Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Tau truncation in the pathogenesis of Alzheimer's disease:a narrative review

Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.

Mental health status among COVID-19 patients survivors of critical illness in Saudi Arabia:A 6-month follow-up questionnaire study

BACKGROUND Psychological assessment after intensive care unit(ICU)discharge is increasingly used to assess patients'cognitive and psychological well-being.However,few studies have examined those who recovered from coronavirus disease 2019(COVID-19).There is a paucity of data from the Middle East assessing the post-ICU discharge mental health status of patients who had COVID-19.AIM To evaluate anxiety and depression among patients who had severe COVID-19.METHODS This is a prospective single-center follow-up questionnaire-based study of adults who were admitted to the ICU or under ICU consultation for>24 h for COVID-19.Eligible patients were contacted via telephone.The patient’s anxiety and depression six months after ICU discharge were assessed using the Hospital Anxiety and Depression Scale(HADS).The primary outcome was the mean HADS score.The secondary outcomes were risk factors of anxiety and/or depression.RESULTS Patients who were admitted to the ICU because of COVID-19 were screened(n=518).Of these,48 completed the questionnaires.The mean age was 56.3±17.2 years.Thirty patients(62.5%)were male.The main comorbidities were endocrine(n=24,50%)and cardiovascular(n=21,43.8%)diseases.The mean overall HADS score for anxiety and depression at 6 months post-ICU discharge was 11.4(SD±8.5).A HADS score of>7 for anxiety and depression was detected in 15 patients(30%)and 18 patients(36%),respectively.Results from the multivariable ordered logistic regression demonstrated that vasopressor use was associated with the development of anxiety and depression[odds ratio(OR)39.06,95% confidence interval:1.309-1165.8;P<0.05].CONCLUSION Six months after ICU discharge,30% of patients who had COVID-19 demonstrated a HADS score that confirmed anxiety and depression.To compare the psychological status of patients following an ICU admission(with vs without COVID-19),further studies are warranted.

Cases studies of application of model-informed drug development in early phase clinical trials

Model-informed drug develop⁃ment(MIDD)is the application of a various math⁃ematical,statistical,and biological models to facilitate drug development,decision making and regulatory review.As a quantitative tool,MIDD approaches allow an integration of information obtained from non-clinical studies and clinical trials in a drug development program.General understandings of the underlying biology,patho⁃physiology,and pharmacology can also be incor⁃porated into the model.MIDD is centered on knowledge and inferences generated from inte⁃grated models of the physicochemical character⁃istics of a molecule,its disposition in the body,and its mechanism of action,and how the drug might affect a disease from both an efficacy and a safety perspective.MIDD approaches have the potential to significantly streamline drug develop⁃ment,by improving clinical trial efficiency,opti⁃mizing dose and regimen and waive unneces⁃sary clinical studies.This presentation will use cases studies to demonstrate how to apply MIDD in early phase of clinical trials.

Avoiding misdiagnosis of multilocular thymic cysts as malignant tumors on computer tomography

This editorial provides insights from a case report by Sun et al published in the World Journal of Clinical Cases.The case report focuses on a case where a multilocular thymic cyst(MTC)was misdiagnosed as a thymic tumor,resulting in an unnecessary surgical procedure.Both MTCs and thymic tumors are rare conditions that heavily rely on radiological imaging for accurate diagnosis.However,the similarity in their imaging presentations can lead to misinterpretation,resulting in unnecessary surgical procedures.Due to the ongoing lack of comprehensive knowledge about MTCs and thymic tumors,we offer a summary of diagnostic techniques documented in recent literature and examine potential causes of misdiagnosis.When computer tomography(CT)values surpass 20 Hounsfield units and display comparable morphology,there is a risk of misdiagnosing MTCs as thymic tumors.Employing various differential diagnostic methods like biopsy,molecular biology,multi-slice CT,CT functional imaging,positron emission tomography/CT molecular functional imaging,magnetic resonance imaging and radiomics,proves advantageous in reducing clinical misdiagnosis.A deeper understanding of these conditions requires increased attention and exploration by healthcare providers.Moreover,the continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses,provide appropriate treatment options,and improve the quality of life for patients with thymic tumors and MTCs in the future.continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses,provide appropriate treatment options,and improve the quality of life for patients with thymic tumors and MTCs in the future.

