The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90％–159％. The mean terminal half-lives of DZ2002 and DZA were 0.3–0.9 and 1.3–5.1 h, respectively. The sample preparation method illustrated here may be adopted for de-termination of other circulating ester drugs and their acid metabolites in rodents.

Objective To evaluate the necessity of arc by arc setup verification in patients with brain metastases receiving stereotactic radiotherapy (SRT) by analyzing the inter-and intra-fraction setup errors and residual errors collected from the ExacTrac X-ray portal image.Methods Clinical data of brain metastases patients treated with SRT in the previous two years were retrospectively analyzed.The ExacTrac X-ray setup images were collected after the normal setup procedure.Setup errors were calculated by registering the cranial bony structures of the ExacTrac X-ray setup images to that of the digitally reconstructed setup images.The inter-and intra-fraction setup errors and residual errors were statistically analyzed.Results Seventy-five patients from 116 lesions received 337 cycles of SRT of the head.The inter-and intra-fraction translational setup errors in the x,y and z directions were (0.93±0.86) mm and (0.15±0.59) mm;(1.83± 1.27) mm and (0.25±0.73) mm;(0.96±0.80) mm and (0.14±0.56) mm,respectively.The inter-and intra-fraction rotational setup errors in the x,y,z directions were (0.65°± 0.62°) and (0.19°± 0.40°);(0.97°±0.94°) and (0.13°± 0.25°);(0.92°± 0.71°) and (0.10°± 0.29°),respectively.The residual translational setup errors in the x,y,z directions were (0.06±0.23) mm,(0.08±0.24) mm and (0.08±0.22)mm,and (0.12°± 0.27°),(0.09°± 0.18°) and (0.06°± 0.19°) for the residual rotational setup errors,respectively.For a reference setup error threshold of 0.7 mm/0.7°,99.1％ of the SRT exceeded the threshold and required setup correction.For 1 006 non-coplanar arcs,rotating the treatment couch from 0° to the treatment angle made 66.4％ of arcs exceed the threshold and require at least once setup correction.Conclusions During SRT for brain metastasis,the inter-and intra-fraction setup errors should be emphasized.It is necessary to perform arc by arc setup error verification.

Objective: To investigate the application of metagenomic next-generation sequencing (mNGS) in detection of the rare or difficult-to-cultivate pathogens. Methods: One patient with acute lymphoblastic leukemia who went through allogeneic hematopoietic stem cell transplantation (allo-HSCT) developed symptoms of infection after transplantation. Conventional microbial culture, polymerase chain reaction (PCR), and mNGS combined with biological information analysis were performed with plasma and cerebrospinal fluid samples, the anti-infective treatment was adjusted according to the test results, and the efficacy was assessed. Results: No suspected pathogens were detected by microbial culture and PCR in the cerebrospinal fluid and plasma samples since the patient developed infection symptoms. However, Legionella pneumophila was analyzed by mNGS in the cerebrospinal fluid specimen on day 23 after allo-HSCT (reads count: 19 655), and it was considered as the principal pathogen after comprehensively evaluating the patient's clinical manifestations and the test results. Then the antimicrobial treatments were adjusted according to the patient's clinical manifestations and laboratory test results, and the number of gene sequences of Legionella pneumophila was monitored by mNGS method. Azithromycin, tigecycline, and other antibiotics effective for Legionella pneumophila were used after detecting this pathogen. A total of 15 mNGS analysis were performed during the 5-month period, and the highest number of Legionella pneumophila sequences monitored in the cerebrospinal fluid was 2 226, the lowest was 253 and eventually turned negative. The clinical symptoms and treatment outcomes were consistent with the mNGS monitoring results. Conclusions The mNGS technology has significant value in detection of the rare and difficult-to-cultivate pathogens. The mNGS technology provides a valuable supplement to microbial culture and PCR methods.

Objective To analyze and investigate the risk factors for intraoperative and postoperative bleeding complications of stent implantation for ruptured intracranial aneurysms(from rupture to operation time ≤14 d). Methods A total of 249 consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH)treated with stent intravascular interventional therapy at the Department of Neurosurgery,Tangdu Hospital,the Second Hospital Affiliated to Air Force Medical University(the Fourth Military Medical University)from August 2014 to July 2017 were enrolled retrospectively.According to whether having intraoperative and postoperative bleeding complications,they were divided into either a hemorrhage complication group(n=33)or a non-complication group(n=216).The baseline data,clinical data,and aneurysm characteristics,including age,sex,hypertension,Glasgow Coma Scale(GCS)score,aSAH to the patients were documented and analyzed,and multivariate logistic regression analysis was used to analyze the risk factors for bleeding complications. Results (1)The incidence of perioperative bleeding complications was 13. 3% (33 /249). (2)There was significant difference in GCS scores between the bleeding complication group and the non-complication group (P < 0. 05). There were no significant differences in age,male,hypertension,and aSAH to operation time between the two groups (all P >0. 05). (3)There were significant differences in Hunt-Hess grade (χ2 = 10. 392,P = 0. 001),Fisher score (χ2 = 7. 370,P =0. 007),number of aneurysms (χ2 = 4. 825,P = 0. 028),and aneurysm location (χ2 = 6. 818, P = 0. 033)between the bleeding complication group and the non-complication group. There were no significant differences in Raymond grade between the two groups (P > 0. 05). (4)Taking the occurrence of bleeding complications as a dependent variable,a further multivariate logistic regression analysis on Hunt- Hess grades Ⅲ-Ⅴ and multiple aneurysms was performed after variable screening,the results showed that Hunt-Hess grades Ⅲ-Ⅴ(OR,3. 658,95% CI 1. 660 -8. 061)and multiple aneurysms (OR,2. 667,95% CI 1.178-6.036)were the independent risk factors for stent placement in the treatment of bleeding complications of ruptured intracranial aneurysms(all P <0.05). Conclusions The single stent and stent-assisted coils can be used for endovascular treatment of rupture intracranial aneurysms,but preoperative Hunt-Hess grades Ⅲ-Ⅴ and multiple aneurysms are easy to cause perioperative bleeding complications in patients with aSAH.

