Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Effects of Postural Resonance on Skin Sympathetic Nerve Activity and Blood Pressure: A Pilot Study Evaluating Vascular Tone Baroreflex Stimulation Through Biofeedback.

Heart rate and vascular tension baroreflex exhibit resonance characteristics at approximately 0.1 and 0.03 Hz. In this study, we aimed to induce postural resonance (PR) through rhythmic postural adjustments. To assess the viability of this technique, we investigated the acute impacts of postural resonance on blood pressure, sympathetic nerve activity, and mood. Fifteen healthy study participants, consisting of 8 males and 7 females, were selected for this self-controlled study. Skin sympathetic nerve activity was continuously monitored during both the intervention and stress test on the experimental day. After PR intervention, the diastolic blood pressure and mean arterial pressure in the PR group exhibited significant reductions compared to the CON group (P = 0.032, CON = 71.67 ± 2.348, PR = 64.08 ± 2.35; P = 0.041, CON = 75.00 ± 2.17, PR = 81.67 ± 2.17). After PR intervention both left brachial ankle pulse wave velocity and right brachial ankle pulse wave velocity exhibited a significant reduction compared to pre-intervention levels (from 1115.86 ± 150.08 to 1048.43 ± 127.40 cm/s, p < 0.001; 1103.86 ± 144.35 to 1060.43 ± 121.35 cm/s, p = 0.018). PR intervention also led to a significant decrease in burst frequency and duration (P = 0.049; CON = 8.96 ± 1.17, PR = 5.51 ± 1.17) and a noteworthy decrease in burst amplitude and burst threshold during the cold-pressor test (P = 0.002; P = 0.002). Additionally, VAS scores exhibited a substantial increase following PR (P = 0.035, CON = 28.4 ± 4.49, PR = 42.17 ± 4.10). PR can induce resonance effects within the cardiovascular system, resulting in the effective reduction of blood pressure, skin sympathetic nerve activity and pulse wave velocity, and decreased burst amplitude and burst threshold of the sympathetic nerve during the cold-pressor test.

PRRSV Infection Induces Gasdermin D-Driven Pyroptosis of Porcine Alveolar Macrophages through NLRP3 Inflammasome Activation.

For more than 3 decades, mounting evidence has associated porcine reproductive and respiratory syndrome virus (PRRSV) infection with late-term abortions and stillbirths in sows and respiratory disease in piglets, causing enormous economic losses to the global swine industry. However, to date, the underlying mechanisms of PRRSV-triggered cell death have not been well clarified, especially in the pulmonary inflammatory injury characterized by the massive release of pro-inflammatory factors. Here, we demonstrated that PRRSV infection triggered gasdermin D-mediated host pyroptosis in vitro and in vivo. Mechanistically, PRRSV infection triggered disassembly of the trans-Golgi network (TGN); the dispersed TGN then acted as a scaffold for NLRP3 activation through phosphatidylinositol-4-phosphate. In addition, PRRSV replication-transcription complex (RTC) formation stimulated TGN dispersion and pyroptotic cell death. Furthermore, our results indicated that TMEM41B, an endoplasmic reticulum (ER)-resident host protein, functioned as a crucial host factor in the formation of PRRSV RTC, which is surrounded by the intermediate filament network. Collectively, these findings uncover new insights into clinical features as previously unrecognized mechanisms for PRRSV-induced pathological effects, which may be conducive to providing treatment options for PRRSV-associated diseases and may be conserved during infection by other highly pathogenic viruses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the pathogens responsible for major economic losses in the global swine industry. Characterizing the detailed process by which PRRSV induces cell death pathways will help us better understand viral pathogenesis and provide implications for therapeutic intervention against PRRSV. Here, we showed that PRRSV infection induces GSDMD-driven host pyroptosis and IL-1ß secretion through NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in vitro and in vivo. Furthermore, the molecular mechanisms of PRRSV-induced NLRP3 inflammasome activation and pyroptosis are elucidated here. The dispersed trans-Golgi network (TGN) induced by PRRSV serves as a scaffold for NLRP3 aggregation into multiple puncta via phosphatidylinositol 4-phosphate (PtdIns4P). Moreover, the formation of PRRSV replication-transcription complex is essential for TGN dispersion and host pyroptosis. This research advances our understanding of the PRRSV-mediated inflammatory response and cell death pathways, paving the way for the development of effective treatments for PRRSV diseases.

