[Multiple locus variable number tandem repeat analysis genotype polymorphism of Bacillus anthracis in China].

Objective: To analyze the multiple locus variable number tandem repeat analysis (MLVA) genotype polymorphism of Bacillus (B.) anthracis and establish a MLVA genotype database of B. anthracis in China. Methods: B. anthracis strains isolated from different sources in China since 1947 were collected. Genotype identification was carried out using the MLVA15 genotyping protocol based on 15 variable number tandem repeat loci. The genotypes were uniformly numbered and named. The distribution characteristics of the MLVA genotypes of strains were analyzed. Software Bionumerics was used to construct clustering diagrams to analyze the genetic relationships. Results: The MLVA15 clustering analysis subdivided the isolates into 4 major groups and 91 genotypes, 54 of which were unique to China. The genotypes from MLVA15-CHN1 to MLVA15-CHN6 were widely distributed throughout China and in all eras, while other genotypes were restricted to certain regions or eras. Conclusions: This study established a MLVA genotype database of B. anthracis, which provides basis for the understanding of MLVA genetic polymorphisms and the control and molecular source tracing of the anthrax outbreaks in China.

Increased risk of temporomandibular joint disorders and craniofacial deformities in patients with juvenile idiopathic arthritis: a population-based cohort study.

Juvenile idiopathic arthritis (JIA) is an autoimmune disease that has been proposed to involve the temporomandibular joint (TMJ). The aim of this study was to identify the relationships between JIA, TMJ disorders, and craniofacial deformities. This cohort study included patients diagnosed with clinically active JIA between 1999 and 2013 through a nationwide longitudinal health registry. The primary outcome was the presence of a TMJ disorder. The secondary outcome was the presence of a JIA-associated craniofacial deformity. A total of 2791 patients with JIA were included in the case group; 11,164 propensity score-matched individuals without JIA were selected from the same database as controls. TMJ disorders were present in 142 individuals: 48 (1.72%) in the case group and 94 (0.84%) in the control group (relative risk 2.047, 95% confidence interval 1.446-2.898). Craniofacial deformities were present in 374 individuals: 112 (4.01%) in the case group and 262 (2.35%) in the control group (relative risk 1.722, 95% confidence interval 1.380-2.148). Patients with JIA showed a significantly greater likelihood of developing TMJ disorders and craniofacial deformities compared to matched controls.

[Analysis of epidemic characteristics of anthrax in China from 2017 to 2019 and molecular typing of Bacillus anthracis].

Objective: To analyze the epidemiological characteristics of anthrax in China from 2017 to 2019 and molecular typing of Bacillus anthracis isolated from some provinces (autonomous regions). Methods: Surveillance data of anthrax cases reported from 2017 to 2019 in the Infectious Disease Surveillance information System of China Disease Prevention and Control and the Public Health Emergency Reporting and Management Information System were collected, and descriptive epidemiological methods were used to analyze the epidemic characteristics, including the temporal, geographic and demographic distribution of this disease. A total of 47 strains of Bacillus anthracis isolated from 2017 to 2019 were analyzed by canSNP and MLVA15. Results: A total of 951 cases of anthrax were reported from 2017 to 2019, of which 938 were cutaneous anthrax, representing 98.63% of the total number reported. It was mainly distributed in the west and northeast of China, and the three provinces with the highest number of cases were Gansu (215), Sichuan (202) and Qinghai (191). Cases had been reported throughout the year, more cases occurred in the summer and autumn, and August was the month with the most cases,66.35% (211/318), 72.32% (243/336) and 68.01% (202/297) of cases were reported during June to September. The age distribution was mainly between 20 and 59 years old, accounting for more than 80% of all cases. The number of male cases was significantly higher than that of female cases, the ratio of male to female was about 3∶1. The occupations were mainly herdsmen and farmers, accounting for 49.70% to 58.18% and 31.45% to 36.70%, respectively. Public health events occurred every year, and 29 events had been reported from 2017 to 2019. canSNP analysis showed that 37 of the 47 strains belonged to the A.Br.001/002 subgroup and 10 belonged to the A.Br.Ames subgroup. MLVA15 analysis showed that there were 17 genotypes, of which 10 genotypes contained only one strain. Conclusion: Cutaneous anthrax was the predominant clinical type in China from 2017 to 2019.The seasonal, geographic and demographic distribution characteristics were evident.Molecular typing methods such as canSNP and MLVA15 can be used to trace the source of infectious diseases and provide technical support for anthrax prevention and control.

