Publications by authors named "Jin-Hua Hu"

58 Publications

Severe acute liver injury in patients with exertional heat stroke associated with poor short-term prognosis.

World J Emerg Med 2022 ;13(2):124-129

Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.

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http://dx.doi.org/10.5847/wjem.j.1920-8642.2022.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861344PMC
January 2022

The diagnostic performance of ultrasound computer-aided diagnosis system for distinguishing breast masses: a prospective multicenter study.

Eur Radiol 2022 Jun 23;32(6):4046-4055. Epub 2022 Jan 23.

Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China.

Objectives: To evaluate the diagnostic value of computer-aided diagnosis (CAD) software on ultrasound in distinguishing benign and malignant breast masses and avoiding unnecessary biopsy.

Methods: This prospective, multicenter study included patients who were scheduled for pathological diagnosis of breast masses between April 2019 and November 2020. Ultrasound images, videos, CAD analysis, and BI-RADS were obtained. The AUC, accuracy, sensitivity, specificity, PPV, and NPV were calculated and compared with radiologists.

Results: Overall, 901 breast masses in 901 patients were enrolled in this study. The accuracy, sensitivity, specificity, PPV and NPV of CAD software were 89.6%, 94.2%, 87.0%, 80.4%, and 96.3, respectively, in the long-axis section; 89.0%, 91.4%, 87.7%, 80.8%, and 94.7%, respectively, in the short-axis section. With BI-RADS 4a as the cut-off value, CAD software has a higher AUC (0.906 vs 0.734 vs 0.696, all p < 0.001) than both experienced and less experienced radiologists. With BI-RADS 4b as the cut-off value, CAD software showed better AUC than less experienced radiologists (0.906 vs 0.874, p < 0.001), but not superior to experienced radiologists (0.906 vs 0.883, p = 0.057). After the application of CAD software, the unnecessary biopsy rate of BI-RADS categories 4 and 5 was significantly decreased (33.0% vs 11.9%, 37.8% vs 14.5%), and the malignant rate of biopsy in category 4a was significantly increased (11.6% vs 40.7%, 7.4% vs 34.9%, all p < 0.001).

Conclusions: CAD software on ultrasound can be used as an effective auxiliary diagnostic tool for differential diagnosis of benign and malignant breast masses and reducing unnecessary biopsy.

Clinical Trial Registration: ClinicalTrials.gov (NCT03887598) KEY POINTS: • Prospective multicenter study showed that computer-aided diagnosis software provides greater diagnostic confidence for differentiating benign and malignant breast masses. • Computer-aided diagnosis software can help radiologists reduce unnecessary biopsy. • The management of patients with breast masses becomes more appropriate.
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http://dx.doi.org/10.1007/s00330-021-08452-1DOI Listing
June 2022

The periscreen strip is an accurate and rapid method to diagnose spontaneous bacterial peritonitis among patients with acute-on-chronic liver failure.

Eur J Gastroenterol Hepatol 2021 12;33(1S Suppl 1):e206-e213

Liver Failure Treatment and Research Center, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

Background: Leukocyte esterase reagent strips may help diagnose spontaneous bacterial peritonitis (SBP), but their effective application among patients with acute-on-chronic liver failure (ACLF) remains unknown.

Aim: This study aimed to assess the performance of periscreen strips in the rapid diagnosis of SBP among patients with ACLF.

Methods: Periscreen strips were used to test 261 ascites samples taken from 251 inpatients with ACLF between January 2014 and June 2019. The colors of the reagent strip were divided into four colorimetric graduations ('negative', 'trace', 'small', and 'large'), among which 'trace' is used as the SBP detection threshold. The polymorphonuclear neutrophils (PMN) of ascites ≥250/mm3 was used as the gold standard for SBP diagnosis.

Results: SBP was detected in 92 (35.2%) ascite samples. The ascites PMN count of 'negative' (32.5/mm3) was lower than those of 'trace' (248.2/mm3), 'small' (379.0/mm3), and 'large' (7426.0/mm3) (P < 0.001). The colorimetric graduations of the strips were positively correlated with ascites PMN count (r = 0.867, P < 0.001). Periscreen strips had 100% sensitivity, 91.1% specificity, 86.0% positive predictive value, 100% negative predictive value, 11.3 positive likelihood ratios, and 0 negative likelihood ratios. For patients with negative results judged by the gold standard, ascites white blood cells count [odds ratio (OR) = 1.007) and ascites PMN count (OR = 1.028) were independent predictors of false-positive cases.

Conclusion: Liver failure did not affect the diagnostic performance of periscreen strips. Therefore, these strips can efficiently and rapidly diagnose SBP among patients with ACLF.
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http://dx.doi.org/10.1097/MEG.0000000000002007DOI Listing
December 2021

[Mean microvessel density of the prepuce and its relationship with the severity of hypospadias and early postoperative complications].

Zhonghua Nan Ke Xue 2021 Aug;27(8):725-728

Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510000, China.

Objective: To investigate the mean preputial microvessel density (mMVD) and features of hypospadias and their relationship with the severity and early postoperative complications of the disease.

Methods: Sixty children with hypospadias and another 14 age-matching ones with phimosis (the control group) underwent penile curvature correction, Snodgrass procedure or staged surgery, the excessive dorsal foreskin trimmed and retained. We determined the mMVD in the prepuce tissue of the patients by immunohistochemistry, and followed up those treated by Snodgrass procedure.

