Objective:To investigate the mortality-related factors affecting patients with gastrointestinal perforation who are transferred to the intensive care unit (ICU) and to establish a prediction model, and to evaluate the predictive performance of the model.Methods:A retrospective analysis was performed on the medical records of 306 patients who underwent gastrointestinal perforation surgery in Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2021 to January 2024 and were transferred to intensive care unit after surgery, including 176 males and 130 females, aged from 28 to 92 years with the average of (66.07±16.03) years. According to the prognosis, patients were divided into survival group ( n=264) and death group ( n=42). Clinical characteristics of the two groups were compared, univariate and multivariate Logistic regression was used to analyze the risk factors of perioperative death, and the related risk factors were selected to establish a nomogram prediction model, the subject work curve was drawn, and the area under the curve (AUC) was calculated. Evaluate its predictive effectiveness; The calibration chart and clinical decision curve were further used to evaluate the prediction accuracy and clinical application value of the model. Results:Clinical data analysis showed that age, white blood cell count, procalcitonin, lactic acid level, preoperative shock, preoperative underlying diseases (cerebral infarction, hormone history), intraoperative blood loss, postoperative lung infection in the death group were higher than those in the survival group ( P<0.05), and hemoglobin was lower than those in the survival group ( P<0.05). Multivariate Logistic regression analysis showed age ( OR=1.422, 95% CI: 1.205-1.680, P<0.001), hemoglobin ( OR=0.945, 95% CI: 0.904-0.987, P=0.012), white blood cell count ( OR=1.832, 95% CI: 1.341-2.501, P<0.001), procalcitonin ( OR=1.099, 95% CI: 1.012-1.192, P=0.024), lactic acid level ( OR=16.435, 95% CI: 3.729-72.425, P<0.001), reoperative shock ( OR=172.358, 95% CI: 13.059-2274.773, P<0.001), intraoperative blood loss ( OR=1.041, 95% CI: 1.017-1.065, P=0.001) and postoperative pulmonary infection ( OR=38.670, 95% CI: 3.449-433.553, P=0.003) was an independent risk factor for perioperative death in intensive care patients after DTP. Based on the screened independent risk factors ( P<0.05), a nomogram model was established and receiver operating characteristic (ROC) curve was drawn. The model area under the curve was 0.985. The accurate graph shows that the predicted results of the model are in good agreement with the actual clinical results, and the analysis of clinical decision curve indicates that the model has high clinical prediction value. Conclusion:Age>71.5 years, hemoglobin< 109 g/L, white blood cell count>17.9×10 9/L, procalcitonin>6.225 ng/mL, lactate level>2.25 mmol/L, preoperative shock, intraoperative blood loss>45 mL and postoperative pulmonary infection are independent risk factors for perioperative death in intensive care patients after DTP.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective:To compare the efficacy and safety of omacycline with meropenem plus linezolid in the treatment of patients with pulmonary infection.Methods:The clinical data of 58 patients with pulmonary infection admitted to the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou Red Cross Hospital and Jiande First People’s Hospital from December 2021 to May 2022 were retrospectively analyzed. The patients were divided into the omacycline group ( n=29) and the meropenem combined with linezolid group (combined group, n=29). The omacycline group was given intravenous omacycline 200 mg or 100 mg, q. d, and the combined group was given intravenous meropenem (1 000 mg, t.i.d) and linezolid (600 mg, b. i.d). The clinical efficacy and drug-related adverse events of two groups were observed. SPSS 22.0 statistical software was used for data analysis. Results:In the omacycline group, 8 cases (27.6%, 8/29) were cured, 19 cases (65.5%, 19/29) were improved, and 2 cases (6.9%, 2/29) were worsened. In the combined group, 1 case (3.4%, 1/29) was cured, 26 cases (89.7%, 26/29) were improved, and 2 cases (6.9%, 2/29) died. There was a statistically significant difference between the two groups ( χ2=6.533, P=0.038). The respiratory failure occurred in 3 cases (10.3%, 3/29) of the omacycline group and 5 cases (17.2%, 5/29) of the combined group ( χ2=0.580, P=0.446). In those patients who were cured or improved, the median time from treatment initiation to disease remission was 3.0 (2.0, 5.5) d in the omacycline group and 5.0 (4.0, 6.0) d in the combined group ( Z=-2.122, P=0.034). There was no significant difference in the incidence of adverse reactions between the two groups [6.9% (2/29) vs. 13.8% (4/29), χ2=0.744, P=0.389]. Conclusion:Omacycline exhibits a good efficacy and safety in the treatment of patients with pulmonary infection, which may be prioritized for the treatment of pulmonary infections.

