A Study on the Correlation of Various Factors in Patients With Severe Traumatic Brain Injuries.

INTRODUCTION: Traumatic brain injury (TBI), ranging from minor impacts to severe cases, affects temporal and frontal brain areas, contributing to mortality and disability worldwide. The Glasgow Coma Scale (GCS) evaluates consciousness levels, aiding in prioritizing emergency care, while the Disability Rating Score (DRS) assesses overall function, particularly in severe cases, with greater sensitivity than GCS for clinical changes in TBI patients. OBJECTIVES: To correlate various factors with each other in patients presented with severe TBIs. MATERIALS AND METHODS: The retrospective study analyzed data from patients with severe TBIs admitted to the hospital from February 2023 to April 2024. Patients' demographic and clinical data, including GCS and DRS scores, were collected. Statistical analysis, including logistic regression, assessed mortality predictors. RESULTS: The study revealed significant correlations (p<0.05) between age and marital status (p=0.002) and surgery (p=0.003). Surgery also correlated significantly with the mechanism of injury (p<0.001). Furthermore, a negative correlation was found between GCS after 24 hours and change in GCS (p<0.001), while a positive correlation existed between DRS after 24 hours and DRS on the 14th day (p<0.001). These findings highlight the complex interplay between demographic factors, medical interventions, and clinical outcomes in TBI patients. CONCLUSION: The study found that older individuals, particularly those involved in road traffic accidents, had poorer recovery outcomes and higher rates of surgery, with a strong correlation between changes in GCS and DRS scores.

Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters.

Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.

Clinicopathological Parameters and Biomarker Profile in a Cohort of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

INTRODUCTION:  Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region, commonly termed as head and neck squamous cell carcinoma (HNSCC). Data related to biomarker expression in HNSCC are scarcely available, especially in our population. This study aimed to evaluate the association of immunohistochemical (IHC) expression of p16, epidermal growth factor receptor (EGFR), p27, and p53 in HNSCC with clinical and pathological parameters. METHODS:  This retrospective cross-sectional study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan from February 2017 to January 2022. A total of 308 cases of HNSCC with upfront surgical resection were included in the study. IHC analysis was performed for EGFR, p16, p27, and p53, and association with clinicopathological parameters was sought. RESULTS:  p16, EGFR, and p53 positivity were noted in 22.1%, 18.8%, and 66.2% cases, respectively, whereas loss of p27 expression was seen in 14.3% cases of HNSCC. A significant association of p16 expression was observed with age, tumor size, tumor site, nodal metastasis, extranodal extension (ENE), and perineural invasion (PNI). Cases aged over 50 years were more significantly associated with positive p16. Similarly, cases with oral cavity SCC were more significantly associated with positive p16. HNSCC with larger tumor size, the presence of nodal metastasis, and ENE and PNI were associated with negative p16 expression. Similarly, a significant association of EGFR expression was observed with age, tumor size, tumor site, histological subtype, histological differentiation, nodal metastasis, ENE, and PNI (p < 0.05). Cases of HNSCC with age less than 50 years were associated with positive EGFR expression. Similarly, oral cavity and lip SCCs were associated with positive EGFR expression compared with other sites. Moreover, positive EGFR expression was significantly associated with nodal metastasis, ENE, moderate histological differentiation, and the presence of PNI. Loss of p27 expression was significantly associated with nodal stage and ENE; low nodal stage and absence of ENE were associated with p27 loss of expression, whereas no significant association was seen with other pathological parameters. Alternatively, a significant association of mutant-type p53 expression was noted with gender, nodal stage, and histological subtype. Females with HNSCC show a higher frequency of mutant-type p53 expression than males. Moreover, higher nodal stage (N2b and higher) and non-keratinizing SCCs were significantly associated with mutant-type p53 expression. CONCLUSION:  Our study found a high expression of EGFR and mutant-type p53 expression in HNSCC. Conversely, p16 expression and loss of p27 expression were low. Moreover, EGFR and mutant-type p53 expression were associated with poor pathological parameters, whereas p16 expression was associated with better histological features.

