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Background: The transjugular intrahepatic portosystemic shunt (TIPS) is an important technique for treating complications related to portal hypertension in patients with cirrhosis, and the number of publications in the TIPS field continues to rise., Aim: To facilitate an understanding of the research status and hotspots in the field of TIPS using CiteSpace bibliometric analysis., Methods: CiteSpace is a software that depicts the strength of relationships through graphics and connections with diverse functionalities and can be used to analyze the status and hotspots of areas of research. Articles on TIPS in the Web of Science Core Collection were retrieved, and CiteSpace software was used to visualize and analyze the number of publications, journals, countries, institutions, authors, keywords, and citations., Results: A total of 985 relevant documents were included in the analysis. From January 2013 to December 2022, the number of publications increased annually. The journal, institution, and author with the greatest number of publications in the field of TIPS are the Journal of Vascular and Interventional Radiology , the University of Bonn, and Jonel Trebicka, respectively. The main keywords used in this field are "transjugular intrahepatic portosystemic shunt", "portal hypertension", "cirrhosis", "management", "stent", "hepatic encephalopathy", "refractory ascite", "survival", "risk", and "variceal bleeding". The greatest obstacle to TIPS placement is currently the occurrence of hepatic encephalopathy. The research hotspots are the mechanism, risk factors, management, and control of hepatic encephalopathy., Conclusion: This bibliometric analysis reported the research status and hotspots of TIPS. Research on postoperative hepatic encephalopathy is the research hotspot in this field., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among men who have sex with men (MSM) are escalating public health concerns. This study aimed to explore (1) the reliability of self-reported sexual positioning as an indicator for rectal CT and NG screening, and (2) factors associated with rectal CT and NG infections in Shenzhen, China., Methods: A cross-sectional study was conducted in 2 settings in Shenzhen, China, from April 1, 2021, to March 31, 2022. Data on sociodemographic characteristics, sexual behaviors, and basic CT knowledge were collected. Urine and self-collected rectal swabs were collected for CT and NG testing., Results: In total, 195 MSM participated in the study, and 5.1% tested positive for urogenital CT, 29.2% for rectal CT, 1.0% for urogenital NG, and 8.2% for rectal NG. Among those who reported exclusively insertive anal sex, 69.2% of CT infections and 85.7% of NG infections would have remained undetected with urine testing alone. Risk factors for rectal CT infection included engaging in both insertive and receptive anal sex, with a significant association found for coinfection with rectal NG., Conclusions: Self-reported sexual positioning was found to be an unreliable indicator for CT and NG screening, as a substantial proportion of infections would have remained undetected. The findings suggest that CT and NG screening in China should be offered to all MSM regardless of self-reported sexual positioning, and that the dual CT/NG testing is recommended., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare no conflict of interest. This study was supported by the Sanming Project of Medicine in Shenzhen (No. SZSM201611077)., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: This study aimed to identify use of various treatments and their association with the use of antibiotics and patient reported clinical recovery in Chinese adults with acute cough., Methods: An online survey recruiting people who had recently experienced cough was conducted. Their sociodemographic, clinical characteristics, treatments received and their perceived changes in symptoms were collected. Factors influencing avoidance of antibiotics and improvement in symptoms were explored., Results: A total of 22,787 adults with recent acute cough completed the questionnaire, covering all 34 province-level administrative units in China. Most respondents were male (68.0%), young (89.4%, aged 18-45), educated to university/degree or postgraduate level (44.6%), with a median cough severity of 6/10 on a numerical rating scale. Nearly half of the participants (46.4%) reported using antibiotics, among which 93.1% were for presumed upper respiratory tract infections (URTIs). Pharmacies (48.8%) were the most common source of antibiotics. Fewer patients took antibiotics after taking CHM (14.9%), compared to those who started with home remedies (18.0%), or allopathic non-antibiotic medication (25.0%). Antibiotics, allopathic non-antibiotic medications, CHM and home remedies were all perceived beneficial in relieving cough., Conclusions: Chinese adult responders report use of a considerable variety of treatments alone or in combination for acute cough. Patient-reported clinical recovery was similar regardless of treatment. There is likely a high proportion of inappropriate use of antibiotics for treatment of simple acute cough. As the majority of respondents did not use antibiotics as a first-line, and use of CHM was associated with relief of cough symptoms and reduction in the use of antibiotics, this presents an important opportunity for prudent antibiotic stewardship in China., (© 2023 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Objective: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors., Methods: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes., Results: A total of 528 patients were enrolled in the study. Based on both the psychometric hepatic encephalopathy score and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Multivariate analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.022-1.063, P < 0.001), duration of education (OR 0.891, 95% CI 0.832-0.954, P = 0.001), comorbidities of cardiovascular diseases, hypertension, cerebral apoplexy or diabetes mellitus (OR 2.072, 95% CI 1.370-3.133, P < 0.001), Child-Pugh score (OR 1.142, 95% CI 1.029-1.465, P = 0.025), and blood urea nitrogen concentration (OR 1.126, 95% CI 1.038-1.221, P = 0.004) were associated with CHE episodes. According to the Chronic Liver Disease Questionnaire, CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), indicating a poor health-related quality of life. Based on a stepwise Cox regression hazard model, we established a nomogram for determining the probabilities of CHE episodes, and the area under the receiver operating characteristic curve was 0.733 (95% CI 0.679-0.788) and 0.713 (95% CI 0.628-0.797) in the training and validation cohorts., Conclusions: CHE is a common complication of cirrhosis in China. Large-scale studies with long-term follow-up are needed to determine the natural history of Chinese CHE patients., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To summarize the clinical features of special portal hypertension-Abernethy malformation reported at home and abroad. Methods: The relevant literature on Abernethy malformation published at home and abroad from January 1989 to August 2021 was collected. Patients'clinical features, imaging and laboratory test results, diagnosis, treatment, and prognosis were analyzed. Results: A total of 380 cases were included from 60 and 202 domestic and foreign literatures. Among them, there were 200 cases of type I, with 86 males and 114 females, and the average age was (17.08±19.42) years, while there were 180 cases of type II, with 106 males and 74 females, and the average was (14.85±19.60) years. The most common reason for the first visit of an Abernethy malformation patient's was gastrointestinal system symptoms such as hematemesis and hematochezia caused by portal hypertension (70.56%). Multiple malformations were present in 45.00% of type Ⅰ and 37.80% of type Ⅱ patients. The most prevalent condition was congenital heart disease (62.22%, and 73.53%). Complications related to Abernethy malformation was occurred in 127 and 105 cases with type I and type II, respectively, with liver lesions in 74.02% (94/127) and 39.05% (42/105) and hepatopulmonary syndrome of 33.07% (42/127) and 39.05% (41/105), respectively. The imaging diagnosis of type I and type II Abernethy malformations were mainly based on abdominal computed tomography (59.00%, and 76.11%). Liver pathology was performed in 27.10% of patients. Blood ammonia increased by 89.06% and 87.50%, and AFP increased by 29.63% and 40.00% in laboratory findings. 9.76% (8/82) and 6.92% (9/130) died, while 84.15% (61/82) and 88.46% (115/130) had improved conditions after medical conservative, or surgical treatment. Conclusion: Abernethy malformation is a rare disease in which congenital portal vein development abnormalities lead to significant portal hypertension and portasystemtic shunt. Patients often seek medical treatment for gastrointestinal bleeding and abdominal pain. Type Ⅰ is more common in women, often associated with multiple malformations, and prone to secondary intrahepatic tumors. Liver transplantation is the main treatment method. Type Ⅱ is more prevalent in males, and shunt vessel occlusion is the first treatment choice. Overall, type Ⅱ has a better therapeutic impact than type Ⅰ.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population., Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies., Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035)., Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action., Competing Interests: Authors X-FQ and YL are employed by OrigiMed Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chen, Lin, Zhang, Lai, Li, Lin, Guo, Xiao, Mok, Ren, Wen, Cao, Lin, Qi, Liu and Liao.)

