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Objective:To establish optimal gestational weight gain (GWG) in Chinese pregnant women by Chinese-specific BMI categories and compare the new recommendations with the Institute of Medicine (IOM) 2009 guidelines.Design:Multicentre, prospective cohort study. Unconditional logistic regression analysis was used to evaluate the OR, 95 % CI and the predicted probabilities of adverse pregnancy outcomes. The optimal GWG range was defined as the range that did not exceed a 1 % increase from the lowest predicted probability in each pre-pregnancy BMI group.Setting:From nine cities in mainland China.Participants:A total of 3731 women with singleton pregnancy were recruited from April 2013 to December 2014.Results:The optimal GWG (ranges) by Chinese-specific BMI was 15·0 (12·8–17·1), 14·2 (12·1–16·4) and 12·6 (10·4–14·9) kg for underweight, normal weight and overweight pregnant women, respectively. Inappropriate GWG was associated with several adverse pregnancy outcomes. Compared with women gaining weight within our proposed recommendations, women with excessive GWG had higher risk for macrosomia, large for gestational age and caesarean section, whereas those with inadequate GWG had higher risk for low birth weight, small for gestational age and preterm delivery. The comparison between our proposed recommendations and IOM 2009 guidelines showed that our recommendations were comparable with the IOM 2009 guidelines and could well predict the risk of several adverse pregnancy outcomes.Conclusions:Inappropriate GWG was associated with higher risk of several adverse pregnancy outcomes. Optimal GWG recommendations proposed in the present study could be applied to Chinese pregnant women.

Xiaorong Zhou,1,* Yuxu Feng,2,* Siwen Liu,1 Chenchen Li,1 Yue Teng,1 Xiaoyou Li,1 Jianwei Lu1 1Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009 Jiangsu Province, People’s Republic of China; 2Department of Orthopedics, The Pukou Centre Hospital, Nanjing, 210009 Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyou Li; Jianwei LuDepartment of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, No. 42 Baiziting, Xuanwu District, Nanjing 210009, Jiangsu Province, People’s Republic of ChinaTel +86-25-83283597Email chchsina@126.com; lujw@medmail.com.cnBackground: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, and it is also the most frequently diagnosed cancer. Previous studies indicate that IL-33 plays a crucial role in the development of NSCLC. In recent years, the role of miRNAs in cancer has become increasingly clear. However, reports focused on the relation between IL-33 and miRNAs in NSCLC have been limited.Methods: The expression of IL-33 and miR-128-3p was detected by qPCR. MTT, EdU, and colony formation assays were used to detect the proliferation ability of NSCLC cells. Transwell assay was used to investigate the migration and invasion of NSCLC cells. The expression of bax, cyt-c, and caspase 3 was detected by Western blot. Finally, in vivo tumor xenograft was used to detect the effects of IL-33 and miR-128-3p on tumor growth capacity.Results: IL-33 was notably increased in the serum and tumor tissue of NSCLC patients. The in vitro function study revealed that IL-33 significantly promotes the proliferation, migration, and invasion of the NSCLC cells. In vivo experiments further confirmed the pro-tumor effect of IL-33 on NSCLC. The study on the underlying mechanism elucidated that IL-33 regulates the expression of miR-128-3p, which can directly target and inhibit the expression of CDIP1. Furthermore, IL-33 regulates the expression of downstream apoptotic proteins such as bax, cyt-c, and caspase3. Rescue experiments demonstrated that miR-28-3p can reverse the effect of IL-33.Conclusion: These findings indicated that IL-33 and miR-128-3p may play a potential role in the diagnosis and treatment of NSCLC.Keywords: IL-33, NSCLC, miR-128-3p, CDIP1

Hypoalbuminemia usually predicts higher mortality, longer hospital stay, and more frequent re-admission1 . About 40%-60% of COVID-19 patients develop hypoalbuminemia at admission2, 3 . This may be due to an increase of capillary permeability caused by systemic inflammatory response4 , which leads to the leakage of serum albumin into interstitial space5 , poor nutritional status, and impaired liver function1 . COVID-19 patients with hypoalbuminemia are more severe and/or critical2 , and have a higher probability of intensive care unit (ICU) admission and higher risk of death6, 7 . However, few studies have evaluated the dynamic change of serum albumin level in COVID-19 patients with hypoalbuminemia on the patients' death. This article is protected by copyright. All rights reserved.

Rheumatoid arthritis (RA) is characterized by joint leukocyte infiltration, synovial inflammation and bone damage result from osteoclastogenesis. Bruton’s tyrosine kinase (BTK) is a key regulator of B cell receptor (BCR) and Fc gamma receptor (FcγR) signaling involved in the pathobiology of RA and other autoimmune disorders. SOMCL-17-016 is a potent and selective tricyclic BTK inhibitor, structurally distinct from other known BTK inhibitors. In present study we investigated the therapeutic efficacy of SOMCL-17-016 in a mouse collagen-induced arthritis (CIA) model and underlying mechanisms. CIA mice were administered SOMCL-17-016 (6.25, 12.5, 25 mg·kg(−1)·d(−1), ig), or ibrutinib (25 mg·kg(−1)·d(−1), ig) or acalabrutinib (25 mg·kg(−1)·d(−1), ig) for 15 days. We showed that oral administration of SOMCL-17-016 dose-dependently ameliorated arthritis severity and bone damage in CIA mice; it displayed a higher in vivo efficacy than ibrutinib and acalabrutinib at the corresponding dosage. We found that SOMCL-17-016 administration dose-dependently inhibited anti-IgM-induced proliferation and activation of B cells from CIA mice, and significantly decreased anti-IgM/anti-CD40-stimulated RANKL expression in memory B cells from RA patients. In RANKL/M-CSF-stimulated RAW264.7 cells, SOMCL-17-016 prevented osteoclast differentiation and abolished RANK-BTK-PLCγ2-NFATc1 signaling. In summary, this study demonstrates that SOMCL-17-016 presents distinguished therapeutic effects in the CIA model. SOMCL-17-016 exerts a dual inhibition of B cell function and osteoclastogenesis, suggesting that it to be a promising drug candidate for RA treatment.

The prognostic value of 18F-FDG PET/CT for primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) patients has not been determined. This prompted us to explore the value of 18F-FDG PET/CT for prognostic stratification in patients with PI-DLBCL treated with an R-CHOP-like regimen. Seventy-three PI-DLBCL patients who underwent baseline PET/CT between January 2010 and May 2019 were included in this retrospective study. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were computed using the 41% SUVmax thresholding method. Progression-free survival (PFS) and overall survival (OS) were used as endpoints to evaluate prognosis. During the follow-up period of 3–117 months (29.0 ± 25.5 months), high TLG, non-germinal center B-cell-like (non-GCB) and high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) were significantly associated with inferior PFS and OS. TLG, cell-of-origin and NCCN-IPI were independent predictors of PFS, and both TLG and NCCN-IPI were independent predictors of OS. The grading system was based on the number of risk factors (high TLG, non-GCB, high NCCN-IPI) and patients were divided into 4 risk groups (PFS: χ2 = 33.858, P

Modeling SARS-CoV-2 in mice Among the research tools necessary to develop medical interventions to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, high on the list are informative animal models with which to study viral pathogenesis. Gu et al. developed a mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia. Adaptation of this viral strain in the mouse appeared to be dependent on a critical amino acid change, Asn501 to Tyr (N501Y), within the receptor-binding domain of the viral spike protein. The new mouse model was used to study neutralizing antibodies and a vaccine candidate against the virus. Science, this issue p. 1603, A SARS-CoV-2 mouse model is used to study viral responses and the development of vaccine candidates., The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

Aim: This study profiled differentially expressed long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LSCC) to predict LSCC overall survival (OS) using The Cancer Genome Atlas data. Materials & methods: The RNA-seq and clinical dataset of 475 LSCC patients was retrieved from The Cancer Genome Atlas database and statistically analyzed. Results: There were 67 upregulated and 32 downregulated lncRNAs in LSCCs and 12 lncRNAs associated with OS. The seven-lncRNA signature was associated with poor OS and RP11-150O12.6 and CTA-384D8.35 were associated with better OS (p < 0.001). The seven lncRNAs-mRNA interaction network analysis showed their association with 187 protein-coding genes for cancer development, cell migration, adhesion, proliferation, apoptosis, angiogenesis and the MAPK signaling pathways. Conclusion: This seven-lncRNA signature is useful to predict LSCC OS.

