Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

The Mid-Long Term Outcome of Breast-Conserving Patients with Different Ages

OBJECTIVE Breast-conserving surgery has been a standard treatment for relatively small size of breast cancer. Younger breast cancer patients have more desire to conserve their breasts. This study was to investigate the clinicopathological characteristics and prognosis of younger breast cancer patients who received breastconserving treatment in China. METHODS The data of 232 breast cancer patients who received breast-conserving treatment in Cancer Hospital of Chinese Academy of Medical Science from January Ist, 1999 to December 31st, 2005, were collected and retrospectively analyzed. According to the age, the patients were divided into 2 groups： younger group （age ≤ 35 at the time of diagnosis） and elder group （age 〉35）. The clinical features of the patients in the 2 groups were compared, and their clinical characteristics, recurrence, metastasis and survival status were summarized. RESULTS In the 232 cases, younger patients accounted for 15.9% （37/232）, the elder 84.1% （195/232）. By December 2008, the median time of follow-up was 54 months （ranging from 2 months to 118 months）. Two patients （5.41% , 2/37） in the younger group and 5 patients （2.56% 5/195） in the elder group died. The 5-year overall survival rate （OS） in the younger and elder groups was 96.08% and 97.19%, respectively （X2= 0.69, P = 0.4066）. Local recurrence （LR） or distant metastasis （DM） presented in 5 patients （5/37, 13.51%） in younger group. LR or DM presented in 10 patients （10/195, 5.13%） in elder group. The 5-year disease-free survival （DFS） rate in the younger and elder groups was 82.58% and 95.52%, respectively （X2 = 4.02, P = 0.0451）. Lymph node status and the age of 35 years old or younger were the prognosis factors affecting the DFS of patients who received breast-conserving treatment （OR = 3.467, 95%CI： 1.048-11.472, P 〈0.05; OR = 0.245, 95%CI： 0.069-0.863, P 〈 0.05）. Lymph node status was the only prognostic factor affecting the DFS of younger group patients （OR = 7.357, 95%CI： 1.030-52.563, P 〈0.05）. CONCLUSION Though the younger and elder patients have the same mid-long term survival rate, younger patients are more likely to have recurrence or metastasis than the elder patients. Breast-conserving surgery given to the younger patients especially to the younger patients with lymph nodes positive should be contemplated cautiously.

Breast-conserving therapy and modified radical mastectomy for primary breast carcinoma:a matched comparative study

Background- To compare two types of therapy for primary breast carcinoma, breast-conserving therapy （BCT） and modified radical mastectomy （MRM）, in a matched cohort study. Methods： A series of 1,746 patients with primary breast cancer treated with BCT or MRM in a single Chinese institute between January 2000 and February 2009 were analyzed retrospectively to compare their outcomes with respect to the incidence of local recurrence （LR）, distant metastasis, and survival. The patients were matched with regard to age at diagnosis, spreading to axillary lymph nodes, hormone receptor status, the use of neoadjuvant chemotherapy and maximal tumor diameter. The match ratio was 1：1, and each arm included 873 patients. Results： The median follow-up period was 71 months. The 6-year disease-free survival （DFS） and 6-year distant disease-free survival （DDFS） rates differed significantly between two groups. The 6-year local recurrence-free survival （LRFS） rates were 98.2% [95% confidence interval （CI）： 0.973-0.989] in the BCT group and 98.7% （95% CI： 0.980-0.994） in the MRM group （P=0.182）, respectively. DFS rates in BCT and MRM groups were 91.3% （95% CI： 0.894-0.932） and 86.3% （95% CI： 0.840-0.886） （P〈0.001）, respectively, whereas the DDFS rates in BCT and MRM groups were 93.6% （95% CI： 0.922-0.950） and 87.7% （95% CI： 0.854-0.900） （P〈0.001）, respectively. Conclusions： BCT in eligible patients is as effective as MRM with respect to local tumor control, DFS and DDFS, and may result in a better outcome than MRM in Chinese primary breast cancer patients.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Breast-conserving surgery and combined therapy for women breast cancer: a report of 216 cases

