[Epidemiological characteristics of typhoid fever and paratyphoid fever in China, 2004-2020].

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever and paratyphoid fever in China from 2004 to 2020, understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The descriptive epidemiological method and spatial analysis method were applied to analyze the epidemiological characteristics of typhoid fever and paratyphoid fever in China during this period by using the surveillance data collected from the National Notifiable Infectious Disease Reporting System of Chinese Center for Disease Control and Prevention. Results: A total of 202 991 cases of typhoid fever were reported in China from 2004 to 2020. More cases occurred in men than in women (sex ratio: 1.18∶1). Most cases were reported in adults aged 20-59 years (53.60%). The incidence rate of typhoid fever decreased from 2.54/100 000 in 2004 to 0.38/100 000 in 2020. The highest incidence rate was reported in young children aged <3 years after 2011, ranging from 1.13/100 000 to 2.78/100 000, and during this period the proportion of cases in this age group increased from 3.48% to 15.59%. The proportion of the cases in the elderly aged ≥60 years increased from 6.46% in 2004 to 19.34% in 2020. The hotspot areas existed in Yunnan, Guizhou, Guangxi and Sichuan Provinces and expanded to Guangdong, Hunan, Jiangxi, and Fujian Provinces. A total of 86 226 paratyphoid fever cases were reported from 2004 to 2020, the male to female ratio of the cases was 1.21∶1. Most cases were reported in adults aged 20-59 years (59.80%). The incidence rate of paratyphoid fever decreased from 1.26/100 000 in 2004 to 0.12/100 000 in 2020. The highest incidence rate of paratyphoid fever was in young children aged <3 years after 2007, ranging from 0.57/100 000 to 1.19/100 000, and during this period the proportion of the cases in this age group increased from 1.48% to 30.92%. The proportion of the cases in the elderly aged ≥60 years increased from 4.52% in 2004 to 22.28% in 2020. The hotspot areas expanded to the east, including Guangdong, Hunan and Jiangxi Provinces, from Yunnan, Guizhou, Sichuan, and Guangxi Provinces. Conclusions: The results showed a low level of incidence of typhoid fever and paratyphoid fever in China with a trend of decreasing per year. The hotspots were mainly in the of Yunnan, Guizhou, Guangxi and Sichuan Provinces, with an expanding trend to eastern China. It is necessary to strengthen the typhoid fever and paratyphoid fever prevention and control in southwestern China, among young children aged <3 years and the elderly aged ≥60 years.

[Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021].

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

Prognosis of direct pregnancy in untreated atypical endometrial hyperplasia: a case report.

BACKGROUND: An increasing number of atypical endometrial hyperplasia (AEH) or endometrial cancer (EC) patients with fertility requirements choose conservative management, such as oral high-dose progesterone. Most of them use assisted reproductive technology (ART) to become pregnant after experiencing remission. However, the outcome of pregnancy is not ideal, probably because of long-term drug application in large doses or invasive uterine cavity treatment. CASE REPORT: We presented a case of AEH who underwent direct pregnancy with good results without any treatment for her pathological endometrium. We described her endometrial histological results pre-and post-pregnancy in detail, hitherto absent from reports on this topic. CONCLUSIONS: Patients with a strong desire to bear children at the time of an AEH diagnosis could consider taking 1-2 years to try a pregnancy before treating their AEH.

[Incidence and risk factors of thromboembolism in patients with lung cancer receiving immunotherapy].

Objective: To evaluate the incidence of thromboembolism in a cohort of patients with lung cancer who received immune checkpoint inhibitors (ICIs), and explore relevant clinical risk factors. Methods: We retrospectively collected and analyzed the clinical data of patients with confirmed primary lung cancer and treated with ICIs between March 2018 and June 2021 at three hospitals in China (Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Fudan University Shanghai Cancer Center and Zhongshan Hospital of Fudan University). The cumulative incidence and risk factors of thromboembolism in these patients were analyzed using a competitive risk model. Results: A total of 804 patients were enrolled, there were 623 males and 181 females, with a median age of 59 years (ranged 28-86 years). Of these, 62 patients encountered 65 thromboembolic events, including 51 venous thromboembolism events (VTE) and 14 arterial thromboembolism events. The cumulative incidence of thromboembolism events at 3, 6, 12 and 24 months were 4.3%, 6.1%, 10.1% and 16.8%, respectively. And the cumulative incidence of venous thromboembolism events at 3, 6, 12 and 24 months were 3.4%, 4.7%, 9.0% and 13.3%, respectively. Multivariate analysis showed that history of thromboembolism (HR=6.345, 95%CI: 2.917-13.802,P<0.001),liver metastasis (HR=2.249, 95%CI: 1.123-4.502,P=0.022) and peripherally inserted central venous catheter (HR=3.674, 95%CI: 1.751-7.712, P<0.001) were independent risk factors for venous thromboembolism during ICIs therapy in patients with lung cancer. Conclusions: Patients with lung cancer under ICIs therapy are at high risk of thromboembolism. And history of thromboembolism, liver metastasis and peripherally inserted central venous catheter are risk factors of venous thromboembolism.

