水稻典型品种日本晴和IR24根系微生物组的解析

植物的各项生命活动与其根系微生物组密不可分,且根系微生物组的组成易受到植物生长环境和基因型的影响。为进一步探究中国北方地区种植的不同品种水稻根系微生物组的差异及其相互作用机制,本研究以种植于北京昌平和上庄农场的水稻典型品种日本晴(Nipponbare)和IR24为研究对象,基于16S rRNA基因扩增子测序技术获得根系微生物组序列,利用多样性分析、组成型分析、机器学习的随机森林和网络分析等方法,对旺盛生长期的两种不同品种的水稻根系微生物组进行详细比较。研究发现,种植地点和水稻基因型显著影响了水稻根系微生物组的群落结构,不同基因型导致了根系微生物组在物种分类组成上以及细菌间相互关系的差异,而且根系微生物组能作为生物标记跨地点区分宿主的基因型。本研究结果为深入理解我国北方种植的水稻根系微生物组的组成规律以及从根系微生物与植物互作的角度对品种进行改良提供了数据和理论基础。

Pravastatin alleviates lipopolysaccharide-induced placental TLR4 over-activation and promotes uterine arteriole remodeling without impairing rat fetal development

Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been suggested as potential prevention or treatment of preeclampsia,although evidence remains inadequate.Herewith,we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide（LPS）-induced rat preeclampsia model,through targeting the TLR4/NF-κB pathway.The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day（GD） 12,（101.33±2.49） mmHg vs.（118.3±1.37） mmHg,P〈0.05] and urine protein level [maximum decline on GD9,（3,726.23± 1,572.86） μg vs.（1,991.03 ±609.37）μg,P〈 0.05],which were elevated following LPS administration.Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats（34.10% vs.8.99%,P〈0.05）.Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment.These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum.Additionally,no obvious abnormalities in fetal liver,brain,and kidney were found after administration of pravastatin.These results provide supportive evidence for use of pravastatin in preventing preeclampsia.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host’s ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

Clinical Study of Acupotomy Trinity Lysis Combined with Rehabilitation Training for Spastic Paralysis after Stroke

Objective:To study the clinical efficacy of acupotomy trinity lysis combined with rehabilitation training in the treatment of spastic paralysis after stroke,and to provide guidance for clinical diagnosis and treatment.Methods:From July 2019 to November 2020,119 patients with post-stroke spastic paralysis who were admitted to our hospital's encephalopathy department were selected as the research objects,and 61 patients were divided into acupuncture combined with rehabilitation training group as the observation group by random number table method.58 patients were divided into the rehabilitation training group as the control group.After 21 days of treatment,they passed the modified Ashworth Spasm Scale(MAS)grading scale score,Clinical Spasm Index(clinical spasm index,CSI)assessment,Fugl,Meyer exercise function scale(FMA)Score,Modified Barthel Index Score,and compare the clinical efficacy after treatment.Results:After treatment,the total effective rate of the observation group(95.08%)was higher than that of the control group(86.21%),and the difference was statistically significant(P<0.05);Before treatment,the contrast difference of MAS,FMA,CSI scores and modified Barthel index scores of the two groups of patients is not statistically significant;After treatment,the MAS scores and CSI scores of the elbow and knee joints of the observation group[(1.52±0.81)(1.46±0.83)(5.87±2.12)]were significantly lower than those of the control group[(2.17±0.68)(2.03±0.79)(8.36±2.41)];FMA upper limb and lower limb scores and modified Barthel index[(51.87±4.41)(30.21±5.05)(72.41±5.81)]of the observation group were significantly higher than those of the control group[(44.26±4.78)(28.45±4.23)(68.65±6.09)],the difference was statistically significant(P<0.05).Conclusion:Acupotomy trinity lysis combined with rehabilitation training is effective in treating patients with post-stroke spastic paralysis.It provides a safe,reliable and clinically effective new program,which is worthy of popularization and application.

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.