Results: The mMVD was significantly lower in the patients with severe hypospadias than in those with mild hypospadias and the controls (15.51 ± 3.53 vs 19.27 ± 4.42 and 22.09 ± 6.15, P < 0.05), with a median of 21.8 in the control group. The incidence of postoperative complications was obviously lower in the high mMVD (≥ 21.8) than in the low mMVD (< 21.8) group.

Conclusions: The preputial mMVD is significantly lower in patients with severe hypospadias than in normal children, decreasing in a severity-dependent manner. The lower the preputial mMVD, the higher the incidence rate of postoperative complications. The preputial mMVD of 21.8 can be used as a reference index for evaluating the prognosis of surgery clinically. ?
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August 2021

Added Value of a New Strain Elastography Technique in Conventional Ultrasound for the Diagnosis of Breast Masses: A Prospective Multicenter Study.

Front Oncol 2021 9;11:779612. Epub 2021 Nov 9.

Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: This study aimed to explore the value of elasticity score (ES) and strain ratio (SR) combined with conventional ultrasound in distinguishing benign and malignant breast masses and reducing biopsy of BI-RADS (Breast Imaging Reporting and Data System) 4a lesions.

Methods: This prospective, multicenter study included 910 patients from nine different hospitals. The acquisition and analysis of conventional ultrasound and strain elastography (SE) were obtained by radiologists with more than 5 years of experience in breast ultrasound imaging. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) of conventional ultrasound alone and combined tests with ES and/or SR were calculated and compared.

Results: The optimal cutoff value of SR for differentiating benign from malignant masses was 2.27, with a sensitivity of 60.2% and a specificity of 84.8%. When combined with ES and SR, the AUC of the new BI-RADS classification increased from 0.733 to 0.824 ( < 0.001); the specificity increased from 48.1% to 68.5% ( < 0.001) without a decrease in the sensitivity (98.5% . 96.4%, = 0.065); and the PPV increased from 52.2% to 63.7% ( < 0.001) without a loss in the NPV (98.2% . 97.1%, = 0.327). All three combinations of conventional ultrasound, ES, and SR could reduce the biopsy rate of category 4a lesions without reducing the malignant rate of biopsy (from 100% to 68.3%, 34.9%, and 50.4%, respectively, all < 0.001).

Conclusions: SE can be used as a useful and non-invasive additional method to improve the diagnostic performance of conventional ultrasound by increasing AUC and specificity and reducing the unnecessary biopsy of BI-RADS 4a lesions.
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http://dx.doi.org/10.3389/fonc.2021.779612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631107PMC
November 2021

Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial.

Hepatol Int 2021 Dec 29;15(6):1431-1441. Epub 2021 Nov 29.

Medical Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, 100039, China.

Background: Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood.

Methods: This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated.

Results: During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group.

Conclusions: Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.
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http://dx.doi.org/10.1007/s12072-021-10199-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651584PMC
December 2021

The pharmacodynamic effect of terlipressin versus high-dose octreotide in reducing hepatic venous pressure gradient: a randomized controlled trial.

Ann Transl Med 2021 May;9(9):793

Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Vasoactive drugs can reduce portal venous pressure and control variceal bleeding. However, few studies have explored the hemodynamic effects of terlipressin and high-dose octreotide in such patients. Our purpose was to evaluate the hemodynamic changes and safety of using terlipressin and high-dose octreotide in patients with decompensated liver cirrhosis.

Methods: A multi-center randomized controlled trial was conducted. Cirrhotic patients with a history of variceal bleeding were included. Terlipressin or high-dose octreotide was administered during the procedure of measuring hepatic venous pressure gradient (HVPG). Hemodynamic parameters and symptoms were recorded.

Results: A total of 88 patients were included. HVPG was significantly reduced at 10, 20, and 30 min after drug administration in the terlipressin group (16.3±6.4 14.7±5.9, 14.0±6.1, and 13.8±6.1, respectively, P<0.001) and the high-dose octreotide group (17.4±6.6 15.1±5.8, 15.3±6.2, and 16.1±6.0, respectively P<0.01). Decreased heart rate and increased mean arterial pressure were more often observed in the terlipressin group. The overall response rates were not significantly different between the groups (52.8% 44.8%, P=0.524). The terlipressin group had significantly higher response rates at 30 min compared to the high-dose octreotide group in those with alcoholic liver cirrhosis [6/6 (100%) 0/4 (0%), P=0.005]. The incidence of adverse drug events was rare and similar in the two groups.

Conclusions: Both terlipressin and high-dose octreotide were effective and safe for reducing HVPG. The pharmacodynamic effect of terlipressin persisted longer. The terlipressin group had higher response rates in those with alcoholic cirrhosis (trial number: NCT02119884).
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http://dx.doi.org/10.21037/atm-20-6774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246168PMC
May 2021

Assessment of different modalities for repeated tissue acquisition in diagnosing malignant biliary strictures: A two-center retrospective study.

J Dig Dis 2021 Feb 27;22(2):102-107. Epub 2020 Dec 27.

Department of Gastroenterology, Changhai Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.

Objective: Various modalities are applied for pathological diagnosis of malignant biliary strictures (MBS), including brush cytology (BC), forceps biopsy (FB) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We aimed to assess the value of these modalities in a repeated tissue acquisition process for biliary strictures with initially inconclusive pathological outcomes.

Methods: Patients who were suspected of having MBS and underwent a BC in two large teaching hospitals were retrospectively included. The sensitivity, specificity, positive and negative predictive values, and accuracy of the initial and repeated BC, FB and EUS-FNA were analyzed. Their performances were compared to determine which modality was superior in repeated tissue acquisition.

