1.Anti-SARS-CoV-2 prodrug ATV006 has broad-spectrum antiviral activity against human and animal coronaviruses.
Tiefeng XU ; Kun LI ; Siyao HUANG ; Konstantin I IVANOV ; Sidi YANG ; Yanxi JI ; Hanwei ZHANG ; Wenbin WU ; Ye HE ; Qiang ZENG ; Feng CONG ; Qifan ZHOU ; Yingjun LI ; Jian PAN ; Jincun ZHAO ; Chunmei LI ; Xumu ZHANG ; Liu CAO ; Deyin GUO
Acta Pharmaceutica Sinica B 2025;15(5):2498-2510
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.
2.A study of the intervention effect of nose pads and elastic adjustment clasps on the fit of KN95 masks
Yingyin ZHANG ; Qifan HUANG ; Xiaotang SU ; Xi ZHONG ; Zepeng LI ; Xi LUO ; Shibiao SU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(3):164-169
Objective:To investigate the fit of dust-exposed workers wearing KN95 masks in a city of Guangdong Province, and to discuss the intervention effect of nose pads and elastic adjustment clasps on the fit of KN95 masks.Methods:In January 2024, 145 dust-exposed workers from a stone processing enterprise in a city of Guangdong Province were selected as study subjects by convenience sampling, and 4 types of KN95 masks commonly used by dust-exposed workers were selected as test masks. The head and face dimensions of the study subjects were measured using a right-angle gauge and a curved-angle gauge, and the fit factor (FF) of the KN95 masks was tested using the quantitative fit test for respiratory protective equipment, and the intervention of adding nose pads or elastic adjustment clasps was given to those who failed the first fit test. The paired t-test was used to compare the changes of workers' FF before and after the intervention. Results:The coverage rate of the study population in the facial subsection of the Chinese Han population was 71.0% (103/145). Before intervention, the overall passing rate of the fit test of 4 types of KN95 masks was 16.6% (24/145), and the passing rate of 4 types of masks had statistical significance ( χ2=19.73, P<0.001). After intervention, the overall passing rate of the fit test of masks was 33.9% (41/121), and the geometric mean of the total FF after intervention increased from 15.9 to 62.7 ( t=-13.53, P<0.001), among which 88.4% (107/121) workers' FF improved after intervention, and 11.6% (14/121) of workers had reduced FF. Conclusion:Dust-exposed workers in a city of Guangdong Province have a low coverage rate of facial subsection among Chinese Han population, and the passing rate of KN95 mask fit test is low. Interventions using additional nose pads or elastic adjustment clasps can partially improve the fit of the mask, and it is still necessary to continue to explore interventions to improve the fit of mask wearers.
3.Analysis of the actual protective effect and its influencing factors of respiratory protective equipment for trichloroethylene-exposed workers
Qifan HUANG ; Yingyin ZHANG ; Zhuandi ZHAO ; Weitao LIN ; Jiaheng HE ; Zepeng LI ; Xi ZHONG ; Xi LUO ; Shibiao SU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(3):170-174
Objective:To understand the current status of the actual protective effect of respiratory protective equipment (RPE) for workers exposed to trichloroethylene (TCE), and to explore the factors affecting the actual protective effect.Methods:From July to December 2023, a total of 75 workers occupationally exposed to TCE from 21 hardware and electronics manufacturing facilities in a province were selected as research objects by convenient sampling method. Workplace protection factor (WPF) was used as an index to evaluate the actual protective effect of workers' RPE. The concentration of TCE inside and outside the RPE was detected to calculate WPE, and the temperature, humidity and wind speed near the working place were measured, as well as the forced vital capacity, respiratory rate, heart rate and other indicators of the worker were measured. The log-transformed WPF value (lgWPF) followed a normal distribution. One-sample t-test was used to compare the difference between the mean lgWPF and the log value of the assigned protection factor (APF) of the half mask (lgAPF=1). Multiple linear regression model was used to investigate the influencing factors of lgWPF. Results:The lgWPF of 75 TCE-exposed workers ranged from 0.40 to 1.32 (0.84±0.22). The mean of lgWPF was lower than that of lgAPF, and the difference was statistically significant ( t=-6.37, P<0.001). After adjusting for confounding factors, the results of multiple linear regression showed that humidity, forced vital capacity and respiratory rate were negatively correlated with lgWPF ( β=-0.008, -0.079, -0.021, P<0.05) . Conclusion:The actual protective efficacy of RPE among workers exposed to TCE is suboptimal. High humidity, elevated forced vital capacity, and increased respiratory rate may be contributing factors to the diminished protective performance of RPE.
