Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase.

BACKGROUND: Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. AIM: To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. METHODS: The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. RESULTS: Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. CONCLUSION: Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.

Impact of telomere length and mitochondrial DNA copy number variants on survival of newborn cloned calves.

An established technology to create cloned animals is through the use of somatic cell nuclear transfer (SCNT), in which reprogramming the somatic cell nucleus to a totipotent state by enucleated oocyte cytoplasm is a necessary process, including telomere length reprogramming. The limitation of this technology; however, is that the live birth rate of offspring produced through SCNT is significantly lower than that of IVF. Whether and how telomere length play a role in the development of cloned animals is not well understood. Only a few studies have evaluated this association in cloned mice, and fewer still in cloned cows. In this study, we investigated the difference in telomere length as well as the abundance of some selected molecules between newborn deceased cloned calves and normal cows of different ages either produced by SCNT or via natural conception, in order to evaluate the association between telomere length and abnormal development of cloned cows. The absolute telomere length and relative mitochondrial DNA (mtDNA) copy number were determined by real-time quantitative PCR (qPCR), telomere related gene abundance by reverse-transcription quantitative PCR (RT-qPCR), and senescence-associated ß-galactosidase (SA-ß-gal) expression by SA-ß-gal staining. The results demonstrate that the newborn deceased SCNT calves had significantly shortened telomere lengths compared to newborn naturally conceived calves and newborn normal SCNT calves. Significantly lower mtDNA copy number, and significantly lower relative abundance of LMNB1 and TERT, higher relative abundance of CDKN1A, and aberrant SA-ß-gal expression were observed in the newborn deceased SCNT calves, consistent with the change in telomere length. These results demonstrate that abnormal telomere shortening, lower mtDNA copy number and abnormal abundance of related genes were specific to newborn deceased SCNT calves, suggesting that abnormally short telomere length may be associated with abnormal development in the cloned calves.

The efficacy of using a multiparametric magnetic resonance imaging-based radiomics model to distinguish glioma recurrence from pseudoprogression.

OBJECTIVE: The early differential diagnosis of the postoperative recurrence or pseudoprogression (psPD) of a glioma is of great guiding significance for individualized clinical treatment. This study aimed to evaluate the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics model to distinguish between the postoperative recurrence and psPD of a glioma early on and in a noninvasive manner. METHODS: A total of 52 patients with gliomas who attended the Hainan Provincial People's Hospital between 2000 and 2021 and met the inclusion criteria were selected for this study. 1137 and 1137 radiomic features were extracted from T1 enhanced and T2WI/FLAIR sequence images, respectively.After clearing some invalid information and LASSO screening, a total of 9 and 10 characteristic radiological features were extracted and randomly divided into the training set and the test set according to 7:3 ratio. Select-Kbest and minimum Absolute contraction and selection operator (LASSO) were used for feature selection. Support vector machine and logistic regression were used to form a multi-parameter model for training and prediction. The optimal sequence and classifier were selected according to the area under the curve (AUC) and accuracy. RESULTS: Radiomic models 1, 2 and 3 based on T1WI, T2FLAIR and T1WI + T2T2FLAIR sequences have better performance in the identification of postoperative recurrence and false progression of T1 glioma. The performance of model 2 is more stable, and the performance of support vector machine classifier is more stable. The multiparameter model based on CE-T1 + T2WI/FLAIR sequence showed the best performance (AUC:0.96, sensitivity: 0.87, specificity: 0.94, accuracy: 0.89,95% CI:0.93-1). CONCLUSION: The use of multiparametric MRI-based radiomics provides a noninvasive, stable, and accurate method for differentiating between the postoperative recurrence and psPD of a glioma, which allows for timely individualized clinical treatment.

Theoretical Investigation on Dialumenes toward Dihydrogen Activation: Mechanism and Ligand Effect.

