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Dengue, a climate-sensitive mosquito-borne viral disease, is endemic in many tropical and subtropical areas, with Southeast Asia bearing the highest burden. In China, dengue epidemics are primarily influenced by imported cases from Southeast Asia. By integrating monthly maximum temperature and precipitation from Southeast Asia and local provinces in China, we aim to build models to predict dengue incidence in high-risk areas of China. From 2005–2023, a total of 117,839 dengue cases were reported, with Guangdong and Yunnan provinces accounting for 57.8 % and 26.2 % of cases, respectively. Large outbreaks occurred in 2014 (47,052 cases), 2019 (22,688 cases), and 2023 (19,936 cases), with peak incidence typically observed from August to October. The number of provinces reporting cases and outbreaks gradually linearly increased from 10 and 0 in 2005 to a peak of 30 and 11 in 2019, respectively, before declining in 2021 and 2022, then rebounding to 29 and 8 in 2023. Of the 13,927 imported cases, 91.3 % were from Southeast Asia, primarily from Myanmar (41.3 %) and Cambodia (27.3 %). Predictive models for dengue incidence in Guangdong Province showed high adjusted R2 values (0.993–0.999) and deviance explained values (0.975–0.989). The models from Cambodia, Thailand, and the Philippines outperformed the other six models. In Yunnan, adjusted R2 values and deviance explained values ranged from 0.81–0.84 and 0.90–0.92, respectively, with models from Laos, Myanmar and Cambodia achieving the best predictive performance. Incorporating meteorological data from Southeast Asia along with local data from China, we were able to develop accurate predictive models for dengue incidence in the high-risk areas of China.

IntroductionIn 2019, China experienced massive dengue outbreaks with high incidence and expanded outbreak areas. The study aims to depict dengue’s epidemiology and evolutionary dynamics in China and explore the possible origin of these outbreaks.MethodsRecords of confirmed dengue cases in 2019 were obtained from the China Notifiable Disease Surveillance System. The sequences of complete envelope gene detected from the outbreak provinces in China in 2019 were retrieved from GenBank. Maximum Likelihood trees were constructed to genotype the viruses. The median-joining network was used to visualize fine-scale genetic relationships. Four methods were used to estimate the selective pressure.ResultsA total of 22,688 dengue cases were reported, 71.4% of which were indigenous cases and 28.6% were imported cases (including from abroad and from other domestic provinces). The abroad cases were predominantly imported from Southeast Asia countries (94.6%), with Cambodia (3,234 cases, 58.9%), and Myanmar (1,097 cases, 20.0%) ranked as the top two. A total of 11 provinces with dengue outbreaks were identified in the central-south of China, of which Yunnan and Guangdong provinces had the highest number of imported and indigenous cases. The primary source of imported cases in Yunnan was from Myanmar, while in the other ten provinces, the majority of imported cases were from Cambodia. Guangdong, Yunnan and Guangxi provinces were China’s primary sources of domestically imported cases. Phylogenetic analysis of the viruses in outbreak provinces revealed three genotypes: (I, IV, and V) in DENV 1, Cosmopolitan and Asian I genotypes in DENV 2, and two genotypes (I and III) in DENV 3. Some genotypes concurrently circulated in different outbreak provinces. Most of the viruses were clustered with those from Southeast Asia. Haplotype network analysis showed that Southeast Asia, possibly Cambodia and Thailand, was the respective origin of the viruses in clade 1 and 4 for DENV 1. Positive selection was detected at codon 386 in clade 1.ConclusionDengue importation from abroad, especially from Southeast Asia, resulted in the dengue epidemic in China in 2019. Domestic transmission between provinces and positive selection on virus evolution may contribute to the massive dengue outbreaks.

