Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To analyze the application effect of whole-course multi-disciplinary nutrition model in elderly patients undergoing hip surgery.Methods A total of 90 elderly patients undergoing hip surgery admitted to Wenzhou Central Hospital from October 2021 to December 2023 were selected and divided into control group and study group according to random number table method,with 45 cases in each group.The control group was treated with dietary management model,while the study group was treated with whole-course multi-disciplinary nutrition model.Recovery,nutritional status,quality of life,hip function and satisfaction were compared between two groups.Results The hospital stay and fracture healing time in study group were significantly shorter than those in control group(P<0.05).After intervention,prealbumin(PA),albumin(Alb),hemoglobin(Hb),dimensions scores of 36-item short form health survey(SF-36)and Harris hip scores of patients in two groups were significantly higher than before intervention(P<0.05).PA,Alb,Hb,dimensions scores of SF-36 and Harris hip scores in study group were significantly higher than those in control group(P<0.05).The satisfaction of patients in study group was significantly higher than that in control group(χ2=5.075,P=0.024).Conclusion The application of whole-course multi-disciplinary nutrition model in hip surgery in elderly patients can improve their nutritional status,improve their quality of life,enhance hip function,and facilitate postoperative recovery.

Objective:To investigate the application value of cystic plate approach (CPA) for extrahepatic right hepatic pedicle dissection in minimally invasive anatomical hepatectomy (MIALR).Methods:The retrospective cohort study was conducted. The clinicopathological data of 42 patients with primary liver cancer who underwent laparoscopic right hemi-hepatectomy in Nanfang Hospital of Southern Medical University from August 2020 to August 2022 were collected. There were 36 males and 6 females, aged (55±13)years. Of the 42 patients, 25 cases undergoing CPA for extrahepatic right hepatic pedicle dissection were divided into the CPA group, and 17 cases undergoing traditional approach for extrahepatic right hepatic pedicle dissection were divided into the traditional approach group. Observation indicators: (1) surgical situations; (2) postoperative situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( IQR), and comparison between groups was conducted using the Mann?Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi?square test or Fisher exact probability. Comparison of ordinal data was conducted using the non‐parameter rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent laparoscopic right hemi-hepatectomy successfully, with the surgical margin as negative. The operative time, volume of intraoperative blood loss, time of dissection of the targeted hepatic pedicle, cases undergoing dissection of the trunk of right anterior hepatic pedicle and its operation time, cases undergoing dissection of the trunk of right posterior hepatic pedicle and its operation time, cases with hepatic pedicle injury, cases with hepatic tissue injury, cases with dissection space as large and small were 150.00(130.00)minutes, 100.00(100.00)mL, 472.00(201.00)seconds, 10 and 366.00(94.75)seconds, 9 and 564.00(138.50)seconds, 2, 2, 25, 0 in patients of the CPA group, versus 140.00(113.00)minutes, 100.00(125.00)mL, 670.00(107.00)seconds, 8 and 663.00(136.00)seconds, 7 and 783.00(189.00)seconds, 8, 5, 2, 19 in patients of the traditional approach group. There were significant differences in the time of dissection of the targeted hepatic pedicle, time of dissection of the trunk of right anterior hepatic pedicle, time of dissection of the trunk of right posterior hepatic pedicle, hepatic tissue injury, dissection space between the two groups ( Z=-4.809, -3.254, -3.188, χ2=6.493, 34.314, P<0.05) and there was no significant difference in the operation time, volume of intraoperative blood loss, dissection of the trunk of right anterior hepatic pedicle, dissection of the trunk of right posterior hepatic pedicle, hepatic tissue injury between the two groups ( Z=-0.282, -0.412, χ2=0.095, 0.002, 1.976, P>0.05). (2) Postoperative situations. There was no patient undergoing postoperative hemorrhage in both of the two groups. The alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and prothrombin time (PT) at postoperative day 3, cases with postoperative biliary fistula, pathological type of tumor (hepatocellular carcinoma, intrahepatic cholangiocarcinoma) were 68.00(48.50)U/L, 52.00(35.50)U/L, 28.30(12.35)mmol/L, 12.40(2.40)seconds, 2, 21, 4 in patients of the CPA group. The above indicators were 58.00(25.00)U/L, 41.00(19.50)U/L, 26.80(14.25)mmol/L, 12.50(2.95)seconds, 5, 15, 2 in patients of the traditional approach group. There was no significant difference in the ALT, AST, TBil, PT at postoperative day 3, cases with postoperative biliary fistula between the two groups ( Z=-1.218, -1.488, -0.205, -0.320, χ2=1.976, P>0.05), and there was no significant difference in the pathological type of tumor between the two groups ( P>0.05). Conclusion:Application of CPA for extrahepatic right hepatic pedicle dissection in MIALR is safe and feasible.

