[Carrier screening for 223 monogenic diseases in Chinese population: a multi-center study in 33 104 individuals].

OBJECTIVE: To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale, multicenter carrier screening. METHODS: This study was conducted among a total of 33 104 participants (16 610 females) from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods. RESULTS: The overall combined carrier frequency was 55.58% for 197 autosomal genes and 1.84% for 26 X-linked genes in these participants.Among the 16 669 families, 874 at-risk couples (5.24%) were identified.Specifically, 584 couples (3.50%) were at risk for autosomal genes, 306(1.84%) for X-linked genes, and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A, 393 couples), HBA1/HBA2(α-thalassemia, 36 couples), PAH (phenylketonuria, 14 couples), and SMN1(spinal muscular atrophy, 14 couples).The most frequently detected X-linked at-risk genes were G6PD (G6PD deficiency, 236 couples), DMD (Duchenne muscular dystrophy, 23 couples), and FMR1(fragile X syndrome, 17 couples).After excluding GJB2 c.109G>A, the detection rate of at-risk couples was 3.91%(651/16 669), which was lowered to 1.72%(287/16 669) after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95% of at-risk couples, while screening for the top 54 genes further increased the detection rate to over 99%. CONCLUSION: This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing, genetic counseling for specific genes or gene variants can be challenging, and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

[Diagnostic value and influencing factors of endobronchial ultrasound-guided transbronchial needle aspiration combined with Xpert MTB/RIF for intrathoracic lymph node tuberculosis].

Objective: To evaluate the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) puncture to obtain intrathoracic lymph node samples combined with Xpert MTB/RIF (Xpert) detection for the diagnosis of intrathoracic lymph node tuberculosis. Methods: From March 2018 to June 2021, 106 patients [55 males and 51 females, age (45.1±18.6) years] with suspected intrathoracic lymph node tuberculosis and EBUS-TBNA were collected in Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, including 64 patients with subsequent diagnosis of intrathoracic lymph node tuberculosis and 42 patients without tuberculosis. Xpert test and traditional etiology test were performed on the patients' intrathoracic lymph node puncture specimens. The positive results of different detection methods and different methods were analyzed, and the influencing factors of Xpert independent detection positive were analyzed by univariate and multivariate logistic regression. Results: The sensitivity of Xpert was 65.6% (95%CI: 52.7%-77.1%), the specificity was 97.6% (95%CI: 87.4%-99.9%), the positive predictive value was 97.7% (95%CI: 85.7%-99.7%), the negative predictive value was 65.1% (95%CI: 57.0%-72.4%). The positive rate of Xpert alone (65.6%, 42/64) was not significantly different from that of MGIT960, histopathology and Xpert combined detection (70.3%, 45/64) (P<0.05). Multivariate logistic regression analysis showed that the location of the diseased lymph nodes in the mediastinum (OR=5.84, 95%CI: 1.112-30.704, P=0.037), necrosis in the lymph nodes (OR=6.32, 95%CI: 1.460-27.384, P=0.014), and the axial depth of the lymph nodes≥17 mm (OR=6.61, 95%CI: 1.408-30.969, P=0.017) were the promoting factors for the positive Xpert test. Conclusions: EBUS-TBNA combined with Xpert detection has a high clinical diagnostic value for intrathoracic lymph node tuberculosis. When the number of puncture samples is small, Xpert detection can be preferred. The positive rate of Xpert detection can be improved by selecting lymph nodes with mediastinal lesions, lymph nodes necrosis, and axial lymph nodes depth≥17 mm for puncture.

Obesity medications: A narrative review of current and emerging agents.

The aim of this narrative review is to synthesize the available data describing the efficacy and safety of medications approved for obesity management and to provide an overview of upcoming agents in development. A literature search of PubMed, Medline, and Embase databases identified relevant articles describing medications approved in the U.S., Australia, U.K., and/or Europe. Papers were selected based on relevance and originality, with phase 3 clinical trials and meta-analyses preferentially included. Six medications are widely approved for long-term weight management in conjunction with lifestyle interventions in people with body mass index (BMI) ≥30 â€‹kg/m2 or BMI ≥27 â€‹kg/m2 and at least one medical condition related to excess weight. Compared with lifestyle interventions alone, all medications approved for obesity management are more effective for long-term weight loss and improvements in cardiometabolic risk factors. Older obesity medications are associated with mean weight losses in the range of 5-10%. The new generation of agents, including the injectable incretin analogues semaglutide and tirzepatide are associated with sustained mean weight reductions of 15-20%, along with substantial benefits on a range of health outcomes. Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years. As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Other important challenges for clinical practice and research include the need for long-term strategies to prevent and manage weight regain and loss of lean muscle and bone mineral density.

Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25.0 kg/m2), overweight (25.0≤BMI<30.0 kg/m2), and obese (BMI≥30.0 kg/m2). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.