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Transcranial magnetic stimulation (TMS) is a popular modulatory technique for the noninvasive diagnosis and therapy of neurological and psychiatric diseases. Unfortunately, current modulation strategies are only modestly effective. The literature provides strong evidence that the modulatory effects of TMS vary depending on device components and stimulation protocols. These differential effects are important when designing precise modulatory strategies for clinical or research applications. Developments in TMS have been accompanied by advances in combining TMS with neuroimaging techniques, including electroencephalography, functional near-infrared spectroscopy, functional magnetic resonance imaging, and positron emission tomography. Such studies appear particularly promising as they may not only allow us to probe affected brain areas during TMS but also seem to predict underlying research directions that may enable us to precisely target and remodel impaired cortices or circuits. However, few precise modulation strategies are available, and the long-term safety and efficacy of these strategies need to be confirmed. Here, we review the literature on possible technologies for precise modulation to highlight progress along with limitations with the goal of suggesting future directions for this field.
ABSTRACT
Transcranial magnetic stimulation (TMS) is a popular modulatory technique for the noninvasive diagnosis and therapy of neurological and psychiatric diseases. Unfortunately, current modulation strategies are only modestly effective. The literature provides strong evidence that the modulatory effects of TMS vary depending on device components and stimulation protocols. These differential effects are important when designing precise modulatory strategies for clinical or research applications. Developments in TMS have been accompanied by advances in combining TMS with neuroimaging techniques, including electroencephalography, functional near-infrared spectroscopy, functional magnetic resonance imaging, and positron emission tomography. Such studies appear particularly promising as they may not only allow us to probe affected brain areas during TMS but also seem to predict underlying research directions that may enable us to precisely target and remodel impaired cortices or circuits. However, few precise modulation strategies are available, and the long-term safety and efficacy of these strategies need to be confirmed. Here, we review the literature on possible technologies for precise modulation to highlight progress along with limitations with the goal of suggesting future directions for this field.
Subject(s)
Brain/diagnostic imaging , Electroencephalography , Magnetic Resonance Imaging , Neuroimaging , Transcranial Magnetic StimulationABSTRACT
Cardiovascular disease (CVD), a chronic disease endangering human health, remains the highest morbidity and mortality globally. The human gut is inhabited by communities of bacteria and viruses, along with their genome, are collectively known as the gut microbiota. Recent reserch suggests that gut microbiota affects various metabolic pathways in the host by producing and releasing important metabolites such as trimethylamine oxide, bile acids and short chain fatty acids, and play an important role in pathologies of CVD, such as atherosclerosis, hypertension, myocardial infarction, heart failure and dyslipidemia. Individual treatment based on gut microbiota, including diet intervention, fecal microbiota transplantation and small molecule antimicrobial enzyme therapeutics, may provide a potential novel strategy for therapeutics.
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Valproic acid is a commonly used and broad-spectrum antiepileptic drug in clinical practice with a narrow therapeutic window. Valproic acid has a great individual difference in its metabolism which is influenced by many factors. The gene polymorphism of drug metabolic enzymes is one of the critical factors. Through consulting relevant articles, the affection of genomics and clinical treatment on valproic acid clinical application were reviewed in this paper, which provided a reference for clinical individualized treatment.
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Objective@#This project aimed to explore the effectiveness of estimating individual treatment effect on real data, among the heterogeneous population, with Causal Forests (CF) method, to find out the characteristics of heterogeneous population.@*Methods@#We designed and conducted four computer simulation schemes to verify the effect of estimating on individual treatment, using the CF under four different environments of the treatment effects. Real data was then analyzed for the catheterization on right heart.@*Results@#Results from the simulation process showed that the values on individual treatment effect that were estimated by causal forests were consistent with the population effect as well as in line with the expected distribution under the setting of four different effect values. Results of real data analysis showed that values of individual treatment effect among most patients appeared positive, so the use of RHC could cause an increase of the '180-day mortality rate’ in the sampled population. Patients with lower predicted probability of 2-mo survival and albumin were more likely to have a lower risk of death after using the RHC.@*Conclusion@#CF method could be effectively used to estimate the individual treatment effect and helping the individuals to make decision on the receipt of treatment.