Abstract Background Identifying and projecting the epidemiological burden of gastric cancer (GC) can optimize the control strategies, especially in high-burden areas. Methods We collected incidence, deaths, disability-adjusted life-years (DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized DALY rate (ASDR) of GC from 1990 to 2019 in China, Japan, South Korea, and Mongolia from the Global Burden of Disease Study 2019. The average annual percentage change (AAPC) was calculated to quantify the temporal trends, and the projection was estimated by applying the Bayesian age-period-cohort model. Results In China, the ASIR of GC declined slightly from 37.56/100000 in 1990 to 30.64/100000 in 2019 (AAPC of − 0.41), while the declines of ASMR and ASDR were pronounced (AAPC of − 1.68 and − 1.98, respectively), which were weaker than Japan and South Korea. Although the age-standardized rates of gastric cancer in most countries have declined overall in the past 30 years, the downward trend in the last 4 years has become flattened. Smoking remained one main contributor to DALYs of GC in China, Japan, South Korea, and Mongolia, with more than 24%. The contribution from high-sodium diet was similar between men and women, and kept relatively stable over the three decades. The predicted ASMRs among the four East Asian countries continued to decline until 2030, but the absolute deaths would still increase significantly, especially in South Korea and Mongolia. Conclusions Although the age-standardized rates of GC in most countries have declined, the absolute burden of GC in the world, especially in China and Mongolia, is on the rise gradually. Low socio-demographic index and aging along with Helicobacter pylori infection, smoking, and high-salt diet were the main risk factors of GC occurrence and should be paid more attention.

Abstract Background Clinically, there are no clear guidelines on the extent of lymphadenectomy in patients with T1 esophageal cancer. Studying the minimum number of lymph nodes for resection may increase cancer-specific survival. Methods Patients who underwent esophagectomy and lymphadenectomy at T1 stage were selected from the Surveillance, Epidemiology and End Results Program (United States, 1998–2014). Maximally selected rank and Cox proportional hazard models were used to examine three variables: the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio. Results Approximately 18% had lymph node metastases, where the median values were 10, 10 and 0 for the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio, respectively. All three examined variables were statistically associated with cancer-specific survival probability. Dividing patients into two groups shows a clear difference in cancer-specific survival compared to four or five groups for all three variables: there was a 29% decrease in the risk of death with the number of lymph nodes examined ≥14 vs 0.05 vs ≤ 0.05. Conclusions The extent of lymph node dissection is associated with cancer-specific survival, and the minimum number of lymph nodes that need to be removed is 14. The number of negative lymph nodes and the lymph node ratio also have prognostic value after lymphadenectomy among T1 stage patients.

Understanding the spatio-temporal patterns of the disease burden attributable to ambient PM2.5 across the world is essential for the prevention of related diseases, as well as ambient PM2.5 control. Following the framework and methodology of the Global Burden of Disease Study (GBD) in 2019, the global, regional, and national data on ambient PM2.5-attributable death and disability-adjusted life years (DALYs), and the age-standardized rates of mortality (ASMR) and disability-adjusted life years (ASDR) were summarized based on age, gender, year, location and specific diseases. We calculated the average annual percentage change (AAPC) to depict the secular trends of ASMR and ASDR from 1990 to 2019. In 2019, the global ambient PM2.5-related deaths and DALYs were 4,140,970 and 118.2 million, respectively, with 1,702,150 deaths and 47.5 million DALYs for females and 2,438,820 deaths and 70.7 million DALYs for male. In the 13 level-three causes, ischemic heart disease, stroke, chronic obstructive and pulmonary disease (COPD) were the leading three causes of deaths and DALYs attributable to ambient PM2.5. The number of global deaths and DALYs attributable to ambient PM2.5 has increased by 102.3% and 67.7% from 1990 to 2019, respectively. However, ASMR and ASDR showed little change. In the 13 level-three diseases, ischemic heart disease, stroke, COPD, diabetes mellitus, and lung cancer were the top five contributors to the increase of global deaths or DALYs, among which diabetes mellitus had the fastest increase of ASMR and ASDR, with AAPC of 1.5 (95% CI: 1.43, 1.58) and 2.21 (95% CI: 2.15, 2.27), respectively. The population attributable fractions (PAF) of causes in ASMR or ASDR varied significantly across regions, of which PAF of COPD, stroke and lung cancer were the top three. Regarding the GBD region, high PAF mainly occurred in North Africa and Middle East, South Asia, and East Asia. The age-specific PAFs of ischemic heart disease and stroke deaths and DALYs due to ambient PM2.5 were negatively correlated with age. ASMR and ASDR of overall PM2.5 related-burden showed an inverted “V/U” relationship with the socio-demographic index (SDI). The AAPC of ASMR and ASDR of the overall causes showed a strong negative correlation with SDI in 2019, especially at the SDI larger than 0.5. The deaths and DALYs attributable to ambient PM2.5 continued to increase under the context of population growth and aging. Decision-makers should consider controlling the PM2.5 emission when developing the economy.