Background Due to the relatively higher tendency of postsurgery scars, insufficient cartilage support, and low surgical acceptability, nasal defect repair with forehead flap in Asian patients needs further study. Objective We aim to determine the necessity of tissue expansion, timing of pedicle division, and the importance of cartilage scaffold reinforcement and scar prevention at the donor site during nasal reconstruction in Asian patients with paramedian forehead flap. Methods A retrospective analysis was performed on patients who underwent nasal reconstruction with forehead flap at our hospital from January 2013 to January 2018. The demographical information, surgery details, and postoperative complications of all patients were recorded. The reconstructed nose, scars, and eyebrow deformities were evaluated by digital photographs, and the overall satisfaction of the patients was documented. Results The study included 15 patients (7 males and 8 females). All nasal defects involved at least two aesthetic units and included seven full-thickness defects. Only one patient underwent two revision operations. Complications like hematoma, infection, and necrosis were not detected, except in one patient with partial necrosis of the flap. All patients were satisfied with the reconstructed nose and did not report any respiratory dysfunction. No obvious scars or eyebrow deformities were observed. Conclusion Three-stage full-thickness forehead flap should be used to repair nasal defects in Asian patients, with immediate cartilage scaffold reconstruction at stage one and reinforcement at stage two. Botox injection into the forehead can refine the scar.

Xian Liu,1,&ast; Lei Wang,1,&ast; Xiaohang Zuo,2,&ast; Chen Li,3 Yue Teng3 1Department of Reproductive Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Teng Email navimoon@126.comBackground: Polycystic ovary syndrome (PCOS) is quite common among women of reproductive age and can cause infertility and adverse pregnancy outcomes. Current studies on PCOS mainly focus on the effect of PCOS on pregnancy. So far, it remains unelucidated whether a history of infertility or early pregnancy loss (EPL) has differential effects on obstetric outcomes for PCOS women.Methods: This is a retrospective case control study. Ninety-two Chinese PCOS patients with a history of EPL or infertility were recruited in our study. A total of 112 Chinese non-PCOS patients with a history of EPL or infertility were taken as control group. Measurements included anthropometric data, serum total testosterone, fasting and two-hour plasma glucose levels, and antral follicle count. After they got pregnant (naturally or via assisted reproductive technology), all obstetric outcomes were observed and analyzed.Results: PCOS women with a history of EPL showed a much higher cesarean section (CS) rate than PCOS women with primary infertility. PCOS women with a history of EPL showed a much higher possibility of GDM (gestational diabetes mellitus) compared with PCOS women with primary infertility. PCOS women with a history of EPL showed a much higher possibility of GDM compared with non-PCOS women with a history of EPL. PCOS women with a history of EPL showed increased possibility of GDM as their BMI increased. When BMI is above 28, the incidence of GDM is significantly higher in PCOS women with a history of EPL compared with that in PCOS women with infertility.Conclusion: Both a history of EPL and obesity are risk factors for GDM for PCOS women, and higher BMI indicates a higher possibility of GDM among PCOS women with a history of EPL. Timely intervention is in need for PCOS women with EPL and a higher BMI.Keywords: polycystic ovarian syndrome, early pregnancy loss, infertility, obstetric complication, gestational diabetes mellitus

Background: Patients with coronavirus disease 2019 (COVID-19) can present with gastrointestinal (GI) symptoms. However, the prevalence of GI symptoms and their association with outcomes remain controversial in COVID-19 patients.Methods: All COVID-19 patients consecutively admitted to the Wuhan Huoshenshan hospital from February 2020 to April 2020 were collected. Disease severity and outcomes were compared between COVID-19 patients with and without GI symptoms. Logistic regression analyses were performed to evaluate the association of GI symptoms with the composite endpoint and death in COVID-19 patients. A composite endpoint was defined as transfer to intensive care unit, requirement of mechanical ventilation, and death. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.Results: Overall, 2,552 COVID-19 patients were included. The prevalence of GI symptoms was 21.0% (537/2,552). Diarrhea (8.9%, 226/2,552) was the most common GI symptom. Patients with GI symptoms had significantly higher proportions of severe COVID-19 and worse outcomes than those without. Univariate logistic regression analyses demonstrated that GI symptoms were significantly associated with the composite endpoint (OR = 2.426, 95% CI = 1.608–3.661; P < 0.001) and death (OR = 2.137, 95% CI = 1.209–3.778; P = 0.009). After adjusting for age, sex, and severe/critical COVID-19, GI symptoms were still independently associated with the composite endpoint (OR = 2.029, 95% CI = 1.294–3.182; P = 0.002), but not death (OR = 1.726, 95% CI = 0.946–3.150; P = 0.075). According to the type of GI symptoms, GI bleeding was an independent predictor of the composite endpoint (OR = 8.416, 95% CI = 3.465–20.438, P < 0.001) and death (OR = 6.640, 95% CI = 2.567–17.179, P < 0.001), but not other GI symptoms (i.e., diarrhea, abdominal discomfort, nausea and/or vomiting, constipation, acid reflux and/or heartburn, or abdominal pain).Conclusion: GI symptoms are common in COVID-19 patients and may be associated with their worse outcomes. Notably, such a negative impact of GI symptoms on the outcomes should be attributed to GI bleeding.

Background Breast cancer is a common malignant tumor, threatening the general health of women worldwide. Estrogen-related receptor alpha (ERRα) is a member of nuclear receptor family and has been shown to involve in the pathophysiology of breast cancer. However, the specific relationship between ERRα and the triple negative breast cancer (TNBC), is not clear yet. Objective This study examined the relevance between ERRα expression and different clinical features of breast cancer patients. Methods The expression level of ERRα in 150 human breast cancer tissues (which contains 48 human triple negative breast cancer tissues) and 53 human benign breast tumor tissues using immunohistochemical staining. Results ERRα protein level was significantly higher in breast cancer tissues than that in benign tumors. High expression of ERRα was significantly associated with the high grade but not the clinical stage and human epidermal growth factor receptor 2 of the breast cancer tissues. Its high expression was also positively correlated with triple negative breast cancer in pathological grade 2 and 3, but not in grade 1. high expression of ERRα was positively correlated with triple negative breast cancer in each clinical stage. In addition, high expression of ERRα was associated with shorter overall survival of breast cancer patients. Conclusion In conclusion, highly expressed ERRα was associated with higher pathological grades triple-negative breast cancer and shorter overall survival. Future studies were required to recruit more patients to consolidate the current findings.