Objective:To analyze the changes of serum lipidomics in patients with sepsis and healthy controls, search for the differences of lipid metabolites, and reveal the changes of lipidomics in the process of sepsis.Methods:A prospective observational study was conducted. From September 2019 to April 2020, morning blood samples of upper extremity superficial veins were collected from 30 patients with definite sepsis diagnosed in intensive care unit (ICU) of Shanxi Bethune Hospital and 30 age-matched healthy subjects during the same period. Serum lipid metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and the quality control samples were analyzed by base peak spectroscopy (BPC) and verified experimental repetition. Student t-test and fold change (FC) were used for screening significant differences in lipid metabolites and determining their expression changes. Principal component analysis (PCA) and orthogonal projectionto latent structure discriminant analysis (OPLS-DA) were used to determine the entire allocation of experimental groups apiece, access the quality of being near to the true value of model, and screen the differential lipid metabolites with variable importance of projection (VIP). Finally, Metabo Analyst platform database was used to analyze lipid molecular metabolic pathways. Results:BPC results showed that the experimental repeatability was good and the experimental data was reliable. The main parameter model interpretation rate of PCA model R 2X = 0.511, indicating that the model was reliable. The main parameter model interpretation rate of OPLS-DA model R 2Y = 0.954, Q 2 = 0.913, indicating that the model was stable and reliable. With FC > 2.0 or FC < 0.5, P < 0.05, a total of 72 differential lipid metabolites were obtained based on VIP > 1. Based on Metabo Analyst 5.0, 24 distinguishable lipid metabolites were identified including 8 phosphatidylethanolamine (PE), 7 lysophosphatidylcholine (LPC), 6 phosphatidylcholine (PC), 2 lysophosphatidylethanolamine (LPE) and 1 phosphatidylserine (PS). Compared with healthy volunteers, the lipid molecules expression proved down-regulated in most sepsis patients, including PC, LPC, LPE, and some PE, while some PE and PS were up-regulated, which was mainly related to the PE (18∶0p/20∶4), PC (16∶0/16∶0) and LPC (18∶1) metabolic pathways in glycerophospholipids. Conclusions:There are significant differences in lipid metabolites between the sera of sepsis patients and healthy volunteers. PE (18∶0p/20∶4), PC (16∶0/16∶0) and LPC (18∶1) may be new targets for sepsis prediction and intervention.