Background: Aberrant activation of Wnt/β-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/β-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity., Methods: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/β-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of β-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo., Results: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with β-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase β-Trcp1 for β-catenin binding, thereby decreasing β-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner β-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with β-catenin expression levels., Conclusions: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/β-catenin signaling via SHARPIN-mediated stabilization of β-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive β-catenin signaling in a subset of human gastric cancers.

Background: Chinese herbal medicine is widely used in combination with usual care for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China. Chinese patent medicine Shufeng Jiedu (SFJD) capsules is widely used for respiratory infectious diseases. This review aims to evaluate effectiveness and safety of SFJD for AECOPD., Methods: A systematic review of randomised controlled trials (RCTs) in patients with AECOPD, who received SFJD as a single intervention or as add-on treatment to usual care. PubMed, the Cochrane Library, EMBASE, Scopus, Web of Science and four Chinese databases were searched from inception to April 2019. Two authors screened trials, extracted data, and assessed risk of bias, independently. Meta-analysis was performed using RevMan 5.3 software. We performed subgroup analyses and sensitivity analyses according to the predefined protocol. Quality of evidence was assessed using GRADE., Results: Thirteen RCTs (1036 patients, with 936 inpatients) were included, all compared SFJD in combination with usual care (including antibiotics) to usual care alone. The mean age of participants ranged from 52 to 67 years, with approximately 60% male. Due to lack of blinding and other factors, all trials were of high risk of bias. SFJD was associated with a significant reduction in treatment failure, from 20.1 to 8.3% (11 trials; 815 patients; relative risk 0.43, 95% confidence interval [CI] 0.30 to 0.62), and duration of hospital stay (2 trials; 79 patients; mean difference - 4.32 days, 95% CI - 5.89 to - 2.75 days). No significant difference in adverse events was found between SFJD and control groups., Conclusion: Low certainty evidence suggests SFJD may bring additional benefit in reducing treatment failure, shorten hospital stay, and improving symptoms. Further large, high quality RCTs are needed to confirm its benefit and safety., Trial Registration: PROSPERO CRD42019133682.

Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells in vitro and their dissemination at distal organs in vivo . Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and β-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors. SIGNIFICANCE: These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4869/F1.large.jpg., (©2019 American Association for Cancer Research.)

Objective: The effects of low molecular weight heparin (LMWH) on severe acute pancreatitis (SAP) have been controversial. We aimed to evaluate the efficacy of LMWH on prognosis of SAP by systematic review and meta-analysis., Methods: We searched relevant studies published up to March 2019 in five databases (MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials in Cochrane Library, China National Knowledge Infrastructure, and the Chinese Journal of Science and Technology of VIP database)., Results: Sixteen randomized controlled trials with 1625 patients were included in the final analysis. Most studies were from China. In analysis of laboratory parameters and clinical scores, SAP patients receiving LMWH treatment had lower white blood cell counts, C-reactive protein level, Acute Physiology and Chronic Health Evaluation II score, and computed tomography severity index. In clinical outcomes, SAP patients who received LMWH treatment had shorter hospital stay (pooled mean difference [95% confidence interval; CI] -8.79 [-11.18, -6.40], P < .01), lower mortality (pooled risk ratio [RR] [95% CI] 0.33 [0.24-0.44], P < .01), lower incidences of multiple organ failure (pooled RR [95% CI] 0.34 [0.23-0.52], P < .01), pancreatic pseudocyst (pooled RR [95% CI] 0.49 [0.27-0.90], P = .02), and operation rate (pooled RR [95% CI] 0.39 [0.31-0.50], P < .01)., Conclusions: LMWH could improve the prognosis of SAP, and has a potential role in reducing hospital stay, mortality, incidences of multiple organ failure, pancreatic pseudocyst, and operation rate., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: The aim of this study was to evaluate the efficacy of artificial neural networks (ANN) in predicting intra-abdominal infection in moderately severe (MASP) and severe acute pancreatitis (SAP) compared with that of a logistic regression model (LRM)., Methods: Patients suffering from MSAP or SAP from July 2014 to June 2017 in three affiliated hospitals of the Army Medical University in Chongqing, China, were enrolled in this study. A univariate analysis was used to determine the different parameters between patients with and without intra-abdominal infection. Subsequently, these parameters were used to build LRM and ANN., Results: Altogether 263 patients with MSAP or SAP were enrolled in this retrospective study. A total of 16 parameters that differed between patients with and without intra-abdominal infection were used to construct both models. The sensitivity of ANN and LRM was 80.99% (95% confidence interval [CI] 72.63-87.33) and 70.25% (95% CI 61.15-78.04), respectively (P > 0.05), whereas the specificity was 89.44% (95% CI 82.89-93.77) and 77.46% (95% CI 69.54-83.87), respectively (P < 0.05). ANN predicted the risk of intra-abdominal infection better than LRM (area under the receiver operating characteristic curve: 0.923 [0.883-0.952] vs 0.802 [0.749-0.849], P < 0.001)., Conclusions: ANN accurately predicted intra-abdominal infection in MSAP and SAP and is an ideal tool for predicting intra-abdominal infection in such patients. Coagulation parameters played an important role in such prediction., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Multiple organ failure (MOF) is a serious complication of moderately severe (MASP) and severe acute pancreatitis (SAP). This study aimed to develop and assess three machine-learning models to predict MOF., Methods: Patients with MSAP and SAP who were admitted from July 2014 to June 2017 were included. Firstly, parameters with significant differences between patients with MOF and without MOF were screened out by univariate analysis. Then, support vector machine (SVM), logistic regression analysis (LRA) and artificial neural networks (ANN) models were constructed based on these factors, and five-fold cross-validation was used to train each model., Results: A total of 263 patients were enrolled. Univariate analysis screened out sixteen parameters referring to blood volume, inflammatory, coagulation and renal function to construct machine-learning models. The predictive efficiency of the optimal combinations of features by SVM, LRA, and ANN was almost equal (AUC = 0.840, 0.832, and 0.834, respectively), as well as the Acute Physiology and Chronic Health Evaluation II score (AUC = 0.814, P > 0.05). The common important predictive factors were HCT, K-time, IL-6 and creatinine in three models., Conclusions: Three machine-learning models can be efficient prognostic tools for predicting MOF in MSAP and SAP. ANN is recommended, which only needs four common parameters.

