Does health economics research align with the disease burden in the Middle East and North Africa region?A systematic review of economic evaluation studies on public health interventions

Introduction:Economic evaluation studies demonstrate the value of money in health interventions and enhance the efficiency of the healthcare system.Therefore,this study reviews published economic evaluation studies of public health interventions from 26 Middle East and North Africa(MENA)countries and examines whether they addressed the region’s major health problems.Methods:PubMed and Scopus were utilized to search for relevant articles published up to June 26,2021.The reviewers independently selected studies,extracted data,and assessed the quality of studies using the Consolidated Health Economic Evaluation Reporting Standards(CHEERS)checklist.Results:The search identified 61 studies.Approximately half(28 studies;46%)were conducted in Israel and Iran.The main areas of interest for economic evaluation studies were infectious diseases(21 studies;34%),cancers(13 studies;21%),and genetic disorders(nine studies;15%).Five(8%),39(64%),16(26%),and one(2%)studies were classified as excellent,high,average,and poor quality,respectively.The mean of CHEERS checklist items reported was 80.8%(SD 14%).Reporting the structure and justification of the selected model was missed in 21 studies(37%),while price and conversion rates and the analytical methods were missed in 21 studies(34%).Conclusions:The quantity of economic evaluation studies on public health interventions in the MENA region remains low;however,the overall quality is high to excellent.There were obvious geographic gaps across countries regarding the number and quality of studies and gaps within countries concerning disease prioritization.The observed research output,however,did not reflect current and upcoming disease burden and risk factors trends in the MENA region.

Cell membrane-coated mRNA nanoparticles for enhanced delivery to dendritic cells and immunotherapy

Cationic polymers such as polyethylenimine have been considered promising carriers for mRNA vaccines.However,their application is hindered by their inherent toxicity and a lack of targeted delivery capability.These issues need to be addressed to develop effective cancer vaccines.In this study,we investigated whether dendritic cell membrane-coated polyethylenimine/mRNA nanoparticles(DPN)could effectively deliver mRNA to dendritic cells and induce immune responses.For comparison,we employed red blood cell membrane-coated polyethylenimine/mRNA(RPN)and plain polyethylenimine/mRNA polyplex(PN).The dendritic cell membrane coating altered the zeta potential values and surface protein patterns of PN.DPN demonstrated significantly higher uptake in dendritic cells compared to PN and RPN,and it also showed greater mRNA expression within these cells.DPN,carrying mRNA encoding luciferase,enhanced green fluorescent protein,or ovalbumin(OVA),exhibited higher protein expression in dendritic cells than the other groups.Additionally,DPN exhibited favorable mRNA escape from lysosomes post-internalization into dendritic cells.Inmice,subcutaneous administration of DPN containing ovalbumin mRNA(DPN_(OVA))elicited higher titers of anti-OVA IgG antibodies and a greater population of OVA-specific CD8^(+)T cells than the other groups.In a B16F10-OVA tumor model,DPNOVA treatment resulted in the lowest tumor growth among the treated groups.Moreover,the population of OVA-specific CD8^(+)T cellswas the highest in the DPNOVA-treated group.While we demonstrated DPN’s feasibility as an mRNA delivery system in a tumor model,the potential of DPN can be broadly extended for immunotherapeutic treatments of various diseases through mRNA delivery to antigen-presenting cells.

Prevention and treatment of hypoxia-induced colorectal cancer damage in albino Wister rats

Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood vessels.Tumor heterogeneity arises from both tumor cells and distinct microenvironments.Maldistribution of blood vessels,creates hypoxic regions within the tumors,fostering cancer stem cell-like properties due to reduced oxygen and nutrient supply.Under hypoxia,tumor cells shift to a glycolytic pathway,producing more lactic acid that acidifies the microenvironment and leads to unstable heart rate variability(HRV)factors,weight disparity,and a higher incidence of aberrant crypt foci(ACF).These hypoxic-induced parameters promote cancer cell invasion,increase radiation resistance,and facilitate cancer cell migration.Methods:In this study,we induced hypoxia-preneoplastic colon damage in albino Wister rats by administrating 1,2-dimethyl hydrazine(DMH).After successfully creating a hypoxic environment in albino Wister rats,resulting in preneoplastic colon damage,we randomly allocated Wistar albino rats into seven groups,each containing 8 animals,and conducted a 6-week study.Group 1-Normal control(administered 1 mM EDTA+saline,2 ml/kg/day,p.o.);group 2-Toxic control(administered DMH,30 mg/kg/week,s.c.);group 3-Standard treatment(DMH,30 mg/kg/week,s.c.for 6 weeks),followed by 5-fluorouracil and Leucovorin(25 mg/kg each on 1^(st),3^(rd),7^(th),and 10^(th) days,i.p.after 6 weeks administration of DMH);group 4-Low dose of P1(DMH,30 mg/kg/week,s.c.+P1,2 mg/kg,i.v.,weekly for 3 weeks);group 5-High dose P1(DMH,30 mg/kg/week,s.c.+P1,4 mg/kg,i.v.,weekly for 3 weeks),group 6-Low dose of P2(DMH,30 mg/kg/week,s.c.,+P2,2 mg/kg,i.v.,weekly for 3 weeks),group 7-High dose of P2(DMH,30 mg/kg/week,s.c.,+P2,4 mg/kg,i.v.weekly for 3 weeks).Results:DMH-treated rats exhibited alterations in HRV factors,weight disparity,elevated gastric pH,increased total acidity,a higher incidence of ACF,and changes in antioxidant markers(TBARs,SOD,catalase,GSH).Brightfield microscopy at 40x magnification revealed the presence of large crypts within aberrant crypt foci in the toxic control group.Conclusion:Treatment groups P1 and P2 containing triazine derivatives initiated proteasomal degradation of Hypoxia Inducible Factor-1α(HIF-1α)by activating Prolyl Hydroxylase(PHDs)pathways.HIF-1αunder a hypoxic environment is responsible for activating a multitude of genes involved in angiogenesis,metastasis,invasiveness,pH changes,metabolic reprogramming,stem cell maintenance,resistance to radiation,and downstream regulation of the immune system.Treatment with P1 and P2 groups helped minimize the ACF count and restored HRV factors,weight disparity,pH levels,total acidity,and oxidative balance.Our findings emphasize the potential role of 1,2,4-triazine derivatives in suppressing hypoxia-induced colon carcinogenesis.

美罗培南输液在便携式冷冻输液泵中的稳定性

目的 :研究美罗培南输液在输液泵中的稳定性。方法 :选用浓度为 2 0 ,30mg·ml-1的美罗培南输液 ,在两种条件下试验其在 2 4h内的稳定性。用高效液相色谱法测定药物浓度变化。结果 :两种浓度的美罗培南输液在两种条件下 ,2 4h内的浓度值变化率均小于 10 %。结论 :美罗培南输液在本试验的输液泵中 ,可稳定 2 4h。这对临床应用提供了依据。

Green tea compounds in breast cancer prevention and treatment

Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the develop-ment and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer.

Pharmacological properties of Datura stramonium L. as a potential medicinal tree:An overview

India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The troublesome weed,D.stramonium is a plant with both poisonous and medicinal preperties and has been proven to have great pharmacological potential with a great utility real usage in folklore medicine.D.stromonium has been scientifically proven to contain alkaloids,tannins,carbohydrates and proteins.This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities.The present paper presents an exclusive review work on the ethnomedical,phytochemical,pharmacological activities of this plant.