Objective To explore effect of Yiqi-Huoxue decoction in combination with exercise rehabilitation therapy on functional recovery of hemiplegic limbs and surface electromyography (Surface electromyography,sEMG) during cerebral infarction convalescence.Methods According to random number table,80 cerebral infarction patients in convalescence stage who met the inclusion criteria were divided into the combination therapy group and rehabilitation therapy group,40 in each group.Rehabilitation therapy group received hemiplegia rehabilitation therapy;combination therapy group took Yiqi-Huoxue decoction on the basis of rehabilitation treatment.The 2 groups were treated for 3 months.In hemiplegic upper limb,Fugl-Meyer Assessment (FMA) was scored and Root Mean Square (RMS) and Median Frequency (MDF) of sEMG on biceps brachii were tested before and after each course of treatment respectively.Results After 1-,2-,or 3-month treatment,FMA score of combination therapy group was significantly higher than that of rehabilitation therapy group (t=2.702,4.595,4.444,respectively;all P＜0.01).At 2 or 3 months after treatment,the RMS of combination therapy group (t=7.188,5.405,respectively;all P＜0.01) and the MDF (t=3.336,4.584,respectively;all P＜0.01) were significantly higher than that of rehabilitation therapy group.Conclusions The Yiqi-Huoxue decoction in combination with exercise rehabilitation therapy can improve motor function and muscle tension of hemiplegic limbs during cerebral infarction convalescence.

Objective To investigate the mid-term clinical outcomes of arthroscopic anatomical re-construction of double bundles of the anterior cruciate ligament ( ACL ) . Methods The clinical data of 78 patients diagnosed with ACL rupture from April 2012 to July 2014 were analyzed retrospectively. They were 60 males and 18 females, aged from 19 to 56 years ( mean, 26. 8 years ) . The time from injury to surgery ranged from one week to 23 months ( mean, 5. 8 months ) . All of them obtained positive results in anterior drawer test and Lachman test preoperatively. Their preoperative KT-1000 examinations showed an average side-to-side difference of 8. 29 ± 1. 81 mm in anterior laxity. They were all treated with arthroscopic anatomical recon-struction of double bundles of the anterior cruciate ligament using autologous hamstrings. The International Knee Documentation Committee ( IKDC ) and Lysholm scores were used to assess their knee function at the last follow-up. Results All the 78 patients were followed up for 34. 6 months on average ( range, from 25 to 56 months ) . At the last follow-up, the IKDC and Lysholm scores were significantly increased from preoper-ative 42. 6 ± 9. 5 and 44. 4 ± 8. 5 to postoperative 92. 9 ± 2. 8 and 94. 2 ± 3. 4, respectively ( P <0. 05 ) . The Lachman test was negative in 73 cases ( 93. 6％) and the pivot shift test was negative in 69 cases ( 88. 5％) . The KT-1000 examinations showed that the side-to-side difference in anterior laxity averaged 1. 47 ± 0. 68 mm, significantly improved from the preoperative values ( P <0. 05 ) . At their last follow-up, 29 patients underwent MRI scans which showed continuity of the anteromedial and posterolateral bundles of the anterior cruciate liga-ment. Conclusion The arthroscopic anatomical reconstruction of double bundles of the anterior cruciate ligament can restore the knee stability and achieve fine mid-term clinical outcomes.

