Individualized intensive insulin therapy of diabetes: Not only thegoal, but also the time

Intensive insulin therapy has been extensively used to control blood glucose levels because of its ability to reduce the risk of chronic complications of diabetes.According to current guidelines,intensive glycemic control requires individu-alized glucose goals rather than as low as possible.During intensive therapy,rapid blood glucose reduction can aggravate microvascular and macrovascular complications,and prolonged overuse of insulin can lead to treatment-induced neuropathy and retinopathy,hypoglycemia,obesity,lipodystrophy,and insulin antibody syndrome.Therefore,we need to develop individualized hypoglycemic plans for patients with diabetes,including the time required for blood glucose normalization and the duration of intensive insulin therapy,which deserves further study.

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.

Clinical Effects of Intensive Insulin Therapy Treating Traumatic Shock Combined with Multiple Organ Dysfunction Syndrome

The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome （MODS） were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups： control group （n=56） treated with conventional therapy, and intensive insulin therapy group （n=58） treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells （WBC） counts, prothrombin time （PT）, serum creatinine （SCr）, alanine aminotransferase （ALT）, serum albumin and PaO2 were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced （P0.05）, but the level of serum albumin was significantly increased （P0.05） at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 （P0.01） after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased （P0.01）. The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

Influence of Intensive Insulin Therapy on Vascular Endothelial Growth Factor in Patients with Severe Trauma

The influence of early-stage intensive insulin therapy on the plasma levels of vascular en- dothelial growth factor （VEGF） and the related parameters in patients with severe trauma and the clini- cal implication were investigated. Sixty-four cases of severe trauma （injury severity score 〉20） with stress hyperglycemia （blood glucose 〉9 mmol/L） were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient grada- tion one-step process were used to determine plasma VEGF, endothelin-1 （ET-1）, and the number of circulating endothelial cells （CECs） at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF （ng/L）, 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P〈0.05, 0.01, 0.05, 0.05 respectively; for ET-1 （ng/L）, 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P〈0.05, 0.01, 0.01, 0.01 respectively; for CRP （mg/L）, 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P〈0.05; for CECs （/0.9 μL）, 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P〈0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.

Effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy

AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. METHODS: Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance. RESULTS: Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026). CONCLUSION: There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.

Risk factors, incidence, and morbidity associated with antibioticassociated diarrhea in intensive care unit patients receiving antibiotic monotherapy

BACKGROUND This study aimed to identify factors associated with antibiotic-associated diarrhea(AAD)in patients in the department of intensive care medicine who received antibiotic monotherapy in order to reduce the incidence of AAD and improve rational use of antibiotics in these patients.AIM To report the incidence of AAD and the factors associated with AAD in patients receiving antibiotic monotherapy.METHODS The study used a single-center retrospective design.A total of 209 patients were enrolled.Patients were divided into two groups:No-AAD group(without AAD)and AAD group(with AAD).There were 45 cases in the AAD group and 164 cases in the no-AAD group.Clinical data of all patients were collected.Data were analyzed using SPSS(version 18.0),and statistical significance was set at P<0.05.RESULTS The overall incidence of AAD was 21.53%.Age[odds ratio(OR)1.022,95%confidence interval(CI):1.001-1.044,P=0.040],proton pump inhibitor usage time(OR 1.129,95%CI:1.020-1.249,P=0.019),antibiotic usage time(OR 1.163,95%CI:1.024-1.320,P=0.020),and intensive care unit(ICU)stay time(OR 1.133,95%CI:1.041-1.234,P=0.004)were associated with AAD in ICU patients receiving antibiotic monotherapy.mean±SD ICU stay time was lower in the no-AAD group(8.49±6.31 vs 15.89±10.69,P<0.001).However,there was no significant difference in ICU-related mortality rates between the two groups(P=0.729).CONCLUSION Older age,longer ICU stay time,duration of use of proton pump inhibitors,and duration of antibiotic increase the incidence of AAD in ICU patients receiving antibiotic monotherapy.

Neonatal Death Rates: Lack of Equal Access to Hospital Obstetric Service and Intensive Therapy

