Brucellosis caused by Brucella melitensis is considered to be one of the most important zoonotic diseases in China In this study, Conventional bio-typing, MLVA (multiple locus variable-number tandem repeat analysis), and WGS (whole-genome sequencing)-SNP (single nucleotide polymorphism) were used to study the genetic similarity of B melitensis in northern and southern China and analyze its relationship with worldwide lineages Currently, the distribution of species/biovars of B melitensis has obviously changed, and B melitensis has become the dominant species in southern regions of China Strains from the southern had a common geographic origin with strains from the northern Many MLVA-16 events were shared in the genotypes of the southern and northern strains, suggest that genotypic movement occurred from north to south Based on WGS-SNP analysis, strains from different provinces were closely related and may have descended from one common ancestor, suggests that the southern strains originated from northern China These data indicate that B melitensis is a latent "travel bacterium" that spread and expanded from North China to South China Moreover, B melitensis strains from China are also genetically related to strains from other Asian regions (Kazakhstan, Russia, Mongolia, and India) The movement of infected sheep and their products requires control

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2020.1788995

Brucella melitensis, a latent "travel bacterium," continual spread and expansion from Northern to Southern China and its relationship to worldwide lineages.

Hinggan League is located in the Northeast of the Inner Mongolia Autonomous Region, the historically endemic area of animal and human brucellosis In this study, the epidemiological characteristics of human brucellosis were analyzed, and the genotypic profile and antimicrobial susceptibilities of Brucella melitensis strains isolated from humans in Hinggan League were investigated The epidemic characteristics were described using case number, constituent ratio, and rate The 418 human blood samples were collected and tested by bacteriology, and suspect colonies were isolated and identified by conventional biotyping assays, the VITEK 20 microbial identification system, and AMOS (Brucella abortus, B melitensis, B ovis, and B suis)-PCR Subsequently, all strains were genotyped using multiple-locus variable-number tandem repeat analysis (MLVA) assays, and the antimicrobial susceptibility pattern of Brucella strains against the 10 most commonly used antibiotics was determined by microdilution method A total of 22 848 cases of human brucellosis were reported from 2004 to 2019, with an annual average incidence of 872/100 000 The incidence rates in developed areas of animal husbandry (Horqin Youyi Qianqi [1612/100 000] and Horqin Youyi Zhongqi [1121/100 000]) were significantly higher than those in forest areas (Arxan [192/100 000]) (χ2 = 32561, P < 0001) In addition, peak morbidity occurred during May–August, accounting for 726% (16582/22 848) of cases The highest number of cases occurred in the 40+ age group, accounting for 444% (10 137/22484) of cases, and morbidity in males was significantly higher than that in females in all age groups (χ2 = 29997, P < 0001), the most common occupation was farmers A total of 54 B melitensis strains were divided into 37 genotypes (GT1–37) with 80–100% genetic similarity All 25 strains were sensitive to seven tested antibiotics, phenotypic resistance to cotrimoxazole and azithromycin was observed in 5 (20%) and 25 (100%) of the isolates, respectively Human brucellosis exhibited a significant increasing trend and B melitensis is the main pathogen responsible for human brucellosis in this region Improved surveillance of infected animals (sheep) and limiting their transfer and trade are optional strategies for decreasing the incidence of this disease

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Epidemiologically characteristics of human brucellosis and antimicrobial susceptibility pattern of Brucella melitensis in Hinggan League of the Inner Mongolia Autonomous Region, China.

Depression is one of the most common mental health problems in middle-aged and elderly people. The establishment of risk factor-based depression risk assessment model is conducive to early detection and early treatment of high-risk groups of depression. Five machine learning models (logistic regression (LR); back propagation (BP); random forest (RF); support vector machines (SVM); category boosting (CatBoost) were used to evaluate the depression among 8374 middle-aged people and 4636 elderly people in the NHANES database from 2011 to 2018. In the 2011-2018 cycle, the estimated prevalence of depression was 8.97% in the middle-aged participants and 8.02% in the elderly participants. Among the middle-aged and elderly participants, CatBoost was the best model to identify depression, and its area under the working characteristic curve (AUC) reaches the highest. The second is LR model and SVM model, while the performance of BP and RF model was slightly worse. The primary influencing factor of depression in middle-aged male is alanine aminotransferase. All five machine learning models can identify the occurrence of depression in the NHANES data set through social demographics, lifestyle, laboratory data and other data of middle-aged and elderly people, and among five models, the CatBoost model performed best.