Objective:To investigate the application value of cystic plate approach (CPA) for extrahepatic right hepatic pedicle dissection in minimally invasive anatomical hepatectomy (MIALR).Methods:The retrospective cohort study was conducted. The clinicopathological data of 42 patients with primary liver cancer who underwent laparoscopic right hemi-hepatectomy in Nanfang Hospital of Southern Medical University from August 2020 to August 2022 were collected. There were 36 males and 6 females, aged (55±13)years. Of the 42 patients, 25 cases undergoing CPA for extrahepatic right hepatic pedicle dissection were divided into the CPA group, and 17 cases undergoing traditional approach for extrahepatic right hepatic pedicle dissection were divided into the traditional approach group. Observation indicators: (1) surgical situations; (2) postoperative situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non‐parameter rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent laparos-copic right hemi-hepatectomy successfully, with the surgical margin as negative. The operation time, volume of intraoperative blood loss, time of dissection of the targeted hepatic pedicle, cases under-going dissection of the trunk of right anterior hepatic pedicle and its operation time, cases under-going dissection of the trunk of right posterior hepatic pedicle and its operation time, cases with hepatic pedicle injury, cases with hepatic tissue injury, cases with dissection space as large and small were 150.00(130.00)minutes, 100.00(100.00)mL, 472.00(201.00)seconds, 10 and 366.00(94.75)seconds, 9 and 564.00(138.50)seconds, 2, 2, 25, 0 in patients of the CPA group, versus 140.00(113.00)minutes, 100.00(125.00)mL, 670.00(107.00)seconds, 8 and 663.00(136.00)seconds, 7 and 783.00(189.00)seconds, 8, 5, 2, 19 in patients of the traditional approach group. There were significant differences in the time of dissection of the targeted hepatic pedicle, time of dissection of the trunk of right anterior hepatic pedicle, time of dissection of the trunk of right posterior hepatic pedicle, hepatic pedicle injury, dissection space between the two groups ( Z=-4.809, -3.254, -3.188, χ2=6.493, 34.314, P<0.05) and there was no significant difference in the operation time, volume of intraoperative blood loss, dissection of the trunk of right anterior hepatic pedicle, dissection of the trunk of right posterior hepatic pedicle, hepatic tissue injury between the two groups ( Z=-0.282, -0.412, χ2=0.095, 0.002, 1.976, P>0.05). (2) Postoperative situations. There was no patient under-going postoperative hemorrhage in both of the two groups. The alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and prothrombin time (PT) at postoperative day 3, cases with postoperative biliary fistula, pathological type of tumor (hepatocellular carcinoma, intrahepatic cholangiocarcinoma) were 68.00(48.50)U/L, 52.00(35.50)U/L, 28.30(12.35)mmol/L, 12.40(2.40)seconds, 2, 21, 4 in patients of the CPA group. The above indicators were 58.00(25.00)U/L, 41.00(19.50)U/L, 26.80(14.25)mmol/L, 12.50(2.95)seconds, 5, 15, 2 in patients of the traditional approach group. There was no significant difference in the ALT, AST, TBil, PT at postoperative day 3, postoperative biliary fistula between the two groups ( Z=-1.218, -1.488, -0.205, -0.320, χ2=1.976, P>0.05), and there was no significant difference in the pathological type of tumor between the two groups ( P>0.05). Conclusion:Application of CPA for extrahepatic right hepatic pedicle dissection in MIALR is safe and feasible.