Abietane derived diterpenoids as Ca_(v)3.1 antagonists from Salvia digitaloides

Nineteen diterpenoids, including saldigitin A(1) bearing an unprecedented 10-methylated 6/7/6 carbon ring system, two new icetexanes(2, 3), and two new nor-abietanes(5, 6) were characterized from the roots of Salvia digitaloides. Their structures were elucidated by the analysis of the spectroscopic data,X-ray crystallography, and TDDFT calculations of ECD spectra. The novel architecture of 1 should be biogenetically derived through the cleavage and re-cyclization of the B/C rings from the normal abietane skeleton. Biologically, 1–5 exhibited noticeable inhibitions on Ca_(v)3.1 low voltage-gated Ca2+channel(LVGCC), with IC50values in the range of 3.43–11.70 μmol/L. They are the first example of diterpenoids with 6/7/6 carbon rings system as Ca_(v)3.1 antagonists.

Using the Delphi Technique to Achieve Consensus on Prevention and Treatment of Preterm Single Birth in China

Objective::This study aimed to reach a consensus among obstetric experts on the prevention and treatment of preterm single births in China.Methods::Based on the scoping literature review and the 2014 edition of preterm birth of Clinical Diagnosis and Treatment guidelines,we generated the Delphi survey statements with five evaluation dimensions,including the definition of preterm birth,exclusion of risk factors for preterm birth,prevention,and prediction of preterm birth,treatment of preterm birth,and evaluation of intervention outcomes of preterm birth.Obstetric experts from the Obstetrics and Gynecology Branch of the Chinese Medical Association formed the expert group for this survey.All the obstetric experts participated two-round modified Delphi survey via an anonymous online survey and an online panel.Mean scores,rank sum,full score ratio,and the lowest score ratio were calculated to reflect the concentration of expert opinions.The coefficient of variation and Kendall W coefficient were used to reflect the expert opinion coordination degree of the survey statement.Results::The expert response rate for both rounds of surveys was 100%(41/41).Experts reached an agreement on 36 statements in five dimensions of preterm birth prevention and treatment in the first round of the survey and reached a consensus on the remaining 13 statements in the second round.A total of 49 statements(mean scores≥3,full score ratio≥20%,coefficient of variation≤0.3)were explicitly included in this guideline to form recommendations,while the remaining three clinical issues that did not reach a consensus require further determination based on evidence quality.The Kendall W coefficient in the two rounds of the Delphi survey were 0.20(P<0.001)and 0.29(P<0.001).Conclusion::The five dimensions and 49 statements,agreed upon through a two-round Delphi study,determined the recommended statements to be included in the updated guidelines for the prevention and treatment of preterm birth in China.The defined lower limit is set at≥28 gestational weeks;however,an update has been made to the definition of premature birth,specifying that"with the consent of the mother and her family,treatment is not abandoned for viable infants≥26 gestational weeks."

IL-32-driven neutrophil activation in preeclampsia

Preeclampsia(PE),a pregnancy-specific syndrome,is the leading cause of maternal and fetal morbidity and mortality and has been labeled the“great obstetrical syndrome”[1,2].Although the etiology and pathophysiology of PE are still not precisely understood,uncontrolled excessive inflammatory responses in the maternal decidua basalis and circulation have been identified as key contributors to PE development.

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility

Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.

Upregulation of CD81 in trophoblasts induces an imbalance of Treg/Th17 cells by promoting IL-6 expression in preeclampsia

The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia(PE),in which an imbalance between the inflammation-limiting regulatory T cells(Tregs)and the inflammationmediating Th17 cells plays an essential role.Previously,we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells(fetal component)participated in the pathogenesis of PE.However,as one of the potential immune regulatory molecules,whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified.Thus,we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers.Here,we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate(placental maternal side)and peripheral blood of patients with PE.In vitro culture of naïve T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs,which was dependent on the paracrine signaling of IL-6 in trophocytes,induced by CD81.In a CD81-induced PE rat model,we found a significant shift of T cell differentiation towards Th17 cells,and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells.These results define a vital regulatory cascade involving trophocyte-derived CD81,IL-6,and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.

