Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature.

BACKGROUND: Clostridium difficile (C. difficile) infection (CDI) is a rare clinical disease caused by changes in the intestinal microenvironment, which has a variety of causes and a poor prognosis, and for which there is no standardized clinical treatment. CASE SUMMARY: A patient experienced recurrent difficulty in bowel movements over the past decade. Recently, symptoms worsened within the last ten days, leading to a clinic visit due to constipation. The patient was subsequently referred to our department. Preoperatively, the patient was diagnosed with obstructed colon accompanied by gallstones. Empirical antibiotics were administered both before and after surgery to prevent infection. On the fourth day post-surgery, symptoms of CDI emerged. Stool cultures confirmed the presence of C. difficile DNA. Treatment involved a combination of vancomycin and linezolid, resulting in the patient's successful recovery upon discharge. However, the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later. CONCLUSION: CDI is the leading cause of nosocomial post-operative care, with limited clinical cases and poor patient prognosis, and comprehensive clinical treatment guidelines are still lacking. This infection can be triggered by a variety of factors, including intestinal hypoxia, inappropriate antibiotic use, and bile acid circulation disorders. In patients with chronic bowel disease and related etiologies, prompt preoperative attention to possible CDI and preoperative bowel preparation is critical. Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Can alterations in cathepsin levels restrain the development of skin cancer?: A bidirectional multivariate Mendelian-randomization study.

Malignant skin tumors mainly include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. There is currently observational research suggesting that changes in cathepsin (CTS) may be a factor in the development of malignant skin tumors, but no studies have yet demonstrated a causal relationship between tissue protease changes and the occurrence of malignant skin tumors. Current studies have shown that cathepsin is involved in tumor cell invasion and metastasis by regulating growth factors and cellular immune function in tumor microenvironment, decomposing extracellular matrix and basement membrane, and promoting angiogenesis. In this study, we conducted a bidirectional Mendelian-randomization study using publicly available genome-wide association study (GWAS; GWAS Catalog) data. This study applies a bidirectional multivariate Mendelian randomization (MR) approach to investigate the causal relationship between cathepsin, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. In cases where multiple cathepsins are implicated as etiological factors in certain diseases, a multivariable analysis is conducted to assess the direct and indirect causal effects of the exposure factors. In this study, we present a comprehensive MR analysis to investigate the relationship between 9 cathepsin and basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Based on our MR analysis using the largest GWAS Catalog dataset available, we are able to draw relatively reliable conclusions. In the MR study, we found that tissue protease L2 can promote skin cancer, Cathepsin O, and Cathepsin F are associated with an increased risk of basal cell carcinoma. Cathepsin H can inhibit basal cell carcinoma and malignant melanoma. In the reverse MR study, it was found that squamous cell carcinoma may cause an increase in Cathepsin O expression. In the multivariate analysis, it was found that Cathepsin H is a direct factor in reducing the occurrence of skin cancer and melanoma, with no apparent causal relationship to non-melanoma skin cancer. Cathepsin has a dual impact on skin cancer cells, and the expression of different cathepsins at the edge of skin tumors may indicate different developmental tendencies of skin cancer. Cathepsin may serve as effective biomarkers for predicting tumors.

Research progress of ectopic thyroid cancer in thyroglossal duct cyst: A case report and literature review.

RATIONALE: Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease. PATIENT CONCERNS: A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities. DIAGNOSES: Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma. INTERVENTIONS: A Sistrunk operation and ipsilateral thyroidectomy were performed. OUTCOMES: Postoperative recovery was satisfactory. LESSONS: Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.

Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: A multicenter, double-blind, placebo-controlled, randomized trial.

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.

Renal pelvis sarcomatoid carcinoma with renal vein tumor thrombus: A case report and literature review.

BACKGROUND: Renal pelvis sarcomatoid carcinoma (RPSC) is a rare and aggressive malignancy whose diagnosis is difficult because radiological imaging results can lead to misclassification as a more common type of renal tumor. In addition, clinical management of patients with RPSC is difficult because of the limited efficacy of available treatments. In this study, we present a comprehensive description of a patient who presented with RPSC and a simultaneous renal vein tumor thrombus. CASE SUMMARY: During April, 2020, a 64-year-old female presented with an isolated episode of hematuria accompanied by abdominal pain. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a lesion in the right renal pelvis. We therefore performed a radical nephrectomy of the right kidney. The subsequent histopathological and immunological results verified the diagnosis of RPSC. Despite administration of 6 cycles of a gemcitabine-cisplatin regimen, the patient's condition progressively deteriorated, and she died about 15 mo after the nephrectomy. CONCLUSION: We performed a comprehensive analysis of a patient with RPSC that included CT, MRI, immunohistochemistry, and genetic testing. The insights from our detailed analysis of this patient and our concomitant review of the literature may assist clinicians in their diagnosis and treatment of RPSC.