4.Research on the protective effects and influencing factors of hearing protection device in different industries
Shibiao SU ; Xi ZHONG ; Qifan HUANG ; Qinyu OU ; Yingyin ZHANG ; Zepeng LI ; Xi LUO ; Simin CHEN ; Zhaoying HUANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(7):508-512
Objective:To evaluate the current situation of the protective effect of hearing protection device (HPD) worn by manufacturing workers and discuss their possible influencing factors.Methods:A total of 3634 noisy workers were surveyed and tested. The study conducted surveys of workers on the use of HPD. The 3M TM E-A-R Fit TM binaural verification system was used to measure the personal attenuation device (PAR) of workers wearing HPD. Results:The M ( Q1, Q3) of baseline PAR obtained by 3634 workers was 12 (2, 19) dB. There was a statistically significant difference in baseline PAR among the three types of HPDs ( H=336.39, P<0.01) . After pairwise comparison, it was found that the baseline PAR of workers wearing foam earplugs and earmuffs was higher than that of pre-molded earplugs ( P<0.01) . There were differences in baseline PAR among workers in different industries ( Z=359.73, P<0.01) . Education level, age of using HPD, types of HPDs, noise exposure intensity, with or without knowledge of correct methods, and comfort evaluation were the main factors affecting baseline PAR ( P<0.05) . There were 1536 workers (43.4%) failed the baseline PAR test. After the intervention, the median PAR increased significantly from 1 (0, 6) dB (baseline) to 18 (14, 22) dB (after the intervention) ( P<0.01) . The follow-up test found that the follow-up PAR of 328 workers was higher than the baseline PAR of the initial test, and the follow-up PAR was higher than the post-intervention PAR of the initial test ( P<0.01) . Conclusion:Under the conditions of this study, the protective effect of HPD was affected by factors such as incorrect understanding of wearing methods, exposure to high-intensity noise, low education level, a short period of time of HPD use and low comfort of hearing protectors. The protective effect could be improved through training, optimizing the wearing of hearing protector models, and follow-up interventions. Enterprises should use suitability verification to ensure the correct selection and wearing of noisy workers.
5.Role of Toll-like receptor 4 in regulation of homocysteine-induced ferroptosis in macrophages
Jun-jie ZHAI ; Shaoying WEN ; Xinru LI ; Rui SUN ; Ning QI ; Qifan ZHANG ; Li YANG ; Hui HUANG ; Lingju MA ; Yinju HAO ; Yideng JIANG ; Guizhong LI ; Shengchao MA
The Journal of Practical Medicine 2025;41(3):313-321
Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.
6.Risk score model based on clinical and multimodal ultrasound features for differentiating benign and malignant BI-RADS 4A breast lesions
Qifan LIU ; Shuai CUI ; Wenjing GUO ; Wei LI ; Hailong WANG ; Husha LI ; Jundong YAO ; Zhoulong ZHANG
Chinese Journal of Interventional Imaging and Therapy 2025;22(1):22-26
Objective To evaluate the value of risk score model based on clinical and multimodal ultrasound features for differentiating benign and malignant breast imaging reporting and data system(BI-RADS)4A lesions in breast.Methods Totally 177 patients with BI-RADS 4A lesions detected by multimodal breast ultrasound were prospectively enrolled,and the patients were divided into training set(n=123)and test set(n=54)at the ratio of 7∶3.Univariate and multivariate logistic regression analyses were used to analyze patients'clinical,gray-scale ultrasound,CDFI and elastography ultrasound parameters of lesions,and the independent risk factors for differentiating benign and malignant BI-RADS 4A lesions in breast were screened,so as a risk score model was constructed.Based on the results of sungical pathology or follow-up,the cut-off value of the model for differentiating benign and malignant BI-RADS 4A lesions in breast was obtained by receiver operating characteristic(ROC)curve,and the patients were divided into high-risk and low-risk subgroups according to the cut-off value,and the efficacy of the model was evaluated.Results Among 177 cases,39 were with benign lesions and 138 were with malignant lesions.Patients'age>58 years,diameter of lesion>15.1 mm,lesions with irregular shape,lesions with grade 1 or 2 of blood flow and standard deviation of sound touch elastography of a 2 mm circular area around the lesion(shell)(shell-STESD)>16.33 kPa were all independent risk factors of malignant BI-RADS 4A lesions in breast.The cut-off value of risk score model for differential diagnosis was 6.5 points,and its sensitivity was 84.69%(83/98)and specificity was 88.00%(22/25)in distinguishing high-risk and low-risk subgroups in training set,while its sensitivity was 77.50%(31/40)and specificity was 71.43%(10/14)in test set.Conclusion Risk score model based on clinical and multimodal ultrasound features could effectively differentiate benign and malignant BI-RADS 4A lesions in breast.
7.CT and MRI findings of mucosa-associated lymphoid tissue lymphoma of salivary gland
Yujie OUYANG ; Qifan MA ; Gongxin YANG ; Chunye ZHANG ; Xiaofeng TAO ; Ying YUAN
Journal of Practical Radiology 2025;41(2):202-205
Objective To explore the CT and MRI manifestation of salivary gland mucosa-associated lymphoid tissue(MALT)lymphoma.Methods The preoperative CT and MRI images of 89 patients with salivary gland MALT lymphoma who were confirmed by surgical pathology were analyzed retrospectively.Results Salivary gland MALT lymphoma were mainly located in the parotid gland(64 cases,71.9%).The ratio of male to female was 1 ≤ 5.Sixty-nine cases(77.5%)showed concomitant Sjogren's syndrome(SS).Typical imaging findings were round or lobulated well-marginated solid masses with moderate to severe enhancement.Atypical imaging findings were all from parotid gland MALT lymphoma,including cyst-solid mixed masses(34 cases,38.2%),poorly marginated boundaries(9 cases,10.1%),and punctuate calcification(5 cases,5.6%).The average apparent diffusion coefficient(ADC)value of lesions was(0.59±0.09)× 10-3 mm2/s and the time-signal intensity curve(TIC)type was mainly type Ⅱ(66.7%).Conclusion Salivary gland MALT lymphoma exhibits certain clinical and imaging characteristics.But when occur in parotid gland,some lesions may present atypically,which require diagnosis with the aid of functional MRI.
