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.

A Biochemical Study on Combined Treatment of Experimental Silicosis with Tetradrine-PVNO and Tetradrine-QOHP in Rats

A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monoamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats

Biochemical changes in grape rootstocks resulted from humic acid treatments in relation to nematode infection

Objective:To investigate the effect of humic acid on nematode infected,resistant and susceptible grapes in relation to lipid peroxidation and antioxidant mechanisms on selected biochemical parameters known as proactive substances.Methods:The grape rootstocks,superior,superior/ freedom and freedom were reacted differently to Meloidogyne incognita and Rotylenchulus reniformis according to rootstock progenitor.Two weeks after inoculation,two commercial products of humic acid were applied at the rate of(2,4 mL or grams/plant) as soil drench.After 4 months,nematode soil populations were extracted and counted.A subsample of roots from each plant was stained and gall numbers,embedded stages per root were calculated,final population, nematode build up(Pf/Pi),average of eggs/eggmass were estimated.Subsamples of fresh root of each treatment were chemically analyzed.Results:Freedom reduced significantly the nematode criteria and build up.Humic acid granules appeared to be more suppressive to nematode build up on superior and the higher dose on superior/freedom than liquid treatments.On freedom,all treatments reduced significantly the nematode build up regardless to the material nature.The higher dose was more effective than the lower one.As a result of humic acid applications,the malondialdehyde(MDA) and H_2O_2 contents were significandy reduced after humic acid treatments while the antioxidant compounds glutathione(GSH),ascorbic acid(ASA) and total phenol contents were significandy increased when compared with check.Antioxidant defense enzymes ascorbate peroxidase(AFX),superoxide dismutase(SOD),catalase(CAT) and polyphenol oxidase(PPO) showed significant increase in their specific activities in treated plants compared with nematode treated check.Conclnsions:Humic acid treatments improve we yield of grape by increasing the contents of antioxidant compounds and the specific activities of antioxidant enzymes.

Changes in biochemical constituents and induction of early sprouting by triadimefon treatment in white yam(Dioscorea rotundata Poir.) tubers during storage

The ability of triadimefon （TDM）, a triazolic fungicide, to alter the biochemical constituents and thereby minimizing the days required for sprouting in white yam （Dioscorea rotundata Poir.） tubers during storage under （30±2） ℃ in the dark, was studied. TDM at 20 mg/L was given to tubers by dipping the tubers in treatment solution containing 20 mg/L TDM on 10, 25 and 40 d after storage （DAS）. Starch, sugars, protein, amino acid contents as well as protease and a-amylase activities were estimated on 15, 30 and 45 DAS from two physiological regions viz., apical and basal regions of the tubers. In normal conditions （control） sprouting occurred on 70 to 80 DAS. The starch content decreased, while protein, amino acid, sugar contents and protease and a-amylase activities were increased due to TDM treatment and led to early sprouting.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes.Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)cells.However,the role of autophagy in GI diseases remains controversial.This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

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.

Changes of biochemical indexes in patients with acute cerebral infarction after treatment with simvastatin

