New progress of tuberculosis scar carcinoma.

It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).

A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression.

BACKGROUND: This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications. METHODS: This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification. RESULTS: In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status. CONCLUSION: HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Clinical evaluation of deep learning-based risk profiling in breast cancer histopathology and comparison to an established multigene assay.

PURPOSE: To evaluate the Stratipath Breast tool for image-based risk profiling and compare it with an established prognostic multigene assay for risk profiling in a real-world case series of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients categorized as intermediate risk based on classic clinicopathological variables and eligible for chemotherapy. METHODS: In a case series comprising 234 invasive ER-positive/HER2-negative tumors, clinicopathological data including Prosigna results and corresponding HE-stained tissue slides were retrieved. The digitized HE slides were analysed by Stratipath Breast. RESULTS: Our findings showed that the Stratipath Breast analysis identified 49.6% of the clinically intermediate tumors as low risk and 50.4% as high risk. The Prosigna assay classified 32.5%, 47.0% and 20.5% tumors as low, intermediate and high risk, respectively. Among Prosigna intermediate-risk tumors, 47.3% were stratified as Stratipath low risk and 52.7% as high risk. In addition, 89.7% of Stratipath low-risk cases were classified as Prosigna low/intermediate risk. The overall agreement between the two tests for low-risk and high-risk groups (N = 124) was 71.0%, with a Cohen's kappa of 0.42. For both risk profiling tests, grade and Ki67 differed significantly between risk groups. CONCLUSION: The results from this clinical evaluation of image-based risk stratification shows a considerable agreement to an established gene expression assay in routine breast pathology.

Development and validation of a nomogram model of depression and sleep disorders and the risk of disease progression in patients with breast cancer.

BACKGROUND: In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. METHODS: A total of 750 postoperative patients with breast cancer were selected from the First People's Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. RESULTS: SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685-0.8613), 0.768 (0.727-0.809), and 0.7661 (0.724--0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848-0.918) and 0.937 (0.893-0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848-0.919) and 0.885 (0.818-0.951), respectively. CONCLUSION: We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.

The synergistic impact of probiotics and dietary fiber on constipation management in chlorpromazine-induced schizophrenia patients: exploring the modulation of intestinal microbiota and neurotrophic factors.

OBJECTIVE: To explore the improvement effect of probiotics combined with dietary fiber on constipation in patients with schizophrenia. METHODS: To compare the improvement scores of constipation, constipation symptoms, quality of life, neurotrophic factors-related indicators, and clinical efficacy between the two groups. RESULTS: There was no statistically significant difference in Cleveland Constipation Scoring System (CCS) scores in the control group before and after treatment (p > 0.05), while the CCS scores in the observation group decreased significantly after treatment (p < 0.05); Patient Assessment of Constipation Symptoms scores significantly decreased in the observation group compared to the control group (p < 0.05), with no significant difference in Patient Assessment of Constipation Quality of Life scores between the two groups pre- and post-treatment; Neuron-specific enolase levels decreased significantly in both groups post-treatment, while brain-derived neurotrophic factor, neuregulin-1, and nerve growth factor levels increased significantly, with a more pronounced rise in the observation group (p < 0.05). Additionally, the total effective rate of clinical treatment in the observation group was higher than that in the control group (p < 0.05). CONCLUSION: Probiotics combined with dietary fiber can improve constipation symptoms in patients with schizophrenia accompanied by constipation, effectively maintain the balance of intestinal microbiota, and improve the quality of life of patients. Additionally, levels of neurotrophic factors associated with bowel function and neurological health increased significantly, with a higher total effective rate of clinical treatment observed in the probiotics and dietary fiber group. These findings suggest the potential efficacy of probiotics and dietary fiber in managing constipation in this patient population.

The "4+4" Medical Doctor (MD) Pilot Program at PUMC: Implementation, Performance, and Prospects.

Peking Union Medical College (PUMC) launched the "4+4" Medical Doctor (MD) pilot program in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" MD pilot class at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "Medicine + X" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, and reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

TGFß1 Stimulates Lymphatic Endothelial Cells to Produce IL7 and IL15, Which Act as Chemotactic Factors for Breast Cancer Cells with Mesenchymal Properties.