Objective To characterize the distribution and assess the exposure to phthalic acid esters （PAEs） in the indoor dust of Shanghai City. Methods Samples were collected from 33 sampling sites， including homes， hotels， offices and public places， in Shanghai in 2018， 2019， and 2020. The samples were pretreated by 100 sieves， extracted and concentrated， and then analyzed by gas chromatography-mass spectrometry in selected ion mode （SIM）. Results Results on the characteristics of PAEs in indoor dust in different places showed that concentrations of PAEs were in a range of <0.01-2 464 mg·kg^-1.The average concentration of 16 PAEs was 613 mg·kg^-1. Bis（2-ethylhexyl） phthalate （DEHP）， di-iso-butyl phthalate （DiBP）， di-n-butyl phthalate （DBP） and di-n-octyl phthalate （DnOP） were the main components of PAEs in indoor dust， accounting for approximately 99.5% of 16 PAEs. The intake of DEHP， DBP， DEP and BBP was lower than the tolerable daily intake （TDI） and reference doses （RfD） set by EU CSTEE and U.S. EPA. Conclusion Average daily dose （ADD） via indoor dust is estimated， and the order of intake through different pathways is hand-oral intake>skin contact>respiratory inhalation. Exposure risk of PAEs in children is greater than that in adults.

Objective To investigate the expression of melanoma antigen- encoding gene (MAGE) A1 protein in esophageal squamous cell carcinoma, and explore its correlation with the clinicopathological factors and prognosis. Methods A retrospective analysis was performed on 197 patients with esophageal squamous cell carcinoma who accepted radical surgical treatment from January 2006 to December 2012. The expressions of MAGEA1 protein in these specimens of cancer tissue and cancer adjacent tissue were detected by immunohistochemistry with tissue microarray technology. Results MAGEA1 protein was expressed in cytoplasm and nucleus of tumor cells. The positive expression rate of MAGEA1 protein in cancer tissue was significantly higher than that in cancer adjacent tissue: 73.6％ (145/197) vs. 5.6％ (11/197), and there was statistical difference (P<0.01). The positive expression of MAGEA1 protein had no correlations with sex, age, history of smoking/drinking, family history of upper gastrointestinal cancer, depth of tumor invasion, lymph node metastasis, tumor differentiation, location and TNM stage (P>0.05). Kaplan-Meier survival analysis result showed that the 5-year survival rate in patients with MAGEA1 protein positive expression was significantly lower than that in patients with MAGEA1 protein negative expression (37.2％ vs. 53.8％), and there was statistical difference (P=0.018). Multivariate analysis result showed that MAGEA1 protein positive expression was an independent predictor of prognosis in esophageal squamous cell carcinoma patients (HR=1.91, 95％CI 1.22 to 2.98, P = 0.004). Conclusions The expression of MAGEA1 protein is abundant in esophageal squamous cell carcinoma, and is related to worse clinical outcome. MAGEA1 protein could be a candidate target for tumor immunotherapy.

