Investigating the causal association between gut microbiota and type 2 diabetes: a meta-analysis and Mendelian randomization.

Background: Studies have shown that gut dysbiosis contributes to the pathophysiology of type 2 diabetes mellitus (T2DM). Identifying specific gut microbiota dysbiosis may provide insight into the pathogenesis of T2DM. Purpose: This study investigated the causal relationship between gut microbiota and T2DM using meta-analysis and Mendelian randomization (MR). Methods: In the first part, we searched for literature on gut microbiota and T2DM, and conducted a meta-analysis. We observed differences in glycosylated hemoglobin and fasting blood glucose levels in both groups. Second, we obtained GWAS data from genome-wide association study database 19 (GWAS). We used two-sample MR analysis to verify the forward and reverse causal associations between gut microbiota and T2DM. Additionally, we selected the European GWAS data from the European Bioinformatics Institute (EBI) as a validation set for external validation of the MR analysis. In the third part, we aimed to clarify which gut microbiota contribute to the degree of causal association between group disorders and T2DM through multivariate MR analysis and Bayesian model averaging (MR-BMA). Results: 1. According to the meta-analysis results, the glycated hemoglobin concentration in the gut probiotic intervention group was significantly lower than in the control group. Following treatment, fasting blood glucose levels in the intervention group were significantly lower than those in the control group. 2. The results of two samples MR analysis revealed that there were causal relationships between six gut microbiota and T2DM. Genus Haemophilus and order Pasteurellaceae were negatively correlated with T2DM. Genus Actinomycetes, class Melanobacteria and genus Lactobacillus were positively correlated. Reverse MR analysis demonstrated that T2DM and gut microbiota did not have any reverse causal relationship. The external validation data set showed a causal relationship between gut microbiota and T2DM. 3. Multivariate MR analysis and MR-BMA results showed that the independent genus Haemophilus collection had the largest PP. Conclusion: Our research results suggest that gut microbiota is closely related to T2DM pathogenesis. The results of further MR research and an analysis of the prediction model indicate that a variety of gut microbiota disorders, including genus Haemophilus, are causally related to the development of T2DM. The findings of this study may provide some insight into the diagnosis and treatment of T2DM. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO.

Exploring explainable AI features in the vocal biomarkers of lung disease.

This review delves into the burgeoning field of explainable artificial intelligence (XAI) in the detection and analysis of lung diseases through vocal biomarkers. Lung diseases, often elusive in their early stages, pose a significant public health challenge. Recent advancements in AI have ushered in innovative methods for early detection, yet the black-box nature of many AI models limits their clinical applicability. XAI emerges as a pivotal tool, enhancing transparency and interpretability in AI-driven diagnostics. This review synthesizes current research on the application of XAI in analyzing vocal biomarkers for lung diseases, highlighting how these techniques elucidate the connections between specific vocal features and lung pathology. We critically examine the methodologies employed, the types of lung diseases studied, and the performance of various XAI models. The potential for XAI to aid in early detection, monitor disease progression, and personalize treatment strategies in pulmonary medicine is emphasized. Furthermore, this review identifies current challenges, including data heterogeneity and model generalizability, and proposes future directions for research. By offering a comprehensive analysis of explainable AI features in the context of lung disease detection, this review aims to bridge the gap between advanced computational approaches and clinical practice, paving the way for more transparent, reliable, and effective diagnostic tools.

Lovastatin-Induced Mitochondrial Oxidative Stress Leads to the Release of mtDNA to Promote Apoptosis by Activating cGAS-STING Pathway in Human Colorectal Cancer Cells.

Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon genes (STING) signaling pathway has been suggested to not only facilitate inflammatory responses and the production of type I interferons (IFN), but also activate other cellular processes, such as apoptosis. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by statin treatment in human colorectal cancer cells. In this study, we reported that lovastatin impaired mitochondrial function, including the depolarization of mitochondrial membrane potential, reduction of oxygen consumption, mitochondrial DNA (mtDNA) integrity, and mtDNA abundance in human colorectal cancer HCT116 cells. The mitochondrial dysfunction markedly induced ROS production in mitochondria, whereas the defect in mitochondria respiration or depletion of mitochondria eliminated reactive oxygen species (ROS) production. The ROS-induced oxidative DNA damage by lovastatin treatment was attenuated by mitochondrial-targeted antioxidant mitoquinone (mitoQ). Upon DNA damage, mtDNA was released into the cytosol and bound to DNA sensor cGAS, thus activating the cGAS-STING signaling pathway to trigger a type I interferon response. This effect was not activated by nuclear DNA (nuDNA) or mitochondrial RNA, as the depletion of mitochondria compromised this effect, but not the knockdown of retinoic acid-inducible gene-1/melanoma differentiation-associated protein 5 (RIG-I/MDA5) adaptor or mitochondrial antiviral signaling protein (MAVS). Moreover, lovastatin-induced apoptosis was partly dependent on the cGAS-STING signaling pathway in HCT116 cells as the knockdown of cGAS or STING expression rescued cell viability and mitigated apoptosis. Similarly, the knockdown of cGAS or STING also attenuated the antitumor effect of lovastatin in the HCT116 xenograft model in vivo. Our findings suggest that lovastatin-induced apoptosis is at least partly mediated through the cGAS-STING signaling pathway by triggering mtDNA accumulation in the cytosol in human colorectal cancer HCT116 cells.

