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.

ObjectiveTo analyze the results of fit testing and its influencing factors on half-mask respirator among workers exposed to organic solvents. Methods A total of 84 workers exposed to organic solvents were selected as the research subjects using a convenience sampling method. The qualitative fit test apparatus of respiratory protection was tested after the workers had put on the half-mask respirats, and 11 facial indicators of the subjects were measured. Results The overall pass rate of the respirator fit testing was 71.4% (60/84). The lowest pass rate was 63.1% (53/84), which occurred during bending movements of workers. The head width, minimum forehead width, face length, nose length, nose depth, head circumference and head length were higher in workers who passed respirator fit testing, compared with those in the failing group (all P<0.05). The result of binary logistic regression analysis showed that gender and face width were influencing factors of the respirator fit testing (both P<0.05). Female workers had a lower pass rate of the fit testing than male workers, and workers with larger face width had a lower pass rate in the fit testing. Conclusion Drastic movement may lead to a decrease in the seal of half-mask respirator of workers exposed to organic solvents. When providing half-mask respirator to workers exposed to organic solvents, employers need to pay attention to the fit of respirators of female works and those with larger face width to ensure the effectiveness of respiratory protection for workers.

ObjectiveTo explore the protective effect of hearing protectors worn by noise-exposed workers and its influencing factors. Methods A total of 329 occupational noise-exposed workers were selected as the research subjects by judgment sampling method. A questionnaire survey on the use of ear protectors and individual suitability tests was conducted. Intervention was carried out for those whose personal attenuation rating (PAR) did not pass the baseline standard. Results The median (M) and the 25th and 75th percentiles of baseline PAR were 17.0 (5.0, 22.5) dB. The baseline PAR of the workers who were male, aged 25-<35 years, with a working experience of 5-<15 years, with a college degree or above, wearing ear protectors for 5-<15 years, knowing the right way to wear ear protectors, and workers who wore ear protectors correctly during work was relatively high (all P<0.01). The unqualified rate of baseline PAR of the study subjects was 32.8%. The unqualified rate of baseline PAR of workers in automobile manufacturing enterprises was lower than that of workers in plastic enterprises and textile enterprises (9.2% vs 43.6%, and 9.2% vs 50.0%, both P<0.01). The M of the 108 unqualified worker on baseline PAR was improved after intervention (22.0 vs 1.0 dB, P<0.01). The rates of knowing the right way to wear ear protectors, wearing ear protectors correctly during work, and receiving training on wearing ear protectors correctly for the research subjects were 88.1%, 84.8%, and 86.6%, respectively. Workers in automobile manufacturing enterprises and plastic enterprises had higher rates of knowing the right way to wear ear protectors, wearing ear protectors correctly during work, and receiving training on wearing ear protectors correctly than those in textile enterprises (all P<0.01). Conclusion Gender, age, working experience, education level, duration of wearing ear protectors, knowledge and use of ear protectors correctly are influencing factors of the protective effect of ear protectors for noise-exposed workers.

Respiratory protective equipment (RPE) is an effective measure to protect the health of workers. The domestic and foreign facial classfication of fit testing of RPE is mainly categorized into Los Alamos National Laboratory (LANL) classification, National Institute for Occupational Safety and Health (NIOSH) classification, principal component analysis (PCA) classification, Chinese Han adult facial classification, and Chinese young male facial classification. The LANL classification has low applicability. The NIOSH classification included different ethnicity and region of the study subjects, which is more representative for the American population. The PCA facial classification is complex to use and has low matching with RPE sizes. The Chinese Han adult facial classification and Chinese young male facial classification included more facial data of Chinese Han population and young population. There are qualitative and quantitative fit testing. Qualitative methods include the isoamyl acetate method, saccharin solution aerosol method, aerosol bitter testing solution method, and irritant smoke method which are cost-effective and easy to use, but are highly subjective to the study subjects. Quantitative methods include the aerosol generated method, environmental aerosol condensation nucleus counting method, and the controlled negative pressure method, which accurately quantify the facial fit of RPE but require specific testing equipment and high costs. It is necessary to include occupational populations from multiple industries, combine facial fit testing and fit testing methods of RPE, and establish a follow-up database based on digital information platforms, to achieve dynamic monitoring of respiratory protection levels among different occupational populations in the future.

