Using multi-omics analysis to explore diagnostic tool and optimize drug therapy selection for patients with glioma based on cross-talk gene signature

Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.

Current status of drug therapy for alveolar echinococcosis

Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The primary treatment for AE is surgical resection of the lesions;however,owing to its long incubation period and insidious disease progression,many patients are diagnosed only after the onset of complications such as liver cirrhosis,jaundice,and portal hypertension,which preclude curative surgical intervention.For patients who are unwilling or unable to undergo surgery,lifelong administration of anti-AE medications is necessary.Benzimidazole compounds,such as albendazole and mebendazole,are the current mainstays of treatment,offering good efficacy.Nevertheless,these medications primarily inhibit parasite proliferation rather than eradicate the infection,and their long-term use can lead to significant drug-related toxic effects.Consequently,there is an urgent need to develop new therapeutic strategies that convey better efficacy and reduce the adverse effects associated with current treatments.Recent advancements in AE therapy include novel synthetic compounds such as antiviral agents,antibiotics,antineoplastic agents,immunosuppressants,and antiangiogenic agents,as well as natural compounds derived from traditional Chinese and Tibetan medicine.These new drugs show promising clinical potential because they interfere with parasitic metabolic pathways and cellular structures.This review aims to discuss recent research on AE drug therapy,including mechanisms of action,dosing regimens,signalling pathways,and therapeutic outcomes,with a goal of providing new insights and directions for the development of anti-AE drugs and summarizing current advancements in AE pharmacotherapy.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Advances in Drug Therapy for Alzheimer’s Disease

Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the development of drug therapy for AD worldwide.Many drug therapies are currently under development or in clinical trials,based on two known mechanisms of AD,namely,Aβtoxicity and the abnormal Tau hyperphosphorylation.Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation,neurotransmitter imbalance,oxidative damage and mitochondrial dysfunction,neuron loss and degeneration.Even so,the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited.However,multi-drug combinations may provide a new avenue for drug therapy for AD.In addition,early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.

Endovascular treatment vs drug therapy alone in patients with mild ischemic stroke and large infarct cores

BACKGROUND Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct.Medical care alone may result in suboptimal treatment efficacy,and endovascular treatment may be accompanied by safety issues.Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies.AIM To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores.METHODS Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021.Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods.In the endovascular therapy group,there were 28 patients with minor stroke and 22 patients with large infarct cores.The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores.The National Institutes of Health Stroke Scale(NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation.The modified Rankin scale(m RS) and/or activity of daily living were assessed at hospital discharge.RESULTS There was no significant difference in NIHSS scores between the two groups before the operation(P > 0.05).NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge(all P < 0.05).The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group(P < 0.05).At hospital discharge,the m RS score was lower in the endovascular treatment group than in the drug therapy group,and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group(all P < 0.05).During a follow-up of 3 mo,17 patients(34.0%) had good prognosis(m RS ≤ 2),33 patients(66.0%) had poor prognosis(m RS > 2),and 11 patients(22.0%) died.In the medical treatment group,16 patients(m RS ≤ 2) had good prognosis(32.0%),34 patients(m RS > 2) had poor prognosis(68.0%),and 14 patients(28.0%) died.There was no significant difference in prognosis and mortality between the two groups(P > 0.05).CONCLUSION Endovascular therapy can improve NIHSS score and m RS score in patients with mild ischemic stroke and large infarct cores.It is suitable for clinical application.

Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

Objective The aim of the study was to evaluate the safety and efficacy of capecitabine mono-chemotherapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m^2 twice daily （D1-14） for 21 days constituted a cycle. The effect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total effective rate was 30.6% （11/36） and the disease control rate was 72.2% （26/36）. The number of patients with clinical comptete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was effective, the median time to progression was 6 months and the median overall survival was 9.5 months. The main adverse events were gastrointestinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients （12.5%） and hand-foot syndrome in 1 patient （6.7%）. Conclusion Capecitabine monotherapy was effective in controlling disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.

