in multiple different planes, 3-dimensional fluoroscopy or arthroscopic examination should be considered.

Infectious disease surveillance systems provide vital data for guiding disease prevention and control policies, yet the formalization of methods to optimize surveillance networks has largely been overlooked. Decisions surrounding surveillance design parameters-such as the number and placement of surveillance sites, target populations, and case definitions-are often determined by expert opinion or deference to operational considerations, without formal analysis of the influence of design parameters on surveillance objectives. Here we propose a simulation framework to guide evidence-based surveillance network design to better achieve specific surveillance goals with limited resources. We define evidence-based surveillance design as an optimization problem, acknowledging the many operational constraints under which surveillance systems operate, the many dimensions of surveillance system design, the multiple and competing goals of surveillance, and the complex and dynamic nature of disease systems. We describe an analytical framework-the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework-for the identification of optimal surveillance designs through mathematical representations of disease and surveillance processes, definition of objective functions, and numerical optimization. We then apply the framework to the problem of selecting candidate sites to expand an existing surveillance network under alternative objectives of: (1) improving spatial prediction of disease prevalence at unmonitored sites; or (2) estimating the observed effect of a risk factor on disease. Results of this demonstration illustrate how optimal designs are sensitive to both surveillance goals and the underlying spatial pattern of the target disease. The findings affirm the value of designing surveillance systems through quantitative and adaptive analysis of network characteristics and performance. The framework can be applied to the design of surveillance systems tailored to setting-specific disease transmission dynamics and surveillance needs, and can yield improved understanding of tradeoffs between network architectures., Competing Interests: The authors have declared that no competing interests exist.

Background: The purpose of this study was to prospectively recruit patients treated with limb malformation and to explore the prevalence and the clinical and epidemiological features of Heart-Hand Syndrome (HHS) in China., Methods: The consecutive patients treated for congenital upper limb malformation in Beijing Ji Shui Tan Hospital from October 1st, 2016 to October 1st, 2019 were prospectively recruited. We reviewed the patients' medical records and identified patients with abnormal electrocardiogram (ECG) and/or abnormal ultrasonic cardiogram as well as their basic demographic and clinical characteristics., Results: A total 1653 (1053 male and 600 female) patients with congenital upper extremity malformations were prospectively recruited. Among them, 200 (12.1%) had abnormal ultrasonic cardiogram (181patients, 10.9%) and/or abnormal ECG (19 patients, 1.1%). The commonest type of abnormal heart structure was atrial septal defect (69/181 38.1%), and the commonest abnormal ECG was wave patterns (7/19, 36.8%). HHS patients had a higher comorbidity rate (11%) than non-HHS patients (6.9%). Patients with HHS were classified into four groups by the types of congenital upper extremity malformations, among which the most common group was thumb type (121/200, 60.5%)., Conclusions: HHS occurred frequently among patients with congenital upper extremity malformation in China, particularly for those with multiple congenital malformations. The commonest type of hand malformations of HHS patients was thumb malformation.

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility., Competing Interests: The authors declare no competing interest.

Temperature is widely known to influence the spatio-temporal dynamics of vector-borne disease transmission, particularly as temperatures vary across critical thermal thresholds. When temperature conditions exhibit such 'transcritical variation', abrupt spatial or temporal discontinuities may result, generating sharp geographical or seasonal boundaries in transmission. Here, we develop a spatio-temporal machine learning algorithm to examine the implications of transcritical variation for West Nile virus (WNV) transmission in the Los Angeles metropolitan area (LA). Analysing a large vector and WNV surveillance dataset spanning 2006-2016, we found that mean temperatures in the previous month strongly predicted the probability of WNV presence in pools of Culex quinquefasciatus mosquitoes, forming distinctive inhibitory (10.0-21.0°C) and favourable (22.7-30.2°C) mean temperature ranges that bound a narrow 1.7°C transitional zone (21-22.7°C). Temperatures during the most intense months of WNV transmission (August/September) were more strongly associated with infection probability in Cx. quinquefasciatus pools in coastal LA, where temperature variation more frequently traversed the narrow transitional temperature range compared to warmer inland locations. This contributed to a pronounced expansion in the geographical distribution of human cases near the coast during warmer-than-average periods. Our findings suggest that transcritical variation may influence the sensitivity of transmission to climate warming, and that especially vulnerable locations may occur where present climatic fluctuations traverse critical temperature thresholds.