Research Progress on Pathological Fibrosis of Sinoatrial Node.

ABSTRACT: Human heart rhythm is mainly regulated and controlled by the sinoatrial node. Fibrosis plays an important regulating role in adjusting the structural and functional integrity of the sinoatrial node pacemaker complex. In physiological state, the fibrosis degree of sinoatrial node is negatively correlated with heart rate, positively correlated with age and heart size, and can maintain a relatively stable heart rate. Pathological fibrosis of sinoatrial node can induce various types of arrhythmias which can result in sudden death. Determination of the mechanisms related to sinoatrial node pathological fibrosis could provide a target for clinical treatment of sinoatrial node fibrosis and diagnosis basis for forensic pathologists. This paper reviews the main mechanism of sinoatrial node pathological fibrosis, including abnormal activation of cardiac fibroblast cells in sinoatrial node, hyperplasia of epicardial adipose tissue, calcium clock disorder, artery stenosis, etc., introduces the test methods, diagnostic criteria as well as its role in sudden cardiac death and discusses the potential application, to provide reference for relevant research and application.

[Epidemiological characteristics of severe cases of hand, foot, and mouth disease in China, 2008-2018].

Objective: To characterize the epidemiology of severe hand, foot and mouth disease (HFMD) in China from 2008 to 2018 and provide evidence for the prevention and control of severe HFMD. Methods: The incidence data of severe HFMD cases from 2008 to 2018 were collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze distributions, pathogen constituent and change of severe HFMD. Joinpoint regression model was used to analyze the trends of severity rate, proportion of severe cases and severe fatality rate. Results: From 2008 to 2018, a total of 157 065 cases of severe HFMD were reported in China, with an average annual case-severity rate of 1.05/100 000, a severe case proportion of 0.76% and a severity-fatality rate of 2.34%. The severity rate and the proportion of severe cases showed a downward trend after 2010, and severe fatality rate decreased significantly after 2014. The severe cases mainly occurred in infants aged ≤3 years (91.47%), more boys were affected than girls (1.78∶1). The median age of severe HFMD cases caused by EV-A71 was highest (1.99 years) and increased year by year, other enterovirus infection cases accounted for a higher proportion in infants aged ≤1 year (66.56%). The incidence peak occurred during April-July, other enteroviruses replaced EV-A71 as the predominant serotype in 2018 (61.97%). The incidence of severe HFMD were high in some provinces in southwestern, central and eastern China. Conclusion: The overall severity rate, proportion of severe cases and severe fatality rate of HFMD in the mainland of China have shown a downward trend. The predominant pathogen in some provinces has changed from EV-A71 to other enteroviruses. It is necessary to strengthen the prevention and control of HFMD in key population, high incidence seasons and areas and carry out the surveillance of various pathogens of HFMD.

[Clinical efficacy of cyberknife in patients with primary large hepatocellular carcinoma over 70 years old].

Objective: To analyze the clinical efficacy and safety of cyberknife in the treatment of patients with primary large hepatocellular carcinoma over 70 years old. Methods: A total of 82 patients (58 males and 24 females) with large hepatocellular carcinoma aged over 70 years (70 to 85 years, (75±4) years) with a median tumor diameter of 6.7 cm (5.0~10.0 cm) were retrospectively collected. All patients were diagnosed by pathology or radiography in the Cancer Radiotherapy Center of the Fifth Medical Center of the PLA General Hospital from March 2014 to December 2018, and treated with cyberknife stereotactic radiotherapy. Progression free survival rate (PFS), local control rate (LC), overall survival rate (OS) and adverse reactions were observed at 1, 2 and 3 years. Kaplan-Meier was used for survival analysis, and Cox regression model was used to analyze survival-related factors. Results: All 82 patients successfully completed radiation therapy with a median survival time of 20 months, a median PFS of 10 months, an objective response rate of 64.63% (53/82), and a disease control rate of 85.37% (70/82). After treatment, the PFS at 1, 2, and 3 years were 39.0% (32/82), 22.1% (18/82), and 17.1% (14/82), respectively; the LC at 1, 2, and 3 years were 95.1% (78/82), 92.3% (76/82), and 92.3% (76/82), respectively; and the OS at 1, 2, and 3 years were 68.3% (56/82), 48.8% (40/82) and 31.7% (26/82), respectively. Nine patients suffered from radiation-induced liver disease (RILD), and there were no deaths due to RILD. Cox regression analysis showed that alpha-fetoprotein (AFP) was an independent risk factor for OS (HR=2.304, 95%CI 1.118-4.747;P<0.05). Conclusion: Cyberknife treatment for patients with primary large hepatocellular cancer over 70 years old has higher LC and OS, better curative effect, and less treatment-related adverse reactions.