Lateral root (LR) formation and development play a vital role in plant development by permitting the establishment of branched root systems. It is well known that nutrient availability controls LR development. Moreover, LR development is fine-tuned by a myriad of hormonal signals. Many transcription factors (TFs) participate in LR development. Here, we discuss the TFs involved in the nitrate and auxin signaling pathways and how these function in the regulation of LR formation and development in chrysanthemum. AtTCP20 is a plant-specific TF, which can modulate LR development in response to nitrate. The roles of CmTCP20 in LR development were identified by overexpression in chrysanthemum and heterologous expression in Arabidopsis. Overexpression of CmTCP20 significantly increased the number and average length of LRs compared with the wild type in chrysanthemum and Arabidopsis. We also found that CmTCP20 positively influenced auxin accumulation in the LRs at least partly by improving auxin biosynthesis, transport and response, thereby promoting LR development. Moreover, we found that CmTCP20 interacts with an auxin response factor, CmARF8, which also can be induced by nitrate and combined to proximal sites in the upstream promoter region of CmCYCB1;1 to positively regulate the cell cycle. The CmTCP20-CmARF8 heterodimer links nitrate and auxin signaling and converts cell-cycle signals to regulate LR initiation and growth., (� The Author(s) 2019. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Human tumorigenesis resembles embryogenesis by aberrant activation of several developmental pathways including Wnt/β-catenin signaling. Norrin is an atypical ligand for Frizzled receptor that is preferentially expressed in the endothelium to promote retinal vascularization during development. However, its expression pattern and potential roles in human cancers remain unclear. Here we report that Norrin expression is elevated in the parenchymal cells, but not endothelial cells, in gastric cancer (GC). Moreover, Norrin is required for growth and invasion of GC cells and its expression status is associated with unfavorable outcomes. However, analysis of the TGCA database demonstrates that Norrin expression status is not correlated with key target genes of Wnt/β-catenin signaling. Among several signaling pathways hyperactivated in cancer, Norrin-depleted GC cells also display down-regulated AKT signaling except the canonical Wnt/β-catenin signaling. Consistently, small molecule-induced cytosolic activation of AKT partially rescues the proliferative and invasive capability of Norrin-depleted cells. Together, these findings suggest a novel role of Norrin in gastric tumorigenesis that could be exploited for adjuvant therapy against the deadly malignancy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC). We identify a member of the microrchidia (MORC) protein family, MORC2, as an inhibitor of the Hippo pathway by controlling upstream Hippo regulators, neurofibromatosis 2 (NF2) and kidney and brain protein (KIBRA). Mechanistically, MORC2 forms a complex with DNA methyltransferase 3A (DNMT3A) at the promoters of NF2 and KIBRA, leading to their DNA hyper-methylation and transcriptional repression. As a result, NF2 and KIBRA are crucial targets of MORC2 to regulate confluence-induced activation of Hippo signaling and contact inhibition of cell growth under both physiological and pathological conditions. The MORC2-NF2/KIBRA axis is critical for maintaining self-renewal, sorafenib resistance, and oncogenicity of HCC cells in vitro and in nude mice. Furthermore, MORC2 expression is elevated in HCC tissues, associated with stem-like properties of cancer cells, and disease progression in patients. Collectively, MORC2 promotes cancer stemness and tumorigenesis by facilitating DNA methylation-dependent silencing of Hippo signaling and could be a potential molecular target for cancer therapeutics.

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.

Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1, also known as PTPN6) is a nonreceptor protein tyrosine phosphatase that acts as a negative regulator of inflammation. Emerging evidence indicates that SHP-1 plays a role in inhibiting the progression of hepatocellular carcinoma (HCC). However, the role of SHP-1 in hepatocarcinogenesis remains unknown. Here, we find that levels of SHP-1 are significantly downregulated in human HCC tissues compared with those in noncancerous tissues ( P < 0.001) and inversely correlate with tumor diameters ( r = -0.4130, P = 0.0002) and serum α-fetoprotein levels ( P = 0.047). Reduced SHP-1 expression was associated with shorter overall survival of patients with HCC with HBV infection. Overexpression of SHP-1 suppressed proliferation, migration, invasion, and tumorigenicity of HCC cells, whereas knockdown of SHP-1 enhanced the malignant phenotype. Moreover, knockout of Ptpn6 in hepatocytes ( Ptpn6 HKO ) enhanced hepatocarcinogenesis induced by diethylnitrosamine (DEN) as well as metastasis of primary liver cancer in mice. Furthermore, systemic delivery of SHP-1 by an adenovirus expression vector exerted a therapeutic effect in an orthotopic model of HCC in NOD/SCID mice and DEN-induced primary liver cancers in Ptpn6 HKO mice. In addition, SHP-1 inhibited the activation of JAK/STAT, NF-κB, and AKT signaling pathways, but not the MAPK pathway in primary hepatocytes from DEN-treated mice and human HCC cells. Together, our data implicate SHP-1 as a tumor suppressor of hepatocarcinogenesis and HCC progression and propose it as a novel prognostic biomarker and therapeutic target of HCC. Significance: The nonreceptor protein tyrosine phosphatase SHP-1 acts as a tumor suppressor in hepatocellular carcinoma. Cancer Res; 78(16); 4680-91. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Background: Our previous study has demonstrated that hepatocyte nuclear factor 1α (HNF1α) exerts potent therapeutic effects on hepatocellular carcinoma (HCC). However, the molecular mechanisms by which HNF1α reverses HCC malignancy need to be further elucidated., Methods: lncRNA microarray was performed to identify the long noncoding RNAs (lncRNAs) regulated by HNF1α. Chromatin immunoprecipitation and luciferase reporter assays were applied to clarify the mechanism of the transcriptional regulation of HNF1α to HNF1A antisense RNA 1 (HNF1A-AS1). The effect of HNF1A-AS1 on HCC malignancy was evaluated in vitro and in vivo. RNA pulldown, RNA-binding protein immunoprecipitation and the Bio-Layer Interferometry assay were used to validate the interaction of HNF1A-AS1 and Src homology region 2 domain-containing phosphatase 1 (SHP-1)., Results: HNF1α regulated the expression of a subset of lncRNAs in HCC cells. Among these lncRNAs, the expression levels of HNF1A-AS1 were notably correlated with HNF1α levels in HCC cells and human HCC tissues. HNF1α activated the transcription of HNF1A-AS1 by directly binding to its promoter region. HNF1A-AS1 inhibited the growth and the metastasis of HCC cells in vitro and in vivo. Moreover, knockdown of HNF1A-AS1 reversed the suppressive effects of HNF1α on the migration and invasion of HCC cells. Importantly, HNF1A-AS1 directly bound to the C-terminal of SHP-1 with a high binding affinity (KD = 59.57 ± 14.29 nM) and increased the phosphatase activity of SHP-1. Inhibition of SHP-1 enzymatic activity substantially reversed the HNF1α- or HNF1A-AS1-induced reduction on the metastatic property of HCC cells., Conclusions: Our data revealed that HNF1A-AS1 is a direct transactivation target of HNF1α in HCC cells and involved in the anti-HCC effect of HNF1α. HNF1A-AS1 functions as phosphatase activator through the direct interaction with SHP-1. These findings suggest that regulation of the HNF1α/HNF1A-AS1/SHP-1 axis may have beneficial effects in the treatment of HCC.

Root system architecture is an important agronomic trait by which plants both acquire water and nutrients from the soil and adapt to survive in a complex environment. The adaptation of plant root systems to environmental constraints largely depends on the growth and development of lateral roots (LRs). MADS-box transcription factors (TFs) are important known regulators of plant growth, development, and response to environmental stimuli. However, the potential mechanisms by which they regulate LRs development remain poorly understood. Here, we identified a MADS-box chrysanthemum gene CmANR1, homologous to the Arabidopsis gene AtANR1, which plays a key role in the regulation of LR development. qRT-PCR assays indicated that CmANR1 was primarily expressed in chrysanthemum roots and was rapidly induced by exposure to high nitrate concentrations. Ectopic expression of CmANR1 in Arabidopsis significantly increased the number and length of emerged LRs compared to the wild-type (col) control, but had no obvious affect on primary root (PR) development. We also found that CmANR1 positively influenced auxin accumulation in LRs at least partly by improving auxin biosynthesis and transport, thereby promoting LR development. Furthermore, we found that ANR1 formed homo- and heterodimers through interactions with itself and AGL21 at its C-terminal domain. Overall, our findings provide considerable new information about the mechanisms by which the chrysanthemum MADS-box TF CmANR1 mediates LR development by directly altering auxin accumulation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of carotid artery stenting(CAS) on cognitive function and brain function based on changes of a battery of neuropsychological tests and magnetic resonance imaging. Methods: Thirty-three patients were included with 17 in the stent-placement group and 16 in the control group (receiving medical treatment), among whom, the unilateral or bilateral severe internal carotid artery stenosis was confirmed by cerebral vascular angiography in the department of Interventional Radiology and Vascular Surgery of Zhongda Hospital Southeast University from June 2015 to September 2016.Neuropsychological tests and rest-state blood oxygenation level dependent fMRI were performed at the baseline and six months follow-up.The baseline characteristics and follow-up changes were compared in each group. Results: The overall cognitive function of the stent-placement group was statistically significantly improved ( P <0.05) compared with control group, mainly in the executive function, memory, attention and other aspects.The value of amplitude of low-frequency fluctuation(ALFF) showed statistically significant increase ( P <0.05, Alphasim correction) in left prefrontal cortex ( t =5.861 3, P <0.05), the somatosensory association cortex in left superior parietal lobe( t =5.601 2, P <0.05) and bilateral motor cortical area in posterior frontal lobe ( t =5.288 5, P <0.05). The ALFF showed statistically significant decrease ( P <0.05, Alphasim correction) in left retrosplenial cingulate cortex( t =-5.590 4, P <0.05), left insular cortex ( t =-6.340 8, P <0.05), right insular cortex ( t =-8.129 9, P <0.05) and left dorsal anterior cingulate cortex ( t =-5.584 8, P <0.05). There was no statistically significant difference ( P >0.05, Alphasim correction)between baseline and follow-up results in control group.Besides, the ALFF changes of the left insular cortex ( r =-0.591, P =0.033) and bilateral motor cortical area ( r =-0.659, P =0.014) were negatively correlated with auditory verb learning test (AVLT) score changes.The ALFF change of bilateral motor cortical area was negatively correlated with the AVLT-delay score change ( r =-0.588, P =0.034). And the ALFF change on right insular cortex and the frontal assessment battery (FAB) score change was positively correlated ( r =0.638, P =0.025). Conclusions: The overall cognitive function of patients with carotid artery stenosis significantly improve after CAS compared with medical treatment.The change of ALFF value in related brain area is also statistically significant.ALFF Change most in area of Default Mode Network may suggest a mechanism of postoperative neurological recovery in patients with carotid artery stenosis.

