Butylphthalide combined with donepezil for the treatment of vascular dementia: a meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of butylphthalide combined with donepezil versus butylphthalide monotherapy for the treatment of vascular dementia. METHODS: Randomized controlled trials were searched in electronic databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database (VIP), Wan Fang, and China Biology Medicine from inception to 29 November 2022. Two reviewers independently screened the papers and extracted data from the included studies. The data were processed using RevMan5.4 statistical software. RESULTS: Nine randomized controlled trials (n = 1024) were included in this meta-analysis. Regarding the primary outcomes, compared with butylphthalide monotherapy, combined butylphthalide and donepezil treatment exhibited significantly greater total clinical efficacy (relative risk = 1.24, 95% confidence interval [1.17, 1.31]) and did not increase the adverse event rate (relative risk = 1.39, 95% confidence interval [0.91, 2.14]). Regarding the secondary outcomes, the meta-analysis results for the Mini-Mental State Examination, abilities of daily living, and Montreal Cognitive Assessment scores and the interleukin-6, tumor necrosis factor-α, and superoxide dismutase blood levels all supported combined butylphthalide and donepezil treatment. CONCLUSION: Butylphthalide combined with donepezil may be a better treatment strategy than donepezil alone for the treatment of vascular dementia in clinical practice.

Interaction Between Genetic Susceptibility and COVID-19 Pathogenesis in Pediatric Multisystem Inflammatory Disorders: The Role of Immune Responses.

Numerous studies have highlighted the emergence of coronavirus disease (COVID-19) symptoms reminiscent of Kawasaki disease in children, including fever, heightened multisystem inflammation, and multiorgan involvement, posing a life-threatening complication. Consequently, extensive research endeavors in pediatric have aimed to elucidate the intricate relationship between COVID-19 infection and the immune system. COVID-19 profoundly impacts immune cells, culminating in a cytokine storm that particularly inflicts damage on the pulmonary system. The gravity and vulnerability to COVID-19 are closely intertwined with the vigor of the immune response. In this context, the human leukocyte antigen (HLA) molecule assumes pivotal significance in shaping immune responses. Genetic scrutiny of HLA has unveiled the presence of at least one deleterious allele in children afflicted with multisystem inflammatory syndrome in children (MIS-C). Furthermore, research has demonstrated that COVID-19 exploits the angiotensin-converting enzyme 2 (ACE-2) receptor, transmembrane serine protease type 2, and various other genes to gain entry into host cells, with individuals harboring ACE-2 polymorphisms being at higher risk. Pediatric studies have employed diverse genetic methodologies, such as genome-wide association studies (GWAS) and whole exome sequencing, to scrutinize target genes. These investigations have pinpointed two specific genomic loci linked to the severity and susceptibility of COVID-19, with the HLA locus emerging as a notable risk factor. In this comprehensive review article, we endeavor to assess the available evidence and consolidate data, offering insights into current clinical practices and delineating avenues for future research. Our objective is to advance early diagnosis, stabilization, and appropriate management strategies to mitigate genetic susceptibility's impact on the incidence of COVID-19 in pediatric patients with multisystem inflammation.

Efficacy and Possible Mechanisms of Astragali Radix and its Ingredients in Animal Models of Osteoporosis: A Preclinical Review and Metaanalysis.

BACKGROUND: Astragali Radix (AR) has a long history as a traditional Chinese medicine for anti-osteoporosis (OP) treatment. The aim of the study was to explore the effect and optimal regimens of AR and its main ingredients (IAR) in OP treatment. METHODS: Eligible animal studies were searched in seven databases (PubMed, Web of Science, MEDLINE, SciELO Citation Index, Cochrane Library, China National Knowledge Infrastructure and Wanfang). The primary outcomes were bone metabolic indices. The secondary outcome measure was the anti-OP mechanism of IAR. RESULTS: 21 studies were enrolled in the study. The primary findings of the present article illustrated that IAR could significantly increase the bone mineral density (BMD), bone volume over the total volume, trabecular number, trabecular thickness, bone maximum load and serum calcium, while trabecular separation and serum C-terminal telopeptide of type 1 collagen were remarkably decreased (P < 0.05). In subgroup analysis, the BMD in the long treatment group (≥ 10 weeks) showed better effect size than the short treatment group (< 10 weeks) (P < 0.05). Modeling methods and animal sex were factors affecting serum alkaline phosphatase and osteocalcin levels. CONCLUSION: The findings suggest the possibility of developing IAR as a drug for the treatment of OP. IAR with longer treatment time may achieve better effects regardless of animal strain and age.

Emerging strategies in nanotechnology to treat respiratory tract infections: realizing current trends for future clinical perspectives.