Herein, we report a computation study based on the density functional theory calculations to understand the mechanism and ligand effect of the base-stabilized dialumenes toward dihydrogen activation. Among all of the examined modes of dihydrogen activation using the base-stabilized dialumene, we found that the concerted 1,2-hydrogenation of the Al═Al double bond is kinetically more preferable. The concerted 1,2-hydrogenation of the Al═Al double bond adopts an electron-transfer model with certain asynchrony. That is, the initial electron donation from the H-H σ bonding orbital to the empty 3p orbital of the Al1 center is followed by the backdonation from the lone pair electron of the Al2 center to the H-H σ antibonding orbital. Combined with the energy decomposition analysis on the transition states of the concerted 1,2-hydrogenation of the Al═Al double bond and the topographic steric mapping analysis on the free dialumenes, we ascribe the higher reactivity of the aryl-substituted dialumene over the silyl-substituted analogue in dihydrogen activation to the stronger electron-withdrawing effect of the aryl group, which not only increases the flexibility of the Al═Al double bond but also enhances the Lewis acidity of the Al═Al core. Consequently, the aryl-substituted dialumene fragment suffers less geometric deformation, and the orbital interactions between the dialumene and dihydrogen moieties are more attractive during the 1,2-hydrogenation process. Moreover, our calculations also predict that the Al═Al double bond has a good tolerance with the stronger electron-withdrawing group (-CF3) and the weaker σ-donating N-heterocyclic carbene (NHC) analogue (e.g., triazol carbene and NHSi). The reactivity of the dialumene in dihydrogen activation can be further improved by introducing these groups as the supporting ligand and the stabilizing base on the Al═Al core, respectively.

Quality assessment of videos on social media platforms related to gestational diabetes mellitus in China: A cross-section study.

Purpose: This study aimed to systematically evaluate the quality of content and information in videos related to gestational diabetes mellitus on Chinese social media platforms. Methods: The videos on various platforms, TikTok, Bilibili, and Weibo, were searched with the keyword "gestational diabetes mellitus" in Chinese, and the first 50 videos with a comprehensive ranking on each platform were included for subsequent analysis. Characteristic information of video was collected, such as their duration, number of days online, number of likes, comments, and number of shares. DISCREN, JAMA (The Journal of the American Medical Association) Benchmark Criteria, and GQS (Global Quality Scores) were used to assess the quality of all videos. Finally, the correlation analysis was performed among video features, video sources, DISCERN scores, and JAMA scores. Results: Ultimately, 135 videos were included in this study. The mean DISCERN total score was 31.84 ± 7.85, the mean JAMA score was 2.33 ± 0.72, and the mean GQS was 2.00 ± 0.40. Most of the videos (52.6%) were uploaded by independent medical professionals, and videos uploaded by professionals had the shortest duration and time online (P < 0.001). The source of the video was associated with numbers of "likes", "comments", and "shares" for JAMA scores (P < 0.001), but there was no correlation with DISCERN scores. Generally, videos on TikTok with the shortest duration received the most numbers of "likes", "comments", and "shares", but the overall quality of videos on Weibo was higher. Conclusion: Although the majority of the videos were uploaded by independent medical professionals, the overall quality appeared to be poor. Therefore, more efforts and actions should be taken to improve the quality of videos related to gestational diabetes mellitus.

Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

PURPOSE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP. METHODS: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group. RESULTS: Baseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population. CONCLUSIONS: ICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.

Pyrosequencing analysis of bacterial community changes in dental unit waterlines after chlorogenic acid treatment.

Introduction: The contamination of dental unit waterlines (DUWLs) poses a significant risk of cross-infection in dentistry. Although chemical disinfectants have been effective in reducing number of bacteria, they do have limitations. Methods: This study aimed to investigate the potential of chlorogenic acid, a natural substance with broadspectrum antibacterial properties, for treating DUWLs. Over a period of three months, we analyzed the microbial communities in 149 DUWLs samples collected from 5 dental units using high-throughput pyrophosphate sequencing. Results: The results revealed that chlorogenic acid treatment had a significant impact on the microbial community profile in the DUWLs, with the most significant changes occurring within the first 15 days and stabilization observed in the last 30 days. The predominant genera detected in the samples were Bacteroides, Lactobacillus, Streptococcus, Methylobacterium, and Phreatobacter. Additionally, the relative abundance of certain beneficial bacteria, such as Alloprevotella, Roseburia, and Blautia, increased, while the presence of opportunistic pathogens like Mycobacteria significantly decreased. The functional prediction analysis using the KEGG database indicated a decrease in the pathogenicity of the bacterial community in the DUWLs following chlorogenic acid treatment. Discussion: This study introduces a novel approach for the prevention and treatment of infections associated with dental care.