Objective： To explore the therapeutic effect and associated techniques of breast-conserving therapy on patients with clinical stage Ⅰ and stage Ⅱ breast cancer. Methods： 216 female patients with breast cancer underwent breast-conserving therapy from December 1993 to October 2004. Their data were analyzed retrospectively. The breast-conserving therapy consisted of lumpectomy or quadrant removal of the breast, postoperative radiotherapy, chemotherapy and endocrine therapy. Of them, 209 patients underwent axillary lymph node dissection. Results： There were no operative complications. 216 patients were followed-up 3 to 147 months, the medial follow-up time was 78 months. The local recurrence rate was 1.85%. Two patients died and one of them was not related with breast cancer. Presence or absence of fibrosis, shape of breast, asymmetry, pigmentation and handle were taken into consideration for cosmetic evaluation by the patients and experienced breast surgeon. Breasts were scored cosmetically as excellent and good in 199 patients, the rate of satisfactory was 92.13%. Conclusion： Breast-conserving therapy for early breast cancer is e safe end effective therapy. It has less trauma end less complications and can also raise the quality of life in the patients. But we must obey the strict indications and reasonable techniques.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Clinical significance of S100A7 protein in predicting recurrence of breast cancer in patients undergoing breast-conserving surgery with radiotherapy

Objective To investigate the relationship between the expression of S100A7 protein and prediction of recurrence and prognosis of breast cancer in patients undergoing breast-conserving surgery combined with radiotherapy.Methods 349 samples of carcinoma tissue wax blocks were selected from January 2011 to January 2014 in Qingdao Central Hospital.All the patients had undergone breast-conserving surgery.We analyzed S100A7 expression in tumor tissue by immunohistochemical staining.Using univariate and multivariate analyses,we evaluated the relationship between S100A7 and clinical results,to explore independent risk factors for local regional recurrence(LRR).Results The positive expression of S100A7 in the recurrence group(66.7%)was significantly higher than in the non-recurrence group(38.4%),P=0.025.A log-rank test showed that high S100A7 expression was significantly correlated with 5-year regional recurrence free survival rate(RFS)(94.9%vs 89.5%,P=0.0408),distant metastasis free survival rate(DFS)(95.4%vs 83.5%,P<0.001),and overall survival rate(OS)(99.0%vs 92.5%,P=0.0011).Histological grade,vessel carcinoma embolus,lymph node metastasis,S100A7 expression,and tumor size were factors that influenced RFS.Multivariate analysis of the Cox proportional hazard model showed that high S100A7 expression was an independent risk factor that affected breast cancer RFS(HR=6.864,95%CI:1.575-29.915,P=0.01).Thus,we concluded that high S100A7 expression is associated with increased risk of LRR and distant metastasis of breast cancer after breast-conserving surgery and postoperative radiotherapy.S100A7 can be used as a molecular marker to screen for patients with high recurrence risk after breast-conserving surgery.

Factors Predicting the Relapse of Radiation-Induced Organizing Pneumonia after Breast-Conserving Therapy

