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Objective: To discuss the presentation, evaluation, and management of congenital laryngeal webs with subglottic stenosis. Methods: The clinical data of six children were retrospectively analyzed. Results: The median age of these children who came to our hospital was 14 months (range 1–26 months). A tracheotomy was performed in all these six children. The median age of the patients who underwent tracheotomy was 4 months (range 1–11 months). The surgical method was T-tube implantation combined with cricoid cartilage reconstruction. The median age of these patients at the time of operation was 22 months (range 13–35 months). The T-tube remained in place for 3–8 months, with a median time of 6 months. The tracheal tubes in all these children were successfully removed. All patients were followed up for more than 2 years without recurrence. Conclusions: Children who have congenital laryngeal webs with subglottic stenosis required early tracheotomy. Open laryngoplasty combined with T-tube implantation and cricoid cartilage reconstruction may play a crucial role in the treatment of these children. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries. Oxidative stress plays a critical role in the progression of NAFLD. Modern pharmacological study and clinical trials have demonstrated the remarkable antioxidant activity of Gynostemma pentaphyllum (GP) in chronic liver disease. One aim of this study was to explore the potential protective effects and mechanisms of action of GP extract on NAFLD. The in vivo results showed that GP extract could alleviate fatty degeneration and haptic fibrosis in NAFLD mice. For exploring the hepatoprotective mechanisms of GP, we used network pharmacology to predict the potential active components of GP and their intracellular targets in NAFLD. Based on the network pharmacology results, we further utilized biomedical assays to validate this in silico prediction. The results showed that Gypenoside XL could upregulate the protein level of PPARα in NAFLD; the transcription level of several PPARα downstream target genes such as acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-1 (CPT-1) also increased after Gypenoside XL treatment. The overexpression of ACO and CPT-1 may involve the hepatoprotective effects of GP and Gypenoside XL on NAFLD by regulating mitochondrial fatty acid β-oxidation. [ABSTRACT FROM AUTHOR]

The objective of the present study was to construct a novel type of non-viral gene delivery vector with high delivery efficiency and specific tumor cell-targeting ability. The CP9 peptide (CYGGRGDTP) containing Arg-Gly-Asp sequence was employed to be conjugated onto polyethylenimine (PEI) to act as the role of the targeting moiety. The chemical linker, N-succinimidyl-3-(2-pyridyldithio) propionate, was applied during the synthesis of the vector (CP9-PEI). The physicochemical characteristics of the vector were evaluated by the methods of ¹H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel retardation assay, electron microscope observation and particle size detection. HepG2 cells were used to verify the gene delivery efficiency and targeting ability by gene delivery procedure and free CP9 peptide inhibition tests. The results showed that the successful synthesis of CP9-PEI and the synthesized vector may efficiently condense plasmid DNA into round particles with diameters of ~200 nm at a polymer/pDNA ratio of 10. CP9-PEI may deliver the reporter gene into HepG2 cells with higher efficiency and the efficiency may be inhibited by the free CP9 peptide. The present study suggested that the modification of PEI with the CP9 peptide is an effective method to construct a novel tumor cell-targeting non-viral vector, and that the novel vector exhibits great prospect in the field of cancer gene therapy. [ABSTRACT FROM AUTHOR]

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs. [ABSTRACT FROM AUTHOR]

Various Chinese herbal medicines (CHMs) have shown beneficial liver protection effects. Jian-Gan-Bao (JGB), a functional herbal formula, consists of three famous CHMs, including Coriolus versicolor, Salvia miltiorrhiza and Schisandra chinensis, which has been used as a folk medicine for several chronic liver diseases. In the present study, we aim systemically to evaluate the effects of JGB on acute and chronic alcoholic liver diseases (ALD) as well as non-alcoholic fatty liver disease (NAFLD) in mouse models, and identify its potential bioactive components and mechanism of action. JGB showed preventive effects for acute and chronic ALD as well as NAFLD, while post-treatment of JGB showed no significant effect, suggesting the nature of JGB as a health supplement rather than a drug. Furthermore, a compound-target network was constructed to identify the potential bioactive compounds and pathways that regulate its hepatoprotective effects. There are 40 bioactive compounds and 15 related targets that have been identified via this network pharmacology study. Among them are miltirone, neocryptotanshinone II and deoxyshikonin, with desirable pharmaceutical properties. Pathways relating to inflammation, fatty acid oxidation, tumor necrosis factor (TNF) production and cell proliferation were predicted as bioactive compounds and potential underlying mechanisms, which should be the focus of study in this field in the future. [ABSTRACT FROM AUTHOR]