A Critical Appraisal of the Congress of Neurological Surgeons Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma.

Background and objective Thoracolumbar spine trauma (TST) is frequently associated with spinal cord injury and other soft tissue and bony injuries. The management of such injuries requires an evidence-based approach. This study used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to assess the methodological quality of clinical guidelines for the management of TST published by the Congress of Neurological Surgeons (CNS). Methods All clinical guidelines on TST published by CNS until 2020 were assessed. Five appraisers from three international centers evaluated the quality of eligible clinical guidelines by using AGREE II. Mean AGREE II scores for each domain were determined. In higher-quality domains, the scores for individual items were analyzed. Results A total of 12 guidelines published by CNS on TST were assessed. Mean scores for all six domains were as follows: Scope and Purpose (75.2%), Stakeholder Involvement (45.4%), Rigor of Development (57.0%), Clarity of Presentation (58.7%), Applicability (16.9%), and Editorial Independence (64.1%). The mean score for the overall quality of all CNS guidelines was 52.9% [95% confidence interval (CI): 52.2-53.5%]. The overall agreement among appraisers was excellent [intra-class correlation coefficients (ICCs) for each guideline ranged from 0.903 to 0.963]. Conclusions CNS guidelines for the management of TST demonstrated acceptable quality across most domains; however, the domains of Applicability and Stakeholder Involvement could be further improved in future guideline updates. The assessors concluded that all guidelines could still be recommended for clinical practice with or without modifications.

Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer.

BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.

Research Progress on the Geomechanical Properties of Block-in-Matrix Rocks.

The differences in geomechanical properties and the uncertainty in the spatial distribution of Bimrock pose significant challenges to the construction and disaster prediction of geotechnical engineering. To clarify the geomechanical characteristics of Bimrock, this paper summarizes the basic concepts and classification methods of Bimrock at home and abroad. It discusses the methods and characteristics of determining the geometric features of Bimrock blocks and explores the influencing factors and laws of failure modes and strength under different stress states of Bimrock. The study finds that the failure mode of Bimrock is mainly influenced by factors such as block proportion, degree of welding between blocks and matrix, strength ratio between blocks and matrix, and geometric properties of blocks. Among these factors, block proportion is the most significant, and the degree of welding is a controlling factor. However, due to the complexity of Bimrock structures, there is a lack of applicable methods and mechanical models for the evaluation of geomechanical characteristics of Bimrock in engineering practice. This article also explores the influence and research methods of the geological characteristics of Bimrock in slope and tunnel engineering and, finally, provides prospects for the future research trends relating to Bimrock.

Microwave coagulation for liver metastases.