Results: In total, 476 patients were included. The sensitivity, specificity and accuracy in diagnosing MBS for the initial BC were 30.3%, 100% and 55.0%, respectively. Altogether 39, 27 and 44 patients underwent a repeat BC, FB and EUS-FNA, respectively. The sensitivity for repeated BC, FB and EUS-FNA was 41.2%, 61.1% and 44.4%, respectively, whereas their specificity all reached 100%. When comparing diagnostic accuracy, none of the modalities was superior (74.4% vs 74.1% vs 54.5%, P = 0.173). In the repeated process, one patient who underwent BC and two underwent FB developed mild pancreatitis.

Conclusions: Repeated tissue acquisition achieves a conclusive diagnosis of MBS in nearly half patients who have an initially inconclusive cytological diagnosis. None of the tissue acquisition methods is significantly superior in the repeated process.
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http://dx.doi.org/10.1111/1751-2980.12964DOI Listing
February 2021

Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.

Biomed Pharmacother 2021 Jan 9;133:110868. Epub 2020 Nov 9.

Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital and Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

Male infertility has become an important health problem that is primarily caused by testicular dysfunction with abnormal spermatogenesis. In this study, we demonstrated that the neuropeptide, substance P (SP), is essential for spermatogonia proliferation in a seminiferous tubule culture system. In addition, SP (5 nmol/kg) treatment markedly restored spermatogenesis, improved sperm quality, and increased the number of ZBTB16 or LIN28 undifferentiated spermatogonia as well as STRA8 differentiated spermatogonia in a busulfan-induced non-obstructive azoospermic mouse model. Furthermore, 100 nM SP treatment in vitro significantly stimulated the proliferation of GC-1 spg cells (a spermatogonia cell line) via activation of the Erk1/2 signaling pathway. Moreover, the sperm quality and the number of spermatogonia were significantly reduced after treatment with RP67580, a selective NK-1 receptor antagonist, suggesting that SP-NK1R signaling plays an important role in spermatogenesis. Taken together, these results suggest that SP may be a potential therapeutic agent for male infertility by accelerating the restoration of spermatogenesis.
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http://dx.doi.org/10.1016/j.biopha.2020.110868DOI Listing
January 2021

Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study.

BMC Gastroenterol 2020 Sep 29;20(1):320. Epub 2020 Sep 29.

Peking University 302 Clinical Medical School, Beijing, China.

Background: Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China.

Methods: We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated.

Results: A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection.

Conclusions: Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.
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http://dx.doi.org/10.1186/s12876-020-01473-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526233PMC
September 2020

A report on Lineage switch at relapse of CD19 CAR-T therapy for Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia.

Chin Med J (Engl) 2020 08;133(16):2001-2003

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China.

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http://dx.doi.org/10.1097/CM9.0000000000000962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462201PMC
August 2020

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure.

World J Clin Cases 2020 Mar;8(6):1042-1055

Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.

Background: Acute-on-chronic liver failure (ACLF), which includes hepatic and multiple extra-hepatic organ failure, is a severe emergency condition that has high mortality. ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation. Bacterial infections (BIs) trigger ACLF and play pivotal roles in the deterioration of clinical course.

Aim: To investigate the clinical characteristics and 28-d outcomes of first BIs either at admission or during hospitalization in patients with hepatitis B virus (HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B (COSSH).

Methods: A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016. The characteristics of BIs, the 28-d transplant-free survival rates, and the independent predictors of the 28-d outcomes were evaluated.

Results: A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF. Among the episodes, 13.4% were community-acquired, 46.4% were healthcare-associated, and 40.2% belonged to nosocomial BIs. Pneumonia (40.7%), spontaneous bacterial peritonitis (SBP) (34.5%), and bloodstream infection (BSI) (13.4%) were the most prevalent. As the ACLF grade increased, the incidence of SBP showed a downward trend ( = 0.021). Sixty-one strains of bacteria, including 83.6% Gram-negative bacteria and 29.5% multidrug-resistant organisms, were cultivated from 50 patients with ACLF. (44.3%) and (23.0%) were the most common bacteria. As the ACLF grade increased, the 28-d transplant-free survival rates showed a downward trend (ACLF-1, 55.7%; ACLF-2, 29.3%; ACLF-3, 5.4%; < 0.001). The independent predictors of the 28-d outcomes of patients with HBV-ACLF were COSSH-ACLF score (hazard ratio [HR] = 1.371), acute kidney injury (HR = 2.187), BSI (HR = 2.339), prothrombin activity (HR = 0.967), and invasive catheterization (HR = 2.173).

Conclusion: For patients with HBV-ACLF combined with first BIs, pneumonia is the most common form, and the incidence of SBP decreases with increasing ACLF grade. COSSH-ACLF score, acute kidney injury, BSI, prothrombin activity, and invasive catheterization are the independent predictors of 28-d outcomes.
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http://dx.doi.org/10.12998/wjcc.v8.i6.1042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103966PMC
March 2020

High-dependency units play a key role in the treatment of a Chinese military patient who developed liver failure while abroad.

Mil Med Res 2019 09 16;6(1):29. Epub 2019 Sep 16.

Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.

High-dependency units (HDUs) provide high-level care to patients who suffer from single organ failure, with the exception of respiratory failure requiring mechanical ventilation; HDUs serve as an intermediary between general wards and Intensive Care Units. Due to military and civilian needs, our hospital has established a unique HDU for patients with liver disease in China. A Chinese military officer in the United Nations Peacekeeping Forces in South Sudan was transferred to our HDU for liver failure treatment in 2018. The patient's disease status, nutrition, sleep habits, and psychological behaviour were monitored on different scales. The patient was provided with vascular monitoring, telemetry, pulse oximetry, drug treatment, nutritional support, sleep intervention, psychological intervention, and humanistic care by a multidisciplinary treatment team. After treatment, the patient recovered and avoided liver transplantation. Based on the experience with this HDU, this new model may create an efficient treatment process for military and civilian patients with severe liver disease at home or abroad.
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http://dx.doi.org/10.1186/s40779-019-0220-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745794PMC
September 2019

Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure.