Collagen-binding basic fibroblast growth factor improves functional remodeling of scarred endometrium in uterine infertile women: a pilot study

Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2(b FGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of b FGF100 μg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients(2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved.Histological study showed blood vessel density increased obviously. Three patients(3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the b FGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.

Placenta-derived IL-32β activates neutrophils to promote preeclampsia development

Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia(PE).Neutrophils(PMNs)are activated in PE patients,but the mechanism and consequences of PMN activation need to be further explored.Here,we demonstrated that interleukin-32(IL-32)expression was significantly upregulated in syncytiotrophoblasts(STBs)and that IL-32β was the major isoform with increased expression in the placenta of severe PE(sPE)patients.Furthermore,the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients,indicating that IL-32 in the serum is derived mainly from the placenta.Then,in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells(HUVECs)and enhance the expression of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)in HUVECs,which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870.In addition,we showed that IL-32β mainly activated PMNs by binding to proteinase 3.Finally,IL-32β administration induced a PE-like phenotype in a pregnant mouse model.This study provides evidence of the involvement of IL-32β in the pathogenesis of PE.

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman＇s syndrome

Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1^+ Cells

In order to clarify the effects of 17β-estradiol （E2） on natural killer （NK） cells and the possibly regulatory mechanisms, we obtained highly purified and viable NK cells from C57BL/6J mouse spleen by a magnetic cell sorter （MACS）. These cells were treated with E2 and then their cytotoxicity and proliferative capacity were examined. To further investigate the mechanisms on the effect of E2 on NK cells, expressions of activationassociated markers （CD69, CD122） and inhibitory receptors （CD94, Ly49）, and intracellular cytokine production were analyzed. At last, we performed the cDNA microarray to explore the possible involved genes. We found that E2 could suppress NK cell cytotoxicity and proliferative capacity in vitro. E2 reduced NK cell cytotoxicity and proliferative capacity, which may be through influencing the phenotypes and cytokine expression of NK cells, mainly involving CD94 and IFN-γ. Furthermore, regulation of Stat4, Fyn, Sh2d1a, Eat2, Cd244, Irf1, Runxl, Irf7, Irf5, Esrra and Nr5a1 genes may be related to the cytotoxicity, proliferation and cytokine production of E2-mediated purified NK ceils.

A Summary of Chinese Expert Consensus on Fetal Growth Restriction (An Update on the 2019 Version)

Fetal growth restriction(FGR)is a common complication of pregnancy associated with higher rates of perinatal mortality and morbidity,as well as a variety of long-term adverse outcomes.To standardize the clinical practice for the management of FGR in China,Fetal Medicine Subgroup,Chinese Society of Perinatal Medicine,Chinese Medical Association and Maternal-Fetal Medicine Committee,Chinese Society of Obstetrics and Gynecology,Chinese Medical Association organized an expert committee to provide official consensus-based recommendations on FGR.We evaluated the evidence provided by relevant high-quality literature,performed a three-round Delphi study and organized face-to-face meetings with experts from multidisciplinary backgrounds.The consensus includes the definition,prenatal screening,prevention,diagnosis,monitoring and management of FGR.

CSOG MFM Committee Guideline: Management of Hepatitis B During Pregnancy and Prevention of Mother-to-Child Transmission of Hepatitis B Virus (2020)