Construction of a knowledge graph for breast cancer diagnosis based on Chinese electronic medical records: development and usability study.

BACKGROUND: Electronic medical records (EMRs) contain a wealth of information related to breast cancer diagnosis and treatment. Extracting relevant features from these medical records and constructing a knowledge graph can significantly contribute to an efficient data analysis and decision support system for breast cancer diagnosis. METHODS: An approach was proposed to develop a workflow for effectively extracting breast cancer-related features from Chinese breast cancer mammography reports and constructing a knowledge graph for breast cancer diagnosis. Firstly, the concept layer of the knowledge graph for breast cancer diagnosis was constructed based on breast cancer diagnosis and treatment guidelines, along with insights from clinical experts. .Next, a BiLSTM-Highway-CRF model was designed to extract the mammography features, which formed the data layer of the knowledge graph. Finally, the knowledge graph was constructed by combining the concept layer and the data layer in a Neo4j graph data platform, and then applied in visualization analysis, semantic query and computer assisted diagnosis. RESULTS: Mammographic features were extracted from a total of 1171 mammography examination reports. The overall extraction performance of the model achieved an accuracy rate of 97.16%, a recall rate of 98.06%, and a F1 score of 97.61%. Additionally, 47,660 relationships between entities were identified based on the four different types of relationships defined in the concept layer. The knowledge graph for breast cancer diagnosis was constructed after inputting mammographic features and relationships into the Neo4j graph data platform. The model was assessed from the concept layer, data layer, and application layer perspectives, and showed promising results. CONCLUSIONS: The proposed workflow is applicable for constructing knowledge graphs for breast cancer diagnosis based on Chinese EMRs. This study serves as a reference for the rapid design, construction, and application of knowledge graphs for diagnosis and treatment of other diseases. Furthermore, it offers a potential solution to address the issues of limited data sharing and format inconsistencies present in Chinese EMR data.

TRAF6 promotes chemoresistance to paclitaxel of triple negative breast cancer via regulating PKM2-mediated glycolysis.

Ample evidence reveals that glycolysis is crucial to tumor progression; however, the underlying mechanism of its drug resistance is still worth being further explored. TRAF6, an E3 ubiquitin ligase, is well recognized to overexpress in various types of cancer, which predicts a poor prognosis. In our study, we discovered that TRAF6 was expressed more significantly in the case of triple-negative breast cancer (TNBC) than in other of breast cancers, promoting chemoresistance to paclitaxel; that inhibited TRAF6 expression in the chemoresistant TNBC (TNBC-CR) cells enhanced the sensitivity by decreasing glucose uptake and lactate production; that TRAF6 regulated glycolysis and facilitated chemoresistance via binding directly to PKM2; and that overexpressing PKM2 in the TNBC-CR cells with TRAF6 knocked down regained significantly TRAF6-dependent drug resistance and glycolysis. Additionally, we verified that TRAF6 could facilitate PKM2-mediated glycolysis and chemoresistance in animal models and clinical tumor tissues. Thus, we identified the novel function of TRAF6 to promote glycolysis and drug resistance in TNBC with the regulation of PKM2, which could provide a potential molecular target for TNBC treatment.

Retroperitoneal undifferentiated pleomorphic sarcoma with total nephrectomy: a case report and literature review.