Tumor microenvironment-responsive size-switchable drug delivery nanosystems.

INTRODUCTION: Compared with ordinary chemotherapeutic drugs, the variable-size nanoparticles (NPs) have better therapeutic effects and fewer side effects. AREAS COVERED: This review mainly summarizes the strategies used to construct smart, size-tunable nanocarriers based on characteristic factors of tumor microenvironment (TME) to dramatically increase the penetration and retention of drugs within tumors. EXPERT OPINION: Nanosystems with changeable sizes based on the TME have been extensively studied in the past decade, and their permeability and retention have been greatly improved, making them a very promising treatment for tumors.

Cell therapy for nonischemic dilated cardiomyopathy: A systematic review and meta-analysis of randomized controlled trials.

Cell therapy involves transplantation of human cells to promote repair of diseased or injured tissues and/or cells. Only a limited number of mostly small-scale trials have studied cell therapy in nonischemic cardiomyopathy (NICM). We performed a meta-analysis of randomized clinical trials (RCTs) to assess the safety and efficacy of cell therapy in NICM. Electronic databases were searched for relevant RCTs from inception until August 2020. Outcomes assessed were left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter or volume (LVEDD), quality of life (QoL) indices, and major adverse cardiac events (MACEs). Weighted mean differences (MDs) and standardized mean differences (SMDs) were calculated using random-effects methods. Eleven RCTs with 574 participants were included in the analysis. There was a significant increase in mean LVEF (MD, 4.17%; 95% confidence interval [CI] = 1.66-6.69) and modest decrease in LVEDD (SMD, -0.50; 95% CI = -0.95 to -0.06) in patients treated with cell therapy compared with controls. Cell therapy was also associated with improvement in functional capacity, as assessed by the 6-minute walking distance (MD, 72.49 m; 95% CI = 3.44-141.53). No significant differences were seen in MACEs and QoL indices between treated and control groups. This meta-analysis suggests that cell therapy may improve LV systolic function and may be associated with improvement in LVEDD and functional capacity compared with maximal medical therapy. Cell therapy was safe, with no significant difference in MACEs between treatment and control groups. However, given the limitations of current studies, larger well-designed RCTs are needed to evaluate the efficacy of cell therapy in patients with NICM.

The reversal of chemotherapy-induced multidrug resistance by nanomedicine for cancer therapy.

Multidrug resistance (MDR) of cancer is a persistent problem in chemotherapy. Scientists have considered the overexpressed efflux transporters responsible for MDR and chemotherapy failure. MDR extremely limits the therapeutic effect of chemotherapy in cancer treatment. Many strategies have been applied to solve this problem. Multifunctional nanoparticles may be one of the most promising approaches to reverse MDR of tumor. These nanoparticles can keep stability in the blood circulation and selectively accumulated in the tumor microenvironment (TME) either by passive or active targeting. The stimuli-sensitive or organelle-targeting nanoparticles can release the drug at the targeted-site without exposure to normal tissues. In order to better understand reversal of MDR, three main strategies are concluded in this review. First strategy is the synergistic effect of chemotherapeutic drugs and ABC transporter inhibitors. Through directly inhibiting overexpressed ABC transporters, chemotherapeutic drugs can enter into resistant cells without being efflux. Second strategy is based on nanoparticles circumventing over-expressed efflux transporters and directly targeting resistance-related organelles. Third approach is the combination of multiple therapy modes overcoming cancer resistance. At last, numerous researches demonstrated cancer stem-like cells (CSCs) had a deep relation with drug resistance. Here, we discuss two different drug delivery approaches of nanomedicine based on CSC therapy.

Redox-responsive hyaluronic acid-based nanoparticles for targeted photodynamic therapy/chemotherapy against breast cancer.