BackgroundUnderstanding the epidemiological characteristics of various cancers can optimize the prevention and control strategies in the national cancer control plan. This study aimed to report the burden differences, pattern trend, and potential risk factors of all neoplasm types in China in recent 30 years, and further compared with top economies in the world.MethodsThe disability-adjusted life-years (DALYs) and age-standardized DALY rate (ASDR) of all neoplasms with the attributable risk factors from 1990 to 2019 in China, Japan, European Union, USA, and the world were extracted from the Global Burden of Disease Study 2019. The temporal trend analysis was estimated using the joinpoint regression model.ResultsIn 2019, about 251.4 million DALYs worldwide were caused by all neoplasms, and nearly 26.9% (67.5 million DALYs) occurred in China with the ASDR in 2019 of 342.09/10 000, which was higher than European Union (334.25/10 000), USA (322.94/10 000), and Japan (250.36/10 000). Although the cancer burden of the colorectum, non-Hodgkin lymphoma, oral cavity, ovary, and kidney in China was lower than in Japan, European Union and USA, the corresponding ASDR gradually increased in China over the past 30 years, but declined in the three developed areas. Around 46.29% of overall neoplasms DALYs in China in 2019 were attributed to 22 identified risk factors, and the specific risk attributable-fraction for several neoplasm types varied greatly in these regions.ConclusionThe ASDR of cancers of the lung, colorectum, pancreas, non-Hodgkin lymphoma, oral cavity, ovary, kidney, and chronic lymphoid leukemia increased in China compared to 30 years ago. With the population aging and the social transformation in China, the increasing burden of neoplasms and the changing spectrum of neoplasms suggest that effective comprehensive prevention and treatment measures should be adopted to reduce the burden, including public health education, strict tobacco-control policy, healthier lifestyles, along with expanding vaccination programs and early cancer screening.

BackgroundIn addition to traditional cardiovascular risk factors, gender-specific factors may also contribute to intracranial atherosclerosis. This study aimed to comprehensively investigate the association between asymptomatic intracranial atherosclerosis (aICAS) and menstrual or reproductive history (MRH), namely, menstruation, pregnancy, childbirth, menopause, and contraception.MethodsParticipants in this study were selected from the Kongcun town aICAS study. MRH was collected through structured case report forms, in which menarche age, menstrual regularity, dysmenorrhea, number of pregnancies, number of childbirths, age of first pregnancy, breastfeeding, menopause, menopause age, and contraceptive methods were all involved. All characteristics were compared by chi-squared and nonparametric tests as applicable. Logistic regression model and sensitivity analysis were used to analyze the association between aICAS and MRH.ResultsA total of 1,052 female participants were involved in this study, of which 5.7% had moderate to severe aICAS. Tubal ligation was significantly associated with aICAS in univariate analysis [crude odds ratio (OR), 2.85; 95% CI, 1.22–6.62; P = 0.015]. This association was still significant among female participants over 60 years old after multivariate adjustment (adjusted OR, 4.36; 95% CI, 1.55–12.24; P = 0.005). Sensitivity analysis showed a similar result (adjusted OR, 3.76; 95% CI, 1.24–11.41; P = 0.020). Menopause lost significant association with aICAS after multivariate adjustment (adjusted OR, 1.68; 95% CI, 0.66–4.24; P = 0.275). No other MRH factors were found to be associated with aICAS.ConclusionTubal ligation may be associated with a higher prevalence of aICAS in Chinese elderly women. This provides a new perspective to study the epidemiological characteristics of ICAS.