Traditional Chinese medicine use may reduce medical utility in patients with asthma: a nationwide population-based retrospective cohort study.

BACKGROUND: Many patients with atopic diseases, including asthma, have sought complementary and alternative medicine and traditional Chinese medicine (TCM) treatments. But, limited clinical studies have yet examined TCM effects on medical utility in asthma patients. AIM: To assess the medical utility of TCM in patients with asthma. DESIGN: Population-based retrospective cohort study. METHODS: We performed a 13-year population-based retrospective cohort study. A total of 5235 asthma patients who were TCM users and 5235 propensity-score matched asthma patients who never used TCM were sampled from the Taiwan National Health Insurance Research Database from 2000 to 2012. We compared these two groups of patients to calculate their medical utility, including numbers of emergency visits and hospitalizations until 2013. Univariate analyses were performed using Chi-square tests for dichotomous variables and t-tests for continuous variables. Cox proportional hazard models were conducted to investigate the medical utility of asthma after TCM use. RESULTS: Compared with non-TCM patients, TCM patients had a significantly decreased medical utility of asthma admission [adjusted odds ratio (OR) = 0.63; 95% confidence interval (CI): 0.46-0.85; P < 0.05], especially in patients who used TCM for >60 days. Asthma medical utility in asthma emergencies was significantly higher for male than for female patients (adjusted OR = 1.45; 95% CI: 1.08-1.96). The most frequently used TCMs for asthma control or cough treatment were antitussive agents. CONCLUSION: This population-based retrospective cohort study showed a significantly decreased medical utility of emergency visits and admissions in TCM patients, especially using TCM for >60 days.

Dementia and the Risk of Periodontitis: A Population-Based Cohort Study.

Dementia and Alzheimer's disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score-matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score-matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent (P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.

Risk of stroke with antivenom usage after venomous snakebite in Taiwan: a population-based cohort study.

BACKGROUND AND PURPOSE: Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study. METHODS: This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors. RESULTS: The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41-5.26). CONCLUSION: Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.

[Histopathological features of squamous cell carcinoma of lung neoadjuvant immunotherapy focusing on responses].

Objective: To analyze the pathologic features of responses to neoadjuvant immunotherapy of squamous cell carcinoma (SCC) of the lung. Methods: The study included 31 patients with resected lung SCC post neoadjuvant immunotherapy. All patients were recruited from the neoadjuvant anti-PD-1 (Sintilimab) phase Ⅰb clinical trial (ChiCTR-OIC-17013726). The histopathological morphology and different degrees of pathologic response to immunotherapy were evaluated basing on irPRC standard. Results: According to the percentage of residual viable tumor (% RVT), pathologic responses of complete pathologic response (cPR), major pathologic response (MPR) and non-MPR were noted in 19% (n=6), 29% (n=9), and 52% (n=16) of patients respectively. In addition, extensive immune activation phenomena (immune cell infiltration, including infiltration of lymphocytes, plasma cells, foamy macrophages, lymphocyte aggregation and tertiary lymphoid structures formation) and tissue repair features (giant cells, granuloma formation, proliferative fibrosis and neovascularization) were observed in tumor regression bed. Conclusions: Neoadjuvant immunotherapy has favorable effect on lung SCC. Pathologic assessment of resected lung cancer specimens after neoadjuvant immunotherapy shows unique histopathological features consistent with its mechanism.