Objective To compare the safety and short-term efficacy of laparoscopic repeat hepatectomy (LRH) with open repeat hepatectomy (ORH) for recurrent hepatocellular carcinoma (rHCC).Methods The clinical data of 33 patients with rHCC who underwent hepatectomy at Nanfang Hospital,Southern Medical University from August 2015 to November 2017 were retrospectively analyzed.There were 24 males and 9 females.The patients were divided into LRH group (n=15) and ORH group (n=18).The preoperative clinical data,operative and postoperative data of the two groups were compared.Results No significant differences were observed in the preoperative clinical data of the two groups,including the extent of the previous hepatectomy,the interval between the two surgeries,the number of tumors,and the maximum diameter of tumors.No significant differences were observed in the liver resection method,portal occlusion time and operation duration between the two groups.Blood loss was significantly lower in the LRH group [(66.7±86.1) ml vs.(251.1±75.6) ml,P＜0.05].The total hospitalization expenses,first postoperative white blood cell count,and hepatic insufficiency in the two groups were not significantly different (P＞0.05).The postoperative diet recovery was significantly shorter (1.2±0.4) days vs.(2.9± 1.4) days,the inflammation indicator NEU％ was significantly decreased (83.6±4.8)％ vs.(88.2±3.7)％,and the length of postoperative hospital stay (6.3±2.9) days vs.(9.8± 3.7)days was significantly shorter in the LRH group (P＜0.05).Conclusions LRH was safe and effective in the treatment of rHCC,LRH was superior in reducing intraoperative blood loss,promoting postoperative recovery and shortening hospital stay when compared to ORH.

Objective To evaluate the value of precise hepatectomy in treatment of early-stage primary liver cancer after radical resection. Methods Between June 2012 and July 2014,174 patients undergoing radical resection of hepatocellular carcinoma were enrolled in this comparative study at Nan fang Hospital. 118 patients with liver resection under precise hepatectomy were assigned to precise resection group and 56 patients with liver resection under Pringle maneuver were assigned to occlusion group. The two groups were compared in terms of preoprational clinical pathological and laboratory data ,volume of intraoperative bleeding and blood transfusion , postoperative hepatic function recovery,hospitalization days,and postoperative tumor-free survival rate of 1,2 years. Results There was no significant difference between the two groups in the sex,age,liver disease,preo-pration albumin,ALT,AST,alcohol intake and liver cirrhosis(P>0.05). No differences between the two groups were found about the volume of intraoperative bleeding and blood transfusion as well as surgery cost (P > 0.05). The recovery of hepatic function was accelerated and the incidence of complications ,hospitalization days and peri-od of drainage were significantly reduced in the precise resection group compared with the occlusion group (P <0.05). The 1,2-years postoperative tumor-free survival rate was 79.7%(94/118),60.9%(46/118)in the precise group and 50.0%(28/56),46.4%(26/56) in the occlusion group ,with significant difference between them (χ2=4.741,8.722,P<0.05). Conclusions For early-stage liver cancer patients,the precise hepatectomy during radical resection results in quick recovery and fewer complications ,thus it should be the first choice of clinical operation.

Objective To explore the risk factors and prognosis of the microvascular invasion of hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 220 patients with HCC who were admitted to the Nanfang Hospital of Southern Medical University from July 2012 to July 2015 were collected.Among 220 patients,63 were confirmed with microvascular invasion of HCC by postoperative pathological examination after radical resection of HCC and 157 were not confirmed with microvascular invasion of HCC.Observation indicators:(1) univariate and multivariate analyses affecting microvascular invasion of HCC;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival and tumor recurrence up to July 2016.The univariate and multivariate analyses were done using the Logistic regression model.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Univariate and multivariate analyses affecting microvascular invasion of HCC:the results of univariate analysis showed that maximum diameter of tumor,preoperative alpha-fetoprotein (AFP) and preoperative platelet (PLT) were related factors affecting microvascular invasion of HCC [OR =4.542,1.576,3.655,95％ confidence interval (CI):2.433-8.470,1.084-2.292,1.985-6.831,P＜0.05].The results of multivariate analysis showed that maximum diameter of tumor,preoperative AFP and preoperative PLT were independent factors affecting microvascular invasion of HCC (RR=3.386,1.563,2.247,95％CI:1.703-6.729,1.054-2.318,1.135-4.451,P＜0.05).(2) Follow-up and survival situations:220 patients were followed up for 12-48 months,with a median time of 26 months.The postoperative overall 1-and 2-year survival rates,postoperative 1-and 2-year tumor-free survival rates were 77.3％,50.0％,47.3％,38.0％ in 63 patients with microvascular invasion of HCC and 92.4％,77.2％,74.5％,69.4％ in 157 patients without microvascular invasion of HCC,with statistically significant differences (x2 =10.480,19.605,14.677,18.461,P＜ 0.05).Conclusion The maximum diameter of tumor,preoperative AFP and preoperative PLT are independent factors affecting microvascular invasion of HCC,and patients with microvascular invasion of HCC have poor clinical prognosis.