Specific cellular uptake and sufficient drug release in tumor tissues are important for effective cancer therapy. Hyaluronic acid (HA), a skeleton material, could specifically bind to cluster determinant 44 (CD44) receptors highly expressed on the surface of tumor cells to realize active targeting. Cystamine (cys) is sensitive highly reductive environment inside tumor cells and was used as a connecting arm to connect docosahexaenoic acid (DHA) and chlorin e6 (Ce6) to the HA skeleton to obtain redox-sensitive polymer HA-cys-DHA/Ce6 (CHD). Nanoparticles were fabricated and loaded with chemotherapeutic drug docetaxel (DTX) by physical encapsulation. The prepared nanoparticles had significantly increased uptake by MCF-7 cells that overexpressed CD44 receptors, and DTX was effectively released at high reducing condition. Compared with mono-photodynamic therapy (PDT) or mono-chemotherapy, the prepared nanoparticles exhibited superior anti-tumor effect by inhibiting microtubule depolymerization, blocking cell cycle and generating reactive oxygen species (ROS). In vivo anti-tumor experiments proved that DTX/CHD nanoparticles had the best antitumor response versus DTX and CHD nanoparticles under near-infrared (NIR) irradiation. These studies revealed that redox-responsive DTX-loaded CHD nanoparticles held great potential for the treatment of breast cancer.

A sonosensitiser-based polymeric nanoplatform for chemo-sonodynamic combination therapy of lung cancer.

BACKGROUND: Lung cancer is the most common type of tumour worldwide. Its relative lethality is considerably high. However, since the tumour tissues are located deep within the human body, traditional technologies, such as photodynamic therapy, do not have the desired effect. Sonosensitisers can penetrate deeply into tissues, and sonodynamic therapy (SDT) effectively inhibits tumours by generating reactive oxygen species. Ultrasound can also penetrate deeply, with a favourable tumour inhibition effect. RESULTS: A redox/ultrasound-responsive Rhein-chondroitin sulphate-based nano-preparation encapsulating docetaxel was fabricated. The nanoparticles displayed increased cellular uptake with quick drug release, good stability, and a monodispersed form in the physiological environment. Rhein induced apoptosis and altered mitochondrial membrane potential, which enhanced the expression of apoptosis-related proteins. SDT inhibited the metastasis and angiogenesis of cancer cells and activated anti-tumour capacity by reducing the expression of M2 macrophages. CONCLUSIONS: The potential of Rhein for SDT was demonstrated. Production of reaction oxygen species was markedly enhanced after ultrasound treatment. The nanoplatform enhanced the synergistic anti-tumour effects of SDT and chemotherapeutic efficacy. The approach was biocompatibility. The findings could inform investigations of chemo-SDT for different cancers.

Retroperitoneal Sclerosing Lipogranuloma in an Adolescent With Congenital Atresia of the Inferior Vena Cava: Case Report and Literature Review.

Sclerosing lipogranuloma (SLG) in children is a rare, benign disease of unknown etiology suspected to be due to abnormal fatty tissue reaction. A 13-year-old girl presented with progressively worsening back pain. Cross-sectional imaging identified a retroperitoneal mass compressing the left ureter as well as infrarenal inferior vena cava atresia with extensive venous collaterals and chronic partially occlusive thromboses of the iliac veins. Surgical biopsy was consistent with SLG and it resolved spontaneously. SLG is typically a disease of adulthood but may be seen in children. The association between inferior vena cava atresia with venous thrombosis and development of SLG has not been reported previously.

A novel progress of drug delivery system for organelle targeting in tumour cells.

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity. This requires drugs to be specifically transported to the target organs, tissues, cells, and even specific organelles, like mitochondria, nuclei, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus (GA). The nano drug delivery system can not only protect drugs from degradation but also facilitate functional modification and targeted drug delivery to the tumour site. This article mainly reviews the targeting of nano drug delivery systems to tumour cytoplasmic matrix, nucleus, mitochondria, ER, and lysosomes. Organelle-specific drug delivery system will be a major mean of targeting drug delivery with lower toxicity, less dosage and higher drug concentration in tumour cells.