Background: Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133+ cells and their sensitivity to pharmacological inhibition.Methods: GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a cancer stem cell marker. Cell proliferation was determined using the WST-1 assay. An intracranial mouse model and bioluminescence imaging were used to assess the effects of drugs on tumor growth in vivo.Results: CD133+ cells expressed stem cell markers and exhibited self-renewal and enhanced tumor formation. Minocycline (Mino) was more effective in reducing the survival rate of CD133+ cells, whereas CD133- cells were more sensitive to inhibition by the signal transducer and activator of transcription 3 (STAT3) inhibitor. Inhibition of STAT3 decreased the expression of CD133+ stem cell markers. The combination of Mino and STAT3 inhibitor synergistically reduced the cell viability of glioma cells. Furthermore, this combination synergistically suppressed tumor growth in nude mice.Conclusion: The results suggest that concurrent targeting of different subpopulations of glioblastoma cells may be an effective therapeutic strategy for patients with malignant glioma. [ABSTRACT FROM AUTHOR]

In this study, the therapeutic efficacy of third-generation cephalosporins (3GCs) was compared with that of broader-spectrum β-lactams (BSBLs) [fourth-generation cephalosporins (4GCs) and carbapenems] as empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia. Compared with those in the 3GC group ( n  = 477), a significantly higher proportion of patients in the BSBL group ( n  = 141) had initial presentation with severe sepsis or septic shock, critical illness (Pitt bacteraemia score ≥4) at bacteraemia onset and fatal co-morbidities (McCabe classification). For propensity score matching, 318 of the 477 patients in the 3GC group were matched with 106 patients in the BSBL group with the closest propensity scores on the basis of five independent predictors of 28-day mortality. After appropriate matching, no significant differences were observed in major baseline characteristics between the 3GC and BSBL groups in terms of causative micro-organism, bacteraemia severity, major source of bacteraemia, major co-morbidities and severity of co-morbidity. Consequently, the early clinical failure rate (12.9% vs. 12.3%; P  = 0.87), bacteraemia severity (Pitt bacteraemia score ≥4; 4.6% vs. 8.2%; P  = 0.17) at Day 3, and 3-day (3.8% vs . 7.5%; P  = 0.11) and 28-day (13.2% vs . 17.0%; P  = 0.33) crude mortality rates between the two groups were similar. These data suggest that the efficacy of 3GCs is similar to that of 4GCs or carbapenems when used as empirical antimicrobial therapy for community-onset Enterobacteriaceae bacteraemia. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease (WD) is one of the few hereditary diseases that can be successfully treated with medicines. We conduct this survey research to assess treatment persistence among patients with WD and try to identify what factors affect the treatment persistence. Methods: We employed WeChat which is the most popular social software in China to carry out this anonymous questionnaire research. The questionnaire included medication adherence scale. We also collected available medical records related to demographic and clinical characteristics. All the patients were divided into group of persistence with drug treatment (PDT) and nonpersistence with drug treatment (n‐PDT). Results: We collected 242 qualified questionnaires. Only 66.5% of patients were PDT during the mean 12.6 years of follow‐up. In PDT group, better outcomes were observed: improvement (78.3%) and no change (16.1%) versus those in n‐PDT (55.6%; and 28.4%, respectively). In PDT group, only nine patients deteriorated (6.8%) in comparison with 13 patients in n‐PDT (16.0%). The adverse events (AEs) in PDT group were significantly less than those in n‐PDT group. There were no significant differences in clinical type, gender, age, education level, and family knowledge about WD between the two groups. There were significant differences in AEs and family position toward treatment. Conclusion: Medication Adherence of Chinese WD patients was low. One third of the patients (33.5%) were unable to PDT, and it had an important negative effect on clinical outcome. AEs and family support had an important impact on treatment persistence. [ABSTRACT FROM AUTHOR]