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Objective To analyze the current drug treatment against clonorchiasis in China, in order to promote the standardization of drug treatment and national deworming for clonorchiasis. Methods All the 10 provinces were enrolled, which reported clonorchiasis in the work report for important helminthiasis in 2016. Then, 20 counties were selected from these 10 provinces. The data on drug treatment including both mass chemotherapy and individual treatment against clonorchiasis were collected and compared. Results All the 10 provinces had no guideline for mass chemotherapy, while only 3 had that for individual treatment against clonorchiasis. Out of 20 counties, only 1 implemented mass chemotherapy. Among these 20 counties, 13 applied praziquantel in individual treatment, while other 7 employed albendazole. In the 12 counties with clear protocol for praziquantel, the total dosage for a man of 60 kg ranged from 3.6 to 18.0 g, the days and times for administration ranged from 1 to 6 and from 3 to 18, respectively. In the 4 counties with clear protocol for albendazole, the total dosage for a man of 60 kg ranged from 0.8 to 8.4 g, the days and times for administration ranged from 2 to 7 and from 2 to 14, respectively. Conclusions Nowadays, the guideline on mass chemotherapy for clonorchiasis is inadequate in China. Although individual treatment is applied in many areas, the protocols vary in drugs, dosage, and days and times for treatment. Thus, the national guideline of mass chemotherapy for clonorchiasis should be established, while the protocols for individual treatment should be standardized.
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Objective To analyze the current drug treatment against clonorchiasis in China, in order to promote the standardization of drug treatment and national deworming for clonorchiasis. Methods All the 10 provinces were enrolled, which reported clonorchiasis in the work report for important helminthiasis in 2016. Then, 20 counties were selected from these 10 provinces. The data on drug treatment including both mass chemotherapy and individual treatment against clonorchiasis were collected and compared. Results All the 10 provinces had no guideline for mass chemotherapy, while only 3 had that for individual treatment against clonorchiasis. Out of 20 counties, only 1 implemented mass chemotherapy. Among these 20 counties, 13 applied praziquantel in individual treatment, while other 7 employed albendazole. In the 12 counties with clear protocol for praziquantel, the total dosage for a man of 60 kg ranged from 3.6 to 18.0 g, the days and times for administration ranged from 1 to 6 and from 3 to 18, respectively. In the 4 counties with clear protocol for albendazole, the total dosage for a man of 60 kg ranged from 0.8 to 8.4 g, the days and times for administration ranged from 2 to 7 and from 2 to 14, respectively. Conclusions Nowadays, the guideline on mass chemotherapy for clonorchiasis is inadequate in China. Although individual treatment is applied in many areas, the protocols vary in drugs, dosage, and days and times for treatment. Thus, the national guideline of mass chemotherapy for clonorchiasis should be established, while the protocols for individual treatment should be standardized.
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Objective To dynamically monitor the changes of peripheral blood lymphocyte subsets of renal transplant recipients and investigate the relationship between lymphocyte subsets with infection and rejection.Methods The clinical data of allogenic kidney transplantation recipients and living relative donors in the Department of Kidney Transplantation of the First Affiliated Hospital of Zhengzhou University were prospectively collected from June 2015 to December 2016.The data of lymphocyte subsets and other related indexes were obtained from renal transplant recipients and relatives of the same period.Results Sixty-four cases of living-relative donors and 351 cases of renal transplant recipients were enrolled in this study,and the recipients were divided into 3 groups:infection group (67 cases),acute rejection group (46 cases),and stable group (238 cases),according to the diagnostic criteria.There was significant difference in the concentration distribution of lymphocytes between the stable group and the control group (P<0.05).The stable frequency distribution range of the stable group was as follows (cells/μL):Lym (1 000-1 500),T (<1 500),CD4+ (<1 000),CD8+ (<1 000),B (<300),NK (100-300),CD4+/CD8+ (0.5-1.0).The number of Lym,T,CD4+,CD8+,NK and B cells in the preoperative patients was less than that in the healthy population (P<0.05);The number of Lym,T,CD4+, CD8+,B and NK cells was gradually decreased in the postoperative infection group,which was less than that in the stable group (P<0.05).After treatment the indicators gradually restored to the level in the stable group level;the number of T,CD4+,CD8+,B cells was highly correlated with infection.The number of T and CD4+ cells,and CD4+/CD8+ ratio were significantly increased in acute rejection group as compared with the stable group,and gradually decreased after the rejection was reversed.The number of T,CD4+,CD8+ cells was highly correlated with rejection.Lymphocyte subsets had a predictive effect on infection and rejection of recipients,and CD4+ cell count and CD4+/CD8+ ratio were independent risk factors.Conclusion The monitoring of lymphocyte subsets has an important clinical value in the evaluation of immune status and individual treatment of renal recipients.