Liver cancer is a common malignant tumor. Although the overall incidence and mortality rates of liver cancer has been decreasing in recent years, the incidence of nonalcoholic fatty liver disease (NAFLD)-associated liver cancer tends to increase. The health and social issues brought by NAFLD-associated liver cancer have attracted more and more attention, and its epidemiology, pathogenesis, and diagnosis and treatment await further research. This article summarizes the current epidemiology and pathogenesis of NAFLD-associated liver cancer.

Hordei Fructus Germinatus has been always used by "stir-frying" as a traditional medicine and the endpoint judgment of "fragrant" and "yellow" has been the focus and difficulty in frying process research. In this study, a quantitative calibration model between index components and NIRS was established in order to rapidly detect the contents of reducing sugar, total amino acids, total flavonoids, A420 and moisture; besides, an endpoint judgment method of frying process was put forward based on the "component change rate". Near-infrared spectra of samples with different frying time were collected, and a quantitative analysis model based on near-infrared spectroscopy was established to optimize the parameters such as spectral pretreatment and modeling band. HCA and PLS-DA were used to study the relationship between component and "stir-frying", and the endpoint of frying process was determined. The established calibration model had a good performance that the correlation coefficients between the predicted results and the actual measured values were both more than 0.9, with predicted relative deviations less than 10%. Hordei Fructus Germinatus with different frying time was divided into 4 categories by HCA analysis. PLS-DA analysis showed that total reducing sugar had a significant contribution to distinguishing the Hordei Fructus Germinatus of different frying time. When the change rate of total reducing sugar was 80%, it could judge that the endpoint of frying had been obtained. Results showed that NIRS could not only quickly and accurately determine the contents of reducing sugar, total amino acid, total flavonoid, A420 and moisture in Hordei Fructus Germinatus samples of different frying time, but also judge the endpoint of frying in the process. This study provided a new method for the evaluation and endpoint judgment of "stir-frying" process in research of traditional Chinese medicine., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

It is not scientific to explain that fried Fructus Hordei Germinatus is more effective than row Fructus Hordei Germinatus in resolving food stagnation from the aspects of amylase, tricine and other "active ingredients". In the present experiment, the contents of active ingredients including quercetin, tricine, kaempferol, catechin, ferulic acid and inactive ingredients including 5-hydroxymethyl furfural, acrylamide in frying process were determined by HPLC. The dynamic change rules of active ingredient and inactive ingredients in the frying process were investigated by HCA, PCA and PLS-DA analysis. The results showed that the Fructus Hordei Germinatus samples with different frying temperatures were classified into 4 groups by HCA and PCA analysis. PLS-DA analysis showed that frying temperature mainly impacted the contents of inactive ingredients including 5-hydroxymethyl furfural and acrylamide, with less effects on the contents of active ingredients. Simultaneously, with the increase of time in frying process, the content of 5-hydroxymethyl furfural was significantly increased from 2 min and became stable at 16 min, while the content of acrylamide was increased continuously from 18 min. Based on the variation of the contents of various ingredients, samples at different frying time were classified into 5 groups. The results showed that the content changes of "inactive ingredients" were closely related to the duration and degree of frying process, and the dynamic change rules of "inactive ingredients" can provide scientific basis for evaluating the frying process and elucidating the efficacy mechanism of Fructus Hordei Germinatus., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Field experiments, including four levels of N application 0, 18, 24, 30 g N·m -2 , were carried out to clarify the effects of nitrogen fertilization on N accumulation and translocation in lea-ves as well as the seed quality of oil peony (Paeonia ostii 'Fengdan Group'). The results showed that the nitrogen application significantly increased the height, canopy, flower diameter and flower dry mass. The heights under the treatments 24 and 30 g N·m -2 increased by 14.7% and 15.2% compared with CK, respectively. Moreover, the nitrogen application improved seed yield. The highest seed yields were acquired under the treatments 24 and 30 g N·m -2 , which were 15.2% and 15.4% higher than that of CK, respectively. The N accumulation and translocation in leaves and the N accumulation in seeds all increased with the nitrogen application level. The greatest leaf contribution proportion was acquired under the treatment 24 g N·m -2 . The nitrogen application significantly increased the contents of protein N, total amino acid, and some saturated and unsaturated fatty acids in seeds. In this experiment, the N input of 24 g N·m -2 was optimal to obtain the higher N translocation amount, N translocation efficiency and N contribution proportion from leaves to seeds, seed yield as well as the contents of protein N, amino acid and unsaturated fatty acids.

Previous studies provided substantial evidence of a striking suppressive effect of hepatocyte nuclear factor 4α (HNF4α) on hepatocellular carcinoma (HCC). Apoptosis signal-regulating kinase 1 (ASK1) is involved in death receptor-mediated apoptosis and may acts as a tumor suppressor in hepatocarcinogenesis. However, the status and function of ASK1 during HCC progression are unclear. In this study, we found that HNF4α increased ASK1 expression by directly binding to its promoter. ASK1 expression was dramatically suppressed and correlated with HNF4α levels in HCC tissues. Reduced ASK1 expression was associated with aggressive tumors and poor prognosis for human HCC. Moreover, ASK1 inhibited the malignant phenotype of HCC cells in vitro. Intratumoral ASK1 injection significantly suppressed the growth of subcutaneous HCC xenografts in nude mice. More interestingly, systemic ASK1 delivery strikingly inhibited the growth of orthotopic HCC nodules in NOD/SCID mice. In addition, inhibition of endogenous ASK1 partially reversed the suppressive effects of HNF4α on HCC. Collectively, this study highlights the suppressive effect of ASK1 on HCC and its biological significance in HCC development. These outcomes broaden the knowledge of ASK1 function in HCC progression, and provide a novel potential prognostic biomarker and therapeutic target for advanced HCC., Competing Interests: No potential conflicts of interest were disclosed by the authors.

