Longitudinal assessment of coronary plaque regression related to sodium-glucose cotransporter-2 inhibitor using coronary computed tomography angiography.

BACKGROUND: Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) is a novel oral drug for treating type 2 diabetes mellitus (T2DM) with demonstrated cardiovascular benefits. Previous studies in apolipoprotein E knockout mice have shown that SGLT2i is associated with attenuated progression of atherosclerosis. However, whether this effect extends to T2DM patients with coronary atherosclerosis in real-world settings remains unknown. METHODS: In this longitudinal cohort study using coronary computed tomography angiography (CCTA), T2DM patients who underwent ≥ 2 CCTA examinations at our center between 2019 and 2022 were screened. Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and not intervened during serial CCTAs. Exclusion criteria included a CCTA time interval < 12 months, prior SGLT2i treatment, or initiation/discontinuation of SGLT2i during serial CCTAs. Plaque volume (PV) and percent atheroma volume (PAV) were measured for each study plaque using CCTA plaque analysis software. Patients and plaques were categorized based on SGLT2i therapy and compared using a 1:1 propensity score matching (PSM) analysis. RESULTS: The study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%). Following SGLT2i treatment for a median duration of 14.6 (interquartile range: 13.0, 20.0) months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased (all p < 0.001). Meanwhile, reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated compared to non-SGLT2i-treated plaques (all p < 0.001). PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (- 11.77 mm3 vs. 4.33 mm3, p = 0.005), non-calcified PV (- 16.96 mm3 vs. - 1.81 mm3, p = 0.017), overall PAV (- 2.83% vs. 3.36%, p < 0.001), and non-calcified PAV (- 4.60% vs. 0.70%, p = 0.003). These findings remained consistent when assessing annual changes in overall and compositional PV and PAV. Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively (all p < 0.05). The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups (all p for interaction > 0.05). CONCLUSIONS: In this longitudinal CCTA cohort of T2DM patients, SGLT2i therapy markedly regressed coronary overall PV and PAV, mainly result from a significant reduction in non-calcified plaque.

Four new species of Russulasubsect.Cyanoxanthinae from China (Russulales, Russulaceae).

Four new species of Russulasubsect.Cyanoxanthinae, viz. Russulaatrochermesina Y.L. Chen & J.F. Liang, R.lavandula Y.L. Chen, B. Chen & J.F. Liang, R.lilaceofusca Y.L. Chen & J.F. Liang and R.perviridis Y.L. Chen, B. Chen & J.F. Liang, from China are proposed, based on morphological and molecular evidence. Russulaatrochermesina can be distinguished by its violet pileus with tuberculate-striate margin, distant lamellae that stain greyish-yellow when bruised, basidiospores ornamented by isolated warts, wide hymenial cystidia on lamellae edges, cystidia content negative reaction in sulphovanillin and branched subterminal cells in pileipellis. Russulalavandula has a purplish-white to violet red pileus with a yellow centre, frequently present lamellulae and furcations, stipe often with pale yellow near the base, isolated basidiospores ornamentation and unbranched cuticular hyphal terminations, while R.lilaceofusca is characterised by its lilac brown to dark brown pileus, crowded lamellae with lamellulae and furcations, stipe often turning reddish-yellow when bruised, subreticulate basidiospores ornamentation and clavate hymenial cystidia often with capitate appendage whose contents that change to reddish-black in sulphovanillin. Russulaperviridis is characterised by its large basidiomata, smooth pileus surface, frequently present lamellulae and furcations, stipe with yellow-brown tinge, globose to broadly ellipsoid basidiospores with subreticulate ornamentation, long hymenial cystidia that turn greyish-black in sulphovanillin and symbiotic with Quercussemecarpifolia. Phylogenetic analyses, based on multi-gene ITS+LSU+mtSSU+rpb2, indicate that R.atrochermesina, R.lavandula, R.lilaceofusca and R.perviridis are closely related to R.pallidirosea and R.purpureorosea, R.banwatchanensis, R.lakhanpalii and R.nigrovirens, respectively.

Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

A coronary CT angiography-derived myocardial radiomics model for predicting adverse outcomes in chronic myocardial infarction.