A boom in respiratory tract infection cases has inflicted a socio-economic burden on the healthcare system worldwide, especially in developing countries. Limited alternative therapeutic options have posed a major threat to human health. Nanotechnology has brought an immense breakthrough in the pharmaceutical industry in a jiffy. The vast applications of nanotechnology ranging from early diagnosis to treatment strategies are employed for respiratory tract infections. The research avenues explored a multitude of nanosystems for effective drug delivery to the target site and combating the issues laid through multidrug resistance and protective niches of the bacteria. In this review a brief introduction to respiratory diseases and multifaceted barriers imposed by bacterial infections are enlightened. The manuscript reviewed different nanosystems, i.e. liposomes, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, nanogels, and metallic (gold and silver) which enhanced bactericidal effects, prevented biofilm formation, improved mucus penetration, and site-specific delivery. Moreover, most of the nanotechnology-based recent research is in a preclinical and clinical experimental stage and safety assessment is still challenging.

Effects of Monthly Intramuscular High-Dose Vitamin D2 on Serum 25-Hydroxyvitamin D and Immune Parameters in Very Elderly Chinese Patients with Vitamin D Deficiency.

PURPOSE: Vitamin D deficiency is highly prevalent among the very elderly and is associated with a wide variety of clinical conditions other than musculoskeletal diseases. This study aims to ascertain the efficacy and safety of high-dose intramuscular vitamin D2 in very elderly Chinese patients with vitamin D deficiency. METHODS: Very elderly (aged 80 years or over) Chinese patients with vitamin D deficiency were recruited to receive monthly intramuscular injections of 600,000 IU vitamin D2 until their serum 25-hydroxyvitamin D (25(OH)D) reached ≥30 ng/mL. The serum levels of 25(OH)D2, 25(OH)D3, iPTH, BTMs, immune parameters, and other biochemical parameters were measured at baseline and one month after each dose. RESULTS: Of the 30 very elderly Chinese patients who had been recruited into the study, 27 (90.0%) had their vitamin D deficiency corrected, and 26 (86.7%) reached vitamin D sufficiency. The mean time (±SD) was 3.1 (±1.3) months for vitamin D deficiency to be corrected, and 6.1 (±0.8) months for vitamin D sufficiency to be reached. The mean (±SD) serum level of 25(OH)D2 increased from 0.69 (±1.51) ng/mL to 29.07 (±5.68) ng/mL, while the mean (±SD) serum level of 25(OH)D3 decreased from 9.82 (±2.75) ng/mL to 5.30 (±3.09) ng/mL (both P < 0.001). The total T cells in serum remained unchanged (P > 0.05), and the CD4 and B cells (CD19+) were increased significantly (both P < 0.05). In addition, no significant change was observed in the serum levels of iPTH and BTMs. CONCLUSION: Monthly intramuscular injection of 600,000 IU vitamin D2 is an effective and safe dosing regimen to reach vitamin D sufficiency and enhances immune function in the very elderly Chinese patients with vitamin D deficiency.

Surface-engineered smart nanocarrier-based inhalation formulations for targeted lung cancer chemotherapy: a review of current practices.

Lung cancer is the second most common and lethal cancer in the world. Chemotherapy is the preferred treatment modality for lung cancer and prolongs patient survival by effective controlling of tumor growth. However, owing to the nonspecific delivery of anticancer drugs, systemic chemotherapy has limited clinical efficacy and significant systemic adverse effects. Inhalation routes, on the other hand, allow for direct delivery of drugs to the lungs in high local concentrations, enhancing their anti-tumor activity with minimum side effects. Preliminary research studies have shown that inhaled chemotherapy may be tolerated with manageable adverse effects such as bronchospasm and cough. Enhancing the anticancer drugs deposition in tumor cells and limiting their distribution to other healthy cells will therefore increase their clinical efficacy and decrease their local and systemic toxicities. Because of the controlled release and localization of tumors, nanoparticle formulations are a viable option for the delivery of chemotherapeutics to lung cancers via inhalation. The respiratory tract physiology and lung clearance mechanisms are the key barriers to the effective deposition and preservation of inhaled nanoparticle formulations in the lungs. Designing and creating smart nanoformulations to optimize lung deposition, minimize pulmonary clearance, and improve cancerous tissue targeting have been the subject of recent research studies. This review focuses on recent examples of work in this area, along with the opportunities and challenges for the pulmonary delivery of smart nanoformulations to treat lung cancers.

Zoledronate-induced acute anterior uveitis: a three-case report and brief review of literature.

