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ObjectiveTo explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes. MethodsHyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine (T4) at 0.1 mg/kg for 30 days. β-catenin inhibitor MSAB (14 mg/kg) was administrated for 30 days. We used western blot to detect the expression of myocardial hypertrophy marker ANP, β-catenin and FoxO1; immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1. Hyperthyroidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine (T3) into cultured primary neonatal rat cardiomyocytes for 24 hours. β-catenin siRNA (30 nmol/L) was used to down-regulate β-catenin expression in cardiomyocytes. Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy. ResultsFollowing Wnt/β-catenin activation, β-catenin was found increased nuclear expression, to bind to the nuclear transcriptional factors and regulate the gene expression. β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats, but no change was found in the expression of typical transcriptional factor TCF7l2. Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling. Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes. Conclusionsβ-catenin/FoxO1 is activated in hyperthyroidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyocyte hypertrophy.
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A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Subject(s)
Humans , Adrenocorticotropic Hormone , Hot Temperature , Medicine, Chinese Traditional , Adenosine TriphosphateABSTRACT
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a new imaging technique with label-free, rapid, and high throughput features. It has bloomed in the analysis on the spatial distribution of biomolecules such as drugs, metabolites, peptides and proteins on the tissue surface in virtue of providing high data throughput from non-targeted full analysis and high accuracy from targeted analysis. The acquisition of MSI signal response with high sensitivity, high spatial resolution, and good stability is directly depended on the appropriate sample preparation approaches, and flexible and various data processing tools will help the non-target data mining to meet the demands of visualization, spatial distribution and multiple index applications so as to reveal the scientific rules beneath the data. This review briefly summarizes the key advances in MALDI-MSI from aspects of sample preparation procedures, data processing and visualization. It also illustrates the characteristics, difficulties and probable solutions derived from these key techniques.
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Objective To investigate the prevalence and genotypes of Cryptosporidium spp. and Giardia lamblia in dogs and cats from a pet hospital in Shanghai Municipality. Methods A total of 145 fresh fecal samples were collected from pet dogs and cats in a pet hospital in Shanghai Municipality during the period from November 2021 to June 2022, including 99 dog fecal samples and 46 cat fecal samples. The small subunit ribosomal ribonucleic acid (SSU rRNA) gene of Cryptosporidium and the triose phosphate isomerase (TPI) gene of G. lamblia were amplified using nested PCR assay, and the positive amplification products were sequenced from both directions. The sequence assembly was performed using the software Clustal X 2.1, and sequence alignment was conducted using BLAST. A phylogenetic tree was created with the Neighbor-Joining method using MEGA 11.0 to identify parasite species or genotype. Results The overall prevalence of Cryptosporidium and G. lamblia was 20.00% (29/145) in 145 pet dog and cat fecal samples, with the prevalence of 0.69% (1/145) and 19.31% (28/145) in Cryptosporidium and G. lamblia, respectively. G. lamblia was only detected in dog fecal samples, with prevalence of 18.18% (18/99), while the detection rates of Cryptosporidium and G. lamblia were 2.17% (1/46) and 21.74% (10/46) in cat fecal samples. Nucleotide sequence analysis showed that one Cryptosporidium positive sample was characterized as C. felis, and 28 G. lamblia positive samples were all characterized as Giardia assemblage A, which showed 100% sequence homology with human isolates of Giardia. Phylogenetic analysis revealed that the sequences obtained in this study belonged to the same branch with the reported Giardia assemblage A. Conclusions Cryptosporidium and G. lamblia infection was prevalent in pet dogs and cats from the study pet hospital in Shanghai Municipality, and there is a zoonotic risk for the species and genotype. Intensified surveillance of Cryptosporidium and Giardia infection is recommended in pets and their owners, and improved management of pet keeping is required.
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Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.