ObjectiveTo explore the influence of climatic, environmental and socioeconomic factors on SFTS occurrence in Shandong Province, China.MethodsWe used generalized additive model to estimate the association between SFTS cases and climatic factors, environmental factors and socioeconomic factors, including annual average temperature, precipitation, land cover, normalized difference vegetation index, altitude, population density, meat production, milk production, and gross domestic product (GDP).ResultsThere were a total of 4,830 cases reported in 100 (70.9%) counties and districts in Shandong Province from 2010 to 2020. The results showed that the annual average temperature, precipitation, forest and grassland coverage rate, altitude and meat production (square root transform) had a reversed “V” relationship with SFTS occurrence, with the inflection points around 12.5–13.0°C in temperature, around 650 mm in precipitation, around 0.3 in forest and grassland coverage rate, around 300 m in altitude, and around 200–300 tons in meat production (square root transform), respectively. SFTS occurrence had a “V” relationship with milk production (square root transform) and GDP (square root transform), with the inflection points around 100–200 tons in milk production (square root transform), and around 150,000–200,000 yuan in GDP (square root transform), respectively.ConclusionsClimatic, environmental, and socioeconomic factors contributed to the heterogeneous distribution of SFTS in Shandong Province, and the influence of these factors on SFTS occurrence was nonlinear.

IntroductionDengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited.MethodsRecords of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China.ResultsA total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province.ConclusionsDengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.

Abstract Purpose Although homocysteine (Hcy) has been proven to be associated with the incidence of white matter hyperintensities (WMH) in patients with stroke, this association remains unclear in participants with asymptomatic intracranial arterial stenosis (aICAS). This study aimed to investigate the association of Hcy with WMH in participants with aICAS. Materials and methods This was a cross‐sectional study based on the Kongcun Town Study. Participants diagnosed with aICAS by magnetic resonance angiography in the Kongcun Town Study were enrolled in this study. Data on demographics, lifestyle, medical histories, and Hcy levels were collected via interviews, clinical examinations, and laboratory tests. The volume of WMH was calculated using the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging. The association between Hcy and WMH volume was analyzed using linear and logistic regression analyses. Results A total of 137 aICAS participants were enrolled in the present study. Hcy was associated with the incidence of severe WMH (4th quartile, ≥4.20 ml) after adjustment for certain covariates [Hcy as a continuous variable, odds ratio (95% confidence interval) (OR (95% CI)): 1.09 (1.00, 1.19), p = .047; as a categorical variable (Hcy ≥15 μmol/L), OR (95% CI): 3.74 (1.37, 10.19), p = .010)]. After stratification according to the degree of aICAS, this relationship remained significant only in the moderate‐to‐severe stenosis group (stenosis ≥50%). (Hcy as continuous variable, OR (95% CI): 1.14 (1.02, 1.27), p = .025; as a categorical variable (Hcy ≥15 μmol/L), OR (95% CI): 5.59 (1.40, 15.25), p = .015). Conclusion Serum Hcy concentration may be positively associated with the volume of WMH in rural‐dwelling Chinese people with moderate‐to‐severe (stenosis ≥50%) aICAS.

Metabolic syndrome (MetS) can worsen cerebral arterial atherosclerosis stenosis in patients with stroke; however, its effect on patients without stroke remains ambiguous. This study explored the association of MetS and its individual components with asymptomatic intracranial arterial stenosis (aICAS) and asymptomatic extracranial arterial stenosis (aECAS) among older Chinese adults. A total of 1988 participants from the Kongcun Town study aged ≥40 years and without a history of stroke were enrolled. The baseline data were obtained via face-to-face interviews. MetS was defined according to International Diabetes Federation criteria. Detection of aICAS was conducted using transcranial Doppler ultrasound, followed by diagnosis via magnetic resonance angiography. The evaluation of aECAS was performed using bilateral carotid ultrasonography. The aICAS and aECAS groups were 1:1 matched separately to the non-stenosis group by age and sex. The association between MetS and aICAS or aECAS was analyzed using multivariate logistic regression. Among the 1988 participants, 909 were diagnosed with MetS. The prevalence of MetS was higher in the aICAS group than in the non-stenosis group (P

Background. Popularization of cervical ultrasound led to higher detection of papillary thyroid carcinoma (PTC) and primary hyperparathyroidism (PHPT), as well as increasing percentage of asymptomatic PHPT in China. Although the coexistence of PTC and PHPT has been reported, it is unknown whether the clinicopathological features of PTC differ between asymptomatic and symptomatic PHPT patients. Methods. We retrospectively reviewed the medical records of 304 PHPT patients treated in our hospital between January 2009 and July 2020, including 217 females and 87 males with the average age of 53.27 ± 13.54 years. Of the 304 patients, 181 were symptomatic PHPT patients and 123 were asymptomatic PHPT patients. We analyzed the laboratory results, postoperative pathology, and the TNM stage of PTC between asymptomatic and symptomatic PHPT patients. Results. Concurrent thyroid nodules were found in 61.51% of PHPT patients, and the prevalence of PTC in thyroidectomized PHPT patients was 29.89% in our cohort. Lower serum parathyroid hormone (PTH) (p