PURPOSE: This three-case report aims to highlight the ocular adverse effects induced by bisphosphonate therapy and to call clinicians' attention. METHODS: Three cases of acute anterior uveitis secondary to the initial dose of zoledronate infusion were reported with focus on their symptoms, treatment regimens, and outcomes. A review of published reports provided a basis for discussion. RESULTS: Three cases of acute anterior uveitis were either bilateral or unilateral. They demonstrated typical manifestations of bisphosphonate-induced acute anterior uveitis such as eye pain, blurred vision, conjunctival and ciliary hyperemia, keratic precipitates, and flare in the anterior chamber. After topical corticosteroid-containing comprehensive treatments, these symptoms resolved completely without any vision loss and long-term sequelae. CONCLUSIONS: Acute anterior uveitis may be part of the acute phase reaction induced by zoledronate. Patients should be informed of its symptoms in advance and be monitored closely during and after administration. Clinicians should have a good awareness of the zoledronate-associated acute anterior uveitis and to treat it in a prompt and appropriate manner.

The most important biomarker associated with coagulation and inflammation among COVID-19 patients.

Coronavirus disease 2019 (COVID-19) induced by SARS-Cov-2 can be related to coagulopathy. Also, the infection-induced inflammatory changes are found in patients with disseminated intravascular coagulopathy (DIC). The lack of previous immunity to COVID-19 has caused infection of a large number of patients worldwide and unpredictability regarding the management of the complications that appear in the course of this viral illness. Lungs are the most important target organ of the SARS-COV-2. In COVID-19 patients, acute lung injury leads to respiratory failure. However, multiorgan failure can also occur in these patients. The primary coagulopathy of COVID-19 is marked by a considerable elevation of D-dimer, ferritin, and fibrinogen degradation products. In comparison, abnormalities in platelet count, prothrombin time, and partial thromboplastin time are partly uncommon in initial presentations. Inflammatory biomarkers including CRP, LDH, and IL-6 are significantly elevated in the early stages of the disease. In this regard, inflammation-associated biomarkers and coagulation test screening, including the assessment of IL-6, CRP, LDH, D-dimer, platelet count, PT&PTT time, ferritin, and fibrinogen levels are suggested for detecting infection by this virus. Overall, COVID-19-associated coagulopathy should be managed like other patients with critical conditions, and supportive care and thromboembolic prophylaxis should be used for severe patients.

Bacteria-Instructed Click Chemistry between Functionalized Gold Nanoparticles for Point-of-Care Microbial Detection.

Bacterial infections pose mounting public health concerns and cause an enormous medical and financial burden today. Rapid and sensitive detection of pathogenic bacteria at the point of care (POC) remains a paramount challenge. Here, we report a novel concept of bacteria-instructed click chemistry and employ it for POC microbial sensing. In this concept of bacteria-instructed click chemistry, we demonstrate for the first time that pathogenic bacteria can capture and reduce exogenous Cu2+ to Cu+ by leveraging their unique metabolic processes. The produced Cu+ subsequently acts as a catalyst to trigger the click reaction between gold nanoparticles (AuNPs) modified with azide and alkyne functional molecules, resulting in the aggregation of nanoparticles with a color change of the solution from red to blue. In this process, signal amplification from click chemistry is complied with the aggregation of functionalized AuNPs, thus presenting a robust colorimetric strategy for sensitive POC sensing of pathogenic bacteria. Notably, this colorimetric strategy is easily integrated in a smartphone app as a portable platform to achieve one-click detection in a mobile way. Moreover, with the help of the magnetic preseparation process, this smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity (40 colony-forming units/mL) in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.

microRNA-526b servers as a prognostic factor and exhibits tumor suppressive property by targeting Sirtuin 7 in hepatocellular carcinoma.

