Current status of drug therapy for chronic hepatitis B

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

Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

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.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

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.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy

BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unresectable HCC who received conversion therapy.METHODS One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort(n=120)and a validation cohort(n=30).Using the independent risk factors in the training cohort,a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection.The nomogram was internally validated with the bootstrapping method.The predictive performance of nomogram was assessed by Harrell’s concordance index(C-index),calibration plot and timedependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.RESULTS Multivariate Cox analysis identified that albumin,blood urea nitrogen,gamma-glutamyl transpeptidase to platelet ratio,platelet to lymphocyte ratio,macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model.The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS,which were higher than those of the six conventional HCC staging systems(0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort).The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS.Decision curve analyses indicated satisfactory clinical utility.With a total nomogram score of 196,patients were accurately classified into low-risk and high-risk groups.Furthermore,we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.CONCLUSION The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy,which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

Research Progress of Atomizers and Drugs Used in Atomization Therapy

At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.

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 Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Inflammation and dysregulation of immune response in Alzheimer disease, the drug target for the future

It has been demonstrated that inflammation and dysregulation of immune response are involved in the pathogenesis of Alzheimer disease (AD). Inflammation is an early event in AD development, especially inflammasome and pro-inflammatory molecules are pathogenic factor in AD. Our data showed that activated immune cells may contribute to the pathogenesis of AD, since the mice with immune cells knock out demonstrated differentsings in the neurodegenerative process and T cells aid clearance of plaques in mice and infiltrating parenchymal T-cell in AD brain mainly in the light of amyloid pathology, and immune treatment is effective, etc. However, the direct evidence on T and B cells infiltrating into the brain of APP transgenic mice have not yet found. Whether aged T cells are pathogenic in AD?How is role of aged B cells? These questions are still unclear. In conclusion, activated immune cells,and inflammatory molecules may play important roles in neurodegenerative disorders, such as AD. The mechanisms of behind this are needed to further study. Inhibiting inflammation in the early phase of AD and restore normal immune regulation are new drug target for the future.

Efficacy of Ulinastatin Combined with Continuous Renal Replacement Therapy in the Treatment of Sepsis Acute Kidney Injury and Its Effects on Systemic Inflammation, Immune Function and miRAN Expression

Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.

Cellular Nutrition,Inflammation in Cancer Prevention and Therapy

Chronic inflammation is known to contribute to human tumorigenesis,with an estimated 20%of adult cancers being attributable to chronic inflammatory conditions caused by infectious agents as well as chronic noninfectious inflammatory diseases.Recently,chronic inflammation is regarded as an‘enabling characteristic’of human cancer.In addition,the impact of chronic inflammation is also noticed on the outcome of cancer therapy and design of new therapeutic approaches.Nutrients are necessary for maintaining general health,and most of researches have focused on their beneficial effects on immune functions.However,the effects of nutrition in regulating inflammation deserve a close attention.Naturally,the nutrition-decreased inflammation reduces the risk of cancer in healthy individuals and normalizes the physical state of cancer patients.Therefore,it is valuable to understand the cellular nutrition in modulating inflammation.In the present review,I will summarize the impacts of inflammation on tumorigenesis and discuss the benefits of nutrition in regulating inflammation and the underlying mechanisms.It is believed that nutritional approaches to regulating inflammation will open a new window for cancer prevention and therapy.

Role of autophagy in tumorigenesis,metastasis,targeted therapy and drug resistance of hepatocellular carcinoma

Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.

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.

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

Multidrug resistance(MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse.Combination therapy is an effective strategy for overcoming MDR. However, the different pharmacokinetic(PK) profiles of combined drugs often undermine the combination effect in vivo, especially when greatly different physicochemical properties(e.g.,those of macromolecules and small drugs) combine. To address this issue, nanotechnology-based codelivery techniques have been actively explored. They possess great advantages for tumor targeting, controlled drug release, and identical drug PK profiles. Thus,a powerful tool for combination therapy is provided, and the translation from in vitro to in vivo is facilitated. In this review, we present a summary of various combination strategies for overcoming MDR and the nanotechnology-based combination therapy.

Hepatic inflammation and progressive liver fibrosis in chronic liver disease

Chronic liver inflammation drives hepatic fibrosis,and current immunosuppressive,anti-inflammatory,and anti-viral therapies can weaken this driver.Hepatic fibrosis is reversed,stabilized,or prevented in 57%-79%of patients by conventional treatment regimens,mainly by their anti-inflammatory actions.Responses,however,are commonly incomplete and inconsistently achieved.The fibrotic mechanisms associated with liver inflammation have been clarified,and anti-fibrotic agents promise to improve outcomes as adjunctive therapies.Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes.Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species.Anti-oxidants(Nacetylcysteine,S-adenosyl-L-methionine,and vitamin E)and angiotensin inhibitors(losartin)have had antifibrotic actions in preliminary human studies,and they may emerge as supplemental therapies.Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease.

Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.