BACKGROUND: This study aimed to explore the added prognostic value of baseline metabolic volumetric parameters and cell of origin subtypes to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in nodal diffuse large B-cell lymphoma (DLBCL) patients. METHODS: A total of 184 consecutive de novo nodal DLBCL patients who underwent baseline positron emission tomography/computed tomography (PET/CT) were included in this study. Kaplan-Meier estimates were generated to evaluate the clinical, biological, and PET/CT parameters’ prognostic value. The Cox proportional hazards model was performed to examine the potential independent predictors for progression-free survival (PFS) and overall survival (OS). RESULTS: With a median follow-up of 35 months, the 3-year PFS and OS were 65.2% and 73.0%, respectively. In univariate analysis, total lesion glycolysis (TLG), cell-of-origin subtypes, and NCCN-IPI were both PFS and OS predictors. High TLG (≥1,852), non-germinal center B (non-GCB), as well as high NCCN-IPI (≥4), were shown to be independently significantly associated with inferior PFS and OS after multivariate analysis. Based on the number of risk factors (high TLG, non-GCB, and high NCCN-IPI), a revised risk model was designed, and the participants were divided into four risk groups with very different outcomes, in which the PFS rates were 89.7%, 66.2%, 51.7%, and 26.7% (χ(2)=30.179, P

Systemic lupus erythematosus (SLE) increases the risk of adverse pregnancy outcomes and fetal complications. Placenta percreta, involving placental attachment to another organ, is a rare but severe placental abnormality. We report a 26-year-old woman, G2P1, with a 6-year history of SLE with coexisting pernicious placenta previa and placenta percreta detected by second trimester ultrasound. She discontinued prednisone 5 months before admission, without consultation, and active SLE was diagnosed on admission. Because of her progressive condition, the patient underwent infrarenal abdominal aorta balloon occlusion and double J ureteral catheter placement, followed by elective cesarean at 27+6weeks gestation. Despite aggressive management, she experienced severe bleeding requiring internal iliac artery ligation and peripartum hysterectomy. The placenta had penetrated the uterus walls and attached to the bladder apex, necessitating bladder repair. Thrombosis was detected in the common iliac artery and common femoral artery in the right leg 1 day postoperatively. Conservative antithrombotic therapy had little effect, and embolectomy by arteriotomy was performed on the 6th post-cesarean day, and an arterial thrombus was removed. Infrarenal abdominal aorta balloon occlusion may increase the risk of postoperative thrombosis in pregnant women with active SLE and coagulation disorders. These patients therefore require close monitoring and timely anticoagulation.

Gefitinib is the first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), which is used in the treatment of NCSLC patients through interrupting EGFR signaling pathway. Although gefitinib prolongs patients' progression-free survival (PFS), acquired resistance occurs in advanced NSCLC patients. In this study, we mainly investigated the effects of antagonist for ghrelin-R (D-lys-3-GHRP-6) on conquering acquired gefitinib resistance in human lung cancer cells. We found that GHSR was overexpressed in our established HCC827/GR cells compared with parental cells, accompanied with increase of p-AKT and p-ERK1/2. Treatment of D-lys-3-GHRP-6 significantly decreased p-AKT and p-ERK1/2 expression in HCC827/GR cells. H1650 cells and HCC827/GR cells were treated with control, gefitinib, D-lys-3-GHRP-6 and D-lys-3-GHRP-6 + gefitinib, respectively. In H1650 and HCC827/GR cells, combination of D-lys-3-GHRP-6 and gefitinib significantly inhibited cell proliferation and Bcl2 protein level, induced the cell apoptosis and cleaved-caspase3 protein level compared with control group, while there was no significant difference between control and gefitinib group.

Necroptosis refers to a programmed form of necrosis, which involves the receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). In this study, to investigate the role of necroptosis in the pathogenesis of acute-on-chronic hepatitis B liver failure (ACHBLF), we retrospectively analyzed 122 patients with ACHBLF, 131 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs). Using quantitative real-time polymerase chain reaction (RT-qPCR), we measured RIPK3 mRNA levels in peripheral blood mononuclear cells (PBMCs). ELISA was performed to measure the serum levels of MLKL, TNF-α and caspase-8. We found that RIPK3 mRNA levels were significantly higher in patients with ACHBLF than those with CHB or HCs. RIPK3 mRNA levels in patients with ACHBLF were positively correlated with serum levels of TNF-α or MLKL and negatively correlated with caspase-8 levels. Univariate and multivariate analysis revealed that RIPK3 mRNA level was predictive of 3-month mortality of ACHBLF. The area under receiver operating characteristic curve (AUC) of RIPK3 mRNA levels was 0.810 (95% CI: 0.729-0.876), which was higher than that of MELD scores (0.766, 95% CI: 0.681-0.838). The optimal cut-off point of 8.81 was determined for RIPK3 mRNA levels, which showed a sensitivity of 80.7% and a negative predictive value of 80.4%. These results indicate that elevated RIPK3 mRNA levels in PBMCs are associated with poor prognosis of ACHBLF. We thus propose that necroptosis may play an important role in pathogenesis of ACHBLF.

Coronavirus disease (COVID-19) patients frequently develop liver biochemical abnormality. However, liver biochemical abnormality in COVID-19 patients with liver cirrhosis is under-recognized.Patients hospitalized during COVID-19 pandemic in China (ie, from February to April 2020) were screened. All of 17 COVID-19 patients with liver cirrhosis consecutively admitted to the Wuhan Huoshenshan Hospital were identified. Meanwhile, 17 age-, sex-, and severity-matched COVID-19 patients without liver cirrhosis admitted to this hospital were selected as a control group; all of 14 cirrhotic patients without COVID-19 consecutively admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command were selected as another control group. Incidence of liver biochemical abnormality and decompensated events were primarily compared.Among the COVID-19 patients with liver cirrhosis, the incidence of liver biochemical abnormality at admission and during hospitalization were 76.50% and 84.60%, respectively; 7 (41.20%) had decompensated events at admission; 1 was transferred to intensive care unit due to gastrointestinal bleeding. Among the COVID-19 patients without liver cirrhosis, the incidence of liver biochemical abnormality at admission and during hospitalization were 58.80% (P = .271) and 60.00% (P = .150), respectively. Among the cirrhotic patients without COVID-19, the incidence of liver biochemical abnormality at admission and during hospitalization were 69.20% (P = .657) and 81.80% (P = .855), respectively; 11 (78.60%) had decompensated events at admission (P = .036). None died during hospitalization among the three groups.Liver biochemical abnormality is common in COVID-19 patients with liver cirrhosis. Management of decompensated events in cirrhotic patients without COVID-19 should not be neglected during COVID-19 pandemic.

Background This study sought to examine the efficacy and adverse reactions of capecitabine and lobaplatin in the treatment of metastatic human epidermal growth factor receptor 2 (HER-2) negative breast cancer (BC). Methods This retrospective study examined 45 patients diagnosed with advanced HER-2 negative BC. Patients were enrolled in this study from November 2015 to June 2019. The patients received capecitabine and lobaplatin combination therapy. The therapeutic efficacy and side effects were evaluated after at least 2 cycles of treatment. Results Therapeutic efficacy and adverse reactions were evaluated in 38 patients, comprising 12 cases of partial response (PR), 19 cases of stable disease (SD), and 7 cases of progressive disease (PD). Among these, 3 patients required treatment delays or dose reductions for subsequent cycles, and 2 patients discontinued treatment. The overall response rate (ORR) was 31.58% and the disease control rate (DCR) was 81.58%. The ORR and DCR for hormone receptor positive, HER-2 negative (HR+/HER-2-) and triple negative breast cancer (TNBC) patients were 31.82% and 31.25%, and 86.36% and 75%, respectively. The median progression free survival (PFS) was 8 months, 6 months, and 6 months in patients receiving the therapeutics as a first-line, second-line, or third-line and beyond treatment, respectively. The main side effects were myelosuppression, including granulocytopenia, thrombocytopenia, and anemia. Among patients with grade 1 side effects or above, 28 patients (73.68%) had myelosuppression, and 13 patients (34.21%) had gastrointestinal reactions. Further, we investigated the association between side effects and clinical outcomes, and found that PFS was increased in patients with myelosuppression and gastrointestinal reactions. Conclusions Capecitabine and lobaplatin combination therapy was effective and well tolerated among patients with advanced HER-2 negative BC.

BACKGROUND Most of the widely used methods for the assessment of keloid treatment are subjective grading scales based on the opinion of an individual clinician or patient. There is a growing need for objective methods to evaluate keloid treatment. OBJECTIVE This study aimed to evaluate the value of laser speckle contrast imaging (LSCI) as an objective method for the assessment of dual-wavelength laser therapy for keloids. METHODS This prospective study included 21 patients with 54 keloids. All patients were treated with a combined 585-nm pulsed dye laser and 1,064 nm neodymium-doped yttrium aluminum garnet dual-wavelength laser at 4 weeks to 6 weeks intervals. Keloids were assessed using the Vancouver Scar Scale (VSS) and LSCI. RESULTS The total VSS score significantly decreased after 4 sessions of treatment (p < .05). Blood perfusion in keloids as measured by LSCI was significantly reduced after treatment (p < .05). The improvement of chest keloids in terms of the total VSS score and blood perfusion was significantly greater than that of scapular keloids (p < .05). There was a positive correlation between decreased perfusion and reduced total VSS score (R2 = 0.84). CONCLUSION Blood perfusion in keloids significantly decreased after dual-wavelength laser therapy. Laser speckle contrast imaging is a promising objective method for assessing the improvement of keloids treated with laser therapy.

