Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Objective To analyze the clinical characteristics and factors influencing adverse treatment outcomes in elderly patients with multidrug-resistant pulmonary tuberculosis (MDR-TB) to guide the clinical diagnosis and treatment of elderly MDR-TB patients. Methods Clinical data of elderly patients with multidrug-resistant pulmonary tuberculosis initially treated at Beijing Chest Hospital from 2008 to 2023 were retrospectively collected. Complications/comorbidities, adverse drug reactions, drug resistance during initial treatment, and retreatment were statistically described. Factors influencing adverse treatment outcomes were analyzed using the chi-square test and logistic regression analysis. Results A total of 238 elderly patients with MDR-TB were collected, of which 152 (63.9%) had adverse drug reactions, 184 (77.3%) were retreated MDR-TB, 27 (11.3%) were extensively drug-resistant tuberculosis (XDR-TB), 41 were cured, 6 completed treatment, 39 failed treatment, 6 died, 107 lost to follow-up, 31 could not be evaluated, 8 did not finish treatment, and the treatment success rate was 20.4% (47/230). The adverse outcome of treatment accounted for 79.6% (183/230). Univariate analysis showed that differences in age groups, the occurrence of drug adverse reactions, and patient sources had a statistically significant impact on treatment outcomes (P<0.05). Logistic regression analysis was performed using good and adverse treatment outcomes as dependent variables for the three factors, which showed that being aged 70 and above, the occurrence of drug adverse reactions during treatment, and being a non-local patient were factors influencing adverse treatment outcomes [OR (95%CI): 2.507 (1.027-6.121), 3.253 (1.635-6.473), 2.563 (1.285-5.111), respectively]. Conclusions Elderly patients with MDR-TB exhibit a high prevalence of complications/comorbidities, a high incidence of drug adverse reactions, and unfavorable treatment outcomes. Out-of-town medical treatment, advanced age, and experiencing drug adverse reactions are risk factors for adverse treatment outcomes.

Tuberculosis (TB) remains a significant global health challenge, ranking second only to COVID-19 as the leading cause of death from a single infectious agent, with 1.3 million TB-related deaths reported in 2022. Treatment efficacy has been compromised by the emergence of drug-resistant strains, including rifampin-resistant TB (RR-TB), multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Although first-line drugs like isoniazid, rifampicin, pyrazinamide, and ethambutol form the cornerstone of TB therapy, the rise of resistant strains necessitates the use of second-line drugs, which often come with increased toxicity and limited accessibility. Recent advances have focused on repurposing existing compounds and developing new drugs with novel mechanisms of action. Promising agents such as second-generation bedaquiline analogs (TBAJ-587, TBAJ-876), sudapyridine (WX-081), delamanid, pretomanid, and TBI-166 (pyrifazimine) have shown efficacy against resistant Mtb strains. Innovative treatment regimens like the BPaLM protocol-combining bedaquiline, pretomanid, linezolid, and moxifloxacin-offer shorter, all-oral therapies with higher cure rates. Personalized treatment durations and dose optimizations are becoming feasible through risk stratification algorithms and pharmacokinetic/pharmacodynamic studies. Immunotherapy is emerging as a complementary strategy to enhance the host's immune response against Mtb. Agents such as vitamin D, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), statins, metformin, and biological agents like interleukins and granulocyte-macrophage colony-stimulating factor are under exploration. Additionally, cell therapies involving mesenchymal stem cells and immune effector cells present new therapeutic avenues. Despite these advancements, significant challenges remain in achieving the World Health Organization's "End TB Strategy" goals, particularly as the COVID-19 pandemic has diverted resources and attention. Ongoing research and global collaboration are crucial to develop novel therapeutic strategies, optimize treatment regimens, and ultimately reduce the global burden of TB.
Humans ; Antitubercular Agents/therapeutic use* ; COVID-19/epidemiology* ; Tuberculosis/epidemiology*

OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Carcinoma, Renal Cell/diagnosis* ; Retrospective Studies ; Kidney ; Carcinoma ; Kidney Neoplasms/diagnosis*

