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.

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.

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.

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.

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.

Severe acute respiratory syndrome-coronavirus-2(SARS-COV-2)infection of pneumocytes with vaccination and drug therapy:Mathematical analysis and optimal control

We propose a mathematical model studying a within-host infection dynamics of SARSCoV-2 in pneumocytes.This model incorporates immune response,vaccination and antiviral drugs.The crucial properties of the model-the existence,positivity and boundary of solutions are established.Equilibrium points and the basic reproduction number are calculated.The stability of each equilibrium point is analyzed.Optimal control is applied to the model by adding three control variables:vaccination,treatment by Favipiravir and treatment by Molnupiravir.Numerical results show that each individual control could reduce SARS-CoV-2 infection in some aspects;however,with a combination of three controls,we obtain the best results in reducing SARS-CoV-2 infection.This study has emphasized the importance of prevention by vaccine and the antiviral treatments.

Intensive care drug therapy and its potential adverse effects on blood pressure and heart rate in critically ill children

Background Owing to complex treatment,critically ill children may experience alterations in their vital parameters.We investigated whether such hemodynamic alterations were temporally and causally related to drug therapy.Methods In a university pediatric intensive care unit,we retrospectively analyzed hemodynamic alterations defined as values exceeding the limits set for heart rate(HR)and blood pressure(BP).For causality assessment,we used the World Health Organization–Uppsala Monitoring Center(WHO–UMC)system,which categorizes the probability of causality as“certain,”“probable,”“possible,”and“unlikely.”Results Of 315 analyzed patients with 43,200 drug prescriptions,59.7%experienced at least one hemodynamic alteration;39.0%were affected by increased HR,19.0%by decreased HR,18.1%by increased BP,and 16.2%by decreased BP.According to drug information databases,83.9%of administered drugs potentially lead to hemodynamic alterations.Overall,88.3%of the observed hemodynamic alterations had a temporal relation to the administration of drugs;in 80.2%,more than one drug was involved.Based on the WHO–UMC system,a drug was rated as a“probable”causing factor for only 1.4%of hemodynamic alterations.For the remaining alterations,the probability ratings were lower because of multiple potential causes,e.g.,several drugs.Conclusions Critically ill children were frequently affected by hemodynamic alterations.The administration of drugs with potentially adverse effects on hemodynamic parameters is often temporally related to hemodynamic alterations.Hemodynamic alterations are often multifactorial,e.g.,due to administering multiple drugs in rapid succession;thus,the influence of individual drugs cannot easily be captured with the WHO–UMC system.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

Treatment of Recurrent Respiratory Infection with Chinese Drug Therapy of Tonifying-Shen(肾) and Solidifying Superficiality—A Clinical Case Report

Children recurrent respiratory infection （CRRI） indicates that children suffer from frequent infections along the upper or lower respiratory tract for a certain number of times. It is not an independent disease but a clinical syndrome mostly brought about by some basic diseases such as nonspecific immunity, specific immune suppression or deficiency disease, congenital bronchopulmonary dysplasia, vitamin or microelement deficiency, or is induced by some factors such as smoking, cross infection, and nursing errors.（2） Clinically, CRRI is commonly treated by anti-infective agents, symptomatic and supportive treatment, and immune-regulatory therapy. However, the therapeutic effectiveness is always imperfect, which could even lead to a premium on asthma, or nephritis, etc.

Drug therapy in patients with Parkinson’s disease

Parkinson`s disease(PD)is a progressive,disabling neurodegenerative disorder with onset of motor and non-motor features.Both reduce quality of life of PD patients and cause caregiver burden.This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other.MAO-B-Inhibitors,NMDA antagonists,dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD.This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms.These PD features predominantly result from non dopaminergic neurodegeneration.Autonomic features,such as seborrhea,hyperhidrosis,orthostatic syndrome,salivation,bladder dysfunction,gastrointestinal disturbances,and neuropsychiatric symptoms,such as depression,sleep disorders,psychosis,cognitive dysfunction with impaired execution and impulse control may appear.Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions,-side effects,and altered pharmacokinetic behaviour of applied compounds.Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms.This complicates the differentiation from the disease process itself and influences therapeutic options,which are often limited because of additional morbidity with necessary concomitant drug therapy.

