Objective To assess the contractility of levator ani muscle in postpartum female using pelvic floor three-dimensional ultrasound and to provide an effective imaging basis for the change of levator ani muscle contractility in postpartum female.Methods Totally 75 postpartum women (55 underwent spontaneous vaginal delivery and 20 underwent selective cesarean delivery) and 40 nulliparas were examined by pelvic floor three-dimensional ultrasound.The images were obtained at rest and at maximal levator ani muscle contraction.The sagittal hiatal length (L) on the two-dimensional sagittal images,the area of levator hiatus (A) and the circumference of levator hiatus (C) were measured on the three-dimensional images,and the difference value between rest and contraction were calculated to get the △L,△A,△C.Then the △L,△A,△C between different groups were compared.Results The △L,△A,△C in spontaneous vaginal delivery group and selective cesarean delivery group were smaller than those in nulliparas group (P ＜0.05),and there was no statistical difference between spontaneous vaginal delivery and selective cesarean delivery group (P ＞ 0.05).Conclusions Three-dimensional ultrasound can effectively assess the the contractility of levator ani muscle,the levator ani muscle contractility of postpartum female was poorer than nulliparas,and between spontaneous vaginal delivery and selective cesarean delivery women there is no obvious difference.

ObjectiveTo observe the morphology and structure of the urogenital hiatus in late pregnancy women using transperineal three-dimensional (3D) pelvic floor ultrasonography.Methods Twenty five nulliparas and fifty late pregnancy women were examined by transperineal 3D pelvic floor ultrasonography.The images of urogenital hiatus were obtained and compared to study their differences between nulliparas and late pregnancy women.Results Compared to nulliparas,urogenital hiatus in late pregnancy women tended to be circular and with an offset position.The puborectalis were bended and could be avulsed.Pelvic floor connective tissue could be loose.The morphology of vaginal might be abnormal and pelvic organ might prolapsed slightly.ConclusionsThe morphology and structure of urogenital hiatus in late pregnancy women are different to those in nulliparas,the hiatus tend to be slackness.3D pelvic floor ultrasonography is an effective imaging method to observe the morphology and structure of urogenital hiatus in pregnancy women.

Objective To investigate the wake-promoting effect of vagus nerve stimulation (VNS) on coma rats after traumatic brain in-jury (TBI), and the related mechanism. Methods A total of 168 healthy Sprague-Dawley rats were randomly divided into blank group, TBI group, antagonist group and VNS group, 42 rats in each group. The latter three groups were established TBI model with impact, and the rats in coma at least 30 minutes were included. VNS group accepted VNS, the antagonist group were injected intralateroventricularly Orexin A receptor 1 (OXR1) antagonist SB334867, and TBI group accepted sham VNS. Their behaviors were observed to determine the level of con-sciousness six, twelve and 24 hours after intervention, while the expression ofγ-aminobutyric acid b1 receptor (GABAb1R) in prefrontal cortex was detected with immunohistochemistry and Western blotting. Results There were 42 rats in the blank group, 11 rats in TBI group, 13 rats in the antagonist group, and 28 rats in VNS group awakened finally. The expression of GABAb1R in prefrontal cortex ranged as TBI group, antagonist group, blank group and VNS group from more to less twelve and 24 hours after intervention under Western blotting (F>60.412, P<0.001), and it ranged as TBI group, antagonist group, VNS group and blank group under immunohistochemistry (H=15.121, P=0.002), with no significant difference among time points (H=3.028, P=0.220). Conclusion VNS can promote waking from coma in rats after TBI, which may relate with the decrease of GABAb1R in prefrontal cortex that induced by Orexin A.

Objective To evaluate the changes of levator ani muscle contractility in different postpartum periods by observing the contractility of postpartum women's levator ani muscle.Methods Forty-six postpartum women and 43 nulliparous women were included in the object.All of those went through translabial pelvic floor ultrasound examinations.Images of their levator hiatus would be recorded at the conditions of rest and contraction.The hiatal length (L)and the area (A)of levator hiatus were measured,then the differences were obtained between rest and contraction conditions,recording as ΔL andΔA.Relevant data were analyzed.Results There was no obvious statistical difference of L and A between the groups (P >0.05).The ΔL and ΔA of the 6-8 weeks were the minimum in this objective(P <0.05). However,there was no statistical difference between nulliparous women and the postpartum 6-8 month's women(P >0.05).Conclusions After delivery,the contractility of levator ani muscle became weaker,but could recovery effectively after about half a year.

