Goal-directed therapy in intraoperative fluid and hemodynamic management

Intraoperative fluid management is pivotal to the outcome and success of surgery, especially in high-risk proce- dures. Empirical formula and invasive static monitoring have been traditionally used to guide intraoperative fluid management and assess volume status. With the awareness of the potential complications of invasive procedures and the poor reliability of these methods as indicators of volume status, we present a case scenario of a patient who underwent major abdominal surgery as an example to discuss how the use of minimally invasive dynamic monitoring may guide intraoperative fluid therapy.

Use of Early Goal-Directed Therapy in the Emergency Department before and after the Sepsis Trilogy

The management of sepsis evolved recently with the publication of three large trials (referred to as the sepsis trilogy) investigating the efficacy of early goal-directed therapy (EGDT). Our goal was to determine if the publication of these trials has influenced the use of EGDT when caring for patients with severe sepsis and septic shock in the emergency department (ED). In February 2014, we surveyed a sample of board-certified emergency medicine physicians regarding their use of EGDT in the ED. A follow-up survey was sent after the publication of the sepsis trilogy. Data was analyzed using 95% confidence intervals to determine if there was a change in the use of EGDT following the publication of the above trials. Subgroup analyses were also performed with regard to academic affiliation and emergency department volume. Surveys were sent to 308 and 350 physicians in the pre-and post-publication periods, respectively. Overall, ED use of EGDT did not change with publication of the sepsis trilogy, 48.7% (CI 39.3% - 58.2%) before and 50.5% (CI 40.6% - 60.3%) after. Subgroup analysis revealed that academic-affiliated EDs significantly decreased EGDT use following the sepsis trilogy while nonacademic departments significantly increased EGDT use. Use of EGDT was significantly greater in community departments versus academic departments following the publication of the sepsis trilogy. There was no change overall in the use of EGDT protocols when caring for patients with severe sepsis and septic shock, but subgroup analyses revealed that academic departments decreased their use of EGDT while community departments increased use of EGDT. This may be due to varying rates of uptake of the medical literature between academic and community healthcare systems.

Simplified Intraoperative Goal-Directed Therapy Using the FloTrac/Vigileo System: An Analysis of Its Usefulness and Safety

Purpose: We investigated whether the simplified intraoperative Goal-Directed Therapy (GDT) could improve the factors affecting medical costs, and contribute in standardizing intraoperative fluid management. Methods: The enrolled patients underwent esophagectomy, pancreatoduodenectomy, or aortic stent grafting in 2012, and between March 2013 and October 2014. We conducted a comparison study on the effects of GDT, between the before-GDT historical control group (n = 100) and GDT group (n = 100). The hemodynamic indices used for control group patients were conventional: Blood pressure, heart rate, and urine output. For GDT group, additionally, we used stroke volume variation (SVV) and stroke volume index (SVI). The primary outcomes were the length of intensive care unit (ICU) stay and hospital stay (LOS). Regression analysis was used to identify factors affecting LOS. The secondary outcomes were the albumin use, the fluid amount administered, and the variation in the fluid administration rate. Results: The control and GDT groups comprised 96 and 99 patients, respectively. The patient characteristics were similar. The length of ICU stay was significantly shorter (2.1 ± 2.1 days vs. 2.8 ± 1.9 days, P = 0.0009) and LOS was shorter but without statistical significance (24.5 ± 17.7 days vs. 27.7 ± 20.1 days, P = 0.21) in the GDT group than in the control group. The fluid amount administered and the presence/ absence of albumin use were factors affecting LOS. The variation of the fluid administration rate was significantly lower in the GDT group. Conclusion: The simplified GDT may contribute to the improvement of medical economics and standardize the fluid management.

Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery

Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications.We further tested the role of this mediation effect using mean arterial pressure,a hemodynamic indicator.Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis.We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications.We conducted mediation analysis using the mediation package in R(version 3.1.2),based on 5,000 bootstrapped samples,adjusting for covariates.Results Among the 300 patients in the study,40%(120/300)developed postoperative complications within 30 days.GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders(odds ratio:0.460,95%CI:0.278,0.761;P=0.003).The total effect of GDFT on postoperative complications was-0.18(95%CI:-0.28,-0.07;P<0.01).The average causal mediation effect was-0.08(95%CI:-0.15,-0.04;P<0.01).The average direct effect was-0.09(95%CI:-0.20,0.03;P=0.17).The proportion mediated was 49.9%(95%CI:18.3%,140.0%).Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications.Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

Hepatic Perfusion Alterations in Septic Shock Patients： Impact of Early Goal-directed Therapy