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is the main cause of chronic hepatitis B. The prevention of MTCT plays a critical role in control chronic hepatitis B. The main purpose of the present clinical guidelines is to aid healthcare providers in managing pregnant women with positive HBsAg and in preventing MTCT of HBV. We recommend: (1) all pregnant women require prenatal screen for hepatitis B serological markers;(2) newborn infants of mothers with negative hepatitis B surface (HBsAg) require administration of hepatitis B vaccine on a 0, 1, and 6 month-schedule;(3) newborn infants of mothers with positive HBsAg need hepatitis B immunoglobulin (HBIG) and birth dose vaccine within 12 hours (the sooner the better) after birth, followed by injection of the second and third dose of hepatitis B vaccine at the age of one and six months respectively;(4) in preterm neonates or neonates with poor health conditions born to HBsAg-positive mothers, the immunoprophylaxis measures should be appropriately taken;(5) to further reduce MTCT of HBV, pregnant women with HBV DNA levels >2×105 IU/mL or positive hepatitis B e antigen may receive oral antivirals, starting from 28 to 32 weeks of gestation and discontinuing the drug on the delivery day;(6) cesarean section is not recommended to reduce MTCT of HBV;(7) breastfeeding is recommended in infants of HBsAg-positive mothers, regardless of maternally positive hepatitis B e antigen, maternal nipple injury or bleeding, oral mucosal injury in neonates or infants;(8) breastfeeding is recommended in infants born to HBsAg-positive mothers who require continuation of antiviral therapy after delivery, and the infants should be followed up to observe whether adverse effects develop;and (9) the infants born to HBsAg-positive mothers should be tested for hepatitis B serological markers at the age of 7-12 months, and those who are negative for HBsAg and anti-HBs should receive three doses of hepatitis B vaccine on the 0, 1, and 6 month-schedule as soon as possible.

CD81,a new actor in the development of preeclampsia

CD81 is a widely expressed transmembrane protein that provides a scaffold for signaling molecules and orchestrates interactions among membrane-associated proteins to initiate signaling cascades related to cell migration,adhesion,and fusion1.CD81 exerts a wide range of regulatory effects on immune cells.In B cells,CD81 facilitates the assembly of CD19-CR2/CD21 and B-cell receptor complexes at tetraspanin-enriched signaling microdomains,lowering the threshold dose of antigen required to trigger B-cell clonal expansion and antibody production.

Conservative Evolution of Hepatitis B Virus Precore and Core Gene During Immune Tolerant Phase in Intrafamilial Transmission

Hepatitis B virus(HBV)is characterized with high mutations,which is attributed to the lack of proof-reading of the viral reverse transcriptase and host immune pressure.In this study,31 HBV chronic carriers from 14 families were enrolled to investigate the evolution of the same original HBV sources in different hosts.Sequences of pre-C and C(pre-C/C)genes were analyzed in eight pairs of HBV-infected mothers with longitudinal sera(at an interval of 6.0–7.2 years)and their children(5.5–6.7 years old),and in 15 adults(21–78 years old)from six families with known intrafamilial HBV infection.The pre-C/C sequences had almost no change in eight mothers during 6.0–7.2 years and their children who were in immune tolerant phase.The pre-C/C sequences from the 15 adults of six families,mostly in the immune-clearance phase or the low replicative phase,showed various diversified mutations between individuals from each family.Compared to a reference stain(GQ205441)isolated nearby,the pre-C/C in individuals in immune tolerant phase showed 98.56%–99.52%homology at nucleotide level and 99.5%–100%homology at amino acid level.In contrast,multiple mutations were developed in the immune-clearance phase or the low replicative phase,affecting immune epitopes in core gene and G1896 in pre-C gene.The results indicate that the evolution of new HBV variants is not mainly resulted from the spontaneous error rate of viral reverse transcription,but from the host immune pressure.

Umbilical cord artery-derived perivascular stem cells for treatment of ovarian failure through CD146 signaling

Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cells(PSCs),known as mural cells covering the vasculature,are essential for blood vessel formation and postulated as progenitors of mesenchymal stem cells(MSCs).2,3 We previously established umbilical cord artery-derived PSCs(UCA-PSCs)and Wharton’s jelly-derived MSCs(WJ-MSCs)and UCAPSCs display optimal angiogenic capacity in vitro.4 Therefore,we explored the angiogenesis and pro-angiogenesis mechanisms of UCA-PSCs and provided them as an efficient treatment strategy for ovarian failure.

Advancements in endometrial epithelial stem cell research

The human endometrium is a dynamic tissue that undergoes approximately 400 cycles of proliferation,decidualization,shedding,and regeneration.With the observation that superficial stratum functionalis loss and swift reepithelization occur every month,an original hypothesis is that stem cells,especially endometrial epithelial stem cells harbored in the deeper basalis,take on the responsibility of repairing and regenerating the endometrial functionalis.