Meta-Analysis Comparing Endovascular Treatment Modalities for Femoropopliteal Peripheral Artery Disease.

Endovascular interventions are commonly utilized for treatment of femoropopliteal peripheral artery disease. The relative efficacy of these interventions remains unclear. A Bayesian network meta-analysis was performed comparing 5 endovascular treatment modalities: balloon angioplasty (BA), bare metal stent (BMS), covered stent (CS), drug-coated balloon (DCB), drug-eluting stent (DES) for femoropopliteal peripheral artery disease. The primary efficacy end points were freedom from target lesion revascularization (TLR) and primary patency at 12 months. BA was the reference treatment. Twenty-two trials including 4,381 participants provided data on TLR. Sixteen trials including 3,691 participants provided data on primary patency. Point estimates for DCB suggested that it was the most efficacious treatment for freedom from TLR (odds ratio [OR] 4.23; 95% credible intervals [CrI] 2.43 to 7.66) followed by CS (OR 3.65; 95% CrI 1.11 to 12.55), DES (OR 2.64; 95% CrI 0.72 to 9.77), and BMS (OR 2.3; 95% CrI 1.11 to 4.76). Similarly, point estimates for primary patency were highest with DES (OR 8.93; 95% CrI 3.04, 27.14) followed by CS (OR 3.91; 95% CrI 1.18, 13.84), DCB (OR 3.32; 95% CrI 1.8, 6.25), and BMS (OR 3.5; 95% CrI 1.58, 7.99). In conclusion, DCB has the lowest need for TLR whereas DES has the highest primary patency rate. DCB, CS, and BMS were associated with significant reductions in TLR compared with BA, whereas DCB, DES, CS, and BMS were associated with significantly improved primary patency compared with BA.

Do you really get what you are looking for? Exploring the medical call writing trend in tertiary care hospitals.

OBJECTIVE: To explore the trend of medical call writing by doctors working in tertiary care hospitals. METHODS: A quantitative descriptive cross-sectional study was carried out to evaluate the quality of medical calls written by the doctors at three tertiary care hospitals of Peshawar, Khyber Pakhtunkhwa between June 2016 to June 2017. An instrument was developed following AMEE Guide 87. Its content validity and reliability were established by 33 consultants from twenty specialties. A total of 198 medical calls (66 each) were collected from medicine, surgery and allied specialties and evaluated on the basis of validated instrument. RESULTS: During instrument development, six items with content Validity Ratio of 0.78 & Kappa value of 0.70 were deemed most significant in every medical call written. Among all the calls, the great majority (96% and 84.34%) mentioned the reason for referral (item 1) and history of presenting problem (item 2), respectively, while item 6 (explicit mention of the doctor who will receive the call) was addressed the least (17.6%). Item 3 (Result of physical examination) and 4 (what tests have been done/arranged by the referring doctor and a summary of the main findings) were stated in < 30% of the calls whereas item 5 (diagnosis/provisional diagnosis) was specified in less than half of the calls. CONCLUSION: In this study, the written medical calls of different specialties were evaluated using specifically designed six items instrument. Unfortunately, the content of medical calls assessed was found to be inadequate probably because medical call writing is not explicitly taught at under and postgraduate levels.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Chondroitin sulfate derived theranostic and therapeutic nanocarriers for tumor-targeted drug delivery.

