[Progress in novel biomarkers of anti-tuberculosis drug-induced liver injury].

Anti-tuberculosis drug-induced liver injury(ATB-DILI) is the most common adverse reaction during anti-tuberculosis therapy in tuberculosis patients. At present, the diagnosis of ATB-DILI is mainly based on traditional biomarkers such as transaminases, but these indicators have low specificity for liver toxicity, they cannot explain the mechanism of liver injury and the early onset of ATB-DILI. Based on the prediction of disease severity, treatment and prevention, this paper described the current potential biomarkers of ATB-DILI.

[Annual progress of interventional diagnosis and treatment of tuberculosis in 2023].

A series of studies on the interventional diagnosis and treatment of tuberculosis(TB)were carried out by domestic and foreign researchers in 2023. The combination of minimally invasive interventional procedures with endoscopes, guidance, material acquisition techniques by multiple ways and multichannel and highly accurate laboratory testing techniques is becoming more and more widely practiced clinically, which has played an important role in the accurate diagnosis of problematic TB. Diagnostic procedures for pulmonary TB, tracheobronchial TB, mediastinal lymphatic TB and extrapulmonary TB included conventional flexible bronchoscopy and specific types of bronchoscopy(ultrathin bronchoscopy and endobronchial ultrasound), transbronchial needle aspiration biopsy, endobronchial ultrasound and virtual bronchoscopic navigation system-guided forceps biopsy, thoracoscopic cryobiopsy of pleura, percutaneous biopsy, and so on. The time to diagnosis has been significantly reduced and the diagnostic efficacy has been improved by the clinical specimen detection using either Gene Xpert MTB/RIF, Ultra, loop-mediated isothermal amplification, metagenomic next-generation sequencing, or nanopore sequencing, etc. Interventional therapy was focused on the following diseases: pulmonary TB with massive hemoptysis, tracheobronchial TB, pleural TB and TB-related fistulas. Interventional treatment of tracheobronchial TB mainly included the application of rigid bronchoscopy, bronchoscopic cold and thermal ablation treatment, endoscopic clamp, dilatations of narrow airway with balloon and stent placement, etc. The interventional treatment of pulmonary TB complicated by massive hemoptysis included endovascular embolization, coated stent placement, etc. Interventional treatment of pleural TB involved the application of thoracoscopy, endoscopic forceps, the implantation of stent and other occlusive devices and the closure of fistulas with autologous fat transplantation. In this article, we reviewed the progress of interventional diagnosis and treatment of TB by the search of published literatures from October 2022 to September 2023.

[Diffuse lung lesions and multiple enlarged lymph nodes: a case report].

This article reported a case of an elderly female patient with diffuse lung lesions and multiple enlarged lymph nodes. In the early stages of diagnosis, many clues, obtained through cellular immunology and molecular biology tests on a variety of samples including blood and bronchoalveolar lavage fluid, pointed to the diagnosis of tuberculosis. At the same time, a peripheral lymph node biopsy was conducted, which led to the diagnosis of lymphoma coexisting with tuberculosis, a"dual-diagnosis". In the subsequent treatment, lymphoma therapy was actively pursued while the patient's tuberculosis infection was treated, with good results observed in the follow-up treatments. When diagnosing the disease, the differential diagnosis must be integrated into the overall disease process, and avoiding rigid adherence to a "unitary"diagnostic concept.

[Annual progress on molecular biological diagnosis of tuberculosis 2022].

