Demand and Analysis of Clinical Research Curriculum in Medical Universities

Objective:To investigate the needs of medical students regarding clinical research curricula to provide scientifically sound offerings and cultivate their clinical research thinking.Methods:From June to October 2022,medical students at medical universities in Shaanxi Province were surveyed using online questionnaires.The survey covered their demographic information,awareness of their major,understanding of clinical research,and preferences for curriculum content.Results:A total of 341 valid questionnaires were analyzed.Medical students demonstrated a strong awareness of their majors but a relatively low awareness of clinical research.There was significant demand for clinical research courses,with preferences for professionally oriented(81.8%),market-oriented(100%),theoretically and practically integrated teaching(78.6%),and application-focused(73.0%)courses.Conclusion:Medical colleges and universities should align clinical research curricula with the actual needs of medical students and clinical practice.Reforms in curriculum design and teaching methods are essential to better prepare students for careers in public health.

Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Molecular Docking Studies of Botanical Beverage Mix Berries (LIFEGREENTM) against Breast Cancer Cells from Targeted Protein 1QQG, 7B5Q & 7B5O & Uterine Fibroid from Targeted Protein 2AYR, 6T41 & 3GRF

Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.

Association of Human Whole-blood NAD+Levels with Nabothian Cyst

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese women.Methods Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian cysts.Results The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)quartiles.As compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/L.Conclusion:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.

Research on the characteristics of atmospheric air dielectric barrier discharge under different square wave pulse polarities

Energy efficiency limits the application of atmospheric pressure dielectric barrier discharge(DBD),such as air purification,water treatment and material surface modification.This article focuses on the electrical and optical effects of the DBD under three square wave pulses polarities-positive,negative and bipolar.The result shows that under the same voltage with the quartz glass medium,the discharge efficiency of bipolar polarity pulse is the highest due to the influence of deposited charge.With the increase of air gap distance from 0.5 to 1.5 mm,average power consumed by the discharge air gap and discharge efficiency decrease obviously under alumina,and increase,and then decrease under quartz glass and polymethyl methacrylate(PMMA).Through spectrum diagnosis,in the quartz glass medium,the vibration temperature is the highest under negative polarity pulse excitation.Under bipolar pulse,the vibration temperature does not change significantly with the change of air gap distance.For the three dielectric materials of quartz glass,alumina and PMMA,the molecular vibration temperature is the highest under the quartz glass medium with the same voltage.When the gap spacing,pulse polarity or dielectric material are changed,the rotational temperature does not change significantly.

Quantitative parameters in novel spectral computed tomography:Assessment of Ki-67 expression in patients with gastric adenocarcinoma

BACKGROUND The level of Ki-67 expression has served as a prognostic factor in gastric cancer.The quantitative parameters based on the novel dual-layer spectral detector computed tomography(DLSDCT)in discriminating the Ki-67 expression status are unclear.AIM To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma(GC).METHODS Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma.Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt(kev),the slope of the spectral curve(λ_(HU)),iodine concentration(IC),normalized IC(nIC),effective atomic number(Z^(eff))and normalized Z^(eff)(nZ^(eff))in the arterial phase(AP)and venous phase(VP)were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma.Spearman’s correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status.Receiver operating characteristic(ROC)curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups.RESULTS Thirty-seven and 71 patients were classified as having low and high Ki-67 expression,respectively.CT_(40 kev-VP),CT_(70 kev-VP),CT_(100 kev-VP),and Z^(eff)-related parameters were significantly higher,but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status,and other analyzed parameters showed no statistical difference between the two groups.Spearman’s correlation analysis showed that CT_(40 kev-VP),CT_(70 kev-VP),CT_(100 kev-VP),Z^(eff),and n Z^(eff) exhibited a negative correlation with Ki-67 status,whereas IC and nIC had positive correlation with Ki-67 status.The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status[area under the curve(AUC)=0.967;sensitivity 95.77%;specificity 91.89%)].Nevertheless,the differentiating capabilities of singlevariable model were moderate(AUC value 0.630-0.835).In addition,the nZ_(VP)^(eff) and nIC_(VP)(AUC 0.835 and 0.805)showed better performance than CT_(40 kev-VP),CT_(70 kev-VP) and CT_(100 kev-VP)(AUC 0.630,0.631 and 0.662)in discriminating the Ki-67 status.CONCLUSION Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma.Z^(eff) and IC may be useful parameters for evaluating the Ki-67 expression.