The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor ß1 (TGFß1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGFß1 stimulated breast cancer cells with mesenchymal properties to migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and corresponding receptors that could be involved in guiding breast cancer cells through the lymphatic system. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL7/IL7R and IL15/IL15R as pairs of chemokines and receptors with potential roles in promoting chemotactic migration of breast cancer cells with mesenchymal properties towards the lymphatics. The results demonstrate the capacity of TGFß1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells and warrant further studies to explore the roles of IL7 and IL15 in promoting lymph metastasis of breast cancer.

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease.

OBJECTIVES: The aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD. METHODS: We performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results. RESULTS: We identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD. TOP2A_B cells and TOP2A_T cells had stemness signatures, and trajectory analysis showed that TOP2A_B cells may differentiate into IgG4+plasma cells and that TOP2A_T cells may differentiate into T follicular helper (Tfh) cells. ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD. CONCLUSION: Our data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

Real-world efficacy of belimumab in systemic lupus erythematosus: a prospective cohort from a single center in China.

OBJECTIVES: To explore the efficacy and safety of belimumab among Chinese patients with systemic lupus erythematosus (SLE) in a real-world setting. METHODS: A prospective cohort study was performed, and SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were consecutively enrolled from June 2021 to December 2022. Based on baseline characteristics, patients were divided into three groups: the newly diagnosed group, the relapsed group and the refractory group. Patients in the newly diagnosed group were newly diagnosed with SLE within 4 weeks of starting belimumab. Patients in the relapse group experienced a severe flare. Refractory patients were patients with unsatisfactory glucocorticoid taper and/or disease activity control. Clinical data were collected, and disease assessments were conducted regularly. Newly diagnosed patients with SoC alone and healthy controls (HCs) were also enrolled. RESULTS: A total of 123 SLE patients were included in the analysis, with a median follow-up period of 12 months (range 3-18 months). Thirty-three out of 123 patients were newly diagnosed, 32 had relapsed disease, and 58 had refractory disease. The SRI-4 response was achieved with good tolerance by 55.77% of patients at 3 months, 56.63% at 6 months, 63.24% at 9 months, 63.64% at 12 months, and 57.14% at 18 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall and in each group. Among the 3 groups, the newly diagnosed group had the highest SRI-4 rate as well as the greatest improvement in serological parameters and SLEDAI-2K. Compared with newly diagnosed patients with SoC alone, the cumulative prednisone intake of newly diagnosed patients taking belimumab was significantly decreased. CONCLUSION: Our data supported the efficacy of belimumab in Chinese SLE patients in a real-life setting. Our study also provided new evidence showing remarkable achievement of the SRI-4 response during belimumab treatment in newly diagnosed SLE patients.

Target Exposome for Characterizing Early Gestational Exposure to Contaminants of Emerging Concern and Association with Gestational Diabetes Mellitus.

Characterization of gestational exposure to complex contaminants of emerging concern (CECs) is critical to the identification of environmental risk factors for pregnancy complications. However, determination of various CECs with diverse physicochemical properties in biological fluids is technically challenging. In the present study, we developed a target exposome protocol, consisting of simple liquid-liquid extraction-based sample preparation and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, to determine 325 CECs covering 11 subclasses, including poly- and perfluoroalkyl substances, organophosphate esters, ultraviolet (UV) stabilizers, synthetic antioxidants, phthalate esters, and several others. The protocol exhibits exceptional advantages over traditional approaches in the coverage of chemicals, sample volume demand, and time and financial cost. The protocol was applied in a prospective nested gestational diabetes mellitus (GDM) study including 120 cases and 240 matched healthy controls. Thirty-three CECs were detected in >70% of the samples, with a combined concentration of 17.0-484.7 ng/mL. Bayesian kernel machine regression analysis showed that exposure to the CEC mixture was significantly associated with a higher GDM risk. For example, when increasing all CECs in the mixture from 50th percentile to 75th percentile, the estimated probit of GDM incidence had an increase of 92% (95% CI: 56%, 127%). Meanwhile, perfluorohexanesulfonic acid, 1,3-diphenylguanidine, and dibutyl fumarate were identified as the key CECs driving the joint effect. This work demonstrates great potential of our target exposome protocol for environmental risk factor identification in large-scale epidemiology or biomonitoring studies.

Snap29 Is Dispensable for Self-Renewal Maintenance but Required for Proper Differentiation of Mouse Embryonic Stem Cells.