Objective To evaluate the left atrial(LA) function in patients with severe preeclampsia ( SPE) by full-volume imaging technology. Methods Forty-two patients of SPE were randomly chosen as SPE group,34 healthy pregnant women were selected as the control group. LA related function parameters including LA maximum volume( LAVmax),LA minimum volume( LAVmin),LA pre-atrium contraction volume(LAVpre),LA reservoir volume(LARV),LA passive emptying volume(LAPEV),LA contraction volume(LACV),LA expansion index(LAEI),LA passive emptying fraction(LAPEF),LA passive emptying fraction( LAAEF ) were separately required by biplane area-length method and full-volume imaging technology in antepartum and postpartum. Results Compared with control group before delivery,the parameters of SPE group before delivery such as LAVmax,LAVmin,LAVpre were higher,LAEI,LAPEF, LAAEF indexed to body surface area(BSA) were lower(all P ＜0.01).Compared with control group before delivery,the parameters of control group after delivery such as LAVmax,LAVmin,LAVpre were lower( all P ＜0.05),LAEI, LAAEF calculated as ratio to BSA were somewhat reduced,LAPEF calculated as ratio to BSA was relatively higher(all P ＞0.05).Compared with SPE group before delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were lower,LAEI,LAPEF,LAAEF indexed to BSA were higher( all P ＜0.01). Compared with control group after delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were still incresed ( all P ＜ 0.05 ), LAEI,LAPEF, LAAEF indexed to BSA were relatively lower( all P ＞0.05). Conclusions Full-volume imaging technology can quantitatively evaluate the LA function. LA reservoir function,conduit function and booster pump function are reduced in SPE before delivery,LA rereservoir function,conduit function and booster pump function are basically recovery in SPE after delivery.

Objective To investigate the suppressive effect of prostaglandin E2 (PGE2),hepatocyte growth factor (HGF) and indoleamine 2,3-dioxygenase (IDO) whose secretion was promoted by human umbilical cord mesenchymal stem cells(MSCs) on the activated peripheral blood CD4+ T cells in primary Sj(o)gren syndrome (pSS) in vitro.Methods Primary cultured umbilical cord MSCs were identified by flow cytometry,and peripheral blood CD4+ T cells were sorted in pSS patients.CD4+ T cells were cultured with CD3,CD28 antibody for 72 h to be the activated(control group);the activated CD4+ T cells were co-cultured with MSCs for 72 h(MSCs group) or MSCs were pre-stimulated with interferon-γ (IFN-γ),then the activated CD4+ T cells were co-cultured with pre-stimulated MSCs for 72 h (pre-stimulated group).The suspension of CD4+ T cells were collected and counted.PGE2,HGF and IDO in the supernatants were detected by ELISA.Mean in groups were compared using ANOVA,and multiple comparisons were used with LSD method.Results The concentrations of PGE2 in the supernataut of the control group,MSCs group and pre-stimulated group were (111 ±4) pg/ml,(2 814±6) pg/ml and (2 716±8) pg/ml (F=167 292.12,P＜0.01) respectively.The concentrations of HGF in the above groups were (597±9) pg/ml,(383±9) pg/ml and (727±12) pg/ml(F=878.61,P＜0.01) respectively.The concentrations of IDO in the above groups were (143±4) pg/ml,(835±5) pg/ml and (588±3) pg/ml (F=21 104.41,P＜0.01) respectively.Compared with the control group,levels of PGE2 significantly increased in the MSCs group and the pre-stimulated group that CD4+ T cells were co-cultured with MSCs (t=509.88,P＜0.01 and t=491.48,P＜0.01),and levels of IDO also significantly increased (t=202.69,P＜0.01 and t=130.39,P＜0.01),while the activation and proliferation of CD4+T cells were inhibited (t=-16.20,P＜0.01 and t=-31.48,P＜0.01).Compared with MSCs group,levels of PGE2 and IDO significantly decreased in pre-stimulated group (t=-18.40,P＜0.01 and t=-72.30,P＜0.01),and levels of HGF significantly increased in pre-stimulated group(t=41.51,P＜0.01),while the activation and proliferation of CD4+ T cells were further inhibited (t=-15.28,P＜0.01).Conclusion MSCs can inhibit the activation and proliferation of CD4+ T cells in pSS in vitro.The suppressive effect of MSCs may be achieved by promoting secretion of cytokines such as PGE2,HGF and IDO.HGF plays a more important role in the suppressive effect of MSCs pre-stimulated with IFN-γ.Too much PGE2 or IDO propably results in negative feedback regulation of MSCs.

Since 2007, the State Administration of TCM has implemented the preventive treatment of TCM health project, support the development of the Preventive treatment Section, issued the TCM health management service standards for special groups, and vigorously established the TCM preventive health service system. The thought of preventive treatment in TCM fully embodies the thinking mode of preventive and health care for TCM, but health management is a specific process of monitoring, evaluation, intervention and follow-up of health risk factors. In this paper, through comparative research methods, we analyzed the similarities and differences between preventive treatment of TCM and health management from historical origins, ideological content, guiding ideology, and key strategies and techniques, and we have discovered preventive treatment of TCM has more obvious advantages in theoretical height and comprehensive conditioning, and modern health management is more advanced in the application process and technical means. Their common points in the pursuit of health promotion and disease prevention, the emphasis on holistic medical concepts, and the focus on health risk factors, and the possible fusion of preventive treatment of TCM and health management in core ideas, theory and practice and technical methods, especially for prevention, treatment and rehabilitation of sub-health, constitution bias, chronic diseases and other groups. The phased monitoring-assessment-intervention approach under the guidance of the idea of preventive treatment can provide suggestions for the development ideas of TCM health management. Research on TCM health risks monitoring and assessment in different life cycles needs to be strengthened.