8.Application of telemedicine in patients with breast cancer-related lymphedema: a scoping review
Siyi ZHANG ; Famei TU ; Yufen XIE ; Xin ZHANG ; Qifan FENG ; Jimin WU
Chinese Journal of Modern Nursing 2025;31(5):576-583
Objective:To conduct a scoping review on the application of telemedicine in patients with breast cancer-related lymphedema (BCRL), to generalize and summarize the intervention methods, application forms, outcome indicators and effects of telemedicine, so as to provide a reference for healthcare professionals to implement interventions.Methods:Computerized searches of PubMed, Web of Science, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, and VIP were performed with a search period from their establishment to June 1, 2024. The included articles were screened, summarized and analyzed.Results:A total of 14 papers were included. Telemedicine intervention methods included tele-education, tele-exercise, tele-monitoring, tele-consultation, tele-psychological interventions, tele-visits, and tele-evaluation. Application forms involved web-based cloud platforms, social network service systems, telemedicine APPs, and remote portable monitoring devices. Outcome indicators included physical indicators, psychological indicators, quality of life, incidence of lymphedema, degree of lymphedema symptoms, and feasibility indicators.Conclusions:Telemedicine relies on web-based platforms and social network service software to conduct tele-education, tele-consultation, and tele-exercise for BCRL patients, and its feasibility and effectiveness have been proven. In the future, it is necessary to accelerate the establishment of breast cancer telemedicine centers, optimize the telemedicine service team, and increase the investment in the development of portable lymphedema telemonitoring equipment, so as to build a comprehensive and perfect breast cancer telemedicine system and improve the effectiveness of the prevention and treatment of BCRL.
9.Role of Toll-like receptor 4 in regulation of homocysteine-induced ferroptosis in macrophages
Jun-jie ZHAI ; Shaoying WEN ; Xinru LI ; Rui SUN ; Ning QI ; Qifan ZHANG ; Li YANG ; Hui HUANG ; Lingju MA ; Yinju HAO ; Yideng JIANG ; Guizhong LI ; Shengchao MA
The Journal of Practical Medicine 2025;41(3):313-321
Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.
10.Risk score model based on clinical and multimodal ultrasound features for differentiating benign and malignant BI-RADS 4A breast lesions
Qifan LIU ; Shuai CUI ; Wenjing GUO ; Wei LI ; Hailong WANG ; Husha LI ; Jundong YAO ; Zhoulong ZHANG
Chinese Journal of Interventional Imaging and Therapy 2025;22(1):22-26
Objective To evaluate the value of risk score model based on clinical and multimodal ultrasound features for differentiating benign and malignant breast imaging reporting and data system(BI-RADS)4A lesions in breast.Methods Totally 177 patients with BI-RADS 4A lesions detected by multimodal breast ultrasound were prospectively enrolled,and the patients were divided into training set(n=123)and test set(n=54)at the ratio of 7∶3.Univariate and multivariate logistic regression analyses were used to analyze patients'clinical,gray-scale ultrasound,CDFI and elastography ultrasound parameters of lesions,and the independent risk factors for differentiating benign and malignant BI-RADS 4A lesions in breast were screened,so as a risk score model was constructed.Based on the results of sungical pathology or follow-up,the cut-off value of the model for differentiating benign and malignant BI-RADS 4A lesions in breast was obtained by receiver operating characteristic(ROC)curve,and the patients were divided into high-risk and low-risk subgroups according to the cut-off value,and the efficacy of the model was evaluated.Results Among 177 cases,39 were with benign lesions and 138 were with malignant lesions.Patients'age>58 years,diameter of lesion>15.1 mm,lesions with irregular shape,lesions with grade 1 or 2 of blood flow and standard deviation of sound touch elastography of a 2 mm circular area around the lesion(shell)(shell-STESD)>16.33 kPa were all independent risk factors of malignant BI-RADS 4A lesions in breast.The cut-off value of risk score model for differential diagnosis was 6.5 points,and its sensitivity was 84.69%(83/98)and specificity was 88.00%(22/25)in distinguishing high-risk and low-risk subgroups in training set,while its sensitivity was 77.50%(31/40)and specificity was 71.43%(10/14)in test set.Conclusion Risk score model based on clinical and multimodal ultrasound features could effectively differentiate benign and malignant BI-RADS 4A lesions in breast.

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