BACKGROUND: Liver metastases (i.e. secondary hepatic malignancies) are significantly more common than primary liver cancer. Long-term survival after radical surgical treatment is approximately 50%. For people in whom resection for cure is not feasible, other treatments must be considered. One treatment option is microwave coagulation utilising electromagnetic waves. It involves placing an electrode into a lesion under ultrasound or computed tomography guidance. OBJECTIVES: To evaluate the beneficial and harmful effects of microwave coagulation versus no intervention, other ablation methods, or systemic treatments in people with liver metastases regardless of the location of the primary tumour. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest date of search was 14 April 2023. SELECTION CRITERIA: Randomised clinical trials assessing beneficial or harmful effects of microwave coagulation and its comparators in people with liver metastases, irrespective of the location of the primary tumour. We included trials no matter the outcomes reported. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. Our primary outcomes were: all-cause mortality at the last follow-up and time to mortality; health-related quality of life (HRQoL); and any adverse events or complications. Our secondary outcomes were: cancer mortality; disease-free survival; failure to clear liver metastases; recurrence of liver metastases; time to progression of liver metastases; and tumour response measures. We used risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) to present the results. Two review authors independently extracted data and assessed the risk of bias using the Cochrane RoB 1 tool. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS: Three randomised clinical trials fulfilled the inclusion criteria. The control interventions differed in the three trials; therefore, meta-analyses were not possible. The trials were at high risk of bias. The certainty of evidence of the assessed outcomes in the three comparisons was very low. Data on our prespecified outcomes were either missing or not reported. Microwave coagulation plus conventional transarterial chemoembolisation (TACE) versus conventional TACE alone One trial, conducted in China, randomised 50 participants (mean age 60 years, 76% males) with liver metastases from various primary sites. Authors reported that the follow-up period was at least one month. The trial reported adverse events or complications in the experimental group only and for tumour response measures. There were no dropouts in the trial. The trial did not report on any other outcomes. Microwave ablation versus conventional surgery One trial, conducted in Japan, randomised 40 participants (mean age 61 years, 53% males) with multiple liver metastases of colorectal cancer. Ten participants were excluded after randomisation (six from the experimental and four from the control group); thus, the trial analyses included 30 participants. Follow-up was three years. The reported number of deaths from all causes was 9/14 included participants in the microwave group versus 12/16 included participants in the conventional surgery group. The mean overall survival was 27 months in the microwave ablation and 25 months in the conventional surgery group. The three-year overall survival was 14% with microwave ablation and 23% with conventional surgery, resulting in an HR of 0.91 (95% CI 0.39 to 2.15). The reported frequency of adverse events or complications was comparable between the two groups, except for the required blood transfusion, which was more common in the conventional surgery group. There was no intervention-related mortality. Disease-free survival was 11.3 months in the microwave ablationgroup and 13.3 months in the conventional surgery group. The trial did not report on HRQoL. Microwave ablation versus radiofrequency ablation One trial, conducted in Germany, randomised 50 participants (mean age 62.8 years, 46% males) who were followed for 24 months. Two-year mortality showed an RR of 0.62 (95% CI 0.26 to 1.47). The trial reported that, by two years, 76.9% of participants in the microwave ablationgroup and 62.5% of participants in the radiofrequency ablation group survived (HR 0.63, 95% CI 0.23 to 1.73). The trial reported no deaths or major complications during the procedures in either group. There were two minor complications only in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial reported technical efficacy in 100% of procedures in both groups. Distant recurrence was reported for 10 participants in the microwave ablation group and nine participants in the radiofrequency ablation group (RR 1.03, 95% CI 0.50 to 2.08). No participant in the microwave ablation group demonstrated local progression at 12 months, while that occurred in two participants in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial did not report on HRQoL. One trial reported partial support by Medicor (MMS Medicor Medical Supplies GmbH, Kerpen, Germany) for statistical analysis. The remaining two trials did not provide information on funding. We identified four ongoing trials. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of microwave ablation in addition to conventional TACE compared with conventional TACE alone on adverse events or complications. We do not know if microwave ablation compared with conventional surgery may have little to no effect on all-cause mortality. We do not know the effect of microwave ablation compared with radiofrequency ablation on all-cause mortality and adverse events or complications either. Data on all-cause mortality and time to mortality, HRQoL, adverse events or complications, cancer mortality, disease-free survival, failure to clear liver metastases, recurrence of liver metastases, time to progression of liver metastases, and tumour response measures were either insufficient or were lacking. In light of the current inconclusive evidence and the substantial gaps in data, the pursuit of additional good-quality, large randomised clinical trials is not only justified but also essential to elucidate the efficacy and comparative benefits of microwave ablation in relation to various interventions for liver metastases. The current version of the review, in comparison to the previous one, incorporates two new trials in two additional microwave ablation comparisons: 1. in addition to conventional TACE versus conventional TACE alone and 2. versus radiofrequency ablation.

Damage of polyethylene microplastics on the intestine multilayer barrier, blood cell immune function and the repair effect of Leuconostoc mesenteroides DH in the large-scale loach (Paramisgurnus dabryanus).