Recent studies have reported that microRNA-526b (miR-526b) is implicated in the growth and metastasis of cancer cells. However, the clinical significance of miR-526b and its role as well as underlying mechanisms are largely unknown in hepatocellular carcinoma (HCC). Here, we detected miR-526b expression difference between HCC and matched nontumor tissues with qRT-PCR. We found that miR-526b displayed lower expression in HCC patient tissues and cells. Clinical analysis revealed that low miR-526b expression correlated with large tumor size, venous infiltration, advanced tumor-node-metastasis (TNM) stage. Furthermore, miR-526b underexpression independently predicted poor prognosis of HCC patients. Functionally, we demonstrated that miR-526b inhibited proliferation, migration and invasion of HCC cells in vitro. Moreover, miR-526b overexpression restrained the tumor growth and pulmonary metastasis in vivo. Mechanistically, we proved that miR-526b could directly bind to 3'UTR of sirtuin 7 (SIRT7) mRNA and repressed its expression. miR-526b and SIRT7 showed a negative correlation in HCC tissues. More importantly, up-regulating SIRT7 expression antagonized miR-526b-inhibited proliferation, migration and invasion in SMMC-7721 cells. Furthermore, miR-526b suppressed epithelial-to-mesenchymal transition (EMT) of HCC cells. Immunoblotting analysis indicated that miR-526b reduced the levels of phosphorylated ERK (p-ERK), c-Myc, Cyclin D1, c-Jun, SNAIL and SLUG in HCC cells. SIRT7 restoration promoted phosphorylation of ERK and EMT in miR-526b overexpressing SMMC-7721 cells. Taken together, this is the first time we demonstrated that miR-526b might function as a prognostic biomarker and suppressed SIRT7 expression, and subsequently led to the growth and metastasis of HCC. Our findings provide miR-526b/SIRT7 axis as a promising drug target for HCC.

Overexpression of Musashi-1 protein is associated with progression and poor prognosis of gastric cancer.

Musashi-1, an evolutionally conserved RNA-binding protein, has been implicated in the promotion of pathological stem cell proliferation, including tumorigenesis. The objective of the present study was to evaluate the expression of Musashi-1 protein and its implications in the progression and prognosis of gastric cancer. The expression level of Musashi-1 protein in gastric cancer was determined by western blotting and immunohistochemistry, and compared with the clinicopathological parameters. The present study revealed that the expression level of Musashi-1 protein in gastric cancer was significantly upregulated and correlated with the tumor size, tumor-node-metastasis (TNM) stage, Lauren classification, depth of invasion, vessel invasion, lymph node metastasis and distant metastasis. The mean survival time for patients with low expression levels of Musashi-1 was significantly longer compared with patients with high expression levels of Musashi-1. For each TNM stage, the mean survival time for patients with a low Musashi-1 expression levels was also significantly longer compared with patients with a high Musashi-1 expression level. Notably, TNM stage II patients with a low Musashi-1 expression level demonstrated a longer mean survival time compared with TNM stage I patients with high Musashi-1 expression level (56.8 vs. 42.3 months; P=0.001), and TNM stage III patients with low Musashi-1 expression level exhibited a longer mean survival time compared with TNM stage II patients with a high Musashi-1 expression level (44.0 vs. 33.8 months; P=0.034). Multivariate Cox's regression test demonstrated that Musashi-1 protein expression level was an independent prognostic indicator for the survival rate of the patients with gastric cancer. The results of the present study highlighted an important role for Musashi-1 protein in the progression of gastric cancer. The detection of the Musashi-1 protein expression level alone or in combination with TNM staging may aid the prediction of the prognosis of patients with gastric cancer.

Reference intervals of ß-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide and osteocalcin for very elderly Chinese men.

AIM: The present study was intended to establish the reference intervals of ß-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide and osteocalcin for very elderly (aged 80 years or more) Chinese men. METHODS: A total of 1316 very elderly Chinese men were recruited into the study, and subjected to a survey of clinical characteristics, measurements of bone mineral density and assays of bone turnover markers. The relationships between underlying diseases and bone turnover markers were investigated, and the reference intervals of ß-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide and osteocalcin for very elderly Chinese men were established through defining the central 95% range of all observations. RESULTS: We found that type 2 diabetes mellitus, chronic obstructive pulmonary disease and abnormal bone mass were associated with serum bone turnover markers (P < 0.01), and thereby identified 208 men without type 2 diabetes mellitus, chronic obstructive pulmonary disease and/or abnormal bone mass as healthy participants from 1316 very elderly Chinese men. The reference intervals for very elderly Chinese men were 0.13-0.63 ng/mL for ß-C-terminal telopeptide of type I collagen, 18-94 ng/mL for procollagen type I N-terminal propeptide and 9-28 ng/mL for osteocalcin, respectively. The three turnover markers were moderately correlated to each other (P < 0.001), and all negatively associated with the bone mineral density of three sites (P < 0.05). CONCLUSIONS: We have established the reference intervals of ß-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide and osteocalcin for very elderly Chinese men. Geriatr Gerontol Int 2017; 17: 773-778.

Factors associated with low femoral neck bone mineral density in very elderly Chinese males.