Objective:To screen lipid biomarker in sepsis patients with different survival outcome based on ultra high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS) technique.Methods:From September 2019 to April 2020, 30 septic patients admitted in Department of Intensive Care Unit and 30 cases of physical examination at the same time in Shanxi Bethune Hospital were studied. Lipid metabolite in serum were detected by UHPLC-MS/MS technique. According to the 28 day survival outcome of sepsis patients, they were divided into survival group (21 cases) and death group (9 cases). The baseline data of case group and control group, survival group and death group were compared respectively. Independent sample t-test and orthogonal partial least squares discriminant analysis (OPLS-DA) were further performed to identify lipid biomarkers related to sepsis survival outcome. Receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of differential lipids on the survival outcome of biomarker sepsis patients. Results:There were 32 lipid subclasses and 1 437 differential lipid molecules in the sepsis group compared with the control group. 196 differential lipid molecules in the sepsis survival group and the death group were screened according to the OPLS-DA model (variable weight of projection (VIP)>1), which were glycerophosphingolipids (129), sphingolipids (52), glycerides (14), and sterols (1).All the original data were statistically analyzed by univariate independent sample t-test. There were statistically significant differences in 15 lipid molecules between the two groups. Combined with VIP > 1 and P < 0.01, three lipid molecules were finally screened, which were sphingomyelin (SM) lipid molecules, SM (d30∶1), SM (d32∶2), SM (d32∶1). ROC curve analysis showed that the areas under curves of the above three lipid molecular were 0.915, 0.892, 0.898, respectively. The sensitivity was 77.27%, 95.45%,72.73%. The specificity was 100.0%, 87.5%,100.0%. Further Z-test showed that there was no significant difference in the area under the ROC curve ( Z(SM (d30∶1) and SM (d32∶1)) =0.36, P=0.722; Z(SM (d30∶1) and SM (d32∶2))=0.34, P=0.732; Z(SM (d32∶1) and SM (d32∶1))=0.07, P=0.942). Conclusions:Sphingomyelin may be involved in the formation of different clinical outcomes of sepsis, and has a good predictive effect on the survival outcome of sepsis.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.

OBJECTIVE：To study the improvem ent effects of total flavonoids from Morus alba on glycolipid metabolism ， inflammation and oxidative stress in gestational diabetes mellitus （GDM）model rats ，and to investigate the potential mechanism. METHODS：After feeding high fat diet for 8 weeks，female SD rats with FBG ＜6.67 mmol/L were caged with male SD rats . Pregnant female rats were randomly divided into control group ，GDM group ，M. alba total flavonoids low-dose ，medium-dose and high-dose groups （50，100，200 mg/kg），with 10 rats in each group. Except for control group ，other groups were given intraperitoneal injection of streptozotocin 25 mg/kg once to induce GDM model. After injection ，rats in each administration group were given corresponding drugs intragastrically ，control group and GDM group were given normal saline 10 mL/kg intragastrically ， once a day ，for consecutive 18 days. The levels of FBG were determined on the 3rd，7th and 18th day of pregnancy （G3d，G7d and G18 d）；the levels of blood lipids （TG，TC，LDL-C，HDL-C）and inflammatory factors （TNF-α，IL -6，IL-8），oxidative stress indicators（MDA，SOD，GSH，CAT）in serum were determined on G 18d. The protein and mRNA expressions of PPARγ and NF-κB， the expression of AMPK mRNA and p-AMPK protein were measured by Real-time-PCR and Western blotting. RESULTS ： Compared with control group ，the levels of FBG （G3d，G7d，G18d），TG，TC，LDL-C，TNF-α，IL-6，IL-8 and MDA ，protein and mRNA expression of NF-κB in GDM group were significantly increased，while the levels of SOD ，GSH and CAT ，the expressions of PPARγ protein and mRNA，AMPK mRNA and p-AMPK fcksjf@126.com protein were significantly decreased （P＜0.01）. Compared with GDM group ，the levels of FBG （G3 d，G7 d，G18 d），TG， huawei99@163.com TC，LDL-C in M. alba total flavonoids medium-dose and high- dose groups and the levels of TNF-α，IL-6，IL-8 and MDA ，protein and mRNA expression of NF-κB in M. alba total flavonoids groups were significantly decreased ；the levels of SOD ，GSH and CAT ，the expressions of PPARγ protein and mRNA， AMPK mRNA and p-AMPK protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Total flavonoids from M. alba can improve the glycolipid metablism ，inflammation and oxidative stress in GDM model rats ，the mechanism of which may be related to the activation of PPARγ pathway.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg^-1·d^-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group. Conclusions Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.