Clinicopathological features of intravascular large B-cell lymphoma and collision tumors of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.

C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery / 中华外科杂志

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above the Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Spatial distribution of Oncomelania hupensis spread in Hubei Province from 2020 to 2022 / 中国血吸虫病防治杂志

OBJECTIVE@#To identify the spatial distribution pattern of Oncomelania hupensis spread in Hubei Province, so as to provide insights into precision O. hupensis snail control in the province.@*METHODS@#Data pertaining to emerging and reemerging snails were collected from Hubei Province from 2020 to 2022 to build a spatial database of O. hupensis snail spread. The spatial clustering of O. hupensis snail spread was identified using global and local spatial autocorrelation analyses, and the hot spots of snail spread were identified using kernel density estimation. In addition, the correlation between environments with snail spread and the distance from the Yangtze River was evaluated using nearest-neighbor analysis and Spearman correlation analysis.@*RESULTS@#O. hupensis snail spread mainly occurred along the Yangtze River and Jianghan Plain in Hubei Province from 2020 to 2022, with a total spread area of 4 320.63 hm2, including 1 230.77 hm2 emerging snail habitats and 3 089.87 hm2 reemerging snail habitats. Global spatial autocorrelation analysis showed spatial autocorrelation in the O. hupensis snail spread in Hubei Province in 2020 and 2021, appearing a spatial clustering pattern (Moran's I = 0.003 593 and 0.060 973, both P values < 0.05), and the mean density of spread snails showed spatial aggregation in Hubei Province in 2020 (Moran's I = 0.512 856, P < 0.05). Local spatial autocorrelation analysis showed that the high-high clustering areas of spread snails were mainly distributed in 50 settings of 10 counties (districts) in Hubei Province from 2020 to 2022, and the high-high clustering areas of the mean density of spread snails were predominantly found in 219 snail habitats in four counties of Jiangling, Honghu, Yangxin and Gong'an. Kernel density estimation showed that there were high-, secondary high- and medium-density hot spots in snail spread areas in Hubei Province from 2020 to 2022, which were distributed in Jingzhou District, Wuxue District, Honghu County and Huangzhou District, respectively. There were high- and medium-density hot spots in the mean density of spread snails, which were located in Jiangling County, Honghu County and Yangxin County, respectively. In addition, the snail spread areas negatively correlated with the distance from the Yangtze River (r = -0.108 9, P < 0.05).@*CONCLUSIONS@#There was spatial clustering of O. hupensis snail spread in Hubei Province from 2020 to 2022. The monitoring and control of O. hupensis snails require to be reinforced in the clustering areas, notably in inner embankments to prevent reemerging schistosomiasis.

Clinicopathological features of rectal adenocarcinoma with enteroblastic differentiation / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.

Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.

The Longitudinal Analysis of Convergent Antibody VDJ Regions in SARS-CoV-2 Positive Patients Using RNA-seq

The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has infected over 600 million individuals and caused over 6.5 million deaths. To understand the immune response individuals have from the SARS-CoV-2 infection, we studied the immunoglobulins against the viruss antigens. The diversified complementarity determining region 3 (CDR3) can be used to characterize an antibody. We downloaded four public RNA-seq data sets that were collected be-tween March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. In total, there were 269 SARS-CoV-2 positive patients and 26 negative patients who served as a control group. Samples were grouped based on their SARS-CoV-2 variant type and/or the time they were collected. Among 629,137 immunoglobulin V(D)J sequences identified by reconstructing the V(D)J sequences, we found 1011 common V(D)Js (same V gene, J gene and CDR3 sequences in each SARS-CoV-2 positive group) shared by more than one patient in each group and no common V(D)Js were from the negative control group. In our clustering analysis, we identified 129 convergent clusters from the SARS-CoV-2 positive groups. One of these convergent clusters matched the protein sequence of crystal 3D structures of the antibodies against SARS-CoV-2 in the Protein Data Bank (PDB). In our longitudinal analysis between the Alpha and Omicron variant, we found 2.7% of common CDR3s were shared although the longitudinal profiling of common V(D)Js was variant specific. Although diverse immunoglobulin profiles were observed, the convergence of common V(D)Js suggests that there exists antibodies with similar antigenic specificities across patients in different groups over various stages of the pandemic.