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Aim To evaluate the therapeutic effect of apigenin on liver fibrosis in mice anrl the pharmacologi¬cal mechanism.Methods Carbon tetrachloride ( CC14) -induced liver fibrosis mouse model was estab¬lished.The mice were divided into six groups of con¬trol, model, silibinin(55 mg • kg 1 • d 1 ) , apigenin in high dosage (60 mg • kg 1 • d 1 ) , apigenin in mid¬dle dosage( 30 mg • kg 1 • d 1 ) and apigenin in low dosage( 15 mg • kg 1 • d 1 ).The general life status, body weight and liver coefficient of the mice in every group were recorded.HE staining, Masson staining, immunohistochemistry and Western blot were used to e- valuate the effect of apigenin on the pathological chan¬ges, the markers related to epithelial-mesenchymal transition and signaling pathways of liver tissues.Re¬sults In CCI4-induced liver fibrosis mice, middle and high-dosage of apigenin could improve the general life status, increase body weight, decrease liver coeffi¬ cient, and significantly improve liver lesions.Middle and high-dosage of apigenin significantly increased the expression of the epithelial marker protein E-cadherin and significantly decreased the expression of the mes¬enchymal marker protein Vimentin in liver tissues of mice with the disease.The further results showed that middle and high-dosage apigenin could significantly in¬hibit the expression of phosphorvlated PDK1 and phos- phorvlated AKT protein in liver tissues of model mice.Conclusions Apigenin can inhibit EMT by inhibiting PDK1/AKT signaling pathway, which plays an anti-fi- brosis role.The apigenin has the potential to be further developed as a drug to protect the liver and treat liver fibrosis.
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BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Subject(s)
Aged , Humans , Antibodies, Viral , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Immunization, Passive , Recombinant Fusion Proteins , SARS-CoV-2ABSTRACT
Advances in high-throughput sequencing (HTS) have fostered rapid developments in the field of microbiome research, and massive microbiome datasets are now being generated. However, the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field. Here, we systematically summarize the advantages and limitations of microbiome methods. Then, we recommend specific pipelines for amplicon and metagenomic analyses, and describe commonly-used software and databases, to help researchers select the appropriate tools. Furthermore, we introduce statistical and visualization methods suitable for microbiome analysis, including alpha- and beta-diversity, taxonomic composition, difference comparisons, correlation, networks, machine learning, evolution, source tracing, and common visualization styles to help researchers make informed choices. Finally, a step-by-step reproducible analysis guide is introduced. We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the biological significance behind the data.
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Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E
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Objective: To explore clinical features and prognosis of anastomotic leak (AL) after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients. Methods: A retrospective cohort study was performed. Data were retrieved from colorectal cancer database of the Sixth Affiliated Hospital, Sun Yat-sen University. The clinical data of 470 patients with rectal cancer who underwent anterior resection after neoadjuvant chemoradiotherapy at our department from September 2010 to December 2018 were enrolled. Clinical features and outcome of postoperative AL were analyzed. The primary outcomes were the short-term and long-term incidence and severity of AL (ISREC grading standard was adopted). The secondary outcomes were the prognostic indicators of AL, including the secondary chronic presacral sinus, anastomotic stenosis and persistent stoma. Patients received regular follow-up every 3-6 months after surgery, including physical examination, blood test, colonoscopy and image; those received follow-up once a year after postoperative 2-year; those who did not return to our hospital received telephone follow-up. Data of this study were retrieved up to January 2020. Univariate χ(2) test and multivariate logistic analysis were used to identify risk factors of AL and prognostic factors of persistent stoma. Results: There were 331 males (70.4%) with the average age of (53.5±11.6) years. Distance from tumor to anal verge ≤ 5 cm was found in 228 (48.5%) patients. The diverting stoma was performed in 440 (93.6%) patients. After a median follow-up of 28 months, AL was found in 129 (27.4%) patients, including 67 (14.3%) patients with clinical leak (ISREC grade B-C). The median time for diagnosis of AL was 70 days (2-515 days) after index surgery. Common symptoms included sacrococcygeal pain (27.9%, 36/129), purulent discharge through anus (25.6%, 33/129), and rectal irritation (17.8%, 