Chin Med J (Engl) 2019 Jul;132(13):1541-1549

Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.

Background: As a large, prospective, multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score (COSSH-ACLFs), has been approved by some foreign scholars; however, its predictive value needs to be verified. This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.

Methods: This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014. Spearman method was used to assess the correlation of COSSH-ACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSH-ACLFs and short-term prognosis in patients with HBV-ACLF, and stratified analysis was used to further verify the stability of this relationship. We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve (AUROC) and Z-test.

Results: A total of 975 patients with HBV-ACLF were screened, and 751 were analyzed (623 male and 128 female). COSSH-ACLFs was the highest in patients with end-stage ACLF, followed by those with middle- and early-stage ACLF (H = 211.8, P < 0.001). In the fully adjusted model, COX multivariate regression analysis revealed that COSSH-ACLFs (as a continuous variable) was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days (hazard ratio [HR]: 1.37 [1.22, 1.53], P < 0.001) and 90 days (HR: 1.43 [1.29, 1.58], P < 0.001). The same trend could be observed in the crude model and minimally adjusted model. The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792, respectively, indicating a stronger predictive accuracy than those of classic models.

Conclusions: COSSH-ACLFs, with a superior predictive accuracy compared with other classical scores, can strongly predict short-term prognosis in Chinese patients with HBV-ACLF.
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http://dx.doi.org/10.1097/CM9.0000000000000298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616238PMC
July 2019

Bioactivity of CD34+ cells in patients with acute-on-chronic liver failure.

Int J Clin Exp Pathol 2017 1;10(11):10781-10791. Epub 2017 Nov 1.

Liver Failure Treatment and Research Center, 302 Hospital of PLA Beijing, China.

Liver failure is a life-threatened serious disease with many complications and high mortality rate. Stem cells have been applied to replacement therapy, gene therapy and tissue engineering for its capacity of self-renewal and multi-lineage differentiation. To investigate the bioactivity of the peripheral blood hematopoietic stem cells (PBHSC) in patients with acute-on-chronic liver failure, we isolated CD34+ cells from peripheral blood of patients with acute-on-chronic liver failure and healthy controls. After cultured it in serum-free medium (SFEM), we studied the bioactivity of CD34+ cells by observing the morphology, recording growth curve, detecting cell cycle and cell apoptosis. CD34+ cells and culture solution were collected at the time points of 3, 5, 7, 10, 12 and 14 days, and the levels of hepatocyte growth factor (HGF), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in culture solution were detected by ELISA. Also, the expressions of pyruvate kinase muscle isoenzyme 2 (PKM2), integrin-β1 and liver-type pyruvate kinase (LPK) were detected by RT-PCR and immunofluorescence. Our results showed the bioactivity of CD34+ cells from patients with acute-on-chronic liver failure was identified to be similar with that from healthy controls. HGF, MMP-9, TNF-α and IL-6 were found in cell culture medium. RT-PCR and immunofluorescence results indicated that PKM2, Integrin-β1 expressed on CD34+ cells from patients with acute-on-chronic liver failure. In conclusion, bioactivity of CD34+ cells of patients with acute-on-chronic liver failure was demonstrated to be normal, which could secrete HGF, MMP-9, TNF-α and IL-6, promote the growth of hepatocytes, and differentiate along a direction to hepatocyte lineage.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965859PMC
November 2017

Associations between gene polymorphisms and Wilms' tumor susceptibility.

Oncotarget 2017 Aug 7;8(31):50665-50672. Epub 2017 Apr 7.

Department of Pediatric Urology, Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.

Wilms' tumor is the most common childhood renal malignancy. A genome-wide association study identified LIM domain only 1 (LMO1) as having oncogenic potential. We examined the associations between gene polymorphisms and susceptibility to Wilms' tumor. In this hospital-based, case-control study, we recruited 145 children with Wilms' tumor and 531 cancer-free children. Four polymorphisms (rs110419 A>G, rs4758051 G>A, rs10840002 A>G and rs204938 A>G) were genotyped using Taqman methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the associations between selected polymorphisms and Wilms' tumor susceptibility. Only rs110419 AG was found to be protective against Wilms' tumor (adjusted OR = 0.62, 95% CI = 0.41-0.94, = 0.024) when compared to rs110419 AA. Wilms' tumor risk was markedly greater in children with 1-4 risk genotypes (nucleotide alterations) than in those with no risk genotypes (adjusted OR = 1.84, 95% CI = 1.25-2.69, = 0.002). In a stratified analysis, the protective effect of rs110419 AG/GG was predominant in males. The association of 1-4 risk genotypes with Wilms' tumor risk was limited to subgroups of children who were >18 months old, female, and in clinical stages III+IV. Thus, gene polymorphisms may contribute to Wilms' tumor risk, but this conclusion should be validated in other populations and larger studies.
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http://dx.doi.org/10.18632/oncotarget.16926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584185PMC
August 2017

Differential characteristics and prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure defined by European Association for the Study of the Liver - Chronic Liver Failure criteria.

Hepatol Res 2018 Feb 4;48(2):153-164. Epub 2017 Jun 4.

Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China.

