Transmission dynamics of Tuberculosis in a high-burden area of China: an 8-year population-based study using whole genome sequencing.

OBJECTIVES: This study investigated the transmission patterns of tuberculosis and its associated risk factors in Hunan province to inform the development of prevention and control strategies in the region. METHODS: An 8-year retrospective population-based genomic epidemiological study was conducted. Genomic clusters were defined using distance thresholds of 12-single-nucletide-polymorphisms. Risk factors associated with TB transmission were analyzed using logistic regression model. Kernel Density analysis was used to locate hotspots where transmission occurred. RESULTS: Among 2649 TB cases included in this study, 275 clusters were identified, with an overall clustering rate of 24.7% (654/2649). Nearly 95% (620/654) of clustered strains were isolated from the same county. Of the 275 clusters, 23 (8.4%, 23/275) had differences in drug-resistant profiles, with FQs resistance mutations occurring most frequently (52.2%, 12/23). Multivariate analysis identified male TB patients, those aged 30-60 years, ethnic minorities, non-farmers, retreated TB patients, and individuals infected with MDR/RR-TB as independent risk factors for TB transmission (P<0.05). CONCLUSION: Recent transmission in the region is predominantly occurring within counties. The risk factors related to the TB transmission and the hotspots where transmission occurs can provide a scientific basis for the formulation of targeted tuberculosis prevention and control strategies.

Intravenous leiomyomatosis in the inferior vena cava and right atrium with pulmonary benign metastasizing leiomyoma secondary to a pelvic arteriovenous fistula: a case report and literature review.

BACKGROUND: To report the diagnosis and treatment of a rare disease of intravenous leiomyomatosis (IVL) originating from the uterus, growing in the inferior vena cava (IVC) and extending into the right atrium (RA) associated with a pelvic arteriovenous fistula (AVF). This is the first reported case of IVL in the IVC and RA with pulmonary benign metastasizing leiomyoma (PBML) secondary to a pelvic AVF despite the use of GnRH agonists in a non-menopausal woman. CASE PRESENTATION: The patient was a 50-year-old premenopausal woman with a history of surgical resection for and anti-estrogen conservative drug for pulmonary benign metastasizing leiomyoma (PBML) 5 years. The patient nevertheless developed IVL in the IVC, internal iliac vein and RA accompanied by AVF. Vaginal ultrasound combined with echocardiography and Computerized tomographic venography imaging assists in the diagnosis of IVL combined with AVF, with histopathology and immunohistochemistry ultimately confirming the diagnosis. the patient ultimately was performed with a combination of hysterectomy, bilateral adnexectomy, and resection of tumors in the IVC and RA without cardiopulmonary bypass and sternotomy. CONCLUSION: BML may be difficult to control with incomplete removal of the uterus and ovaries even with the use of anti-estrogenic medications, and medically induced AVF resulting from fibroid surgery may accelerate this process and the development of IVL.

Drug-Resistant Profiles and Genetic Diversity of Mycobacterium Tuberculosis Revealed by Whole-Genome Sequencing in Hinggan League of Inner Mongolia, China.

Background: Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China. Methods: This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models. Results: A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052-4.210) and male patients (AOR = 3.858, 95% CI: 1.416-10.511) were identified as independent risk factors associated with DR-TB. Conclusion: Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.

Placenta-targeted Treatment Strategies for Preeclampsia and Fetal Growth Restriction: An Opportunity and Major Challenge.

The placenta plays a crucial role in maintaining normal pregnancy. The failure of spiral artery remodeling (SAR) is a key factor leading to placental ischemia and poor perfusion which is strongly associated with obstetric diseases, including preeclampsia (PE) and fetal growth restriction (FGR). Existing interventions for PE and FGR are limited and termination of pregnancy is inevitable when the maternal or fetus condition deteriorates. Considering the safety of the mother and fetus, treatments that may penetrate the placental barrier and harm the fetus are not accepted. Developing targeted treatment strategies for these conditions is urgent and necessary. With the proven efficacy of targeted therapy in treating conditions such as endometrial cancer and trophoblastic tumors, research on placental dysfunction continues to deepen. This article reviews the studies on placenta-targeted treatment and drug delivery strategies, summarizes the characteristics proposes corresponding improvement measures in targeted treatment, provides solutions for existing problems, and makes suggestions for future studies.

Impact of MSMEG5257 Deletion on Mycolicibacterium smegmatis Growth.

Mycobacterial membrane proteins play a pivotal role in the bacterial invasion of host cells; however, the precise mechanisms underlying certain membrane proteins remain elusive. Mycolicibacterium smegmatis (Ms) msmeg5257 is a hemolysin III family protein that is homologous to Mycobacterium tuberculosis (Mtb) Rv1085c, but it has an unclear function in growth. To address this issue, we utilized the CRISPR/Cas9 gene editor to construct Δmsmeg5257 strains and combined RNA transcription and LC-MS/MS protein profiling to determine the functional role of msmeg5257 in Ms growth. The correlative analysis showed that the deletion of msmeg5257 inhibits ABC transporters in the cytomembrane and inhibits the biosynthesis of amino acids in the cell wall. Corresponding to these results, we confirmed that MSMEG5257 localizes in the cytomembrane via subcellular fractionation and also plays a role in facilitating the transport of iron ions in environments with low iron levels. Our data provide insights that msmeg5257 plays a role in maintaining Ms metabolic homeostasis, and the deletion of msmeg5257 significantly impacts the growth rate of Ms. Furthermore, msmeg5257, a promising drug target, offers a direction for the development of novel therapeutic strategies against mycobacterial diseases.

Transmission characteristics in Tuberculosis by WGS: nationwide cross-sectional surveillance in China.

China, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR = 2.77), smear-positive (cOR = 2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.

The Recent Transmission and Associated Risk Factor of Mycobacterium tuberculosis in Golmud City, China.

Background: Tuberculosis (TB) remains a severe public health problem globally, and it is essential to comprehend the transmission pattern to control tuberculosis. Herein, we evaluated the drug-resistant characteristics, recent transmission, and associated risk factors of TB in Golmud, Qinghai, China. Methods: In this study, we performed a population-based study of patients diagnosed with TB in Golmud from 2013 to 2018. Drug-susceptibility testing and whole-genome sequencing were performed on 133 Mycobacterium tuberculosis strains. The genomic clustering rate was calculated to evaluate the level of recent transmission. Risk factors were identified by logistic regression analysis. Results: Our results showed that 46.97% (62/132) of strains were phylogenetically clustered and formed into 23 transmission clusters, suggesting a high recent transmission of TB in the area. 12.78% (17/133) strains were multidrug-resistant/rifampicin tuberculosis (MDR/RR-TB), with a high drug-resistant burden. Based on drug resistance gene analysis, we found 23 strains belonging to genotype MDR/RR-TB, where some strains may have borderline mutations. Among these strains, 65.2% (15/23) were found within putative transmission clusters. Additionally, risk factor analysis showed that recent transmission of TB happened more in patients with Tibetan nationality or older age. Conclusion: Overall our study indicates that the recent transmissions of MTB strains, especially genotypic MDR/RR strains, drive the tuberculosis epidemic in Golmud, which could contribute to developing effective TB prevention and control strategies.