BACKGROUND: The prognostic efficacy of a coronary computed tomography angiography (CCTA)-derived myocardial radiomics model in patients with chronic myocardial infarction (MI) is unclear. METHODS: In this retrospective study, a cohort of 236 patients with chronic MI who underwent both CCTA and cardiac magnetic resonance (CMR) examinations within 30 days were enrolled and randomly divided into training and testing datasets at a ratio of 7:3. The clinical endpoints were major adverse cardiovascular events (MACE), defined as all-cause death, myocardial reinfarction and heart failure hospitalization. The entire three-dimensional left ventricular myocardium on CCTA images was segmented as the volume of interest for the extraction of radiomics features. Five models, namely the clinical model, CMR model, clinical+CMR model, CCTA-radiomics model, and clinical+CCTA-radiomics model, were constructed using multivariate Cox regression. The prognostic performances of these models were evaluated through receiver operating characteristic curve analysis and the index of concordance (C-index). RESULTS: Fifty-one (20.16%) patients experienced MACE during a median follow-up of 1439.5 days. The predictive performance of the CCTA-radiomics model surpassed that of the clinical model, CMR model, and clinical+CMR model in both the training (area under the curve (AUC) of 0.904 vs. 0.691, 0.764, 0.785; C-index of 0.88 vs. 0.71, 0.75, 0.76, all p values <0.001) and testing (AUC of 0.893 vs. 0.704, 0.851, 0.888; C-index of 0.86 vs. 0.73, 0.85, 0.85, all p values <0.05) datasets. CONCLUSIONS: The CCTA-based myocardial radiomics model is a valuable tool for predicting adverse outcomes in chronic MI, providing incremental value to conventional clinical and CMR parameters.

Cardiac magnetic resonance feature tracking derived left atrial strain in the diagnosis of patients with constrictive pericarditis and restrictive cardiomyopathy.

Objective: To explore the diagnostic value of cardiac magnetic resonance feature tracking (CMR-FT) divided left atrial (LA) strain in differentiating constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). Methods: Patients with CP (n = 40) and RCM (n = 40), and another 40 normal control group were retrospectively enrolled over a period of 8 years at a tertiary cardiac centre. Left ventricular (LV) and biatrial strain and strain rate (SR) were measured. Atrial strain was used to differentiate between patients with CP and RCM. Then, patients were grouped according to their left ventricular ejection fraction (LVEF), either ≥50% or < 50%. A deeper analysis was done to evaluate the diagnostic value of atrial strain in these subgroups. Receiver operating characteristic curves (ROC) were used to assess the accuracy of myocardial strain based on CMR FT for the differential diagnosis of CP and RCM. Results: LV and LA strain and SR were significantly lower in patients with CP and RCM than those in the normal controls (P < 0.05). LA strain and SR were significantly lower in the RCM group than in the CP group (P < 0.05). In patients with either LVEF≥50% or＜50%, LA strain were lower in the RCM group than in the CP group (P < 0.05). ROC analysis showed that LA stored strain (LA-εs) had a good differential diagnostic value for CP and RCM, with an area under the curve (AUC) of 0.811 and an optimal cutoff value of 6.98%, above this value it tends to develop CP. Further, an excellent differential diagnostic value was found in patients with LVEF＜50%, with an AUC of 0.955. Conclusion: LA strain analysis obtained by CMR-FT provides good differential diagnostic value for distinguishing CP from RCM, especially in patients with LVEF＜50%.

Cardiac magnetic resonance analysis of left atrium function in patients with pre-apical hypertrophic cardiomyopathy.