Pluripotent embryonic stem cells (ESCs) can self-renew indefinitely and are able to differentiate into all three embryonic germ layers. Synaptosomal-associated protein 29 (Snap29) is implicated in numerous intracellular membrane trafficking pathways, including autophagy, which is involved in the maintenance of ESC pluripotency. However, the function of Snap29 in the self-renewal and differentiation of ESCs remains elusive. Here, we show that Snap29 depletion via CRISPR/Cas does not impair the self-renewal and expression of pluripotency-associated factors in mouse ESCs. However, Snap29 deficiency enhances the differentiation of ESCs into cardiomyocytes, as indicated by heart-like beating cells. Furthermore, transcriptome analysis reveals that Snap29 depletion significantly decreased the expression of numerous genes required for germ layer differentiation. Interestingly, Snap29 deficiency does not cause autophagy blockage in ESCs, which might be rescued by the SNAP family member Snap47. Our data show that Snap29 is dispensable for self-renewal maintenance, but required for the proper differentiation of mouse ESCs.

Trpc5-regulated AMPKα/mTOR autophagy pathway is associated with glucose metabolism disorders in low birth weight mice under overnutrition.

Previous studies have shown that low birth weight (LBW) individuals are at higher risk of glucose metabolism disorders compared with normal birth weight (NBW) individuals under overnutrition conditions, but the mechanism remains unclear. To explore the underlying mechanism of glucose metabolism disorders induced by LBW under overnutrition in adulthood, the prenatal malnutrition method was applied to ICR mice to establish the LBW mice model and high-fat diets were used to mimic overnutrition conditions. Then the mechanism was further explored on Hepg2 cells treated with nutritional deprivation plus palmitic acid. The results showed that LBW plus high-fat interventions will cause glucose metabolism disorders and inhibit autophagy flux in adulthood. Moreover, the expression of TRPC5-regulated AMPK/mTOR autophagy pathway was downregulated by LBW with high-fat interventions. Collectively, LBW plus high-fat intervention increased the risk of glucose metabolism disorders, which may be related to the alteration of TRPC5 expression level and its regulation of the AMPKα/mTOR autophagy pathway. This study may provide a fundamental basis for the molecular mechanism of glucose metabolism disorders induced by LBW with high-fat diets in adulthood and a new target for the treatment of metabolic diseases in LBW individuals.

Prediction of drug resistance profile of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolates from newly diagnosed case by whole genome sequencing (WGS): a study from a high tuberculosis burden country.

OBJECTIVES: Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China. METHODS: We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS. RESULTS: The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd. CONCLUSIONS: WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China.

OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

Congenital adrenal hyperplasia with homozygous and heterozygous mutations: a rare family case report.

BACKGROUND: Congenital adrenal hyperplasia (CAH), characterized by defective adrenal steroidogenesis, is transmitted in an autosomal recessive manner. Mutations in the steroid 21-hydroxylase gene CYP21A2 causing steroid 21-hydroxylase deficiency account for most cases of CAH. The c.145l-1452delGGinsC gene mutation is rare, and only one case has been reported, but the form of gene mutation is different from this case, resulting in different clinical phenotype. The most common pathogenic genotype of CAH is a homozygous or compound heterozygous mutation, but CAH patients homozygous for the p.I173N mutation and heterozygous for the c.1451-1452delGGinsC mutation have not been reported previously. We report herein a familial case of CAH, in which both siblings carry the rare homozygous p.I173N mutation and heterozygous c.1451-1452delGGinsC mutation. CASE PRESENTATION: The proband showed amenorrhea, infertility, polycystic ovaries, and increased levels of androgen, rather than the typical clinical manifestations of CAH such as an adrenal crisis or masculine vulva, so was misdiagnosed with polycystic ovary syndrome for many years. Following a correct diagnosis of CAH, she was given glucocorticoid treatment, her menstruation became more regular, and she became pregnant and delivered a healthy baby girl. CONCLUSIONS: The genotypes may be p.I173N homozygous or p.I173N/c.1451-1452delGGinsC heterozygous, both mutations could be pathogenic. This complex combination of mutations has not been reported or studied before. Through the report and analysis of this genotype, the content of CAH gene bank is enriched and the misdiagnosis rate of CAH is reduced.

