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 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.

Background Most of the studies on grading and classification of occupational health compre-hensive risks for specific employers still remain in the establishment and description of methodology, and practical application studies are rarely reported. Objective To explore the application of an occupational disease hazards comprehensive risk assessment method issued by the National Disease Control and Prevention Bureau in conjunction with the National Health Commission and a self-developed occupational health grading and classification method in petroleum refining enterprises, and to provide practical experience for the implementation of differentiated law enforcement by relevant regulatory authorities. Methods Two occupational health grading and classification methods were practiced in three petroleum refining enterprises in Guangdong Province. The occupational hazards comprehensive risk assessment method was provided by the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement of the National Disease Control and Prevention Bureau and the National Health Commission. The principle was to derive the occupational health risk level according to nature of occupational hazards, exposure level, and number of workers exposed to them in an employer, and then to classify them into Class A, Class B, and Class C by combining with local occupational health management status level. The occupational health grading and classification method was self-developed according to available domestic and foreign occupational health risk assessment methods. Its principle was to calculate the risk level of each workstation in an employer based on published carcinogenicity classification or LD₅₀/LC₅₀ of chemical toxicants, level of noise, exposure parameters such as exposure level and exposure frequency, estimate the comprehensive risk R_o of the target employer by the Romanian comprehensive risk calculation method, and then calculate a comprehensive risk R_o' weighted by the occupational health management index of the target employer and classify it into class A, class B, and class C. Finally, assessment results, scope of application, inquired indicators, advantages,disadvantages and professional competence requirements of the two grading and classification methods were compared. Results The occupational hazards that were evaluated in three enterprises in this study were benzene, toluene, xylene, gasoline, hydrogen sulfide, and noise. The exposure levels of benzene, toluene, xylene, and gasoline were all below 10% OEL (occupational exposure limit), and hydrogen sulfide and noise were disqualified. Occupational hazards such as benzene and hydrogen sulfide were serious occupational hazards in the three enterprises, and the number of workers exposed was 461, 912, and 224, respectively; the HRs (hazard ratings) of benzene, toluene, xylene, gasoline, hydrogen sulfide, and noise were level 5, 3, 2, 3, 5, and 3 respectively. The occupational health management status of the three enterprises was graded as B, A, and B, respectively by the occupational disease hazards comprehensive risk assessment method. The occupational health management index of the three enterprises was graded as B, A, and A, respectively by the occupational health grading and classification method. The comprehensive risk assessment results showed that two enterprises classified into as the highest class C and one into class B by the occupational disease hazards comprehensive risk assessment method, while all three enterprises were classified into class B by the occupational health grading and classification method. Conclusion The two grading and classification methods are not consistent in the evaluation results of petroleum refining enterprises, and there are differences in the evaluation scope, indicators to be collected, and professionalism. It is recommended that occupational health regulators should fully consider the advantages and disadvantages of the two methods and choose the appropriate assessment method according to the actual regulatory purpose.

Magnetic ferrite nanoparticles (MFNPs) have great application potential in biomedical fields such as magnetic resonance imaging, targeted drugs, magnetothermal therapy and gene delivery. MFNPs can migrate under the action of a magnetic field and target specific cells or tissues. However, to apply MFNPs to organisms, further modifications on the surface of MFNPs are required. In this paper, the common modification methods of MFNPs are reviewed, their applications in medical fields such as bioimaging, medical detection, and biotherapy are summarized, and the future application directions of MFNPs are further prospected.
Ferric Compounds ; Magnetic Resonance Imaging/methods* ; Magnetics ; Magnetite Nanoparticles/therapeutic use* ; Nanoparticles

Objective To establish a SYBR Green real-time PCR detection method with tissue-specific miRNAs and explore a novel approach for forensic body fluid identification. Methods The frequently reported 6 standard miRNAs were synthesized to establish a SYBR Green method, and verify with body fluid. The relative expression data for the 6 miRNAs were obtained using SYBR Green real-time PCR method in peripheral blood, menstrual blood, saliva and semen. Results The assays showed that miRNA205 permitted the unequivocal identification among different fluids. miRNA451 and miRNA144 could be used to distinguish blood from non-blood. Menstrual blood or peripheral blood could be identified through miRNA214. miRNA888 and miRNA891 was highly expressed in semen. Conclusion The results of this study indicate that miRNA SYBR Green profiling may provide a feasible and effective approach to body fluid identification for forensic casework.