Association of sepsis with risk for osteoporosis: a population-based cohort study.

We conducted a large, retrospective cohort study using data from Taiwan's National Health Insurance Research Database to evaluate whether the risk of developing osteoporosis is associated with sepsis. Our study found that adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis. INTRODUCTION: There have been limited studies regarding the osteoporosis risk associated with sepsis. Our purpose is to evaluate whether the risk of developing osteoporosis is associated with sepsis. METHODS: We conducted a large, retrospective cohort study using data from Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,178 patients diagnosed with sepsis from 2000 to 2012 were included in the sepsis cohort, and a propensity score-matched cohort included 13,178 individuals without sepsis. To calculate the incidence of osteoporosis, both groups were followed until 2013. Cox regression analysis was performed to obtain the hazard ratios (HRs) to assess the risk of developing osteoporosis. The Kaplan-Meier method was used to estimate the cumulative incidence of osteoporosis. RESULTS: The overall incidences of osteoporosis (per 1,000 person-years) in the sepsis and non-sepsis groups were 10.2 and 10.7, respectively. The risk of osteoporosis significantly increased in the presence of sepsis (adjusted HR = 1.17, 95% confidence interval (CI) = 1.04-1.31). The risk of osteoporosis in the sepsis group was significantly higher than that in the non-sepsis group for young patients aged 20-49 years and patients aged 50-64 years (adjusted HR = 1.93, 95% CI = 1.08-3.44; adjusted HR = 2.01, 95% CI = 1.52-2.65, respectively). The Kaplan-Meier curves of cumulative probability also showed a significantly increased risk of osteoporosis in patients aged 20-49 years and aged 50-64 years with sepsis compared with non-sepsis (P = 0.025; P < 0.001, respectively). CONCLUSION: Adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis.

LncRNA ANRIL knockdown ameliorates retinopathy in diabetic rats by inhibiting the NF-κB pathway.

OBJECTIVE: To evaluate the impacts of long non-coding ribonucleic acid (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) on diabetic retinopathy (DR) in rats and the underlying mechanism. MATERIALS AND METHODS: A total of 60 adult male Sprague Dawley (SD) rats were randomly divided into 3 groups: the Sham group (n=20), DR group (n=20) and DR + lncRNA ANRIL knockdown group [DR + lncRNA ANRIL small interfering RNA (siRNA) group, n=20]. DR model in rats was established by intraperitoneal injection of streptozocin (STZ; 60 mg/kg). Meanwhile, a certain dose of lncRNA ANRIL siRNA was added dropwise into rat eyes of DR + lncRNA ANRIL siRNA group during model induction to downregulate lncRNA ANRIL expression in the retina. 16 weeks later, rat retinal tissues were taken to extract total RNA and protein. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was applied to detect the expression levels of lncRNA ANRIL, interleukin-1 (IL-1), IL-6 and monocyte chemotactic protein-1 (MCP-1) in each group of the rat retina. Pathological structure of rat retinal tissues in each group was observed via hematoxylin and eosin (H&E) staining. Immunohistochemistry was adopted to measure the expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and P65 in each group of retinal tissues. In addition, the retinal vascular permeability in each group of rats was detected by fluorescent staining. Finally, Western blotting was utilized to determine the expressions of genes in the P65 signaling pathway. RESULTS: Compared with rats in the Sham group, lncRNA ANRIL was upregulated in rat retinal tissues harvested from the DR + lncRNA ANRIL siRNA group (p<0.05). After knockdown of lncRNA ANRIL in the retinal tissues of DR rats, pathologic damage was alleviated notably, and the levels of inflammatory markers (IL-1, IL-10 and MCP-1) were lowered markedly (p<0.05). The protein expressions of Bax and P65 decreased evidently, while the protein level of Bcl-2 increased markedly (p<0.05) in DR rats with ANRIL knockdown. Furthermore, Western blotting results revealed that inhibition of lncRNA ANRIL could prominently repress the phosphorylation level of P65 in the retinal tissues of DR rats (p<0.05). CONCLUSIONS: LncRNA ANRIL knockdown can significantly ameliorate the retinopathy in diabetic rats by blocking the nuclear factor-kappa B (NF-κB) signaling pathway.