Objective: To learn the spatial and temporal patterns of primary syphilis and secondary syphilis in Shenzhen and to provide evidence for carrying out further research on syphilis., Methods: Primary syphilis and secondary syphilis cases among residents in Shenzhen between 2005 and 2009 (n = 11 303) were geocoded at street office level (n = 55) based on residence at the time of diagnosis. Both spatial and space-time scan statistics were used to identify clusters of street office by using SaTScan software., Results: In the purely spatial analyses, clusters were seen in the junction of the Baoan district and Nanshan district (Xinan, Xixiang, Nanshan and Nantou street office) and in the region near Hong Kong (Dongmen, Shekou, and Futian street office), as well as in the other streets where entertainment industry was relatively developed (Longhua, Huafu, Huangbei and Cuizu street office). The clusters had not changed much in the first four years, but nine clusters appeared in 2009. Annually, the most likely clusters were located in Longhua (2005, P ≤ 0.001, RR = 3.34), Bamboo (2006, P ≤ 0.001, RR = 9.59), Huafu (2007, 2008 years, P ≤ 0.001, RR values were 4.18 and 4.75) and Cuizu (2009, P ≤ 0.001, RR = 8.02). In the space-time scan analysis, we found 16 significant clusters, which were similar to the pure spatial analyses. However, regional difference were also found, with the most likely cluster was the Guiyuan street office in 2006., Conclusion: Spatial and space-time scan statistics seemed to be effective ways in describing the circular disease clusters. We have had a better understanding on spatial and temporal patterns of primary syphilis and secondary syphilis in Shenzhen through spatial and space-time scan statistics of syphilis surveillance data in the recent years. The changes of spatial and temporal patterns of primary syphilis and secondary syphilis were also described by SaTScan software, which also provided useful reference for the preventive strategies on sexually transmitted diseases as well as on HIV. Useful information was also provided for financial investment and cost-effective studies.

Objective: To explore the risk factors underlying congenital syphilis (CS) and to build a hazards model to assess the risk of CS in offspring born to mothers with syphilis treated in gestation., Methods: This prospective study observed 554 pregnant women with syphilis and their offspring recruited from August 2002 to May 2007 in Shenzhen Centre for Chronic Disease Control and Prevention. After treatment, all the women were followed up until the diagnosis of CS in their offspring was confirmed or denied. Comparisons were made between women bearing infants with CS and women bearing infants without CS to reveal the risk factors for CS. ORs and their 95% CI were calculated for each risk factor by using logistical regression analysis., Results: Twenty-nine (5.2%) infants were diagnosed with CS. Univariable analyses showed that the reciprocal logarithm of the titre of non-treponemal antibodies in mothers (log (1/T); OR=11.18, p<0.001), gestational week (GW) at treatment (OR=1.10, p<0.001) and the interaction between these two variates (OR=1.09, p<0.001) was associated with CS. Multivariable analysis showed that only the interaction was significantly associated with CS (OR=1.09, p=0.047)., Conclusions: The risk of CS could be predicted by the interaction between GW x log (1/T). Early treatment given to women with syphilis during antenatal care may be the only effective method to decrease the risk of CS.

Information on the prevalence and incidence of sexually transmitted infections is important for developing prevention and control strategies and allocating human and financial resources. However, there are no available estimates of such information for many areas in China. In this study, we used the existing data to make a preliminary estimation of syphilis infections in Shenzhen city, in south-eastern China. Data on prevalence rates of syphilis infections among different populations were obtained from the local HIV/sexually transmitted disease second-generation surveillance programme, and the sizes of different populations were estimated based on the most recently available figures. It was estimated that 83,760 (range 77,490-90,020) people are currently infected with syphilis, giving a prevalence of 0.71-0.82% (0.76% on average) in Shenzhen. Around 18% of these syphilis infections occur among men who have sex with men and another 15.8% and 8.7% occur among female sex workers and their clients, respectively. These estimates suggest that a combination of unprotected paid sex and sex between men may be sustaining the epidemic of syphilis in the study area. The preliminary estimates will assist the government in planning and improving its comprehensive intervention programmes for the future control and prevention of syphilis.

Recombinant thanatin analog (TH1) is a cationic 20-amino-acid antibacterial peptide with a conserved cysteine disulfide bond. It exhibits a broad antibacterial spectrum. Different strategies have been developed to produce small antibacterial peptides using recombinant techniques. To date, no efforts to obtain large quantities of active recombinant TH1 have been reported. This study describes the synthesis of TH1 gene, the heterologous fusion expression of the peptide in Escherichia coli, and the bioactive assay of released TH1. By constructing the expression plasmid (pET32a-TH1), high yields of soluble TH1 fusion protein (0.416 g/L) can be obtained in E. coli. Further optimization studies have been carried out to increase the expression of TH1 in different culture conditions, with the final amount of pure TH1 being 13.2 mg/L. The results show that the expression system provides a simple and reliable strategy for generating large quantities of TH1 by soluble fusion expression in E. coli.

Objective: To observe the effect of human cytomegalovirus infection on the host cellular DNA synthesis and expression of cyclones., Methods: HCMV infected cell was established in vitro by incubating passage cultured HEL and HCMV AD169 strain with different titres. The cells were synchronized in the G0/G1 stage by contact inhibition and infected with strain AD169 of HCMV at an MOI of 5 PFU per cell. We harvested infected cell at different time 0 h, 3 h, 6 h, 24 h, 72 h and 96 h post infection. Then the cell cycle progress was measured. Meanwhile, the DNA content and expression of proteins of cycline E, cycline A and cycline D1 were determined with FCM and Western Blot respectively., Results: We found that the amount of S stage cell infected by HCMV had increased dramatically, and that of G2/M stage cell reduced during 24 h-96 h PI, and no G2/M stage cell was detected within 96 h PI. The content of 2N DNA maintained unchangeable for 24 h after infection and the content of total DNA in infected cells began to increase within 48 h PI, and the substantial cell with 2N DNA were observed 72 h after infection. However, DNA content was not altered in control group of normal HEL and HCMV PAA group. CyclinE protein was induced 12 h PI and peak induction occurred 24 h PI in contact-inhibited cells. CyclinA protein expression was not induced in HCMV infected density-arrested cells. The abundance of cyclinD1 decreased 24 h PI., Conclusion: The expression of cyclinE and activity of cyclinE/Cdk2 kinase are increased obviously in G0/G1 stage cells infected with HCMV, which may induce the cell cycle to overpass G1/S restriction point and make the cell cycle arrested in later G1 stage. HCMV can not activate cellular DNA synthesis, and increase of total DNA content in infected cells result from the viral DNA replication.