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Liver failure is characterized by hepatic encephalopathy, jaundice, hypo-coagulation and high mortality.Artificial liver support aims to temporarily replace hepatic function until liver function recover or bridge to liver transplantation.Individualized artificial liver support should be balanced and cover the following aspects: removing albumin bound toxins and/or water soluble toxins, eliminating inflammatory mediators and correcting blood coagulation disorders, in order to support metabolism and modulate immune function and to promote the regeneration of hepatocyte and reverse multiple organ failure that may lead to death of patients.Traditional non-biological artificial liver support can't meet individualized treatment.Recently developed hybrid blood purification model, such as albumin dialysis, fractionated plasma separation and adsorption (Prometheus system) and plasma diafiltration (PDF) have provided more and better choices for individualized artificial liver support.Based on the characteristics of pathophysiology and organ dysfunction of liver failure, the author has designed an alignment diagram of individualized artificial liver support for clinical selection.
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Cancer is a group of heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes .Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies .Patient-derived xenografts ( PDX) models are generated by implanting sectioned patient tumor fragments into immunodeficient mice .PDX models retain many of the key characteristics of patients ' tumors including histology , genomic signature , cellular heterogeneity , and drug responsiveness .These models cannot only serve as a platform for co-clinical trials by enabling the integration of clinical data , genomic profiles , and drug responsiveness data to determine precisely targeted therapies , but also be applied to the development of biomarkers for drug responsiveness and personalized drug selection .This review summarizes our current knowledge of this field , including methodologic aspects , applications in drug development , challenges and limitations , and utilization for precision cancer medicine .
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Objective To investigate the application value of clinical typing in the treatment of BuddChiari syndrome (BCS).Methods The retrospective corss-sectional study was adopted.The clinical data of 95 patients with BCS who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to September 2015 were collected.Based on patients' compensation and clinical symptoms,3 clinical typing and 8 subtypes of BCS were proposed,and each subtype was treated with corresponding strategies.Observation indices included (1) the clinical typing of BCS,(2) selection of treatment,(3) treatment effect,(4) follow-up situations.Follow-up using telephone interview and outpatient examination was performed once within 3 months after the first treatment and then once every 6 months up to December 2015 or death,loss to follow-up and experienced decompensation.During follow-up,color Doppler ultrasound and blood bio-chemistry test were performed regularly,and CT angiography was also conducted when necessary.Count data were presented as the case or percentage.The survival rate was calculated using Kaplan-Meier method and the survival curve was drawn.Results (1) BCS clinical typing of 95 patients:4 were detected in type Ⅰ (3 in type Ⅰ a and 1 in type Ⅰ b),7 in typeⅡ (4 in type Ⅱa and 3 in type Ⅱb),and 84 in type Ⅲ(43 in type Ⅲa,4 in type Ⅲb,32 in type Ⅲc,and 5 in type Ⅲd).(2) Selection of treatment in 95 patients:① among the 3 patients with type Ⅰ a,2 of them received inferior vena cava balloon angioplasty while 1 patient had to give up the operation due to failure in opening the occlusion.This patient underwent close observation and follow-up afterwards.② The patient with type Ⅰ b underwent cavity-antrum artificial blood vessel bypass operation due to failure in opening the occlusion.