Aim: To determine the differential characteristics and prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) detected using Asian Pacific Association for the Study of the Liver (APASL) criteria and then classified using European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria.

Methods: We retrospectively reviewed 316 HBV-related APASL ACLF patients treated at Beijing 302 Hospital or Beijing You'An Hospital (both Beijing, China) between February 2015 and February 2016. Clinical characteristics and mortality rates were compared among patients with different EASL-CLIF ACLF severity grades (no ACLF, and ACLF grades 1-3).

Results: According to the EASL-CLIF criteria, 138 patients had no ACLF, 123 had ACLF at enrollment, and 55 developed ACLF during hospitalization. Both 28-day and 90-day transplant-free mortality were dramatically lower in patients without EASL-CLIF ACLF (0.7% and 5.1%, respectively) than in patients with EASL-CLIF ACLF (40.7% and 63.2%, respectively; both P < 0.001). Liver failure rates were similar in patients with and without EASL-CLIF ACLF, but extrahepatic organ failure was rare in patients without EASL-CLIF ACLF. Baseline serum creatinine, new bacterial infection and new acute kidney injury during hospitalization, maximum rising rates of CLIF-C ACLF score, and Model for End-stage Liver Disease score were independent predictors of EASL-CLIF ACLF after enrollment.

Conclusions: The EASL-CLIF ACLF classification can accurately prognosticate the short-term mortality of patients with HBV-related APASL ACLF. It can also distinguish distinct clinical characteristics and prognoses in patients with and without EASL-CLIF ACLF.
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http://dx.doi.org/10.1111/hepr.12909DOI Listing
February 2018

The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children.

J Clin Lab Anal 2018 Jan 16;32(1). Epub 2017 Mar 16.

Southern Medical University, Guangzhou, Guangdong, China.

Background: Wilms tumor (WT) is the most common urologic cancer in children. However, genetic bases underlying WT remain largely unknown. Previous studies indicated that Lin28 homolog B (LIN28B) level is significantly elevated in some WTs. Enforced expression of Lin28b during kidney development could induce WT. Genetic variations in the LIN28B gene may be related to WT susceptibility.

Method: In this study, we aimed to assess the association between LIN28B gene polymorphisms and WT susceptibility in Chinese children. Four potentially functional polymorphisms in the LIN28B gene (rs314276 C>A, rs221634 A>T, rs221635 T>C and rs9404590 T>G) were genotyped in 145 cases and 531 cancer-free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.

Results: Our results showed that the rs314276 CA genotype was associated with a decreased WT risk (CA vs CC: adjusted OR=0.65, 95% CI=0.43-0.98, P=.042). Moreover, we found that carriers of the 1-3 risk genotypes had a significantly increased WT risk when compared to the non-carriers (adjusted OR=1.51, 95% CI=1.03-2.20, P=.035). The association with risk genotypes was more predominant in children 18 month old or younger and in females.

Conclusion: In summary, these results indicated that the LIN28B gene rs314276 C>A polymorphism alone and three combined polymorphisms may be able to modify WT susceptibility in Southern Chinese children. Our findings call for further validation in large studies with different ethnicities involved.
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http://dx.doi.org/10.1002/jcla.22200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817198PMC
January 2018

BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility.

EBioMedicine 2017 Feb 31;16:101-105. Epub 2017 Jan 31.

Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China. Electronic address:

BRCA1-associated RING domain protein 1 (BARD1) is a tumor suppressor, which forms a heterodimer with BRCA1. Three BARD1 gene polymorphisms (rs7585356 G>A, rs6435862 T>G and rs3768716 A>G) were initially identified as high-risk neuroblastoma susceptibility loci by a previous GWAS. Because of the general tumor-suppressing function of BARD1, we hypothesized that these BARD1 gene polymorphisms might modify the susceptibility to nephroblastoma. We genotyped these polymorphisms in 145 cases and 531 controls using Taqman methods. Out of three polymorphisms, only the rs7585356 G>A polymorphism was significantly associated with increased susceptibility to nephroblastoma [AA vs. GG: adjusted odds ratio (OR)=1.78, 95% confidence interval (CI)=1.01-3.12]. Combined analysis of three polymorphisms indicated that subjects with 3 risk genotypes exhibited significantly elevated nephroblastoma risk, when compared with subjects with 0-2 risk genotypes (adjusted OR=1.72, 95% CI=1.02-2.89). Stratified analysis revealed that in term of clinical stage, rs7585356 AA carriers were associated with increased risk of developing clinical stage I+II nephroblastoma. The presence of three risk genotypes was significantly associated with nephroblastoma risk in females and clinical stage I+II nephroblastoma. Our results suggested that BARD1 rs7585356 G>A may be associated with nephroblastoma risk.
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http://dx.doi.org/10.1016/j.ebiom.2017.01.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474516PMC
February 2017

NFKB1 -94insertion/deletion ATTG polymorphism and cancer risk: Evidence from 50 case-control studies.

Oncotarget 2017 Feb;8(6):9806-9822

Department of Pediatric Urology, Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.