Optimal vaccination ages for emerging infectious diseases under limited vaccine supply.

Rational allocation of limited vaccine resources is one of the key issues in the prevention and control of emerging infectious diseases. An age-structured infectious disease model with limited vaccine resources is proposed to explore the optimal vaccination ages. The effective reproduction number [Formula: see text] of the epidemic disease is computed. It is shown that the reproduction number is the threshold value for eradicating disease in the sense that the disease-free steady state is globally stable if [Formula: see text] and there exists a unique endemic equilibrium if [Formula: see text]. The effective reproduction number is used as an objective to minimize the disease spread risk. Using the epidemic data from the early spread of Wuhan, China and demographic data of Wuhan, we figure out the strategies to distribute the vaccine to the age groups to achieve the optimal vaccination effects. These analyses are helpful to the design of vaccination schedules for emerging infectious diseases.

[Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model].

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1ß and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1ß, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

Spatiotemporal pattern recognition and dynamical analysis of COVID-19 in Shanghai, China.

Shanghai suffered a large outbreak of Omicron mutant of COVID-19 at the beginning of March 2022. To figure out the spatiotemporal patterns of the epidemic, a retrospective statistical investigation, coupled with a dynamic model, is implemented in this study. The hotspots of SARS-CoV-2 transmissions are identified, and strong aggregative effects in the decay stage are found. Besides, the visualization of disease diffusion is provided to show how COVID-19 disease invades all districts of Shanghai in the early stage. Furthermore, the calculations from the dynamic model manifest the effect of detections to suppress the epidemic dissemination. These results reveal the strategies to improve the spatial control of disease.

Analysis of the Geographic Transmission Differences of COVID-19 in China Caused by Population Movement and Population Density.

The coronavirus disease (COVID-19) has led to a global pandemic and caused huge healthy and economic losses. Non-pharmaceutical interventions, especially contact tracing and social distance restrictions, play a vital role in the control of COVID-19. Understanding the spatial impact is essential for designing such a control policy. Based on epidemic data of the confirmed cases after the Wuhan lockdown, we calculate the invasive reproduction numbers of COVID-19 in the different regions of China. Statistical analysis indicates a significant positive correlation between the reproduction numbers and the population input sizes from Wuhan, which indicates that the large-scale population movement contributed a lot to the geographic spread of COVID-19 in China. Moreover, there is a significant positive correlation between reproduction numbers and local population densities, which shows that the higher population density intensifies the spread of disease. Considering that in the early stage, there were sequential imported cases that affected the estimation of reproduction numbers, we classify the imported cases and local cases through the information of epidemiological data and calculate the net invasive reproduction number to quantify the local spread of the epidemic. The results are applied to the design of border control policy on the basis of vaccination coverage.

Rutin promotes white adipose tissue "browning" and brown adipose tissue activation partially through the calmodulin-dependent protein kinase kinase ß/AMP-activated protein kinase pathway.

Promoting white adipose tissue (WAT) "browning" and brown adipose tissue (BAT) activation could contribute to increasing energy expenditure. We explored the mechanisms by which the natural compound rutin induced adipose tissue differentiation and ameliorated obesity in vivo and in vitro. 3T3-L1 preadipocytes were cultured in adipogenic differentiation media with/out rutin. Male C57BL/6 mice (n = 6) were fed a high-fat diet (HFD) for 12 weeks with/out rutin. In HFD-fed mice, rutin treatment significantly inhibited weight gain, improved the metabolic profile of plasma samples, decreased the weights of epididymal WAT (eWAT), inguina WAT (iWAT), and liver, and adipocyte size. Furthermore, rutin also increased the expression of uncoupling protein 1 (Ucp-1) and other thermogenic markers in the WAT and BAT. In 3T3-L1 cells, rutin effectively reduced the formation of lipid droplets, stimulated the expression of thermogenic markers, and reduced the expression of adipogenic genes. Additionally, rutin markedly upregulated the AMP-activated protein kinase (AMPK) pathway, and these effects were diminished by treatment with the AMPK inhibitor compound C (CC). Pretreatment with the calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor STO-609 blocked the induction of thermogenic markers in 3T3-L1 cells by rutin. Our results indicated that rutin increased energy consumption, induced WAT "browning" and BAT activation, and thus was a promising target for the development of new therapeutic approaches to improve adipose tissue energy metabolism.