[Epidemiological characteristics of fatal cases of hand, foot, and mouth disease in children under 5 years old in China, 2008-2018].

Objective: To understand the epidemiological characteristics and risk factors of fatal cases of hand, foot, and mouth disease (HFMD) in children under 5 years old in China from 2008 to 2018, and provide evidence for the development of targeted prevention and control measures and reduction of the incidence of fatal HFMD cases. Methods: The incidence data of reported HFMD cases in China during 2008-2018 were collected from the National Notifiable Disease Surveillance Reporting System of China for the analyses on the demographic characteristics, spatial distribution, diagnosis or reporting and pathogen spectrum of the HFMD cases. Then the risk factors causing deaths were analyzed by using logistic regression model. Results: From 2008 to 2018, a total of 3 646 fatal cases of HFMD in children under 5 years old were reported in China. There were more fatal HFMD cases in boys than in girls (1.82∶1), the death mainly occurred in age group 0 to 2 years (87.71%). Adjusted mortality rate of HFMD in children under 5 years old in China declined from 0.87 per 100 000 in 2010 to 0.11 per 100 000 in 2018 (APC=-23.20%). In the 2 523 laboratory-confirmed deaths, 2 323 (92.07%) were EV-A71 infections, but the constituents of CV-A16 and other enterovirus infections increased. The interval from onset to diagnosis M=2(P(25)-P(75):2-4)d. The interval from onset to death M=3(P(25)-P(75):2-4)d. Age between 0 and 1 years, EV-A71 infection, longer interval between onset and diagnosis, and living in rural area were the risk factors causing fatal HFMD cases. Conclusions: The number of the fatal cases, the rate of mortality and case fatality HFMD in China had shown downward trends since 2010. EV-A71 is still the main pathogen causing fatal cases, but we should pay more attention to gene pattern of the other enteroviruses except EV-A71 and CV-A16. To reduce the risk of the fatal cases we should strengthen the health education about the immunization of EV-A71 inactivated vaccines and reduce the interval from onset to diagnosis in young children in western provinces and rural areas.

[Application of moving epidemic method in establishing epidemic intensity threshold of hand, foot, and mouth disease in southern China].

Objective: To evaluate the incidence intensity of hand, foot, and mouth disease (HFMD) in 2018/2019 season in southern China by Moving Epidemic Method (MEM), and compare the intensity among provinces, so as to provide basis for optimizing the allocation of public health resources. Methods: The weekly incidence data of HFMD of children under 5 years old in 15 provinces of southern China from March 1, 2012 to February 28, 2019 were collected from Disease Surveillance Reporting System of Chinese Center for Disease Control and Prevention, and the epidemic intensity threshold of each province in southern China during this period was calculated and evaluated by MEM. Results: In the first incidence peak of 2018/2019 HFMD season, in 15 provinces in the south China, 6 provinces (Jiangsu, Zhejiang, Jiangxi, Chongqing, Sichuan and Yunnan) reported very high incidence rates in children under 5 years old while Guangdong, Guangxi and Hainan provinces had low incidence level. In the second incidence peak, the incidences in 6 provinces (Shanghai, Jiangsu, Zhejiang, Chongqing, Sichuan and Yunnan) reached very high levels. The incidences in remaining provinces also reached medium or high levels. In most provinces, the thresholds in the first incidence peak were higher than those in the second incidence peak, but Chongqing and Sichuan were different. The results of model validation showed that the sensitivity and specificity of MEM were higher than 70% except for Hainan, Chongqing and Yunnan. Conclusions: For southern provinces with two incidence peaks in HFMD season, MEM can be used to determine the epidemic intensity thresholds of different incidence peaks by dividing the disease season to analyze the incidence intensity of HFMD in different stages. The epidemic intensity threshold established by MEM integrates the historical data, and the province (city) with extremely high epidemic level identified represents that the province (city) has an abnormal increase compared with the historical incidence level, which requires more attention from all areas and timely implementation of prevention and control measures.