Nuclear factor-kappa B1 (NF-κB1) is a pleiotropic transcription factor and key contributor to tumorigenesis in many types of cancer. Numerous studies have addressed the association of a functional insertion (I)/deletion (D) polymorphism (-94ins/delATTG, rs28362491) in the promoter region of NFKB1 gene with the risk of various types of cancer; however, their conclusions have been inconsistent. We therefore conducted a meta-analysis to reevaluate this association. PubMed, EMBASE, China National Knowledge infrastructure (CNKI), and WANFANG databases were searched through July 2016 to retrieve relevant studies. After careful assessment, 50 case-control studies, comprising 18,299 cases and 23,484 controls were selected. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to determine the strength of the association. The NFKB1 -94ins/delATTG polymorphism was associated with a decreased risk of overall cancer in the homozygote model (DD vs. II): OR = 0.75, 95% CI = 0.64-0.87); heterozygote model (ID vs. II): OR = 0.91, 95% CI = 0.83-0.99; recessive model (DD vs. ID/II): OR = 0.81, 95% CI = 0.71-0.91; dominant model (ID/DD vs. II): OR = 0.86, 95% CI = 0.78-0.95; and allele contrast model (D vs. I): OR = 0.88, 95% CI = 0.81-0.95). Subgroup and stratified analyses revealed decreased risks for lung cancer, nasopharyngeal carcinoma, prostate cancer, ovarian cancer, and oral squamous cell carcinoma, and this association held true also for Asians (especially Chinese subjects) in hospital-based studies, and in studies with quality scores less than nine. Well-designed, large-scale case-control studies are needed to confirm these results.
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http://dx.doi.org/10.18632/oncotarget.14190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354772PMC
February 2017

Twelve-week ribavirin-free direct-acting antivirals for treatment-experienced Chinese with HCV genotype 1b infection including cirrhotic patients.

Hepatol Int 2016 Sep 21;10(5):789-98. Epub 2016 Jul 21.

Second Liver Cirrhosis Diagnosis and Treatment Center, Beijing 302 Hospital, Beijing, China.

Background: Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis.

Methods: One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment.

Results: All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001).

Conclusion: Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.
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http://dx.doi.org/10.1007/s12072-016-9755-0DOI Listing
September 2016

Comparison of laparoscopic excision versus open transvesical excision for symptomatic prostatic utricle in children.

J Pediatr Surg 2016 Oct 13;51(10):1597-601. Epub 2016 Jun 13.

Department of pediatric urology, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, China; Southern Medical University, Guangzhou, Guangdong, 510000, China. Electronic address:

Purpose: The aims of this study were to report our clinical experience with laparoscopic excision (LE) and to compare the outcomes of LE versus open transvesical excision (OTE) for the management of prostatic utricle (PU) in children.

Patients And Methods: This was a retrospective single-center study of 14 children who underwent OTE or LE for managing symptomatic PU between April 2003 and December 2014. Age, utricle size, operative time, estimated blood loss, duration of hospital stay, indwelling time of the urethral catheter, presence of residual postoperative utricular stump, and complications were compared between the two groups.

Results: There were no significant differences in age or utricle size between the two groups. Compared to the OTE group, the LE group experienced shorter operative times, lower estimated blood losses, and shorter hospital stays. Indwelling time of the urethral catheter was nearly 8days in the OTE group and 6days in the LE group. All patients had a follow-up visit between 6months and 2years after surgery. Two patients in the OTE group had transient UTI. Postoperative VCUG showed minimal residual utricular stump for 3 patients in the OTE group. However, no patient in either group required further operative therapy.

Conclusions: LE is a safe and feasible procedure for symptomatic PU in children. Compared to OTE, LE can provide minimally invasive access for achieving good exposure with good short-term outcomes.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.06.004DOI Listing
October 2016

PIK3CA polymorphisms associated with susceptibility to hepatocellular carcinoma.

Int J Clin Exp Pathol 2015 1;8(11):15255-9. Epub 2015 Nov 1.

Department of Gastroenterology Surgery, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.

Purpose: Our study was carried out to explore the relationship of PIK3CA rs17849071 and rs17849079 polymorphisms with the susceptibility to hepatocellular carcinoma (HCC) in Chinese Han population.

Methods: 150 HCC patients and 152 healthy individuals were recruited in the case and control groups respectively. The genotypes of PIK3CA rs17849071 and rs17849079 polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The linkage disequilibrium and haplotypes were analyzed with Haploview software. Differences in frequencies of genotypes, alleles, and haplotypes between the case and control groups were checked with χ(2) test. The controls were matched with the cases in age and gender. The relative risk of HCC was represented by odds ratio (OR) and 95% confidence interval (95% CI).

Results: Significant difference in frequencies of GG genotype and G allele in PIK3CA rs17849071 polymorphism existed between the two groups (P=0.040; P=0.028), indicating that rs17849071 was closely related to the increased risk of HCC (OR=2.919, 95% CI=1.007-8.460; OR=1.642, 95% CI=1.051-2.564). Furthermore, TT genotype also significantly increased the susceptibility to HCC (OR=3.438, 95% CI=1.050-11.250) and so was T allele (OR=1.521, 95% CI=1.052-2.199). The haplotype analysisshowed that G-T haplotypes were higher in cases than that of controls (P=0.030), which suggested that G-T might be a susceptible haplotype to HCC.

Conclusions: The PIK3CA rs17849071 and rs17849079 polymorphisms may increase the risk of HCC either independently or synergistically.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713662PMC
October 2016

Association of PTEN gene polymorphisms with liver cancer risk.

Int J Clin Exp Pathol 2015 1;8(11):15198-203. Epub 2015 Nov 1.

Department of Gastroenterology Surgery, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.

Objective: To find out if there are any relationship between three single nucleotide polymorphisms (SNPs) of phosphatase and tensin homolog (PTEN) gene (rs1234213, rs1234220, and rs2299939) and the susceptibility of liver cancer.