We investigated the factors predicting radiation-induced organizing pneumonia (RIOP) relapse after tangential breast irradiation. The participants included 23 patients diagnosed with RIOP at the St. Marianna University School of Medicine Hospital between January 2008 and March 2015. Relapse was defined as the appearance of new lesions on diagnostic images during follow-up or after commencing treatment. The relapse-free survival rate and the following 9 parameters were compared between patients with and without RIOP relapse: 1) age (less than vs. equal to or more than the median);2) white blood cell count (less than vs. equal to or more than the median);3) C-reactive protein (CRP) level at the time of RIOP diagnosis (less than normal, more than normal/ less than borderline, and more than borderline);4) boost irradiation (yes vs. no);5) maximum lung depth on linacgraphy (less than vs. equal to or more than the median);6) hormone therapy (yes vs. no);7) chemotherapy (yes vs. no);8) RIOP ratio in the whole lung (less than vs. equal to or more than the median) at the time of RIOP diagnosis;and 9) use of corticosteroids (yes vs. no). The Kaplan-Meier method was used for statistical analysis, with relapse as the cutoff. The follow-up period spanned the date of RIOP onset to May 30, 2015. The level of significance for 2-sided tests was p < 0.05. Relapse was evident in 14 patients (60.8%). The relapse-free survival rate was significantly greater in the normal CRP group (less than 0.30 mg/dl) than in the abnormal CRP group (more than 0.36 mg/dl) (p = 0.044) and in the normal/borderline CRP group (less than 0.36 mg/dl) than in the high CRP group (more than 0.70 mg/dl) (p < 0.01). The CRP level at RIOP onset may be a useful predictor of relapse after breast-conserving therapy.We investigated the factors predicting radiation-induced organizing pneumonia (RIOP) relapse after tangential breast irradiation. The participants included 23 patients diagnosed with RIOP at the St. Marianna University School of Medicine Hospital between January 2008 and March 2015. Relapse was defined as the appearance of new lesions on diagnostic images during follow-up or after commencing treatment. The relapse-free survival rate and the following 9 parameters were compared between patients with and without RIOP relapse: 1) age (less than vs. equal to or more than the median);2) white blood cell count (less than vs. equal to or more than the median);3) C-reactive protein (CRP) level at the time of RIOP diagnosis (less than normal, more than normal/ less than borderline, and more than borderline);4) boost irradiation (yes vs. no);5) maximum lung depth on linacgraphy (less than vs. equal to or more than the median);6) hormone therapy (yes vs. no);7) chemotherapy (yes vs. no);8) RIOP ratio in the whole lung (less than vs. equal to or more than the median) at the time of RIOP diagnosis;and 9) use of corticosteroids (yes vs. no). The Kaplan-Meier method was used for statistical analysis, with relapse as the cutoff. The follow-up period spanned the date of RIOP onset to May 30, 2015. The level of significance for 2-sided tests was p < 0.05. Relapse was evident in 14 patients (60.8%). The relapse-free survival rate was significantly greater in the normal CRP group (less than 0.30 mg/dl) than in the abnormal CRP group (more than 0.36 mg/dl) (p = 0.044) and in the normal/borderline CRP group (less than 0.36 mg/dl) than in the high CRP group (more than 0.70 mg/dl) (p < 0.01). The CRP level at RIOP onset may be a useful predictor of relapse after breast-conserving therapy.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis:A network meta-analysis

BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Interleukins in liver disease treatment

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Hydrothermal treatment of pearl millet grains:Effects on nutritional composition,antinutrients and flour properties

Pearl millet(Pennisetum glaucum)is one of the major millets with high nutritional properties.This crop exhibits exceptional resilience to drought and high temperatures.However,the processing of pearl millet poses a significant challenge due to its high lipid content,enzyme activity,and presence of antinutrients.Consequently,it becomes imperative to enhance the quality and prolong the shelf life of pearl millet flour by employing suitable technologies.Hydrothermal treatment in the food industry has long been seen as promising due to its potential to reduce microbial load,inactivate enzymes,and improve nutrient retention.This study aims to investigate the effects of hydrothermal treatment on the quality characteristics of pearl millet.The independent variables of the study were soaking temperature(35,45,55℃),soaking time(2,3,4 h),and steaming time(5,10,15 min).Treatment conditions had a statistically significant effect on nutrient retention.Major antinutrients like tannins and phytates were reduced by 0.99% to 5.94% and 0.36% to 6.00%,respectively,after the treatment.Lipase activity decreased significantly up to 10% with the treatment conditions.The findings of this study could potentially encourage the use of pearl millet flour in the production of various food items and promote the application of hydrothermal treatment in the field of food processing.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.