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).

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

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.

Current status of drug therapy for chronic hepatitis B

In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

Professor Chen Xianhai's experience of herb pairs in the treatment of pulmonary diseases

According to the theory of traditional Chinese medicine,based on the four properties and five flavors of traditional Chinese medicines,the lifting and lowering theory and channel tropism,Professor Chen combined with the theory of traditional Chinese medicine and constitution identification to prescribe for patients and used herb pairs to treat many kinds of pulmonary diseases.And he has achieved good clinical effect by"treatment methods selection according to syndromes".His experience in medication and compatibility mechanism are worthy of further exploration and promotion by scholars.

Study on the mechanism of“Salvia chinensis and Radix Ranunculi Ternati”drug pair in the treatment of lung cancer

Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.

Network pharmacology study of drug pair Tubeimu-Zhebeimu in the treatment of breast cancer

Objective:Breast cancer is a malignant tumor endangering women’s safety and health.Clinical medication experience and related studies show that the drug pairs Tubeimu-Zhebeimu has an excellent therapeutic effect on patients with breast cancer,but its treatment mechanism is unclear.In this study,network pharmacology and molecular docking were used to analyze and explore the mechanism of“Tubeimu-Zhebeimu”in treating breast cancer.Methods:Traditional Chinese Medicine Database and Analysis Platform were used to retrieve the chemical constituents of Tubeimu and Zhebeimu,and the relevant targets were predicted through the Swiss Target Prediction Database.Searching the Gene cards,Therapeutic Target Database and Disgenet Database with the keywords“breast cancer”,“mammary cancer”and“mammary adenocarcinoma”obtain disease-related targets.We intersect the disease target with the drug target to obtain the potential drug therapy target.Then the data was imported into Cytoscape 3.9.1 software to construct a compound network of“Disease-Target-Component-Drug”,and the network.Subsequently,using the String Database a“protein-protein interaction network”was constructed and imported into Cytoscape 3.9.1 software for structural optimization and network topology analysis.DAVID was used for Gene Ontolog function enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses,and the results were visualized.The core targets were molecularly docked through AutoDockTools-1.5.6 software and Auto Dock Vina 1.1.2 software.Results:The results showed that the 20 active ingredients in the“Tubeimu-Zhebeimu”includingβ-sitosterol,Chaksine,saponins,and peimuocinine,can treat breast cancer through 139 potential targets including AKT1,AR,TP53,ESR1.Conclusion:The specific mechanism of the drug pairs Tubeimu-Zhebeimu treating breast cancer may be controlling human hormone levels,inducing cell apoptosis,and participating in the P53 protein signaling pathway and PI3K/Akt/mTOR signaling pathway.

The Assessment of the Clinical Effect of the Drug Compatibility and Course of Treatment to the Brucellar Spondylitis

Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.

Drug treatment of functional dyspepsia

Symptomatic improvement of patients with functional dyspepsia after drug therapy is often incomplete and obtained in not more than 60% of patients. This is likely because functional dyspepsia is a heterogeneous disease. Although great advance has been achieved with the consensus definitions of the Rome I and II criteria, there are still some aspects about the definition of functional dyspepsia that require clarification. The Rome criteria explicitly recognise that epigastric pain or discomfort must be the predominant complaint in patients labelled as suffering from functional dyspepsia. However, this strict definition can create problems in the daily primary care clinical practice, where the patient with functional dyspepsia presents with multiple symptoms. Before starting drug therapy it is recommended to provide the patient with an explanation of the disease process and reassurance. A thorough physical examination and judicious use of laboratory data and endoscopy are also indicated. In general, the approach to treat patients with functional dyspepsia based on their main symptom is practical and effective. Generally, patients should be treated with acid suppressive therapy using proton-pump inhibitors if the predominant symptoms are epigastric pain or gastroesophageal reflux symptoms. Although the role of Helicobacter pylori （H pylon） in functional dyspepsia continues to be a matter of debate, recent data indicate that there is modest but clear benefit of eradication of H pylori in patients with functional dyspepsia. In addition, H pylori is a gastric carcinogen and if found it should be eliminated. Although there are no specific diets for patients with FD, it may be helpful to guide the patients on healthy exercise and eating habits.