The standard chemotherapy is facing the challenges of lack of cancer selectivity and development of drug resistance. Currently, with the application of nanotechnology, the rationally designed nanocarriers of chondroitin sulfate (CS) have been fabricated and their unique features of low toxicity, biocompatibility, and active and passive targeting made them drug delivery vehicles of the choice for cancer therapy. The hydrophilic and anionic CS could be incorporated as a building block into- or decorated on the surface of nanoformulations. Micellar nanoparticles (NPs) self-assembled from amphiphilic CS-drug conjugates and CS-polymer conjugates, polyelectrolyte complexes (PECs) and nanogels of CS have been widely implicated in cancer directed therapy. The surface modulation of organic, inorganic, lipid and metallic NPs with CS promotes the receptor-mediated internalization of NPs to the tumor cells. The potential contribution of CS and CS-proteoglycans (CSPGs) in the pathogenesis of various cancer types, and CS nanocarriers in immunotherapy, radiotherapy, sonodynamic therapy (SDT) and photodynamic therapy (PDT) of cancer are summarized in this review paper.

Transcriptional Profiling of Diffusible Lipopeptides and Fungal Virulence Genes During Bacillus amyloliquefaciens EZ1509-Mediated Suppression of Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a devastating necrotrophic pathogen that infects multiple crops, and its control is an unremitting challenge. In this work, we attempted to gain insights into the pivotal role of lipopeptides (LPs) in the antifungal activity of Bacillus amyloliquefaciens EZ1509. In a comparative study involving five Bacillus strains, B. amyloliquefaciens EZ1509 harboring four LPs biosynthetic genes (viz. surfactin, iturin, fengycin, and bacilysin) exhibited promising antifungal activity against S. sclerotiorum in a dual-culture assay. Our data demonstrated a remarkable upsurge in LPs biosynthetic gene expression through quantitative reverse transcription PCR during in vitro interaction assay with S. sclerotiorum. Maximum upregulation in LPs biosynthetic genes was observed on the second and third days of in vitro interaction, with iturin and fengycin being the highly expressed genes. Subsequently, Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry analysis confirmed the presence of LPs in the inhibition zone. Scanning electron microscope analysis showed disintegration, shrinkage, plasmolysis, and breakdown of fungal hyphae. During in planta evaluation, S. sclerotiorum previously challenged with EZ1509 showed significant suppression in pathogenicity on detached leaves of tobacco and rapeseed. The oxalic acid synthesis was also significantly reduced in S. sclerotiorum previously confronted with antagonistic bacterium. The expression of major virulence genes of S. sclerotiorum, including endopolygalacturonase-3, oxalic acid hydrolase, and endopolygalacturonase-6, was significantly downregulated during in vitro confrontation with EZ1509.

mTOR/HDAC1 Crosstalk Mediated Suppression of ADH1A and ALDH2 Links Alcohol Metabolism to Hepatocellular Carcinoma Onset and Progression in silico.

Hepatocellular carcinoma (HCC) is ranked the third deadliest cancer worldwide whose molecular pathogenesis is not fully understood. Although deregulated metabolic pathways have been implicated in HCC onset and progression, the mechanisms triggering this metabolic imbalance are yet to be explored. Here, we identified a gene signature coding catabolic enzymes (Cat-GS) involved in key metabolic pathways like amino acid, lipid, carbohydrate, drug, and retinol metabolism as suppressed in HCC. A higher expression of deregulated Cat-GS is associated with good survival and less aggressive disease state in HCC patients. On the other hand, we identified mTOR signaling as a key determinant in HCC onset and progression, whose hyperactivation is found associated with poor survival and aggressive disease state in HCC patients. Next, out of Cat-GS, we established two key regulators of alcohol metabolism, alcohol dehydrogenase 1A (ADH1A) and aldehyde dehydrogenase 2 (ALDH2), as being transcriptionally suppressed by histone deacetylase 1 (HDAC1) at the downstream of mTORC1 signaling. Suppressed ADH1A and ALDH2 expression aligns well with HCC-specific molecular profile and can efficiently predict disease onset and progression, whereas higher ADH1A and ALDH2 expression is associated with good survival and less aggressive disease state in HCC patients. Overall, our in silico findings suggest that transcriptional suppression of alcohol metabolism regulators, ADH1A and ALDH2, at the downstream of mTOR signaling is, in part, responsible for triggering oncogenic transformation of hepatocytes resulting in disease onset and progression in HCC.

