Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19

Objective:The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection on self-reported alterations in taste and/or smell function.Methods:Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019(post-COVID-19)chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease.The dependent measure—self-reported total recovery of chemosensory symptoms—was subjected to stepwise logistic regression.Independent predictors included demographic and clinical variables,in addition to specific medications used to mitigate disease symptoms(i.e.,systemic corticosteroids,oseltamivir,vitamin C,ibuprofen,hydroxychloroquine,azithromycin,ivermectin,nitazoxanide,anticoagulants,and zinc).Results:The median time between COVID-19 symptom onset and the interviews was 81 days(interquartile range:60-104).Of the 714 subjects,249(34.9%)reported total recovery of their chemosensory function;437(61.2%)had at least one treatment since the beginning of the disease.Women and those with more comorbidities had undergone more treatments.The recovery rates of the treated and nontreated groups did not differ significantly.Nonetheless,respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery.Those who took oral zinc were less likely to improve.Conclusions:No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal,although nitrazoxide trended in a positive direction.Oral zinc had a negative effect on the reported recovery of these senses.

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.

Advances in pharmacotherapies in cancer-related cachexia

Cancer-related cachexia is highly prevalent in patients with advanced cancer, affecting approximately 50%–80% of patients and seriously interfering with active therapy, quality of life, and survival time. There arecurrently no effective treatments for cachexia. Therefore, new therapeutic strategies are required. In recentyears, advances in understanding the mechanisms underlying cachexia have been made, and new drugshave been developed to combat cachexia muscle wasting and weight loss due to cancer. In this systematicreview, we discuss these novel targets and drug treatments.

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.

Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

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.

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.

Advances in the Pathogenesis and Pharmacologic Treatment of Diabetic Cataracts

Diabetic cataract(DC)is a common complication prior to diabetes mellitus,which is a metabolic disease with pathogenesis including abnormal metabolism of polyphenol pathway(PP)and non-enzymatic glycosylation(NEG)of proteins,etc.The therapeutic drugs are mainly aldose reductase inhibitors(ARIs)and glycosylation inhibitors.The therapeutic regimens for DC are becoming more and more diversified due to the development of biological testing and clinical research technology,thus improving its clinical efficacy.With the development of biological testing and clinical research technology,the treatment options for DC have become increasingly diversified and the treatment specificity has been improved,improving its clinical efficacy.In order to comprehensively analyze the pathogenesis and pharmacological treatment of this disease,the following review is made.

Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

Pancreatic ductal adenocarcinoma(PDAC)is one of the deadliest cancers,mostly due to its resistance to treatment.Of these,checkpoint inhibitors(CPI)are inefficient when used as monotherapy,except in the case of a rare subset of tumors harboring microsatellite instability(<2%).This inefficacy mainly resides in the low immunogenicity and non-inflamed phenotype of PDAC.The abundant stroma generates a hypoxic microenvironment and drives the recruitment of immunosuppressive cells through cancerassociated-fibroblast activation and transforming growth factorβsecretion.Several strategies have recently been developed to overcome this immunosuppressive microenvironment.Combination therapies involving CPI aim at increasing tumor immunogenicity and promoting the recruitment and activation of effector T cells.Ongoing studies are therefore exploring the association of CPI with vaccines,oncolytic viruses,MEK inhibitors,cytokine inhibitors,and hypoxia-and stroma-targeting agents.Adoptive T-cell transfer is also under investigation.Moreover,translational studies on tumor tissue and blood,prior to and during treatment may lead to the identification of biomarkers with predictive value for both clinical outcome and response to immunotherapy.

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.

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.

Progress of clinical therapies for dry age-related macular degeneration

Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or,more notably,reversing it.Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed.A thorough search of Pub Med,Embase,and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated.This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.

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.

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.

Continuing episodes of pain in recurrent acute pancreatitis: Prospective follow up on a standardised protocol with drugs and pancreatic endotherapy

AIM To assess the outcomes of drug therapy(DT)followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis.METHODS DT comprised of pancreatic enzymes and antioxidants failing which,endotherapy(ET;pancreatic sphincterotomy and stent placement)was done.The frequency of pain,its visual analogue score(VAS),quality of life(Qo L),serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET.Response was defined as at least 50%reduction in the severity of pain to below a score of 5.RESULTS Of the thirty nine patients analysed,21(53.9%)responded to DT and 18(46.1%)underwent ET.The VAS for pain(7.0±2.0 vs 1.3±2.5,P<0.001)and the number of days with pain per month decreased[1.0(1.0,2.0)vs 1.0(0.0,1.0),P<0.001],and the Qo L scores[55.0(44.0,66.0)vs 38.0(32.00,51.00),P<0.01]improved significantly during follow up.Similar significant improvements were seen in patients in the subgroups of DT and ET except for Qo L in ET.The serum C-peptide(P=0.001)and FE(P<0.001)levels improved significantly in the entire group and in the two subgroups of patients except for the C peptide levels in patients on DT.CONCLUSION A standardised protocol of DT,followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis,enhanced Qo L and improved pancreatic function.

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.

Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

The ongoing research on pioneering drug candidates for the overactive bladder （OAB） aimed to overcome the limitations of currently licensed pharmacotherapies, such as antimuscarinics, β3-adrenergic agents, and botulinum neurotoxin, has been reviewed performing a systematic literature review and web search. The review covers the exploratory agents alternative to available medications for OAB and that may ultimately prove to be therapeutically useful in the future mana-gement of OAB patients based on preclinical and early clinical data. It emerges that many alternative pharmacological strategies have been discovered or are under investigation in disease-oriented studies. Several potential therapeutics are known for years but still fnd obstacles to pass the clinical stages of development, while other completely novel compounds, targeting new pharmacological targets, have been recently discovered and show potential to translate into clinical therapeutic agents for idiopathic and neurogenic OAB syndrome. The global scenario of investigational drugs for OAB gives promise for the development of innovative thera-peutics that may ultimately prove effective as first, combined or second-line treatments within a realistic timescale of ten years.