Objective To study the change of levator urethra gap(LUG) in postpartum female using pelvic floor three-dimensional ultrasonography.Methods Totally 80 postpartum women and 30 nulliparas were examined by three-dimensional pelvic floor ultrasonography.The images were obtained at maximal pelvic floor muscle contraction,and then the morphology of puborectalis muscle on tomographic ultrasound imaging were observed and the right LUG and left LUG were measured.Results The puborectalis was intact in all nulliparas and 69 postpartum women.The puborectalis avulsion was find in 11 postpartum women.The LUG of postpartum group was greater than that of nullipara group (P ＜0.05).In postpartum group,the LUG of puborectalis avulsion was greater than that of intact puborectalis(P ＜0.05).There was no difference between the right LUG and left LUG in nullipara group and in the postpartum women with intact puborectalis (P ＞ 0.05).ConcIusions LUG is a good imaging parameter to evaluate the levator avulsion in postpartum women.

Objectives: To explore the expression regulation of type 1 and type 2 (Th1 and Th2) cytokines from serum of coal miners and the evaluation in surveillance of coal workers' pneumoconiosis, 630 coal miners were studied. Methods: A total of 90 male patients diagnosed as coal workers' pneumoconiosis (CWP) in a institute for occupational health and 19 male workers newly diagnosed as CWP patients was chosen as CWP group with simple random sampling method from a coal mine group from January 2013 to December in 2015. 180 male coal miners with abnormal but not diagnosed as CWP were selected as CWP suspected group with simple random sampling methods, meanwhile 180 male coal miners with normal chest X-ray photograph was as dust-exposed group by 1∶1 matched as age. And 161 healthy males accepted pre-employed examination were selected as control group, CWP suspected group, dust-exposed group and control group called as non-CWP group. According to screening test and diagnosis test, the basic information and occupational history of all subjects were collected, and cytokines including IL-1β, IL-8, IFN-γ, IL-6 and IL-10 of serum were detected. Receiver operator characteristic (ROC) curve was used to determine the optimal cutoff value of each cytokine. Area under curve (AUC), the validity and reliability were calculated and judged. Results: The average age of control group, dust-exposed group, CWP suspected group and CWP group were (27.4±5.0) , (43.4±10.7) , (48.2±6.2) , (64.7±7.0) years old, respectively. The median level of IL-1β, IL-8, IFN-γ and IL-6 in cases group (1 638.30, 2 099.49, 815.18,140.32 pg/ml) were higher than that of non-cases group (1 445.57, 1 402.26, 736.38, 95.73 pg/ml) (P<0.05) . The level of IL-8 (1 503.99 pg/ml) in CWP suspected group was higher than that of control group (1 295.67 pg/ml) and dust-exposed group (1 376.94 pg/ml) , but the level of IL-10 (654.08 pg/ml) was lower than that of control group (596.64 pg/ml) . The ratio of IFN-γ/IL-6 ranged from 5 to 8, and the ratio in CWP group (5.87) was lower than that of non-CWP group (7.61) . The IL-6 and IL-8 among the subjects of dust-exposed group in terms of the age distribution of among had reached statistical significance. According to ROC, the cutoff value of IL-1β, IL-6, IL-8, IL-10 and INF-γ reached 1 582.65, 116.53, 1 791.54, 581.08 and 792.69 pg/ml, respectively. The AUC was 0.668, 0.895, 0.859, 0.716 and 0.637, respectively. It was found that IL-6 and IL-8 could be used as biomarkers in detecting CWP, the sensitivity and specificity was 82.6% and 84.6%, 78.0% and 84.8%, respectively; Youden's index was 0.674 and 0.628 and the consistency rate was 84.3% and 83.7%, while Kappa value was 0.55 and 0.52. Conclusion There was Type 1 and type 2 cytokine dysregulation in CWP patients. IL-6 and IL-8 can be used as effective biomarkers to forecast lung injury before X-ray changes.

Humans ; Adult ; Invasive Pulmonary Aspergillosis ; Pneumonia, Viral/complications* ; Risk Factors ; Pulmonary Aspergillosis/complications*

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.