Comparison of different preoperative objective nutritional indices for evaluating 30-d mortality and complications after liver transplantation

BACKGROUND The nutritional status is closely related to the prognosis of liver transplant re-cipients,but few studies have reported the role of preoperative objective nutri-tional indices in predicting liver transplant outcomes.AIM To compare the predictive value of various preoperative objective nutritional indicators for determining 30-d mortality and complications following liver transplantation(LT).METHODS A retrospective analysis was conducted on 162 recipients who underwent LT at our institution from December 2019 to June 2022.RESULTS This study identified several independent risk factors associated with 30-d mor-tality,including blood loss,the prognostic nutritional index(PNI),the nutritional risk index(NRI),and the control nutritional status.The 30-d mortality rate was 8.6%.Blood loss,the NRI,and the PNI were found to be independent risk factors for the occurrence of severe postoperative complications.The NRI achieved the highest prediction values for 30-d mortality[area under the curve(AUC)=0.861,P<0.001]and severe complications(AUC=0.643,P=0.011).Compared to those in the high NRI group,the low patients in the NRI group had lower preoperative body mass index and prealbumin and albumin levels,as well as higher alanine aminotransferase and total bilirubin levels,Model for End-stage Liver Disease scores and prothrombin time(P<0.05).Furthermore,the group with a low NRI exhibited significantly greater incidences of intraabdominal bleeding,primary graft nonfunction,and mortality.CONCLUSION The NRI has good predictive value for 30-d mortality and severe complications following LT.The NRI could be an effective tool for transplant surgeons to evaluate perioperative nutritional risk and develop relevant nutritional therapy.

Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma

In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(TKI)and programmed cell death protein-1(PD-1)inhibitor for the treatment of unresectable hepatocellular carcinoma(HCC).Herein,we focus specifically on the mechanisms of this triple therapy,administration sequence and selection of each medication,and implications for future clinical trials.Based on the interaction mechanisms between medications,the triple therapy of TACE+TKI+PD-1 is proposed to complement the deficiency of each monotherapy,and achieve synergistic antitumor effects.Although this triple therapy has been evaluated by several retrospective trials,it is still controversial whether the triple therapy achieves better clinical benefits,due to the flawed study design and heterogeneity in medications.In addition,the administration sequence,which may greatly affect the clinical benefit,needs to be fully considered at clinical decision-making for obtaining better prognosis.We hope that this editorial could contribute to the design and optimization of future trials.

Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

Timing impact on the initiation of pirfenidone therapy on idiopathic pulmonary fibrosis disease progression

In this editorial,we comment on the article by Lei et al,with a specific focus on the timing of the initiation of the antifibrotic agent pirfenidone(PFD)in the management of idiopathic pulmonary fibrosis(IPF)and its impact on lung function of IPF patients.PFD is an antifibrotic agent that is widely used in the management of IPF in both early and advanced stages.It inhibits various pathways and has antifibrotic,anti-inflammatory,and antioxidant properties.Despite dosage lowering,PFD slowed IPF progression and maintained functional capacity.The 6-min walk distance test indicated that patients tolerated adverse events well,and PFD significantly reduced the incidence of progression episodes and death.Even when a single disease-progression event occurred,continuing PFD treatment had benefits.

Mechanism of imipenem-induced mental disorder: A meta-analysis

BACKGROUND Imipenem is a highly effective carbapenem antibiotic,which is widely used in the treatment of many serious bacterial infections.At the same time,it can also cause some adverse reactions,mental abnormalities are the most concerned central nervous system adverse reactions.Different patients respond differently to imipenem,and the effect of imipenem on psychiatric disorders is unclear.Therefore,meta-analysis summarizing the results of multiple previous studies can provide stronger evidence support for clinical guidelines to guide clinical rational use of imipenem to minimize risks.After reviewing the literature published between 2003 and 2017,seven controlled trials with a total of 550 patients were included,with 273 and 277 patients in the control and experimental groups,respectively.The sample size of the study ranged from a minimum of 30 cases to a maximum of 61 cases.Patients in the experimental group were treated with imipenem while the control group was treated with conventional drugs.Meta-analysis showed that the incidence of mental disorders in the experimental group was higher than that in the control group(odds ratio=3.66,95%confidence interval:1.11-12.11,P=0.030);however,there was no significant difference in the incidence of adverse reactions between the two groups(odds ratio=0.05,95%confidence interval:0.00 to 0.10,P=0.060).Funnel diagrams showed that the scattered points of each study were symmetrical and distributed in an inverted funnel shape;therefore,there was no publication bias.CONCLUSION Imipenem can cause mental disorders in patients.However,the low quality of the included literature may have affected the final results.Therefore,it is necessary to conduct a high-quality randomized controlled study with multiple samples to further confirm the mechanism of imipenem-induced mental disorders and provide effective guidance for clinical treatment.