Methods: Genotypes of the three SNPs in the PTEN gene were achieved utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Comparison of genotypes and alleles distribution differences between the case and the control subjects was accomplished with χ(2) test. The analysis of linkage disequilibrium (LD) and haplotypes of the three SNPs was performed using SHEsis software. We adopted odds ratios (ORs) with 95% confidence intervals (95% CIs) to show the relative risk of liver cancer.

Results: TC genotype and C allele of rs1234220 polymorphism showed much more frequently in cases than in controls, reflecting that the TC genotype and the C allele may be linked to the increased risk of liver cancer (OR=2.225, 95% CI=1.178-4.204; OR=1.941, 95% CI=1.124-3.351). Rs2299939 polymorphism showed an opposite result that the GT genotype probably reduce the risk of liver cancer (OR=0.483, 95% CI=0.259-0.900). Statistical significance was not found in the distribution differences of the genotypes of rs1234213 between two groups. LD and haplotype analysis results of the three SNPs showed that the T-C-G haplotype frequency was much higher in cases than in healthy objects, which proved that the T-C-G haplotype might be a susceptibility haplotype for liver cancer (OR=3.750, 95% CI=1.396-10.077).

Conclusions: PTEN gene polymorphisms might relate to liver cancer risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713652PMC
October 2016

Comparison of tubularized incised plate urethroplasty combined with a meatus-based ventral dartos flap or dorsal dartos flap in hypospadias.

Pediatr Surg Int 2016 Apr 18;32(4):411-5. Epub 2016 Jan 18.

Southern Medical University, Guangzhou, 510515, People's Republic of China.

Purpose: Tubularized incised plate urethroplasty (TIPU) is the preferred surgical option for distal and mid-shaft hypospadias repair. Neourethra dartos flap coverage is routinely used as a protective layer with good results. We modified meatus-based ventral dartos flap (MBVDF) to TIPU by dissecting the proximal mid-ventral dartos attached urethra and leaving the subcutaneous fascia connecting the meatus, and retrospectively compared the outcomes of using MBVDF with single dorsal dartos flap (DDF) on the complication rates of TIPU.

Methods: We present 2 surgeons' experiences with 356 patients with distal and mid-shaft hypospadias between January 2010 and December 2014. Patients were divided into two groups. Group DDF included 185 patients (mean age 29 months) underwent TIPU with DDF rotated laterally covering the suture lines of the neourethra. Group MBVDF included 171 patients (mean age 26 months) underwent TIPU with MBVDF covering the suture lines of the neourethra. Statistical analysis of patient basic information and complications was performed by two independent sample t test and Chi square test or Fisher's exact test.

Results: There were no statistical differences in age, type of hypospadias, and follow-up time between the two groups. The mean operative time in the group MBVDF (68.93 ± 8.32 min) was significantly shorter than in the group DDF (73.60 ± 9.06 min). Ventral skin necrosis (2.7%) and penile rotation (3.8%) in group DDF was significantly higher than group MBVDF which did not occur. The differences in other complication rates including fistula rate (2.7 vs 2.9%) between the groups were not statistically significant.

Conclusion: DDF and MBVDF with TIPU are similarly effective methods for decreasing fistula in hypospadias repair. MBVDF with TIPU may be an easier method and can avoid ventral skin necrosis and penile rotation.
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http://dx.doi.org/10.1007/s00383-016-3860-yDOI Listing
April 2016

Significant Association Between Adiponutrin and Hepatocellular Carcinoma Risk.

Medicine (Baltimore) 2015 Nov;94(47):e2019

From the Department of Hepatobiliary Surgery (H-GL, F-FL, H-QZ, XZ, JL, HC) and Department of Gastroenterology Surgery (J-HH), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

ADPN I148M polymorphism has been consistently reported to play a role in liver-associated diseases, such as alcoholic liver disease, chronic hepatitis C, and liver fat and fibrosis in nonalcoholic fatty liver disease. This significant association was also indicated in a series of hepatocellular carcinoma (HCC) studies, where the significance may be affected due to the small sample sizes. The aim of this study was to reexamine the ADPN-HCC association by use of meta-analysis. Biweekly computer-based literature searches plus manual screening were undertaken in an effort to identify all studies that met the predefined inclusion criteria. The Mantel-Haenszel method was selected to estimate risk effects (odds ratio [OR] and 95% confidence interval [CI]). To examine reliability of the pooled risk effects, we additionally performed sensitivity analysis and publication bias tests. Ten studies (1335 HCC patients and 2927 HCC-free controls) were identified for the meta-analysis. We found significantly increased risk of HCC attributable to presence of ADPN I148M polymorphism, with the highest risk associated with the M/M genotype under the recessive model of inheritance (OR = 2.23, 95% CI = 1.87-2.67, between-study heterogeneity: P = 0.468). The significant increase persisted in Caucasian and African when data were stratified by ethnicity. Subgroup analysis according to source of controls revealed similar risk effects. Our meta-analysis indicates that I148M polymorphism in the ADPN gene may independently contribute to the progression of HCC irrespective of the etiologies.
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http://dx.doi.org/10.1097/MD.0000000000002019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058968PMC
November 2015

Is the CARD8 rs2043211 polymorphism associated with susceptibility to Crohn's disease? A meta-analysis.

Autoimmunity 2015 14;48(8):524-31. Epub 2015 Oct 14.

a Department of Health Toxicology , Second Military Medical University , Shanghai , China and.

