Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective: To investigate the epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools. Methods: Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA). Results: A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range. Conclusions The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.

BACKGROUND:The impact of the endometrium's structure and spiral artery blood flow parameters on the pregnancy rate of artificial insemination by husband remains unclear.This study identified the independent factors and constructed a prediction model with good clinical application efficacy after calibration of other confounding factors. OBJECTIVE:To construct and validate a clinical pregnancy prediction model for artificial insemination by husband based on endometrial structure and uterine spiral artery blood flow parameters. METHODS:A retrospective analysis was conducted on 1 299 patients who underwent artificial insemination by husband treatment at Changzhou Maternal and Child Health Hospital from January 2017 to January 2021.The non-pregnancy group consisted of 1 182 patients,while the pregnancy group included 117 patients.Out of these patients,93 cases were successfully matched between the pregnancy and non-pregnancy groups using a 1∶1 propensity score matching method.Single-factor and multi-factor analyses were used to screen the endometrial structure and uterine spiral artery blood flow parameters to determine their influence on artificial insemination by husband outcomes.The optimal cutoff value was established for each independent influencing factor through receiver operating curve analysis and their risk trend affecting artificial insemination by husband pregnancy outcomes was analyzed using a restricted cubic spline.The clinical efficacy of this combined forecast model was tested by using clinical decision curve and clinical influence curve methods. RESULTS AND CONCLUSION:(1)There was no statistical significance in non-endometrial factors between the pregnancy group and the non-pregnancy group,and the data had a good balance by propensity score matching(P>0.05).(2)Single-factor analysis identified several subendometrial parameters as significant influencing factors of artificial insemination by husband pregnancy outcomes,including vascularization index,flow index,vascular flow index,resistance index,pulsatility index,maximum systolic velocity/end-diastolic velocity,thickness of average junction zone and maximum junction zone from the basal endometrium to the outer myometrium inner layer(P<0.05).(3)Multivariate logistic regression analysis revealed that thickness of average junction zone,pulsatility index,and vascular flow index were independent influencing factors of pregnancy outcomes of artificial insemination by husband,vascular flow index>thickness of average junction zone>pulsatility index.(4)Receiver operating characteristic curve analysis indicated that the area under receiver operating characteristic curve of vascular flow index was 0.704(0.629,0.779),and the optimal cutoff value was 6.26;the area under receiver operating characteristic curve of thickness of average junction zone was 0.660(0.582,0.739),and the optimal cutoff value was 6.38;the area under receiver operating characteristic curve of pulsatility index was 0.642(0.563,0.721),and the optimal cutoff value was 1.18.(5)The restricted cubic spline analysis revealed that artificial insemination by husband pregnancy outcomes were significantly positively affected when the vascular flow index was>6.24 or the thickness of average junction zone was≤6.55 mm,while a negative risk was associated with pulsatility index>1.27.(6)The clinical decision curve and clinical influence curve analyses exhibited that the combined prediction model had the maximum clinical net benefit at the threshold probability value of 0.17-0.93,and the ratio of loss to benefit was consistently less than 1 in the threshold probability range,indicating that the model had good clinical efficacy.(7)It is concluded that after adjusting for other confounding factors outside of the endometrium using propensity score matching and multifactorial logistic regression,the thickness of average junction zone,pulsatility index and vascular flow index were independent factors that influenced pregnancy outcomes of artificial insemination by husband.Through determining their optimal cutoff values and assessing their risk trends,it was confirmed that the combined prediction model had good predictive value and clinical efficacy.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.

Objective:To explore the risk factors and their interation in the incidence of monozygotic twins dur-ing in vitro fertilization-embryo transfer(IVF-ET).Methods:The cohort for this investigation comprised 4537 pa-tients who underwent IVF-ET with single embryo transfer,resulting in live births at Changzhou Maternal and Child Health Care Hospital spanning from January 2011 to December 2021.Among this cohort,76 paitients with monozygotic twins were enrolled in the monozygotic twin group.Employing a 5∶1 propensity score matching strategy,380 patients with monozygotic singletons were enrolled in monozygotic singleton group.Using single fac-tor and Lasso regression analysis to correct for the influencing factors of monozygotic twins,using multiple factor Logistic regression to screen for independent risk factors of monozygotic twins and analyze their impact weights,and then performing multiplication and addition interaction analysis on them.Results:The results of univariate analysis showed that there were statistically significant differences(P＜0.05)between the two groups of patients in terms of age,fertilization method,assisted hatching,embryo type for transfer,embryo transfer method,embryo culture duration,and HCG day estradiol(E2)level.The results of multivariate Logistic regression showed that blas-tocyst transfer(OR 2.847,95％CI 1.559-5.199),frozen-thawed embryo transfer(OR 2.640,95％CI 1.354-5.145),and HCG day E2 level(OR 1.783,95％CI 1.033-3.077)were independent risk factors for monozygotic twins(P＜0.05),demonstrating a hierarchical impact sequence of blastocyst transfer(11.60)＞frozen-thawed embryo transfer(6.54)＞HCG day E2(4.32)level.Notably,there was a significant positive additive interaction between embryo transfer type and HCG day E2 level,with an interaction index(S)of 4.690(95％CI 1.896-11.598),relative excess risk due to interaction(RERI)of 4.128(95％CI 2.236-6.019),and attributable propor-tion due to interaction(AP)of 0.661(95％CI 0.536-0.786).Conclusions:Blastocyst transfer,frozen-thawed embryo transfer,and HCG day E2 level are risk factors for monozygotic twins,and there is a significant positive additive interaction between embryo transfer type and HCG day E2 level.