Effect of morphine use on oral P2Y12 platelet inhibitors in acute myocardial infarction: Meta-analysis.

BACKGROUND: Morphine is the recommended analgesic in acute myocardial infarction (AMI). This recommendation has come under scrutiny because of possible slow uptake of oral antiplatelet agents. OBJECTIVE: We performed a meta-analysis of all available studies in AMI patients treated with prasugrel or ticagrelor (P2Y12 inhibitors) that reported use of morphine prior to loading the antiplatelet agents to critically assess the safety of co-administration of morphine and the newer P2Y12 inhibitors. METHODS: Several sources were searched from inception to December 2017 with inclusion of eight studies, largely observational. Mean difference (MD) was calculated for continuous variables, and standardized mean difference (SMD) for platelet function was assessed by the various platelet assays, 2 h after the loading dose of oral P2Y12 inhibitors. RESULTS: Higher platelet activity was noted among morphine group [SMD = 0.8, 95% confidence interval (CI) = 0.4-1.1, p < 0.01]. Morphine use caused higher odds of "high residual platelet reactivity" at 2 h (odds = 3.3, 95 %CI = 2.2-5.1, p < 0.01). Ticagrelor reached a lower plasma concentration in morphine group (MD = -481.8 ng/ml, 95% CI = -841.2 to -122.4 ng/ml, p < 0.01) with a higher vomiting rate (odds = 5.3, 95% CI = 2.5-11.1, p < 0.01). However, the composite of in-hospital mortality, stroke, and re-infarction was not significantly different between the groups (p = 0.83). CONCLUSION: Co-administration of morphine with P2Y12 inhibitors possibly decreases their efficacy in platelet inhibition. However, this did not translate into higher adverse outcomes because of low event rates, inadequate for analysis. A large randomized study is needed to evaluate the narcotic-P2Y12 interaction.

Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs.

The selective infiltration of cell membranes and tissue barriers often blocks the entry of most active molecules. This natural defense mechanism prevents the invasion of exogenous substances and limits the therapeutic value of most available molecules. Therefore, it is particularly important to find appropriate ways of membrane translocation and therapeutic agent delivery to its target site. Cell penetrating peptides (CPPs) are a group of short peptides harnessed in this condition, possessing a significant capacity for membrane transduction and could be exploited to transfer various biologically active cargoes into the cells. Since their discovery, CPPs have been employed for delivery of a wide variety of therapeutic molecules to treat various disorders including cranial nerve involvement, ocular inflammation, myocardial ischemia, dermatosis and cancer. The promising results of CPPs-derived therapeutics in various tumor models demonstrated a potential and worthwhile scope of CPPs in chemotherapy. This review describes the detailed description of CPPs and CPPs-assisted molecular delivery against various tissues and organs disorders. An emphasis is focused on summarizing the novel insights and achievements of CPPs in surmounting the natural membrane barriers during the last 5 years.

Pluronic F127-functionalized molybdenum oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy.

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX) + WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

The progresses in curcuminoids-based metal complexes: especially in cancer therapy.

Curcuminoids (CURs), a series of derivatives in turmeric (Curcuma longa), are commonly discovered to control the deterioration of cancers. However, the physiochemical properties and the original side effects of many CURs complexes put barriers in their medical applications. To address them, the investigation of metal-based complexes with CURs is in progress. The complexes were summarized according to articles in recent years. The results showed that the complexes improved the physicochemical properties or therapeutic performances compared with pure CURs. Further, it is possible for the novel complexes to be applied in chemical detecting, paramagnetic-luminescent and bio-imaging fields. Therefore, the formation of the metal-based CURs complexes (MBCCs) is beneficial for the development of CURs especially in medical fields.