Background: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant soft tissue sarcoma with a poor prognosis and no clear effective clinical means for treatment, and there has been no significant progress in research within this field in recent years. This study aimed to investigate the epidemiology, etiology, clinical features, diagnostic modalities, various treatment modalities, and prognosis of retroperitoneal undifferentiated pleomorphic sarcoma and to contribute to the clinical management of this type of disease. In this study, we report a case of undifferentiated pleomorphic sarcoma with a primary origin in the retroperitoneum. Undifferentiated pleomorphic sarcoma occurring in the retroperitoneum is rarely reported. Case description: A 59-year-old man with abdominal distension and pain for 4 months presented to our hospital after the failure of conservative treatment. A 9.6 cm by 7.4 cm mass in the left retroperitoneum was found on a CT scan of the whole abdomen with three degrees of enhancement. After surgical treatment, the tumor and the left kidney were completely removed, and pathological examination and genetic sequencing showed an apparent undifferentiated pleomorphic sarcoma. The patient subsequently declined follow-up treatment and is currently alive and well. Conclusions: At the current level of clinical technology, the treatment of undifferentiated pleomorphic sarcoma is still in the exploratory stage, and the scarcity of clinical cases of this disease may have hindered the acquisition of clinical trials and research data for this disease. At present, the first choice of treatment for undifferentiated pleomorphic sarcoma is still radical resection. In the existing clinical studies, there are no strong data to support the effect of preoperative neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy in clinical practice. Similar to other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential treatment for this disease in the future. Targeted therapy for this disease still needs further exploration, and we need more reports on related diseases to promote future treatment and research on this disease.

Comparation of intraureteral stent and conventional stent at different stages: a systematic review with meta-analysis.

INTRODUCTION: Stent related symptom (SRS) is the most common adverse effect of ureteral stenting. In recent years, many efforts have been made to develope modified ureteral stents to ameliorate SRS. It has been reported that intraureteral stents have the potential to improve the tail end adverse effect of the bladder and alleviate SRS. However, there still lack of evidence for the efficacy and the safety of clinically applying intraureteral stents. The aim of this work is to investigate the efficacy and safety of intraureteral stents. EVIDENCE ACQUISITION: A systematic review was performed by using the PubMed, Web of Science, Medline, Embase, and Cochrane library. The studies published before February 2023 were included. The study selection was following the guideline from Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The searching strategy was: "Pigtail suture stent" OR "Intra-ureteric stent" OR "Suture Stent" OR "Intraureteral stent" AND "Ureteroscopy" OR "Urinary calculi" OR "Stent-related symptoms" OR "Lower urinary tract symptoms". The data from randomized clinical trials which meet the selection criteria were extracted. Revman 5.4 was employed to proceed the meta-analysis. EVIDENCE SYNTHESIS: A total of six randomized clinical trials of intraureteral stents were included in this systematic review and meta-analysis. According to the different investigation time, the results could be divided into four stages: early-stage, middle-stage, late-stage, and long-term evaluation. Urinary symptoms, pain score, and general health were significantly improved in intraureteral stents group at middle stage. For late-stage, intraureteral stent achieved better outcomes in urinary symptoms index, VAS score, quality of life, general health, and pain score. However, for early-stage and long-term evaluation, there was no significant difference between two groups. CONCLUSIONS: This systematic review and meta-analysis reveal that regardless of the stage of treatment, the efficacy and safety of intraureteral stent are no worse than that of conventional stent. During 7-14 days postoperation, which is the most commonly time for clinically using ureteral stent, most of the outcomes of intraureteral stent are better than those of conventional stent. Hence, it is confirmed that intraureteral stent is worth for more clinical study and application.

Combination therapy for high-volume versus low-volume metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis.

Purpose: To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: Qualified publications were searched in the PubMed, Embase, and Cochrane CENTRAL databases. Overall survival (OS) and radiographic progression-free survival (rPFS) were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve, respectively. Adverse events (AEs) were also compared. Results: Eighteen publications from 12 trials were analyzed in the NMA. In the overall population, triplet therapy was ranked first for OS (hazard ratio [HR]: 0.57, 95% credible interval [CrI]: 0.48-0.67) and rPFS (HR: 0.33, 95% CrI:0.26-0.41) compared with androgen deprivation therapy (ADT) with or without standard non-steroidal antiandrogen. In high-volume mHSPC, triplet therapy was also ranked first in OS (HR, 0.57; 95% CrI:0.44-0.75) and rPFS(HR, 0.29; 95% CrI: 0.23-0.37). Specifically, abiraterone triplet therapy was ranked first in OS (HR, 0.52; 95% CrI:0.38-0.72) and rPFS (HR, 0.28; 95% CrI:0.21-0.38) among all therapies. ADT plus rezvilutamide was ranked first among doublet therapies (OS: HR, 0.58; 95% CrI:0.44-0.77; rPFS: HR, 0.44; 95% CrI:0.33-0.58). In low-volume mHSPC, doublet and triplet therapies were ranked first in OS (HR:0.68, 95% CrI:0.58-0.80) and rPFS (HR:0.37, 95% CrI:0.25-0.55), respectively. ADT plus apalutamide was ranked first in OS among all therapies (HR:0.53, 95% CrI:0.35-0.79), whereas enzalutamide triplet therapy was ranked first in rPFS (HR:0.27, 95% CrI:0.15-0.51). ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapies (OR:1.00, 95% CrI:0.31-3.15), and a lower risk of specific AEs among doublet therapies, particularly regarding seizure (OR, 0.29; 95% CrI:0.01-8.18) and fatigue (OR, 0.96; 95% CrI:0.63-1.46). Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs. Conclusion: Triplet therapy was the best treatment option for the overall population. In high-volume mHSPC, triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients. Patients with low-volume mHSPC were most likely to benefit from ADT plus androgen receptor-targeted agents. Triplet therapy was associated with a higher risk of AEs than the other therapies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375347, identifier PROSPERO:CRD42022375347.