③Among the 4 patients with type Ⅱ a,one of them underwent hepatic vein balloon angioplasty.The other 3 patients underwent close observation and follow-up because of failure in intervention therapy,such as segmental occlusion of hepatic vein or difficulty in finding the hepatic vein.④ Among the 3 patients with type Ⅱ b,due to the history of upper gastrointestinal bleeding,2 patients received modified spleen-lung fixation and intestine-cavity blood vessels bypass,respectively,and 1 patient received intestine-cavity artificial blood vessels bypass due to severe peritoneal effusion.⑤ Among the 43 patients with type Ⅲ a,35 patients underwent inferior vena cava balloon angioplasty due to failure in hepatic vein intervention therapy (6 of them received firstly thrombolysis treatment due to combined thrombosis.Four patients received inferior vena cava and hepatic vein balloon angioplasties.Another 4 patients received close observation and follow-up due to failure in both inferior vena cava and hepatic vein intervention therapy.⑥Among the 4 patients with type Ⅲ b,2 underwent inferior vena cava balloon angioplasty and intestine-cavity artificial blood vessel bypass.The other 2 patients only received modified spleen-lung fixation because of failure in inferior vena cava intervention therapy.⑦ Among the 32 patients with type Ⅲ c,3 underwent inferior vena cava and hepatic vein balloon angioplasties,and 27 patients underwent only inferior vena cava balloon angioplasty due to failure in hepatic vein intervention therapy (7 of them received balloon angioplasty following thrombolysis treatment due to combined thrombosis).On account of failure in both inferior vena cava and hepatic vein intervention therapy,2 patients underwent resection of lesion membranes and cavity-antrum artificial blood vessel bypass,respectively.⑧ Among the 5 patients with type Ⅲ d,1 underwent inferior vena cava balloon angioplasty and intestine-cavity artificial blood vessel bypass,and 4 underwent only modified spleen-lung fixation due to failure ininferior vena cava intervention therapy.(3) Treatment efficacy:of 95 patients,8 received followup observation,and 87 patients recovered to varied extent after interventional therapies and operations,with symptomatic relief of leg edema,ulcer,peritoneal effusion and esophageal varicosity.Eighty-seven patients went through the perioperative period safely,and no death occurred.The incidence of postoperative complications was 10.3％ (9/87).The complications mainly include venous thrombosis in lower limbs during catheter-directed thrombolysis therapy,pleural effusion,pneumatosis,and peritoneal effusion after surgery,all of which were cured after symptomatic treatment.(4) Follow-up results:87 were followed up for 3-42 months with an average time of 19 months.During the follow-up,5 patients (1 in type Ⅰ a and 4 in type Ⅲa) received recanalization surgery because of the reocclusion after the inferior vena cava balloon angioplasty,and no decompensation occurred.However,decompensation was found in 11 patients (disease progression in 4 patients and symptom relapse in 7 patients).The survival rates of patients without decompensation at 0.5,1.0,2.0 and 3.0 years after the first treatment were 96.5％,95.0％,83.4％ and 80.5％,respectively.Conclusion According to patients' compensation and clinical symptoms,clinical typing of BCS and treatment strategiesis are determined,and it will provide a satisfactory clinical efficacy.
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Valproate is commonly used as a first-line broad-spectrum anti-epileptic drug. Valproate has a narrow therapeutic window, its metabolism is affected by many factors, and it has great individual differences, which makes individualized drug dosage regime needed for valproate. Population pharmacokinetics: is a population analytical method developed in recent years. This paper reviewed the in viva metabolic process and the population pharmacokinetics of valproate in recent years, and analyzed the factors that may affect the metabolism of valproate, including demographic factors, genetic factors and concomitant medications, hoping to provide reference for clinical individualized drug dosage regime.