Accuracy of implant placement via dynamic navigation and autonomous robotic computer-assisted implant surgery methods: A retrospective study.

OBJECTIVE: Optimal implant planning and placement allows the prosthesis to be well designed to achieve a satisfactory aesthetic and functional outcome. We aimed to compare deviations between implant planning and placement with the assistance of dynamic computer-assisted implant surgery (d-CAIS) or autonomous robotic computer-assisted implant surgery (r-CAIS) methods in a clinical setting. METHODS: The retrospective analysis of medical records between 2021 July and 2022 December was conducted to compare the implantation accuracy of the d-CAIS and r-CAIS system in partially edentulous patients through cone-beam computed tomography. Patient-reported outcomes (PROs) were recorded using a visual analogue scale (VAS). The Kolmogorov-Smirnov test was used to check the data distribution. Student's t-test or Mann-Whitney U-test was used as appropriate, with a defined significant difference (p < .05). RESULTS: Seventy-seven patients were analysed (124 implants), with 38 patients (62 implants) in the d-CAIS group and 39 patients (62 implants) in the r-CAIS group. The differences between d-CAIS and r-CAIS were 4.09 ± 1.79° versus 1.37 ± 0.92° (p < .001) in angular deviation; 1.25 ± 0.54 versus 0.68 ± 0.36 mm (p < .001) in coronal global deviation; 1.39 ± 0.52 versus 0.69 ± 0.36 mm (p < .001) in apical global deviation; the results of the PROMs showed no statistical difference between the two groups. CONCLUSIONS: r-CAIS allows more accurate implant placement than the d-CAIS technology. And both groups achieved overall satisfactory outcomes via VAS (Chinese Clinical Trial Registry ChiCTR2300072004).

A nomogram for predicting the risk of preeclampsia in women with intrahepatic cholestasis of pregnancy based on prenatal monitoring time: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a special liver disease during pregnancy, characterized by abnormal bile acid metabolism. However, there is no consensus on how to group women with ICP based on the time of diagnosis worldwide. This study aimed to adopt a new grouping model of women with ICP, and the time from diagnosis to delivery was defined as the monitoring period. METHODS: This retrospective real-world data study was conducted across multiple centers and included 3172 women with ICP. The study first evaluated the significant difference in medication and nonmedication during different monitoring times. The least absolute shrinkage and selection operator (LASSO) model was then used to screen nine risk factors based on the predictors. The model's discrimination, clinical usefulness, and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve, and calibration analysis. RESULTS: The incidence of preeclampsia risk in ICP patients without drug intervention increased with the extension of the monitoring period. However, the risk of preeclampsia decreased in ICP patients treated with ursodeoxycholic acid. A predictive nomogram and risk score model was developed based on nine risk factors. The area under the ROC curve of the nomogram was 0.765 [95% confidence interval (CI): 0.724-0.807] and 0.812 (95% CI: 0.736-0.889) for the validation cohort. CONCLUSIONS: This study found that a longer ICP monitoring period could lead to adverse pregnancy outcomes in the absence of drug intervention, especially preeclampsia. A predictive nomogram and risk score model was developed to better manage ICP patients, maintain pregnancy to term delivery, and minimize the risk of severe adverse maternal and fetal outcomes.

Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on ß654-Thalassemia.

ß-thalassemia is an inherited blood disease caused by reduced or inadequate ß-globin synthesis due to ß-globin gene mutation. Our previous study developed a gene-edited mice model (ß654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the ßIVS2-654 (C > T) mutation site and the 3' splicing acceptor site at 579 and corrected abnormal ß-globin mRNA splicing in the ß654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from ß654-ER mice on ß-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted ß654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the ß-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from ß654-ER mice on ß-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future.