The Efficacy and Safety of Botulinum Toxin Type A Injections in Improving Facial Scars: A Systematic Review and Meta-Analysis.

BACKGROUND: Botulinum toxin type A (BTA) has a wide range of clinical applications, and its use in improving aesthetics is one of them. The aim of this study was to better assess the efficacy and safety of BTA in patients with facial scars. SUMMARY: We extracted the data of the visual analog scale (VAS) score, Vancouver scar scale (VSS) score, scar width, observer scar assessment scale (OSAS), patient scar assessment scale (PSAS), and/or drug-related adverse events. Five studies provided the data of VAS score, and the results showed that the VAS score in the BTA group was significantly higher than that in the control group. Three randomized controlled trials (RCTs) reported the VSS score. A statistically significant difference exists between the BTA group and the control group. Three RCTs reported the scar width after BTA treatment. A more favorable change was found in the BTA group with scar width even without statistical significance. Data about the OSAS and PSAS scores were available in two trials. There was no significant difference in OSAS and PSAS scores between the BTA group and the control group. Only three studies recorded three slight adverse events. There were no reports of severe complications. In conclusions, this study demonstrated that BTA has the potential to improve facial scars with an acceptable safety profile.

Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome.

INTRODUCTION AND OBJECTIVES: Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymph-adenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human RAG1 gene cause OS. MATERIALS AND METHODS: In this study, we investigated a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure. Parents of the proband were phenotypically normal. RESULTS: Karyotype analysis and chromosomal microarray analysis found no chromosomal structural abnormalities (46, XY) and no pathogenic copy number variations (CNVs) in the proband. Whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene in the proband. Sanger sequencing confirmed that both the proband parents were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters and one elder brother of the proband and in the 100 ethnically matched normal healthy individuals. This novel homozygous deletion (c.2662delC) leads to the frameshift, which finally results in the formation of the truncated protein (p.Leu888Phefs*3) V(D)J recombination-activating protein 1 with 890 amino acids compared with the wildtype V(D)J recombination-activating protein 1 of 1043 amino acids. Hence, it is a loss-of-function variant. CONCLUSIONS: Our present study expands the mutational spectrum of the RAG1 gene associated with OS. We also strongly suggested the importance of whole-exome sequencing for the genetic screening of patients with OS.

Vaccination games in prevention of infectious diseases with application to COVID-19.

Vaccination coverage is crucial for disease prevention and control. An appropriate combination of compulsory vaccination with voluntary vaccination is necessary to achieve the goal of herd immunity for some epidemic diseases such as measles and COVID-19. A mathematical model is proposed that incorporates both compulsory vaccination and voluntary vaccination, where a decision of voluntary vaccination is made on the basis of game evaluation by comparing the expected returns of different strategies. It is shown that the threshold of disease invasion is determined by the reproduction numbers, and an over-response in magnitude or information interval in the dynamic games could induce periodic oscillations from the Hopf bifurcation. The theoretical results are applied to COVID-19 to find out the strategies for protective immune barrier against virus variants.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

Association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects in offspring: a prospective cohort study. / å­•æœŸé‡é‡‘å±žå ƒç´ å’Œå¾®é‡å ƒç´ æ°´å¹³ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— ç›¸å ³æ€§çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS: Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.

Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment.

The mortality rate of critically ill patients with acute respiratory distress syndrome (ARDS) is 30.9% to 46.1%. The emergence of the coronavirus disease 2019 (Covid-19) has become a global issue with raising dire concerns. Patients with severe Covid-19 may progress toward ARDS. Mesenchymal stem cells (MSCs) can be derived from bone marrow, umbilical cord, adipose tissue and so on. The easy accessibility and low immunogenicity enable MSCs for allogeneic administration, and thus they were widely used in animal and clinical studies. Accumulating evidence suggests that mesenchymal stem cell infusion can ameliorate ARDS. However, the underlying mechanisms of MSCs need to be discussed. Recent studies showed MSCs can modulate immune/inflammatory cells, attenuate endoplasmic reticulum stress, and inhibit pulmonary fibrosis. The paracrine cytokines and exosomes may account for these beneficial effects. In this review, we summarize the therapeutic mechanisms of MSCs in ARDS, analyzed the most recent animal experiments and Covid-19 clinical trial results, discussed the adverse effects and prospects in the recent studies, and highlight the potential roles of MSC therapy for Covid-19 patients with ARDS.

