Short-term outcome of ascending aorta replacement combined with total aortic arch fenestration technique for acute type A aortic dissection / 中国胸心血管外科临床杂志

@#Objective    To report our clinical experience and outcomes of thoracic endovascular aortic repair (TEVAR) for acute Stanford type A dissection using ascending aorta replacement combined with implantation of a fenestrated stent-graft of the entire aortic arch through a minimally invasive technique. Methods    From 2016 to 2020 in our hospital, 24 patients (17 males and 7 females, aged 45-72 years) with complicated Stanford type A aortic dissection, underwent replacement of the proximal ascending aorta with TEVAR. None of the patients with dissection involved the three branches of the superior arch, and all patients were replaced with artificial blood vessels of the ascending aorta under non-hypothermic cardiopulmonary bypass, preserving the arch and the three branches above the arch, and individualized stent graft fenestration. Results    Surgical technical success rate was 100.0%. There was no intraoperative complication or evidence of endo-leak in 1 month postoperatively. Hospital stay was 10±5 d. During postoperative follow-up, the stent was unobstructed without displacement, the preserved branch of the aortic arch was unobstructed, and the true lumen of the descending aorta was enlarged. Conclusion     This hybrid technique by using TEVAR with fenestrated treatment is a minimally invasive and effective method to treat high-risk patients with acute Stanford type A aortic dissection.

Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of coronavirus SARS-CoV-2. Existing direct-acting antiviral (DAA) drugs cannot be applied immediately to new viruses because of virus-specificity, and the development of new DAA drugs from the beginning is not timely for outbreaks. Thus, host-targeting antiviral (HTA) drugs have many advantages to fight against a broad spectrum of viruses, by blocking the viral replication and overcoming the potential viral mutagenesis simultaneously. Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knocking-out cells. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. Notably, S416 is reported to be the most potent inhibitor with an EC50 of 17nM and SI value >5882 in SARS-CoV-2-infected cells so far. This work demonstrates that both our self-designed candidates and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-repression may have clinical potentials not only to influenza but also to COVID-19 circulating worldwide, no matter such viruses mutate or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Correlation between TGF-B gene promoter-509C/T polymorphism and IgA nephropathy in core families in Guangxi Zhuang Autonomous Region and the therapeutic effect of dendrobium / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation between transformation growth factor (TGF- B) polymorphisms and IgA nephropathy and the therapeutic effect of dendrobium on IgA nephropathy.</p><p><b>METHODS</b>Polymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) and direct sequencing were used for analysis of 118 patients with IgA nephropathy from core families in Guangxi Zhuang Autonomous Region. The imbalanced transfer of TGF iso1-509 C/T in the affected offsprings was observed by transfer imbalance test and HRR analysis. The TGF-B genotype of the patients and the core family members were detected. The therapeutic effects of Dendrobium candidum combined with hormone and ACEI/ARB treatments were evaluated by observing the patient's urine protein (24 hUpr), serum albumin (ALB), creatinine (Scr) and urea nitrogen (BUN) levels.</p><p><b>RESULTS</b>In the 118 patients with IgA nephropathy, we identified TGF-B 1 promoter -509C/T genotype CC in 32 (27.1%) cases, CT in 58 (49.2%) cases, and TT in 28 (23.7%) cases. In the core family of the patients, CC genotype was found in 33 (28.0%) cases, CT in 55 (46.6%) cases, and TT in 30 (28.0%) cases. The treatments significantly lowered 24 hUpr, Scr, and BUN levels ( > 0.05) in patients with CC genotype, significantly lowered 24 hUpr and BUN levels in patients with CT genotype ( < 0.05), and significantly lowered 24 hUpr and BUN level and increased ( < 0.05) ALB level ( < 0.01) in patients with TT genotype.</p><p><b>CONCLUSIONS</b>There is no significant correlation between TGF-B promoter - 509C/T polymorphism and IgA nephropathy. The patients with CC genotype are sensitive to the treatments with hormone and ACEI/ ARB and show a stronger response to combined treatments with dendrobium.</p>

Expression and clinical significance of small fragments of P28 and P43 in papillary thyroid carcinoma after TRa1 gene transcription / 实用肿瘤学杂志

