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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 pandemic, is rapidly evolving. Due to the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOC), including the currently most prevalent Delta variant, orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously we showed that adenosine analogue 69-0 (also known as GS-441524), possesses potent anti-SARS-CoV-2 activity. Herein, we report that esterification of the 5-hydroxyl moieties of 69-0 markedly improved the antiviral potency. The 5-hydroxyl-isobutyryl prodrug, ATV006, showed excellent oral bioavailability in rats and cynomolgus monkeys and potent antiviral efficacy against different VOCs of SARS-CoV-2 in cell culture and three mouse models. Oral administration of ATV006 significantly reduced viral loads, alleviated lung damage and rescued mice from death in the K18-hACE2 mouse model challenged with the Delta variant. Moreover, ATV006 showed broad antiviral efficacy against different mammal-infecting coronaviruses. These indicate that ATV006 represents a promising oral drug candidate against SARS-CoV-2 VOCs and other coronaviruses.
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OBJECTIVE: To observe the efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase (ALK) positive advanced lung adenocarcinoma. METHODS: From Aug. 2015 to May 2017, 72 patients with ALK positive advanced lung adenocarcinoma were selected from our hospital. According to the simple random method, the patients were divided into control group and observation group, with 36 patients in each group. The control group was given Pemetrexed disodium for injection 500 mg/m2,d1, ivgtt+ Cisplatin for injection 75 mg/m2,d1-3,ivgtt; Dexamethasone acetate tablets 0.75 mg were given orally one day before administration, once in the morning and again in the evening; 7 days before administration, Folic acid tablets 0.4 mg were given orally till 21 days after the last administration of cisplatin; Vitamin B12 1 mg injection was injected intramuscularly every 3 weeks after intramuscular injection of cisplatin. Isotonic Glucose injection 100 g was intravenously dripped 1 day before medication; on the day of chemotherapy, isotonic Sodium chloride injection or Glucose injection was infused intravenously for 3 000-3 500 mL; at the same time, Potassium chloride injection 0.5 g, Mannitol injection 50 g, Furosemide injection 20 mg were given to ensure daily urine volume of 2 000-3 000 mL; a treatment course lasted for 21 d, and there were 2 courses in total. Observation group was additionally given Crizotinib capsules 250 mg orally, once at 7:00 in the morning and evening, swallowing whole capsule, not chewed or dissolved, for 42 days. The clinical efficacies, survival quality and the occurrence of toxic reaction were observed in 2 groups. RESULTS: Total response rate (61.11%) and stable rate of survival quality (83.33%) in observation group were significantly higher than those (27.78%, 44.44%) of control group (P<0.05); incidence of grade Ⅰ-Ⅳ myelosuppression, gastrointestinal reaction, abnormal liver function, peripheral neuritis and alopecia in observation group were significantly lower than those of control group; incidence of grade Ⅰ-Ⅳ visual effect in observation group was significantly higher than control group(P<0.05). There was no statistical significance in the incidence of edema between 2 groups(P>0.05). CONCLUSIONS: Based on routine chemotherapy, additional application of crizotinib can significantly improve therapeutic efficacy of patients with advanced ALK positive lung adenocarcinoma, and effectively improve survival quality of patients without increasing the occurrence of toxic reaction of other tissues or organs, but the incidence of toxic reaction is in high level relatively.
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The establishment of a scientific salary system is a key measure to improve the incentive and re-straint mechanisms, adjust and optimize the relations of the production, release the reform “bonus”, and is also an important health care reform today. In order to establish a scientific salary system of medical personnel adapting to the health industry characteristics, the paper makes an investigation on the salary level in the years of 2010—2012 in Shanghai, and analyzes the main problems of the present performance pay policy. On this basis, starting from the point of the health industry characteristics, the paper builds the salary system of medical personnel containing the comprehensive budget management, theoretical workload for approval, authorized personnel, performance appraisal and distribution, structural proportion within the industry, fund distribution management through the establishment of the salary level’s average wage and social linkage mechanism, and builds a theoretical framework on salary system of medical personnel in Shanghai.
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The authors discussed about how to integrate the advantages of different medical research resources to construct Shanghai Academy of Medical Sciences,which will provide substantial support for medical innovation in Shanghai.Principles were proposed concerning the administrative system and management mechanism to enhance the performance.The Academy is expected to improve medical research and clinical performance,especially to help resolve some major diseases and incurable diseases.Ultimately,the Academy will develop into an advanced research center linking laboratory research and clinical medicine.