Aim: To identify the association between access to obstetric and neonatal hospital service and neonatal death rates. Method: Quantitative and retrospective research retrieved from Declaration of Live Newly-born Children;Declaration of Death;Investigation Chart on Municipal Child Mortality, between 2000 and 2009, at the Nucleus of Information on Mortality Rates. The population studied comprised 537 neonatal deaths and mothers with residence in the municipality, and investigated by the work team of the Committee for the Investigation of Mother-Child Deaths. Data were analyzed in Epi Info 2002? computer program and the Statistical Package for the Social Sciences? was used. Chi-square Test and Fischer’s Exact Test were applied at p < 0.05. Results: 63.7% of 537 neonates were born in hospitals with maternities and neonatal intensive therapy unit;60.7% weighed ≤1.500 grams;76.7% had a pregnancy age of ≤36 weeks;73% died of asphyxia in the 1st minute and 73.5% died during the perinatal period. Throughout the ten years of analysis, access to hospital obstetric service without NITU reduced death rate from 25% in 2000 to 6.8% in 2009. There was a significant statistical association between place of delivery and maternal socio-demographic variables (maternal age bracket p = 0.028;schooling p = 0.000;family income p = 0.000);occupation p = 0.000) and neonatal variables (race/skin color p = 0.007;type of delivery p = 0.000;weight at birth p = 0.000;pregnancy age p = 0.000 and Apgar Score 1st minute p = 0.000 and Apgar Score 5th minute p = 0.007). Conclusion: Although the municipal government provides obstetric services and specialized neonatal care, this right is not extensive to all;gaps at different levels in mother-child care should be identified to reduce neonatal deaths.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Effect of Intensive Therapy of Multiple Factors Intervention on Vascular Complications in Type 2 Diabetes

The effects of intensive versus regular therapy on incidence and progress of microalbuminuria in type 2 diabetes were compared. During a follow-up of 3 years, 96 cases of diabetes mellitus were randomized to intensive and regular therapy groups. HbA 1c goal was same in the two groups, but the goal of blood pressure (Bp) and lipid was more strict in the intensive therapy group than in the regular therapy group. There was statistically significant difference in the incidence and progression of vascular complications between the two groups. Logistic stepwise-regression analysis (odds ration, OR) showed that there was significant difference in the progression of nephropathy (OR 0.24, 95 % CI 0.12-0.76), retinopathy (OR 0.38, 95 % CI 0.16-0.88), peripheral neuropathy (OR 0.42, 95 % CI 0.22-0.86) and autonomic neuropathy (OR 0.29, 95 % CI 0.12-0.86) between the two groups (P<0.01). It was concluded that intensive blood glucose controlling could retard diabetic vascular complications. Intensive therapy of multiple factors interventions (controlling Bp, regulating blood lipid, improving microcirculation) could decrease various risk factors for diabetic vascular complications.

Efficacy and Safety of Insulin Glulisine in Intensive Insulin Therapy: Bolus Insulin Adjust Nice Control by apiDRA Study (BANDRA Study)

Background: Treatment for postprandial glycemia using rapid-acting insulin analogues sometimes resulted in preprandial hypoglycemia or weight gain. Objective: This study evaluated the efficacy and safety of switching bolus insulin from insulin lispro (Lis) to insulin glulisine (Glu) in patients with inadequately controlled diabetes on intensive insulin therapy with Lis and glargine (Gla). Methods: Seventy-two outpatients with inadequate glycemic control (glycated hemoglobin [HbA1c] ≥7.0%, glycated albumin [GA] ≥20%) on intensive insulin therapy comprising Lis and Gla for ≥24 weeks were enrolled. We switched treatment from Lis to Glu with a stepwise increase in the dose by 1 unit per meal to obtain a GA level of ≤20% for 24 weeks, and the efficacy and safety were evaluated. Patients’ treatment satisfaction was also evaluated using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) after the treatment. Results: After switching from Lis to Glu, both HbA1c and GA levels significantly lowered from 8.26% ± 0.13% to 7.71% ± 0.13% (P < 0.01) and from 23.9% ± 1.8% to 21.4% ± 1.9% (P < 0.01), respectively. Furthermore, switching from Lis to Glu improved patients’ treatment satisfaction;scores for 7 of the 8 items, such as “satisfaction” and “convenience” were significantly improved (P < 0.001), with no significant change in the scores for “improvement of hypoglycemia” (P = 0.91). Conclusions: Our present study suggests that switching bolus insulin from Lis to Glu by the addition of 1 unit of Glu per meal may be a useful treatment option for patients with inadequate glycemic control receiving intensive insulin therapy with Lis and Gla.

Intensive Insulin Therapy Has No Effect on Mortality and Morbidity in Cardiac Surgery Patients: A Meta-Analysis

Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy (IIT) (maintain glucose p = 0.628), ICU LOS (MD = -0.073 days, 95% CI = -0.324 to 0.178;p = 0.568), or hospital LOS (MD = 0.269, 95% CI = -2.158 to 2.696;p = 0.828). No difference in AF rates (RR = 0.887, 95% CI = 0.681 to 1.155;p = 0.375) or deep sternal infection (RR = 0.985, 95% CI = 0.357 to 2.720;p = 0.977) were observed. Conclusion: IIT targeting blood sugar levels of 80 - 120 mg/dl have no effect on perioperative outcomes in cardiac surgery patients. IIT is associated with similar mortality, ICU LOS, hospital LOS, AF rates, and deep sternal infection rates compared to more liberal glycemic strategies. IIT should not replace CIT as the standard of care in cardiac surgery patients.