Introduction Recent studies have shown that insulin resistance (IR) is correlated to atherosclerosis development. However, few studies have investigated the association between IR and asymptomatic intracranial arterial stenosis (aICAS).Research design and methods This cross-sectional study enrolled 2007 rural residents in China who were aged ≥40 years without a clinical history of stroke and transient ischaemic attack. We used transcranial Doppler ultrasonography in combination with magnetic resonance angiography to diagnose aICAS (stenosis ≥50%). IR was defined as a homeostasis model assessment of insulin resistance ≥3.0 based on the 75th percentile for all the participants. Multivariate logistic regression models were employed to assess the relationship of diabetic parameters with aICAS in all participants, as well as with aICAS in non-diabetic participants, and further stratified by sex.Results After adjusting for age, gender, smoking habit, drinking habit, low-density lipoprotein cholesterol, raised blood pressure, triglycerides, high-density lipoprotein cholesterol and waist circumference, diabetes mellitus (DM) (OR=2.09, 95% CI 1.31 to 3.32), fasting plasma glucose (FPG) (OR=1.34, 95% CI 1.14 to 1.57), and IR (OR=1.75, 95% CI 1.11 to 2.75) were associated with aICAS in the total study population; however, these relationships remained significant only in men after the analyses were stratified by sex (DM: OR=3.40, 95% CI 1.62 to 7.13; FPG: OR=1.64, 95% CI 1.26 to 2.13; IR: OR=3.04, 95% CI 1.44 to 6.42). When further excluding the diabetic participants from the total study population, positive associations between IR and aICAS were similarly observed only in men (OR=4.65, 95% CI 1.69 to 12.82).Conclusions IR might predict the prevalence of aICAS independently of major cardiovascular risk factors and metabolic syndrome components among men living in rural China.

Purpose The population-based Kongcun Town Asymptomatic Intracranial Artery Stenosis (KT-aICAS) study aims to investigate the prevalence of aICAS and major cardiovascular risk factors (CRFs) or biomarkers related to the development and prognosis of aICAS.Participants The KT-aICAS study included 2311 rural residents who were aged ≥40 years and living in Kongcun Town, Shandong Province, China. Baseline examination was conducted from October 2017 to October 2018, during which information on demographics, socioeconomics, personal and family medical history, and lifestyle factors was collected through face-to-face interviews, physical examination and blood tests. aICAS was initially screened using transcranial Doppler examination and then diagnosed using magnetic resonance angiography. Atherosclerosis in carotid arteries was diagnosed via carotid ultrasonography. High-resolution MRI was further used to evaluate the vessel wall of aICAS. Neuropsychological assessments were performed in the participants diagnosed with aICAS and the age-matched and sex-matched controls.Findings to date Of the 2311 participants, 2027 (87.7%) completed the diagnostic procedure and aICAS was detected in 154 persons, resulting in an overall prevalence of 7.6%. The prevalence of aICAS increased with advancing age from 5.1% in participants aged 40–49 years to 12.7% in those aged ≥70 years (p

Objective: To explore the epidemiological trend of dengue in mainland China. Methods: Data on dengue cases reported from 2005 to 2015 were collected, and epidemiological trends, including average age, occupation, seasonal distribution, and interval from illness onset to confirmation, were analyzed using SPSS 19.0 and R 3.1.1. Results: A total of 59 334 dengue cases were recorded in China during the years 2005–2015. Most dengue cases occurred in individuals aged between 21 years and 50 years. Of note, the median age of dengue cases did not show a trend towards becoming younger; the median age was significantly older than that of cases in dengue endemic areas. The proportion of cases occurring during September and October was higher in 2012–2015 than in 2005–2011. The number of affected provinces ranged between 10 and 27 and the number of affected counties ranged between 42 and 415. The median time from illness onset to confirmation of dengue decreased sharply in 2015, indicating that comprehensive measures have been taken in mainland China. Conclusions: Although the number of dengue cases has increased and the affected areas have expanded in recent years, dengue is still an imported disease and does not present an endemic trend in mainland China.

Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C > T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P

Dengue virus serotype 4 (DENV 4) has had a relatively low prevalence worldwide for decades; however, likely due to data paucity, no study has investigated the epidemiology and evolutionary dynamics of DENV 4 genotype I (DENV 4-I). This study aims to understand the diversity, epidemiology and dynamics of DENV 4-I. We collected 404 full length DENV4-1 envelope (E) gene sequences from 14 countries using two sources: Yunnan Province in China (15 strains during 2013-2016) and GenBank (489 strains up to 2018-01-11). Conducting phylogenetic and phylogeographical analyses, we estimated the virus spread, population dynamics, and selection pressures using different statistical analysis methods (substitution saturation, likelihood mapping, Bayesian coalescent inference, and maximum likelihood estimation). Our results show that during the last 60 years (1956-2016), DENV 4-I was present in mainland and maritime Southeast Asia, the Indian subcontinent, the southern provinces of China, parts of Brazil and Australia. The recent spread of DENV 4-I likely originated in the Philippines and later spread to Thailand. From Thailand, it spread to adjacent countries and eventually the Indian subcontinent. Apparently diverging around years 1957, 1963, 1976 and 1990, the different Clades (Clade I-V) were defined. The mean overall evolution rate of DENV 4-I was 9.74 (95% HPD: 8.68-10.82) × 10-4 nucleotide substitutions/site/year. The most recent common ancestor for DENV 4-I traces back to 1956. While the demographic history of DENV 4-I fluctuated, peaks appeared around 1982 and 2006. While purifying selection dominated the majority of E-gene evolution of DENV 4-I, positive selection characterized Clade III (Vietnam). DENV 4-I evolved in situ in Southeast Asia and the Indian subcontinent. Thailand and Indian acted as the main and secondary virus distribution hubs globally and regionally. Our phylogenetic analysis highlights the need for strengthened regional cooperation on surveillance and sharing of sample sequences to improve global dengue control and cross-border transmission prevention efforts.

Background During the winter of 2014–2015, a rarely reported norovirus (NoV) genotype GII.17 was found to have increased its frequency in norovirus outbreaks in East Asia, surpassing the GII.4 NoV infections. GII.17 genotype has been detected for over three decades in the world. The aim of this study is to examine the evolutionary dynamics of GII.17 over the last four decades. Methods NoV GII.17 sequences with complete or nearly complete VP1 were downloaded from GenBank and the phylogenetic analyses were then conducted. Results The maximum likelihood analysis showed that GII.17 genotype could be divided into four different clades (Clades A–D). The strains detected after 2012, which could be the cause of the outbreaks, were separated into Clades C–D with their mean amino acid distance being 4.5%. Bayesian Markov chain Monte Carlo analyses indicated that the rate of nucleotide substitution per sites was 1.68 × 10−3 nucleotide substitutions/site/year and the time of the most recent common ancestor was 1840. The P2 subdomain of GII.17 was highly variable with 44% (56/128) amino acids variations including two insertions at positions 295–296 and one deletion at position 385 (Clades C and D) and one insertion at position 375 (Clade D). Variations existed in Epitopes A, B and D corresponding to GII.4 and human histo-blood group antigens binding site I in P2 subdomain. Conclusion The novel GII.17 strains that caused outbreaks in 2013–2015 may have two new variants. The evolvement of HBGAs binding site and epitopes in P2 subdomain might contribute to the novel GII.17 strains predominance in some regions.

Background The current TNM classification system does not consider tumor length for patients with esophageal carcinoma (EC). This study explored the effect of tumor length, in addition to tumor depth and lymph node involvement, on survival in patients with esophageal squamous cell carcinoma (ESCC). Methods A total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study. Pathological details were collected, which included tumor type, TNM stage, differentiation. Other collected information were: the types of esophageal resection, ABO blood group, family history and demographic and lifestyle factors. A time-dependent receiver operating characteristic (ROC) curve and a regression tree for survival were used to identify the cut-off point of tumor length, which was 3 cm. Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC. Results & Discussion The 1-, 3-, 5-year overall survival rates were found to be 82.5%, 55.6%, and 35.1%, respectively. Patients who had larger tumor length (>3 cm) had a higher risk for death than the rest patients. From the univariate Cox proportional hazards regression model, the overall survival rate was significantly influenced by the depth of the tumor and lymph node involvement (either as dummy or continuous variables), Sex, and tumor length. Using these four variables in the multivariate Cox proportional hazard regression model, we found that the overall survival was significantly influenced by all variables except Sex. Therefore, in addition to the depth of the tumor and lymph node involvement (as either dummy or continuous variables), the tumor length is also an independent prognostic factor for ESCC. The overall survival rate was higher in a group with smaller tumor length (≤3 cm) than those patients with larger tumor length (>3 cm), no matter what the tumor stage was. Conclusion The tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy. The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.