Background: Patients presenting with unexplained T wave inversion on electrocardiogram combined with thickened left ventricular apex but less than 15 mm had been proposed as a preclinical scope of apical hypertrophy cardiomyopathy (pre-ApHCM). However, analysis of left atrial (LA) function in these patients has not been studied. This study aims to evaluate the LA function in pre-ApHCM patients and compare it with patients with ApHCM using cardiac magnetic resonance (CMR) imaging. Methods: In this retrospective case-control study, a total of 3,593 CMR reports from Beijing Anzhen Hospital, Capital Medical University, China were reviewed. Finally, 31 pre-ApHCM patients were identified and 40 ApHCM and 31 normal controls were included for comparison. LA volumetric and strain were analyzed by CMR. Two-tailed one-way ANOVA was used to analyze the difference of three groups. Pearson correlation test was used for correlation analysis. Results: All of the volumetric parameters in pre-ApHCM group were higher than those in control group. LA reservoir (LA total EF, εs) and conduit function (LA passive EF, εe) parameters, were significantly different among the three groups, which were the lowest in the ApHCM group, intermediate in the pre-ApHCM group, and the highest in the control group ((all P<0.001). Compared with the control group, the LA booster pump function, both the booster EF and booster pump strain (εa) in ApHCM were impaired (P=0.003 and P=0.002 respectively). Meanwhile, only the εa was impaired (P=0.016) while LA booster EF was not (P=0.064) in the pre-ApHCM group, neither εa nor the booster EF show difference between the ApHCM and pre-ApHCM (P=0.272 and P=0.518 respectively). Conclusions: LA function features in pre-ApHCM patients were similar to ApHCM but different from the normal controls. In pre-ApHCM and ApHCM patients, LA reservoir and conduit function impaired earlier before left atrium enlarged and decreased progressively as apex thickens. These findings may help to understand the LA functional change from pre-ApHCM to ApHCM, and to detect subclinical changes in patients with pre-ApHCM before overt hypertrophy or clinical symptoms develop.

Prognostic Value of Left Ventricular Longitudinal Function and Myocardial Fibrosis in Patients With Ischemic and Non-Ischemic Dilated Cardiomyopathy Concomitant With Type 2 Diabetes Mellitus: A 3.0 T Cardiac MR Study.

BACKGROUND: Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients. PURPOSE: To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values. STUDY TYPE: Retrospective cohort. POPULATION: Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM). FIELD STRENGTH/SEQUENCE: 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences. ASSESSMENT: Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months. STATISTICAL TESTS: Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%). RESULTS: ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM. CONCLUSIONS: T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: 5.

Morphology and Molecular Phylogeny Reveal Five New Species of Laccaria (Hydnangiaceae, Agaricales) from Southern China.

The genus Laccaria is a type of cosmopolitan and ecologically important fungal group. Members can form ectomycorrhizal associations with numerous trees, and some species are common edible fungi in local markets. Although some new species from China are recently published, the species diversity of Laccaria is still unclear in China. In this study, some samples of Laccaria were collected from southern China, and morphological characteristics and phylogenetic analyses based on the multilocus dataset of ITS-LSU-tef1-rpb2 confirmed five new species. Laccaria miniata, L. nanlingensis and L. neovinaceoavellanea were collected from subtropical broad-leaved forests, and L. rufobrunnea and L. umbilicata were collected from subtropical mixed forests of southwest China. Full descriptions, illustrations, comparisons with similar species and phylogenetic analysis are provided.

Impaired cardiac pump function assessment with normalized cardiac power using cardiac magnetic resonance in patients with hypertrophic cardiomyopathy.