23/129). Sixty five point one percent (84/129) of the defect site was at the posterior wall of the anastomosis. Transanal incision and drainage or lavage (27.9%, 36/129) and percutaneous drainage under ultrasound or CT (17.1%, 22/129) were the most common management. Chronic presacral sinus tract could not be evaluated in 12 patients because imaging was performed more than 1 year after the operation. Evaluation beyond 1 year showed that 73 of 458 eligible patients (15.9%) were found with chronic presacral sinus, accounting for 62.4% (73/117) of patients with AL; 69 of 454 (15.2%) were diagnosed with anastomotic stenosis, of whom 49 were secondary to AL; 59 of 470 (12.6%) had persistent stoma due to AL. Univariate analysis showed that male, operative duration > 180 minutes, intraoperative blood loss >150 ml, and pelvic radiation injury were associated with AL (all P<0.05). Multivariate analysis showed that male (OR=1.72, 95% CI: 1.04-2.86, P=0.036), intraoperative blood loss > 150 ml (OR=1.82, 95% CI: 1.11-2.97, P=0.017), and pelvic radiation injury (OR=4.90, 95% CI: 3.09-7.76, P<0.001) were independent risk factors of AL after anterior resection. For patients with AL, clinical leak (ISREC grade B-C) (OR=9.59, 95% CI: 3.73-24.69, P<0.001), age ≤55 years (OR=3.35, 95% CI: 1.35-8.30, P=0.009), distance from tumor to anal verge ≤ 5 cm (OR=3.33, 95% CI: 1.25-8.92, P=0.017), and pelvic radiation injury (OR=3.29, 95% CI: 1.33-8.14, P=0.010) were independent risk factors of persistent stoma. Conclusions: AL after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients is common. Among patients with AL, the proportion of those needing persistent stoma is high. Pelvic radiation injury is significantly associated with occurrence of AL and subsequent persistent stoma. Sphincter-preserving surgery for rectal cancer should be selectively used based on the risk of pelvic radiation injury, which is beneficial to reduce the incidence of AL and improve the quality of life.
Subject(s)
Adult , Aged , Humans , Male , Middle Aged , Anastomosis, Surgical , Anastomotic Leak , Chemoradiotherapy , Neoadjuvant Therapy , Prognosis , Quality of Life , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
BACKGROUND: Medical ozone is a strong oxidant, can kill bacteria, resist inflammation, improve circulation, relieve pain and promote regeneration. It has been reported that medical ozone has a positive effect on ulcer wounds such as caries. OBJECTIVE: To explore the clinical effect of ozone bath on the control of diabetic foot ulcer’s infection and the promotion of wound healing. METHODS: According to the treatment methods, 100 patients with type 2 diabetic foot ulcer who met the inclusion criteria were divided into two groups randomly. In the experimental group, ozone bath was applied to the wound for 30 minutes after cleaning the wound with local normal saline; in the control group, air bath was applied to the wound for 30 minutes after cleaning the wound with local normal saline, once a day. Three weeks later, the bacterial control (quantitative analysis of bacteria, distribution of pathogenic bacteria), the degree of decline of inflammation index, the reduction of ulcer wound, the rate of wound healing and the visual analogue scale score of wound pain were counted in both groups. The expression levels of vascular endothelial growth factor, transforming growth factor-β and platelet-derived growth factor in wound tissues were measured before and after treatment. The protocols were approved by the Ethics Committee of Beijing Shijitan Hospital Affiliated to Capital Medical University. Patients and their family member signed the informed consent. RESULTS AND CONCLUSION: After 3 weeks of treatment, bacteria were still detected in 46 patients in the control group and 5 patients in the experimental group. The number of pathogenic bacteria was 73 before treatment and 66 after treatment in the control group, 74 before treatment and 7 after treatment in the experimental group. Bacterial quantitative analysis was significantly higher in the control group than in the experimental group after treatment. The indexes of ulcer healing, including the reduction of ulcer wound, the visual analogue scale score of wound pain, and the degree of decline of inflammation index, were better in the experimental group than those in the control group (P < 0.05). (4) The expression levels of vascular endothelial growth factor, transforming growth factor-β and platelet-derived growth factor in local wound tissues were significantly higher in the experimental group than in the control group (P < 0.05). The percentage of wound healing in the experimental group was significantly higher than that in the control group (P < 0.05). To conclude, ozone bath can significantly control the local infection of diabetic foot, reduce the distribution of pathogenic bacteria on the wound surface, relieve the inflammatory pain of the wound, stimulate the secretion of growth factor in wound, and improve the wound healing rate.