BACKGROUND:There was a dengue epidemic in several regions of China in 2013. No study has explored the dynamics of dengue transmission between different geographical locations with dengue outbreaks in China. The purpose of the study is to analyze the epidemiological characteristics and to explore the dynamic transmission of dengue in China, 2013. METHODOLOGY AND PRINCIPAL FINDINGS:Records of dengue cases of 2013 were obtained from the China Notifiable Disease Surveillance System. Full E-gene sequences of dengue virus detected from the outbreak regions of China were download from GenBank. Geographical Information System and heatmaps were used to describe the epidemiological characteristics. Maximum Likelihood phylogenetic and Bayesian phylogeographic analyses were conducted to explore the dengue dynamic transmission. Yunnan Province and Guangdong Province had the highest imported cases in the 2013 epidemic. In the locations with local dengue transmission, most of imported cases occurred from June to November 2013 while local dengue cases developed from July to December, 2013. There were significant variations for the incidences of dengue, in terms of age distributions, among different geographic locations. However, gender differences were identified in Guangzhou, Foshan and Xishuangbanna. DENV 1-3 were detected in all locations with the disease outbreaks. Some genotypes were detected in more than one locations and more than one genotypes have been detected in several locations. The dengue viruses introduced to outbreak areas were predominantly from Southeast Asia. In Guangdong Province, the phylogeographical results indicated that dengue viruses of DENV 1 were transmitted to neighboring cities Foshan and Zhongshan from Guangzhou city, and then transmitted to Jiangmen city. The virus in DENV 3 was introduced to Guangzhou city, Guangdong Province from Xishuangbanna prefecture, Yunnan Province. CONCLUSIONS:Repeated dengue virus introductions from Southeast Asia and subsequent domestic dengue transmission within different regions may have contributed to the dengue epidemics in China, 2013.

INTRODUCTION:Dengue is endemic in more than 100 countries, mainly in tropical and subtropical regions, and the incidence has increased 30-fold in the past 50 years. The situation of dengue in China has become more and more severe, with an unprecedented dengue outbreak hitting south China in 2014. Building a dengue early warning system is therefore urgent and necessary for timely and effective response. METHODOLOGY AND PRINCIPAL FINDINGS:In the study we developed a time series Poisson multivariate regression model using imported dengue cases, local minimum temperature and accumulative precipitation to predict the dengue occurrence in four districts of Guangzhou, China. The time series data were decomposed into seasonal, trend and remainder components using a seasonal-trend decomposition procedure based on loess (STL). The time lag of climatic factors included in the model was chosen based on Spearman correlation analysis. Autocorrelation, seasonality and long-term trend were controlled in the model. A best model was selected and validated using Generalized Cross Validation (GCV) score and residual test. The data from March 2006 to December 2012 were used to develop the model while the data from January 2013 to September 2014 were employed to validate the model. Time series Poisson model showed that imported cases in the previous month, minimum temperature in the previous month and accumulative precipitation with three month lags could project the dengue outbreaks occurred in 2013 and 2014 after controlling the autocorrelation, seasonality and long-term trend. CONCLUSIONS:Together with the sole transmission vector Aedes albopictus, imported cases, monthly minimum temperature and monthly accumulative precipitation may be used to develop a low-cost effective early warning system.