Tuberculosis (TB) continues to be a global public health issue that threatens human health, and rapid and accurate pathogen detection is the key to early diagnosis and effective treatment. In recent years, the pathogenic diagnosis of tuberculosis is expanding from traditional bacteriological diagnosis to molecular diagnosis. In the past year, Xper MTB/RIF Ultra technology with good diagnostic performance has been applied more often to the detection of non-respiratory samples, and Xpert XDR and second-generation linear probe technology provided more basis for early and accurate diagnosis of multidrug resistance; genome sequencing technology has also been developed and applied more often to the detection of non-culture sample detection, and the cost and time required for detection have been relatively reduced. Truenat technology, which is more suitable for primary care centers, is more widely used; new TB detection technologies, such as cell-free DNA testing and mass spectrometry, are also being developed and are expected to become important tools for early and rapid diagnosis of TB and drug-resistant TB. In this review, we synthesized the major research results of molecular biology diagnosis of tuberculosis around the world from 1st October 2021 to 30th September 2022, and comprehensively evaluated the advantages, disadvantages and current application of molecular biology detection technologies to provide a significant basis for clinical decision-making.

[Annual progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis in 2022].

At present, the number of cases with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in China ranks fourth in the world, and the prevention and control situation is still serious. Chemotherapy, as the most important treatment for MDR/RR-TB, was studied and explored by domestic and foreign researchers in 2022. New chemotherapeutic drugs such as delpazolid, sutezolid, telacebec and independently developed anti-tuberculosis drugs such as pyrifazimine, sudapyridine and JBD0131 are still in clinical trials. The efficacy, safety, tolerability, adverse reactions and drug resistance of bedaquiline, linezolid, delamanid and pretomanid have been studied extensively. Meanwhile, different new chemotherapy regimens centered on new drugs have been explored in-depth by international scholars. In this article, we reviewed the progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis from October 2021 to September.

[Effect of Mycobacterium tuberculosis protein Rv0309 on intracellular survival of Mycobacterium smegmatis by inhibiting macrophage autophagy via protein STUB1].

Objective: To investigate the molecular regulatory mechanism of Mycobacterium tuberculosis (MTB) protein Rv0309 to promote the survival of Mycobacterium smegmatis (Ms) in macrophages. Methods: Using Ms as a model to study Mycobacterium tuberculosis, recombinant Ms transfected with pMV261 and PMV261-RV0309 in the control group and RAW264.7 cells were constructed. The effect of Rv0309 protein on intracellular survival of Ms was investigated by counting colony forming units (CFUs). Mass spectrometry was used to screen proteins interacting with host protein Rv0309, and immunocoprecipitate (Co-IP) was used to verify that host protein STUB1 could interact with host protein Rv0309. STUB1 gene knock-out RAW264.7 cells were infected with Ms, and CFUs were counted to explore the effect of protein Rv0309 on intracellular survival of Ms after STUB1 gene knock-out. STUB1 gene knock-out RAW264.7 cells were infected with Ms, and after obtaining samples, Western blotting assay was performed to explore the effect of protein Rv0309 on autophagy function of macrophages after STUB1 gene knock-out. Statistical analysis was performed using GraphPad Prism 8 software. T-test was selected for analysis in this experiment, with P<0.05 was considered statistically significant. Results: Western blotting showed that Rv0309 was expressed in M. smegmatis and secreted extracellularly. The CFUs of the Ms-Rv0309 group was higher than that of Ms-pMV261 group at 24 h after THP-1 macrophage infection, and the difference was statistically significant (P<0.05). The trend of infected RAW264.7 macrophages was the same as that of infected THP-1 macrophages. The Co-IP results showed that the corresponding Flag and HA bands appeared in the results of immunoprecipitation (IP):Flag and IP: HA. The level of CFUs in the experimental group with STUB1 deletion was significantly higher than that in the control group without STUB1 deletion. Compared with Ms-pMV261, the CFUs in the Ms-Rv0309 group was significantly higher than that in the Ms-pMV261 group. The gray scale of LC3Ⅱ bands of Ms-Rv0309 in experimental group was lighter than that of Ms-pMV261 in the control group at the corresponding time point, and the result was most significant at 8 h (LC3Ⅱ/ß-actin: 0.76±0.05 vs 0.47±0.07), the difference being statistically significant (P<0.05). After STUB1 genome knock-out, the gray level of LC3Ⅱ bands at the corresponding time was lighter than that without STUB1 genome knock-out. Comparison of the results of Ms-pMV261 and Ms-Rv0309 strains revealed that LC3Ⅱ band gray Rv0309 group was lighter at the corresponding time compared with pMV261 group. Conclusions: MTB protein Rv0309 can be successfully expressed in M. smegmatis and secreted extracellularly, which can inhibit the autophagy process of macrophages. Protein Rv0309 interacts with host protein STUB1 to inhibit macrophage autophagy and promote intracellular survival of Ms.