DRUG THERAPY OF PAROXYSMAL ATRIAL FIBRILLATION IN THE ELDERLY OVER 75 YEARS OLD

Objective To investigate the effectiveness and safety of various agents on paroxysmal atrial fibrillation in the elderly over 75 years old.Methods Totally 264 in-patients (75-91 years old, 185 males and 79 females) with atrial fibrillation history of less than 7 days were enrolled in this study.A total of 611 atrial fibrillation episodes were recorded, but 130 episodes (22.3%) of atrial fibrillation were auto-converted to sinus rhythm.The rest 481 episodes of atrial fibrillation were divided into six groups based on the drug used.Results The cardioversion ratio of atrial fibrillation were 9.5%, 46.9%, 71.7%, 55.9%, 32.7%, and 73.6% in control, cedilanid, amiodarone, propafenone, verapamil, and quinidine groups, respectively.Ventricular rate control were 5.4%, 83.6%, 84.9%, 77.9%, 78.8%, and 11.3% in those groups, respectively.The total effective rates of amiodarone and cedilanid groups were the highest. When the ventricular rate was controlled to below 90 bpm, the patients would almost complain of no discomfort. No severe side-effect was observed in each group.Conclusion Amiodarone and cedilanid may be the proper drugs for the treatment of paroxysmal atrial fibrillation in the elderly.The above antiarrhythmics in each therapeutic group were relatively safe and effective.

Ribavirin monotherapy increases sustained response rate in relapsers of end treatment virologic responders

AIM: To assess the efficacy of ribavirin monotherapy in patients with biochemical relapse after combination therapy.METHODS: Twenty-four weeks of ribavirin monotherapy was given to biochemical relapsers of end treatment biochemical responders within 6 mo after combination therapy, including non-responders with HCV-RNA level ≤0.2 Meq/mL and end treatment virologic responders (ETVRs) with or without reappearance of HCV-RNA.RESULTS: Sixty-two chronic HCV-infected patients completed 24 wk of interferon-α plus ribavirin combination therapy. Fifty patients (80%) achieved end treatment biochemical response including 16 non-responders and 34 of 36 ETVRs. Twenty-six patients (41.9%) were nonresponders. Ribavirin monotherapy was given to 20biochemical relapsers including 12 non-responders with HCV-RNA levels ≤0.2 Meq/mL, four of eight HCV-RNA reappearing ETVRs, and four HCV-RNA negative ETVRs.After 24 wk of ribavirin monotherapy, one of 12 nonresponders, two of four HCV-RNA reappearing ETVRs and all four RNA-negative biochemical relapsers of ETVRs showed sustained virologic response. Two of 12monotherapy treated non-responders showed persistent normalization of liver function test. In total, 50% (31/62)of patients achieved sustained virologic response.CONCLUSION: Resumption of ribavirin monotherapy in ETVRs at signs of viral rebound and recurrent biochemical abnormalities rather than continuation of monotherapy appears to be the key to success of ribavirin monotherapy after interferon-related combination therapy.

Real world studies are essential for drug therapy in Parkinson's disease

Prospective real-world data from large patient samples, which re- port on the long-term effectiveness of the employed different drug therapies, are rare in Parkinson＇s disease （PD）. The non interven- tional ＂Transdermal Rotigotine User Surveillance Study＂ （TRUST） trial represents such a real-world study. It investigated long-term treatment with different dopamine substituting treatment regimens in 2195 PD patients （Mfiller et al., 2018）. Participation in TRUST meant that the treating neurologists were only asked to document and modify the dopaminergic drug regimen without any prior PD patient selection criteria. Thus this unique trial design reflects the real world of patient maintenance.