Treatment of Hepatitis C in Patients Undergoing Immunosuppressive Drug Therapy

With 185 million people chronically infected globally,hepatitis C is a leading bloodborne infection.All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable.However,trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation.Yet,these patients-most often suffering from malignancy or autoimmune diseases-could stand to benefit from these treatments.In this study,we systematically review the literature on the treatment of hepatitis C in these neglected populations.Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically.Our systematic review produced 2273 unique works,of which 56 met our inclusion criteria and were used in our review.The quality of data was low;only 3 of the 56 studies were randomized controlled trials.Sustained virologic response was reported sporadically.Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals.Severe adverse effects and death were rare.Data on all-oral regimens were sparse,but in the most robust study,rates of sustained virologic response were again comparable to immunocompetent individuals (40/41).Efficacy and safety of interferoncontaining regimens and all-oral regimens were similar to rates in immunocompetent individuals;however,there were few interventional trials.The large number of case reports and case series makes conclusions vulnerable to publication bias.While firm conclusions are challenging,given the dearth of high-quality studies,our results demonstrate that antiviral therapy can be safe and effective.The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects.Preliminary data reveal that these regimens may confer such benefits in immunosuppressed individuals as well.More prospective interventional trials would greatly benefit the many patients with chronic hepatitis C on immunosuppressive therapies.

Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative treatment.Even for patients who can undergo resection for curative treatment of HCC,up to 50%recur.For patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local treatments.Such patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate.There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors.This minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis.We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

The“1＋1”Therapy for Drug Addicts

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Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Efficacy and Safety of Iron Isomaltoside Compared with an Oral Iron Supplement in the Management of Patients with Iron Deficiency Anemia

Objective: To evaluate the treatment outcome of iron isomaltoside compared with an oral iron supplement in the management of iron deficiency anemia (IDA). Methods: The study included patients with IDA who visited the Outpatient Clinic of the Department of Hematology, the Affiliated Hospital of Qingdao University from October 2021 to August 2022 and met the inclusion and exclusion criteria. According to the actual application of iron supplementation, the patients were divided into two groups: iron isomaltoside treatment group and oral iron treatment group. Baseline measurements were collected before the start of treatment, and measurements were collected subsequently at intervals of 1 week, 1 month, and 3 months. The hematological parameters analyzed included Hemoglobin (Hb), Mean corpuscular hemoglobin (MCH), Mean Hemoglobin content (MCH), Mean corpuscular Hemoglobin concentration (MCHC), and Platelet (Plt). Safety data and adverse event profiles were recorded. Results: Intra-group comparisons: After 1 month of treatment, the Hb significantly improved (P 0.05). Inter-group comparisons: The biochemical parameters were significantly improved (P 0.05) in the iron isomaltoside group compared with those in the oral iron group after 1 month of iron supplementation in patients with mild and moderate anemia. Adverse reactions were tolerable for the patients in both iron isomaltoside group and oral iron group. Only 1 patient in iron isomaltoside group developed anaphylactic shock during medication and recovered after aggressive rescue. Conclusions: Iron isomaltoside which increases Hb more rapidly compared with the oral iron supplementation has few adverse reactions and good acceptance.

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.

Medical therapy for clinical benign prostatic hyperplasia:α1 Antagonists,5α reductase inhibitors and their combination

Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.

Clinical Study of Drug-resistant Pulmonary Tuberculosis Treated by Combination of Anti-Tuberculosis Chemicals and Compound Astragalus Capsule(复方黄芪胶囊)

Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8% , focal absorption effective rate 91. 3% , cavity closing rate 58. 7% and 10-day symptom improving rate 54. 4% , while in the control group, the corresponding rates were 65.2% , 73. 9 % , 37.0% and 26.1 % , respectively. Comparison between the groups showed significant difference in all the parameters (P<0.05, P<0.05, P<0.05 and P<0.01). The incidence of adverse reaction and 2-year bacteriological recurrence rate in the treated group were 23. 9% and 2.6% respectively, while those in the control group 50. 0% and 16. 7% , which were higher than the former group with significant difference ( P<0. 01 and P<0. 05, respectively). Conclusion: The therapeutic effect of combined treatment with anti-TB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.