[Progress on health-related quality of life and its influencing factors in patients with tuberculosis sequelae].

With the emergence of new tuberculosis patients, the number of patients with tuberculosis sequelae is increasing, which not only increases the medical burden of tuberculosis sequelae year by year, but also affects the health-related quality of life (HRQOL) of patients. The HRQOL of patients with tuberculosis sequelae has gradually received attention, but there are few relevant studies. Studies have shown that HRQOL is related to various factors such as post-tuberculosis lung disease, adverse reaction to anti-tuberculosis drugs, decreased physical activity, psychological barriers, low economic status and marital status. This article reviewed the current situation of HRQOL in patients with sequelae of tuberculosis and its influencing factors, in order to provide a reference for improving the quality of life of patients with sequelae of tuberculosis.

[Risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis].

Objective: To investigate the risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis(TBTB). Methods: Clinical data of adult patients (≥18 years old) with TBTB from February 2018 to December 2021 in Public Health Clinical Center of Chengdu were retrospectively analyzed. A total of 258 patients were included, with a male to female ratio of 1∶1.43. The median age was 31(24, 48) years. Clinical data including clinical characteristics, previous misdiagnoses/missed diagnoses before admission, pulmonary atelectasis, the time from symptom onset to atelectasis and bronchoscopy, bronchoscopy and interventional treatment were collected according to the inclusion and exclusion criteria. Patients were divided into two groups according to whether they had pulmonary atelectasis. Differences between the two groups were compared. Binary logistic regression was used to analyze the risk factors for pulmonary atelectasis. Results: The prevalence of pulmonary atelectasis was 14.7%, which was most common in the left upper lobe (26.3%). The median time from symptom onset to atelectasis was 130.50(29.75,358.50)d, and the median time from atelectasis to bronchoscopy was 5(3,7)d. The median age, the proportion of misdiagnosis of TBTB before admission, and the time from symptom onset to bronchoscopy in the atelectasis group were higher than those without atelectasis, and the proportion of receiving bronchoscopy examination and interventional therapy previously, and the proportion of pulmonary cavities were lower than those without atelectasis (all P<0.05). The proportions of cicatrices stricture type and lumen occlusion type in the atelectasis group were higher than those without atelectasis, while the proportions of inflammatory infiltration type and ulceration necrosis type were lower than those without atelectasis (all P<0.05). Older age (OR=1.036, 95%CI: 1.012-1.061), previous misdiagnosis(OR=2.759, 95%CI: 1.100-6.922), longer time from symptom onset to bronchoscopy examination (OR=1.002, 95%CI: 1.000-1.005) and cicatrices stricture type (OR=2.989, 95%CI: 1.279-6.985) were independent risk factors for pulmonary atelectasis in adults with TBTB (all P<0.05). Of the patients with atelectasis who underwent bronchoscopy interventional therapy, 86.7% had lung reexpansion or partial reexpansion. Conclusions: The prevalence of pulmonary atelectasis is 14.7% in adult patients with TBTB. The most common site of atelectasis is left upper lobe. The TBTB type of lumen occlusion is complicated by pulmonary atelectasis in 100% of cases. Being older, misdiagnosed as other diseases, longer time from onset of symptoms to bronchoscopy examination, and being the cicatrices stricture type are factors for developing pulmonary atelectasis. Early diagnosis and treatment are needed to reduce the incidence of pulmonary atelectasis and increase the rate of pulmonary reexpansion.