An Efficient Numerical Scheme for Biological Models in the Frame of Bernoulli Wavelets

This article considers three types of biological systems:the dengue fever disease model,the COVID-19 virus model,and the transmission of Tuberculosis model.The new technique of creating the integration matrix for the Bernoulli wavelets is applied.Also,the novel method proposed in this paper is called the Bernoulli wavelet collocation scheme(BWCM).All three models are in the form system of coupled ordinary differential equations without an exact solution.These systems are converted into a system of algebraic equations using the Bernoulli wavelet collocation scheme.The numerical wave distributions of these governing models are obtained by solving the algebraic equations via the Newton-Raphson method.The results obtained from the developed strategy are compared to several schemes such as the Runge Kutta method,and ND solver in mathematical software.The convergence analyses are discussed through theorems.The newly implemented Bernoulli wavelet method improves the accuracy and converges when it is compared with the existing methods in the literature.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

A review of the research on music therapy in hospice care

Objective:To summarize the research progress of music therapy in hospice care and to provide reference for further research.Methods:A wide range of literatures on music therapy and hospice care at home and abroad were searched and read,and the literature was integrated,judged,analyzed,and summarized.Results:The related research on music therapy in hospice care mainly focused on western developed countries such as Europe and the United States.China is still in the stage of theoretical exploration,lacking qualitative research based on case investigation and empirical research based on data statistics.Conclusions:Music therapy supports the management of symptoms in hospice care,which can meet the diverse needs of patients and their family members including physical,psychological,social,and spiritual.

An Improved Soft Subspace Clustering Algorithm for Brain MR Image Segmentation

In recent years,the soft subspace clustering algorithm has shown good results for high-dimensional data,which can assign different weights to each cluster class and use weights to measure the contribution of each dimension in various features.The enhanced soft subspace clustering algorithm combines interclass separation and intraclass tightness information,which has strong results for image segmentation,but the clustering algorithm is vulnerable to noisy data and dependence on the initialized clustering center.However,the clustering algorithmis susceptible to the influence of noisydata and reliance on initializedclustering centers andfalls into a local optimum;the clustering effect is poor for brain MR images with unclear boundaries and noise effects.To address these problems,a soft subspace clustering algorithm for brain MR images based on genetic algorithm optimization is proposed,which combines the generalized noise technique,relaxes the equational weight constraint in the objective function as the boundary constraint,and uses a genetic algorithm as a method to optimize the initialized clustering center.The genetic algorithm finds the best clustering center and reduces the algorithm’s dependence on the initial clustering center.The experiment verifies the robustness of the algorithm,as well as the noise immunity in various ways and shows good results on the common dataset and the brain MR images provided by the Changshu First People’s Hospital with specific high accuracy for clinical medicine.

Compatibility mechanism of Chinese medicine formula:state of the art and perspectives

Traditional Chinese medicine(TCM)has been practiced in China and surrounding countries for thousands of years and has gradually attracted the attention of Western countries.After reasonable compatibility,TCMs could play the key role of enhancing efficacy and reducing toxicity,which has significant therapeutic advantages in the treatment of complex diseases in clinical practice.While the TCM compatibility is not the simple addition of drugs.Under the appropriate dosage ratio,multiple TCMs can play a synergistic role to realize the overall regulation of TCM treatment.Therefore,it is of critical essential to study the compatibility of TCM formula to promote TCM modernization,new drug development and clinical application.Recently,under the guidance of TCM theory,many researches on the composition,pharmacodynamic activity and pharmacokinetic properties of TCM formula have emerged by integrating new technologies and new methods,revealing the scientific connotation of the compatibility of TCM formula from different perspectives and levels.This paper introduces the research progress of compatibility rules from different levels of compatibility,compatibility for synergistic enhancement and detoxification,and application of cutting-edge technology,with representative cases,in order to provide ideas and references for further study on TCM compatibility.