[Distribution, Sources, and Behavioral Characteristics of Microplastics in Farmland Soil].

Microplastics (MPs) are widely present in farmland soil as an emerging contaminant. This paper serves as a comprehensive and systematic review of research progress on the characteristics of distribution, abundance, sources, shape, polymer composition, size, and migration of MPs in farmland soils around the world. Moreover, research prospects were also proposed. MPs have been detected in farmland soils around the world, mainly coming from agricultural plastic films, organic fertilizers, sludge, surface runoff, agricultural irrigation, atmospheric deposition, and tire wear particles. The morphology of MPs in soil mainly includes debris, fibers, and films. MPs polymer forms mainly include polyethylene, polypropylene, and polystyrene. Farmland land use significantly affects soil MPs abundance. Additionally, the abundance of MPs increase with the reduction in size. MPs in soil can migrate to deep soil through tillage, leaching, bioturbation, and gravity. Research on soil MPs detection methods, database establishment, safety thresholds, migration and transformation laws, potential ecological health risk assessment, and the construction of prevention and control technology systems should be strengthened in the future. The paper can provide a reference for the risk control and governance of farmland soil MPs pollution.

Vitamin B complex blocks the dust fall PM2 .5 -induced acute lung injury through DNA methylation in rats.

This study aimed to explore whether vitamin B complex (folic acid, B6 , and B12 ) could avert DNA methylation changes associated with inflammation induced by acute PM2.5 exposure. Sprague-Dawley rats were administered by gavage with different concentrations of vitamin B complex once a day for 28 days, and then by intratracheal instillation with saline or PM2.5 once every 2 days for three times. Vitamin B continued to be taken during the PM2.5 exposure. Rats were sacrificed 24 h after the last exposure. The results showed that vitamin B complex could block the pathological changes and injury in lungs induced by PM2.5 . Meanwhile, vitamin B complex could prevent the abnormal DNA methylation of IL-4 and IFN-γ to antagonize the imbalance of IL-4/IFN-γ associated with inflammation. It was further found that vitamin B complex could regulate DNA methyltransferases (DNMTs) and increase the S-adenosylmethionine (SAM)/S-Adenosyl-L-homocysteine (SAH) ratio to reverse the hypomethylation of genomic DNA and the abnormal DNA methylation of IL-4 and IFN-γ. In conclusion, vitamin B complex has a protective effect on acute lung injury by attenuating abnormal DNA methylation induced by PM2.5 in rats. This study may provide a new insight into the physiological function of vitamin B to prevent the health effects induced by PM2.5 .

Eosinophilic solid and cystic renal cell carcinoma: a review of literature focused on radiological findings and differential diagnosis.

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a rare type of renal cell carcinoma with inert biological behavior that has not yet been included in the 2016 World Health Organization (WHO) classification, and its imaging manifestations are unclear due to its rarity. Although there have only been a few cases, the CT and MRI findings of ESC-RCC are characterized by its cystic solid structure, according to the proportion of cystic and solid components observed on images, ESC-RCC can be categorized into three types. Especially the Type I, when the cystic-solid components are almost equal, the imaging findings are illustrated as "lotus root-like," which may be helpful in the differential diagnosis of ESC-RCC from other types of renal tumors. In fact, ESC-RCC has diverse radiological appearances, and the differentiation of clear cell renal cell carcinoma, renal oncocytoma, chromophobe renal cell carcinoma, and renal angiomyolipoma remains challenging. This review aims to discuss ESC-RCC with a focus on the radiological findings and differential diagnosis of ESC-RCC.

Urinary incontinence rehabilitation of after radical prostatectomy: a systematic review and network meta-analysis.