Influence of lncRNA-MALAT1 on neuronal apoptosis in rats with cerebral infarction through regulating the ERK/MAPK signaling pathway.

OBJECTIVE: To investigate the regulatory effect of long non-coding ribonucleic acid (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway, and to explore its influence on neuronal apoptosis in rats with cerebral infarction. MATERIALS AND METHODS: A total of 45 adult male Sprague-Dawley rats were randomly divided into sham group (n=15), model group (n=15) and MALAT1 low-expression group (n=15). The model of cerebral infarction was successfully established in the model group and MALAT1 low-expression group via middle cerebral artery occlusion (MCAO). After 3 d, the nerve injury in each group was evaluated using Zea-Longa score. Meanwhile, the area of cerebral infarction in each group was detected via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. After the cortical tissues were separated, the expression level of lncRNA-MALAT1 was detected via quantitative Polymerase Chain Reaction (qPCR). The apoptotic level of neurons in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The expression levels of inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the expression levels of apoptosis-related proteins and ERK/MAPK signaling pathway-related proteins were detected via Western blotting. RESULTS: Compared with the sham group, the behavioral score and area of cerebral infarction in the model group were significantly increased (p<0.01). The low expression of MALAT1 could effectively reduce the behavioral score and area of cerebral infarction in the model group (p<0.01). The expression level of lncRNA-MALAT1 in cortical tissues of the model group was markedly higher than that of the sham group and MALAT1 low-expression group (p<0.01). Compared with the sham group, the content of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cortical tissues was significantly increased (p<0.01). However, the content of IL-10 was remarkably decreased in the model group (p<0.01). Low expressed MALAT1 could markedly reduce the content of TNF-α and IL-6 and increase the content of IL-10 in cortical tissues (p<0.01). The level of apoptosis in cortical tissues was increased in the model group when compared with that of the sham group (p<0.01). Meanwhile, low expression of MALAT1 could effectively reduce the apoptosis level in cortical tissues in model group (p<0.01). In the model group, the expression levels of B-cell lymphoma-2/Bcl-2 associated X protein (Bcl-2/Bax), p-ERK and matrix metalloproteinase-2 (MMP-2) in cortical tissues were significantly declined than the sham group (p<0.01). However, the protein expression level of cleaved caspase-3 was markedly increased (p<0.01). Furthermore, the low expression of MALAT1 could remarkably increase the expressions of Bcl-2/Bax, p-ERK and MMP-2 (p<0.01), as well as decrease the expression of cleaved caspase-3 (p<0.01). CONCLUSIONS: LncRNA-MALAT1 may increase the release of inflammatory cytokines by inhibiting the ERK/MAPK signaling pathway, thereby up-regulating the level of neuronal apoptosis and aggravating the cerebral injury in rats with cerebral infarction.

Association of gout medications and risk of cataract: a population-based case-control study.

BACKGROUND: The relationship between gout medication use and cataract development is controversial. Moreover, limited clinical studies have evaluated this relationship. AIM: To assess the effects of colchicine, allopurinol and benzbromarone on the risk of cataract in patients with gout. DESIGN: Population-based nested case-control study. METHODS: We enrolled 7900 patients who had received a new diagnosis of cataract >3 years after gout diagnosis into the study group and 33 475 patients who did not receive a diagnosis of cataract into the control group by matching for age, sex and the year of gout diagnosis at a ratio of 1:1. We used World Health Organization's defined daily dose (DDD) as a measure to assess the dosage of colchicine, allopurinol and benzbromarone exposure. Logistic regression was used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of cataract. RESULTS: The risk of cataract significantly increased in patients who received colchicine at a cumulative DDD of ≥66.5 (OR = 1.17, 95% CI = 1.01-1.36, P = 0.041). In the age-stratified analysis, patients with gout aged >60 years had a higher risk of cataract (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011) than did patients aged <60 years. Allopurinol and benzbromarone had no association with cataract. CONCLUSIONS: In this population-based nested case-control study, we observed that colchicine use increased the risk of cataract in patients with gout, especially in those aged >60 years who received colchicine at a cumulative DDD of >66.5.

Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjögren syndrome.

OBJECTIVES: To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS). METHODS: This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription. RESULTS: Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05-0.92). CONCLUSIONS: HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.

Risk of systemic lupus erythematosus in patients with human papillomavirus infection: a population-based retrospective cohort study.

BACKGROUND: Viral infection contributing to systemic lupus erythematosus (SLE) development has been largely reported. However, the SLE risk in patients with human papillomavirus (HPV) infection is unknown. METHODS: Data were retrieved from the Longitudinal Health Insurance Database (2000) in Taiwan. We identified 43,567 patients with HPV infection and 174,268 age- and sex-matched uninfected controls from 2002 to 2012. Individuals were followed up from index date (first date of diagnosis with HPV) until the occurrence of SLE, at the end of the study (December 2013), or when they were withdrawn from the insurance program. The incidence rate ratio (IRR) was calculated using the univariate Poisson regression. The adjusted hazard ratios (aHRs) were calculated, and sensitive and subgroups analyses were also conducted. RESULTS: Compared with the non-HPV controls, the IRR of SLE in HPV patients was 1.52 (95% confidence interval (CI): 1.09-2.12). The risk of SLE in HPV-infected individuals was significantly high (aHR: 1.48, 95% CI: 1.06-2.06) after adjusting for age, sex, and comorbidities. Men aged between 16 and 45 years were more susceptible to developing SLE (aHR: 21.57, 95% CI: 2.52-184.60, p = 0.0051). CONCLUSION: Our study showed a significantly higher risk of SLE among HPV-infected patients, especially in men aged between 16 and 45 years.

Syncope caused by complete heart block and ventricular arrhythmia as early manifestation of systemic lupus erythematosus in a pregnant patient: a case report.

Systemic lupus erythematosus (SLE) can affect all heart structures including the conduction system, with either reversible or permanent derangement. However, only a few cases of adult SLE and complete atrioventricular (AV) block have been reported. We describe a young pregnant woman who initially presented with complete AV block on electrocardiography before the diagnosis of SLE. Syncope subsequently developed during the postpartum period due to frequent nonsustained polymorphic ventricular tachycardia, suggesting lupus myocarditis. The ventricular arrhythmia was successfully treated by intravenous corticosteroids, lidocaine and implantation of a permanent pacemaker. This may represent the first report of complete AV block with polymorphic ventricular tachycardia, which was identified before the other clinical features of SLE fully manifested. SLE should be considered if a patient presents with complete AV block without other clinical features. It may warn for early diagnosis and appropriate treatment of SLE including lupus-related heart disease.

Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants.

OBJECTIVE: To determine the association between antenatal steroids administration and intraventricular hemorrhage rates. METHODS: We used cross-sectional data from the California Perinatal Quality Care Collaborative during 2007 to 2013 for infants ⩽32 weeks gestational age. Using multivariable logistic regression, we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by gestational age. RESULTS: In 25 979 very-low-birth weight infants, antenatal steroid use was associated with a reduction in incidence of any grade of intraventricular hemorrhage (odds ratio=0.68, 95% confidence interval: 0.62, 0.75) and a reduction in incidence of severe intraventricular hemorrhage (odds ratio=0.51, 95% confidence interval: 0.45, 0.58). This association was seen across gestational ages ranging from 22 to 29 weeks. CONCLUSIONS: Although current guidelines recommend coverage for preterm birth at 24 to 34 weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even before 24 weeks of gestational age.