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ObjectiveTo explore the effect of different methods of drainage tube and catheter drainage in the treatment of intraventricular hematoma.MethodsThe analysis was conducted in 83 cases,who were randomly divided into two groups,the treatment group with 48 cases adopting lateral venticle catheterization combined with bulletshaped tube,and the control group with 35 cases adopting conventional catheterization.The contrasted study was conducted on the clearance rate of cerebroventricular hematoma and the effect of the different drainages.ResultsThe clearance rate in treatment group was 27.1% ( 13/48 ),50.0% (24/48),14.6% (7/48),at the time of < 24h,24 ~72h,> 72h after the operation,and 5.7 % ( 2/35 ),17.1% ( 6/35 ),48.6% ( 17/35 ) in the control group.It showed statistical significance(x2 =6.2425,9.4678,11.3757,all P <0.01 ).The cases with type Ⅰ of ADL stage in treatment group (47.9%)were more than control group( x2 =6.8347,P <0.01 ).The morbidity in treatment group was 12.5%,which was lower than control group( x2 =6.9636,P <0.01 ).ConclusionThe lateral venticle catheterization drainage combined with bullet-shaped tube could avoid the obstruction,reduce the morbidity,and improve the therapeutic effect.
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During the course of standardized residents training,the performance appraisal management of the residents was used besides other regular management methods.The allowances of residents were decided monthly by the evaluation and assessment of many kinds of tests or examinations.Through this new measure,the learning enthusiasm of residents could be fully motivated.The authoritative effectiveness of management was enhanced enormously.Meanwhile,the quality of the educational and training has also been improved greatly.This method could be very useful for the training process.
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This study surveyed medical research institutions in Shanghai for the structure set, input and output, development orientation, bottleneck and other aspects. Problems were found with their relationship management, discipline arrangement, research efficacy and else.
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Objective To study the surgical techniques of the extended subfrontal epidual approach to resect chordoma in skull base.Methods 18 cases of chordoma in skull base treated mierosurgically were analyzed retrospectively.Results Total resection were achieved in 15 patients(83%),gross resection in 3 patients(17%).There was no complication in all cases.Conclusion The microsurgery for chordoma in skull base via the extended subfrontal epidual approach is of the benefits such as clear and wide fields of vision,and minimize brain trauma.Lumber drain placement and the skull base reconstruction could improve the rate of total tumor removal and reduce complications.
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Objective: To establish the culture system of hairy root of Isatis indigotica and to induce the regeneration plant of hairy root. Methods: Hairy root of Isatis indigotica was obtained from infected cotyledon explants after infection with Agrobacterium rhizogenes strains A4, R1601 and ATCC15834. The better lines were selected. The growth curve was surveyed and extrinsic factors affecting the growth of hairy roots were investigated. The regeneration plant was induced on MS media with different hormones. The transformation of Ri T DNA was examined through high voltage paper electrophoresis. Results: The hairy root was originally obtained from Isatis indigotica . The regeneration plant was induced on MS media with BA. The result of high voltage paper electrophoresis confirmed the transformation of T DNA from Ri plasmid to the hairy root and regeneration plant. Conclusion: The acquisition of hairy root of Isatis indigotica and regeneration plant of it lay a foundation for the production of active component and introduction of foreign gene. [
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Objective: To study the proper medium for tissue culture of the explants from Hypericum perforatum . Methods: The root, stem with node and leaf of the Hypericum perforatum seedling were used as explants, and cultured in basic Murashige and Skoog (MS) medium supplemented with different kinds and different concentrations of hormones. The callus, buds and roots were induced. The cultivation of the tube seedling were carried out. Results: Different hormones and explants had different effects on the induction of callus and the formation of buds. 2,4 D could promote the formation of the callus of Hypericum perforatum . Among cytokinins, 6 BA had great effect on the formation of buds, but the effects of KT and ZT were insignificant. The combination of NAA 1 mg/L and 6 BA 0.2 mg/L was found most effective in promoting the rooting of Hypericum perforatum . Conclusion: The results indicate that the callus is easy to be induced when MS medium supplemented with 2,4 D. The root of explants is most suitable for the rosette bud rapid induction.
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In order to maintain and develop the overall advantages and distinguishing features of medicine in Shanghai, the citys health system implemented the program of constructing centers for clinical medicine. The program involved not only the optimization and integration of health resources in the whole city but also the structural readjustment and resources regrouping within the citys health system and each individual hospital. After more than two years construction, 33 centers for clinical medicine have been set up in the city, resulting in primary achievements in expertise improvement, effect of scale, and quality benefits. By analyzing the hardware and software construction process, it can be seen that the centers for clinical medicine have made primary achievements in such aspects as ideological construction, work efficiency, interdisciplinary cooperation, academic status enhancement, medical quality improvement, and reform in the system of personnel distribution.
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Object To establish the culture system of hairy root of Eclipta prostrata (L.) L.. Methods Hairy root of E. prostrata was obtained from infected cotyledon explants after infection with Agrobacterium rhizogenes strains A4, R1601 and ATCC15834, elite strains were screened and growth curves determined. The transformation of Ri T DNA was examined through high voltage paper electrophoresis. Results The hairy root was originally obtained from E.prostrata. The result of high voltage paper elctrophoresis confirmed the transformation of T DNA from Ri plasmid to the hairy root. Conclusion The acquisition of hairy root of E. prostrata provided further a foundation for the industrial production of active drug component.