Background: Cardiac power (CP; CP = 0.222 × cardiac output × mean blood pressure) output in patients with heart failure has been studied previously, but its importance in patients with hypertrophic cardiomyopathy (HCM) remains unclear. The present study aimed to explore the role of normalized CP (normalized CP = CP/ventricle mass) in assessing cardiac function in patients with HCM with normal ejection fraction using cardiac magnetic resonance (CMR). Methods: This cross-sectional study enrolled 99 patients with HCM who underwent CMR from December 2020 to January 2022 at Beijing Anzhen Hospital, and these patients were classified into heart failure or non-heart failure subgroups. Meanwhile, a control group comprising 65 gender- and age-matched healthy volunteers was also enrolled. The baseline clinical characteristics and cardiac functional parameters were compared between the patients with HCM and the controls, and multivariable linear regression analysis was performed to analyze the relationship between normalized CP and the relevant factors. Results: Significantly higher CP (1.19 vs. 1.01 W; P=0.03) but lower normalized CP (0.73 vs. 1.12 W/100 g; P<0.001) were found in patients with HCM as compared with the controls. Multivariable analysis showed that HCM correlated well with normalized CP [ß=-0.235; 95% confidence interval (CI): -0.341 to -0.129; P<0.001]. In the HCM group, there were 34 cases with heart failure and 65 with non-heart failure, and the patients with HCM with heart failure showed similar CP (1.14 vs. 1.24 W; P=0.06) but significantly lower normalized CP (0.54 vs. 0.78 W/100 g; P<0.001). The correlation analysis of normalized CP and functional parameters revealed that normalized CP was inversely correlated with left ventricle mass/body surface area (R=-0.509; 95% CI: -0.646 to -0.341; P<0.001) in patients with HCM. Conclusions: Normalized CP decreased significantly and was negatively correlated with ventricle mass, indicating impaired cardiac pump function in patients with HCM. Normalized CP might play a critical role in detecting and evaluating impaired cardiac pump function in patients with HCM with preserved ejection fraction.

A Novel CT Perfusion-Based Fractional Flow Reserve Algorithm for Detecting Coronary Artery Disease.

BACKGROUND: The diagnostic accuracy of fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFR-CT) needs to be further improved despite promising results available in the literature. While an innovative myocardial computed tomographic perfusion (CTP)-derived fractional flow reserve (CTP-FFR) model has been initially established, the feasibility of CTP-FFR to detect coronary artery ischemia in patients with suspected coronary artery disease (CAD) has not been proven. METHODS: This retrospective study included 93 patients (a total of 103 vessels) who received CCTA and CTP for suspected CAD. Invasive coronary angiography (ICA) was performed within 2 weeks after CCTA and CTP. CTP-FFR, CCTA (stenosis ≥ 50% and ≥70%), ICA, FFR-CT and CTP were assessed by independent laboratory experts. The diagnostic ability of the CTP-FFR grouped by quantitative coronary angiography (QCA) in mild (30-49%), moderate (50-69%) and severe stenosis (≥70%) was calculated. The effect of calcification of lesions, grouped by FFR on CTP-FFR measurements, was also assessed. RESULTS: On the basis of per-vessel level, the AUCs for CTP-FFR, CTP, FFR-CT and CCTA were 0.953, 0.876, 0.873 and 0.830, respectively (all p < 0.001). The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CTP-FFR for per-vessel level were 0.87, 0.88, 0.87, 0.85 and 0.89 respectively, compared with 0.87, 0.54, 0.69, 0.61, 0.83 and 0.75, 0.73, 0.74, 0.70, 0.77 for CCTA ≥ 50% and ≥70% stenosis, respectively. On the basis of per-vessel analysis, CTP-FFR had higher specificity, accuracy and AUC compared with CCTA and also higher AUC compared with FFR-CT or CTP (all p < 0.05). The sensitivity and accuracy of CTP-FFR + CTP + FFR-CT were also improved over FFR-CT alone (both p < 0.05). It also had improved specificity compared with FFR-CT or CTP alone (p < 0.01). A strong correlation between CTP-FFR and invasive FFR values was found on per-vessel analysis (Pearson's correlation coefficient 0.89). The specificity of CTP-FFR was higher in the severe calcification group than in the low calcification group (p < 0.001). CONCLUSIONS: A novel CTP-FFR model has promising value to detect myocardial ischemia in CAD, particularly in mild-to-moderate stenotic lesions.

Modified Cap-Assisted Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for the Treatment of Rectal Neuroendocrine Tumors ≤10 mm: A Randomized Noninferiority Trial.