Predictive value of MRI pelvic measurements for "difficult pelvis" during total mesorectal excision / 中华胃肠外科杂志

Objective: Total mesorectal resection (TME) is difficult to perform for rectal cancer patients with anatomical confines of the pelvis or thick mesorectal fat. This study aimed to evaluate the ability of pelvic dimensions to predict the difficulty of TME, and establish a nomogram for predicting its difficulty. Methods: The inclusion criteria for this retrospective study were as follows: (1) tumor within 15 cm of the anal verge; (2) rectal cancer confirmed by preoperative pathological examination; (3) adequate preoperative MRI data; (4) depth of tumor invasion T1-4a; and (5) grade of surgical difficulty available. Patients who had undergone non-TME surgery were excluded. A total of 88 patients with rectal cancer who underwent TME between March 2019 and November 2021 were eligible for this study. The system for scaling difficulty was as follows: Grade I, easy procedure, no difficulties; Grade II, difficult procedure, but no impact on specimen quality (complete TME); Grade III, difficult procedure, with a slight impact on specimen quality (near-complete TME); Grade IV: very difficult procedure, with remarkable impact on specimen quality (incomplete TME). We classified Grades I-II as no surgical difficulty and grades III-IV as surgical difficulty. Pelvic parameters included pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with the difficulty of TME, and a nomogram predicting the difficulty of the procedure was established. Results: The study cohort comprised 88 patients, 30 (34.1%) of whom were classified as having undergone difficult procedures and 58 (65.9%) non-difficult procedures. The median age was 64 years (56-70), 51 patients were male and 64 received neoadjuvant therapy. The median pelvic inlet length, anteroposterior length of the mid-pelvis, pelvic outlet length, pubic tubercle height, sacral length, sacral depth, distance from the pubis to the pelvic floor, anterior pelvic depth, interspinous distance, and inter-tuberosity distance were 12.0 cm, 11.0 cm, 8.6 cm, 4.9 cm, 12.6 cm, 3.7 cm, 3.0 cm, 13.3 cm, 10.2 cm, and 12.2 cm, respectively. Multivariable analyses showed that preoperative chemoradiotherapy (OR=4.97,95% CI: 1.25-19.71, P=0.023), distance between the tumor and the anal verge (OR=1.31, 95% CI: 1.02-1.67, P=0.035) and pubic tubercle height (OR=3.36, 95% CI: 1.56-7.25, P=0.002) were associated with surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC = 0.795, 95%CI: 0.696-0.895). Conclusion: Our research demonstrated that our system for scaling surgical difficulty of TME is useful and practical. Preoperative chemoradiotherapy, distance between tumor and anal verge, and pubic tubercle height are risk factors for surgical difficulty. These data may aid surgeons in planning appropriate surgical procedures.

Evaluation of external contamination on the vial surfaces of some hazardous drugs that commonly used in Chinese hospitals and comparison between environmental contamination generated during robotic compounding by IV: Dispensing robot vs. manual compounding in biological safety cabinet.

OBJECTIVES: The aims of the study were to evaluate the external contamination of hazardous drug vials used in Chinese hospitals and to compare environmental contamination generated by a robotic intelligent dispensing system (WEINAS) and a manual compounding procedure using a biological safety cabinet (BSC). METHODS: Cyclophosphamide, fluorouracil, and gemcitabine were selected as the representative hazardous drugs to monitor surface contamination of vials. In the comparative analysis of environmental contamination from manual and robotic compounding, wipe samples were taken from infusion bags, gloves, and the different locations of the BSC and the WEINAS robotic system. In this study, high-performance liquid chromatography coupled with double mass spectrometer (HPLC-MS/MS) was employed for sample analysis. RESULTS: (1) External contamination was measured on vials of all three hazardous drugs. The contamination detected on fluorouracil vials was the highest with an average amount up to 904.33 ng/vial, followed by cyclophosphamide (43.51 ng/vial), and gemcitabine (unprotected vials of 5.92 ng/vial, protected vials of 0.66 ng/vial); (2) overall, the environmental contamination induced by WEINAS robotic compounding was significantly reduced compared to that by manual compounding inside the BSC. Particularly, compared with manual compounding, the surface contamination on the infusion bags during robotic compounding was nearly nine times lower for cyclophosphamide (10.62 ng/cm2 vs 90.43 ng/cm2), two times lower for fluorouracil (3.47 vs 7.52 ng/cm2), and more than 23 times lower for gemcitabine (2.61 ng/cm2 vs 62.28 ng/cm2). CONCLUSIONS: The external contamination occurred extensively on some hazardous drug vials that commonly used in Chinese hospitals. Comparison analysis for both compounding procedures revealed that robotic compounding can remarkably reduce environmental contamination.