Transcriptome Sequencing Identifies Potential Biomarker for White Matter Lesions Diagnosis in the Hypertension Population.

Hypertension is confirmed to be one of the major risk factors of leukoaraiosis (LA). However, the pathogenesis of LA is not completely understood and there is no reliable indicator for the early diagnosis of LA in the hypertensive population. This study was designed to explore the potential biomarker for LA diagnosis in patients with hypertension. And it serves as the basis for the further study of LA mechanism. In this study, This study included 110 subjects, including 50 in the LA group and 60 in the control group. First, we performed transcriptome sequencing and quantitative PCR (qPCR) in four samples from the LA group, and three from the control group (seven people) to identify relevant long non-coding RNAs (long ncRNAs or lncRNA). The 103 samples were used for qPCR validation of relevant lncRNAs and the results were consistent with the sequencing. In-depth bioinformatics analysis were performed on differentially expressed (DE) lncRNAs and mRNAs. Go-functional enrichment analysis was performed on DE mRNAs. Some DE mRNA were enriched to biological processes associated with LA, And some lncRNAs related to DE mRNAs were traceable through cis/trans analysis, suggesting that they might be regulated in some way. Additionally, potential biomarkers for LA diagnosis in the hypertension population were identified via RT-qPCR and receive operating characteristic curve (ROC) analysis of lncRNA. One lncRNA, AC020928.1, has been demonstrated to be potential biomarkers for LA diagnosis in the hypertension population. The results of the present study indicated that the lncRNA may have an important role in the pathogenesis of LA and may be a novel target for further research. As the relationship between lncRNAs and LA is just beginning to be unraveled, their specific mechanisms require further investigation.

Necrotizing funisitis and calcification of umbilical vein: case report and review.

BACKGROUND: Necrotising funisitis (NF) is a rare, chronic stage of funisitis, a severe inflammation of the umbilical cord and an important risk factor for fetal adverse outcomes. NF is characterized by yellow-white bands running parallel to the umbilical blood vessels. These bands consist of inflammatory cells, necrotic debris, and calcium deposits. Calcification is visible in ultrasonography, which makes it possible to suspect NF when umbilical vascular wall calcification is detected by prenatal ultrasonography. CASE PRESENTATION: Ultrasonography revealed calcification of the umbilical venous wall in an expectant 31-year-old woman who was gravida 1, para 0. The woman required emergency cesarean section because of fetal distress and suspected umbilical cord torsion at 31 weeks gestation. The root of the umbilical cord was quite fragile and broke during the operation. The pathological results on the placenta showed histologic chorioamnionitis and NF. The infant was diagnosed to have neonatal sepsis and acidosis after delivery but was discharged without severe complications after a one-month hospitalization that included antibiotic and supportive therapy. CONCLUSION: NF is a rare and severe inflammation of the umbilical cord. Umbilical vascular wall calcification discovered in prenatal ultrasonography is diagnostically helpful.

Study on the correlation between vaginal bleeding in first trimester and preterm birth: A birth cohort study in Lanzhou, China.

OBJECTS: To investigate the correlation between first trimester vaginal bleeding and preterm birth (PB), and to offer suggestions on the perinatal health care and preterm birth prevention. METHODS: A birth cohort study was conducted on 10 179 pregnant women. Unconditional logistic regression model was used to evaluate the associations between vaginal bleeding and preterm birth in sub-preterm groups. RESULTS: Of the 10 179 pregnant women included, a total of 1001 women suffered from vaginal bleeding during the first trimester, of which 119 suffered from PB. Any vaginal bleeding increased the risk of PB. Severe bleeding was a high-risk factor of PB, associated with 4.8-fold risk of very PB, 2.7-fold risk of spontaneous PB without PROM (premature rupture of membrane) and 4.6-fold risk of medical induced PB. Bleeding prolonged more than 1 week increased 66% risk of PB and 36% risk of PB on initial episode happened in 5-12 weeks of gestation age, especially in moderate PB, in medical-induced PB and in spontaneous PB with PPROM (preterm premature rupture of membrane which is one cause of PB). Mild bleeding or bleeding within 1 week or initial episode happened within 4 weeks of gestation age possibly had no influence on PB. CONCLUSION: Vaginal bleeding in the first-trimester was an independent risk factor for PB. The severity, duration and initial time of vaginal bleeding had different effects on different subtypes of PB.

Modeling HIV Dynamics Under Combination Therapy with Inducers and Antibodies.