Polyethylene microplastics (PE-MPs) has become a global concern due to their widespread distribution and hazardous properties in aquatic habitats. In this study, the accumulation effect of PE-MPs in the intestine of large-scale loach (Paramisgurnus dabryanus) was explored by adding different concentrations of PE-MPs to the water, the destination of PE-MPs after breaking the intestinal barrier and the effects caused. The collected data showed that PE-MPs accumulation for 21d altered the histomorphology and antioxidant enzyme activity of the intestine, induced dysbiosis of the intestinal flora. 10 mg/L of PE-MPs induced a significant increase in the transcript levels of intestinal immunity factors in loach after 21d of exposure. Moreover, the levels of diamine oxidase (DAO) and d-lactic acid (D-Lac) in the gut and serum of loach were significantly increased after exposure to PE-MPs at all concentrations (1, 5, 10 mg/L). Subsequently, the presence of PE-MPs was detected in the blood, suggesting that the disruption of the intestinal multilayer barrier allowed PE-MPs to spill into the circulation. The accumulation of PE-MPs (1,5,10 mg/L) in the blood led to massive apoptosis and necrosis of blood cells and activated phagocytosis in response to PE-MPs invasion. To alleviate the damage, this study further exposure the effect of probiotics on PE-MPs treated loach by adding Leuconostoc mesenteroides DH (109 CFU/g) to the feed. The results showed that DH significantly increased the intestinal index and reduced the levels of DAO and D-Lac. To investigate the reason, we followed the PE-MPs in the intestine and blood of the loach and found that the number of PE-MPs particles was significantly reduced in the probiotic group, while the PE-MPs content in the feces was elevated. Thus, we concluded that DH reducing the accumulation of PE-MPs in the intestinal by increases fecal PE-MPs, which in turn mitigates the damage to the intestinal barrier caused by PE-MPs, and reduces the amount of PE-MPs in the blood. This work offers a robust analysis to understand the mechanisms of damage to the intestinal barrier by MPs and the fate of MPs after escaping the intestinal barrier and provide a new perspective on the application of probiotics in mitigating PE-MPs toxicity.

Histone methylation readers MRG1/2 interact with PIF4 to promote thermomorphogenesis in Arabidopsis.

Warm ambient conditions induce thermomorphogenesis and affect plant growth and development. However, the chromatin regulatory mechanisms involved in thermomorphogenesis remain largely obscure. In this study, we show that the histone methylation readers MORF-related gene 1 and 2 (MRG1/2) are required to promote hypocotyl elongation in response to warm ambient conditions. A transcriptome sequencing analysis indicates that MRG1/2 and phytochrome interacting factor 4 (PIF4) coactivate a number of thermoresponsive genes, including YUCCA8, which encodes a rate-limiting enzyme in the auxin biosynthesis pathway. Additionally, MRG2 physically interacts with PIF4 to bind to thermoresponsive genes and enhances the H4K5 acetylation of the chromatin of target genes in a PIF4-dependent manner. Furthermore, MRG2 competes with phyB for binding to PIF4 and stabilizes PIF4 in planta. Our study indicates that MRG1/2 activate thermoresponsive genes by inducing histone acetylation and stabilizing PIF4 in Arabidopsis.

All-Year High IAA and ABA Contents in Rhizome Buds May Contribute to Natural Four-Season Shooting in Woody Bamboo Cephalostachyum pingbianense.

To explore the regulation mechanism of endogenous phytohormones on rhizome bud germination in Cephalostachyum pingbianense, the contents of IAA, ABA, GA, and CTK in seven above- and under-ground bamboo structure components were determined using enzyme-linked immunosorbent assays (ELISA). The results showed that a higher content of IAA, GA, and CTK all year was found in above-ground components and dormant rhizome buds. Meanwhile, a higher ABA content in young shoots and a lower ABA content in the culm base and dormant rhizome buds were detected during the peak period of shooting. The amounts of emerging shoots and the grown bamboo culms were positively correlated with the content of IAA and the ratio of IAA/ABA and (IAA + CTK + GA)/ABA, while they were negatively correlated with the ratio of CTK/IAA in dormant rhizome buds. The all-year high contents of IAA (19-31 ng/g) and ABA (114-144 ng/g) in rhizome buds, as well as interactions among four hormones, may be the key physiological mechanisms to maintain rhizome bud germination throughout the year in C. pingbianense. As C. pingbianense is a special bamboo species of multi-season shoot sprouting, the above results may supplement scientific data for a comprehensive understanding of physiological mechanisms within the bamboo subfamily.