BACKGROUND: At present, it is believed that the important causes of cerebral infarction are the disorders of lipid metabolism and endothelial function, and the outcomes of clinical treatment can be improved by regulating serum lipids and antiinflammation, etc. OBJECTIVE: To observe the effect of simvastatin, inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on the levels of serum lipids, serum enzymic indexes and inflammatory metabolic indexes in patients with cerebral infarction. DESIGN: A comparative observation. SETTING: Department of Geriatrics, Longquanshan Hospital of Liuzhou City. PARTICIPANTS: Forty-eight patients with acute cerebral infarction were selected from the Department of Geriatrics of Longquanshan Hospital of Liuzhou from March 2004 to February 2006, including 24 males and 24 females, the mean age was (54±12) years, average disease course was (10.0±4.5) days. They were all accorded with the diagnostic standard for cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1999, and cerebral hemorrhage was excluded by cranial CT scanning. The 48 patients were randomly divided into control group (n =24) and treatment group (n =24). Informed consents were obtained from all the participants. METHODS: ① All the patients were treated according to the symptoms, besides those in the treatment group were given simvastatin (Harbin Pharm. Group Sanjing Pharmaceutical Shareholding, Co.,Ltd., No. H20010454; Batch number: 20040218; 5 mg/tablet). The initial dosage was 10 mg per day for 4 weeks, and then increased to 30 mg per day for another 4 weeks. ② Before treatment and within 1 week after treatment, the total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), creatine kinase and C reactive protein in serum were determined with Beckman-cx7 automatic biochemical analytical apparatus in both groups. ③ The differences of intergroup and intragroup data were compared with the independent-samples t test and paired samples t test. MAIN OUTCOME MEASURES: Changes of total cholesterol, triglyceride, HDL-C, LDL-C, AST, creatine kinase and C reactive protein before and treatment in both groups. RESULTS: All the 48 patients with cerebral infarction were involved in the analysis of results. ① Changes of serum lipids: The levels of serum lipids were close between the two groups before treatment (P > 0.05). After treatment, the HDL-C level in the treatment group was obviously higher than that in the control group and that before treatment [(1.34±0.12), (0.92±0.33), (0.93±0.21) mmol/L, t =7.922, 11.699, P < 0.01], and the levels of total cholesterol, triglyceride and LDL-C were obviously lower than those in the control group and those before treatment (t =2.780-7.591, P < 0.01). ② Changes of serum enzymic indexes and C reactive protein in serum: The levels of enzymes and C reactive protein in serum had no obvious differences between the two groups before treatment (P > 0.05). The levels of AST, creatine kinase and C reactive protein in serum after treatment were obviously lower than those before treatment in both groups (t =7.259-17.996, P < 0.01). The levels of levels of creatine kinase and C reactive protein in serum after treatment in the treatment group were obviously lower than those in the control group [(3.061±0.522) μkat/L, (4.6±3.1) mg/L; (4.348±0.580) μkat/L, (12.3±4.8) mg/L, t =7.910, 6.463, P < 0.01]. CONCLUSION: Compared with common treatment according to symptoms, the additional administration of simvastatin is better for improving the serum lipids, serum enzymic indexes of patients with cerebral infarction at acute period, and benefit for repairing their inflammatory damages.

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.

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.

Genetics of biochemical attributes regulating morpho-physiology of upland cotton under high temperature conditions

Background Cotton is a strategically important fibre crop for global textile industry.It profoundly impacts several countries’industrial and agricultural sectors.Sustainable cotton production is continuously threatened by the unpre-dictable changes in climate,specifically high temperatures.Breeding heat-tolerant,high-yielding cotton cultivars with wide adaptability to be grown in the regions with rising temperatures is one of the primary objectives of modern cotton breeding programmes.Therefore,the main objective of the current study is to figure out the effective breed-ing approach to imparting heat tolerance as well as the judicious utilization of commercially significant and stress-tolerant attributes in cotton breeding.Initially,the two most notable heat-susceptible(FH-115 and NIAB Kiran)and tolerant(IUB-13 and GH-Mubarak)cotton cultivars were spotted to develop filial and backcross populations to accom-plish the preceding study objectives.The heat tolerant cultivars were screened on the basis of various morphological(seed cotton yield per plant,ginning turnout percentage),physiological(pollen viability,cell membrane thermostabil-ity)and biochemical(peroxidase activity,proline content,hydrogen peroxide content)parameters.Results The results clearly exhibited that heat stress consequently had a detrimental impact on every studied plant trait,as revealed by the ability of crossing and their backcross populations to tolerate high temperatures.However,when considering overall yield,biochemical,and physiological traits,the IUB-13×FH-115 cross went over particularly well at both normal and high temperature conditions.Moreover,overall seed cotton yield per plant exhibited a posi-tive correlation with both pollen viability and antioxidant levels(POD activity and proline content).Conclusions Selection from segregation population and criteria involving pollen viability and antioxidant levels concluded to be an effective strategy for the screening of heat-tolerant cotton germplasms.Therefore,understanding acquired from this study can assist breeders identifying traits that should be prioritized in order to develop climate resilient cotton cultivars.

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.

Biochemical Mechanism of the Eutrophication and Its Prevention — the Deep Treatment of Waste Water and Its Denitrification and Dephosphorization

Biochemical mechanism of forming the red tide is discussed in this paper. The existence of a large number of nitrates and phosphates in the eutrophic water is the prerequisite of explosive increase of algae and the forming of red tide. Reduction of eutrophication is an important approach to preventing the red tide. The method of deep treatment of the waste water and its denitrification and dephosphorization are introduced, and a new opinion on the red tide formation and fundamental prevention is put forward.

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.