Background： Early goal-directed therapy （EGDT） has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients. Methods： A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients＇ characteristics were compared before treatment （TO）, immediately after EGDT （T 1 ）, and 24 h after EGDT （T2）. This study is registered at ClinicalTrials.org, NCT02060773. Results： Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients： therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate （ICG-PDR） and 15-min retention rate （Rl 5） at TO （ 11.9 ±5.0%/min and 20.0 ±13.2%）, T1 （ 11.4 ± 5.1%/min and 23.6 ± 14.9%）, and T2 （ 11.0 ±4.5%/rain and 23.7 ± 15.3%） （all P 〉 0.05）. Both of the alterations of ICG-PDR and R l 5 showed no differences at TO, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected （P 〉 0.05）.

Intraoperative Goal-Directed Therapies in Femoral and Pelvic Osteotomies in Children and In-Hospital Postoperative Outcomes

Background: Femoral and pelvic osteotomies are potential hemorrhagic interventions where transfusion requirements can be necessary. Objective: We undertook a secondary analysis of patients who underwent femoral and pelvic osteotomy in the initial cohort. The objective of this secondary analysis was to describe intraoperative and postoperative outcomes and to describe intraoperative management in these patients in terms of blood product management and fluid and hemodynamic therapy with the aim of implementing optimization management protocols for postoperative outcome improvement. Methods: A secondary analysis of patients who underwent femoral and pelvic osteotomy surgery was included in the initial retrospective study. Results: There were eighteen patients with a mean age of 104 ± 47.1 months. Four (22.2%) patients had intraoperative and/or postoperative complications. One patient (5.6%) had an intraoperative hemorrhagic shock, two patients (11.1%) had postoperative neurologic failure, and one patient (5.6%) had postoperative wound sepsis. The transfusion rate was 50% in nine patients. Conclusion: Femoral and pelvic osteotomies are interventions where blood, transfusion and fluid requirements can be increased;thus, this implies the necessity of a global patient blood management protocol with point-of-care tests and fluid- and hemodynamic-guided protocols with validated tools in children for intraoperative and postoperative outcome optimization.

Scoliosis in Children: Impact of Goal-Directed Therapies on Intraoperative and Postoperative Outcomes

Background: Scoliosis is among interventions with high postoperative complication rates due to the characteristics of the surgery, where blood loss, transfusion and fluid requirements can be increased. A monocentric retrospective observational study was undertaken earlier to determine predictors of intraoperative and postoperative outcomes in surgical patients. In this initial cohort, there were patients who underwent scoliosis surgery, and a secondary analysis to describe outcomes in these patients was realized and presented here. Objective: To describe intraoperative and postoperative outcomes in patients under 18 years old in scoliosis surgery included in the initial study and to propose improvement and implementation measures. Methods: A secondary analysis of patients undergoing scoliosis surgery from 1 January 2014 to 17 May 2017 was undertaken in our institution—Necker Enfants Malades university hospital. The study was approved by the Ethics Committee. Results: There were 116 patients with a mean age of 147.5 ± 40.2 months. Twenty-eight patients (24.1%) presented intraoperative and/or postoperative complications. The most common intraoperative complication was hemorrhagic shock in 3 patients (2.6%). The most common postoperative organ failure was neurologic in seven patients (6%), respiratory in 3 patients (2.6%), cardio-circulatory in 2 patients (1.7%) and renal failure in 1 patient (0.9%). The most common postoperative infection was surgical wound sepsis in 8 patients (6.9%), urinary sepsis in 3 patients (2.6%), and abdominal sepsis and septicemia in 2 patients (1.7%). 12 patients (10.3%) had reoperations. Fifty-six patients (48.3%) had intraoperative transfusion. There was no in-hospital mortality. Conclusion: The portion of patients with intraoperative and or postoperative complications was 24.1%, integrating goal-directed therapies in this surgical setting could improve postoperative outcomes.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Extension of Goal-Directed Behavior Model for Post-Pandemic Korean Travel Intentions to Alternative Local Destinations: Perceived Risk and Knowledge