Lipid nanoparticle-mediated CRISPR/Cas9 gene editing and metabolic engineering for anticancer immunotherapy

Metabolic engineering of the tumor microenvironment has emerged as a new strategy.Lactate dehydrogenase A(LDHA)is a prominent target for metabolic engineering.Here,we designed a cationic lipid nanoparticle formulation for LDHA gene editing.The plasmid DNA delivery efficiency of our lipid nanoparticle formulations was screened by testing the fluorescence of lipid nanoparticles complexed to plasmid DNA encoding green fluorescence protein(GFP).The delivery efficiency was affected by the ratios of three components:a cationic lipid,cholesterol or its derivative,and a fusogenic lipid.The lipid nanoparticle designated formulation F3 was complexed to plasmid DNA co-encoding CRISPR-associated protein 9 and LDHA-specific sgRNA,yielding the lipoplex,pCas9-sgLDHA/F3.The lipoplex including GFP-encoding plasmid DNA provided gene editing in HeLa-GFP cells.Treatment of B16F10 tumor cells with pCas9-sgLDHA/F3 yielded editing of the LDHA gene and increased the pH of the culture medium.pCas9-sgLDHA/F3 treatment activated the interferon-gamma and granzyme production of T cells in culture.In vivo,combining pCas9-sgLDHA/F3 with immune checkpoint-inhibiting anti-PD-L1 antibody provided a synergistic antitumor effect and prolonged the survival of tumor model mice.This study suggests that combining metabolic engineering of the tumor microenvironment with immune checkpoint inhibition could be a valuable antitumor strategy.

Surface-modified liposomes for syndecan 2-targeted delivery of edelfosine

Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol(MW 2000)lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities(1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%,and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice,AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.

Nanoparticle-Mediated Lipid Metabolic Reprogramming of T Cells in Tumor Microenvironments for Immunometabolic Therapy

We report the activation of anticancer effector functions of T cells through nanoparticle-induced lipid metabolic reprogramming.Fenofibrate was encapsulated in amphiphilic polygamma glutamic acid-based nanoparticles(F/ANs),and the surfaces of F/ANs were modified with an anti-CD3e f(ab′)2 fragment,yielding aCD3/F/ANs.An in vitro study reveals enhanced delivery of aCD3/F/ANs to T cells compared with plain F/ANs.aCD3/F/AN-treated T cells exhibited clear mitochondrial cristae,a higher membrane potential,and a greater mitochondrial oxygen consumption rate under glucose-deficient conditions compared with T cells treated with other nanoparticle preparations.Peroxisome proliferatoractivated receptor-αand downstream fatty acid metabolismrelated genes are expressed to a greater extent in aCD3/F/AN-treated T cells.Activation of fatty acid metabolism by aCD3/F/ANs supports the proliferation of T cells in a glucose-deficient environment mimicking the tumor microenvironment.Real-time video recordings show that aCD3/F/AN-treated T cells exerted an effector killing effect against B16F10 melanoma cells.In vivo administration of aCD3/F/ANs can increase infiltration of T cells into tumor tissues.The treatment of tumor-bearing mice with aCD3/F/ANs enhances production of various cytokines in tumor tissues and prevented tumor growth.Our findings suggest the potential of nanotechnology-enabled reprogramming of lipid metabolism in T cells as a new modality of immunometabolic therapy.

Misuse of prophylactic antibiotics and prevalence of postoperative wound infection in obstetrics and gynecology department in a Sudanese hospital

Purpose: This study was conducted to audit prophylactic antibiotic use and to quantify the rate of wound infection. Methods: Across-sectional prospective study was conducted in the Obstetrics and Gynecology Department in Khartoum Teaching Hospital, Sudan during March 1st to 31st October 2010. All Patients (aged >18 years) were included. Results: Overall 725 patients were included. The performed surgical procedures were 751;of these 578 (76.9%) were Caesarean sections. Overall rate of wound infection was 7.8%. The rate of wound infection among patients operated on for caesarean section and abdominal hysterectomy was 8.3%, and 9.2%, respectively. Multivariate logistic analysis showed that body mass index [BMI] ≥ 30 kg/m2 OR 2.1, 95% CI (1.1 - 4.0), (P = 0.019) was the major independent risk factor for occurrence of wound infection. Evaluation of prescriptions’ parameters against the stated criteria showed that 113 (15.8%) patients were given antibiotics with adequate spectrum of activity, 611 (85.3%) given sub-dose/s, 83 (11.6%) received the first preoperative dose/s in a proper time window, and 716 (100%) had prophylaxis for extended duration. Overall conformity to the stated criteria for the evaluation of prescription’s parameters was not achieved in all prescriptions. Conclusions: In this setting, antibiotics were irrationally used and wound infection rate was high, and the situation calls for multiple interventions to correct the situation, through the activation of the infection control committee in the hospital and development of antimicrobial subcommittee to develop policies for the use and auditing of prophylactic antibiotics.