Purpose: The purpose of this study was to investigate the prognostic relevance of metabolic parameters measured using 18F-FDG PET/CT in patients with metastatic cutaneous malignant melanoma (CMM).Materials and Methods: The prognostic impact of whole-body metabolic tumor volume (wMTV), whole-body tumor lesion glycolysis (wTLG), maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) was evaluated in 42 metastatic CMM patients who underwent 18F-FDG PET/CT. The metabolic parameters were dichotomized by optimal cutoff values using time-dependent receiver operating characteristic (ROC) curves. In addition, univariate and multivariate analyses of the metabolic parameters were performed using the Kaplan-Meier method and Cox proportional hazards models.Results: The optimal cutoff values for disease-free survival (DFS) were 4.63 for SUVmax, 3.31 for SUVmean, 8.22 cm3 for wMTV, and 18.22 for wTLG. The optimal cutoff values for melanoma-specific survival (MSS) were 4.77 for SUVmax, 3.31 for SUVmean, 22.32 cm3 for wMTV, and 51.37 for wTLG. Thirty-two (72%) of the 42 patients experienced recurrence during the follow-up period, and 21 patients (50%) died from the disease. In univariate analysis, SUVmax greater than 4.63 (p= 0.025) and SUVmean greater than 3.31 (p= 0.011) affected DFS, while SUVmax greater than 4.77 (p= 0.039), wMTV greater than 22.32 (p= 0.023) and wMTV greater than 51.37 (p= 0.016) affected MSS. In multivariate analysis after adjustment for the effects of clinical parameters, SUVmax was the best predictive factor for DFS (p = 0.016), and SUVmax, wMTV and wTLG were the best predictive factors for MSS (p = 0.023, p = 0.018, and p = 0.007).Conclusions: SUVmax appears to be a strong independent prognostic factor for recurrence in metastatic CMM, and SUVmax, wMTV and wTLG were found to be the best predictive markers for melanoma-specific death.

As an example of Shenyi capsule on non-small-cell lung cancer combined with chemotherapy, this review discusses the synergistic effect and mechanism of natural drugs in oncotherapy from the yin-yang perspective in ancient Chinese philosophy, so as to reflect the therapeutic principle of natural drugs for tumor more comprehensively. The major focuses of this review are on the philosophical thinking of yin-yang as a tool which can not only explain the effect of Shenyi capsule in NSCLC combined with chemotherapy but also explore the mechanism of Shenyi capsule at the cellular and molecular level. Learning from the “yin-yang” thinking of ancient Chinese philosophy will bring more enlightenment to the research and development of traditional Chinese drugs in the future.

Purpose The aim was to explore whether baseline total lesion glycolysis (TLG) can improve the prognostic value of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients treated with an R-CHOP-like regimen. Materials and methods Ninety-four PG-DLBCL patients who underwent baseline PET/CT between July 2010 and May 2019 were included in this retrospective study. FDG-avid lesions in each patient were segmented to calculate the SUVmax, total metabolic tumor volume (TMTV), and TLG. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate prognosis. Results During the follow-up period of 5 to 108 months (35.3 ± 23.5 months), high TLG and a high NCCN-IPI were significantly associated with poor PFS and OS. Total lesion glycolysis and the NCCN-IPI were independent predictors of PFS and OS. Patients were stratified into 3 groups according to the combination of TLG and the NCCN-IPI for PFS (P 1159.1 and NCCN-IPI 4-8) (PFS and OS, 57.7% and 61.5%, respectively, n = 42), intermediate-risk group (TLG > 1159.1 or NCCN-IPI 4-8) (PFS and OS, both 76.9%, n = 26), and low-risk group (TLG ≤ 1159.1 and NCCN-IPI 0-3) (PFS and OS, 97.6% and 100.0%, respectively, n = 26). Conclusions Both TLG and the NCCN-IPI are independent predictors of PG-DLBCL patient survival. Moreover, the combination of TLG and the NCCN-IPI improved patient risk stratification and might help personalize therapeutic regimens.

Purpose: The aim of the present study was to explore whether pretreatment total metabolic tumor volume (TMTV) combined with MYC/BCL-2 dual expression (DE) would improve the prognostic stratification of patients who were newly diagnosed with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).Materials and methods: Eighty-three patients between March 2011 and November 2019, diagnosed with PGI-DLBCL prior to treatment, were included in this retrospective study. Baseline TMTV on PET/CT scans were calculated automatically using the boundaries of voxels presenting a SUVmax≥2.5. Expression of MYC/BCL-2 were detected at protein levels via immunohistochemistry（IHC）. The distributions of Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method and differences were compared using a log-rank test followed by multivariate analysis using the Cox proportional hazards model.Results: TMTV and DE were significantly associated with a worse PFS and OS. Multivariate analysis revealed that TMTV (HR=6.090, P2=32.178, P2=23.091, PConclusions: TMTV and DE independently predicted survival outcomes in PGI-DLBCL patients. Furthermore, our findings suggest that combination of TMTV and DE may further improve the ability of clinicians to stratify patients in terms of differential prognoses.

Purpose The aim of this study was to explore the prognostic value of total metabolic tumor volume (TMTV) at baseline 18F-FDG PET/CT in patients diagnosed with peripheral T-cell lymphoma (PTCL). Materials and methods Eighty-four newly diagnosed PTCL patients who underwent baseline 18F-FDG PET/CT prior to treatment between March 2009 and January 2019 were enrolled in this retrospective study. The FDG-avid lesions in each patient were segmented using semiautomated software to calculate the maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) values using the boundaries of voxels presenting with the 41% SUVmax threshold method. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate patient prognosis. The log-rank test and Cox regression analyses were used to evaluate PFS and OS. Results ROC curve analysis indicated an ideal TMTV cut-off value of 228.8 cm3. During the 4–131 months (29.2 ± 28.5 months) follow-up period, high TMTV was significantly associated with worse PFS and OS. TMTV and the international peripheral T-cell lymphoma project score (IPTCLP) were independent predictors of PFS and OS with multivariate analysis. The combination of TMTV and the IPTCLP may provide significantly better risk substratification in PFS and OS of PTCL patients. Conclusions Both TMTV and IPTCLP are independent predictors of PTCL patient survival outcomes. Moreover, the combination of TMTV and IPTCLP improved patient risk stratification and may contribute to personalized therapeutic regimens.

Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC.Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan–Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC.Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion.Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.

Granular cell tumors (GCTs) of the neurohypophysis are rare neoplastic diseases of the pituitary. Because of the rare nature of the disease, previous descriptions have been limited to single-case studies, small series, or simple reviews.We reported 3 cases in our medical center and systematically reviewed 98 cases who met inclusion criteria. Data were gathered on different aspects of GCTs' characteristics, including demographics, clinical features, laboratory features, histological features, immunocytochemical features, radiologic features, and treatment to elucidate any associations useful in determining pathogenesis and appropriate treatment.Female sex was significantly associated with GCTs (P0.001). The most common presenting symptom and tentative diagnosis were ophthalmologic defects in 61.2% and pituitary adenoma preoperatively in 18.4%, respectively. Most neurohypophysial GCTs possess immunopositivity for S-100 protein (59.1%, 26/44) and negative staining for glial fibrillary acidic protein (69.8%, 30/43).These findings lend strong support to the suggestion that tumors probably remain in the transitional cell type. To our knowledge, our systematic review presents the largest number of symptomatic cases ever enumerated, with 98 cases meeting the inclusion criteria.