Purpose: The aim of this study is to provide treatment for patients with urinary incontinence at different periods after radical prostatectomy. Methods: The PubMed, Embase, Cochrane, and Web of Science were searched for all literature on the effectiveness on urinary control after radical prostate cancer between the date of database creation and 15 November 2023 and performed a quality assessment. A network meta-analysis was performed using RevMan 5.3 and Stata 17.0 software and evaluated using the surface under the cumulative ranking curve. Results: The results of the network meta-analysis showed that pelvic floor muscle therapy including biofeedback with professional therapist-guided treatment demonstrated better results at 1 month to 6 months; electrical stimulation, biofeedback, and professional therapist guidance may be more effective at 3 months of treatment; professional therapist-guided recovery may be less effective at 6 months of treatment; and combined therapy demonstrated better results at 1 year of treatment. During the course of treatment, biofeedback with professional therapist-guided treatment may have significant therapeutic effects in the short term after surgery, but, in the long term, the combination of multiple treatments (pelvic floor muscle training+ routine care + biofeedback + professional therapist-guided treatment + electrical nerve stimulation therapy) may address cases of urinary incontinence that remain unrecovered long after surgery. Conclusion: In general, all treatment methods improve the different stages of functional recovery of the pelvic floor muscles. However, in the long term, there are no significant differences between the treatments. Given the cost-effectiveness, pelvic floor muscle training + routine care + biofeedback + professional therapist-guided treatment + electrical nerve stimulation therapy within 3 months and pelvic floor muscle + routine care after 3 months may be a more economical option to treat urinary incontinence. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331797, identifier CRD42022331797.

Systemic triplet therapy for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis.

Purpose: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated. Results: Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57-0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59-0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39-0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30-0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68-12.63; OR: 1.07, 95% CrI: 0.03-36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15-2.11). Conclusion: Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.

Dust fall PM2.5-induced lung inflammation in rats is associated with hypermethylation of the IFN-γ gene promoter via the PI3K-Akt-DNMT3b pathway.

Inflammation is one of the major adverse effects of fine particulate matter (PM2.5) on the lung system; however, its mechanisms remain unclear. Rats were exposed to different concentrations of PM2.5 to investigate the mechanism of short-term exposure-induced lung inflammation. The regulation of PI3K-Akt and DNA methyltransferase 3b (DNMT3b) was assessed by using a PI3K inhibitor and a DNA methyltransferase inhibitor. We found that PM2.5 could decrease interferon-γ (IFN-γ) levels and increase interleukin 4 (IL-4), IL-5 and IL-13 levels in bronchoalveolar lavage fluid (BALF) to promote eosinophil infiltration and eventually lead to allergic pulmonary inflammation. Moreover, the CpG island methylation rate of the IFN-γ promoter and the protein expression of DNMT3b, PI3K and p-Akt were increased in lung tissues after PM2.5 exposure. Both inhibitors reversed the CpG island hypermethylation of IFN-γ. In conclusion, in PM2.5-induced lung injury, the activated PI3K-Akt pathway, via an increase in DNMT3b expression, is involved in CpG hypermethylation of the IFN-γ gene promoter.

Machine Learning-Based Models Enhance the Prediction of Prostate Cancer.

Purpose: PSA is currently the most commonly used screening indicator for prostate cancer. However, it has limited specificity for the diagnosis of prostate cancer. We aim to construct machine learning-based models and enhance the prediction of prostate cancer. Methods: The data of 551 patients who underwent prostate biopsy were retrospectively retrieved and divided into training and test datasets in a 3:1 ratio. We constructed five PCa prediction models with four supervised machine learning algorithms, including tPSA univariate logistic regression (LR), multivariate LR, decision tree (DT), random forest (RF), and support vector machine (SVM). The five prediction models were compared based on model performance metrics, such as the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, calibration curve, and clinical decision curve analysis (DCA). Results: All five models had good calibration in the training dataset. In the training dataset, the RF, DT, and multivariate LR models showed better discrimination, with AUCs of 1.0, 0.922 and 0.91, respectively, than the tPSA univariate LR and SVM models. In the test dataset, the multivariate LR model exhibited the best discrimination (AUC=0.918). The multivariate LR model and SVM model had better extrapolation and generalizability, with little change in performance between the training and test datasets. Compared with the DCA curves of the tPSA LR model, the other four models exhibited better net clinical benefits. Conclusion: The results of the current retrospective study suggest that machine learning techniques can predict prostate cancer with significantly better AUC, accuracy, and net clinical benefits.