Objective To genotype mixed samples with next generation sequencing and evaluate its prospects in forensic DNA application. Methods Three mixed biological samples from rapes cases and their reference samples were collected. DNA was extracted using the MagAttract M48 DNA Manual Kit(200). The ForenSeqTMDNA Signature Prep Kit was used for library preparation, and next generation sequencing was performed on the MiSeq FGx system. The ForenSeqTMUniversal Analysis v1.2.1 software was used for data analysis. NGS-based STR results were compared with CE-based genotypes. Results A single length polymorphic STR allele in the mixed profile could be recognized as two sequence polymorphic STR alleles from different donors, which would assist mixed profile analysis. Such phenomenon was observed in D3S1358, D9S1122 and D13S317 in this work. Conclusion Our results suggested that precision STR genotyping of mixed samples based on NGS can provide more information and hints for mixed STR profile separation.

Objective To validate the efficiency of 27-plex single nucleotide polymorphism (SNP) multiplex system for ancestry inference. Methods The 27-plex SNP system was validated for its sensitivity and species specificity. A total of 533 samples were collected from African, Southern Chinese Han, China's ethic minorities (Yi, Hui, Miao, Tibet, and Uygur), European, Central Asian, Western Asian, Southern Asian, Southeast Asian and South American populations for clustering analysis of the genotypes by citing 3 representative continental ancestral groups [East Asia (CHB), Europe (CEU), and Africa (YRI)] from HapMap database. Results The system sensitivity is 0.125 ng. Twenty and six genotypes were detected in chimpanzee and monkeys, respectively. Except in rs10496971, no more products were found in other animals. The system was capable of differentiating intercontinental populations but not of distinguishing between East Asian and Southeast Asian population or between Southern Chinese Han population and Chinese Ethnic populations (Hui, Miao, Yi and Tibet). This system achieved a 100%accuracy for intercontinental population source inference for 46 blind test samples. Conclusion 27-plex SNPs multiplex system has a high sensitivity and species specificity and can correctly differentiate the ancestry origins of individuals from African, European and East Asian for criminal case investigation. But this system is not capable of distinguishing subpopulation groups and more specific ancestry-informative markers are needed to improve its recognition of Southeast Asian and Chinese ethnic populations.

Objective To validate the efficiency of 27-plex single nucleotide polymorphism (SNP) multiplex system for ancestry inference. Methods The 27-plex SNP system was validated for its sensitivity and species specificity. A total of 533 samples were collected from African, Southern Chinese Han, China's ethic minorities (Yi, Hui, Miao, Tibet, and Uygur), European, Central Asian, Western Asian, Southern Asian, Southeast Asian and South American populations for clustering analysis of the genotypes by citing 3 representative continental ancestral groups [East Asia (CHB), Europe (CEU), and Africa (YRI)] from HapMap database. Results The system sensitivity is 0.125 ng. Twenty and six genotypes were detected in chimpanzee and monkeys, respectively. Except in rs10496971, no more products were found in other animals. The system was capable of differentiating intercontinental populations but not of distinguishing between East Asian and Southeast Asian population or between Southern Chinese Han population and Chinese Ethnic populations (Hui, Miao, Yi and Tibet). This system achieved a 100%accuracy for intercontinental population source inference for 46 blind test samples. Conclusion 27-plex SNPs multiplex system has a high sensitivity and species specificity and can correctly differentiate the ancestry origins of individuals from African, European and East Asian for criminal case investigation. But this system is not capable of distinguishing subpopulation groups and more specific ancestry-informative markers are needed to improve its recognition of Southeast Asian and Chinese ethnic populations.

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.