Silibinin is a kind of flavonoid extracted from the dried ripe fruit of Silybum marianum，a plant of compositae. It has a variety of pharmacological activities and can effectively prevent and treat diabetes and its complications. This paper reviews the research progress on the mechanism of silibinin in the prevention and treatment of diabetes and its complications. It is found that silibinin can prevent and treat diabetes by up-regulating the expression of estrogen receptor-α，activating the duodenum-brain-liver axis pathway and stabilizing the protein structure. It can prevent and cure the nervous system diseases of diabetes by activating glucagon-like peptide-1 receptor/protein kinase A signal pathway and inhibiting the hyperphosphorylation of tau protein. It can prevent and treat diabetic retinopathy by down-regulating the expression and activity of pro-inflammatory，pro-oxidative factors and histone deacetylase 6. It can prevent diabetic nephropathy by activating protein kinase B signal pathway and reducing the level of transforming growth factor-β1，and prevent and treat diabete’s obesity by inhibition of hepatobiliary transporter CD36 expression， and suppressing nuclear factor-κB pathway and its downstream expression of pro-inflammatory cytokines（tumor necrosis factor-α and interleukin-1β），etc.

Objective:To analyze the clinical characteristics of pulmonary tuberculosis (PTB) in patients with prediabetes mellitus (PreDM) and improve the understanding and diagnosis of pulmonary tuberculosis complicated by prediabetes mellitus (PreDM-PTB).Methods:The clinical data of 109 inpatients with PTB who underwent glycated hemoglobin A1c (HbA1c) examination admitted to Beijing Chest Hospital, Capital Medical University from January 2015 to January 2016 were retrospectively analyzed. These patients were divided into the PreDM-PTB group ( n = 45) and the non-PreDM-PTB group (N-PreDMPTB group, n = 64) according to HbA1c test results. Patient demographic data, clinical features, imaging data, bacteriological results, and other laboratory results were collected from all patients. Results:The mean age and body mass index (BMI) were higher in the PreDM-PTB group than the N-PreDMPTB group. The proportion of patients having a smoking history was higher in the PreDM-PTB group than the N-PreDMPTB group (46.7% vs. 25.0%). The proportions of patients who had a cough (88.9%), fever (55.6%), anorexia (17.8%), chest tightness (31.1%), shortness of breath (28.9%), weight loss (40.0%), and pleural effusion (22.2%) were higher in the PreDM-PTB group than the N-PreDMPTB group. Patients with PreDM-PTB were more prone to develop anemia (55.6%), hypoproteinemia (55.6%), and increased low-density lipoprotein (26.7%) compared with patients with N-PreDMPTB. The levels of D-Dimer (93.2%), C-reactive protein (86.7%), and erythrocyte sedimentation rate (79.1%) were increased in the PreDM-PTB group compared with the N-PreDMPTB group. Sputum smear results showed that the positivity of mycobacterium tuberculosis was higher in the PreDM-PTB group (74.4%) compared with the N-PreDMPTB group. There was no significant difference in drug resistance between the two groups ( P > 0.05). The positivity of blood tuberculosis antibody and blood T-cell spot test for tuberculosis infection were 60.9% and 84.6% respectively in the PreDM-PTB group and they were 50.9% and 95.2% respectively in the N-PreDMPTB group. There were no significant differences in these two indices between the two groups ( P = 0.321, 0.066). Conclusion:Patients with Pre-DMPTB have different clinical manifestations and auxiliary examination characteristics compared with patients with N-PreDMPTB patients, which should be paid more attention to by clinicians. Early intervention should be actively adopted to prevent diabetes development from pre-DM.

BACKGROUND: Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). METHODS: Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated. RESULTS: Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively. CONCLUSION Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.
Antigens, Bacterial ; Diagnosis, Differential ; Humans ; Latent Tuberculosis/diagnosis* ; Leukocytes, Mononuclear ; Mycobacterium tuberculosis ; Tuberculosis/diagnosis*

OBJECTIVE: To investigate the effect of the chemoprotectant tempol on the anti-tumor activity of cisplatin (DDP). METHODS: The cellular toxicity of tempol in human colon cancer SW480 cells and mouse colon cancer CT26 cells were evaluated using MTT and cell counting kit-8 assays. CalcuSyn software analysis was used to determine the interaction between tempol and DDP in inhibition of the cell viability. A subcutaneous homograft mouse model of colon cancer was established. The mice were randomly divided into control group, tempol group, cisplatin group and tempol + DDP treatment group with intraperitoneal injections of the indicated agents. The tumor size, body weight and lifespan of the mice were measured, and HE staining was used to analyze the cytotoxic effect of the agents on the kidney and liver. Immunohistochemistry and Western blotting were performed to detect the expression of Bax and Bcl2 in the tumor tissue, and TUNEL staining was used to analyze the tumor cell apoptosis. The level of reactive oxygen species (ROS) in the tumor tissue was determined using flow cytometry. RESULTS: Tempol showed inhibitory effects on the viability of SW480 and CT26 cells. CalcuSyn software analysis showed that tempol had a synergistic anti-tumor effect with DDP (CI < 1). In the homograft mouse model, tempol treatment alone did not produce obvious anti-tumor effect. HE staining showed that the combined use of tempol and DDP alleviated DDP-induced fibrogenesis in the kidneys, but tempol also reduced the anti-tumor activity of DDP. Compared with the mice treated with DDP alone, the mice treated with both tempol and DDP had a significantly larger tumor size ( < 0.01) and a shorter lifespan ( < 0.05). Tempol significantly reversed DDP-induced expression of Bax and Bcl2 in the tumor tissue and tumor cell apoptosis ( < 0.001), and obviously reduced the elevation of ROS level in the tumor tissue induced by DDP treatment ( < 0.05). CONCLUSIONS Tempol can attenuate the anti-tumor effect of DDP while reducing the side effects of DDP. Caution must be taken and the risks and benefits should be carefully weighed when considering the use of tempol as an anti-oxidant to reduce the toxicities of DDP.
Animals ; Antineoplastic Agents ; Antioxidants ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin ; Cyclic N-Oxides ; pharmacology ; Drug Resistance, Neoplasm ; Humans ; Mice ; Spin Labels

Objective To explore the clinical characteristics of elderly patients with tuberculous meningitis (TBM) and analyze the causes of misdiagnosis.Methods The clinical data of patients aged 60 years and over with TBM in Beijing Chest Hospital Affiliated to Capital Medical University from January 2011 to January 2017 were retrospectively analyzed.The clinical characteristics of the elderly patients with TBM were analyzed and compared between misdiagnosis and non-misdiagnosis groups.Results Among 60 elderly patients with TBM,32 cases (53.3%) were misdiagnosed before hospitalization.Among 32 misdiagnosed cases,11 (34.4%) were misdiagnosed as pulmonary infection,6 (18.8%) as infectious diseases with unspecified site,4(12.5%) as upper respiratory tract infections and 3 (9.4%) as cerebral vascular diseases,and so on.The onset time of TBM,fever prevalence and CSF glucose levels were 42.5 (20.3,60.0) d,96.9% (31 cases),1.5(1.1,2.3)mmol/L in misdiagnosis group respectively,and 15.0 (10.0,20.0) d,75.0%(21 cases),2.3(1.4,3.2)mmol/L in non-misdiagnosis group respectively,which was statistically significantly different between the two groups (all P< 0.05).There were no statistically significant differences in age,gender,occupation,residence,complications,comorbidities,radiographic signs between the two groups (all P> 0.05).Conclusions Elderly patients with TBM have atypical clinical manifestations,many comorbidities,and less specific imaging,and especially,the cerebrospinal fluid pathogen sensitivity is low,which may result in higher misdiagnosis rate.

Objective To investigate the immune protection of heparin-hinding hemagglutinin ad-hesin(HBHA) and to estimate its potential diagnostic value. Methods Native HBHA were used to stimu-late peripheral blood mononuelear cells (PBMCs) from different infected-cases including PPD negative healthy control, PPD positive latent tuberculosis(LTB) infection, pulmonary tuberculosis, and the IFN-γ/in the supernatant of culture was detected. Meanwhile, HBHA specific IgG antibody in the sera was detected by ELISA. Results The middle level of HBHA specific IFN-γ of the three groups were 49.5 pg/ml, 781.9 pg/ml and 341.8 pg/ml, respectively. IFN-γ of latent tuberculosis group was much higher than that of the control, and slightly higher than that of the patients with pulmonary tuberculosis. And the absorbency of the IgG antibody to HBHA in the three groups was 0.212±0.066, 0.224 ± 0.076 and 0.285±0.078. lgG an-tibody in the patients with pulmonary tuberculosis is higher than that of the healthy, including the control and the latent tuberculosis infection. Conclusion HBHA has good immunogenieity, and it can stimulate the LTB to release high level IFN-γ, suggests that the LTB doesn't develop active tuberculosis may rely on its protection. HBHA specific. IFN-γ release may identify 1,333 from the healthy. Anti-HBHA antibody plays an auxiliary role in the diagnosis of pulmonary tuberculosis.