Objective:To evaluate the accuracy of continuous photoplethysmography algorithms for atrial fibrillation diagnosis and atrial fibrillation burden evaluation via wearable devices.Methods:This study was a self-controlled prospective cohort study. A total of 254 consecutive inpatients were recruited from the Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University from September 2022 to November 2022. All participants were required to wear two devices at the same time: (1) an electrocardiogram (ECG) watch for acquisition of photoplethysmography (watch-recorded-photoplethysmography, W-PPG) and electrocardiogram (watch-recorded-electrocardiogram, W-ECG); (2) an ECG patch for acquisition of electrocardiogram (patch-recorded-electrocardiogram, P-ECG). The results were measured in 30 s data segments and individual participants, separately, which were calculated for sensitivity and specificity by comparing them with the results of expert-read ECG according to the receiver operating characteristic curve. Four groups were separated according to the proportion of the atrial fibrillation burden, and the difference of atrial fibrillation burden from algorithm and expert-read ECG was calculated.Results:All 254 subjects completed the study. The mean age of participants was (63.04±11.04) years old, 99 (38.98%) of them were female, and 97 (38.19%) patients had persistent atrial fibrillation. Expert-read ECG results were taken as standard criteria in all calculations. The P-ECG algorithm had a sensitivity of 94.86% (95% CI: 94.81%-94.91%) and a specificity of 99.30% (95% CI: 99.28%-99.31%) when measured in data segments. The W-PPG algorithm had a sensitivity of 96.07% (95% CI: 95.97%-96.18%) and a specificity of 98.62% (95% CI: 98.59%-98.65%). When measured in terms of individual participants, the P-ECG algorithm had a sensitivity of 92.55% (95% CI: 87.57%-95.71%) and a specificity of 96.39% (95% CI: 93.45%-98.09%), while the W-PPG algorithm had a sensitivity of 93.71% (95% CI: 88.75%-96.67%) and a specificity of 89.62% (95% CI: 85.61%-92.65%). When measured in terms of a single acquisition of W-ECG records, the W-ECG algorithm had a sensitivity of 92.04% (95% CI: 88.14%-94.78%) and a specificity of 96.19% (95% CI: 94.35%-97.47%). For atrial fibrillation burden assessment, the difference between the W-PPG analysis results and the expert-read ECG results was less than 2% in all burden distribution intervals. Conclusions:Continuous photoplethysmography algorithm applied to wearable devices to detect atrial fibrillation is a feasible strategy. Taking expert-read ECG results as standard, continuous monitoring of PPG by a smartwatch is highly accurate for atrial fibrillation diagnosis and can also be used to effectively complete atrial fibrillation burden assessment.

Objective:To explore the causal relationship between gut microbiota and lung function (FEV1/FVC) using two-sample Mendelian randomization method; To explore its application in the TCM field.Methods:This was a Mendelian randomization study. The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function (FEV1/FVC) published by IEU OpenGWAS in the public database were used, and instrumental variables were extracted according to prespecified thresholds. The inverse variance weighted method (IVW) was mainly used for analysis. The results were evaluated according to the effect indicator β value and 95% CI. When the IVW method was statistically significant, further sensitivity analysis was performed. Leave-one-out test, heterogeneity test, horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results. Results:A total of 10 causal relationships between gut microbiota and lung function (FEV1/FVC) were determined using the IVW method: family. BacteroidalesS24.7group ( β=-0.029, P=0.015), family. ClostridialesvadinBB60group ( β=-0.028, P=0.040), family. Streptococcaceae ( β=-0.056, P=0.042), genus. LachnospiraceaeFCS020group ( β=0.025, P=0.029), genus. Lactococcus ( β=-0.024, P=0.038), genus. Peptococcus ( β=0.025, P=0.049), genus. RuminococcaceaeUCG011 ( β=-0.030, P=0.038), genus. Ruminococcus2 ( β=0.028, P=0.033), genus. Terrisporobacter ( β=-0.030, P=0.018), phylum. Cyanobacteria ( β=0.027, P=0.039). Leave-one-out analysis showed that the results were stable, and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed. Conclusion:The gut microbiota may play a role in the changes of lung function, which to a certain extent confirms the TCM theory of "exterior-interior relationship between the lung and large intestine", and can provide certain reference for the research direction of TCM.

Objective:To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) .Methods:Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model.Results:Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy ( P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months ( P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL ( HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions:In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

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 safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum 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 constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

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.