[Significance of micropapillary histopathological subtype of thyroid carcinoma].

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

The role of zinc chelate of hydroxy analogue of methionine in cadmium toxicity: effects on cadmium absorption on intestinal health in piglets.

Cadmium (Cd) is a toxic heavy metal that poses a threat to the health of humans and animals. It can cause serious damage to the small intestine, which is the main absorption site of Cd and the primary target organ after oral administration. Our previous study found that zinc chelate of hydroxy analogue of methionine (Zn-HMTB), a new type of feed additive, decreased Cd accumulation in the liver and kidneys. The aim of this study was to investigate the effect of Zn-HMTB on Cd absorption and Cd-induced toxicity in the small intestine of piglets. Twenty-four piglets (Landrace × Large White, 13.22 ± 0.58 kg BW) were randomly divided into four dietary treatment groups: basal diet, and diets containing 30 mg/kg Cd from CdCl2 and 0, 100 or 200 mg/kg Zn from Zn-HMTB. The experiment lasted 27 days. The feed intake and final BW of each piglet were recorded at the end of the experiment. Gastrointestinal (GI) tract tissue and samples of liver, kidney, spleen, heart, lung and longissimus muscle tissue and faeces were collected. The concentrations of Cd and metal trace elements in the GI tract and organs were analysed, as was the relative messenger RNA (mRNA) expression of inflammatory cytokines and metal element transporters in the small intestine, and epithelial apoptosis in the small intestine. The results showed that, compared with Cd-treated piglets, piglets in the Zn-HMTB and Cd cotreatment groups had less Cd deposition in the stomach, ileum, caecum, colon, liver, kidneys, spleen, lungs, heart and muscles (P < 0.05), and lower Cd concentrations in faeces (P < 0.05), suggesting that Zn-HMTB increased Cd absorption and the excretion of Cd in other forms (possibly urine). Zinc chelate of hydroxy analogue of methionine increased Zn deposition in the jejunum and the relative mRNA expression of divalent metal transporters 1 and zinc transporter 5 in the duodenum (P < 0.05), indicating that Zn-HMTB may promote the absorption and transportation of Cd and Zn together by upregulating metal element transporters. Competition between Zn and Cd may be responsible for accelerating Cd excretion. Furthermore, Zn-HMTB reduced Cd-induced apoptosis of enterocytes and inflammatory stimuli in the small intestine, suggesting that Zn-HMTB reduced Cd-induced toxicity to the small intestine. These results suggest that Zn-HMTB can be helpful in decreasing Cd accumulation in the GI tract and organs of piglets and relieving Cd-induced toxicity to the small intestine but cannot reduce the absorption of Cd.

KLF5 silence attenuates proliferation and epithelial-mesenchymal transition induction in Hep-2 cells through NF-κB signaling pathway.

OBJECTIVE: This study aimed at exploring the role and mechanism of Krüppel-like factor 5 (KLF5) in the migration, invasion, epithelial-mesenchymal transition (EMT) induction and proliferation in laryngeal cancer human epithelial type 2 (Hep-2) cells, and to provide a new sight for the treatment of laryngeal carcinoma. MATERIALS AND METHODS: Hep-2 cells were randomly divided into three groups: control group (Control), KLF5 siRNA group (siKLF5) and control-siRNA group (NC). The effects of KLF5 inhibition on cell proliferation and apoptosis were assessed by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometer, respectively. Wound healing assay and transwell invasion experiments were used to determine cell migration and invasion. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to compare the levels of KLF5, EMT-related genes E-cadherin, N-cadherin, Vimentin and Zinc finger transcription factors (Snail, Slug) expressions. The levels of nuclear transcription factor-κB (NF-κB-p65) and IκBα were also detected by Western blot. RESULTS: Compared with the Control group, the proliferation rate of Hep-2 cells in the siKLF5 group was significantly decreased while the apoptosis rate was increased (p<0.05). Meanwhile, the migration and invasion ability of Hep-2 cells were markedly decreased (p<0.05). E-cadherin protein expression was up-regulated while Vimentin, N-cadherin, Snail, and Slug protein expression levels were downregulated in siKLF5 group (p<0.05). Silencing KLF5 could inhibit the expression of NF-κB phosphorylation at p65 and the IκBα degradation (p<0.05). CONCLUSIONS: These results revealed that silencing KLF5 expression reduced the proliferation, migration and invasion and EMT abilities by inhibiting the NF-κB pathway in Hep-2 cells. Our results suggest that KLF5 may be a potential therapeutic target in laryngeal carcinoma.