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Objective To investigate the therapeutic measures of unresectable primary liver cancer (PLC) with transcatheter arterial chemoembolization(TACE).Methods The clinical data,treatment measures and followed up data of 312 patients with unresectable primary liver cancer from January 1991 to March 2010 were analyzed retrospectively.Of these 312 patients, different dosages, measures of transcatheter arterial chemoembolization together with immunotherapy and nutritional support treatments were given to the patients according to their own statements, including the patency of portal vein (evaluated by portography), the range, blood supply and lipiodol concentration of the lesions (evaluated by hepatic arteriography), and the systemic conditions.Some of these patients also accepted cryotherapy, radio frequency ablation (RFA), percutaneous ethanol injection therapy.Results Two hundred and eighty-seven patients were followed up (92％).Forty-two cases accepted the two-stage operation as the lesions were localized or reduced.In these 42 patients, 34 cases accepted the hepatectomy, 8 cases accepted the cryotherapy.The 1,3 and 5 year survival rate of all patients were 87.6％, 33.1％ and 13.2％.Conclusion TACE for unresectable primary liver cancer should be used individually and comprehensivly.Surgical treatment should be taken once the lesions can be resected.
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Objective To improve the management of blunt pancreatic trauma, and to explore the strategy of preserving the pancreatic endocrine and exocrine function to the full extent. Methods 20 cases of blunt pancreatic trauma were reviewed and analyzed retrospectively. The methods of operative treatment were analysed. Results All patients were cured. Depending on the general condition, abnomial signs and main pancreatic duct(MPD) injuries at the time of admission, patients received immediate operation or nonoperative treatment. Because of severe peritonitis and demonstrated MPD injury, 10 patients underwent immediate operations, including simple drainage in 6 cases, distal pancreatectomy in 1 patient, external drainage of the injured pancreatic duct for the second operation in 3 cases. Without the demonstrated MPD injury or clinical deterioration, 10 patients received nonoperative treatment under strict observation initially. 3 patients completed the nonoperative course and 7 patients underwent delayed operations, including Roux-en-Y pancreatic cyst-jejunostomy in 3 cases, external drainage of pseudocyst in e cases, pancreaticoduodenectomy in 1 patient because of the expanded hematoma in pancreatic head. Conclusions Blunt pancreatic trauma could receive individual pancreas-preserving treatment, which could improve the operational safety, avoid the resection of pancreas and preserve the pancreatic endocrine and exocrine function to the full extent.
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OBJECTIVE:To investigate the feasibility of defined individual treatment course as evaluation index of rational use of drugs.METHODS:The doses of antibiotics and treatment course in 63 patients with type Ⅰ incision operation of our hospital in Jan.2010 were taken as examples.Case analysis,DUI evaluation and defined individual treatment course evaluation were adopted.Similar results were obtained by 3 kinds of methods.RESULTS&CONCLUSION:Results of 3 kinds of methods are consistent.DUI evaluation isn't closely associated with treatment course.Defined individual treatment course is more sensitive and available than DUI based on the introduction of dose and treatment course.
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Objective To compare the clinical effectiveness,safety,cost-effectiveness of Targeting Gene Therapy with conventional therapy on patients with Essential Hypertension by metoprolol.Methods 300 cases of patients with Essential Hypertension were included.165 cases were chosen and assigned to conventional therapy group(Group A)at random.The subjects of Group A were administrated with metoprolol for 100 mg,twice per day.Polymorphism of CYP2D6 and ?1 adenoreceptor gene of the remain 135 subjects were detected,133 cases with of ?1-AR gene carrying Arg 389 allele were devided into three groups according to CYP2D6 genetype:the poor metabolism group(PM,43 cases),intermediate metabolism group(IM,54 cases)and extensive metabolism group(EM,36 cases).The subjects of PM,IM and EM were administrated with metoprolol for 25,100,200 mg/d respectively,twice per day.Blood pressures and side effects were observed during 8-week following-up.The health economic evaluation on Gene Targeting Therapy was determined by using the cost-effectiveness analysis.Results Total effective rate in Group PM,IM or EM were obviously higher than that in Group A(P
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Flavin-containing monooxygenase 3 (FMO3) is an important hepatic microsomal enzyme that oxidizes a number of drugs,xenobiotics and other chemicals.Many variants in the gene encoding FMO3 have been identified,some of which result in altered enzymatic activity,consenquently,altered substrate metabolism.Studies also implicate individual and ethnic differences in FMO3.Thus,it is anticipated that knowledge regarding functionally-relevant FMO3 genetic variability will become increasingly important for drug development and patient therapeutic choices.