Objective To investigate the related factors of early liver cancer recurrence associated with elevated fasting glucose levels after radical resection of liver cancer.Methods The retrospective cohort study was adopted.The clinical data of 145 patients with liver cancer who were admitted to the Nanfang Hospital of Southern Medical University from October 2009 to June 2013 werc collected.After radical resection of liver cancer, 111 patients with average level of fasting blood glucose (FBG) ＜ 6.1 mmol/L and 34 patients with level of FBG ≥ 6.1 mmol/L were divided into the normal group and the hyperglycemic group, respectively.The blood glucose levels of patients during the period of hospital stay and follow-up were observed.The status of early recurrence and risk factors affecting recurrence in the 2 groups were analyzed.Follow-up of outpatient examination was applied to patients up to July 1, 2015 with the first recurrence as the end point.Patients had reexaminations once every month within postoperative month 6 and once every 3 months after 6 months.The general information [gender, age, FBG, underlying hepatopathy, preoperative AFP, alanine transaminase (ALT), aspartate aminotransferase (AST), Child-Pugh stage, Barcelona Clinic Liver Cancer (BCLC) stage, history of alcohol drinking], surgical data (surgical method, operation time, number of blood transfusion, volume of intraoperative blood loss), pathological data (histopathological differentiation, number of tumor nodules, diameter of maximal tumor, liver cirrhosis) and follow-up data (postoperative AFP, imaging findings, recurrence time, preventive chemotherapy) were collected.Measurement data with normal distribution were presented as-x ± s and analyzed by the t test.Measurement data with skewed distribution were presented as M (range) and analyzed by the non-parametric test.Count data were analyzed using the chi-square test.With the first recurrence as the end point, the tumor-free survival rate was drawn using the Kaplan-Meier method, and the comparison was analyzed by the logrank test.The risk factors affecting recurrence were analyzed using the Kaplan-Meier method for proportional hazards assumption test firstly, and then eligible factors were done using Log-rank test in the univariate analysis.The multivariate analysis was done using the COX model.Results The postoperative 1-, 2-year overall recurrence rates of liver cancer were 28.3％ (41/145) and 45.5％ (66/145).And 1-, 2-year recurrence rates of liver cancer were 21.6％ (24/111) and 36.9％ (41/111) in the normal group and 50.0％ (17/34) and 73.5％ (25/34) in the hyperglycemic group, respectively, showing significant differences between the 2 groups (x2=10.335, 14.053, P ＜ 0.05).The univariate analysis showed that FBG, Child-Pugh stage, volume of intraoperative blood transfusion and postoperative AFP were risk factors affecting tumor-free survival rate after radical resection of liver cancer (x2 =17.591,6.492, 10.690,12.820, P ＜ 0.05).The tumor-free survival rates at postoperative month 24 in the normal group and hyperglycemic group were 63.1％ and 26.5％ respectively, showing significant difference between the 2 groups (x2=17.591, P ＜ 0.05).The results of multivariate analysis showed that level of FBG ≥6.1 mmol/L, volume of intraoperative blood transfusion ＞ 200 mL and postoperative level of AFP ＞ 8.1 pg/L were independent risk factors affecting tumor-free survival rate after radical resection of liver cancer (RR =2.542, 2.028, 2.724, 95 ％ condifence interval : 1.529-4.225,1.183-3.479,1.635-4.538, P ＜ 0.05).Conclusions Elevated FBG level has a stimulative effect on early recurrence of tumor after radical resection of liver cancer.As a result, monitoring and controlling of blood glucose after operation is helpful in decreasing the early recurrence rate of patients with liver cancer.