TORCH Infection Status in Women of Childbearing Age in China:A Meta-Analysis

Objective:This paper presents a systematic review and meta-analysis of comprehensive information on the epidemiology of toxoplasmosis(TOX),rubella virus(RV),cytomegalovirus(CMV),and herpes simplex(HSV)also known as TORCH infection in women of childbearing age.Besides,the positive rates of TORCH-Immunoglobulin G(TORCH-IgG)and Immunoglobulin M(IgM)antibodies in women of childbearing age in different regions of China were statistically analyzed,so as to highlight the issue of TORCH infection in women of childbearing age.Methods:A total of 12,694 articles were retrieved by keyword searching.The works were screened according to the inclusion criteria,and 25 studies were included totaling 531,617 women of childbearing age.The OpenMeta[Analyst]software was used to perform a heterogeneity test,and a random-effects model was used for system analysis.Results:The results of the meta-analysis showed that the positive rates of TORCH-IgG antibodies in women of childbearing age nationwide were 3.2%for TOX-IgG,73.4%for RV-IgG,73.8%for CMV-IgG,and 57.4%for HSV-IgG.The positive rates of IgM antibody infection in TORCH were 1.3%for TOX-IgM,6.1%for RV-IgM,9.5%for CMV-IgM,7.6%for HSV-IgM,2.0%for HSV-1-IgM,and 1.9%for HSV-2-IgM.All meta-analyses had I2≥98%and P<0.001,which meant that the results were statistically significant.Conclusions:A meta-analysis of the positive rates of IgG and IgM antibodies of TORCH infection in women of childbearing age found that the early infection rate of HSV was the highest,and the previous infection rate of RV was the highest.This result can provide epidemiological basis for the prevention and treatment of TORCH infection.

Retrospective Analysis of the Effect of Auricular Acupuncture on Pain and Gastrointestinal Motility Recovery After Laparoscopic Surgery for Colorectal Cancer

Objective:To investigate the effect of auricular acupuncture on postoperative pain and gastrointestinal motility recovery after laparoscopic surgery for colorectal cancer.Methods:The clinical data of patients who underwent laparoscopic radical surgery for colorectal cancer in our hospital from April 2020 to December 2021 were collected.Based on the inclusion and exclusion criteria,76 patients were included in the retrospective analysis.Depending on whether they received auricular acupuncture or not,the patients were divided into two groups:46 patients in the experimental group(auricular acupuncture)and 30 patients in the control group.The differences between the two groups were analyzed.Results:The time to first flatus of the experimental group was significantly shorter than that of the control group(52.2±7.36 h versus 66.3±7.83 h;P<0.001).Similarly,the time to first defecation of the experimental group was significantly shorter than that of the control group(76.3±7.76 h versus 86.1±10.79 h;P<0.001).The time to first fluid intake of the auricular group was significantly shorter than that of the control group(90.4±8.92 h versus 107.3±9.66 h,P<0.001).Compared with the control group,the experimental group scored significantly lower on the visual analogue scale on postoperative days 2 and 3(P<0.001).Conclusion:Auricular acupuncture is an effective traditional Chinese medicine external treatment method.It can promote gastrointestinal motility recovery in patients after laparoscopic radical surgery for colorectal cancer and also reduce postoperative pain and discomfort.Furthermore,this therapy is easy to operate and well-accepted by patients.Therefore,it should be strongly promoted in clinical practice.

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies.In this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome.Moreover,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating depression.Additionally,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression.Currently,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment.The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression.Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

Targeting colorectal cancer with Herba Patriniae and Coix seed:Network pharmacology,molecular docking,and in vitro validation

BACKGROUND Herba Patriniae and Coix seed(HC)constitute a widely utilized drug combination in the clinical management of colorectal cancer(CRC)that is known for its diuretic,anti-inflammatory,and swelling-reducing properties.Although its efficacy has been demonstrated in a clinical setting,the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.AIM To identify the active,CRC-targeting components of HC and to elucidate the mechanisms of action involved.METHODS Active HC components were identified and screened using databases.Targets for each component were predicted.CRC-related targets were obtained from human gene databases.Interaction targets between HC and CRC were identified.A“drug-ingredient-target”network was created to identify the core components and targets involved.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted to elucidate the key pathways involved.Molecular docking between core targets and key components was executed.In vitro experiments validated core monomers.RESULTS Nineteen active components of HC were identified,with acacetin as the primary active compound.The predictive analysis identified 454 targets of the active compounds in HC.Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets,including 30 core targets.GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway.Molecular docking showed that acacetin exhibited an optimal interaction with AKT1,identifying PI3K,AKT,and P53 as key genes likely targeted by HC during CRC treatment.Acacetin inhibited HT-29 cell proliferation and migration,as well as promoted apoptosis,in vitro.Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K,p-Akt,and survivin,which likely contributed to CRC apoptosis.CONCLUSION Acacetin,the principal active compound in the HC pair,inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Preoperatively predicting vessels encapsulating tumor clusters in hepatocellular carcinoma:Machine learning model based on contrast-enhanced computed tomography