NPM1 mutation is the most common molecular abnormality in patients with acute myeloid leukemia (AML), especially normal karyotype AML (NK-AML), and is associated with a favorable prognosis in the absence of concomitant FLT3-ITD. Like other molecular abnormalities such as FLT3-ITD, C/EBPα and c-Kit mutation, NPM1 mutation normally presents as a recurrent molecular abnormality. The NPM1 mutation is generally used as a molecular marker in the prognosis evaluation of a patient with AML. Here, we report a different case. He was first diagnosed with NPM1 mutation-positive acute monocytic leukemia. However, he achieved no remission, but the NPM1 mutation dramatically became negative after induction chemotherapy. Finally, he achieved complete remission after salvage chemotherapy and the NPM1 mutation was still negative. To our knowledge, this is a rare case according to the worldwide published literature. [ABSTRACT FROM AUTHOR]

• Efficacy and safety of short-course intravenous (i.v.) antimicrobial therapy for bloodstream infection (BSI) is debated. • Patients receiving short-course versus long-course i.v. antibiotic therapy for community-onset BSI were compared. • Propensity score matching was used to overcome differences in baseline patient characteristics for the two groups. • Higher rates of overall infections and crude mortality following long-course i.v. antibiotic therapy. • Therefore, short-course i.v. antibiotic therapy is recommended. The efficacy and safety of short-course intravenous (i.v.) antimicrobial therapy for bloodstream infections is unknown. Therefore, a retrospective 8-year cohort study including 1431 hospitalised adults was conducted to compare the outcomes of patients receiving short-course (5–10 days) and long-course (11–16 days) i.v. antibiotic therapy for community-onset bacteraemia. Of 1010 patients who received short-course therapy, 726 were matched with 363 patients in the long-course group through propensity score matching at a ratio of 1:2 based on independent predictors of 30-day mortality identified in the multivariate regression model. Following appropriate matching, similarities between the two groups in the proportion of baseline characteristics (age, sex, major co-morbidities, co-morbidity severity, bacteraemia severity at onset and major bacteraemia sources) and 30-day crude mortality rate after bacteraemia onset were observed. Notably, clinical outcomes within 30 days after the end of i.v. therapy, in terms of proportions of post-treatment overall infections (2.2% vs. 6.1%; P = 0.001), infections caused by antimicrobial-resistant pathogens (ARPs) (1.7% vs. 4.4%; P = 0.007), and thereby post-treatment crude mortality (1.4% vs. 3.6%; P = 0.009), were lower in the short-course group. In conclusion, for adults with community-onset uncomplicated bacteraemia, short-course (5–10 days) i.v. antibiotic treatment did not result in an increased risk of mortality but instead decreased the odds of overall and ARP infections after the treatment course. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The arsenic trioxide (ATO) plus all‐trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first‐line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. Methods: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty‐two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP‐MS. Results: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 μmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. Conclusions: In the first‐line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate. [ABSTRACT FROM AUTHOR]

Background Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic. Methods The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous Vitamin C [IVC] plus DCAG [ n  = 39]) or DCAG ( n  = 34) treatment. Results We found that low-dose Vitamin C and decitabine has a synergistic efficacy on proliferation, apoptosis, TET2 expression and activity, compared to drug–alone treatment in HL60 and NB4 cell lines in vitro . In clinic, feasibility and safety evaluations revealed that patients who received A-DCAG regimen have a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; P  = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, P  = 0.039). Patients with adverse cytogenetics did benefit from CR. There was no clinically significant additional toxicity observed with the addition of IVC. Conclusion On the basis of these results, the addition of IVC at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG, in elderly patients with AML. [ABSTRACT FROM AUTHOR]

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients ( n = 409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR) = 19.96; P < 0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR = 13.91; P < 0.001); bacteraemia because of pneumonia (OR = 5.45; P = 0.007); de-escalation after empirical therapy (OR = 0.28; P = 0.03); and isolates with a CTX MIC ≤ 1 mg/L (OR = 0.17; P = 0.02). Of note, isolates with a CTX MIC ≤ 8 mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC ( γ = 1.00; P = 0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC ≤ 1 mg/L. [ABSTRACT FROM AUTHOR]

Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1–34), a surgically implanted synthetic β-tricalcium phosphate bone biomaterial serving as a matrix to support new bone formation. Twelve weeks after bilateral ovariectomy, all rats underwent bone defect in the distal femurs, and β-tricalcium phosphate was implanted into critical sized defects. After defect operation, all animals were randomly divided into four groups and received following subcutaneous injections until death at four and eight weeks: sham rats (group ST); sham rats + parathyroid hormone, 30 µg/kg, three times a week (group SPT); OVX rats (group OT); and OVX rats + parathyroid hormone (group OPT). The distal femurs of rats were harvested for evaluation. The treatment group demonstrating the highest levels of new bone formation was the defects treated with parathyroid hormone as assessed by micro-computed tomography, biomechanical strength, and histological analysis for sham rats. Furthermore, parathyroid hormone showed a stronger effect on accelerating the degradation of β-tricalcium phosphate. Osteoporosis can limit the function of parathyroid hormone and/or β-tricalcium phosphate. The results from our study demonstrate that combination of parathyroid hormone and β-tricalcium phosphate brings better effect to bone tissue repair in non-osteoporosis and/or osteoporosis status. [ABSTRACT FROM AUTHOR]

Background. Safflower Yellow Injection has been reported as a treatment for acute cerebral infarction in recent studies in China. However, there is a lack of availability of the evidence for the efficacy and safety of Safflower Yellow Injection for the treatment of acute ischemic stroke. So we investigated the effects of Safflower Yellow Injection for the treatment of acute cerebral infarction. Method. All subjects were randomly divided into Safflower Yellow Injection group given Safflower Yellow Injection (80 mg) and control group given placebo (0 mg) injection by intravenous drop once daily for 14 days. National Institute of Health Stroke Scale (NIHSS); hemorheological detection; coagulation function; and serum inflammatory markers, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were used to investigate the effects before and 14 days after the treatment. Results. The scores of NIHSS were decreased on day 7 and day 14 after treatment. The hemorheological index of RBC deformation and RBC aggregation were significantly improved, prothrombin time (PT) increased, and fibrinogen (FIB) and TNF-α, IL-1β, and IL-6 were decreased in patients treated with Safflower Yellow injection on day 14 after treatment (P<0.05). Conclusion. Data suggests that Safflower Yellow Injection therapy may be beneficial for acute cerebral infarction. [ABSTRACT FROM AUTHOR]

This paper aims to measure the neutron flux distribution over the cross section of the boron neutron capture therapy epithermal neutron beam at the Tsing Hua Open-pool Reactor (THOR) by using indirect neutron radiography. It is successfully performed using an aluminum plate coupled with an imaging plate (IP). The developed high-resolution image represents the relative distribution of the neutron flux across the aluminum plate. The horizontal profiles of 28Al activity, according to the measurement using IP and calculations using MCNP with different angular source distributions, were given. In addition, horizontal profiles of 56Mn and 198Au activities measured using AuAl and MnNi foils, respectively, were provided. From the comparison between the measurements and calculations, source angular characteristics of the beam were inferred. [ABSTRACT FROM AUTHOR]

Abstract: Bone marrow stroma cells-derived neural stem cells (BMSCs-D-NSCs) transplantation is a promising strategy for the treatment of nervous system disorders. The development of a non-invasive method to follow the fate of BMSCs-D-NSCs in vivo is very important for the future application of this treatment. In this paper, we show for the first time, that BMSCs-D-NSCs from rhesus monkeys can be labeled in vitro with the superparamagnetic iron oxide (SPIO) contrast agent Feridex and Poly-l-lysine (PLL) without affecting morphology, cell cycle, telomerase activity, proliferation and differentiation ability of the labeled cells. Furthermore, when autografted into the striatum, these cells survived, differentiated and were incorporated into the brain, and could be reliably tracked using MRI, as confirmed by histological examination of the grafting sites with PKH67 fluorescence. These results suggest that Feridex labeling of BMSCs-D-NSCs is feasible, efficient and safe for MRI tracing following autografting into the rhesus monkey nervous system. [Copyright &y& Elsevier]

Purpose: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. Methods and Materials: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. Results: No significant differences in overall survival, locoregional failure-free, or distant metastasis–free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis–free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis–free rates were 86% and 74% (p = 0.0053). Conclusions: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation. [Copyright &y& Elsevier]