Since the outbreak of COVID-19,tourists have been increasingly concerned over various risks of international travel,while knowledge of the pandemic appears to vary significantly.In addition,as travel restrictions continue to impact adversely on international tourism,tourism efforts should be placed more on the domestic markets.Via structural equation modeling,this study unearthed different risk factors impacting Korean travelers’choices of alternative local destinations in the post-pandemic era.In addition,this study extended the goal-directed behavior framework with the acquisition of perceived risk and knowledge of COVID-19,which was proven to hold a sig-nificantly superior explanatory power of tourists’decisions of local alternatives over foreign countries during the COVID-19 pandemic.Furthermore,desire was found to play an imminent mediating role in the conceptual mod-el,maximizing the impact of perceived risk on travel intentions.Henceforth,this research offers meaningful the-oretical implication as thefirst empirical study to deepen the goal-directed behaviour framework with perceived risk and knowledge in the context of post-COVID-19 era.It also serves as insightful knowledge for Korean tour-ism authorities and practitioners to understand local tourists’decision-making processes and tailor effective recovery strategy for domestic tourism.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Paradoxical herniation associated with hyperbaric oxygen therapy after decompressive craniectomy: A case report

BACKGROUND Whether hyperbaric oxygen therapy(HBOT)can cause paradoxical herniation is still unclear.CASE SUMMARY A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery.HBOT was administered 22 d after surgery due to speech impairment.Paradoxical herniation appeared on the second day after treatment,and the patient’s condition worsened after receiving mannitol treatment at the rehabilitation hospital.After timely skull repair,the paradoxical herniation was resolved,and the patient regained consciousness and had a good recovery as observed at the follow-up visit.CONCLUSION Paradoxical herniation is rare and may be caused by HBOT.However,the underlying mechanism is unknown,and the understanding of this phenomenon is insufficient.The use of mannitol may worsen this condition.Timely skull repair can treat paradoxical herniation and prevent serious complications.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Goal-directed fluid therapy in gastrointestinal cancer surgery:A prospective randomized study

Objective:To investigate the effects of perioperative goal-directed fluid therapy(GDFT)on intraoperative fluid balance,postoperative morbidity,and mortality.Methods:This is a prospective randomized study,and 90 patients who underwent elective open gastrointestinal cancer surgery between April 2017 and May 2018 were included.Patients were randomized into 2 groups that received liberal fluid therapy(the LFT group,n=45)and goal-directed fluid therapy(the GDFT group,n=45).Patients’Colorectal Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity(CR-POSSUM)physiological score,Charlson Comorbidity Index(CCI),perioperative vasopressor and inotrope use,postoperative AKIN classification,postoperative intensive care unit(ICU)hospitalization,hospital stay,and 30-day mortality were recorded.Results:The volume of crystalloid used perioperatively and the total volume of fluid were significantly lower in the GDFT group compared to the LFT group(P<0.05).CR-POSSUM physiological score and CCI were significantly higher in the GDFT group(P<0.05).Although perioperative vasopressor and inotrope use was significantly higher in the GDFT group(P<0.05),postoperative acute kidney injury development was not affected.Postoperative mortality was determined to be similar in both groups(P>0.05).Conclusion:Although GDFT was demonstrated to be a good alternative method to LFT in open gastrointestinal cancer surgery,and it can prevent perioperative fluid overload,and the postoperative results are comparable in the two groups.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Effect of Goal-Directed Fluid Therapy on Lung Function, Cognitive Function and Inflammatory Response in Patients Undergoing Radical Esophageal Cancer Surgery under One-Lung Ventilation

Objective: To explore the effects of goal-directed fluid therapy (GDFT) on lung function, cognitive function and inflammatory response in patients undergoing radical esophageal cancer surgery under one-lung ventilation. Methods: Sixty-seven patients undergoing radical esophageal cancer surgery were divided into GDFT group (GDFT therapy) and control group (conventional liquid therapy). The changes in patients’ pulmonary function, cognitive function and inflammatory response were evaluated. Results: Both alveolar-arterial oxygen partial pressure difference [P(A-a)O2] and respiratory index (RI) increased at one-lung ventilation for 30 minutes (T2) and decreased at one-lung ventilation for 60 minutes (T3), and after surgery (T4) in the two groups, and the GDFT group was lower than the control group (P < 0.05);theoxygenation index (OI) of the two groups decreased at T2, T3, and T4 compared with that at T1 (before one-lung ventilation), and the GDFT group was higher than the control group (P < 0.05). At T4 and T5, the tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), central nervous system specific protein (S100β), and neuron specific enolase (NSE) in the GDFT group were lower compared to the control group (P < 0.05), while interleukin-10 (IL-10) was higher compared to the control group (P < 0.05);the incidence of perioperative neurocognitive disorder (PND) in the GDFT group was lower than that in the control group (P < 0.05). Conclusion: GDFT can help prevent lung injury during radical esophageal cancer surgery under one-lung ventilation, reduce the body’s inflammatory response, and reduce the incidence of perioperative cognitive disorder to a certain extent.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

Temperature-feedback two-photon-responsive metal-organic frameworks for efficient photothermal therapy

The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.