This article presents the application of a computational fluid dynamics (CFD) finite volume method (FVM) model for a thermo-mechanical coupling simulation of the weld pool used in variable polarity plasma arc welding (VPPAW). Based on the mechanism of the additional pressure produced through self-magnetic arc compression and the jet generated from mechanical plasma arc compression, and considering the influence of arc height and keyhole secondary compression on arc pressure, a three-dimensional transient model of variable polarity plasma arc (VPPA) arc pressure was established. The material flow behaviors of the perforated weld pools were studied. The results show that three kinds of flow behavior existed in the perforation weld pools and it is feasible to predict the weld pool stability by the material flow behaviors of the perforated weld pools. The weld pools can exist stably if the material flow in the bottom of the perforated weld pools can form confluences with moderate flow velocities of 0.45 m/s, 0.55 m/s and 0.60 m/s. The weld pools were cut when the material flowed downward and outward with the maximum velocity of 0.70 m/s, 0.80 m/s. When the maximum material flow velocity was 0.40 m/s, the weld pool collapsed downward under the action of larger gravity. The thermo-mechanical coupling model was verified by the comparison of the simulation and experimental results.

Mycobacterium tuberculosis (MTB) caused 10.4 million cases of tuberculosis and 1.7 million deaths in 2016. The incidence of multidrug-resistant and extensively drug-resistant MTB is becoming an increasing threat to public health and the development of novel anti-MTB drugs is urgently needed. Methionyl-tRNA synthetase (MetRS) is considered to be a valuable drug target. However, structural characterization of M. tuberculosis MetRS (MtMetRS) was lacking for decades, thus hampering drug design. Here, two high-resolution crystal structures of MtMetRS are reported: the free-state structure (apo form; 1.9 Å resolution) and a structure with the intermediate product methionyl-adenylate (Met-AMP) bound (2.4 Å resolution). It was found that free-state MtMetRS adopts a previously unseen conformation that has never been observed in other MetRS homologues. The pockets for methionine and AMP are not formed in free-state MtMetRS, suggesting that it is in a nonproductive conformation. Combining these findings suggests that MtMetRS employs an induced-fit mechanism in ligand binding. By comparison with the structure of human cytosolic MetRS, additional pockets specific to MtMetRS that could be used for anti-MTB drug design were located.

Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and an upper limb malformation. This study revealed the clinical and epidemiological features of HHS in China. The study was based on patients with congenital upper limb malformation treated in Beijing Ji Shui Tan hospital from October 1 st , 2013 to October 1 st , 2016. We reviewed the patients' medical records and identified patients with abnormal ultrasonic cardiogram and/or electrocardiogram (ECG). A total of 1462 patients (910 male and 552 female) were identified to be treated for congenital upper limb malformation. Among them, 172 (11.8%) had abnormal ultrasonic cardiogram and/or ECG. Abnormal heart structure were discovered in 121 patients and 51 patients had abnormal ECG. The most common type of abnormal heart structure was tricuspid regurgitation (53/121, 43.8%), while the most common abnormal ECG was wave patterns (22/51, 43.1%). This hospital-based study suggests that the rate of congenital heart disease is high in patients treated for congenital upper extremity malformation in China. Surgeons and anesthetists should be aware of the comorbidity and preoperational examination of congenital heart diseases is highly needed to avoid complications during operation.