A mathematical model is proposed to simulate the "shock-kill" strategy where broadly neutralizing antibodies (bNAbs) are injected with a combination of HIV latency activators to reduce persistent HIV reservoirs. The basic reproductive ratio of virus is computed to extrapolate how the combinational therapy of inducers and antibodies affects the persistence of HIV infection. Numerical simulations demonstrate that a proper combination of inducers and bNAbs can drive the basic reproductive ratio below unity. Interestingly, it is found that a longer dosage interval leads to the higher HIV survival opportunity and a smaller dosage interval is preferred, which is fundamental to design an optimal therapeutic scheme. Further simulations reveal the conditions under which the joint therapy of inducer and antibodies induces a large extension of viral rebound time, which highlights the mechanism of delayed viral rebound from the experiment (Halper-Stromberg et al. in Cell 158:989-999, 2014). Optimal time for cessation of treatment is also analyzed to aid practical applications.

Long Noncoding RNA loc285194 Expression in Human Papillomavirus-Positive and -Negative Cervical Squamous Cell Carcinoma, C33A, and SiHa Cells and Transforming Growth Factor-ß1.

BACKGROUND This study aimed to investigate the expression of long noncoding RNA (lncRNA) loc285194 in cervical squamous cell carcinoma (CSCC) biopsies that were positive and negative for human papillomavirus (HPV) and in human CSCC cell lines SiHa and C33A and to investigate the overexpression of lncRNA loc285194. MATERIAL AND METHODS Cervical biopsy tissue and plasma samples from 66 patients with histologically confirmed CSCC, that were HPV16-positive (N=22), HPV18-positive (N=27), and HPV-negative (N=17), and healthy controls (N=20) and human CSCC cell lines SiHa (HPV16-positive) and C33A (HPV-negative) were studied. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA loc285194 in cervical biopsies and plasma. Enzyme-linked immunosorbent assay (ELISA) and Western blot were used to measure levels of transforming growth factor-ß1 (TGF-ß1). A lncRNA loc285194 expression vector was constructed and transfected into SiHa and C33A cells that underwent a transwell assay for cell migration. RESULTS Expression of lncRNA loc285194 was downregulated in HPV-positive and HPV-negative tissue samples and plasma from patients with CSCC and distinguished between patients and healthy controls. Plasma levels of loc285194 and TGF-ß1 were significantly correlated with the presence of CSCC. In SiHa and C33A cells, TGF-ß1 expression was downregulated, and cell migration was inhibited following lncRNA loc285194 overexpression. Although lncRNA loc285194 expression was not affected by TGF-ß1 treatment, its effects on cell migration were reduced by TGF-ß1. CONCLUSIONS The expression of lncRNA loc285194 inhibited the migration of CSCC cells in vitro through the inactivation of TGF-ß1.

Folic acid supplementation, dietary folate intake and risk of preterm birth in China.

PURPOSE: Folic acid supplementation has been suggested to reduce the risk of preterm birth. However, results from previous epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake during pre- and post-conception reduces the risk of preterm birth. METHODS: We analyzed data from a birth cohort study conducted between 2010 and 2012 in Lanzhou, China, including 10,179 pregnant women with live singleton births. RESULTS: Compared to non-users, folic acid supplement users with >12-week duration had a reduced risk of preterm birth (OR 0.67, 95 % CI 0.55-0.83) with a significant dose-response relationship (P for trend = 0.01). A similar pattern was observed for spontaneous preterm birth. Stronger associations were seen for ever use of folic acid supplement and very preterm birth (OR 0.50, 95 % CI 0.36-0.69) and spontaneous very preterm birth (OR 0.42, 95 % CI 0.29-0.63). Dietary folate intake during preconception and pregnancy were also associated with reduced risk of preterm birth (OR 0.68, 95 % CI 0.56-0.83, OR 0.57, 95 % CI 0.47-0.70 for the highest quartiles, respectively), particularly for spontaneous very preterm (OR 0.41, 95 % CI 0.24-0.72, OR 0.26, 95 % CI 0.15-0.47 for the highest quartiles, respectively). There were also decreased risks of preterm birth observed per 10-µg increase in dietary folate intake, and similar associations were found after stratification by folic acid supplementation status. CONCLUSIONS: Our results suggest that folic acid supplementation and higher dietary folate intake during preconception and pregnancy reduces the risk of preterm birth, and the protective effect varies by preterm subtypes.