Association of genetic variants in the Sirt1 and Nrf2 genes with the risk of metabolic syndrome in a Chinese Han population.

BACKGROUND: Metabolic syndrome (MetS) is a complex of interrelated risk factors, including central adiposity, increased blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Few studies have reported the genetic variants in the Sirt1 and Nrf2 genes (Sirt1 rs7895833 A > G, Sirt1 rs2273773 C > T and Nrf2 rs6721961 C > A) that increase the risk of type 2 diabetes mellitus and are correlated with some glycemic and metabolic traits in the Chinese Han population. METHODS: Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate the associations between three single nucleotide polymorphisms (SNPs) of Sirt1 and Nrf2 and the risk of MetS in a Chinese Han population using the PCR-CTPP method. RESULTS: This research showed that the risk of MetS was 2.41 times higher for the AA genotype (P = 0.038) and 1.94 times higher for the AG genotype (P = 0.016) compared with carriers of the GG genotype. The serum levels of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P < 0.05) in carriers of the AA genotype of Sirt1 rs7895833 than in carriers of the AG and GG genotypes in the general population. The serum level of total cholesterol in the AA genotype was lower (P = 0.033) than that in the other two genotypes. However, the genotype frequencies of Sirt1 rs2273773 and Nrf2 rs6721961 in the MetS group were not significantly different from those in the control subjects, and those two genetic variants were not correlated with metabolic traits. CONCLUSIONS: These results underscore the contributions of SNPs of Sirt1 rs7895833 to MetS susceptibility as well as glycemic and metabolic traits in a Chinese population.

[Pay attention to prevention and treatment of post-tuberculosis lung disease].

Post-tuberculosis lung disease (PTLD) refers to a group of lung diseases with chronic respiratory abnormalities, with or without clinical symptoms, partly or entirely caused by pulmonary tuberculosis. PTLD has high morbidity, disability rate and mortality, and has a serious impact on individuals, families and society. It is of great significance to fully understand its harm, explore its mechanism, and conduct in-depth research on its prevention, treatment, and rehabilitation.

[Improving tuberculosis diagnosis: rational use of health care resources].

Tuberculosis is a common and frequently-occurring clinical disease, but its clinical manifestations are not specific. Only by adhering to the guidance of relevant consensus and/or guidelines, making full and reasonably utilizing of the effective clinical resources, paying more attention to the incidence and clinical characteristics of tuberculosis, and by properly using auxiliary examination means, and fully and correctly mastering the diagnostic criteria of tuberculosis, can we have ability to avoid misdiagnosis and missed diagnosis of clinical tuberculosis, especially atypical tuberculosis, and improve the diagnosis level of tuberculosis, so as to achieve the goal of terminating tuberculosis as soon as possible, and to benefit human health.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

[SMARCB1 (INI1)-deficient sinonasal carcinoma: a clinicopathological analysis of six cases].

Objective: To study the clinicopathological features, diagnostic features and differential diagnoses of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Six cases of SDSC diagnosed at Eye, Ear, Nose and Throat Hospital, Fudan University from 2016 to 2018 were retrieved; the clinical features, histomorphology, immunophenotype, radiology and outcome were analyzed with review of literature. Results: There were five men and one woman with age range of 37 years to 75 years (mean 56 years). One case was in stage T2, and 5 cases were in stage T4. Computer tomography and magnetic resonance imaging showed a mass occupying the sinonasal cavity with bone destruction in all six patients. Microscopically, the tumors had infiltrative margins. Four tumors were composed mostly of basaloid cells, which possessed high nuclear/cytoplasmic ratio,scant cytoplasm,and minimalnuclear pleomorphism; and the cells were arranged in sheets or nests in a desmoplastic stroma. Two tumors were composed of rhabdoid cells, which possessed abundant, eosinophilic cytoplasm and eccentric nuclei, often growing in a nests or sheets pattern. Immunohistochemical staining showed that 6/6 cases had complete loss of INI1, diffusely and strongly positive for CKpan, and were negative for S-100 and EBER ISH; 4/6 cases were focally positive for p63; 1/5 was focally positive for Syn and p16. The Ki-67 index was 30% to 70%. The follow-up period ranged 1-26 months, with one patient died of extensive metastases, one had local recurrence, and two had lymph node metastases; one was alive without disease, and one was lost to follow-up. Conclusions: SMARCB1 (INI1)-deficient sinonasal carcinoma is mostly aggressive, with rapid progression and poor prognosis. Histomorphological spectrum predominantly consists of basaloid type and rhabdoid type. The complete loss of nuclear expression of INI1 can help to distinguish this tumor from its many mimickers.