Many studies have reported the association between the CARD8 gene polymorphism rs2043211 and the susceptibility to Crohn's disease (CD), but the results have remained quite contradictory. Therefore, the aim of the meta-analysis was to explore whether the CARD8 rs2043211 polymorphism has an effect on CD risk. We performed a systematic literature search for related articles published up to July 2014 in multiple databases. Six eligible articles containing eight studies were selected. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between the CARD8 polymorphism and CD risk in different genotypic models. Heterogeneity analysis was also performed and publication bias was taken into account. Subgroup analyses were conducted according to different ethnicities, as well as different types of CD. In the pooled analyses, no statistical significant association was found between the CARD8 polymorphism and CD risk in the overall population or Caucasian subgroup in the additive model (overall population: OR = 0.93, 95% CI = 0.87-1.01; Caucasian: OR = 0.93, 95% CI = 0.83-1.05). However, subgroup analysis based on different CD types showed a significant association between the CARD8 polymorphism and CD risk in the additive model (ileal CD: OR = 0.83, 95% CI = 0.70-0.98; stenotic or fistulizing CD: OR = 0.81, 95% CI = 0.72-0.92). Our results indicated that CD may involve different types of pathogenesis and have variable clinical manifestations. In patients with ileal, stenotic or fistulizing CD, the mutant-type rs2043211 polymorphism may generate a potentially protective effect.
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http://dx.doi.org/10.3109/08916934.2015.1045581DOI Listing
September 2016

Role of neovibsanin scaffold in preservation of spatial cognitive functions of rats with chronic epilepsy.

Int J Clin Exp Pathol 2015 1;8(7):8692-8. Epub 2015 Jul 1.

Department of Neurology, Zhejiang Provincial Hospital of TCM Hangzhou 310013, China.

The effect of neovibsanin scaffold (NS) on the spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion was investigated. Rats were divided into long-term memory (LTM) and short-term memory (STM) groups with 15 rats in each group. The groups were subdivided into 3 groups: control group comprised of 5 rats without surgery, untreated group of 5 rats left without treatment after 2OV, and NS treatment group with 5 rats receiving 5 mg/kg daily for 12 weeks of 2VO operation. NS-treatment caused a marked decrease in the escape latency time and total distance travelled in the treatment group compared to untreated group which was evident from the working memory test. The animals of treatment group also showed significant improvement over that of untreated group in maze test performance. Furthermore, NS treatment also resulted in significant improvement in the probe memory test performance in treatment group compared to untreated group. These findings suggest that NS exhibits therapeutic effect on the spatial cognitive preservation in rats with chronic epilepsy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555786PMC
June 2016

Common Variants of the Prostaglandin-Endoperoxide Synthase 2 Gene and Hepatocellular Carcinoma Susceptibility.

Medicine (Baltimore) 2015 Sep;94(35):e1116

From the Department of Hepatobiliary Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China (HGL, FFL, XZ, JL, HC); and Department of Gastroenterology Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, 250021, China (JHH).

Hepatocellular carcinoma (HCC) is a heterogeneous disease with substantial genetic constitution. Previous work has evaluated the effect of prostaglandin-endoperoxide synthase 2 (PTGS2) variants (-765G/C, -1195A/G, and +8473T/C) on the development of HCC, but the conclusions are inconsistent. We conducted a meta-analysis in this work. Data from 7 case-control studies were combined to assess the association between PTGS2 variants and HCC. The risk of HCC (OR and 95% CI) was estimated using either the fixed- or the random-effects model according to the Q test. No significant association was identified for -765G/C and +8473T/C. However, we identified a significantly decreased risk in relation to the GG genotype of -1195A/G (OR = 0.70, 95% CI = 0.50-0.98 for GG versus AA). We also observed a similar decrease (OR = 0.47, 95% CI = 0.23-0.95 for GG versus AA) in Caucasian samples. Variant -1195A/G in the promoter PTGS2 may protect against the malignant progression of HCC. This significant association suggests that -1195A/G could be used as a biomarker of HCC.
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http://dx.doi.org/10.1097/MD.0000000000001116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616504PMC
September 2015

Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells.

Mol Carcinog 2016 May 14;55(5):440-57. Epub 2015 Feb 14.

Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.

We recently establish that aspafilioside B, a steroidal saponin extracted from Asparagus filicinus, is an active cytotoxic component. However, its antitumor activity is till unknown. In this study, the anticancer effect of aspafilioside B against HCC cells and the underlying mechanisms were investigated. Our results showed that aspafilioside B inhibited the growth and proliferation of HCC cell lines. Further study revealed that aspafilioside B could significantly induce G2 phase cell cycle arrest and apoptosis, accompanying the accumulation of reactive oxygen species (ROS), but blocking ROS generation with N-acetyl-l-cysteine (NAC) could not prevent G2/M arrest and apoptosis. Additionally, treatment with aspafilioside B induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase. Moreover, both ERK inhibitor PD98059 and p38 inhibitor SB203580 almost abolished the G2/M phase arrest and apoptosis induced by aspafilioside B, and reversed the expression of cell cycle- and apoptosis-related proteins. We also found that aspafilioside B treatment increased both Ras and Raf activation, and transfection of cells with H-Ras and N-Ras shRNA almost attenuated aspafilioside B-induced G2 phase arrest and apoptosis as well as the ERK and p38 activation. Finally, in vivo, aspafilioside B suppressed tumor growth in mouse xenograft models, and the mechanism was the same as in vitro study. Collectively, these findings indicated that aspafilioside B may up-regulate H-Ras and N-Ras, causing c-Raf phosphorylation, and lead to ERK and p38 activation, which consequently induced the G2 phase arrest and apoptosis. This study provides the evidence that aspafilioside B is a promising therapeutic agent against HCC.
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http://dx.doi.org/10.1002/mc.22293DOI Listing
May 2016
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