The best time window of percutaneous coronary intervention (PCI) is within 12 hours for ST-segment elevation myocardial infarction (STEMI). However, there is limited evidence about the proper time of PCI for delayed STEMI patients.From June 2014 to June 2015, a total of 268 patients receiving PCI with second-generation drug-eluting stent in a Chinese hospital after 3 days of STEMI onset were enrolled in this retrospective study, who were divided into the early group (3-14 days) and the late group (>14 days). A propensity score match was conducted to reduce the baseline difference. The primary endpoint of all-cause death and secondary endpoints of major adverse cardiac and cerebrovascular event (myocardial infarction [MI], stroke, emergent revascularization, and rehospitalization due to heart failure) were compared using survival analysis.At last, 182 cases were matched after propensity score match, with no statistical difference in baseline characteristics and PCI data. Kaplan-Meier survival curve demonstrated no difference in all-cause death of the 2 groups (P = .512). However, the early group presented a higher incidence of MI than the late group (P = .036). The multivariate Cox regression analysis also demonstrated that the early PCI was an independent risk factor for MI compared with late PCI (hazard ratio = 3.83, 95%CI [1.91-8.82], P = .001). There was no statistical difference in other major adverse cardiac and cerebrovascular event, including stroke, emergent revascularization, and rehospitalization due to heart failure.Using the 2nd drug-eluting stent, early PCI (3-14 days) and late PCI (>14 days) have comparable efficacy and outcomes. However, patients receiving early PCI are subjected to a relatively higher risk of recurrent MI.

Background Polymeric micellar paclitaxel (PM-paclitaxel) is a novel Cremophor EL-free, nanoparticle-encapsulated paclitaxel formulation administered through intravenous injection. The primary objective of this phase I trial was to determine the first cycle dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PM-paclitaxel. Secondary objectives included the evaluation of the safety, antitumor activity, and pharmacokinetic (PK) profile of PM-paclitaxel in patients with advanced malignancies. Methods The PM-paclitaxel dose was escalated from 175 mg/m2 (level 1) to 435 mg/m2 (level 5). PM-paclitaxel was intravenously administered to patients for 3 h without premedication on day 1 of a 21-day cycle. Results Eighteen patients with confirmed advanced malignancies received PM-paclitaxel. DLT included grade 4 neutropenia (four patients) and grade 3 numbness (one patient), which occurred in one of the six patients who received 300 mg/m2 (level 3) PM-paclitaxel and all three patients who were treated with 435 mg/m2 PM-paclitaxel. Thus, the MTD of PM-paclitaxel was determined as 390 mg/m2 (level 4). Acute hypersensitive reactions were not observed. Partial response was observed in six of 18 patients (33.3%), three of whom had prior exposure to paclitaxel chemotherapy. The peak concentration and area under the curve values of paclitaxel increased with increasing dosage, indicating that PM-paclitaxel exhibits linear PKs. Conclusions PM-paclitaxel showed high MTD without additional toxicity, and exhibited desirable antitumor activity. The recommended dose of PM paclitaxel for phase II study is 300 mg/m2.

Metastasis frequently occurs in advanced ovarian cancer, which not only leads to substantial mortality but also becomes a major challenge to effective treatment. Epithelial-mesenchymal transition (EMT) is a key mechanism facilitating cancer metastasis. Targeting the EMT process with more efficacious and less toxic agents to prevent metastasis is of significant therapeutic value for ovarian cancer treatment. The anti-EMT function and mechanism of ginsenoside Rb1, a monomer composition extracted from the traditional Chinese herb Panax ginseng or P. notoginseng, was investigated in the present study. Western blotting demonstrated that treatment with ginsenoside Rb1 antagonized hypoxia-induced E-cadherin downregulation and vimentin upregulation in SKOV3 and 3AO human ovarian cancer cells. Wound healing assays and in vitro migration assays indicated that ginsenoside Rb1 weakened hypoxia-enhanced cell migration ability. Furthermore, it was demonstrated that microRNA (miR)-25 is upregulated by hypoxia in ovarian cancer cells, which was attenuated by ginsenoside Rb1 treatment. Additionally, forced expression of miR-25 in ovarian cancer cells was identified to not only trigger EMT, but also block the suppressive effects of ginsenoside Rb1 on hypoxia-induced EMT by negatively targeting the E-cadherin transactivator, EP300. In conclusion, ginsenoside Rb1 may reverse hypoxia-induced EMT by abrogating the suppression of miR-25 on EP300 and E-cadherin, which suggests that ginsenoside Rb1 may be a potential therapeutic candidate for the treatment of ovarian cancer.

// Luqing Wang 1, * , Yanjun Hu 2, * , Xiaohong Xiang 3 , Kai Qu 3 and Yue Teng 4 1 Department of Nuclear Medicine, Liaocheng People’s Hospital, Taishan Medical College, Liaocheng 252000, China 2 Department of Clinical Laboratory, Liaocheng People’s Hospital, Taishan Medical College, Liaocheng 252000, China 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China * These authors have contributed equally to this work Correspondence to: Yue Teng, email: navimoon@126.com Kai Qu, email: joanne8601@163.com Keywords: long non-coding RNA, epithelial ovarian cancer, paclitaxel, chemoresistance Received: May 07, 2017 Accepted: June 19, 2017 Published: August 02, 2017 ABSTRACT Ovarian cancer is the most lethal gynecologic malignancy, characterized by late diagnosis, frequent relapse, and easy development of chemoresistance. Recent studies suggest that lncRNAs are involved in ovarian cancer onset and progression, as well as the resistance in paclitaxel-containing chemotherapy. However, the genome-wide expression pattern and associated functional implications of lncRNAs in paclitaxel-resistant ovarian cancer cells remain undetermined. In the present study, we identified a panel of lncRNAs aberrantly expressed in both paclitaxel resistant ovarian cancer tissues and cell lines, including XR_948297, XR_947831, XR_938728, XR_938392, NR_103801, NR_073113, and NR_036503. Moreover, the seven-lncRNA signature showed a relatively high predictive accuracy of chemoresistance with an area under the ROC curve (AUC) of 0.93, and was associated with progression-free survival inovarian cancer patients (HR=2.05, p =0.015). Our function prediction demonstrated that the seven-lncRNA signature was positively correlated with a cluster containing 129 genes enriched in insulin secretion-related pathway. Our findings suggest that the seven-lncRNA signature may be utilized as potent biomarkers for predicting chemoresistance for ovarian cancer patients with paclitaxel-containing chemotherapy.

// Yue Teng 1 , Zhanhai Yin 2 , Jing Li 1 , Kun Li 3 , Xu Li 1 and Yan Zhang 1 1 Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China 2 Department of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China 3 Clinical Laboratory, Shanxi Mineral Hospital, Xi’an, Shaanxi 710014, People's Republic of China Correspondence to: Yan Zhang, email: zhangyan1114@xjtu.edu.cn Xu Li, email: lixuxjtu@163.com Keywords: Sema3A, rheumatoid arthritis, serum-transfer induced mouse model, macrophages Received: May 18, 2017 Accepted: June 28, 2017 Published: August 03, 2017 ABSTRACT Rheumatoid arthritis is a chronic autoimmune disease characterized by infiltration of inflammatory cells into the synovium and destruction of cartilage and bone. Macrophages, fibroblast-like synoviocytes (FLS), and osteoclasts are critical cells driving the pathogenesis of RA. Semaphorin 3A (Sema3A) is recently identified as an essential player in the bone homeostasis, however its role in RA progression especially in the macrophage polarization are poorly understood. In the present study, we found that Sems3A levels were significantly decreased in RA serum and synovial fluid compared to OA controls. There was a negative correlation between Sema3A levels and RA severity. Using in vitro cell cultures, we showed for the first time that Sema3A promoted IL-4 induced M2 macrophage polarization, whereas prohibited LPS/IFN-γ induced M1 polarization. Sema3A inhibited VEGF-induced endothelial cells proliferation and migration, suppressed VEGF-mediated invasion and IL-6 production of FLS while stimulating their apoptosis. In addition, Sema3A retarded osteoclastogenesis. In vivo data demonstrated that Sema3A administration attenuated joint tissue damage and the severity of experimental arthritis. Our findings uncovered Sema3A as a promising diagnostic biomarker and novel prevention and treatment strategies in arthritis treatment.