Advances in epidural labor analgesia:Effectiveness and treatment strategies of butorphanol

In this editorial,we provide a critical review of the article by Tang et al published in the World J Clin Cases,focusing on the utilization of butorphanol for epidural analgesia during labor.Our discussion encompasses recent research developments in epidural labor analgesia,specifically highlighting the current status of clinical applications of butorphanol and associated treatment approaches.Epidural analgesia is widely acknowledged as the primary method for pain management during labor,offering effective and prolonged pain relief while allowing mothers to remain alert and actively participate in the delivery process.Among the various drugs utilized for epidural labor analgesia,butorphanol has received increasing attention due to its potential efficacy and distinctive pharmacological properties.As a synthetic opioid analgesic,butorphanol exhibits both agonistic and antagonistic activity on opioid receptors,striking a balance between analgesia and minimizing side effects.Nevertheless,the safety and efficacy of butorphanol in epidural labor analgesia remains controversial.While certain studies have reported positive outcomes with butorphanol,including effective pain relief and a reduced incidence of side effects,others have raised concerns about its safety and efficacy compared to traditional opioids or alternative analgesics.In addition,the optimal dosing strategy and regimen of butorphanol as an adjuvant in epidural labor analgesia still need to be verified.Through comprehensive synthesis and analysis of existing literature,we aim to evaluate the current evidence regarding the use of butorphanol for epidural labor analgesia,delineate areas of consensus and controversy,and propose future avenues for research and clinical practice in this domain.

Retroperitoneal bronchogenic cyst:A case report and review of literature

BACKGROUND Bronchogenic cysts are rare developmental anomalies that belong to the category of congenital enterogenous cysts.They arise from lung buds and are present at birth.The embryonic foregut is their origin.Typically,they are located within the chest cavity,particularly in the cavum mediastinale of the thoracic cavity or lodged in the pulmonary parenchyma,and are considered a type of lung bud malformation.CASE SUMMARY A 49-year-old male patient was admitted to the hospital due to the detection of a retroperitoneal mass during a physical examination.Two weeks before admission,the patient underwent a physical examination and routine laboratory tests,which revealed a space-occupying mass in the retroperitoneal region.The patient did not report any symptoms(such as abdominal pain,flatulence,nausea,vomiting,high fever,or chills).The computed tomography(CT)revealed a retroperitoneal spaceoccupying lesion with minimal enhancement and a CT value of approximately 36 Hounsfield units.The lesion was not delineated from the boundary of the pancreatic body and was closely related to the retroperitoneum locally.CONCLUSION Following a series of tests,an abdominal mass was identified,prompting the implementation of a laparoscopic retroperitoneal mass excision procedure.During the investigation,an 8 cm×7 cm cystic round-shaped mass with a distinct demarcation was identified in the upper posterior region of the pancreas.Subsequently,full resection of the mass was performed.Postoperative pathological examination reveled a cystic mass characterized by a smooth inner wall.The cystic mass was found to contain a white,viscous liquid within its capsule.

Reassessment of palliative surgery in conversion therapy of previously unresectable hepatocellular carcinoma: Two case reports and review of literature