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus vectored vaccines expressing spike (S) protein have advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD) or dimeric tandem-repeat RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular (Th1-based) immune responses. AdC7-RBD-tr2 showed higher antibody responses compared with both AdC7-S and AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic / 医学前沿

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

Behavioural changes during the COVID-19 pandemic: Results of a nationwide survey in Singapore

INTRODUCTION@#As part of infection control measures for COVID-19, individuals have been encouraged to adopt both preventive (such as handwashing) and avoidant behavioural changes (e.g. avoiding crowds). In this study, we examined whether demographics predicted the likelihood that a person would adopt these behaviours in Singapore.@*METHODS@#A total of 1,145 participants responded to an online survey conducted between 7 March and 21 April 2020. We collected demographic information and asked participants to report which of 17 behaviour changes they had undertaken because of the COVID-19 outbreak. Regression analyses were performed to predict the number of behavioural changes (preventive, avoidant, and total) as a function of demographics. Finally, we sought to identify predictors of persons who declared that they had not undertaken any of these measures following the outbreak.@*RESULTS@#Most participants (97%) reported at least one behavioural change on account of the pandemic, with changes increasing with the number of local COVID-19 cases (@*CONCLUSION@#Our characterisation of behavioural changes provides a baseline for public health advisories. Moving forward, health authorities can focus their efforts on encouraging segments of the population who do not readily adopt infection control measures against COVID-19.

Patient characteristics, clinical care, resource use, and outcomes associated with hospitalization for COVID-19 in the Toronto area

BackgroundPatient characteristics, clinical care, resource use, and outcomes associated with hospitalization for coronavirus disease (COVID-19) in Canada are not well described. MethodsWe described all adult discharges from inpatient medical services and medical-surgical intensive care units (ICU) between November 1, 2019 and June 30, 2020 at 7 hospitals in Toronto and Mississauga, Ontario. We compared patients hospitalized with COVID-19, influenza and all other conditions using multivariable regression models controlling for patient age, sex, comorbidity, and residence in long-term-care. ResultsThere were 43,462 discharges in the study period, including 1,027 (3.0%) with COVID-19 and 783 (2.3%) with influenza. Patients with COVID-19 had similar age to patients with influenza and other conditions (median age 65 years vs. 68 years and 68 years, respectively, SD<0.1). Patients with COVID-19 were more likely to be male (59.1%) and 11.7% were long-term care residents. Patients younger than 50 years accounted for 21.2% of all admissions for COVID-19 and 24.0% of ICU admissions. Compared to influenza, patients with COVID-19 had significantly greater mortality (unadjusted 19.9% vs 6.1%, aRR: 3.47, 95%CI: 2.57, 4.67), ICU use (unadjusted 26.4% vs 18.0%, aRR 1.52, 95%CI: 1.27, 1.83) and hospital length-of-stay (unadjusted median 8.7 days vs 4.8 days, aRR: 1.40, 95%CI: 1.20, 1.64), and not significantly different 30-day readmission (unadjusted 8.6% vs 8.2%, aRR: 1.01, 95%CI: 0.72, 1.42). InterpretationAdults hospitalized with COVID-19 during the first wave of the pandemic used substantial hospital resources and suffered high mortality. COVID-19 was associated with significantly greater mortality, ICU use, and hospital length-of-stay than influenza.

Syndromic Surveillance for COVID-19 in Canada

BackgroundSyndromic surveillance through web or phone-based polling has been used to track the course of infectious diseases worldwide. Our study objective was to describe the characteristics, symptoms, and self-reported testing rates of respondents in three different COVID-19 symptom surveys in Canada. MethodsData sources consisted of two distinct Canada-wide web-based surveys, and phone polling in Ontario. All three sources contained self-reported information on COVID-19 symptoms and testing. In addition to describing respondent characteristics, we examined symptom frequency and the testing rate among the symptomatic, as well as rates of symptoms and testing across respondent groups. ResultsWe found that 1.6% of respondents experienced a symptom on the day of their survey, 15% of Ontario households had a symptom in the previous week, and 44% of Canada-wide respondents had a symptom in the previous month over March-April 2020. Across the three surveys, SARS-CoV-2-testing was reported in 2-9% of symptomatic responses. Women, younger and middle-aged adults (versus older adults) and Indigenous/First nations/Inuit/Metis were more likely to report at least one symptom, and visible minorities were more likely to report the combination of fever with cough or shortness of breath. InterpretationThe low rate of testing among those reporting symptoms suggests significant opportunity to expand testing among community-dwelling residents of Canada. Syndromic surveillance data can supplement public health reports and provide much-needed context to gauge the adequacy of current SARS-CoV-2 testing rates.