It has been demonstrated that glutathione-S-transferase P1 (GSTP1) could protect cells from DNA damage mediated by oxidizing agents or electrophiles in hepatic inflammatory response. Our study evaluated the methylation status and the predictive value for prognosis of GSTP1 promoter region in patients with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF). Methylation status of GSTP1 promoter in peripheral blood mononuclear cells (PBMCs) and plasma was measured in 103 patients with pre-ACHBLF, 80 patients with chronic hepatitis B (CHB) and 30 healthy controls (HCs) by methylation-specific polymerase chain reaction. The mRNA level of GSTP1 was detected by quantitative real-time polymerase chain reaction. The methylation frequency of GSTP1 promoter region in patients with pre-ACHBLF (35/103 in PBMCs and 33/103 in plasma) was significantly higher than CHB (2/80) and HCs (0/30), respectively. The mRNA level of GSTP1 in patients with pre-ACHBLF was significantly lower than CHB and HCs. Additionally, pre-ACHBLF patients with methylated GSTP1 presented strikingly higher incidence of ACHBLF than those without. Of note, GSTP1 methylation presented distinctly better performance than model for end-stage liver disease score [area under the receiver operating characteristic curves (AUCs) 0.825 in PBMCs and 0.798 in plasma VS 0.589; AUC 0.804 in PBMCs and 0.779 in plasma VS 0.622; AUC 0.767 in PBMCs and 0.744 in plasma VS 0.602, respectively] when used to predict the 1-, 2- or 3-month incidence of ACHBLF in patients with pre-ACHBLF. Aberrant methylation of GSTP1 has potential to be a prognostic biomarker for pre-ACHBLF.

Background Rheumatoid arthritis (RA) is a prevalent chronic autoimmune inflammatory disease. Also acute coronary syndrome (ACS) is a prevalent chronic inflammatory disease. Now more and more studies have also shown that coronary heart disease is also associated with immune inflammationWe will discuss Th17 and Treg cell levels in patients with rheumatoid arthritis combined with coronary heart disease and simple rheumatoid joints as well as normal people. Its pathogenesis is closely associated with a failure of endogenous immune tolerance that caused by the imbalance of CD4/CD8.New T subgroup Th17 Treg,T lymphocytes play an important role in the occurrence and development of RA and ACS,Moreover, T lymphocytes are one of the first cells to be recruited into atherosclerotic plaques1, and most adhesion molecules and chemokines that promote the migration of monocytes to the intima are also related to T cell recruitment.T lymphocytes mainly divided into two major subsets of CD4/CD8, including CD4 +T helper cells, which are classified into Th1Th2 and newly discovered Th17 cells and regulatory T cells subgroup, have the effect of the immune response to promote the immune, and CD8 +play the role of killer cells and suppress the immune response,Similar to CD8, (Treg) lymphocytes can reduce the body’s anti-tumor ability by inhibiting cell contact and the production of inhibitory factors and effector T cells Objectives Through clinical studies, we want to explore whether the proportion of Th17/Treg in peripheral blood of RAwithACSpatients is reduced to indicate whether the immune balance is broken, thus providing further data for clinical studies Methods In April 2017 to September 2018 in our hospital Patients with RAand ACS diagnosed by Coronary angiography in our hospital of 20 cases male:9 female:12 into the research object, the diagnosis of ACS combined with clinical data of 20 patients as Observation group, These patients have been diagnosed with rheumatoid arthritis. Another 20 rheumatoid arthritis patientsmale: 11 female:9were collected from the rheumatology department of our hospital, and 20 normal healthy peoplemale:10female:10 were collected from the physical examination center of our hospital,as control group Chart-1 Chart-2 Results Compared with the control group, the proportion of Th17 cells and Treg cells in peripheral blood of RA with ACS and RA groups increased and decreased respectively (P Conclusion Through this rare clinical study, it was found that the levels of Treg cells and Th17 cells in patients with rheumatoid arthritis combined with coronary heart disease were to some extent higher than those in patients with rheumatoid arthritis alone and normal healthy people.We can speculate whether it is possible to find a target for Treg cell Th17 cell levels in patients with RA with ACS expanding the sample study again, so as to intervene as early as possible and regulate the immune balance to avoid the progression of coronary heart disease and adverse cardiovascular events References [1] Libby, P.; Ridker, P. M.; Hansson, G. K.; Leducq Transatlantic Network on, A., Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009, 54 (23), 2129-38. Acknowledgement None Disclosure of Interests None declared

Introduction: Placental abruption (PA) is a serious complication of pregnancy, associated with significant perinatal complications, including intrauterine fetal demise (IUFD). Continuous electronic fetal monitoring (EFM) has been widely applied in China in recent decades. Exploration of potentially PA-specific patterns of EFM contributes to early detection of PA occurrence. Patient concerns and diagnosis: A 33-year-old woman (gravida 3, para 1) was referred to our hospital at 33+3 weeks gestation due to non-reassuring fetal heart rate (FHR) pattern, and suffered sudden onset of severe PA and subsequent intrauterine fetal demise. Interventions: We analyzed the characteristics of her non-stress tests (NSTs) 1 day and 10 min before the detection of PA, aiming to explore potentially PA-specific patterns of EFM and provide reference for early detection of asymptomatic PA occurrence in obstetric practice. Outcomes: Unfavored characteristics of FHR patterns before PA onset are analyzed. Conclusion: For those who sense decreased fetal movements (DFMs), a NST and a biophysical profile (BPP) are recommended for exclusion of potential adverse maternal and fetal complications.

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by high rate of metastasis and recurrence. Recent studies have boosted our understanding that Gankyrin contributes to both of these pathological properties, but the mechanisms underlying its aberrant regulation are poorly understood. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in regulating the expression of oncogenes and anti-oncogenes through various mechanisms. Here, using transcriptome microarray analysis, we identified a long intergenic noncoding RNA termed Linc-GALH that was highly expressed and concordance with Gankyrin expression in HCC. In addition, we revealed that Linc-GALH was an independent unfavorable prognostic indicator for HCC, followed functional experiments showed that Linc-GALH promoted HCC cells migration and invasion in vitro, and enhanced lung metastasis ability of HCC cells in vivo. Mechanistically, we found that Linc-GALH could regulate the expression of Gankyrin through controlling the methylation status of Gankyrin by adjusting the ubiquitination status of DNMT1 in HCC. Collectively, our results demonstrated the role and functional mechanism of Linc-GALH in HCC, and indicated that Linc-GALH may act as a prognostic biomarker and potential therapeutic target for HCC.

// Yue Teng 1, * , Xuan Su 2, * , Xing Zhang 3, * , Yan Zhang 4 , Chen Li 1 , Wenquan Niu 5 , Chang Liu 3 , Kai Qu 3 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China 2 Department of Head and Neck of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China 4 Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China 5 State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China * These authors have contributed equally to this work Correspondence to: Kai Qu, email: qukaixjtu@163.com Chang Liu, email: liuchangdoctor@163.com Keywords: miRNA-200a/c, epithelial ovarian cancer (EOC), Robust Rank Aggregation Received: July 25, 2016 Accepted: October 12, 2016 Published: November 7, 2016 ABSTRACT Extensive effort has been put on miRNA expression signatures in epithelial ovarian cancer (EOC). Unfortunately, consistent conclusion rarely yielded from diverse studies, mainly due to the high inter-lab variability and small sample sizes. To overcome above limitations, an integrated analysis of miRNA expression signature was performed by employing Robust Rank Aggregation (RRA) method. Diagnostic analysis, Kaplan-Meier survival curves and pathway enrichment analysis were used to investigate the clinical values and biological functions of meta-signature miRNAs. A total of 519 EOC and 248 noncancerous samples were included. Seven mostly dysregulated miRNAs were identified by RRA method and two miRNAs (miR-200a-3p and miR-200c-3p) remained statistically significant after Bonferroni-correction. Diagnostic meta-analysis showed reliable diagnostic capacity of miR-200a-3p (with a pooled sensitivity of 0.84 and specificity of 0.83) and miR-200c-3p (with a pooled sensitivity of 0.75 and specificity of 0.66) for EOC. Pathway enrichment analysis and expression correlation analysis suggested miR-200a/c might contribute EOC progression by affecting cellular adhesion process. Kaplan-Meier survival analysis based on two independent cohorts revealed a strong association between miR-200a/c and overall survival in EOC patients. miR-200a/c was identified as the mostly dysregulated miRNAs in EOC and might be novel diagnostic and prognostic biomarkers for patients with EOC.