Background: MicroRNAs(miRNAs)are involved in the initiation and progression of hepatocellular carcinoma. ESC, an extract of Stellerachamaejasme L, had been confirmed as a potential anti-tumor extract of Traditional Chinese Medicine. In light of the important role of miRNAs in hepatocellular carcinoma, we questioned whether the inhibitory effects of ESC on hepatocellular carcinoma (HCC) were associated with miRNAs., Methods: The proliferation inhibition of ESC on HCC cells was measured with MTT assay. The migration inhibition of ESC on HCC cells was measured with transwell assay. The influences of ESC on growth and metastasis inhibition were evaluated with xenograft tumor model of HCC. Protein expressions were measured with western blot and immunofluorescence methods and miRNA profiles were detected with miRNA array. Differential miRNA and target mRNAs were verified with real-time PCR., Results: The results showed that ESC could inhibit proliferation and epithelial mesenchymal transition (EMT) in HCC cells in vitro and tumor growth and metastasis in xenograft models in vivo. miRNA array results showed that 69 differential miRNAs in total of 429 ones were obtained in MHCC97H cells treated by ESC. hsa-miR-107, hsa-miR-638, hsa-miR-106b-5p were selected to be validated with real-time PCR method in HepG2 and MHCC97H cells. Expressions of hsa-miR-107 and hsa-miR-638 increased obviously in HCC cells treated by ESC. Target genes of three miRNAs were also validated with real-time PCR. Interestingly, only target genes of hsa-miR-107 changed greatly. ESC downregulated the MCL1, SALL4 and BCL2 gene expressions significantly but did not influence the expression of CACNA2D1., Conclusion: The findings suggested ESC regressed growth and metastasis of human hepatocellular carcinoma via regulating microRNAs expression and their corresponding target genes.

Background: Epithelial mesenchymal transition (EMT) mediated by TGF-β pays an important role in malignant tumor acquired abilities of migration and invasion. Our previous study showed that the extract of Stellera chamaejasme L. (ESC) was against proliferation of a variety of tumor cells, but there were no studies in the effects of ESC on EMT in tumor cells. In this study, TGF-β was adopted to induce EMT in HepG2 cells and the influence of ESC on EMT was observed., Methods: MTT assay was used to observe the cell viability. Wound healing assay and transwell assay were used to observe the migration and invasion activities. Western blot and immunofluorescence methods were used to observe the expression of proteins., Results: We found that HepG2 cells induced by TGF-β showed mesenchymal morphology, down-regulation of epithelial marker E-cadherin and up-regulation of mesenchymal marker Vimentin, indicating that TGF-β could mediate epithelial mesenchymal induction in HepG2 cells. ESC could reverse the mesenchymal morphology and regulate expressions of marker proteins in HepG2 induced by TGF-β and significantly inhibit TGF-β induced HepG2 cell migration and invasion. We further found that ESC could also significantly depress Smad2 phosphorylation and nuclear translocation, and ESC had coordination with SB432542, a specific inhibitor of TβRI kinases., Conclusions: These results suggested that the ESC could reverse epithelial mesenchymal transition induced by TGF-β via inhibition Smad2 signaling pathway.

Background: Stellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. In our previous study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2 had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC-2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor active fraction of ESC might exist in ESC-2. Here, we further observe the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo., Methods: In this study, we used hollow fiber tumor model to evaluate the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic rates of the cancer cells retrieved from the hollow fibers were measured with flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-α expression were determined with elisa assay and radioimmunoassay respectively., Results: The results showed that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the effect strength, dose and antitumor spectrum, the order of antitumor effects of ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs. ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas-L protein, but TNF-α/TNFR1 protein expression in NCI-H460 cells changed significantly after ESC and ESC-2 treatment., Conclusion: ESC-2 had the similar antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be the main antitumor active fraction of ESC, which was consistent with our previous results in vitro.