Objective: To evaluate the effects of Jinye Baidu Granule ( JYBDG), a traditional Chinese medicine compound prescription, on fetal growth and development with maternal active human cytomegalovirus infection., Methods: A prospective, randomized and controlled trial was adopted during January 1996 to June 2002. From the pregnant women with an abnormal pregnant history, 240 cases were screened to be infected by human cytomegalovirus (HCMV) by enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). They were assigned according to the random number table to two groups. The 122 cases in the treatment group were administrated with JYBDG, one package each time, three times a day for two continuous weeks, while the other 118 in the control group did not receive any treatment. The negative conversion rate of both HCMV-IgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate between the two groups were compared, and fetal growth and development in partial fetuses were also observed., Results: The negative conversion rate of both HCMV-lgM and HCMV late mRNA, the positive rate of HCMV-DNA in placenta and the intrauterine transmission rate in the treatment group were 77. 05% (94/122), 48. 98% (48/98) and 21.74% (10/46) respectively, while those in the control group were 38. 14% (45/118), 67.50% (54/80) and 52.63% (20/38) respectively, all showing significant difference between the two groups (P<0. 01). Totally 35 normal infants and 11 abnormal infants were born in the treatment group, and the number in the control group was 20 and 18 respectively, and comparison between the two groups showed significant difference (P<0.01). Six months of child birth, the scores of both mental development index (MDI) and psychomotor development index (PDI) of infants were higher in the treatment group (20 cases) than those in the control group (20 cases), but there was no significant difference between the two groups (P>0.05)., Conclusion: JYBDG could decrease the intrauterine transmission of HCMV and is beneficial to fetal growth and development.

Objective: To observe histologic changes of human cytomegalovirus (hCMV)-infected explants of first trimester human placenta and expression of hCMV gene in the hCMV-infected explants, and investigate the mechanism of intrauterine transmission of hCMV from mother to fetus., Methods: The first trimester placenta explants cultures were carried out, and they were infected with hCMV for 10 days. The expression of hCMV immediate early protein (IEP) 72-IEP86 were determined using indirect-immuno fluorescent assay, and in situ hybridization method was used to examine the hCMV late gene (LG) mRNA. For histologic evaluation of morphological changes in villi, transmission electron microscope was used., Results: (1) Typical hCMV-induced lesions bearing hCMV IEP72-IEP86 were consistently localized in the trophoblast of covering placenta villi, interstitial cell and vascular endothelia cell 12 hours after infection, and were predominant in cytotrophoblast. (2) Replication of hCMV in placenta explants culture occurred from 12 hours to 24 hours and disappeared since 48 hours after infection with different concentrations of hCMV when examined by in situ hybridization. (3) Tissue integrity and viability of first trimester placenta explants were obtained in culture for 10 days and then explants were infected with different concentrations of hCMV [100 tissue culture infectious doses (TCID(50)), 200 TCID(50) and 300 TCID(50)], the progression of the infection was observed in the tissue that maintained its normal cellular organization under light microscope. But typical inflammation of cellular organization was observed under transmission electron microscope., Conclusions: (1) A flash replication of hCMV in placental explants culture occurs; IEP72-IEP86 may be in intrauterine infection of hCMV for a long time. (2) There are pathological ultrastructure changes in hCMV-infected explants.

Objective: To study the inhibitory effect of Jinye Baidu Preparation (JBP), a Chinese medicinal preparation, on human cytomegalovirus protein kinase pu197 and to explore its molecular mechanism in treating human cytomegalovirus (HCMV) infection., Methods: Expression of the HCMV pu197mRNA in infected cells was measured by semi-quantitative RT-PCR before and after intervention of JBP or Ganciclovir (GCV), and effect of the two medicines on the proliferation activity of the infected cells was observed by MTT., Results: Both JBP and GCV showed obvious inhibitory action on HCMV pu197mRNA. They could significantly enhance the proliferation activity of the cells 72 hours after HCMV infection., Conclusion: JBP could inhibit the gene expression and duplication of HCMV by inhibiting the gene expression of HCMV protein kinase pu197 to enhance the proliferation activity of the infected cells so as to achieve its anti-virus action.

Objective: To explore the clinical efficacy of the combined therapy of zinc supplement and Jinye Baidu granule (JBG) on human cytomegalovirus (HCMV) infection., Methods: One hundred and forty patients with positive HCMV-IgM were randomly divided into four groups, with 35 cases in each group, that is, the control group (only medicated with JBG), the high-, moderate- and low-dose zinc combined groups (treated with JBG combined with zinc gluconate tablet at dose of 30 mg, 20 mg, 10 mg every day respectively). The negative conversion rate of HCMV-IgM was observed., Results: Insignificant difference in the negative conversion rate was shown in comparison of the control group with the low dose group (P > 0.05), and in comparison of the high dose with the moderate dose group (P > 0.05); however, the rate was significantly lower in the control group than that in the moderate dose and high dose group (P < 0.05)., Conclusion: Combined therapy of zinc supplement and JBG can significantly increase the negative conversion rate of HCMV-IgM. The optimal dosage of zinc gluconate tablet was 20 mg once a day.

Objective: To study the relationship between late mRNA and the cytopathic effect(CPE) and ultrastructural features after human cytomegalovirus (HCMV) infection in vitro., Methods: Human embryo fibroblast cells(HEL) were infected with HCMV AD169 strain. The expression of the HCMV late mRNA was measured by semiquantitative RT-PCR, the cytopathic effect (CPE) and the cell ultrastructure were observed by means of light microscopy and electron microscopy, respectively., Results: The HCMV late mRNA could be detected 12 hours postinfection and increased gradually, but the CPE appeared 48 hours postinfection in HEL cells. The HCMV infected cells exhibited significant mitochondrial enlargement and the number of mitochondrial ridge deletion, the cisternae lumen of endoplasmic reticulum (ER) dilation and vacuolization (at the end age). The mature nucleocapsid could be observed 96 hours postinfection., Conclusion: The ultrastructural changes have an intimate correlation with the expression of HCMV late mRNA and play an important role in the life circle of the virus. HCMV late mRNA may serve as a indicator of the clinical effect of treatment in active HCMV infection.

