[Association between HBV viral load and severity of liver inflammation in patients with chronic hepatitis B virus infection].

Objective: To explore the relationship and dynamic changes between virological markers and hepatic pathological damage due to host anti-hepatitis B virus (HBV) immunity in the natural course of disease in chronic HBV infected patients. Methods: Two hundred and thirty-eight adult chronic HBV-infected patients who underwent liver biopsy from January 2016 to June 2022 in Taizhou Hospital, Zhejiang Province, were retrospectively selected. General clinical data such as age, gender, platelets, ALT, AST, albumin, HBV DNA, qHBsAg, HBeAg, and liver pathology diagnostic indexes such as the grade of liver necroinflammation and liver fibrotic stages of the patients were collected. The patients were grouped according to HBeAg status, and subgrouped according to different grades of liver necroinflammation and different HBV DNA loads. Statistical analyses were performed to compare the differences in HBV virologic marker levels between the groups, and the correlation between them and the indicators of hepatic inflammatory injury, such as ALT,AST, and the grade of liver necroinflammation in the patients. Results: The levels of HBV virological markers in HBeAg-positive patients with moderate or higher liver necroinflammatory grade (G≥2) were significantly lower than those with mild (no) liver necroinflammatory grade (G < 2) (P < 0.01); whereas the opposite trend was observed in HBeAg-negative patients, with the levels of HBV DNA, and qHBsAg in the G≥2 subgroup being significantly higher than those in the G < 2 subgroup (P < 0.01). Correspondingly, HBV DNA level and qHBsAg showed weak to moderately strong negative correlation with liver necroinflammatory grade and AST which was an indicator of hepatic inflammatory injury in HBeAg-positive patients (P < 0.05); whereas in HBeAg-negative patients, they showed weak to moderately strong positive correlation with hepatic inflammatory activity and ALT, AST (P < 0.001), in which qHBsAg showed only a weak positive correlation with patients' liver necroinflammatory grade (P = 0.003). Further subgroup analyses of HBeAg-positive patients according to whether the HBV DNA level was > 2×10(6) IU/ml showed weak to moderate negative correlations between HBV virological markers and liver necroinflammatory grade as well as ALT and AST in the subgroup of patients with HBV DNA > 2×10(6) IU/ml (P < 0.05); however, the negative correlation disappeared in patients who were still HBeAg positive and had HBV DNA ≤ 2×10(6) IU/ml. Moreover, HBV DNA and ALT, HBeAg and AST showed moderate positive correlation (P < 0.05). Conclusion: We speculate that the activation of host anti-HBV immunity can efficiently inhibit HBV replication by targeting the infected hepatocytes, but only in the early phase of disease progression in HBeAg positive patients with HBV DNA high (> 2×10(6) IU/ml).

[A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma].

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Randomized phase II adjuvant trial to compare two treatment durations of icotinib (2 years versus 1 year) for stage II-IIIA EGFR-positive lung adenocarcinoma patients (ICOMPARE study).

BACKGROUND: Despite the prolonged median disease-free survival (DFS) by adjuvant targeted therapy in non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations, the relationship between the treatment duration and the survival benefits in patients remains unknown. PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase II trial, eligible patients aged 18-75 years with EGFR-mutant, stage II-IIIA lung adenocarcinoma and who had not received adjuvant chemotherapy after complete tumor resection were enrolled from eight centers in China. Patients were randomly assigned (1 : 1) to receive either 1-year or 2-year icotinib (125 mg thrice daily). The primary endpoint was DFS assessed by investigator. The secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov (NCT01929200). RESULTS: Between September 2013 and October 2018, 109 patients were enrolled (1-year group, n = 55; 2-year group, n = 54). Median DFS was 48.9 months [95% confidence interval (CI) 33.1-70.1 months] in the 2-year group and 32.9 months (95% CI 26.6-44.8 months) in the 1-year group [hazard ratio (HR) 0.51; 95% CI 0.28-0.94; P = 0.0290]. Median OS for patients was 75.8 months [95% CI 64.4 months-not evaluable (NE)] in the 2-year group and NE (95% CI 66.3 months-NE) in the 1-year group (HR 0.34; 95% CI 0.13-0.95; P = 0.0317). Treatment-related adverse events (TRAEs) were observed in 41 of 55 (75%) patients in the 1-year group and in 36 of 54 (67%) patients in the 2-year group. Grade 3-4 TRAEs occurred in 4 of 55 (7%) patients in the 1-year group and in 3 of 54 (6%) patients in the 2-year group. No treatment-related deaths or interstitial lung disease was reported. CONCLUSIONS: Two-year adjuvant icotinib was shown to significantly improve DFS and provide an OS benefit in EGFR-mutant, stage II-IIIA lung adenocarcinoma patients compared with 1-year treatment in this exploratory phase II study.