Novel Pathogenic Mutation of P209L in TRPC6 Gene Causes Adult Focal Segmental Glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a leading kidney disease, clinically associated with proteinuria and progressive renal failure. The occurrence of this disease is partly related to gene mutations. We describe a single affected family member who presented with FSGS. We used high-throughput sequencing, sanger sequencing to identify the pathogenic mutations, and a systems genetics analysis in the BXD mice was conducted to explore the genetic regulatory mechanisms of pathogenic genes in the development of FSGS. We identified high urinary protein (++++) and creatinine levels (149 µmol/L) in a 29-year-old male diagnosed with a 5-year history of grade 2 hypertension. Histopathology of the kidney biopsy showed stromal hyperplasia at the glomerular segmental sclerosis and endothelial cell vacuolation degeneration. Whole-exome sequencing followed by Sanger sequencing revealed a heterozygous missense mutation (c.643C > T) in exon 2 of TRPC6, leading to the substitution of arginine with tryptophan at position 215 (p.Arg215Trp). Systems genetics analysis of the 53 BXD mice kidney transcriptomes identified Pygm as the upstream regulator of Trpc6. Those two genes are jointly involved in the regulation of FSGS mainly via Wnt and Hippo signaling pathways. We present a novel variant in the TRPC6 gene that causes FSGS. Moreover, our data suggested TRPC6 works with PYGM, as well as Wnt and Hippo signaling pathways to regulate renal function, which could guide future clinical prevention and targeted treatment for FSGS outcomes.

Resistant starch and the gut microbiome: Exploring beneficial interactions and dietary impacts.

The intricate relationship between resistant starch (RS) and the gut microbiome presents a dynamic frontier in nutrition science. This review synthesizes current understandings of how RS, an indigestible form of starch found naturally in certain foods and also enhanced through various modification methods, interacts with the gut microbiome. We particularly focus on how RS fermentation in the colon contributes to the production of beneficial volatile fatty acids (VFAs) such as butyrate, acetate, and propionate. These VFAs have been recognized for their vital roles in maintaining gut barrier integrity, modulating inflammation, and potentially influencing systemic health. Additionally, we discuss the dietary implications of consuming foods rich in RS, both in terms of gut health and broader metabolic outcomes. By consolidating these insights, we emphasize the significance of RS in the context of dietary strategies aimed at harnessing the gut microbiome's potential to impact human health.

Dazhu Hongjingtian Injection for Ischemic Stroke: Protocol for a Prospective, Multicenter Observational Study.

BACKGROUND: Although results from in vitro studies and small randomized controlled trials have shown positive effects of Dazhu hongjingtian injection (DZHJTI) on acute ischemic stroke (AIS), their generalizability to routine clinical practice remains to be established. OBJECTIVE: The primary aim of this study is to evaluate the effectiveness of DZHJTI treatment for AIS with regard to changes in the stroke-related neurological deficit from baseline to outpatient follow-up, mortality, subsequent vascular events, disability, and traditional Chinese medicine syndrome in real-world clinical settings. By monitoring for adverse events or significant changes in vital signs and laboratory parameters, we also aim to assess the safety of DZHJTI. METHODS: This prospective, multicenter cohort study plans to enroll 2000 patients with AIS within 14 days of symptom onset from 30 hospitals across China. Eligible patients will be followed up for 6 months after initiating medication treatments. The primary outcome will be the change in the National Institute of Health Stroke Scale score from baseline to outpatient follow-up. The secondary outcomes include overall mortality, stroke recurrence, new-onset major vascular events, global disability, and improvement of traditional Chinese medicine syndrome in 6 months. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of DZHJTI. An augmented inverse propensity weighted estimator will be used to reduce variability and improve accuracy in average treatment effects estimation. RESULTS: The clinical trial registration was approved in October 2022, and the recruitment and enrollment of participants started in November 2022. The study's outcomes are expected to be published in 2025 in reputable, peer-reviewed health-related research journals. CONCLUSIONS: This real-world cohort study is the first to assess the effectiveness and safety of DZHJTI in treating AIS. It may provide additional clinical evidence, including the duration of response, long-term drug effectiveness, and subgroup efficacy data. The study results will be valuable for clinicians and patients seeking optimal treatment for AIS and could lead to better use of DZHJTI and improved patient outcomes. TRIAL REGISTRATION: ITMCTR ITMCTR2022000005; http://tinyurl.com/554ns8m5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52447.

Postoperative Metachronous Metastasis of Bladder Cancer to Penis: A Case Report

Background: Penile metastases are extremely rare events, originating primarily from primary pelvic tumours of the prostate, bladder, and gastrointestinal tract. The underlying mechanism of bladder cancer metastasis to the penis remains unclear. Metastasis to the penis is usually considered a late manifestation of systemic spread. Therefore, the prognosis of patients with penile metastasis remains poor and their survival period is short. Therefore, reporting this rare case will help to better understand the characteristics, diagnosis, and treatment processes of the disease, with the aim of improving the accuracy and efficiency of diagnosis and treatment. Case Description: A 65-year-old male received transurethral resection of a bladder tumor. One year later, he underwent radical cystectomy because of the recurrence and progression of bladder cancer. Postoperative pathology demonstrated that the stage of bladder cancer was T3N0M0. One year later, he discovered a penile mass that gradually grew and became hard, accompanied by urinary retention, but without other clinical symptoms. The patient underwent a complete penectomy. Histopathology and immunohistochemistry results demonstrated the tumour’s origin as a bladder urothelial carcinoma. The patient received systemic chemotherapy after surgery, but died 7 months later. Conclusions: Although penile metastasis of bladder cancer typically indicates an advanced stage of the malignant tumour and poor prognosis, we recommend that male patients with a history of bladder cancer should undergo a regular clinical examination of the penis to rapidly detect the disease and receive early treatment. In this case, despite treatment measures such as systemic chemotherapy and penectomy, the patient’s prognosis remained poor (AU)

Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds.