Drug Therapy Monitoring in Patients with Type 2 Diabetes and Hypertension

The aim of this paper is to detect, prevent and resolve DRP （drug-related problems） and NOM （negative outcomes associated with medication） in hospitalized patients with DM2 （type 2 diabetes） with HTN （hypertension） in a tertiary care clinic. Descriptive cross-sectional interventional study is used. DTM （drug therapy monitoring） was conducted in 73 patients using data obtained from clinical histories and interviews. NOM were detected based on symptoms and laboratory test results. The statistical significance was 0.05. It can be found that 23 DRP were detected, primarily in the category ＂likelihood of adverse effects＂ （30.43%） causing NOM in the ＂non-quantitative safety problem＂ category. The NOM detected were related to safety （62%）, effectiveness （24.5%） and necessity （13.5%）. Of the 68.57% of pharmacist interventions accepted, 48.57% were resolved and 20% were not resolved. A simple linear correlation （r = -0.34） analysis indicated a weak association between patient age and severity ofNOM. DTM made it＇possible to detect suspected DRP and NOM, which were then prevented or resolved, improving the control of HTN and DM2 and helping ensure better drug therapy outcomes for patients.

New Developments in Drug Therapy and Research of Cerebral Vasospasm

In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.

Non-Drug Therapy to Combat Coronavirus

Novel coronavirus is threatening the health of people all over the world and all possible treatment strategies are in urgent. The sensitive of virus to heat proposed temperature treatment as an effective method against coronavirus. Here, we proposed several non-drug therapies including far-infrared, thermal air, thermal oxygen, ozone, hydrogen therapy and plasma physical therapy for immediate clinical trial and implementation. Compared with the drug therapy, these methods are safe without side effects, the highest benefit-to-risk ratio, user-friendly, and low implementation costs. It is urgent and significant to start these non-drug therapeutic design and implementation as early as possible, to determine the safety and effectiveness of these therapeutic methods.

Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment:a meta-analysis of randomized controlled trials

BACKGROUND: It has been demonstrated that only a minority of patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) obtain a sustained response after either interferon (IFN) or nucleos (t)ide analogue monotherapy. Therefore, combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients. We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon (CON-IFN) and pegylated interferon (PEG-IFN) for HBeAg-negative CHB patients. DATA SOURCES: A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches (MEDLINE, OVID, EMBASE, the Cochrane Library Clinical Trials Registry, and the Chinese Medical Database), manual searches, and contact with experts. Sustained virological and biochemical responses were defined as primary efficacy measures. We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups. RESULTS: No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs. 26.7%, odds ratio (OR)=0.98, 95% confidence interval (CI) 0.65-1.50, P=0.94, and 41.8% vs. 40.3%, OR=1.13, 95% CI 0.78-1.65, P=0.51, respectively],though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs. 30.0%, OR=0.16, 95% CI 0.076-0.33, P<0.001]. However, data from one PEG-IFN trial showed greater sustained virological and biochemical rates in patients receiving combination therapy [response rate 19.5% vs. 6.6%, OR=3.42, 95% CI 1.71-6.84, P<0.001 and 60.0% vs. 44.2%, OR=1.88, 95% CI 1.23-2.85, P=0.003, respectively]. CONCLUSIONS: Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine. Combination of PEG-IFN and lamivudine might increase the sustained response, and further clinical trials are needed for confirmation.

Clinical effects of psychological intervention and drug therapy against peptic ulcer

Objective:To evaluate the clinical effects of psychological interventions and drug therapy against peptic ulcer.Methods:96 patients with peptic ulcer were divided into control group with Tagamet 800 mg per evening p.o.and trial group with psychological intervention on the basis of drug treatment.Results:There were significant differences between the two groups(P【0.05), the trial group showed that the anxiety and depression cases declined obviously and effective rate of ulcer therapy was much higlier than control group.Conclusions:In sum,psychological intervention combined with drug therapy provides an effective method for ulcer treatment.

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.

Efficacy of 3 years of adefovir monotherapy in chronic hepatitis B patients with lamivudine resistance

AIM: To study the effect of rescue monotherapy with adefovir (ADV) in patients with chronic hepatitis B (CHB) who developed drug resistance to lamivudine (LAM).