Paradoxical development of pleural-based masses in patients with pleural tuberculosis during treatment: a clinical observational study in China.

BACKGROUND: To explored the clinical, pathological, and bacteriological characteristics of pleural-based masses occurred during anti-tuberculosis (TB) treatment in patients with pleural TB. METHODS: Patients referred with newly diagnosed pleural TB were prospectively enrolled into the study. Patients were followed up throughout the treatment, and clinical data were recorded. Percutaneous biopsy and surgical tissues from pleural-based masses were examined histologically and samples sent for PCR. Cytokines in the pleural effusions and clinical factors were collected and compared between different patients. RESULTS: A total of 122 patients with pleural TB were enrolled, and 34.4% (42/122) displayed newly observed pleural-based mass during the treatment. Twelve cases underwent surgical resection at the 12 ± 0.5 months during the treatment course. Based on the surgical observation, 58.3% (7 /12) were located in pleura, 41.7% (5/12) were located in the lung parenchyma. Pathological observations showed that the pleural-based masses were typed as granulomatous inflammation, fibrous hyperplasia and necrosis. Mycobacterium tuberculosis PCR was positive in 57.1% of the cases (24/42). Any first-line anti-TB drug resistance gene mutations were positive in only 9.5% (4/42). Aside from 12 cases who underwent the surgical operation, 86.7% of the patients (26/30) still had a pleural-based mass at the end of 12 months treatment course. Patients with a pleural-based mass were younger, had a thicker pleural, a higher proportion of pleural adhesive, loculated pleural effusion and residual pleural effusion, and a higher level of LDH, ADA and lower glucose in pleural effusion than those without a pleural-based mass occurrence during the treatment (all Pcorr < 0.05). CONCLUSIONS: Pleural-based masses were observed in about one-third of patients with pleural TB. The masses were in the lung or pleura and were divided into three pathological types.

The efficacy and safety of uniportal video-assisted thoracic surgery on the treatment for stage II-III tuberculous empyema: a single-arm clinical retrospective study from 2016 to 2021 in a thoracic surgery center in China.

BACKGROUND: Surgery is an important adjuvant treatment for tuberculous empyema(TE). We thus conducted a single arm-clinical retrospective study of stage II-III TE patients who underwent uniportal video-assisted thoracic surgery (Uni-VATS) over a 5-year period to evaluate the efficacy and safety of surgery on TE, so as to provide the evidence for the optimal clinical strategies. METHODS: Patients diagnosed as TE with withdrawal of anti-tuberculosis-VATS were retrospectively enrolled from January 2016 to December 2021. All patients were followed up untill 12 months after withdrawal of anti-tuberculosis treatment (ATT). Clinical characteristics and surgical details were observed and analyzed to evaluate the efficacy and safety of the minimally invasive surgery. RESULTS: Totally 439 cases met included criteria were enrolled, no deaths were reported. The mean operative time was 2.6 (1.9, 4.3) hours and the mean intraoperative blood loss was 356 (240, 940) ml. Blood transfusion was performed in 20.50% (90/439) of patients and additional pneumonectomy was occurred in 9.89%(37/439)of patients .The mean postoperative drainage time was 12 (7, 49) days and the mean hospital stay was 6 (4,12) days. All stage II TE achieved complete lung re-expansion after surgery while 84.22%(315/374) of stage III achieved complete lung re-expansion, p 0.00. 15.78% (59/374) of stage III TE achieved incomplete re-expansion, 4 of which underwent a second decortication by Uni-VATS. Recurrences rate was 2.96% (13/439), including 11 cases of early recurrence and 2 cases of late recurrence at TE stage III, 5 of which underwent a second decortication by Uni-VATS. CONCLUSION: Uni-VATS is highly effective safe and minimally invasive for patients with TE, which could be recommended as the mainstream operation in areas with high TB burden.

Copper and chlorpyrifos stress affect the gut microbiota of chironomid larvae (Propsilocerus akamusi).