Systemic oncological therapy in breast cancer patients on dialysis

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

Autonomous VR Exposure Therapy for Anxiety Disorders Using Conversational AI—Ethical and Technical Implications and Preliminary Results

The need for psychotherapy is very high and the lack of care causes a lot of suffering and high costs. This paper presents an interdisciplinary approach to creating an AI-guided exposure therapy for fear of heights in virtual reality (VR). First, ethical principles for the use of conversational AI in psychotherapy were translated into technical requirements and made measurable. Based on this, an autonomous virtual reality exposure therapy was iteratively developed with a therapist. The feasibility and implementation of the ethical principles were tested with a patient. The patient was very satisfied with the VR setup. The AI therapist was also rated positively, although there is still room for improvement regarding conversational skills. Overall, the paper shows how AI can contribute responsibly to improving the psycho-therapeutic supply. It also provides guidelines that make ethical principles tangible and measurable for developers.

Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

Low-frequency repetitive transcranial magnetic stimulation（LF-r TMS） to the contralesional hemisphere and intensive occupational therapy（i OT） have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-r TMS and i OT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient＇s Trail-Making Test part B（TMT-B） performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-r TMS to the contralesional hemisphere and 2 sessions of i OT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-r TMS to the contralesional hemisphere combined with i OT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.

Optimal indicator for changing the filter during the continuous renal replacement therapy in intensive care unit patients with acute kidney injury:A crossover randomized trial

BACKGROUND:The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy(CRRT)in intensive care unit(ICU)patients with acute kidney injury(AKI).METHODS:Patients with AKI requiring CRRT in an ICU were randomly divided into two groups for crossover trial,i.e.,groups A and B.Patients in the group A were firstly treated with continuous veno-venous hemofiltration(CVVH),followed by continuous veno-venous hemodiafiltration(CVVHDF).Patients in the group B were firstly treated with CVVHDF followed by CVVH.Delivered doses of solutes with different molecular weights at the indicated time points between groups were compared.A correlation analysis between the delivered dose and pre-filter pressure(P_(PRE))and transmembrane pressure(P_(TM))was performed.Receiver operating characteristic(ROC)curves were constructed to evaluate the accuracy of P_(TM) as an indicator for filter replacement.RESULTS:A total of 50 cases were analyzed,27 in the group A and 23 in the group B.Delivered doses of different molecular-weight solutes significantly decreased before changing the filter in both modalities,compared with those at the initiation of treatment(all P<0.05).In the late stage of CRRT,the possible rebound of serum medium-molecular-weight solute concentration was observed.P_(TM) was negatively correlated with the delivered dose of medium-molecular-weight solute in both modalities.The threshold for predicting the rebound of serum concentration of medium-molecularweight solute by P_(TM) was 146.5 mm Hg(1 mm Hg=0.133 k Pa).CONCLUSIONS:The filter can be used as long as possible within the manufacturer’s safe use time limits to remove small-molecular-weight solutes.P_(TM) of 146.5 mm Hg may be an optimal indicator for changing the filter in CRRT therapies to remove medium-molecular-weight solutes.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

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.

Determinants of Persistent Sputum Smear Positivity after Intensive Phase Chemotherapy among Patients with Tuberculosis at Rhodes Chest Clinic, Nairobi, Kenya

The prevalence of TB in sub-Sahara Africa has been reported as 511 per 100,000 populations and a mortality of 74 per 100,000 in year 2009. In the same period, incidence was estimated at 350 cases per 100,000. In this regard, the health system requires strengthening to respond to the rising cases of infection, drug resistance and quality of life lost while continuing to seek interventions that improve adherence to medication and case detection among those infected. Methods: This study sought to determine factors that are associated with sputum positivity after intensive phase of chemotherapy in people with tuberculosis. It was a retrospective case-control study conducted in Rhodes chest clinic, a City Council health unit in Nairobi that specializes in treatment of chest infections. The participants were sampled from clinic attendants who had completed two months of intensive phase TB chemotherapy and met inclusion criteria. Results: Seventy participants of whom 25 (36%) were sputum positive at the end of two (2) months intensive phase were included in the study. Skipping medication doses was significantly associated with sputum positivity (p = 0.01). Patients who were sputum positive at the end of the two-month period were more likely to have taken longer time before seeking treatment compared to those who were sputum negative by median (IQR) 8 (3 - 12) and 4 (3 - 8) weeks respectively although this difference was not significant (p = 0.09). Patients who had not disclosed their infection status had a two-fold possibility of remaining sputum positive at the end of intensive phase. Conclusion: Early diagnosis and treatment of TB, and adherence to medication were important factors that affect sputum conversion during intensive phase of TB treatment. Therefore, public health practitioners should advise patients to seek prompt diagnosis and treatment of signs and symptoms of tuberculosis.

A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.