Purpose Bevacizumab plus platinum-based doublet chemotherapy is recommended by the National Comprehensive Cancer Network as a category 1 regimen and is widely used in patients with advanced nonsquamous non–small-cell lung cancer (NS-NSCLC). In China, a common first-line chemotherapy for NS-NSCLC is the pemetrexed-platinum doublet regimen (Pem-Pt). However, limited evaluation exists to show the effectiveness of the Pem-Pt + bevacizumab (Bev) regimen in advanced NS-NSCLC. This study describes the treatment patterns, effectiveness, and safety profile of Pem-Pt + Bev in patients with NS-NSCLC in China in clinical practice. Methods Data from eligible patients with advanced NS-NSCLC who received Pem-Pt with (136 patients) or without (97 patients) bevacizumab from January 2012 to March 2017 were retrospectively evaluated. The effectiveness outcomes included the assessment of progression-free survival (PFS) and objective response rate (ORR) in the overall population, the percentage of patients with pleural effusion or brain metastasis, as well as the percentage of patients receiving maintenance therapy. Moreover, the intracranial remission rate in patients with brain metastasis was estimated. Finally, the adverse events with the 2 treatments were addressed. Findings Compared with the Pem-Pt regimen, the Pem-Pt + Bev regimen was associated with a significantly longer median PFS and a higher ORR in the overall population (P = 0.0002). An improvement in ORR was observed in Pem-Pt + Bev–treated patients with brain metastasis (P = 0.0045). Moreover, patients receiving Pem-Pt + Bev and maintenance therapy not only showed a longer median PFS than that in those whose treatment was interrupted after induction but also a longer median PFS than that in patients who received Pem-Pt and maintenance therapy. The safety profile was acceptable in all groups, with no observations of hypertension, proteinuria, severe bleeding (1 case of grade I epistaxis was reported with Pem-Pt + Bev), or any unexpected findings reported. Implications These results from clinical practice further support the concept that pemetrexed-platinum doublet plus bevacizumab could be an effective and tolerable regimen in patients with advanced NS-NSCLC in China.

Background: The recent global dissemination of chikungunya virus (CHIKV), yellow fever virus (YFV), and Zika virus (ZIKV) has fostered public health concerns worldwide. Assessing and predicting the risk of spatial spread of emerging infectious diseases is key for the development of appropriate local, mitigation strategies. Methods: We constructed a predictive model using state-of-the-art machine learning techniques to identify the main eco-environmental and socio-economic factors underlying the dissemination of emerging infectious diseases, and to forecast the spatio-temporal diffusion of emerging infectious diseases under climate-warming scenarios. Findings: Climatic conditions (temperature, precipitation, and relative humidity) were obvious indicators and there was a high risk of mosquito-borne diseases becoming established throughout Latin America, South Asia, and Africa between 2019 and 2023. The rate of westward spread in Africa was faster than the eastward diffusion patterns across America. Importantly, there was a significant positive correlation between temperature conditions and the diffusion rates of these arbovirus infections. Interpretation: The present study provides valuable evidence-based information for anticipating the global diffusion of mosquito-borne viruses. Our results suggest a role for climate change and global warming in the re-emergence and spread of these diseases. Local authorities should reinforce epidemiological surveillance and environmental monitoring measures to avoid severe epidemics. Funding Statement: State Key Laboratory of Pathogen and Biosecurity Program (no. SKLPBS1408 and no. SKLPBS1451). Declaration of Interests: The authors declare that they have no conflict of interest.

Epithelial ovarian cancer (EOC) is the most lethal and aggressive gynecological malignancy, and abnormal cellular metabolism significantly contributes to cancer onset and progression. Here, we report that miR-29b negatively regulates AKT2/AKT3 expression, causing HK2/PKM2 downregulation and leading to a decreased Warburg effect and slowed ovarian cancer progression. Compared to normal ovaries, ovaries with epithelial cancer exhibited lower miR-29b expression at both cellular/histological levels. Glucose consumption and lactate production experiments confirmed miR-29b's regulation of EOC metabolism. A luciferase reporter assay confirmed the direct binding of miR-29b to AKT2/AKT3 3′ UTRs. miR-29b silencing correlated with increased expression of AKT2/3, pAKT2/3, HK2, and PKM2. Pyruvic acid and NAD+/NADH levels also changed when miR-29b expression was suppressed; this effect could be blocked by specific AKT inhibitors, suggesting the miR-29b-AKT axis regulates the Warburg effect in ovarian cancer. In xenograft mouse models, miR-29b inhibited tumor formation in vivo. In vivo imaging also demonstrated that miR-29b agomir inhibited the relative uptake of 18F-FDG in the xenograft tumors, suggesting that miR-29b over-expression could negatively modulate tumor glucose metabolism in vivo. Taken together, our study suggests that miR-29b regulates the Warburg effect in EOC via AKT2/AKT3 and may provide novel options for future treatments for EOC.

This study was conducted to examine the association of perfluoroalkyl substance (PFAS) exposure with gestational diabetes mellitus (GDM) risk and postpartum fasting blood glucose. We used a 1:2 matched case-control study with 84 GDM subjects and 168 healthy pregnant women from Beijing, China. The maternal blood was collected at 1-2days before delivery, and eight linear isomers and fourteen branched isomers were determined in maternal serum. Logistic regression analyses were performed to evaluate the associations after adjusting for potential confounders. The median of the sum of levels of total PFASs was 4.24ng/mL with a interquartile range (IQR) of 2.82-6.54ng/mL. Although maternal PFAS exposure was not associated with risk of GDM, significant positive associations were observed between evaluated exposure to specific PFAS congeners and increasing blood glucose. The odds ratio (ORs) of the highest category of postpartum fasting blood glucose for perfluoro-1-metylheptylsulfonat (1m-PFOS), perfluoro-3/4-metylheptylsulfonat (3m+4m-PFOS), perfluoro-5-metylheptylsulfonat (5m-PFOS), and perfluorohexane sulfonate (PFHxS) were 2.03 (95% CI: 1.09-3.77), 1.93 (95% CI: 1.04-3.58), 2.48 (95% CI: 1.33-4.65), and 2.26 (95% CI: 1.21-4.21), respectively, suggesting negative effects of maternal exposure to specific PFAS compounds on glucose metabolism.

Zika virus (ZIKV) infection is an emerging global threat that is suspected to be associated with fetal microcephaly. However, the molecular mechanisms underlying ZIKV disease pathogenesis in humans remain elusive. Here, we investigated the human protein interaction network associated with ZIKV infection using a systemic virology approach, and reconstructed the transcriptional regulatory network to analyze the mechanisms underlying ZIKV-elicited microcephaly pathogenesis. The bioinformatics findings in this study show that P53 is the hub of the genetic regulatory network for ZIKV-related and microcephaly-associated proteins. Importantly, these results imply that the ZIKV capsid protein interacts with mouse double-minute-2 homolog (MDM2), which is involved in the P53-mediated apoptosis pathway, activating the death of infected neural cells. We also found that synthetic mimics of the ZIKV capsid protein induced cell death in vitro and in vivo. This study provides important insight into the relationship between ZIKV infection and brain diseases.