Recent Advancements in Nanomedicine for‘Cold’Tumor Immunotherapy

Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI therapy.Considering the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these patients.Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic strategies.This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.

Nanotechnology and vaccine development

Despite the progress of conventional vaccines,improvements are clearly required due to concerns about the weak immunogenicity of these vaccines,intrinsic instability in vivo,toxicity,and the need for multiple administrations.To overcome such problems,nanotechnology platforms have recently been incorporated into vaccine development.Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses.This advantage is attributable to the nanoscale particle size,which facilitates uptake by phagocytic cells,the gut-associated lymphoid tissue,and the mucosa-associated lymphoid tissue,leading to efficient antigen recognition and presentation.Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors,thereby stimulating specific and selective immune responses.In this review,we introduce recent advances in nanocarrierbased vaccine delivery systems,with a focus on the types of carriers,including liposomes,emulsions,polymer-based particles,and carbon-based nanomaterials.We describe the remaining challenges and possible breakthroughs,including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

Analysis and countermeasures of the conflicting between clinical practice and taking test of postgraduate of medical undergraduates

Nowadays,with the expanding enrollment of medical schools in our country,the competitive pressures of employment increase.It is very difficult for the graduates of these schools to find ideal jobs,but medical students with master or doctor degrees are relatively optimistic to the employment situation.As a result,more and more fresh medical graduates pursue the post-graduate education,thus forms a"rush of taking test of postgraduate"phenomenon[1].Clinical students

Liver tonics:review of plants used in Iranian traditional medicine

Considering the fact that liver is one of the most important organs in our body,it deserves special attention and protection.Among various recommended supplements,complementary and alternative medicines particularly herbal remedies have received much attention owing to their truly healing properties.This review profits from Iranian traditional medicine and presents advantageous herbal guide directions for liver protection.According to credible Iranian medical literature such as Al Qanun Fil Tibb.Al-Havi and Makhzan-al-Aadvia.a wide spectrum of plants have been found to be useful for cleansing and protecting the liver.Some herbs such as ghafes(Agrimonia eupatoria),kasni(Cichorium intybus),anar(Punica granatum),darchin(Cinnamomum zeylanicum),za'feran(Crocus sativus),gole-sorkh(Rosa damascena) and zereshk(Berberis vulgaris) appeared to get strong consideration and were well documented as outstanding liver tonics.We conducted a comprehensive review of available Iranian medical resources such as scientific information database and medical sciences databases which cover all in vitro and in vivo studies of medicinal plants as liver tonics and hepatoprotcctive candidates.Literature survey was accomplished using multiple databases including PubMed,ISI web of knowledge,and Google Scholar.

Computer-Aided Drug Design: An Innovative Tool for Modeling

Strategies for CADD vary depending on the extent of structural and other information available regarding the target (enzyme/receptor) and the ligands. Computer-aided drug design (CADD) is an exciting and diverse discipline where various aspects of applied and basic research merge and stimulate each other. In the early stage of a drug discovery process, researchers may be faced with little or no structure activity relationship (SAR) information. The process by which a new drug is brought to market stage is referred to by a number of names most commonly as the development chain or “pipeline” and consists of a number of distinct stages. To design a rational drug, we must firstly find out which proteins can be the drug targets in pathogenesis. In present review we reported a brief history of CADD, DNA as target, receptor theory, structure optimization, structure-based drug design, virtual high-throughput screening (vHTS), graph machines.