Changes of wound area and inflammatory factors in diabetic foot patients after comprehensive nursing of traditional Chinese medicine.

OBJECTIVE: The aim of this study is to analyze the application effect of traditional Chinese medicine (TCM) comprehensive nursing in diabetic foot patients. PATIENTS AND METHODS: 230 patients with diabetic foot admitted to Third people's Hospital of Haikou from January 2019 to April 2022 were classified as two groups, which consisted of a control group (n = 95) and an experimental group (n = 135). The control group took routine nursing intervention, while the experimental group took TCM comprehensive nursing intervention. The effect of intervention was compared by inflammatory factors (B-FGF, EGF, VEGF, and PDGF), wound area, self-rated anxiety scale (SAS), and self-rated depression scale (SDS). RESULTS: After nursing, the levels of B-FGF, EGF, VEGF, and PDGF were higher in the experimental group (all p < 0.05). The total effective rate of diabetic foot recovery in the experimental group was 94.87% (74/78), higher than 87.67% (64/73) in the control group (p = 0.026). After nursing, the scores of SAS and SDS in the experimental group were lower than those in the control group (all p < 0.05). CONCLUSIONS: The application of TCM comprehensive nursing in diabetic foot patients can greatly change the levels of B-FGF, EGF, VEGF, and PDGF in wound tissue, promote the healing of ulcer surface, improve patients' anxiety and depression, and enhance the quality of life of patients.

[Effect of follicular size on clinical outcomes of frozen-thawed embryo transfer induced by hCG on ovulation in natural cycles].

Objective: To investigate the effect of follicular size on the clinical outcomes of frozen-thawed embryo transfer induced by human chorionic gonadotropin (hCG) of natural cycles on ovulation. Methods: Clinical data of 427 cycles of frozen-thawed single blastocyst transfer in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively analyzed. The patients were divided into 15-16 mm group (15≤diameter≤16 mm, n=66), 16-17 mm group (1620 mm group (diameter>20 mm, n=26), according to the maximum follicle diameter on the induction day of hCG ovulation induction. The estradiol and luteinizing hormone (LH) levels, and clinical pregnancy rate, abortion rate and live birth rate were compared in five groups. Results: There were statistically significant differences in estradiol and LH levels among the five groups on the day of hCG induction (all P<0.05). Estradiol levels in 15-16 mm group to >20 mm group gradually increased on the day of hCG induction, and estradiol level in 15-16 mm group was significantly lower than those in 17-18 mm group, 18-20 mm group and >20 mm group (median: 1 002.3 vs 1 103.3 vs 1 171.2 vs 1 539.0 pmol/L), with statistical significances (P=0.034, P<0.001, P=0.002). On the day of hCG induction, LH levels in 15-16 mm group to >20 mm group showed a decreasing trend, and LH level in 15-16 mm group was significantly higher than those in 17-18 mm group and >20 mm group (median: 37.73 vs 28.24 vs 24.11 U/L), with statistically significant differences (P=0.007, P=0.006). There were no significant differences in clinical pregnancy rate, abortion rate and live birth rate in 15-16 mm group to >20 mm group (all P>0.05). Conclusion: In the natural cycle protocol of hCG induced ovulation, the small follicle group could achieve similar clinical outcomes compared with normal sized follicles in the single blastocyst transfer of frozen-thawed embryos.

IL-17A as a new circulating bioindicator for non-small cell lung cancer diagnosis and prognosis.

OBJECTIVE: Lung cancer (LC) is the highest contributor to cancer-associated mortality worldwide. Approximately 85% of all LC incidences involve non-small cell LC (NSCLC). Unfortunately, owing to a significant lack of sensitive and robust bioindicators, most patient diagnoses occur at advanced stages of the disease, thereby resulting in extremely poor patient outcomes. Herein, we elucidated the role of interleukin-17A (IL-17A) among NSCLC patients. MATERIALS AND METHODS: Circulating IL-17A content was measured using enzyme-linked immunosorbent assay (ELISA), and its diagnostic and prognostic abilities were assessed using the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis, respectively. RESULTS: Our analysis revealed that circulating IL-17A levels were significantly augmented among NSCLC vs. control samples. Moreover, based on our area under the curve (AUC) analysis, circulating IL-17A levels fared considerably better than the standard bioindicator carcinoembryonic antigen (CEA) in both testing and validation cohorts. Notably, we also revealed that the circulating IL-17A levels were accurately and reliably predicted in early-stage NSCLC patients. Besides, we demonstrated a strong correlation between elevated circulating IL-17A expression and worse prognosis among NSCLC patients. CONCLUSIONS: Herein, we demonstrated that circulating IL-17A levels can serve as reliable and potent diagnostic and prognostic bioindicators for NSCLC.