Background: Transforming growth factor beta 1 (TGFβ1) can induce epithelial-mesenchymal transition (EMT) in various human cancers, but the complex mechanisms underlying this have not been fully elucidated. Inhibitor of DNA binding 1 (Id-1) has been identified as a novel marker of ovarian cancer progression. This study aims to investigate the role of Id-1 in TGFβ1-induced EMT in human ovarian cancer cells. Methods: Ovarian cancer cells expressing or not expressing Id-1 were incubated with TGFβ1. Changes in the EMT markers E-cadherin, vimentin, N-cadherin, Id-1, and miR-29b were detected using western blotting and qPCR analyses. Wound healing, transwell migration, and invasion assays were performed in cells where Id-1 was either knocked down or overexpressed. The effects of transfecting miR-29b mimics and inhibitors on Id-1 mRNA and protein expression were assessed. The interaction between miR-29b and Id-1 was confirmed using a luciferase reporter assay. Results: Id-1 expression was increased and miR-29b expression was repressed in TGFβ1-responsive ovarian cancer cells. Id-1 overexpression increases and Id-1 knockdown decreases cell migration and invasion capacities. Id-1 silencing leads to a partial blocking of TGFβ1-induced EMT. miR-29b negatively regulates Id-1 expression. Direct binding of miR-29b to the 3'UTR region of Id-1 was confirmed using a luciferase reporter assay. Conclusion: Id-1, a protein repressed by miR-29b, facilitates TGFβ1-induced EMT in human ovarian cancer cells and represents a promising therapeutic target for treating ovarian cancer.

Choroquine (CQ) and valproic acid (VPA) have been extensively studied for biological effects. Here, we focused on efficacy of combined CQ and VPA on osteosarcoma cell lines. Viability of osteosarcoma cell lines (U20S and HOS) was analyzed by MTT assay. Apoptotic assays and colony formation assays were also applied. ROS generation and Western Blotting were performed to determine the mechanism of CQ and VPA combination in the process of apoptosis. The viability of different osteosarcoma cell lines significantly decreased after CQ and VPA combination treatment compared with either drug used alone, and apoptosis was increased significantly. ROS generation was triggered leading to expression of apoptosis related genes being increased and of anti- apoptotic related genes being decreased. From our data shown here, CQ and VPA combination treatment in vitro enhanced cytotoxicy to osteosarcoma cells.

ObjectiveDisordered metabolism of estrogen is believed to play a significant role in endometrial carcinogenesis. Recently, a number of studies have been conducted to identify the role of estrogen-related gene polymorphism in endometrial cancer risk, generating conflicting conclusions. This meta-analysis aimed to assess the association between genetic polymorphisms involving estrogen metabolic enzymes and endometrial cancer risk.MethodsA systematic search of 6 databases was conducted. Fourteen studies on the association of COMT (catechol-O-methyltransferase) Val158Met, CYP1B1 Leu432Val, and CYP1B1 Asn453Ser polymorphisms with endometrial cancer risk were identified, enrolling a total of 4283 cancer cases and 7094 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the relationship.ResultsIn CYP1B1 Leu432Val(rs1056836) analysis, the heterozygous genotype (CG) demonstrated an increased risk for endometrial cancer (Val/Leu vs Leu/Leu: pooled OR, 1.11; 95% CI, 1.01–1.23;P= 0.039;I2= 10.5%; (Val/Val +Val/Leu) vs Leu/Leu: pooled OR, 1.19; 95% CI, 1.03–1.38;P= 0.017;I2= 54.7%). As for CYP1B1 Asn453Ser(rs1800440) polymorphism, a decreased risk was observed in G allele compared with A allele (Ser vs Asn: pooled OR, 0.82; 95% CI, 0.72–0.94;P= 0.005;I2= 0.0%), and heterozygous genotype also showed a decreased risk compared with normal genotype (Ser/Asn vs Asn/Asn: pooled OR, 0.81; 95% CI, 0.69–0.95;P= 0.011;I2= 0.0%). As for COMT Val158Met (rs4680) polymorphism, the heterogeneous genotype showed a decreased risk for endometrial cancer compared with the common homogenous genotype in a fixed-effect model in Asian population (Met/Val vs Val/Val: pooled OR, 0.83; 95% CI, 0.70–0.98;P= 0.033;I2= 29.2%), whereas no positive results are found in other subgroups or models.ConclusionsCOMT Val158Met was seen to show a decreased risk for endometrial cancer in Asian population. CYP1B1 Leu432Val and Asn453Ser polymorphisms demonstrated an increased and decreased risk for endometrial cancer, respectively. Further large and comprehensive studies in various populations with more detailed individual data are needed to confirm our findings.

We developed a dynamic forecasting model for Zika virus (ZIKV), based on real-time online search data from Google Trends (GTs). It was designed to provide Zika virus disease (ZVD) surveillance for Health Departments with early warning, and predictions of numbers of infection cases, which would allow them sufficient time to implement interventions. We used correlation data from ZIKV epidemics and Zika-related online search in GTs between 12 February and 25 August 2016 to construct an autoregressive integrated moving average (ARIMA) model (0, 1, 3) for the dynamic estimation of ZIKV outbreaks. The online search data acted as an external regressor in the forecasting model, and was used with the historical ZVD epidemic data to improve the quality of the predictions of disease outbreaks. Our results showed a strong correlation between Zika-related GTs and the cumulative numbers of reported cases, both confirmed and suspected (both p; Pearson Product-Moment Correlation analysis). The predictive cumulative numbers of confirmed and suspected cases increased steadily to reach 148,510 (95% CI: 126,826-170,195) and 602,721 (95% CI: 582,753-622,689), respectively, in 21 October 2016. Integer-valued autoregression provides a useful base predictive model for ZVD cases. This is enhanced by the incorporation of GTs data, confirming the prognostic utility of search query based surveillance. This accessible and flexible dynamic forecast model could be used in the monitoring of ZVD to provide advanced warning of future ZIKV outbreaks.

The study reviewed coping and help-seeking behaviour among Hong Kong Chinese family care-givers of older people diagnosed with dementia. A convenience sample of those caring for family members with dementia (N=11) was recruited in Hong Kong. Semi-structured interviews were conducted, transcribed and analysed using NVivo. The study found evidence of distinct Chinese coping strategies that focused upon internal self-regulation, forbearance and family obligations. In terms of help-seeking behaviour, these care-givers expressed great concern about bothering their family members. When there is a desperate need for help, they turn to community services. Results are discussed in the context of both traditional Chinese cultural values as well as the modern transformations of the Chinese society. In particular, Eastern philosophical teachings tend to focus on changing personal inner perception and thoughts rather than attempting to change the environment. Although family obligations have been traditionally upheld, many modern Chinese societies are undergoing social and demographic changes, resulting in marked decline in multi-generational households. Our findings can have applications not only for Chinese cities but also may have implications to the West as strong well-established Chinese communities are widespread.

Background and Objectives:To identify clinicopathologic variables that could predict pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer.Methods:The study enrolled 108 patients who underwent neoadjuvant chemotherapy followed by surgery between July

Background The measurement of hydrogen peroxide (H 2 O 2 ) in exhaled breath condensate (EBC) has been proposed as a noninvasive way of monitoring airway inflammation. However, results from individual studies on EBC H 2 O 2 evaluation of asthma are conflicting. The purpose of this study was to explore whether EBC H 2 O 2 is elevated in people with asthma and whether it reflects disease severity and disease control or responds to corticosteroid treatment. Methods Studies were identified by searching PubMed, Embase, Cochrane Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and www.controlled-trials.com for relevant reports published before September 2010. Observational studies comparing levels of EBC H 2 O 2 between patients with asthma who were nonsmokers and healthy subjects were included. Data were independently extracted by two investigators and analyzed using Stata 10.0 software. Results Eight studies (involving 728 participants) were included. EBC H 2 O 2 concentrations were significantly higher in patients with asthma who were nonsmokers compared with healthy subjects, and higher values of EBC H 2 O 2 were observed at each level of asthma, classified either by severity or control level, and the values were negatively correlated with FEV 1 . In addition, EBC H 2 O 2 concentrations were lower in patients with asthma treated with corticosteroids than in patients with asthma not treated with corticosteroids. Conclusions H 2 O 2 might be a promising biomarker for guiding asthma treatment. However, further investigation is needed to establish its role.