OBJECTIVE: This study was designed to identify factors associated with the femoral neck bone mineral density (FNBMD) of the very elderly (aged 80 or more) Chinese males. METHODS: A total of 1177 very elderly Chinese males were recruited into the study, and subjected to FNBMD, biochemical parameters, bone turnover markers, and serum sex steroids assays. Univariate and multivariate regression analyses were performed to identify factors independently related to FNBMD. RESULTS: It was demonstrated that age (ß=-0.003, P=0.035), concomitant chronic obstructive pulmonary disease (COPD, ß=-0.027, P=0.009), serum ß-C-telopeptide of type 1 collagen (ß-CTX, ß=-0.097, P<0.001), and parathyroid hormone (PTH, ß=-0.001, P=0.004) were negatively correlated with the FNBMD, while body mass index (BMI, ß=0.009, P<0.001), and serum estradiol (ß=0.001, P=0.038) were positively related to FNBMD in very elderly Chinese males. CONCLUSION: An integrated intervention should be implemented to increase the BMD of the very elderly males, with special attention to preventing and curing COPD, reducing serum ß-CTX and PTH levels, as well as keeping a proper BMI and serum estradiol level.

Upregulated expression of ADAM17 is a prognostic marker for patients with gastric cancer.

OBJECTIVE: This study was designed to evaluate the expression and prognostic significance of A Disintegrin and Metalloproteinase17 (ADAM17) protein in patients with gastric cancer. BACKGROUND: Tumor invasion and metastasis are primary causes for treatment failure or death among cancer patients. ADAM17 is a multidomain transmembrane glycoprotein involved in the release of several ligands that were shown to promote tumor formation and progression. Elevated expression of ADAM17 was detected in a number of human cancers and was associated with poor progression and prognosis of the diseases. In gastric cancer, however, the expression and prognostic significance of ADAM17 has not been fully elucidated. METHODS: The expressions of ADAM17 and extracellular matrix metalloproteinase inducer (EMMPRIN), a protein implicated in tumor invasion and metastasis, were detected using the tissue microarray technique and immunohistochemical EnVision method and compared with clinicopathological parameters of patients with gastric cancer. RESULTS: The expressions of ADAM17 and EMMPRIN were upregulated in gastric cancer lesions compared with their expressions in adjacent non-cancerous tissues (P < 0.01). High expression of ADAM17 was detected in 35.78% (156/436) of patients with gastric cancer and positively correlated with the expression of EMMPRIN (r = 0.738, P < 0.01). ADAM17 expression was associated with a number of clinicopathological parameters including depth of invasion and TNM stage of the tumor (P < 0.05). In each TNM stage, patients with high ADAM17 expression had a longer mean survival time than those with low expression (P < 0.05). Particularly, the mean survival time of stage II gastric cancer patients with low ADAM17 expression was longer than that of stage I patients with high ADAM17 expression (P < 0.01). Multivariate survival analysis suggested that, along with other parameters, ADAM17 and EMMPRIN expression were independent prognostic factors for patients with gastric cancer. CONCLUSIONS: ADAM17 was implicated in the progression of gastric cancer. On the basis of the TNM stage, detection of ADAM17 expression will be helpful for predicting prognosis of gastric cancer.

[Expression of matrix metalloproteinase-2 and insulin-like growth factor-1 in gastric carcinoma and their clinicopathological significance].

OBJECTIVE: To investigate the expression of matrix metalloproteinase-2 (MMP-2) and insulin-like growth factor-1 (IGF-1) in gastric carcinoma and their clinicopathological significance. METHODS: Expressions of MMP-2 and IGF-1 were examined by using immunohistochemical SP staining and cross-compared with clinicopathological features of gastric carcinoma. RESULTS: High expression of MMP-2 and IGF-1 were observed in 70.4% (307/436) and 49.5% (216/436) of gastric carcinoma tissues respectively, significantly higher than those in non-tumor gastric mucosa (3.3% and 5.4%, respectively; all P < 0.05). The high expression rate of MMP-2 and IGF-1 were significantly associated with the patient age, tumor size, tumor location, Lauren classification, TNM staging, depth of tumor infiltration, presence of vessel invasion, lymph node and distant metastasis (all P < 0.05). In addition, the expression of MMP-2 was positively linked with the expression level of IGF-1 (P < 0.05). Univariate analysis showed that high expression of MMP-2, was significantly associated with poor prognosis of tumor of TNM stage I and II (all P < 0.05), high expression of IGF-1 was significantly correlated with poor prognosis of patients with TNM stage I, II and III tumor (all P < 0.05). Cox multivariate analysis indicated that the high expressions of MMP-2 and IGF-1 could be independent prognostic indices for gastric carcinoma. CONCLUSIONS: High expression of MMP-2 and IGF-1 proteins are significantly correlated with the invasion and metastasis of gastric carcinoma, it is helpful to simultaneously detect the expressions of MMP-2 and IGF-1 proteins in predicting prognosis of patients with gastric carcinoma.