BACKGROUND Most patients with hepatocellular carcinoma(HCC)have lost the opportunity for direct surgery at the time of diagnosis.Transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors or tyrosine kinase inhibitors(TKI)can partially transform some unresectable HCC and improve the prognosis ef-fectively.However,based on the promising prospects of combined targeted and immunotherapy for the effective treatment of HCC,the positive role of palliative surgery in the conversion treatment of advanced HCC urgently needs further in-tensive re-assessment.CASE SUMMARY In this study,we describe two successful cases of"conversion therapy for un-resectable HCC"achieved mainly by palliative surgery combined with TACE plus immunotherapy and TKIs.A 48-year-old patient with newly diagnosed HCC,presenting with a 6-cm mass in the segment VII/VIII of the right liver with mul-tiple intrahepatic metastases,could not undergo one-stage radical surgical resection.He underwent palliative surgery with radiofrequency of metastatic lesions and the palliative resection of the primary mass,and received subsequent TACE treatments twice in the early postoperative period(2 weeks and 6 weeks),in addition to targeted and immune combination therapy with sintilimab injection and oral lenvatinib.No evidence of recurrence was observed during the 11-month follow-up period after surgery.The other patient was a 47-year-old patient with massive HCC(18 cm×15 cm×4.5 cm)in the left liver with severe cirrhosis.The left portal branch was occluded and a tumor thrombus formed,and the tumor partly involved the middle hepatic vein.The patient underwent palliative surgery of left hemihepatectomy(including resection of the middle hepatic vein)for HCC,followed by three TACE procedures and oral TKIs 2 weeks after surgery.Six months later,the re-examination via computed tomography revealed no tumour activity in the remaining right liver,while magnetic resonance imaging revealed slight local tumor enhancement in the caudate lobe of the liver considered,TACE was performed once again,and during the next follow-up of 10 months did not reveal new intrahepatic lesions or distant metastases.CONCLUSION These cases demonstrate that the addition of palliative surgery to conversion therapy in a selected population with a high tumor burden could benefit patients with initially unresectable HCC.

Charcoal Nanoparticles as a Delivery System for Doxorubicin and Sorafenib in Treatment of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obtained for charcoal, doxorubicin/charcoal, and sorafenib/charcoal nanoparticles. The cytotoxic activity of Doxorubicin-ACNP and Sorafenib-ACNP was evaluated in-vitro against HepG2 cell lines and it was observed that Drug loaded ACNP improved anticancer activity when compared to Doxorubicin or Sorafenib alone. Moreover, testing the toxicity potential of DOX-ACNP and Sorafenib-ACNP showed a significant reduction in the hemolysis of red blood cells when compared to Doxorubicin and Sorafenib alone. Conclusion: In conclusion, it is notable to state that this study is regarded as the first to investigate the use of Activated charcoal for the loading of Doxorubicin and Sorafenib for further use in the arena of hepatocellular carcinoma. Doxorubicin-ACNP and Sorafenib-ACNP showed noteworthy anticancer activity along with a reduced potential of RBCs hemolysis rendering it as an efficacious carrier with a low toxicity potential.

Prevalence and Characterization of Pathogens Responsible for Enteric Fever and Assessment of Their Antibiotic Susceptibility Pattern in Bangladesh

In Bangladesh, Enteric fever is a persistent health issue throughout the year, occasionally reaching epidemic levels. The growing antibiotic resistance makes treatment increasingly challenging. Therefore, studying the antibiotic resistance patterns within the population is crucial to ensure a more effective treatment strategy. This study was designed to determine the prevalence, antimicrobial susceptibility profile, and factors associated with Salmonella spp. infections among clinically suspected Enteric fever patients in Bangladesh. This study also aimed to investigate whether there has been a re-emergence in the susceptibility of bacterial strains to conventional drugs. Data were collected from February 2024 to July 2024, from patients suspected Enteric fever (fever less than seven days duration) in a Private Diagnostic Center of Bangladesh. A total of 195 blood samples were cultured, where 53.85% came out positive, among which 79.05% Salmonella typhi and 20.95% Salmonella paratyphi A were found. Prevalence of Typhoid fever was observed high among the school-going age group (0 - 15 years) patients. Both these organisms were susceptible to ceftazidime, cefixime, ceftriaxone and cefepime but resistant to nalidixic acid, ciprofloxacin and levofloxacin. Nalidixic Acid is resistant to all S. paratyphi A and sensitive to few S. typhi. Ciprofloxacin and levofloxacin showed delayed response (36.14% and 22.72% sensitive to S. typhi and S. paratyphi A, respectively) and resistance (63.85% and 77.27% resistant to S. typhi and S. paratyphi A, respectively). In case of S. typhi, the resistance was found against ampicillin (32.53%), chloramphenicol (27.71%), cotrimoxazole (24.09%) and the resistance of S. paratyphi A found against ampicillin (4.54%), chloramphenicol (0%) and cotrimoxazole (0%). This study will provide clinicians with alternative drug options and facilitate the effective treatment of Enteric fever.