Each year there are approximately 390 million dengue infections worldwide. Weather variables have a significant impact on the transmission of Dengue Fever (DF), a mosquito borne viral disease. DF in mainland China is characterized as an imported disease. Hence it is necessary to explore the roles of imported cases, mosquito density and climate variability in dengue transmission in China. The study was to identify the relationship between dengue occurrence and possible risk factors and to develop a predicting model for dengue's control and prevention purpose.Three traditional suburbs and one district with an international airport in Guangzhou city were selected as the study areas. Autocorrelation and cross-correlation analysis were used to perform univariate analysis to identify possible risk factors, with relevant lagged effects, associated with local dengue cases. Principal component analysis (PCA) was applied to extract principal components and PCA score was used to represent the original variables to reduce multi-collinearity. Combining the univariate analysis and prior knowledge, time-series Poisson regression analysis was conducted to quantify the relationship between weather variables, Breteau Index, imported DF cases and the local dengue transmission in Guangzhou, China. The goodness-of-fit of the constructed model was determined by pseudo-R2, Akaike information criterion (AIC) and residual test. There were a total of 707 notified local DF cases from March 2006 to December 2012, with a seasonal distribution from August to November. There were a total of 65 notified imported DF cases from 20 countries, with forty-six cases (70.8%) imported from Southeast Asia. The model showed that local DF cases were positively associated with mosquito density, imported cases, temperature, precipitation, vapour pressure and minimum relative humidity, whilst being negatively associated with air pressure, with different time lags.Imported DF cases and mosquito density play a critical role in local DF transmission, together with weather variables. The establishment of an early warning system, using existing surveillance datasets will help to control and prevent dengue in Guangzhou, China.

BACKGROUND: Norovirus (NoV) has been recognized as the most important cause of nonbacterial acute gastroenteritis affecting all age group people in the world. Genetic recombination is a common occurance in RNA viruses and many recombinant NoV strains have been described since it was first reported in 1997. However, the knowledge of recombinant NoV in China is extremely limited. METHODS: A total of 685 stool specimens were tested for NoV infection from the acute gastroenteritis patients who visited one general hospital in Beijing from April 2009 to November 2011. The virus recombination was identified by constructing phylogenetic trees of two genes, further SimPlot and the maximum chi-square analysis. RESULTS: The overall positive rate was 9.6% (66/685). GII.4 New Orleans 2009 and GII.4 2006b variants were the dominant genotype. Four GII.g/GII.12 and one GII.12/GII.3 recombinant strains were confirmed, and all derived from adult outpatients. The predictive recombination point occurred at the open reading frame (ORF)1/ORF2 overlap. CONCLUSIONS: The GII.g ORF1/GII.12ORF2 recombinant has been reported in several countries and it was the first report of this recombinant in China.

Purpose The population-based Kongcun Town Asymptomatic Intracranial Artery Stenosis (KT-aICAS) study aims to investigate the prevalence of aICAS and major cardiovascular risk factors (CRFs) or biomarkers related to the development and prognosis of aICAS. Participants The KT-aICAS study included 2311 rural residents who were aged ≥40 years and living in Kongcun Town, Shandong Province, China. Baseline examination was conducted from October 2017 to October 2018, during which information on demographics, socioeconomics, personal and family medical history, and lifestyle factors was collected through face-to- face interviews, physical examination and blood tests. aICAS was initially screened using transcranial Doppler examination and then diagnosed using magnetic resonance angiography. Atherosclerosis in carotid arteries was diagnosed via carotid ultrasonography. High-resolution MRI was further used to evaluate the vessel wall of aICAS. Neuropsychological assessments were performed in the participants diagnosed with aICAS and the age-matched and sex-matched controls. Findings to date Of the 2311 participants, 2027 (87.7%) completed the diagnostic procedure and aICAS was detected in 154 persons, resulting in an overall prevalence of 7.6%. The prevalence of aICAS increased with advancing age from 5.1% in participants aged 40–49 years to 12.7% in those aged ≥70 years (p<0.001). aICAS was detected in 305 intracranial arteries, including 221 (72.5%) in the anterior circulation and 84 (27.5%) in the posterior circulation (p<0.001). In addition, major CRFs were highly prevalent among middle-aged and elderly rural dwellers who were free of clinical stroke. Future plans Follow-up examinations will be performed every 3 years following the baseline examination. This study will increase our knowledge about the natural history of aICAS and facilitate studies of aICAS-associated disorders among rural-dwelling Chinese adults, such as ischaemic stroke and vascular cognitive impairment. [ABSTRACT FROM AUTHOR]