Drug treatment of male fertility disorders

Drug treatment remains an active domain in the therapy of male fertility disorders. Although there are only a fewconditions that allow causal treatment, rational approaches are possible in many cases. Best results are obtained in casesrequiring an anti-inflammatory treatment and in patients with an impaired sperm transport. High-dosage administrationof FSH is a promising new development, aimed particularly at improving the disturbed sperm structures. A careful di-agnostic work-up with elucidation of the underlying disease is essential to achieve a successful therapy.

Reliability and Validity of Addiction Severity Index in Drug Users with Methadone Maintenance Treatment in Guizhou Province, China

Objective To evaluate the reliability and validity of the Chinese version of addiction severity index （ASI）-5th version （ASI-C-5）, in illegal drug users receiving methadone maintenance treatment （MMT） in China. Methods One hundred and eighty-six heroin addicts （144 men and 42 women） receivihg MMT at three clinics in Guizhou province, southwest China, were recmited. They were all interviewed with a questionnaire of ASI-C-5 and 35 were re-interviewed at an interval of seven days to assess its test-retest reliability. Results Cronbach＇s alpha for internal consistency of CSs varied from 0.60 to 0.81 in all domains. Test-retest reliability of composite scores （CSs） of ASI-C-5 were satisfactory （r=0.38-0.97）. Based on item analysis and expert＇s suggestions, five items were deleted and one item was modified in ASI-C-5. Criterion validity of ASI-C-5 was found acceptable, as compared to addicts＇ self-rating anxiety scale （SAS） and self-rating depression scale （SDS） （r=0.59 and 0.45） except for social support rating scale （SSRS）. Conclusions ASI-C-5 can be used for heroin addicts receiving MMT with acceptable reliability and validity.

Chemical component analysis of volatile oil in drug pair Herba Ephedrae-Ramulus Cinnamomi by GC-MS and CRM

Active volatile components in drug pair(DP)Herba Ephedrae-Ramulus Cinnamomi(HE-RC),single drug HE and RC were analyzed by gas chromatography/mass spectrometry(GC/MS),chemometric resolution method(CRM)and overall volume integration.By means of CRM,the two-dimensional data obtained from GC-MS instruments were resolved into a pure chromatogram and a mass spectrum of each chemical compound.In total,97,62,and 78 volatile chemical components in volatile oil of HE,RC,and DP HE-RC,were respectively determined qualitatively and quantitatively,accounting for 90.08%,91.62%,and 89.76% total contents of volatile oil of HE,RC,and DP HE-RC respectively.It is further demonstrated that the numbers of volatile components of DP HE-RC are almost the sum of those of two single drugs,but some relative contents of them are changed.Some new components,such as 1,6-dimethylhepta-1,3,5-triene,tetracyclo[4.2.1.1(2,5).0(9,10)]deca-3,7-diene,globulol and(E,E)-6,10,14-trimethyl-5,9,13-pentadecatrien-2-one are found in DP HE-RC because of chemical reactions and physical changes during decoction.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.

Nose-to-brain drug delivery approach：a key to easily accessing the brain for the treatment of Alzheimer＇s disease

Alzheimer＇s disease（AD）：AD,a neurodegenerative disorder and a significant cause of dementia throughout the world mostly affects the older adults but sometimes also seen in young age（early state AD）（Agrawal et al.,2017）.

Incidence of Interpersonal Violence among Individuals with Drug Addiction Receiving Compulsory Treatment: A Survey at Two Drug Detention Centers in Hunan, China

Drug dependence is a serious global health problem.To assist individuals with drug addiction,China alone has established 678 Compulsory Detoxification Detention Centers （CDDCs） that treat over300,000i ndividuals who are required by national law to receive compulsory treatment;because community-based outpatient treatment failed.

Treatment of Functional Retrograde Ejaculation with Acupuncture and TCM Herbal Drugs

Acupuncture at the Taichong (LR 3), Sanyinjiao (SP 6) and Ciliao (BL 32) points combined with TCM drugs for soothing the liver, replenishing the kidney, freeing the seminal passage, and eliminating the stasis showed effective for functional retrograde ejaculation in 25 cases. The total effective rate of 68.0% was significantly better than imipramine used in the control group (P<0.05).