INTRODUCTION: Although recent guidelines recommend endoscopic resection of rectal neuroendocrine tumors (NET) ≤10 mm, there is no consensus on which endoscopic modality should be performed. We aimed to compare the safety and efficacy of modified cap-assisted endoscopic mucosal resection (mEMR-C) and endoscopic submucosal dissection (ESD) methods for the treatment of rectal NET ≤10 mm. METHODS: A randomized noninferiority trial comparing mEMR-C and ESD was conducted. The primary outcome was the histological complete resection rate; the secondary outcomes included en bloc resection rate, operation time, complications, and so on. Subgroup analyses and follow-up were also performed. RESULTS: Ninety patients were enrolled, and 79 patients with pathologically confirmed rectal NET were finally analyzed, including 38 cases of mEMR-C and 41 cases of ESD. Histological complete resection rate was 97.4% in the mEMR-C group and 92.7% in the ESD group. The noninferiority of mEMR-C compared with that of ESD was confirmed because the absolute difference was 4.7% (2-sided 90% confidence interval, -3.3% to 12.2%; P = 0.616). En bloc resection and successful removal of rectal NET were achieved in all patients. Advantages of mEMR-C over ESD included shorter operation time (8.89 ± 4.58 vs 24.8 ± 9.14 minutes, P < 0.05) and lower hospitalization cost ($2,233.76 ± $717.70 vs $2,987.27 ± $871.81, P < 0.05). Postoperative complications were recorded in 4 patients who received mEMR-C and 2 patients in the ESD group (11.5% vs 4.9%, P = 0.509), which were all well managed using endoscopy. Similar findings were observed when subgroup analysis was performed. DISCUSSION: mEMR-C is noninferior to ESD with a similar complete resection rate. In addition, mEMR-C had shorter procedure duration time and lower hospitalization costs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03982264.

Incremental prognostic value of left atrial strain in patients with heart failure.

AIMS: The present study aimed to evaluate the prognostic value of atrial strain and strain rate (SR) parameters derived from cardiac magnetic resonance (CMR) feature tracking (FT) in patients with ischaemic and non-ischaemic dilated cardiomyopathy with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation. METHODS AND RESULTS: A total of 300 patients who underwent CMR with left ventricular ejection fraction (LVEF) ≤ 40% and ischaemic or non-ischaemic dilated cardiomyopathy were analysed in this retrospective study. Major adverse cardiac events (MACEs) include cardiovascular death, heart transplantation, and rehospitalization for worsening HF. Ninety-four patients had MACEs during median follow-up of 3.84 years. Multivariate Cox regression models adjusted for common clinical and CMR risk factors detected a significant association between LA-εs and MACE in ischaemic (HR = 0.94/%; P = 0.002), non-ischaemic dilated cardiomyopathy (HR = 0.88/%; P = 0.001), or all included patients (HR = 0.87; P < 0.001). LA-εs provided incremental prognostic value over conventional outcome predictors (Uno C statistical comparison model: from 0.776 to 0.801, P < 0.0001; net reclassification improvement: 0.075, 95% CI: 0.0262-0.1301). Kaplan-Meier analysis revealed that the risk of MACE occurrence increased significantly with lower tertiles of left atrial reservoir strain (LA-εs) (log-rank P < 0.0001). Patients in the worst LA-εs tertile faced a significantly increased risk of MACEs irrespective of late gadolinium enhancement (LGE) (log-rank P < 0.0001). CONCLUSIONS: LA-εs derived from CMR FT has a significant prognostic impact on patients with ischaemic or non-ischaemic dilated cardiomyopathy, incremental to common clinical and CMR risk-factors.

Real-World Acceptance of COVID-19 Vaccines among Healthcare Workers in Perinatal Medicine in China.

Surveys showed that vaccine hesitancy may influence the acceptance of COVID-19 vaccines in healthcare workers (HCWs) and the general population. Currently, the actual acceptance of COVID-19 vaccination in HCWs has rarely been reported. In the present survey, we investigated the real-world acceptance of COVID-19 vaccination in HCWs in perinatal medicine during the first three-month period of vaccination in China and to identify the main reason for the decline of vaccination. HCWs (1087) who participated in a Chinese national symposium on perinatal medicine during 16-18 April 2021 were invited to answer a 27-question questionnaire online. A total of 1051 HCWs completed the questionnaire. Of them, 86.2% (906/1051) accepted the COVID-19 vaccination and 13.8% (145/1051) declined the vaccination. Because of the vaccine hesitancy, one-fourth of the vaccinated participants did not accept the vaccination until consulted with others or requested by employers. The main reason for the decline of vaccination in 145 unvaccinated HCWs was the concern about vaccine safety. The results indicate that vaccination request by employers may promote vaccine acceptance. More convincing data on the safety of COVID-19 vaccines appears to be important to increase the acceptance of vaccination.