Ischemic stroke (IS), which is the third foremost cause of disability and death worldwide, has inflammation and cell death as its main pathological features. IS can lead to neuronal cell death and release factors such as damage-related molecular patterns, stimulating the immune system to release inflammatory mediators, thereby resulting in inflammation and exacerbating brain damage. Currently, there are a limited number of treatment methods for IS, which is a fact necessitating the discovery of new treatment targets. For this review, current research on inflammation and cell death in ischemic stroke was summarized. The complex roles and pathways of the principal immune cells (microglia, astrocyte, neutrophils, T lymphocytes, and monocytes/macrophage) in the immune system after IS in inflammation are discussed. The mechanisms of immune cell interactions and the cytokines involved in these interactions are summarized. Moreover, the cell death mechanisms (pyroptosis, apoptosis, necroptosis, PANoptosis, and ferroptosis) and pathways after IS are explored. Finally, a summary is provided of the mechanism of action of natural pharmacological active ingredients in the treatment of IS. Despite significant recent progress in research on IS, there remain many challenges that need to be overcome.

Effect of Trans-PRK combined with 0.02% MMC on corneal density in patients with moderate myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the effect of 0.02% mitomycin-C(MMC)on the corneal density after transepithelial photorefractive keratectomy(Trans-PRK). METHODS: Retrospective case analysis. Selected 28 patients with 56 eyes in moderate myopia who underwent Trans-PRK surgery from January 2021 to June 2021 in our hospital. They were divided into MMC group in 28 eyes with a combination of 0.02% MMC 20s during the surgery and the control group in 28 eyes was not use MMC during the surgery. The Pentacam anterior segment analyzer was used to measured the corneal density in different diameter ranges and different thickness layers before and after surgery at 14d, and after surgery at 1 and 3mo.RESULTS: The total corneal density value of MMC group was 16.60(15.70,17.10 )before the surgery, after the surgery at 14d was 16.63(15.90,17.50 ), at 1mo was 16.57(15.10,16.70 ), at 3mo was 16.04(14.60,16.60 ). The total corneal density value of control group was 16.30(15.50,17.30 )before the surgery, after the surgery at 14d was 16.20(15.20,17.10 ), at 1mo was 16.08(14.90,16.40 )and at 3mo was 15.60(14.60,16.40 ). In the zone of 0-2mm diameter was centered on the corneal vertex, the corneal density of the two groups at 14d after the surgery was higher than those before surgery(P<0.001 ). In the zone of 2-6mm diameter, the corneal density of the two groups at 1mo and 3mo after surgery was higher than those before the surgery(P<0.001). In the zone of 6-10mm, the corneal density of the two groups at 14d, 1 and 3mo after surgery was higher than those before the surgery(P<0.001). In the layer of anterior 120 μm, the corneal density of the two groups at 1mo and 3mo after the surgery was decreased than that before surgery(P<0.01). In the middle layer, the corneal density of the two groups at 1mo after the surgery was decreased than those before surgery(P<0.01).CONCLUSION:The use of 0.02% MMC during the operation can reduce the corneal density and increase the corneal light transmittance in the early postoperative period. The occurrence and prognosis of haze can be effectively quantified by observing the changes of corneal optical density in different ranges in different time periods after operation.

Clinical efficacy of surgery via endoscopic-assisted transcallosal approach in intraventricular hemorrhage / 中华神经医学杂志