Background: Dysphagia after acute stroke is associated with poor prognosis, particularly if prolonged. Acupuncture has been widely used for this complication in China. However, its therapeutic effect is unclear., Objectives: To determine the therapeutic effect of acupuncture for dysphagia after acute stroke compared with placebo, sham or no acupuncture intervention., Search Strategy: We searched the Cochrane Stroke Group Trials Register (last searched September 2007), the Chinese Stroke Trials Register and the Trials Register of the Cochrane Complementary Medicine Field (last searched January 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2007). In January 2007 we searched the following databases from the first available date; MEDLINE, EMBASE, CINAHL, AMED, CISCOM, BIOSIS Previews, ProQuest Digital Dissertations, Science Citation Index, ISI Proceedings, ACUBRIEFS, ACP Journal Club, Books@Ovid and Journals@Ovid, Chinese Biological Medicine Database, Chinese scientific periodical database of VIP INFORMATION, China periodical in China National Knowledge Infrastructure, Chinese Evidence-Based Medicine Database, Science China, Chinese Social Science Citation Index, and the Chinese Science and Technology Document Databases. We also searched databases of ongoing trials, conference proceedings, and grey literature, handsearched three Chinese journals and contacted authors and researchers., Selection Criteria: We included all truly randomised controlled trials that evaluated the effect of acupuncture, irrespective of type, in patients with dysphagia within 30 day after the onset of ischaemic or haemorrhagic stroke. All types of acupuncture interventions were eligible. The control intervention could be placebo acupuncture, sham acupuncture, or no acupuncture. The primary outcome was recovery of normal feeding. The secondary outcomes were case fatality, deterioration, late disability, length of hospital stay, quality of life, feeding tube removal, aspiration pneumonia and nutritional measures., Data Collection and Analysis: Two review authors independently selected trials, assessed trial quality, and extracted data. Disagreements were resolved by a third review author., Main Results: Only one trial of 66 participants was included. In the acupuncture group, 12 out of 34 participants recovered to normal feeding (35.3%). In the control group, seven out of 32 participants recovered to normal feeding (21.9%). The relative risk of recovery was 1.61 with a 95% confidence interval of 0.73 to 3.58. No statistical significance was detected., Authors' Conclusions: There is not enough evidence to make any conclusion about the therapeutic effect of acupuncture for dysphagia after acute stroke. High quality and large scale randomised controlled trials are needed.