Influenza vaccination in acute coronary syndromes patients in Thailand： the cost-effectiveness analysis of the prevention for cardiovascular events and pneumonia

Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome （ACS） patients, but the economic perspectives can provide important data to make informed decisions. This study aimed to perform the economic evaluation of lifelong annual influenza vaccination for cardiovascular events and well-established pneumonia prevention. Methods Lifetime costs, life-expectancy, and quality-adjusted live years （QALYs） were estimated beyond one-year cycle length of a six-health states Markov model condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia, no hospitalizations occurred, or death. The comparison of three age-groups of 40-49, 50-65, and 〉 65 years scenario was performed. Incremental cost-effectiveness ratio （ICER） and net monetary benefit （NMB） were presented as a societal perspective in 2016. The model robustness was determined by one-way and prob- abilistic sensitivity analyses. Results The influenza vaccination was cost-effective in all age-groups, by dominant ICERs （lower cost with higher effectiveness） which was completely lower than acceptable willingness-to-pay threshold of Thailand [160,000 THB （4,466.8 USD） per QALYs], with a great incremental value of NMB. Especially, the 50-year-old-and- above scenario was shown as the most benefit at 129,092 THB （3,603.9 USD） for each patient. Conclusions The annually additional influenza vaccination to standard treatment in ACS was cost-effective in all age-groups, which should be considered in clinical practice and health-policy making process.

Anti-Nociceptive Effect in Mice of Thillai Flavonoid Rutin

We investigated the anti-nociceptive effect of Excoecorio ogollocho （E.ogollocho） against chemically and thermally induced nociception, Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction （Alk-CF） of E.ogollocho by oral administration. Compared with controls, AIk-CF decreased the writhing numbers （P〈0.01） in a dose dependent manner. Further we determined that, AIk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as Rutin. Docking simulation demonstrated that Rutin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. In conclusion we have identified peripheral and central anti-nociceptive activities of E.ogollocho that involve opioid receptor, and in which the active compound is Rutin.

Nanomaterials for modulating innate immune cells in cancer immunotherapy

Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies.Whereas chemotherapies use cytotoxic drugs to kill tumor cells,cancer immunotherapy is based on the ability of the immune system to fight cancer.Tumors are intimately associated with the immune system:they can suppress the immune response and/or control immune cells to support tumor growth.Immunotherapy has yielded promising results in clinical practice,but some patients show limited responses.This may reflect the complexities of the relationship between a tumor and the immune system.In an effort to improve the current immunotherapies,researchers have exploited nanomaterials in creating new strategies to cure tumors via modulation of the immune system in tumor tissues.Although extensive studies have examined the use of immune checkpoint-based immunotherapy,rather less work has focused on manipulating the innate immune cells.This review examines the recent approaches and challenges in the use of nanomaterials to modulate innate immune cells.

Anti-ulcer activity of Ficus religiosa leaf ethanolic extract

Objective:To evaluate the anti-ulcer activity and acute toxicity ofFicus religiosa(F. religiosa)leaf ethanolic extract in animal models.Methods:Anti-ulcer activity ofF. religiosaethanolicextract(250 and 500 mg/kg body weight) was studied on stress induced ulcer animal models.Ranitidine was used as standard. The anti-ulcer activity ofF. religiosawas evaluated with thehelp of ulcer area and histopatholgical examination. Preliminary phyto-chemical screeningand acute toxicity studies ofF. religiosaalso carried out.Results:Results showed that theextract treatments prevented ulcer area and gastric secretion in a dose-dependent manner.Administration of 2000 mg/kg extract did not show any acute toxicity in albino mice. Preliminaryphytochemical analysis identified the presence of flavonoids in the ethanolic extract ofF. religiosa.Conclusions:The extract is non-toxic even at relatively high concentrations. The anti-ulceractivity is probably due to the presence of flavanoids.