Dapagliflozin as an oral antihyperglycemic agent in the management of diabetes mellitus in patients with liver cirrhosis

BACKGROUND The use of dapagliflozin in patients with cirrhosis has been relatively restricted due to concerns regarding its overall safety and pharmacological profile in this population.AIM To determine the safety and effectiveness of dapagliflozin in the co-management of diabetes mellitus and cirrhosis with or without ascites.METHODS The patients studied were divided into two groups:100 patients in the control group received insulin,while 200 patients received dapagliflozin.These patients were classified as Child A,B,or C based on the Child–Pugh classification.Child A or B and Child C were administered doses of 10 mg and 5 mg of dapagliflozin,respectively.RESULTS The rate of increased diuretics dose was markedly elevated in the group that received insulin compared to the group that received dapagliflozin.In addition,dapagliflozin treatment substantially reduced weight,body mass index,and fasting blood glucose compared to the insulin group during follow-up.However,there were no significant differences in hemoglobin A1c,liver function,or laboratory investigations between both groups during the follow-up period.The incidence of hypoglycemia,hepatic encephalopathy,variceal bleeding,and urinary tract infection was significantly higher in the insulin group compared to the dapagliflozin group.In contrast,the dapagliflozin group experienced significantly higher rates of frequent urination and dizziness.In addition,the insulin group exhibited a marked worsening of ascites compared to the dapagliflozin group.CONCLUSION Dapagliflozin demonstrated safety and efficacy in the treatment of diabetic patients who have cirrhosis with or without ascites.This resulted in an improvement of ascites,as well as a decrease in diuretic dose and Child–Pugh score.

Comprehensive Assessment of Anxiolytic Properties in 4-HPAA Derivatives: Bridging in Vivo Validation and Molecular Docking Analyses

Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.

Research trends in pharmacogenomics of immune diseases:A bibliometric study

Background:Numerous academic studies have explored the utilization of pharmacogenomics in the context of immunologic diseases in recent years.Despite this,there is a notable absence of scientometric analyses focusing on the literature within this domain.Methods:This study employs bibliometric methods to systematically categorize the literature pertaining to pharmacogenomics in the context of immune diseases,with the aim of identifying research trends,key areas of interest,and prominent research institutions in this field.Results:Scientometric analysis compared 812 international publications with 71 Chinese publications,finding that the prevailing international research focus is on the precise dosing and therapy of immunosuppressants like mercaptopurine,a topic more extensively explored than in Chinese literature.Conclusion:It is found that the research focus is centered on precision medication and therapy,with a particular emphasis on the utilization of different immunosuppressants like mercaptopurine and tacrolimus.Furthermore,it is anticipated that precision dosing of emerging immunosuppressants like sirolimus will be a significant are a of future research.

The Impact of a Clinical Pharmacist in the Emergency Department of an Academic Hospital in the Kingdom of Saudi Arabia

Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without being checked by a pharmacist first, which may lead to an increase in the incidence of patient medication errors （MEs）. Objective： The current study evaluated the needs of the clinical pharmacy service in the DEM at King Saud University Medical City （KSUMC）, Riyadh, Saudi Arabia. Methods： A cross-sectional retrospective study was conducted between Jan 2016 to Dec 2017 and the documentation of clinical pharmacist interventions was extracted from Esihi database. Results： A total of 2,255 interventions for 862 patients were documented. The recommended interventions were as follows： 645 （dose adjustments）, 108 （therapeutic substitutions）, and 354 interventions （initiating drug therapy）. Adverse drug reactions （ADRs） were reported in 16 patients, and drug interactions were managed in 26 patients. The DEM responded to 713 information inquires and 290 pharmacokinetic consultations. Drug discontinuations included 39 incidents （where unjustified drug prescription occurred）, 37 （where contraindications were involved）, and 19 （where duplicate therapy was involved）. The most common interventions were related to the following drugs： antibiotics （34%）, anticoagulants （15%）, and anticonvulsants （10%）. The acceptance rates for the EM clinical pharmacist recommendations increased from 93.9% in 2016 to 99% in 2017. The most common outcome for interventions was to optimize the therapeutic effects of the drugs that were administered （73%）. Reconciliation was done in 796 patients. Conclusions： The clinical pharmacy service plays a critical role in the management of patients in the emergency department （ED）.