Aim: To investigate the suppressive effects of adenoviral vector-mediated expression of NK4, an antagonist of hepatocyte growth factor (HGF), on human colon cancer in an athymic mouse model to explore the possibility of applying NK4 to cancer gene therapy., Methods: A human colon tumor model was developed by subcutaneous implantation of tumor tissue formed by LS174T cells grown in athymic mice. Fifteen tumor-bearing mice were randomized into three groups (n = 5 in each group) at d 3 after tumor implantation and mice were injected intratumorally with phosphate-buffered saline (PBS) or with recombinant adenovirus expressing beta-galactosidase (Ad-LacZ) or NK4 (rvAdCMV/NK4) at a 6-d interval for total 5 injections in each mouse. Tumor sizes were measured during treatment to draw a tumor growth curve. At d 26 after the first treatment, all animals were sacrificed and the tumors were removed to immunohistochemically examine proliferating cell nuclear antigen (PCNA), microvessel density (represented by CD31), and apoptotic cells. In a separate experiment, 15 additional athymic mice were employed to develop a tumor metastasis model by intraperitoneal injection (ip) of LS174T cells. These mice were randomized into 3 groups (n = 5 in each group) at d 1 after injection and were treated by ip injection of PBS, or Ad-LacZ, or rvAdCMV/NK4 at a 6-d interval for total two injections in each mouse. All animals were sacrificed at d 14 and the numbers and weights of disseminated tumors within the abdominal cavity were measured., Results: Growth of human colon tumors were significantly suppressed in the athymic mice treated with rvAdCMV/NK4 (2537.4 +/- 892.3 mm(3)) compared to those treated by either PBS (5175.2 +/- 1228.6 mm(3)) or Ad-LacZ (5578.8 +/- 1955.7 mm(3)) (P < 0.05). The tumor growth inhibition rate was as high as 51%. Immunohistochemical staining revealed a similar PCNA labeling index (75.1% +/- 11.2% in PBS group vs 72.8% +/- 7.6% in Ad-LacZ group vs 69.3% +/- 9.4% in rvAdCMV/NK4 group) in all groups, but significantly lower microvessel density (10.7 +/- 2.4 in rvAdCMV/NK4 group vs 25.6 +/- 3.8 in PBS group or 21.3 +/- 3.5 in Ad-LacZ group, P < 0.05), and a markedly higher apoptotic index (7.3% +/- 2.4% in rvAdCMV/NK4 group vs 2.6 +/- 1.1% in PBS group or 2.1% +/- 1.5% in Ad-LacZ group, P < 0.05) in the rvAdCMV/NK4 group compared to the two control groups. In the tumor metastasis model, the number and weight of disseminated tumors of mice treated with rvAdCMV/NK4 were much lower than those of the control groups (tumor number: 6.2 +/- 3.3 in rvAdCMV/NK4 group vs 22.9 +/- 7.6 in PBS group or 19.8 +/- 8.5 in Ad-LacZ group, P < 0.05; tumor weight: 324 +/- 176 mg in rvAdCMV/NK4 group vs 962 +/- 382 mg in PBS group or 1116 +/- 484 mg in Ad-LacZ group, P < 0.05)., Conclusion: The recombinant adenovirus, rvAdCMV/NK4, can attenuate the growth of colon cancer in vivo, probably by suppressing angiogenesis and inducing tumor cell apoptosis, but not by direct suppression of tumor cell proliferation. Moreover, rvAdCMV/NK4 may inhibit peritoneal dissemination of colon cancer cells in a murine tumor metastasis model. These findings indicate that NK4 gene transfer may be an effective tool for the treatment of colon cancer.

Aim: To investigate the association between Chinese patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the polymorphisms of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene promoter (-318) and exon 1 (+49)., Methods: CTLA-4 promoter (-318 T/C) and exon1 (+49A/G) polymorphisms were genotyped via restriction fragment length polymorphism methods in 62 Chinese AIH patients, 77 Chinese PBC patients and 160 healthy controls., Results: We found a significant association in CTLA-4 gene exon1 49 A/G polymorphism between PBC patients and controls (P = 0.006) and the frequency of G alleles was significantly increased in comparison with controls (P = 0.0046, OR = 1.8). We also found the frequency of C alleles in promoter -318 was significantly increased in AIH patients compared with controls (P = 0.02, OR = 0.41). Although the genotype distribution of the CTLA-4 exon 1-promoter gene was not significantly different between AIH and PBC patients and controls, the occurrence of GG-CC was increased in two groups of patients (AIH: 32.3%, PBC: 37.7%, control: 22.5%)., Conclusion: Polymorphisms of CTLA-4 gene probably confer susceptibility to AIH and PBC in Chinese population.