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Background@#At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The virus has since rapidly spread to all provinces and autonomous regions of China, and to countries outside of China. Patients who become infected with 2019-nCoV may initially develop mild upper respiratory tract symptoms. However, a significant fraction of these patients goes on to subsequently develop serious lower respiratory disease. The effectiveness of adjunctive glucocorticoid therapy uses in the management of 2019-nCoV infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.@*Methods@#The present study will be conducted as an open-labelled, randomised controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at 4 consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.@*Discussion@#The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in severe coronavirus disease 2019 (COVID-19) patients.@*Trial registration@#ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
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Mammalian follicles are composed of oocytes, granulosa cells, and theca cells. Theca cells form in the secondary follicles, maintaining follicular structural integrity and secreting steroid hormones. Two main sources of theca cells exist: Wilms tumor 1 positive (Wt1) cells native to the ovary and Gli1 mesenchymal cells migrated from the mesonephros. Normal folliculogenesis is a process where oocytes, granulosa cells, and theca cells constantly interact with and support each other through autocrine and paracrine mechanisms. The proliferation and differentiation of theca cells are regulated by oocyte-derived factors, including growth development factor 9 and bone morphogenetic protein 15, and granulosa cell-derived factors, including desert hedgehog, Indian hedgehog, kit ligand, insulin-like growth factor 1, as well as hormones such as insulin and growth hormones. Current research on the origin of theca cells is limited. Identifying the origin of theca cells will help us to systematically elaborate the mechanisms of follicular formation and development.
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BACKGROUND@#At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.@*METHODS@#The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.@*DISCUSSION@#The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
Subject(s)
Humans , Betacoronavirus , Coronavirus Infections , Drug Therapy , Glucocorticoids , Therapeutic Uses , Pandemics , Pneumonia, Viral , Drug Therapy , Randomized Controlled Trials as Topic , Severity of Illness IndexABSTRACT
OBJECTIVE: To study improvement effects of Fuling gancao decoction on functional dyspepsia (FD) model rats. METHODS: Sixty SD rats were randomly divided into normal group, model group, Fuling gancao decoction high-dose group (20 g/kg), Fuling gancao decoction low-dose group (10 g/kg), drug combination group (Fuling gancao decoction 10 g/kg+domperidone 0.004 g/kg), domperidone group (0.004 g/kg), with 10 rats in each group. Except for normal group, other groups were givenicy dilute hydrochloric acid intragastrically to establish FD model. After modeling, normal group and model group were given constant volume of distilled water at room temperature intragastrically, and other groups were given relevant drug solution (1 mL/100 g) intragastrically, once a day, for consecutive 7 d. The amount of gastric residue was measured to evaluate the gastric emptying function. Immunohistochemistry SP method was used to detect the protein expression of AQP3, Ghrelin and Substance P in gastric mucosa tissue. The protein expression of Claudin-1, Occludin and VIP were detected by Western blot assay. RESULTS: Compared with normal group, the amount of gastric residue was increased significantly in model group (P<0.01); positive expression of AQP3 and Ghrelin protein in gastric mucosa tissue was decreased significantly, while the positive expression of Substance P protein tended to increase; the protein expression levels of AQP3, Ghrelin, Claudin-1 and Occludin were decreased significantly, while those of Substance P and VIP were increased significantly (P<0.05 or P<0.01). Compared with model group, the amount of gastric residue was decreased significantly in administration groups (P<0.05 or P<0.01); the positive expression of AQP3 and Ghrelin protein tended to increase, while less positive expression of Substance P was found; the protein expression levels of AQP3 and Occludin in gastric mucosa tissue were increased significantly in administration groups, while those of VIP were decreased significantly (P<0.05 or P<0.01); the protein expression levels of Ghrelin and Claudin-1 in gastric mucosa tissue were increased significantly in Fuling gancao decoction high-dose group, Fuling gancao decoction low-dose group and drug combination group, while those of Substance P were decreased significantly (P<0.05). CONCLUSIONS: Fuling gancao decoction may improve the symptom of fluid retention in FD model rats by up-regulating the protein expression of AQP3, Ghrelin, Claudin-1 and Occludin and down-regulating the protein expression of Substance P and VIP in gastric mucosa tissue of rats.
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OBJECTIVE@#To investigate the effects and its potential mechanism of asparaginase on proliferation, cell cycle and apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines.@*METHODS@#CCK-8 assay was used to detect the effect of asparaginase on proliferation of DLBCL cell lines. Flow cytometry was used to analyze cell cycle and apoptosis. Western blot was used to analyze apoptosis and its potential mechanism.@*RESULTS@#Asparaginase obviously inhibited the proliferation of multiple DLBCL cell lines and caused G/G cell arrest. Furtherly, asparaginase inhibited the expression of HIF-1α which related to poor prognosis of patients with DLBCL, up-regulated the expression of DR4 and caspase 8, reduce the expression of c-FLIP. Meanwhile, asparaginase induced the expression of pro-apoptotic protein BAX and inhibited the expression of anti-apoptotic protein MCL-1.@*CONCLUSION@#Asparaginase can inhibit the proliferation of DLBCL cell lines, cause the arrest of cells in G/G and induce apoptosis via the endogenous and exogenous apoptotic pathways.
Subject(s)
Humans , Apoptosis , Asparaginase , Cell Line, Tumor , Cell Proliferation , Lymphoma, Large B-Cell, DiffuseABSTRACT
Shaolin Neigong (internal Qigong) of tuina exercise is a distinctive part of Neigong tuina.Since the 1980s,domestic basic study on Shaolin Neigong has mainly focused on its physiologic effects,and has preliminarily proved that Shaolin Neigong can enhance the aerobic capacity,cardio-pulmonary function,and muscle strength of human body.By summarizing the literatures studying the effects of Shaolin Neigong on respiratory,circulatory,locomotor and nervous systems,this article was to understand the modern research,inheritance and protection of Shaolin Neigong.The results indicate that the modern research on Shaolin Neigong is relatively slow.Continuous development,continuity and innovation in basic research,teaching and clinical practices are required,to enhance the general and therapeutic level of tuina exercises and tuina science of traditional Chinese medicine.
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BACKGROUND: Bioabsorbable biomaterials are of crucial importance in tissue engineering applications, and various factors affect their degradation. OBJECTIVE: To compare the degradation characteristics of concentrated growth factor (CGF) clot and CGF membrane in simulated body fluid (SBF) and simulated saliva fluid (SSF). METHODS: Fifteen volunteers were selected, and human blood samples were collected for the preparation of CGF clot or CGF membrane. All specimens from each subject were averagely divided into four groups: group A, CGF clot in SBF; group B, CGF clot in SSF; group C, CGF membrane in SBF; group D, CGF membrane in SSF. The specimens were subjected to the immersion test. The average daily rate of degradation of each group was calculated after the samples were thoroughly degraded, and weight loss ratio per unit time was also determined. RESULTS AND CONCLUSION: (1) The mean degradation time in groups A-D were (14.0±0.7), (9.7±0.9), (9.9±1.2) and (7.2±0.7) days, respectively. (2) By comparing CGF membrane with CGF clot in the same simulated fluid, the average daily degradation rate of CGF clot (groups A, B) was statistically significantly lower than counterparts of CGF membrane (groups C, D) (P < 0.05). By comparison between SBF and SSF, the average daily degradation rate in the SBF (groups A, B) was significantly lower than counterparts in the SSF (groups C, D) (P <0.05). Overall, the degradation rate of CGF membrane is higher than that of CGF clot under the same degradation environment; for CGF membrane or CGF clot, the degradation rate in SSF is higher than that in SBF.
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BACKGROUND: Absorption of the alveolar bone subsequent to tooth extraction is a long-term process, especially in the anterior tooth region where the buccal part of the ridge undergoes a prominent remodeling process after tooth extraction. Socket shield technique (SST) recently reported may be a new choice for peri-implant tissue preservation. OBJECTIVE: To give an overview on the principle, interface basis and application of SST in implant dentistry. METHODS: The first author searched the PubMed, Ovid, CNKI, VIP and WanFang databases for relevant articles published from January 1990 to October 2017. The keywords were "socket shield technique;root-membrane technique; root-implant; implant proximity to teeth; dental-contected implants; dentointegration;cementum formation on implant surface" in Chinese and English, respectively. RESULTS AND CONCLUSION: SST aims to maintain alveolar bone and gingival tissues by preserving partial tooth root with its periodontium-bundle bone intact, which is an alternative strategy for tissue preservation in esthetics zone.
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Objective :To explore early diagnostic value of carotid intima-media thickness (IMT) and hemodynamic indexes for ischemic cerebrovascular diseases .Methods :A total of 42 cases with cerebral infarction (CI group) ,98 cases with transient ischemic attack (TIA group) and 40 cases without cerebrovascular disease were enrolled as nor-mal control group ,and all patients were received and cured in our hospital from Jan 2014 to Jan 2017. All subjects received Doppler ultrasonography after hospitalization ,IMT at common carotid artery (CCA) bifurcation and its distal end ,peak systolic velocity (PSV) ,end-diastolic velocity (EDV) ,vascular pulsatility index (PI) ,vascular re-sistance index (RI) and ratio of peak wave ascending branch slope to descending branch slope (S1/S2) at CCA ,in-ternal carotid artery (ICA) and vertebral artery (VA) were measured and compared among three groups ,and diag-nostic value of IMT for CI and of hemodynamic indexes for TIA were analyzed .Results : Compared with normal control group and TIA group ,there were significant rise in IMT of CCA bifurcation [ (0.87 ± 0.05) mm ,(0.87 ± 0.04) mm vs.(1.04 ± 0.05) mm] and IMT of CCA bifurcation distal end [ (0.77 ± 0.06) mm ,(0.78 ± 0.04) mm vs.(0.90 ± 0.02) mm] in CI group , P= 0.001 all.There were no significant difference in PSV ,PI and RI at CCA ,ICA and VA among three groups , P>0. 05 all.EDV and S1/S2 at CCA ,ICA and VA of three groups were all accorded with TIA group< CI group< normal control group ,and there was significant difference between any two groups , P<0. 01 all .Sensitivity ,specificity ,negative and positive predictive value of IMT of CCA bifurcation diagnosing CI were higher than those of IMT of CCA bifurcation distal end ,but there were no significant differ-ence , P>0. 05 all.Conclusion :During Doppler ultrasonography ,detecting carotid IMT , EDV and S1/S2 at CCV , ICA and VA contribute to diagnosing cerebral infarction and TIA .