Chironomids are characterized by their ubiquitous distribution, global diversity and tolerant ability to deal with environmental stressors. To our knowledge, this is the first study presenting the gut microbial structure of chironomid larvae and examining the microbial alteration induced by invading chlorpyrifos and copper with different dosages. Lethal bioassay displayed a significantly decreased percentage survival of Propsilocerus akamusi larvae exposed to 800 mg/L copper and 50 µg/L chlorpyrifos at 96 h. Larvae with deficient gut microbiota exhibited a depressed level of glutathione S-transferase activity after stressful exposure. The high-throughput 16S rRNA gene sequencing was adopted to investigate the community structure and it turned out that both copper and chlorpyrifos were able to generate distinguished variations of gut microbiota in the stressor-specific and concentration-dependent manner. Of note, the relative abundance of Comamonas, Stenotrophomonas, and Yersinia remarkably elevated in the presence of copper while chlorpyrifos exposure upregulated the prevalence of certain genera (e.g. Serratia). Flavobacterium was greatly attenuated in chlorpyrifos group with lethal dosage exhibiting more severe impacts. The predicted gene functions of the gut commensals differed between normal samples and those subjected to distinct toxins. Besides, more positive associations and limited modularity of microbial interactions were observed in stressor-challenged larvae, presenting a network with impaired complexity and stability. The appearance of either copper or chlorpyrifos exhibited strong positive correlations with genera belonging to Proteobacteria and Firmicutes. Collectively, this investigation introduces a general outline of gut microbiota obtained from chironomid individuals with latent adaptive tactics to nocuous factors (heavy metal and pesticide), which could build a fundamental basis for us to further explore the protective roles of chironomid gut bacterial colonizers in defending against aquatic contaminants.

Comparison of calcium and ultrasonic treatment on fruit firmness, pectin composition and cell wall-related enzymes of postharvest apricot during storage.

This study was conducted to examine the effects of calcium treatment (2%, 20 min) and ultrasonic treatment (400 W, 20 min) on postharvest apricot fruit during storage. The results showed that after calcium and ultrasonic treatment, compared with the control, the firmness of apricot fruit increased by 41.53% and 3.83% at 16 d, but juice yield and water-soluble pectin (WSP) content decreased by 8.26% and 3.55%, 28.57% and 4.08%, respectively. Both calcium and ultrasonic treatment were more effective in reducing polygalacturonase (PG), ß-Galactosidase (ß-Gal), pectin methylesterase (PME), polyphenol oxidase (PPO) and peroxidase (POD) activity. Moreover, fruit firmness was significantly negatively correlated with juice yield, WSP and PPO, and positively correlated with PG and ß-Gal, PPO and POD. In contrast, calcium treatment was more effective than ultrasonic treatment in delaying postharvest softening of apricot.

lncRNA BSG-AS1 is hypoxia-responsive and promotes hepatocellular carcinoma by enhancing BSG mRNA stability.

Emerging evidence indicates that aberrant changes of lncRNAs expression induced by hypoxia participate in the development of HCC. The present study aimed to identify novel hypoxia-responsive lncRNAs and reveal its role and mechanism in HCC. Hypoxia exposure in HCC tissues was comprehensively estimated based on public data using multiple hypoxia gene signatures. Huh7 cells were treated with hypoxia and RNA-seq was performed. Then we analyzed the changes of lncRNAs in HCC tissues and cells exposed to hypoxia. We found that lncRNA BSG-AS1 was highly expressed in tissues with high hypoxia score. Then we verified the response of lncRNA BSG-AS1 to hypoxia in the cell hypoxia model in vitro. Through functional phenotypic analysis, we found that lncRNA BSG-AS1 can mediate the promoting effect of hypoxia on the proliferation and migration in HCC cells. RNA-seq was used to find the downstream target genes of lncRNA BSG-AS1. Sequencing data and wet experiments showed that mRNA of BSG decreased after knockout of lncRNA BSG-AS1, and mediated the promotive effect of lncRNA BSG-AS1 on proliferation and migration in HCC cells. The mechanism is that lncRNA BSG-AS1 can enhance the stability of BSG mRNA as antisense lncRNA. Finally, the data based on the public cohort and the cohort we collected suggested that the overexpression of lncRNA BSG-AS1 and BSG are related to the poor prognosis. In conclusion, lncRNA BSG-AS1 is a novel hypoxia-responsive lncRNA. LncRNA BSG-AS1 can positively regulate BSG, by maintaining the mRNA stability of BSG, thus promoting the proliferation and migration of HCC. High expression of lncRNA BSG-AS1 and BSG are risk factors for prognosis.