The differential expression of the desired gene product in the target tissue is central for gene therapy. One approach is to use a tissue-specific promoter to drive therapeutic gene expression. UroplakinII (UPII) is a urothelium-specific membrane protein. To investigate the feasibility of targeting gene therapy for bladder cancer, a DNA fragment of 2542-bp upstream of the UPII gene was amplified by PCR and linked to a promoterless firefly luciferase reporter gene. The transient transfection showed that the DNA fragment resulted in preferential expression in bladder carcinoma cells, with negligible expression in nonurothelium cells. Furthermore, the DNA segment located between -2545 and -1608 decided the tissue-specificity of the UPII promoter, the segment located between -328 and -4 being the core promoter of UPII. We generated two recombinant adenoviruses under the control of the UPII promoter: Ad-hUPII-GFP, carrying green fluorescence protein (GFP), and Ad-hUPII-TNF, carrying the tumor necrosis factor alpha (TNFalpha). ELISA revealed that the secretion of TNFalpha by Ad-hUPII-TNF-infected bladder cancer cells was significantly higher than Ad-hUPII-TNF-infected nonurothelium cells. The conditioned medium from Ad-hUPII-TNF-infected bladder cancer cells apparently inhibited the proliferation of L929 cells, a TNFalpha-sensitive cell line, comparing to Ad-hUPII-TNF-infected nonurothelium cells. Intravesical inoculation with Ad-hUPII-TNF inhibited tumor growth in the orthotopic human bladder cancer model. The sustained high level of TNFalpha in urine was identified with ELISA. Taken together, these data suggest that most of the cis elements that confer the bladder-specificity and differentiation-dependent expression of the human UPII gene reside in the 2542-bp sequence, and TNFalpha driven by the human UPII (hUPII) promoter is effective in the specific inhibition of bladder cancer growth both in vivo and in vitro. These results may yield a new therapeutic approach for bladder cancer and provide information on the molecular regulation of urothelial growth, differentiation, and disease.

Mechanisms of angiotensin II and cAMP regulating the expression of angiotensin II type 1 (AT(1)) receptor mRNA were studied in neonatal rat cardiomyocytes. Angiotensin II induced a transient decrease of AT(1)-mRNA expression in time- and dose-dependent manner. Maximal decrease (49.2 +/- 9.5% of control) occurred at 6 h of angiotensin II (10 nmol/l) treatment. AT(1) receptor antagonists 4-ethyl-2-n-propyl-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid (DMP811) and losartan as well as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) reversed the down-regulation of AT(1)-mRNA expression. 6 h of phorbol 12-myristate 13-acetate (PMA) stimulation caused a decrease of AT(1)-mRNA level. Treatment by angiotensin II plus actinomycin D for 6 h produced the same effect as actinomycin D alone. These results suggest that angiotensin II down-regulates AT(1)-mRNA level of rat cardiomyocytes by inhibiting the transcription of AT(1) gene, which is mediated by AT(1) receptor and related to the activation of protein kinase C. Stimulation by forskolin plus 3-isobutyl-1-methyl-xanthine (IBMX) decreased the expression of AT(1)-mRNA to 68.1 +/- 21.5% of control at 6 h treatment; while increased to 207.9 +/- 27.1% of control at 48 h treatment. A series of 5'-upstream deletion mutants of AT(1A) promoter were produced and then were recombined with pGL(3) basic vector utilizing luciferase as reporter gene. Among all the constructors, p(-201/+ 74)Luc was of the highest luciferase activity (5.9 times higher than control) after stimulation by forskolin for 48 h. Further deletion from -201 to -61 resulted in a large decrease of activity. These results indicate that cAMP induces a time-dependent bi-directional regulation of AT(1)-mRNA expression. The cAMP responsible element (CRE) cis-element located in the region -201/-61 of rat AT(1A) promoter is forskolin inducible, which may mediate the up-regulation of AT(1)-mRNA expression induced by cAMP long-lasting stimulation., (Copyright 2002 Elsevier Science B.V.)

Objective: The pooled results of four large-scale clinical trials of antihypertensive treatments carried out in China were assessed, with an overall study population of 10,457 patients., Methods: The fixed effect model was used for data analysis., Results: A pooled analysis at the individual level showed that the average time of treatment was 3.4 years, after which an average reduction in blood pressure of 9/4 mmHg was found. The meta-analysis showed that stroke was reduced by 36% (95% CI 25%-46%, P < 0.001), cardiovascular death and total deaths were reduced by 22% and 20% respectively (P < 0.05) and total cardiovascular events were significantly reduced by 33% (P < 0.001). However, the reduction in coronary heart disease (CHD) was much smaller and was not statistically significant (P > 0.05), whereas the significant reduction in stroke was epidemiologically expected., Conclusion: The benefit of antihypertensive treatment obtained was mostly due to a reduction in the incidence of stroke.