Mechanistic insights into the effects of diuron exposure on Alexandrium pacificum.

Diuron (N-(3,4-dichlorophenyl)-N,N­dimethylurea, DCMU), a ureic herbicide, is extensively used in agriculture to boost crop productivity; however, its extensive application culminates in notable environmental pollution, especially in aquatic habitats. Therefore, the present study investigated the effect of diuron on the dinoflagellate Alexandrium pacificum, which is known to induce harmful algal blooms (HAB), and its potential to biodegrade DCMU. Following a four-day DCMU exposure, our results revealed that A. pacificum proficiently assimilated DCMU at concentrations of 0.05 mg/L and 0.1 mg/L in seawater, attaining a complete reduction (100 % efficiency) after 96 h for both concentrations. Moreover, evaluations of paralytic shellfish toxins content indicated that cells subjected to higher DCMU concentrations (0.1 mg/L) exhibited reductions of 73.4 %, 86.7 %, and 75 % in GTX1, GTX4, and NEO, respectively. Exposure to DCMU led to a notable decrease in A. pacificum's photosynthetic efficacy, accompanied by increased levels of reactive oxygen species (ROS) and suppressed cell growth, with a growth inhibition rate of 41.1 % at 72 h. Proteomic investigations pinpointed the diminished expression levels of specific proteins like SxtV and SxtW, linked to paralytic shellfish toxins (PSTs) synthesis, as well as key proteins associated with Photosystem II, namely PsbA, PsbD, PsbO, and PsbU. Conversely, proteins central to the cysteine biosynthesis pathways exhibited enhanced expression. In summary, our results preliminarily resolved the molecular mechanisms underlying the response of A. pacificum to DCMU and revealed that DCMU affected the synthesis of PSTs. Meanwhile, our data suggested that A. pacificum has great potential in scavenging DCMU.

Epidemiological and clinical profile of pediatric hepatitis B virus infections in Wuhan: a retrospective cohort study.

BACKGROUND: Hepatitis B virus (HBV) remains a substantial public health safety concern drawing considerable attention in China and globally. The detection of HBV serological markers can enable the assessment of HBV infection and replication status in vivo and evaluate the body's protection against HBV. Therefore, this study aims to identify the epidemiological and clinical characteristics of HBV infection in children to prevent and control HBV infection in Wuhan areas. METHODS: We conducted an extensive retrospective cohort analysis of 115,029 individuals aged 0-18 years who underwent HBV serological markers detection for HBV infection in hospital between 2018 and 2021 using Electrochemiluminescence immunoassay. We generated descriptive statistics and analysed HBV infection's epidemiological and clinical characteristics between different sex and age groups. RESULTS: The overall positive detection rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in all participants were 0.13%, 79.09%, 0.17%, 2.81%, and 5.82%, respectively. The positive rate of HBeAb and HBcAb in males was significantly lower than that in females (2.64% vs. 3.13%, 5.56% vs. 6.29%) (P < 0.05). Twenty-two distinct HBV serological expression patterns were revealed. Among them, 8 common expression patterns accounted for 99.63%, while the remaining 14 uncommon expression patterns were primarily observed in neonatal patients with HBV infection. There are no significant differences in serological patterns based on sex (P < 0.05). The overall HBV infection detection rate was 5.82% [range 5.68-5.95] and showed a declining yearly trend. The rate in females was higher than that in males 6.29% [6.05, 6.35] vs. 5.56% [5.39, 5.59]. The overall HBV diagnostic rate over 4 years was 0.20% [0.17, 0.22], and the rate declined yearly. The prevalence of acute infection was higher than that of other infection types before 2019, but the incidence of unclassified infection showed a significant upward trend after 2019. CONCLUSIONS: While the overall HBV infection detection rate in children has decreased year by year, the infection rate remains high in children under one year and between 4 and 18 years. This continued prevalence warrants heightened attention and vigilance.

One-time fertilization of controlled-release urea with compound fertilizer and rapeseed cake maintains rice grain yield and improves nitrogen use efficiency under reduced nitrogen conditions.