[Combined application of immunohistochemical markers to identify pathologic subtypes of ampullary carcinoma and its clinical significance].

Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment.

[Hospitalization burden of hand, foot and mouth disease in Anhua county of Hunan province, 2013-2016].

Objective: To estimate the serotype and age-specific hospitalization burden associated with hand, foot and mouth disease (HFMD) in Anhua county of Hunan province, between October 2013 and September 2016. Methods: We collected hospitalization records of HFMD patients from 6 virological surveillance hospitals, and reimbursement records through new rural cooperative medical system from 23 township health centers to estimate the age-specific hospitalization burden of HFMD in Anhua. Combined with the results of virological surveillance, the serotype-specific hospitalization burden of HFMD in Anhua, was estimated. Results: During the three years, it was estimated that 3 541 clinical diagnosed HFMD cases, including 3 146 laboratory-confirmed HFMD cases, were hospitalized in Anhua, but only one was diaguosed as being severe. The estimated average hospitalization rate was 723/100 000(95%CI: 699/100 000-747/100 000) for clinical diagnosed HFMD and 642/100 000 (95%CI: 620/100 000-665/100 000) for laboratory-confirmed HFMD between October 2013 and September 2016. The cases caused by Cox A16 (208/100 000) and Cox A6 (202/100 000) had higher hospitalization rates compared with the cases caused by EV71 (130/100 000), Cox A10 (38/100 000) and other enterovirus (64/100 000), and the difference was statistically significant (P<0.001). HFMD-associated hospitalization rates peaked in children aged 1 year (3 845/100 000), and then decreased with age. Compared with the hospitalized HFMD caused by EV71 and Cox A16, Cox A6-associated hospitalizations mainly occurred in younger age groups (P<0.001). Conclusion: Our study revealed a substantial hospitalization burden associated with mild HFMD caused by EV71, Cox A16, Cox A6 and Cox A10, especially in young children, in Anhua.

Botryosphaeriaceae from Eucalyptus plantations and adjacent plants in China.

The Botryosphaeriaceae is a species-rich family that includes pathogens of a wide variety of plants, including species of Eucalyptus. Recently, during disease surveys in China, diseased samples associated with species of Botryosphaeriaceae were collected from plantation Eucalyptus and other plants, including Cunninghamina lanceolata, Dimocarpus longan, Melastoma sanguineum and Phoenix hanceana, which were growing adjacent to Eucalyptus. In addition, few samples from Araucaria cunninghamii and Cedrus deodara in two gardens were also included in this study. Disease symptoms observed mainly included stem canker, shoot and twig blight. In this study, 105 isolates of Botryosphaeriaceae were collected from six provinces, of which 81 isolates were from Eucalyptus trees. These isolates were identified based on comparisons of the DNA sequences of the internal transcribed spacer regions and intervening 5.8S nrRNA gene (ITS), and partial translation elongation factor 1-alpha (tef1), ß-tubulin (tub), DNA-directed RNA polymerase II subunit (rpb2) and calmodulin (cmdA) genes, the nuclear ribosomal large subunit (LSU) and the nuclear ribosomal small subunit (SSU), and combined with their morphological characteristics. Results showed that these isolates represent 12 species of Botryosphaeriaceae, including Botryosphaeria fusispora, Cophinforma atrovirens, Lasiodiplodia brasiliense, L. pseudotheobromae, L. theobromae and Neofusicoccum parvum, and six previously undescribed species of Botryosphaeria and Neofusicoccum, namely B. pseudoramosa sp. nov., B. qingyuanensis sp. nov., B. wangensis sp. nov., N. hongkongense sp. nov., N. microconidium sp. nov. and N. sinoeucalypti sp. nov. Aside from B. wangensis, C. atrovirens and N. hongkongense, the other nine Botryosphaeriaceae species were isolated from Eucalyptus trees in South China. Botryosphaeria fusispora (26 % of the isolates from Eucalyptus) is the dominant species, followed by L. pseudotheobromae (23 % of the isolates from Eucalyptus). In addition to species found on Eucalyptus trees, we also found B. pseudoramosa on M. sanguineum; B. wangensis on C. deodara; C. atrovirens on D. longan; L. theobromae on C. lanceolata, D. longan and P. hanceana; and N. hongkongense on A. cunninghamii. Pathogenicity tests showed that the 12 species of Botryosphaeriaceae are pathogenic to three Eucalyptus clones and that Lasiodiplodia species are the most aggressive. The results of our study suggest that many more species of the Botryosphaeriaceae remain to be discovered in China. This study also provides confirmation for the wide host range of Botryosphaeriaceae species on different plants.