Using CatBoost algorithm to identify middle-aged and elderly depression, national health and nutrition examination survey 2011–2018

A time-resolved fluorescence lateral flow immunoassay for rapid and quantitative serodiagnosis of Brucella infection in humans.

Background Human brucellosis imposes a heavy burden on the health and economy of endemic regions. Since 2011, China has reported at least 35,000 human brucellosis cases annually, with more than 90% of these cases reported in the northern. Given the alarmingly high incidence and variation in the geographical distribution of human brucellosis cases, there is an urgent need to decipher the causes of such variation in geographical distribution. Method We conducted a retrospective epidemiological study in Shaanxi Province from January 1, 2005 to December 31, 2018 to investigate the association between meteorological factors and transmission of human brucellosis according to differences in geographical distribution and seasonal fluctuation in northwestern China for the first time. Results Human brucellosis cases were mainly distributed in the Shaanbei upland plateau before 2008 and then slowly extended towards the southern region with significant seasonal fluctuation. The results of quasi-Poisson generalized additive mixed model (GAMM) indicated that air temperature, sunshine duration, rainfall, relative humidity, and evaporation with maximum lag time within 7 months played crucial roles in the transmission of human brucellosis with seasonal fluctuation. Compared with the Shaanbei upland plateau, Guanzhong basin had more obvious fluctuations in the occurrence of human brucellosis due to changes in meteorological factors. Additionally, the established GAMM model showed high accuracy in predicting the occurrence of human brucellosis based on the meteorological factors. Conclusion These findings may be used to predict the seasonal fluctuations of human brucellosis and to develop reliable and cost-effective prevention strategies in Shaanxi Province and other areas with similar environmental conditions.

Spatiotemporal expansion of human brucellosis in Shaanxi Province, Northwestern China and model for risk prediction

The rate of brucellosis, a zoonotic disease, has rapidly increased in humans brucellosis(HB) in recent years. In 1950–2018, a total of 684,380 HB cases (median 2274/year (interquartile range (IQR) 966–8325)) were reported to the National Infectious Disease Surveillance System in mainland China. The incidence of HB peaked in 2014 (4.32/100,000), and then showed a downward trend; we predict that it will maintain a steady downward trend in 2019–2020. Since 2015, the incidence of HB has shown opposite trends in the north and south of China; rates in the north have fallen and rates in the south have increased. In 2004–2018, the most significant increases in incidence of HB were in Yunnan (IQR 0.002–0.463/100,000), Hubei (IQR 0.000–0.338/100,000), and Guangdong (IQR 0.015–0.350/100,000). The areas where HB occurs have little overlap with areas with high per capita GDP in China. The “high–high” clusters of HB are located in northeastern China (Inner Mongolia, Heilongjiang, Jilin, Liaoning, Ningxia, Shanxi, and Gansu), and the “low–low” clusters of HB are located in southern China (Yunnan, Jiangxi, Shanghai, Guangxi, Guangdong, Zhejiang, Guizhou, and Hunan). In recent years, the incidence of HB in China has been controlled to some extent, but the incidence of HB has increased in southern China, and the disease has spread geographically in China from north to south. Further research is needed to address this change and to continue to explore the relationship between the incidence of HB and relevant factors.

https://www.mdpi.com/1660-4601/17/7/2382/pdf

Epidemiological Characteristics and Spatiotemporal Trend Analysis of Human Brucellosis in China, 1950-2018.