Nitrogen (N) rate reduction and simplified fertilization can mitigate environmental impacts and reduce the involvement of manual labor in rice (Oryza sativa L.) production. Controlled-release urea (CRU) has been recommended as an effective alternative technique to conventional urea fertilization, and it can improve rice yield and N use efficiency (NUE) and reduce labor costs. However, the information on the effects of one-time fertilization with CRU on maintaining yield and improving NUE under reduced chemical N conditions is limited. In this study, controlled-release bulk blending fertilizer (CRF), consisting of CRU with release periods of 40 and 100 days, mixed with compound fertilizer, was applied as basal fertilizer. Increased ~20% plant density (ID) and rapeseed cake fertilizer (RC, increase 20% organic N) were combined with CRF, respectively. The N treatments with 20% chemical N reduction were as follows: reduced N fertilizer (RNF), CRF, CRF+ID, and CRF+RC. In addition, a conventional split fertilizer application with 300 kg ha-1 N was applied as the control (CK). Rice yield and its components, dry matter accumulation, N uptake, and NUE were investigated to evaluate whether one-time N fertilization realized stable yield and high NUE under reduced 20% chemical N conditions. Compared with CK, the CRF+RC treatment exhibited a comparable grain yield, while the other reduced N treatments (RNF, CRF, and CRF+ID) had a lower grain yield. Moreover, CRF+ID exhibited a higher rice grain yield than RNF or CRF under the same N level. Irrespective of exogenous organic N, CRF+RC exhibited significantly higher NUE than CK. The CRF+ID treatment showed a significantly higher N partial factor productivity (PFN) than CK but comparable N agronomic efficiency (NAE) and N recovery efficiency (NRE). Therefore, a one-time fertilizer application of CRF+RC maintained grain yield and improved the NUE while reducing the N rate and fertilization times, demonstrating its potential application in rice production.

Mechanisms for enhanced lignin humification with reduced organic matter loss by goethite in biogas residue composting.

In this study, effects of three iron (oxyhydr)oxides on the biogas residue composting, i.e., composting with goethite (CFe1), hematite (CFe2) or magnetite (CFe3), were investigated. Results showed that composting performance of CFe1 was much better than those of CFe2 and CFe3. Addition of goethite increased temperature of CFe1 and enhanced lignin humification. More than 31.49% of Fe(III) in goethite was reduced to amorphous Fe(II) during the composting, suggesting that goethite worked as electron acceptor for microbial metabolism and heat generation. The functional bacteria Chloroflexi and Actinobacteria, and genes encoding key enzymes (AA1 family), which play essential roles in humification of lignin, were enriched in CFe1. Besides, goethite reduced 10.96% organic matter (OM) loss probably by increasing the molecular size and aggregation of OM for its protection during the composting. This study shows that adding goethite is an efficient strategy to enhancing the humification of lignin-rich biowaste.

Diterpenoids from Euphorbia fischeriana with Kv1.3 Inhibitory Activity.

Euphorbia diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed (1-9) and 16 known (10-25) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of Euphorbia fischeriana. The structures were established by analysis of the spectroscopic data as well as by single-crystal X-ray diffraction analysis. Among the isolated diterpenoids, macrocyclic jatrophanes and lathyranes exerted Kv1.3 blocking activity. Compound 8 exhibited good selectivity on the inhibition of the Kv 1.3 channel rather than hERG channel, with a selectivity index over 7.0. The selective activity of lathyrane diterpenoids indicates that macrocyclic diterpenoids have the potential to be further investigated as therapeutic agents for the treatment of autoimmune diseases.

Rational use of drugs to alleviate adverse outcomes caused by COVID-19 quarantine in women with intrahepatic cholestasis of pregnancy.

Purpose: This study aimed to investigate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether the rational use of drugs will change these impacts. Methods: This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period. Results: A total of 3,161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2,345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, fetal growth restriction, pre-eclampsia, preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid. Conclusion: COVID-19 quarantine would increase the incidence of ICP and lead to adverse pregnancy outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should enhance their management and life guidance for women with ICP and speed up developing home quarantine guidelines.