Objective The objective of this study was to investigate the expression of P28 and P43 in papillary thyroid carcinoma(PTC)and its relationship with clinicopathological features after TRa1 gene transcription.Methods Real-time fluorescence quantitative PCR(RT-PCR)and gel electrophoresis were used to determine the target fragments and to isolate the bands of different fragments.The optical density of each band was scanned by UV transmittance analyzer to detect 31 cases of PTC tissue and expression levels of P28 and P43 in para-cancerous tissues.Results The average gray value of P28 in thyroid carcinoma group was 0.77±0.34,which was significantly higher than that in para-cancer group(0.31±0.18).The average gray value of P43(0.85+0.21)in thyroid carcinoma group was significantly higher than that in para-cancer group(0.34±0.15)(P0.05),The expression levels of P43 were not correlated with gender,age,tumor size and lymph node metastasis.(P>0.05)but they were related to clinical pathologic stage(P<0.05).There was no correlation between expression levels of P28 and P43(r=0.266,P=0.071).Conclusion The increased expression of P28 and P43 may have a high degree of malignancy and a certain clinical value in predicting the adverse prognosis of PTC.Both factors are helpful for the prevention and treatment of PTC.

Long-term Therapeutic Observation of Acupuncture at Phenomaxillary Ganglia for Allergic Rhinitis / 上海针灸杂志

ObjectiveTo observe the short-term and long-term efficacies of acupuncture at phenomaxillary ganglia in treating allergic rhinitis.MethodThe recruited subjects were intervened by acupuncture at phenomaxillary ganglia, once a week and 6 times asa treatment course. Visual Analogue Scale (VAS) was adopted to evaluate the general condition and nasal symptoms, and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to estimate the quality of life (QOL). The evaluations were performed before and after intervention, as well as 2 years after the intervention.ResultThe subjects all had significant improvements in the clinical symptoms after 6 sessions, and the VAS scores of the general conditional nasal symptoms and RQLQ score were significantly decreased (P0.05).ConclusionAcupuncture at phenomaxillary ganglia is effective in treating allergic rhinitis, and the efficacy lasts stably within 2 years.

Cumulative Analgesic Effect of Electroacupuncture at Sanyinjiao (SP6), Xuanzhong (GB39) and Non-acupoint for Primary Dysmenorrhea：A Comparative Study / 上海针灸杂志

Objective To compare the cumulative analgesic effects of electroacupuncture at Sanyinjiao (SP6), Xuanzhong (GB39) and non-acupoint in treating primary dysmenorrhea. Method By adopting a multi-centered randomized controlled study method, 501 patients recruited from Dongzhimen Hospital of Beijing University of Chinese Medicine, China-Japan Friendship Hospital, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Huguosi Hospital of Chinese Medicine of Beijing University of Chinese Medicine and the Outpatient of Shandong University of Traditional Chinese Medicine were randomized into a Sanyinjiao group, a Xuanzhong group, and a non-acupoint group, 167 subjects in each group. The electroacupuncture intervention was applied when dysmenorrhea flared up and the Visual Analogue Scale (VAS) ≥40 mm, with frequency at 2/100 Hz and intensity during patient’s endurance, 30 min each time, once a day, and for successive 3 d. Before the first treatment, 30 min after the first treatment, and respectively prior to the second and third treatment, VAS was used to measure the pain intensity. Meanwhile, the Retrospective Symptom Scale (RSS-COX 2) was investigated before the first treatment, right after the removal of needles for the first treatment, before the second and third treatment. Result The decrease of VAS in Sanyinjiao group was more significant than that in Xuanzhong group and non-acupoint group (MD=﹣2.92 mm, P=0.028; MD=﹣3.47 mm, P=0.009), while there was no significant difference between Xuanzhong group and non-acupoint group (MD=﹣0.56 mm, P=0.674); there were no significant differences in comparing the RSS-COX2 total score among the three groups (P=0.086). Conclusion Sanyinjiao (SP6) can produce a more significant cumulative analgesic effect for primary dysmenorrhea patient than Xuanzhong and non-acupoint, and the effects of Xuanzhong and non-acupoit are equivalent.