BACKGROUND Recently,vessels encapsulating tumor clusters(VETC)was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner,and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma(HCC).AIM To develop and validate a preoperative nomogram using contrast-enhanced computed tomography(CECT)to predict the presence of VETC+in HCC.METHODS We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers.Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase.Radiomics features,essential for identifying VETC+HCC,were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set.The model’s performance was validated on two separate test sets.Receiver operating characteristic(ROC)analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets.The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features.ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features,the radiomics features and the radiomics nomogram.RESULTS The study included 190 individuals from two independent centers,with the majority being male(81%)and a median age of 57 years(interquartile range:51-66).The area under the curve(AUC)for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825,0.788,and 0.680 in the training set and the two test sets.A total of 13 features were selected to construct the Rad-score.The nomogram,combining clinicalradiological and combined radiomics features could accurately predict VETC+in all three sets,with AUC values of 0.859,0.848 and 0.757.Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models.CONCLUSION This study demonstrates the potential utility of a CECT-based radiomics nomogram,incorporating clinicalradiological features and combined radiomics features,in the identification of VETC+HCC.

Multiscale and Auto-Tuned Semi-Supervised Deep Subspace Clustering and Its Application in Brain Tumor Clustering

In this paper,we introduce a novel Multi-scale and Auto-tuned Semi-supervised Deep Subspace Clustering(MAS-DSC)algorithm,aimed at addressing the challenges of deep subspace clustering in high-dimensional real-world data,particularly in the field of medical imaging.Traditional deep subspace clustering algorithms,which are mostly unsupervised,are limited in their ability to effectively utilize the inherent prior knowledge in medical images.Our MAS-DSC algorithm incorporates a semi-supervised learning framework that uses a small amount of labeled data to guide the clustering process,thereby enhancing the discriminative power of the feature representations.Additionally,the multi-scale feature extraction mechanism is designed to adapt to the complexity of medical imaging data,resulting in more accurate clustering performance.To address the difficulty of hyperparameter selection in deep subspace clustering,this paper employs a Bayesian optimization algorithm for adaptive tuning of hyperparameters related to subspace clustering,prior knowledge constraints,and model loss weights.Extensive experiments on standard clustering datasets,including ORL,Coil20,and Coil100,validate the effectiveness of the MAS-DSC algorithm.The results show that with its multi-scale network structure and Bayesian hyperparameter optimization,MAS-DSC achieves excellent clustering results on these datasets.Furthermore,tests on a brain tumor dataset demonstrate the robustness of the algorithm and its ability to leverage prior knowledge for efficient feature extraction and enhanced clustering performance within a semi-supervised learning framework.

Zuogui Jiangtang Jieyu Formula ameliorating hippocampal neuronal apoptosis in diabetic rats with depression by inhibiting JNK signaling pathway

Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with depression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assessments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Except for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were observed using HE staining,Nissl staining,TUNEL staining,and transmission electron microscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.

METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer

BACKGROUND N6-methyladenosine(m6A)modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors.However,despite its significance,the comprehensive investigation of METTL5,a key m6A methyltransferase,in colorectal cancer(CRC)remains limited.AIM To investigate the role of METTL5 in CRC.METHODS We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines.To elucidate the downstream targets of METTL5,we performed RNA-sequencing analysis coupled with correlation analysis,leading us to identify Toll-like receptor 8(TLR8)as a potential downstream target.In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays,scratch assays,as well as assays measuring cell migration and invasion.RESULTS Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues,which correlated significantly with an unfavorable prognosis.In vitro experiments unequivocally demonstrated the oncogenic role of METTL5,as evidenced by its promotion of CRC cell proliferation,invasion,and migration.Notably,we identified TLR8 as a downstream target of METTL5,and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation,invasion,and tumor growth.CONCLUSION The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis,thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.