Objective:To investigate the efficacy and safety of surgery via endoscopic-assisted transcallosal approach in intraventricular hemorrhage (IVH).Methods:A retrospective study was performed; the clinical data of 68 IVH patients admitted to our hospital from October 2016 to January 2020 were analyzed. These patients were divided into endoscopic treatment group ( n=34) and drainage group ( n=34) according to the treatment methods. In the endoscopic treatment group, IVH was evacuated via endoscopic-assisted transcallosal approach; in the drainage group, external ventricular drainage and urokinase injection were performed. Gross hematoma clearance rate (clearance rate≥95%) 1, 3, and 7 d after surgery, complication incidence 7 d and 1 month after surgery, and good prognosis rate (ability of daily living [ADL] grading I-III) 3 months after surgery were compared between the two groups. Results:One, 3, and 7 d after surgery, the gross hematoma clearance rate in the endoscopic treatment group was significantly higher than that in the drainage group ( P<0.05). The recurrent hemorrhage rate within 7 d of surgery, intracranial infection rate, and percentage of patients with secondary hydrocephalus requiring shunt within 30 d of surgery in the endoscopic treatment group were significantly lower than those in the drainage group (2.9% vs. 20.6%, 2.9% vs. 23.5%, 5.9% vs. 17.6%, P<0.05). Three months after follow-up, the good prognosis rate of patients in the endoscopic treatment group was significantly higher than that in the drainage group (91.2% vs. 58.9%, P<0.05). Conclusion:Endoscopic-assisted transcallosal approach is recommended in clinical treatment of IVH, which can significantly reduce postoperative complications and improve postoperative prognosis.

Clinical characteristics and related factors of somatization symptoms in outpatients with psychiatric disorders of the department of cardiology in general hospitals / 中华心血管病杂志

Objective@#To explore the clinical characteristics and related factors of somatization symptoms in outpatients with psychiatric disorders of the cardiology department in general hospital.@*Methods@#Cross-sectional survey method was used in this study. From August 2017 to September 2018, 508 outpatients of our department with suspected mental disorders, who complained of physical discomfort and screened by the "Three Questions" method recommended by the Chinese Expert Consensus on Psychological Prescriptions of Cardiovascular Patients in 2014, were consecutively included. General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9), Patient Health Questionnaire-15 (PHQ-15) and self-made general demographic questionnaire (including age, sex, marital status, educational level, occupation, duration of disease, clinical diagnosis and the process of medical treatment for the main somatic symptoms in recent one year) were used to investigate these patients, under the assistance of unified training psychological consultants. The detection rate of anxiety and depression, the degree and distribution of somatization symptoms in outpatients with mental disorders were analyzed, and the related factors affecting the occurrence of somatization symptoms were screened by multivariate logistic regression.@*Results@#The selected patients were (51.3±10.1) years old, of which 37.8% (192/508) were males and 62.2% (316/508) were females. The total detection rate of anxiety/depression was 86.8% (441/508), and the detection rate of somatization symptoms was 93.1% (473/508). The number of positive symptom items in PHQ-15 was 8.0±2.7, and the detection rate of anxiety/depression was 78.6% (372/473) in patients with somatization symptoms. There were significant differences in the proportion of women, the average number of outpatient visits and hospitalizations in the past one year, GAD-7 score and PHQ-9 score among the patients with mild, moderate and severe somatization symptoms (all P<0.05). PHQ-15 score was positively correlated with GAD-7 score (r=0.524 5, P<0.001) and PHQ-9 score (r=0.574 9, P<0.001) in patients with somatization symptoms. Stepwise logistic regression analysis showed that total scores of PHQ-9 (OR=8.020, 95%CI 3.470-18.930, P<0.001) and GAD-7 (OR=6.526, 95%CI 2.903-13.045, P<0.001) and female (OR=4.440, 95%CI 1.059-9.073, P=0.011) were related factors of somatizations.@*Conclusions@#The incidence of somatization symptoms is high in patients with psychological disorders in outpatients of cardiology department in general hospital. Anxiety, depression and gender are the main related risk factors of somatization symptoms in this patient cohort. Degree of anxiety and depression increased in proportion to the severity of somatization symptoms. Anxiety, depression and female is related to somatization symptoms.

Analysis of high risk factors for acute complex appendicitis in adults / 中华胃肠外科杂志