Objective: To investigate the difference of anticytomegaloviral activity of three kinds of traditional Chinese medicines which are the injections of Jinye Baidu, Radix Isatidis and Indigowoa in vitro., Method: The inhibitory activity of three traditional Chinese medicines against human cytomeglovirus (HCMV AD169) infected human embryo lung fibroblasts (HELF) was observed by cytopathic effect method (CPE) and MTT method in vitro. According their value of A, anticytomegaloviral activity has evaluated., Result: Experimental study in vitro showed that the 50% toxicity dose (TD50) of Jinye Detoxifying, Radix Isatidis root and Indigowoa were 20, 10.23, 20.23 g x L(-1) respectively; the 50% inhibitory concertration (IC50) were 5.65, 3, 5.71 g x L(-1) respectively; the therapeutic index (TI) were 3.54, 3.41 and 3.54 respectively. It suggested that three traditional Chinese medicines had anticytomeglovirus activity and their effect increased with their concentration., Conclusion: Three traditional Chinese medicines of the parenteral solution of Jinye Detoxifying, Radix Isatidis root and Indigowoa have antiviral activity when they are diluted in 1:200. They are safe and valuable drug for inhibiting cytomeglovirus infection.

Objective: To investigate the effect of Toxoplasma (Tox) infection during pregnancy to the development of fetus and infant., Methods: Enzyme linked immunoadsorbent assay (ELISA) was employed to detect Tox-IgM in peripheral blood of 3,908 pregnant women. To Tox-IgM positive cases, the umbilical blood of their neonates were sampled to detect Tox-IgM and abortion tissues were sampled to detect Tox-DNA with polymerase chain reaction. Infection group included 95 cases whose Tox-IgM or DNA were positive, and control group consisted of 119 cases without infection. Different supervision methods were used to periodically observe the intelligence development of infants 3 and 12 months after birth in these two groups. After initial intervention, verbal intelligence quotients (VIQs), performance intelligence quotients (PIQs) and full scale intelligence quotients (FSIQs) were assessed when the infants were 1 and 4 years old of these two groups., Results: The incidences of abortion, stillbirth, pre-term delivery, FGR and malformation in infection group were 12 cases (12.6%), 5 cases (5.3%), 4 cases (4.2%), 4 cases (4.2%) and 3 cases (3.2%), while the incidences of these abnormalities in control group were 3 cases (2.7%), 1 cases (0.9%), 2 cases (1.8%), 2 cases (1.8%) and 1 cases (0.9%). Comparing with these two groups, there was significant difference (P < 0.01). Relative risk (RR) of these 5 abnormalities was 4.7, 5.9, 2.3, 2.3 and 3.6 respectively. Mental development index (MDI) and psychomotor development index (PDI) of infants in infection group were 93 +/- 13 and 101 +/- 16. They were significantly lower than that of control group, which were 107 +/- 17 and 111 +/- 13. There was significant difference between these two groups (P < 0.05). After intervention in 1 and 4 years, their VIQs, PIQs and FSIQs were apparently improved (P < 0.05)., Conclusion: Congenital Tox infection is closely correlated with abnormal pregnancy outcomes and infantile mental retardation. Early intervention can improve intelligence development.

Objectives: To investigate the effects of intrauterine human cytomegalovirus (HCMV) infection on pregnancy outcomes and infant development., Methods: The study group consisted of the HCMV-IgM-positive offspring of 75 pregnant women, and a control group of the non-infected offspring of 73 pregnant women. Chorionic villi, amnionic fluid, and umbilical blood were obtained to detect HCMV-late mRNA with a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The pregnancy outcomes were followed up. For all offspring, neurological development was evaluated with neurosonography, audiologic development with the brainstem auditory evoked potential (BAEP), and psychomotor development with the Beyley Scale of Infant Development (BSID)., Results: In the study group the positive rate of late mRNA was 50% in the chorionic villi and 67.65% in the amnionic fluid and the umbilical blood; the incidence of abnormal pregnancy outcomes (abortion, preterm delivery, stillbirth, etc.) was much higher than in the control group (40% vs. 6.57%; chi(2)=24.06; P=0.001); the abnormal rate of neurosonography results at birth and 3 months after birth was higher in the study group than in the control group (P<0.05), as were BAEP values 4 months after birth (chi(2)=8.960; P=0.003). Scores for the Infant Mental Development Index (MDI) were apparently lower than in the control group. When congenitally infected children were tested at the age of 5.5-6.5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), their rate of mental retardation was still found to be approximately 20%., Conclusions: Intrauterine HCMV infection is closely related to abnormal pregnancy outcomes, infant neurological damage, mental retardation, and hearing loss.

Through systematic experimental and clinical studies, the physiological regulation of utero-placental circulation and the relation of the disturbance in this acirculation to pathogenic mechanisms of high risk pregnancies-Intrauterine Growth Retardation (IUGR) and Pregnancy-induced hypertension (PIH) were explored. The pharmacological effects and mechanism of a Chinese herbal medicine-Qingxintong in improving, the utero-placental circulation and the therapeutic efficacy in treatment of IUGR and PIH, both accompanied by disturbance of utero-placental circulation, were investigated as well.

Because of the fluid-filled lungs in the fetus, the ultrasound beam can penetrate to the root of the pulmonary artery perpendicularly. Using M-mode echocardiography, the following dimensions were measured: the pulmonary and aortic valve excursion in 19 fetuses, and the pulmonary and aortic root internal diameter in 70 fetuses, between 18 and 42 weeks, menstrual age. The measured dimensions were then correlated with the biparietal diameter. The correlation coefficients for the measurements ranged from 0.873 to 0.892. Regression analysis showed that the best fit of the data was a linear model from which the 5% and 95% confidence limits were derived for individual predictions of the arterial dimensions. The ratios of the pulmonary/aortic valve excursion and the pulmonary/aortic internal diameter were approximately 1:1. These results are of potential value in the prenatal detection of great arterial valve or root diseases.

411 cases of malformed babies in 1960-1985 were analyzed, giving an incidence of 6.8%. The clinical data and autopsy materials showed that the order of occurrence of malformation in various systems was: nervous system, face and neck, muscle, bone and digestive system. Autopsy rate was 37.4% in this series. The ratio of malformed male babies to female was 1.3 to 1. 46.5% of the mothers with malformed baby were at age of 25-29 years and 66.2% delivered at 37 to 41 weeks of gestation. 69.3% of mothers with malformed baby had gestational complications 11 times as high as those delivering normal neonate in the same period (P less than 0.01). Of them hydramnion, premature rupture of membranes, oligoamnios, neonatal asphyxia were obviously higher than those pregnancies with normal baby (P less than 0.01). There is mainly discussed the clinical value of autopsy and the preventive measures in decreasing birth of malformed babies.