[Study on the prevalence of Beijing genotype Mycobacterium tuberculosis and its relationship with second-line anti-tuberculosis drug resistance].

Objective: To explore the prevalence risk factors of Beijing genotype Mycobacterium tuberculosis (MTB) in Beijing and its correlation with second-line anti tuberculosis drug resistance. Methods: A total of 1 140 clinical MTB positive strains were collected from various districts in Beijing, and the drug sensitivity was detected by proportion method. Beijing genotype and non Beijing genotype MTB were identified by the method of Spoligotyping. Using SPSS 22.0 statistical software, chi square test or Fisher exact probability test was used to analyze the experimental data. Results: Among 1 140 MTB clinical isolates, 941 (82.5%) were Beijing genotype MTB, 199 were non Beijing genotype MTB. There were 663 males (70.5%) in Beijing genotype and 124 males (62.3%) in non Beijing genotype strains. There were significant differences in the proportion of males between the two genotypes [P=0.021, OR (95% CI):1.442 (1.048-1.985)]. There were 441 floating population (46.9%) in Beijing genotype MTB and 78 floating population (39.2%) in non Beijing genotype MTB. There was a significant difference in the proportion of floating population between the two genotypes [P=0.048,OR (95%CI):1.368(1.001-1.869)]. There were 129 patients (13.7%) aged 65 or older in Beijing genotype MTB, 40 patients (20.1%) aged 65 or older in non Beijing genotype MTB. The difference was statistically significant [P=0.021, or (95% CI): 0.631 (0.426-0.936)]. The resistance drug rates of Levofloxacin (Lfx), Amikacin (Am), Capreomycin (Cm), Para-aminosalicylic (PAS) in Beijing genotypes were 5.5% (52/941), 1.3% (12/941), 3.2% (30/941) and 3.0% (28/941), respectively, and those of non Beijing genotypes were 10.6% (21/199), 8.5% (17/199, 12.6% (25/199) and 11.6% (23/199), the difference was statistically significant (all P<0.05). There were 58 (6.2%) multidrug-resistant (MDR) strains in Beijing genotype MTB and 19 (9.5%) multidrug-resistant strains in non Beijing genotype. There was no significant difference in the proportion of MDR strains between Beijing genotype and non Beijing genotype (P>0.05). Conclusions: Beijing genotype MTB is widespread in Beijing and has a higher proportion in male population and floating population. Compared with non Beijing genotype, Beijing genotype MTB has a lower resistance rate to Lfx, Am, Cm and PAS, and there is no significant difference in the proportion of MDR-TB patients between the two genotypes.

Proving Nontrivial Topology of Pure Bismuth by Quantum Confinement.

The topology of pure Bi is controversial because of its very small (∼10 meV) band gap. Here we perform high-resolution angle-resolved photoelectron spectroscopy measurements systematically on 14-202 bilayer Bi films. Using high-quality films, we succeed in observing quantized bulk bands with energy separations down to ∼10 meV. Detailed analyses on the phase shift of the confined wave functions precisely determine the surface and bulk electronic structures, which unambiguously show nontrivial topology. The present results not only prove the fundamental property of Bi but also introduce a capability of the quantum-confinement approach.