Association between serum estradiol level on the human chorionic gonadotrophin administration day and clinical outcome.

BACKGROUND: Estradiol, as an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization embryo transfer (IVF-ET) cycles. The aim of this retrospective study was to evaluate the association between elevated serum estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and IVF-ET pregnancy and birth outcomes. METHODS: A total of 1771 infertile patients with their first fresh IVF-ET cycles were analyzed retrospectively between January 2011 and January 2016 in Peking University First Hospital. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 205), group 2 (serum E2 levels 1001-2000 pg/mL, n = 457), group 3 (serum E2 levels 2001-3000 pg/mL, n = 425), group 4 (serum E2 levels 3001-4000 pg/mL, n = 310), group 5 (serum E2 levels 4001-5000 pg/mL, n = 237), and group 6 (serum E2 levels > 5000 pg/mL, n = 137). The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates of the groups were compared as the first objective of the study. For the 360 women with singleton births among all patients, the area under the corresponding receiver operating characteristic curve (ROC curve) was calculated to assess the predictive value of the E2 change for the probability of low birth weight (LBW) infants as the second objective. RESULTS: The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates gradually increased from groups 1 to 5 but decreased in group 6. The parameters of group 1 were statistically worse than those of the other groups, from group 2 to group 6 (the number of retrieved oocytes, t = 13.096, t = 23.307, t = 23.086, t = 26.376, t = 19.636, P < 0.003; the number of retrieved MII oocytes, t = 10.856, t = 20.868, t = 21.874, t = 23.374, t = 19.092, P < 0.003; the implantation rate, χ = 12.179, χ = 22.239, χ = 23.993, χ = 23.344, χ = 16.758, P < 0.003; the clinical pregnancy rate, χ = 16.415, χ = 28.074, χ = 35.387, χ = 37.025, χ = 24.590, P < 0.003). ROC analysis revealed that when a serum peak E2 of 3148 pg/mL was used to predict LBW. CONCLUSIONS: The results indicate that serum E2 levels have a concentration-dependent effect on clinical outcomes. The optimal range of the E2 level during a fresh IVF-ET cycle is 1000 to 3148 pg/mL.

Effective inhibition of different Japanese encephalitis virus genotypes by RNA interference targeting two conserved viral gene sequences in vitro and in vivo.

Japanese encephalitis is a zoonotic, mosquito-borne, infectious disease caused by Japanese encephalitis virus (JEV), which is prevalent in China. At present, there are no specific drugs or therapies for JEV infection, which can only be treated symptomatically. Lentivirus-mediated RNA interference (RNAi) is a highly efficient method to silence target genes. In this study, two lentiviral shRNA, LV-C and LV-NS5, targeting the conserved viral gene sequences were used to inhibit different JEV genotypes strains in BHK21 cells and mice. The results showed that LV-C significantly inhibited JEV genotype I and genotype III strains in cells and mice. Quantitative RT-PCR analysis showed that JEV mRNA were reduced by 83.2-90.9% in cells by LV-C and that flow cytometry analysis confirmed the inhibitory activity of LV-C. The viral titers were reduced by about 1000-fold in cells and the brains of suckling mice by LV-C, and the pretreatment of LV-C protected 60-80% of mice against JEV-induced lethality. The inhibitory activities of LV-NS5 in cells and mice were weaker than those of LV-C. These results indicate that RNAi targeting of the two conserved viral gene sequences had significantly suppressed the replication of different JEV genotypes strains in vitro and in vivo, highlighting the feasibility of RNAi targeting of conserved viral gene sequences for controlling JEV infection.

Anatomic distribution of nerves and microvascular density in the human anterior vaginal wall: prospective study.

BACKGROUND: The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot. METHODS: Biopsies were drawn from a 12 o'clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5-immunoreactive nerves and smooth muscle actin-immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. RESULTS: Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002). CONCLUSIONS: Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction.