Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

MUC1 promotes cervical squamous cell carcinoma through ERK phosphorylation-mediated regulation of ITGA2/ITGA3.

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.

MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone.

The clinical significance of plasma sCD25 as valuable biomarker for progression and prognosis of tuberculosis.

BACKGROUND: sCD25 is an important immune molecule for T cell regulation. Tracking the detection of plasma sCD25 plays an important role in the evaluation of immune function, progression, and prognosis of tuberculosis (TB) patients. This study analyzed the association of plasma sCD25 levels with clinical, laboratory, CT imaging characteristics, and clinical outcome of TB patients. METHODS: The clinical data of 303 TB patients treated in the Fifth People's Hospital of Suzhou from October 2019 to January 2022 were retrospectively analyzed. The levels of sCD25 in plasma were detected by ELISA. According to the cut-off threshold of plasma sCD25 levels, the patients were divided into a low-value group (Group TB1) and a high-value group (Group TB2). The association of plasma sCD25 levels with clinical, laboratory, and CT imaging characteristics of TB patients, as well as their TB treatment outcome were analyzed. RESULTS: The levels of plasma sCD25 of patients with TB patients were higher than that of the healthy control group (P < 0.01). Among the 303 TB patients, the levels were increased in Group TB2 patients (0.602 ± 0.216 vs. 1.717 ± 0.604 ng/ml, P < 0.001), and there was a progressive reduction after anti-TB treatment. Furthermore, patients in Group TB2 showed higher positive rates in sputum smear (52.0% vs. 34.3%; P = 0.003), sputum culture (69.7% vs. 56.9%; P = 0.032), Xpert MTB/RIF (66.3% vs. 51.2%; P = 0.013) and TB-DNA (51.5% vs. 31.2%; P = 0.001) than those in Group TB1. Patients in Group TB2 had higher incidence in cough (78.8% vs. 62.3%; P = 0.004), expectoration (64.4% vs. 45.1%; P = 0.001), concomitant extrapulmonary TB (14.1% vs. 5.9%; P = 0.016), cavities (47.9% vs. 34.0%; P = 0.022), and unfavorable outcomes after anti-TB treatment. CONCLUSION: The clinical, laboratory and radiological manifestations of TB patients with high plasma sCD25 levels indicate that the disease is more severe. Tracking plasma sCD25 detection of TB patients has evident clinical significance. It is noteworthy that when the plasma sCD25 levels are significantly elevated, patients should be cautious of the TB progression and disease severity.

Machine learning models for prediction of postoperative venous thromboembolism in gynecological malignant tumor patients.

AIM: To identify risk factors that associated with the occurrence of venous thromboembolism (VTE) within 30 days after hysterectomy among gynecological malignant tumor patients, and to explore the value of machine learning (ML) models in VTE occurrence prediction. METHODS: A total of 1087 patients between January 2019 and January 2022 with gynecological malignant tumors were included in this single-center retrospective study and were randomly divided into the training dataset (n = 870) and the test dataset (n = 217). Univariate logistic regression analysis was used to identify risk factors that associated with the occurrence of postoperative VTE in the training dataset. Machine learning models (including decision tree (DT) model and logistic regression (LR) model) to predict the occurrence of postoperative VTE were constructed and internally validated. RESULTS: The incidence of developing 30-day postoperative VTE was 6.0% (65/1087). Age, previous VTE, length of stay (LOS), tumor stage, operative time, surgical approach, lymphadenectomy (LND), intraoperative blood transfusion and gynecologic Caprini (G-Caprini) score were identified as risk factors for developing postoperative VTE in gynecological malignant tumor patients (p < 0.05). The AUCs of LR model and DT model for predicting VTE were 0.722 and 0.950, respectively. CONCLUSION: The ML models, especially the DT model, constructed in our study had excellent prediction value and shed light upon its further application in clinic practice.

In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

The elevated expression of LAG-3 on CD8+T cells correlates with disease severity of pulmonary TB.

OBJECTIVE: Lymphocyte-activation gene 3 (LAG-3) plays an important role in regulating T-cell responses and inducing peripheral tolerance. Our aim in this study was to investigate the relationship between LAG-3 and active tuberculosis (ATB) and the impact of LAG-3 blockade on CD8+T cells. METHODS: Flow cytometry was used to detect the expression of LAG-3 on CD4+T and CD8+T cells in the peripheral blood and bronchoalveolar lavage fluid from ATB patients and to explore the relationship between LAG-3 and ATB. RESULTS: The expression of LAG-3 on CD4+T and CD8+T cells in ATB patients was increased (P < 0.001), and CD8+T cells with high expression of LAG-3 were associated with sputum culture results (P < 0.05). We further analyzed the relationship between the expression of LAG-3 in CD8+T cells and the severity of tuberculosis and found that the expression of LAG-3 on CD8+T cells in smear-positive tuberculosis patients was significantly higher than that in sputum smear-negative tuberculosis patients (P < 0.05). LAG-3 expression on CD8+T cells was negatively correlated with the presence of lung lesions (P < 0.05). After stimulation with a tuberculosis-specific antigen, the expression of LAG-3 on tuberculosis-specific CD8+T cells was also upregulated, and LAG-3-expressing CD8+T cells showed reduced production of IFN-γ, decreased activation, and lower proliferation, while the function of CD8+T cells was restored when LAG-3 signaling was blocked. CONCLUSIONS: This study further explored the relationship between immune exhaustion caused by LAG-3 and immune escape of Mycobacterium tuberculosis and revealed that the elevated expression of LAG-3 on CD8+T cells correlates with functional defects of CD8+T cells and the severity of pulmonary TB.

Reconfigurable Peptide Analogs of Apolipoprotein A-I Reveal Tunable Features of Nanodisc Assembly.

Nanodisc (ND)-forming membrane scaffold proteins or peptides developed from apolipoprotein A-I (apoA-I) have led to considerable promise in structural biology and therapeutic applications. However, the rationale and regularity characteristics in peptide sequence design remain inconclusive. Here, we proposed a consensus-based normalization approach through the reversed engineering of apoA-IΔ1-45 to design reconfigurable apoA-I peptide analogs (APAs) for tunable ND assembly. We present extensive morphological validations and computational simulation analyses on divergent APA-NDs that are generated by our method. Fifteen divergent APAs were generated accordingly to study the assembly machinery of NDs. We show that APA designs exhibit multifactorial influence in terms of varying APA tandem repeats, sequence composition, and lipid-to-APA ratio to form tunable diameters of NDs. There is a strong positive correlation between DMPC-to-APA ratios and ND diameters. Longer APA with more tandem repeats tends to yield higher particle size homogeneity. Our results also suggest proline is a dispensable residue for the APA-ND formation. Interestingly, proline-rich substitution not only provides an inward-bending effect in forming smaller NDs but also induces the cumulative chain flexibility that enables larger ND formation at higher lipid ratios. Additionally, proline-tryptophan residues in APAs play a dominant role in forming larger NDs. Molecular simulation shows that enriched basic and acidic residues in APAs evoke abundant hydrogen-bond and salt bridge networks to reinforce the structural stability of APA-NDs. Together, our findings provide a rational basis for understanding APA design. The proposed model could be extended to other apolipoproteins for desired ND engineering.

Ferroptosis: From regulation of lipid peroxidation to the treatment of diseases.

Ferroptosis is a regulated cell death mainly manifested by iron-dependent lipid peroxide accumulation. The leading cause of ferroptosis is the imbalance of intracellular oxidative systems (e.g., LOXs, POR, ROS) and antioxidant systems (e.g., GSH/GPx4, CoQ10/FSP1, BH4/GCH1), which is regulated by a complex network. In the past decade, this metabolic network has been continuously refined, and the links with various pathophysiological processes have been gradually established. Apoptosis has been regarded as the only form of regulated cell death for a long time, and the application of chemotherapeutic drugs to induce apoptosis of cancer cells is the mainstream method. However, studies have reported that cancer cells' key features are resistance to apoptosis and chemotherapeutics. For high proliferation, cancer cells often have very active lipid metabolism and iron metabolism, which pave the way for ferroptosis. Interestingly, researchers found that drug-resistant or highly aggressive cancer cells are more prone to ferroptosis. Therefore, ferroptosis may be a potential strategy to eliminate cancer cells. In addition, links between ferroptosis and other diseases, such as neurological disorders and ischemia-reperfusion injury, have also been found. Understanding these diseases from the perspective of ferroptosis may provide new insights into clinical treatment. Herein, the metabolic processes in ferroptosis are reviewed, and the potential mechanisms and targets of ferroptosis in different diseases are summarized.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Cu-Doped Polypyrrole with Multi-Catalytic Activities for Sono-Enhanced Nanocatalytic Tumor Therapy.

Nanocatalytic medicine is a burgeoning disease treatment model with high specificity and biosafety in which the nanocatalyst is the core of driving catalytic reaction to generate therapeutic outcomes. However, the robust defense systems in the pathological region would counteract nanocatalyst-initiated therapeutics. Here, a Cu-doped polypyrrole is innovatively developed by a facile oxidative polymerization reaction, which exhibits intriguing multi-catalytic activities, including catalyzing H2 O2 to generate O2 and · OH, and consuming reduced glutathione by a Cu(II)-Cu(I) transition approach. By decorating with sonosensitizers and DSPE-PEG, the obtained CuPPy-TP plus US irradiation can induce severe oxidative damage to tumor cells by amplifying oxidative stress and simultaneously relieving antioxidant capacity in tumors based on the highly effective sonochemical and redox reactions. The notable tumor-specific biodegradability, remarkable cell apoptosis in vitro, and tumor suppression in vivo are demonstrated in this work, which not only present a promising biocompatible antitumor nanocatalyst but also broaden the perspective in oxidative stress-based antitumor therapy.

MALDI-TOF-MS for Rapid Screening and Typing of ß-Globin Variant and ß-Thalassemia through Direct Measurements of Intact Globin Chains.

BACKGROUND: Traditional phenotype-based screening for ß-globin variant and ß-thalassemia using hematological parameters is time-consuming with low-resolution detection. Development of a MALDI-TOF-MS assay using alternative markers is needed. METHODS: We constructed a MALDI-TOF-MS-based approach for identifying various ß-globin disorders and classifying thalassemia major (TM) and thalassemia intermedia (TI) patients using 901 training samples with known HBB/HBA genotypes. We then validated the accuracy of population screening and clinical classification in 2 separate cohorts consisting of 16 172 participants and 201 ß-thalassemia patients. Traditional methods were used as controls. Genetic tests were considered the gold standard for testing positive specimens. RESULTS: We established a prediction model for identifying different forms of ß-globin disorders in a single MALDI-TOF-MS test based on δ- to ß-globin, γ- to α-globin, γ- to ß-globin ratios, and/or the abnormal globin-chain patterns. Our validation study yielded comparable results of clinical specificity (99.89% vs 99.71%), and accuracy (99.78% vs 99.16%) between the new assay and traditional methods but higher clinical sensitivity for the new method (97.52% vs 88.01%). The new assay identified 22 additional abnormal hemoglobins in 69 individuals including 9 novel ones, and accurately screened for 9 carriers of deletional hereditary persistence of fetal hemoglobin or δß-thalassemia. TM and TI were well classified in 178 samples out of 201 ß-thalassemia patients. CONCLUSIONS: MALDI-TOF-MS is a highly accurate, predictive tool that could be suitable for large-scale screening and clinical classification of ß-globin disorders.

Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy.

BACKGROUND: Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25-30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect. METHODS AND RESULTS: In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice. CONCLUSION: In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer.

Construction of Co,N-Coordinated Carbon Dots for Efficient Oxygen Reduction Reaction.

For the sake of the oxygen reduction reaction (ORR) catalytic performance, carbon dots (CDs) doped with metal atoms have accelerated their local electron flow for the past few years. However, the influence of CDs doped with metal atoms on binding sites and formation mechanisms is still uncertain. Herein, Co,N-doped CDs were facilely prepared by the low-temperature polymerization-solvent extraction strategy from EDTA-Co. The influence of Co doping on the catalytic performance of Co-CDs was explored, mainly in the following aspects: first, the pyridinic N atom content of Co-CDs significantly increased from 4.2 to 11.27 at% compared with the CDs, which indicates that the Co element in the precursor is advantageous in forming more pyridinic-N-active sites for boosting the ORR performance. Second, Co-CDs are uniformly distributed on the surface of carbon black (CB) to form Co-CDs@CB by the facile hydrothermal route, which can expose more active sites than the aggregation status. Third, the highest graphite N content of Co-CDs@CB was found, by limiting the current density of the catalyst towards the ORR. Composite nanomaterials formed by Co and CB are also used as air electrodes to manufacture high-performance zinc-air batteries. The battery has good cycle stability and realizes stable charges and discharges under different current densities. The outstanding catalytic activity of Co-CDs@CB is attributed to the Co,N synergistic effect induced by Co doping, which pioneer a new metal doping mechanism for gaining high-performance electrocatalysts.

Upregulation of PD-1 expression on circulating CD8+ but not CD4+ T cells is associated with tuberculosis infection in health care workers.

BACKGROUND: Health care workers (HCWs) are at risk for occupationally acquired Mycobacterium tuberculosis infection and tuberculosis (TB) disease due to repeated exposure to workplace tubercle bacilli. To determine whether continual mycobacterial stimulation correlates with increased expression of inhibitory T cell receptors, here we compared PD-1 receptor expression on surfaces of circulating T cells between naïve (uninfected) HCWs and HCWs with latent TB infection (LTBI). RESULT: Data collected from 133 medical workers who met study selection criteria were included in the final analysis. QuantiFERON-TB Gold In-​Tube (QFT-GIT) testing yielded positive results for 32 HCWs, for an overall LTBI rate of 24.1%. Multivariate analysis identified HCW length of service > 15 years as an independent risk factor for a positive QFT-GIT result. In addition, comparisons of blood T cell subgroup profiles between QFT- and QFT+ groups indicated QFT+ subjects possessed greater proportions of mature (TM), transitional memory (TTM) and effector memory (TEM) CD4+ T cell subgroups and lower proportions of naïve T cells (TN). Moreover, the QFT+ group percentage of CD8+ T cells with detectable surface PD-1 was significantly higher than the corresponding percentage for the QFT- group. Meanwhile, no statistical intergroup difference was observed in percentages of CD4+ T cells with detectible surface PD-1. CONCLUSIONS: Our data demonstrated that upregulated PD-1 expression on circulating CD8+, but not CD4+ T cells, was associated with latent TB infection of HCWs. As compared to other hospitals, occupational TB infection risk in our hospital was substantially mitigated by implementation of multitiered infection control measures.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) pneumonia.

BACKGROUND: There was much evidence suggesting that the serum lactate dehydrogenase (LDH) levels reflect the extent of various pathophysiological processes. However, the current information about dynamic change of LDH in COVID-19 pneumonia has not been well investigated. METHODS: Study was performed in 87 cases confirmed by COVID-19 infection. The serum LDH levels were determined at diagnosis and follow-up visits. The evaluation of clinical response to therapy was based on chest CT scan. We selected the value of LDH around the data of chest CT scan (- 1 ~ + 1 day). RESULTS: At diagnosis, significant differences in LDH levels were found between non-severe and severe group (P < 0.05). It was demonstrated that increase or decrease of LDH was indicative of radiographic progress or improvement (P < 0.05). The time to LDH normalization (5.67 ± 0.55, days) was positively correlated with the time to radiographic absorption (5.57 ± 0.65 days, r = 0.53, P < 0.05). Applying the cut-off value of the increase in LDH has good specificity to predict disease progression. CONCLUSIONS: Serum LDH was validated for its potential usefulness as markers for evaluating clinical severity and monitoring treatment response in COVID-19 pneumonia.

Clinical characteristics and laboratory indicator analysis of 67 COVID-19 pneumonia patients in Suzhou, China.

BACKGROUND: Sudden exacerbations and respiratory failure are major causes of death in patients with severe coronavirus disease 2019(COVID-19) pneumonia, but indicators for the prediction and treatment of severe patients are still lacking. METHODS: A retrospective analysis of 67 collected cases was conducted and included approximately 67 patients with COVID-19 pneumonia who were admitted to the Suzhou Fifth People's Hospital from January 1, 2020 to February 8, 2020. The epidemiological, clinical and imaging characteristics as well as laboratory data of the 67 patients were analyzed. RESULTS: The study found that fibrinogen (FIB) was increased in 45 (65.2%) patients, and when FIB reached a critical value of 4.805 g/L, the sensitivity and specificity、DA, helping to distinguish general and severe cases, were 100 and 14%、92.9%, respectively, which were significantly better than those for lymphocyte count and myoglobin. Chest CT images indicated that the cumulative number of lung lobes with lesions in severe patients was significantly higher than that in general patients (P < 0.05), and the cumulative number of lung lobes with lesions was negatively correlated with lymphocyte count and positively correlated with myoglobin and FIB. Our study also found that there was no obvious effect of hormone therapy in patients with severe COVID-19. CONCLUSIONS: Based on the retrospective analysis, FIB was found to be increased in severe patients and was better than lymphocyte count and myoglobin in distinguishing general and severe patients. The study also suggested that hormone treatment has no significant effect on COVID-19.

Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study.

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18-24 months and has a poor cure rate of 50-60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB.We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome.Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3% versus 55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1% versus 62.1%, p=0.009).Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen.

Longitudinal profiling of gut microbiome among tuberculosis patients under anti-tuberculosis treatment in China: protocol of a prospective cohort study.

BACKGROUND: Anti-tuberculosis therapy requires at least six-month treatment with continuous administration of combined antibiotics, including isoniazid, rifampicin, pyrazinamide, and ethambutol. The long-term exposure to antibiotics could cause consequent changes in gut microbiota, which may alter the gastrointestinal function and drug absorption in patients, thereby affect the outcome of treatment. The study aims to characterize the longitudinal changes of gut microbiota among tuberculosis (TB) patients under standardized first-line treatment and provide an understanding of the association between alterations in gut microbiota composition and unfavorable clinical outcomes. METHODS: The study is a multicenter, observational prospective cohort study. Three study sites are purposively selected in the western (Sichuan Province) and eastern (Jiangsu Province and Shanghai) parts of China. Three-hundred patients with bacteriologically confirmed pulmonary TB are enrolled. All eligible patients should be investigated using structured questionnaires before treatment initiation; and be followed up during the treatment at Day-14, Month-2, Month-5, the end of treatment and the sixth month after ending therapy. Stool samples are to be collected at each visit, consisting of six stool samples from each patient. Additionally, 60 healthy volunteers from Sichuan province and Shanghai city will be recruited as healthy controls to form the baseline of patient gut microbiota in the Chinese population. The dynamic changes of gut microbiota in terms of alpha diversity, beta diversity, taxonomic composition are to be illustrated individually from the time at diagnosis until the sixth month after therapy is completed. Furthermore, the diversity and component of gut microbiota will be compared between the groups with and without unfavorable treatment outcome in terms of adverse effect and treatment failure. DISCUSSION: Studies on the clinical manifestations, adverse reactions, and gut microbiota alterations will provide scientifically-sound evidence on the impact of gut microbiota alterations on TB treatment outcomes. The study is not only useful for guiding personalized TB treatment but also sheds light on the effects of continuous antibiotics administration on gut microbiota. TRIAL REGISTRATION: Chinese Clinical Trial Registry, trial ID: ChiCTR1900023369, May 24, 2019. Retrospectively registered.