OBJECTIVE@#To explore the high risk factors of adult complex appendicitis, and to provide a reference for the development of a reasonable treatment strategy for acute appendicitis.@*METHODS@#A retrospective case-control study was conducted to collect clinical data of 312 adult patients with acute appendicitis confirmed by pathology undergoing appendectomy, including open and laparoscopic surgery, from May 2011 to August 2016 at Affiliated Hospital of Qingdao University. Age <14 years old, pregnant women, complicating abscess around the appendix, AIDS, blood system diseases, autoimmune diseases, inflammatory bowel disease or progressive cancer patients were excluded. According to the intra-operative findings and pathological types, patients were divided into complex appendicitis(112 cases, including gangrene and perforation) and non-complex appendicitis (200 cases, including simple and non-perforated appendicitis, ie suppurative appendicitis). After comparing the clinical data of these two groups, statistically significant variables were induded for multivariate logistic regression analysis to identify risk factors of complex appendicitis, and to establish a regression model. Enter method was applied to establish the regression equation: P=ExpiΣBiXi/1+ExpΣBiXi, and to calculate the relative risk of each variable. Meanwhile, retrospective and prospective verification was performed on this predictive model (cases of acute appendicitis from September 2016 to December 2017 were further collected). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of complex appendicitis were calculated with the regression model.@*RESULTS@#Comparison of the clinical data between the complex appendicitis group and the non-complex appendicitis group showed that differences of 10 preoperative indexes were statistically significant, including period from abdominal pain to admission [(59.1±42.6) hours vs. (47.5±34.4) hours, t=3.051, P=0.002], white blood cell count [(12.9±3.7)×10/L vs. (9.2±4.0)×10/L, t=9.755, P<0.001], neutrophil count [(9.8±4.0)× 10/L vs.(7.1±3.9)×10/L, t=6.020, P<0.001], neutrophil percentage[(84.5±8.7)% vs.(68.2±16.0)%, t=12.754, P<0.001], C-reactive protein levels [(86.0±45.4) μg/L vs. (55.9±35.8) μg/L, t=7.614, P<0.001], serum albumin levels [(334.0±4.8) g/L vs. ( 41.0±4.3) g/L, t=16.055, P<0.001], vomiting ratio [44.6%(50/112) vs. 23.5%(47/200), χ²=14.980, P<0.001], high fever(≥39°C) ratio [16.1%(18/112) vs. 7.5%(15/200), χ²=5.577, P=0.022], the proportion of patients ≥60 years old [22.3%(25/112) vs. 13.0%(26/200), χ²=4.562, P=0.038] and previous history of appendicitis [16.1%(18/112) vs. 7.5%(15/200), χ²=5.577, P=0.022]. The above 10 variables were included in the logistic regression model for multivariate analysis. The results showed that six variables were associated with complex appendicitis. According to their strength, they were old age (≥60 years old) X1(OR=5.094), high fever (≥39°C) X2(OR=4.464), neutrophil count X6 (OR=1.269), neutrophil percentage X4 (OR=1.077), C-reactive protein level X5 (OR=1.027), and serum albumin level X3 (OR=0.763). A predictive regression model was established: P=1/[1+e], whose sensitivity and specificity of judging complex appendicitis were 76.8%(86/112) and 90.0%(180/200),respectively. Sensitivity and specificity for predictive value of complex appendicitis in further prospective validation of the model were 76.2%(48/63) and 81.1% (30/37), respectively.@*CONCLUSIONS@#Age ≥ 60 years old, body temperature ≥39°C, increased neutrophil count, neutrophil percentage and C-reactive protein levels, and hypoalbuminemia are risk factors for complex appendicitis. The establishment of predictive model may help determine complex appendicitis.

Effects of Bisoprolol Combined with Conventional Triple Therapy on the Efficacy and Related Indexes of Pa-tients with Rheumatic Heart Valvular Disease Combined Chronic Heart Failure / 中国药房

OBJECTIVE:To observe the effects of bisoprolol combined with conventional triple therapy on the efficacy and re-lated indexes of patients with rheumatic heart valvular disease (RVD) combined chronic heart failure. METHODS:110 patients with RVD combined with chronic heart failure were randomly divided into observation group(55 cases)and control group(55 cas-es). All patients were treated with oxygen inhalation,anti-infection,correcting electrolyte imbalance,controlling arrhythmia,and giving digitalis drugs and diuretic drugs(it can be disabled after edema symptom being controlled);based on it,control group was given Enalapril tablet with initial dose of 2.5 mg,once to twice a day,then adjusted to 10-20 mg after 1 week,twice a day+20 mg Spironolactone tablet,once a day+10 mg Propranolol tablet,once a day. Observation group was additionally given Bisoprolol fuma-rate tablet initial dose of 1.25 mg,once a day,and then increased to 10 mg based on condition improved and tolerability after a meal,once a day. They were treated for 12 weeks. Clinical efficacy,and LVEF,LVEDD,LVESD,SBP,DBP,HR before and af-ter treatment and incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically significant (P0.05). After treatment,LVEF in 2 groups were significantly higher than before,and observation group was higher than control group,LVEDD,LVESD,SBP, DBP and HR were significantly lower than before,and observation group was lower than control group,the differences were statis-tically significant(P0.05). CONCLU-SIONS:Based on conventional treatment,bisoprolol combined with conventional triple therapy shows good efficacy in the treat-ment of RVD combined chronic heart failure,it can improve cardiac function,with good safety.