Complexity of drug therapy and its implications for quality of diabetes care

Diabetes is a leading cause of mortality,morbidity and disability around the globe.In the past two decades,diabetes care has grown more complex as patients have received multi-component care.Recent studies have illumined the complexity of drug therapy in patients with diabetes.A high level of drug utilization in diabetes patients has serious implications for quality of care,in terms of coordination of care,drug safety and access to care.Practitioners,researchers,payers and policy makers should be aware of these implications and incorporate the complexity of diabetes care into practice guidelines,benefit design and policy formulation to improve the quality of care.

Effect of Antihypertensive Drug Therapy on the Blood Pressure Control among Hypertensive Patients Attending Campus’ Teaching Hospital of Lome, Togo, West Africa

High blood pressure (HBP) is a health problem world—wide. In Togo, that affection constitutes a more and more pre-occupying cause of morbidity and mortality. This study is a prospective one which intended to identify the antihypertensive regimens prescribed and evaluate their effect on patients’ blood pressure (BP) control. Out of the 204 patients enrolled (mean: 55.01 ± 12.55 years;sex ratio: 1.3), 112/176 placed on antihypertensive therapy have controlled their BP (38.39% outpatients vs 61.61% inpatients). Related to the sex factor, we didn’t observe any significant difference in the BP control. Whereas, the mean median value of BP reduction of outpatients (30.00/15.00 mmHg) (p = 0.001) was half lower than that of inpatients (60.00/30.00 mmHg (p = 0.004)). Thirty five outpatients (81.40%) vs 64 inpatients (92.75%) were placed on combination therapy. The bitherapy was prescribed to 23 outpatients (53.49%) against 27 inpatients (39.13%) while the quadritherapy and more than 4 drugs combination were prescribed exclusively to inpatients (20.29%, n = 14). That quadritherapy induced a significant mean reduction of inpatients’ SBP compared to monotherapy (p = 0.043) and to bitherapy (p = 0.004). The favorite combinations were D + CCA, D + ACEI, D + CCA + ACEI and D + CCA + ACEI + CAAD of which the quadruple therapy showed a significant inpatients’ DBP control (p = 0.015) compared to D + CCA combination. The combinations including at least one diuretic induced a significant difference between outpatients (median value: 30.000/10.000 mmHg) (p < 0.001) and inpatients (median value: 60.000 mmHg/30 mmHg) (p < 0.001). The first-line molecules and fixe combinations prescribed in decreasing frequency were among others: hydrochlorothiazide + captopril, nicardipine, α methyldopa for outpatients;furosemide, nicardipine, captopril, α methyldopa, hydrochlorothiazide + captopril for inpatients. Diuretics, CCAs and ACEIs were the 3 favorite pharmacological groups for essential hypertension management in our African resource limited context. Combined to CAAD, they represented the best quadruple combination among inpatients having showed a significant difference in DBP control compared to D + CCA combination.

Type 2 Diabetes Mellitus in Children and Adolescents: Early Prevention and Non-Drug Therapy

The global rate of type 2 diabetes mellitus (T2DM) in youth has increased dramatically in the last 30 years. This increase mirrors the global epidemic of childhood obesity. Studies show that, compared to adults who develop T2DM, youth with T2DM ultimately suffer from more harmful symptoms. The prevalence of T2DM and obesity in youth signals a significant public health issue that financially burdens governments, families, and individuals. Since evidence suggests that T2DM in youth is different from both type 1 and type 2 diabetes in adults, researchers and clinicians face many difficulties in developing new treatments. Most treatment efforts have relied on drugs;however, recent studies suggest that non-drug therapy also effectively reduces obesity and diabetic symptoms. Healthier eating, increased physical exercise, and positive mental health, are often underappreciated factors towards managing obesity. Yet these lifestyle changes empower both young and older patients to independently fight diseases and attain better health. To manage the global health risk of obesity, further research addressing the prevention and nondrug early intervention of T2DM and obesity in youth is urgently needed. The present review focuses on the latest updates in the field.