Hospitalization burden of hand, foot and mouth disease in Anhua county of Hunan province, 2013-2016 / 中华流行病学杂志

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.

Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014 / 中华流行病学杂志

Objective: To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China, and to provide guidance for the implementation of precise intervention. Methods: A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014. Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters. Transmission network was constructed by Cytoscape 3.6.0, which was further used for exploring of the major risk factors. Results: Of the 2 094 sequences, 12.18% (255/2 094) were in clusters. A total of 82 transmission clusters were identified. The numbers of clusters and contained sequences in intra-provincial transmission (61, 173) were significantly more than those in inter-provincial transmission (21, 82). The ratio of transmission clustering in MSM increased over time from 2.41% (2/83) during 1996-2008 to 23.61% (72/305) during 2013-2014, showing a significant upward trend (χ(2)=27.800, df=1, P=0.000). The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters, which increased from 0.67% (2/297) during 1996-2008 to 6.36%(30/472) during 2013-2014, showing a significant upward trend (χ(2)=20.276, df=1, P=0.000). The transmission rate in homosexuals of the inter-transmission clusters (86.59%, 71/82) was higher than that of intra-provincial transmission clusters (56.65%, 98/173), and the difference was statistically significant (χ(2)=22.792, P=0.000). The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33%, 7/21) was higher than that of intra-provincial clusters (13.11%, 8/61), and the difference was statistically significant (χ(2)=4.273, P=0.039). Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22%, 42/82) was significantly higher than that with intra-provincial transmission clusters (26.59%, 46/173), and the difference was statistically significant (χ(2)=14.932, P=0.000). Inter-provincial clusters were mainly detected in and and MSM. Conclusions: Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China. Inter-provincial transmission clusters increased rapidly, MSM played an important role in the wide spread of the strain. More researches in transmission networks are needed to guide the precision intervention.

Human leukocyte antigen polymorphism of HIV infected persons without disease progress for long-term in Henan province, 2011-2016 / 中华流行病学杂志

Objective: To understand the disease progression and human leukocyte antigen (HLA) gene polymorphism of HIV-infected persons without disease progress for long term, also known as long-term non-progressors (LTNPs), in Henan province. Methods: A retrospective study was conducted in 48 LTNPs with complete detection and follow-up information during 2011-2016 in Henan. Changes of CD(4)(+)T cells counts (CD(4)) and viral load (VL) during follow-up period were discussed. Polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) was used for the analyses of HLA-A, HLA-B and HLA-DRB1 alleles between LTNPs and healthy controls. Results: From 2011 to 2016, forty-eight LTNPs showed a decrease of the quartile (P(25)-P(75)) of CD(4) from 601.00 (488.50-708.72)/μl to 494.00 (367.00-672.00)/μl, and the difference was significant (P<0.05). The increase of the quartile (P(25)-P(75)) of log(10)VL from 3.40 (2.87-3.97) to 3.48 (2.60-4.37), but the difference was not significant (P>0.05). HLA polymorphism analysis revealed that HLA-B*13:02 and HLA-B*40:06 were more common in LTNPs (P<0.05), while HLA-B*46:01 and HLA-DRB1*09:01 were more common in healthy controls (P<0.05). Conclusions: The CD(4) of LTNPs in Henan showed a downward trend year by year. HLA-B*13:02 and B*40:06 might be associated with delayed disease progression for HIV infected persons in Henan.

Analysis on epidemiological and temporal-spatial distribution characteristics of hemorrhagic fever with renal syndrome in Shandong province, 2010-2016 / 中华流行病学杂志

Objective: To analyze the epidemiological and temporal-spatial distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shandong province during 2010-2016 and provide references for developing prevention and control measures. Methods: Based on the data of Infectious Disease Reporting Information System in China, the incidence and temporal-spatial distribution of HFRS in Shandong from 2010 to 2016 were analyzed by spatial autocorrelation and space-time scan statistics. Results: A total of 9 114 HFRS cases were reported in Shandong during this period. The cases were mainly distributed in age group 30-70 years, and the male to female ratio of the cases was 2.63 ∶ 1. Most cases were farmers. The higher incidence rate was reported in southeastern Shandong, while the lower incidence rate was reported in northwestern Shandong. Among the epidemic periods, the highest incidence rate was 1.87/100 000 in 2013. The results of spatial autocorrelation and space-time scanning indicated that the high-high clusters of HFRS were concentrated in southeastern Shandong and then spread to central Shandong. The cluster mainly occurred from the end of 2011 to the first half of 2015. Both the incidence rate and the cluster decreased in 2016. Conclusions: The epidemic and cluster of HFRS still existed in Shandong from 2010 to 2016. The key areas for the prevention and control of HFRS were in southeastern and central Shandong.

Prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014 / 中华流行病学杂志

Objective: To investigate the rates on prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014. Methods: A cross-sectional survey was conducted in Beijing between 2013-2014. Stratified multistage random sampling method was used to select representative sample of 13 057 Chinese individuals aged over 15 years, from the general population. Blood pressure was measured for three readings at sitting position after resting for at least five minutes with an average reading recorded. A standardized structured questionnaire was developed to collect history of hypertension and antihypertensive treatment. Results: A total of 4 663 community residents aged over 15 years were hypertensive among the 13 057 individuals, with the standardized prevalence rate as 32.7%, in Beijing area. The age-standardized prevalence rates of hypertension appeared 34.6% in men and 30.8% in women. The age-and sexstandardized prevalence of hypertension rates were 33.3% in urban and 24.6% in rural areas. The prevalence of hypertension increased with age and appeared higher in men than in women, in urban than in rural residents. Among the hypertensive patients, rates of awareness, treatment and control were 66.8%, 64.6% and 31.6%, respectively. Conclusion: High prevalence of hypertension with low rates on awareness and treatment and control, appeared in the general population of Beijing. Related strategies should be developed regarding prevention, control and management of hypertension, to reduce the burden of this disease.

Trends in 30-day case fatality rate in patients hospitalized due to acute myocardial infarction in Beijing, 2007-2012 / 中华流行病学杂志

Objective: To understand the distribution and trends in 30-day coronary heart disease (CHD) case fatality rate in patients hospitalized due to acute myocardial infarction (AMI) in Beijing during 2007-2012. Methods: The clinical data of patients hospitalized due to AMI in Beijing from 1 January 2007 to 31 December 2012 were collected from "The Cardiovascular Disease Surveillance System in Beijing" . A total of 77 943 local patients aged ≥25 years were hospitalized due to AMI in Beijing during the this period. After excluding duplicate records and validation for the completeness and accuracy of the records, the clinical characteristics of the patients and 30-day CHD case fatality rate in the patients were analyzed. Trends in 30-day CHD case fatality rate in the patients were analyzed with Poisson regression models. Results: The age-standardized average 30-day CHD case fatality rate was 9.7% in the 77 943 patients. During this period, a decreasing trend was observed in 30-day CHD case fatality rate after adjusting for age and gender (P<0.001). The age-standardized 30-day CHD case fatality rate decreased by 16.0%, from 10.8% in 2007 to 9.0% in 2012. The decreases of 30-day CHD case fatality rates were noted in both men and women, whereas 30-day CHD case fatality rate was higher in women (14.1%) than in men (7.6%) after adjusting for age. During this period, the proportion of ST-segment elevation myocardial infarction (STEMI) decreased, while the proportion of non-ST-segment elevation myocardial infarction (NSTEMI) increased with year. A significant decline (20.1%) in 30-day case fatality rate of STEMI was found, but no decline was found for 30-day mortality rate of NSTEMI. Conclusion: A decreasing trend in 30-day CHD case fatality rate was observed in the patients aged ≥25 years and hospitalized due to AMI in Beijing during 2007-2012, indicating the improvement in short-term prognosis of patients hospitalized due to AMI. Our findings highlight the urgent need to improve the treatment for woman and NSTEMI patients.

Progress in next-generation sequencing research of non-syndromic oral clefts / 中华流行病学杂志

Non-syndromic oral clefts (NSOC) are among the most common birth defects. The prevalence of NSOC is 1.13-1.30 per 1 000 live births in China, which is higher than those in other major ethnic groups. The etiology of NSOC is complex and heterogeneous, which involves both genetic and environmental risk factors. Although genome-wide association studies have identified a number of risk loci, these loci can only account for a small proportion of the heritability of NSOC. The next-generation sequencing research provides new ideas for further exploring the genetic risk factors of NSOC. This paper summaries the progress in the next-generation sequencing research of NSOC.