To measure the seroprevalence of high-exposure populations in brucellosis endemic areas and report the outcome and duration of seropositive asymptomatic subjects, we screened 595 family members of shepherds in Jilin Province, China and then followed up 15 seropositive asymptomatic subjects for 18 months. We found that the seropositive rate of 15.5%. Nearly half of seropositive asymptomatic subjects (7/15) developed into brucellosis in the short term; others were still seropositive asymptomatic or had decreased SAT titer in a longer time.

Brucellosis screening and follow-up of seropositive asymptomatic subjects among household members of shepherds in China.

The association of depression with use of prescription drugs in adults with noncommunicable diseases: Based on NHANES in 2005-2016.

Background Brucellosis is a critical zoonotic disease in the world, it is the non-specific arthralgia that make brucellosis patients easily misdiagnosed as rheumatoid arthritis (RA) in endemic regions. Elevated rheumatoid factor (RF) is an essential indicator of RA, and the RF in brucellosis patients is significantly higher than healthy people. Therefore, this study further explored the distribution of RF and the relevant factors of the RF positivity in brucellosis patients with arthralgia, in order to strengthen the recognition of physicians for brucellosis patients with RF positivity, especially in brucellosis-endemic areas, so as to avoid misdiagnosis and untimely treatment that may lead to malignant outcomes. Methodology and principal findings The medical records of all 572 brucellosis inpatients were collected in the Sixth People's Hospital of Shenyang, China from 2015 to 2016. After excluding 106 patients without arthralgia, 5 patients who unwilling to perform RF testing and 16 patients with diseases that may affect RF, 445 brucellosis inpatients with arthralgia were involved in this retrospective cross-sectional study. 143 (32.1%) patients with RF >10 IU/ml were classified into the RF positive group, with an average level of 16.5[12.2, 34.7] IU/ml, of which 45 (10.1%) patients were high-positive with RF >30 IU/ml. Multivariate logistic regression model was used to further analyze the relevant factors of the RF positivity and found that age, wrist joint pain and elevated C-reactive protein (CRP) were positively associated with RF positivity, with OR of 1.02 (P = 0.024), 8.94 (P = 0.008) and 1.79 (P = 0.019), respectively. Conclusion The prevalence of positive RF in brucellosis patients with arthralgia was critical, nearly one-third of patients had RF positive. Elderly men brucellosis patients with arthralgia, wrist joint pain and elevated CRP were at high risk of positive RF. It is reminded that physicians should focus on differential diagnosis during clinical diagnosis and treatment, especially in brucellosis-endemic regions.

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Prevalence and relevant factors of positive RF in brucellosis patients with arthralgia.

Birt–Hogg–Dube syndrome is an autosomal dominant condition that arises from germline folliculin (FLCN) mutations. It is characterized by skin fibrofolliculomas, lung cysts, pneumothorax, and renal cancer. Here, we present the case of a 36-year-old woman with asymptomatic, multiple renal tumors and a history of spontaneous pneumothorax. Genetic analysis revealed a hotspot FLCN germline mutation, c.1285dupC (p.H429fs), and a novel somatic mutation, c.470delT (p.F157fs). This information and the results of immunohistochemical analysis of the renal tumors indicated features compatible with a tumor suppressor role of FLCN. Two transcription factors, oncogenic TFEB and TFE3, were shown to be regulated by FLCN inactivation, which results in their nuclear localization. We showed that a deficiency in the tumor suppressor FLCN leads to deregulation of the mammalian target of rapamycin signaling (mTOR) pathway. A potential link between FLCN mutation and ciliary length was also examined. Thus, the mutation identified in our patient provides novel insights into the relationship among FLCN mutations, TFEB/TFE3, mTOR, and cilia. However, an in-depth understanding of the role of folliculin in the molecular pathogenesis of renal cancer requires further study.

Xiangyi Zhang

Papers

Epidemiological Characteristics and Spatiotemporal Trend Analysis of Human Brucellosis in China, 1950-2018.

Brucellosis screening and follow-up of seropositive asymptomatic subjects among household members of shepherds in China.

The association of depression with use of prescription drugs in adults with noncommunicable diseases: Based on NHANES in 2005-2016.

Prevalence and relevant factors of positive RF in brucellosis patients with arthralgia.

Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function: A Case Report