CLINICAL OBSERVATION ON THE TREATMENT OF APOPLEXY BY ACUPUNCTURE COMBINED WITH DRUGS

Apoplexy involves cerebrovascular accident, such as cerebral hemorrhage, cerebralthrombosis, cerebral infarction, subarachaoid hemorrhage, etc. and its sequelae in modern medicine. The author treated 81 cases of apoplexy using acupuncture combined with drugs. AIn0ng them, 36cases were male, accounting for 44%; 45 cases female, accounting for 56 %. The oldest was 82 yearsold, and youngest 28 years old. The shortest course of disease was one day, and the longest over 3years The treatment results show that 60 cases were cured, accounting for 74. 07%; 16 casesmarkedly effect, acc0unting for 19. 75 %; 3 cases improved, accounting for 3. 7 %; 2 cases ineffective,accounting for 2. 48 %. The total effect rate was 97. 52 %.

Natural Tubular Halloysite as Drug Carrier: Effect of Organosilane Modification and Thermal Treatment

Naturally occurring tubular halloysite is a potential drug carrier because of the significant deposit, unique mesoscopic (2-50 nm) or even macroscopic (>50 nm) lumen, and excellent biocompatibility. The drugs loaded on halloysite exhibited slow release under the diffusion limitation by the halloysite nanotube. However, due to the weak interaction between halloysite and guest, the loading capacity of halloysite was relatively low. This drawback severely limits the application of halloysite as carrier in pharmaceutics. In this study, the performance of halloysite as carrier for ibuprofen (IBU) loading was investigated for the first time. The effects of 3-aminopropyltriethoxysilane (APTES) modification and thermal treatment of halloysite on the loading and release of IBU were also studied. The purified halloysites were heated at 120 ℃ and 400 ℃ (labeled as Hal/120 and Hal/400), and then modified with APTES (labeled as Hal/120-A and Hal/400-A). The loading of IBU was achieved by soaking method (labeled as IBU-Hal/120, IBU-Hal/400, IBU-Hal/120-A, and IBU-Hal/400-A.). The in vitro drug delivery assays were performed in phosphate buffer solution. IBU was loaded mainly into the lumen and partially on the external surface of halloysite. The order of IBU contents was as follows: IBU-Hal/400-A (14.8wt%) > IBU-Hal/120-A (12.7wt%) > IBU-Hal/400 (11.8wt%) > IBU-Hal/120 (11.7wt%). The IBU was initially anchored to the surface hydroxyl groups of halloysite by hydrogen bonding, followed by further bonding of IBU with the anchored IBU to form hydrogen-bonded aggregates. The APTES modification of halloysite promoted the loading of IBU by introducing a strong affinity through electrostatic attraction between the introduced aminopropyl groups of APTES and the carboxyl groups of IBU. Thermal treatment at 400°C did not destroy the tubular morphology or the crystal structure of halloysite and had little effect on IBU loading in unmodified halloysite. However, thermal treatment by reducing water content in halloysite restricted the grafting of APTES in the lumen space, and further increased IBU loading. All IBU-loaded samples exhibit a burst release with a following slow release. However, owing to the strong electrostatic attraction in modified samples, the burst release was much more suppressed and the release rate was also lower than that in unmodified ones. The in vitro release profiles of the IBU-loaded samples were well fitted with the modified Korsmeyer-Peppas model. The IBU release mechanism of the unmodified samples was Fickian diffusion; however it was non-Fickian diffusion for the modified samples. The findings are of significance for broadening the use of halloysite as carrier for drugs and other active molecules in the pharmaceutical, pesticides, and coating industries.

Work as An Effective Intervention Strategy and Rehabilitation Treatment Program for People Who Abuse Drugs And Alcohol

Despite years of interventions in the United States, substance abuse continues to be a major national problem in our society. For individuals affected, it can constitute a major disability and a decrease in quality of life. Current American societal expectations are that individuals who identify!they are involved in substance abuse will go to treatment, eventually recover, get off public assistance straightaway, and return to work. Most rehabilitation professionals also maintain the same expectations. The reality is that efforts of prevention do not appear to diminish the number of people with substance abuse. Traditional treatment appears to have minimal, if any, influence upon the cessation of substance abuse, and traditional vocational rehabilitation practices appear unsuited for the unique problems and types of symptoms experienced by substance abusers. Creative, yet sound, alternatives that combine effective treatment strategies and non-traditional vocational rehabilitation methods need to be exqlored and tested for effectiveness, and applied.