[Consideration on the possible etiological mechanisms and countermeasures about severe acute hepatitis of unknown origin in children].

Since April 2022, severe acute hepatitis of unknown origin in children has spread to 35 countries and regions around the world, and more than 1 010 cases have been reported. Since the severe acute hepatitis of unknown origin involves a wide range of areas and has a high rate, it is critical to identify the etiology and establish effective preventive, diagnostic and therapeutic measures as soon as possible. This study discusses the possible mechanisms and countermeasures of the severe acute hepatitis of unknown origin in children. It speculates that the occurrence of the recent severe acute hepatitis might be related to adenovirus, adeno-associated virus infection, and the COVID-19 epidemic, while the difference in HLA polymorphism among different races might be related to the fact that reported cases were more common in Europe and the United States. Based on the currently available evidence, it can be preliminarily judged that the risk of large-scale outbreak of severe acute hepatitis of unknown origin in children would be low in China, but the persistent awareness and vigilance of the etiology is still needed.

[Natural history and disease progression of chronic hepatitis B virus infection].

OBJECTIVE: To better understand and revise the natural history and disease progression of chronic hepatitis B virus (HBV) infection through analysis of a single-center large-scale cohort of indivi-duals with chronic HBV infection. METHODS: Patients with chronic HBV infection who had undergone liver biopsy in the Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital from January 2014 to October 2020 were retrospectively recruited. Based on patient's hepatitis B e antigen (HBeAg) states and pathologic diagnosis, they were categorized into four disease progression statuses (or phases according to the old-terminology in the updated guidelines of chronic hepatitis B (CHB), such as European Association for the Study of the Liver (EASL) 2017, Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection: HBeAg-positive chronic HBV infection (immune tolerance), HBeAg-positive CHB (immune active HBeAg positive), HBeAg-negative chronic HBV infection (inactive carrier), and HBeAg-negative CHB (immune reactive HBeAg negative). Then the demographic, laboratory tests and liver histological results of the patients in different disease progression stages were compared. Age differences between the two groups were evaluated using Mann-Whitney U test. RESULTS: A total of 760 eligible patients with a median age of 29 (interquartile range: 16-39) years were enrolled. Among them, 197 were underage individuals (age < 18 years) and 563 were adults; and 456 were males and 304 females. According to the pathological diagnosis, the patients were classified, and in each of the above four natural disease phases there were 173, 329, 95, and 163 individuals, respectively. Further comparison of the ages of the patients of the four disease progression statuses revealed that patients of HBeAg-negative CHB had a median age at 37 years, which was reasonably higher than those with HBeAg-positive CHB in immune active phase (37 vs. 24 years, P < 0.001), but was relatively younger than those with HBeAg-negative chronic HBV infection (37 vs. 39 years, P= 0.240). CONCLUSION: According to this study, it could be speculated that HBeAg-negative CHB patients probably not all reactivate from individuals of HBeAg-negative chronic HBV infection. Instead, certain HBeAg-negative CHB patients may also come from HBeAg-positive CHB patients who have undergone HBeAg clearance or seroconversion and still remain in the immune active state.

The clinical value of high mobility group box-1 and CRP/Alb ratio in the diagnosis and evaluation of sepsis in children.

OBJECTIVE: To explore the clinical value of high mobility group box-1 (HMGB-1), C-reactive protein (CRP), procalcitonin (PCT), and CRP to albumin (Alb) ratio in the diagnosis and evaluation of the severity of sepsis in children. PATIENTS AND METHODS: A total of 90 children, 50 with sepsis and 40 with general infection, whose symptoms did not meet the criteria for diagnosis of sepsis, were admitted to the Pediatrics Department of Jingzhou Central Hospital in Hubei Province between November 2021 and December 2022, were enrolled and selected as experimental and control group, respectively. The serum of two groups was collected within 24 hours after admission, the levels of HMGB-1 were detected by enzyme-linked immunosorbent assay (ELISA), and CRP, PCT, Alb, and hospitalization days were recorded. The differences in indicators between the two groups were compared, and correlation analysis was performed between hospitalization days and various indicators. The receiver operating characteristic (ROC) curve was drawn to evaluate the independent or combined value of CRP, PCT, HMGB-1, and CRP/Alb ratio in the early diagnosis of sepsis in children. RESULTS: These four indicators of children with sepsis were significantly higher than those in the general infection group (all p=0.000). The levels of CRP, PCT and CRP/Alb ratio were significantly positively correlated with the hospitalization days (r=0.329, 0.333, 0.329; p=0.02, 0.01, 0.002). The area under curve (AUC) of CRP, PCT, HMGB-1, and CRP/Alb ratio for the diagnosis of sepsis in children was 0.798, 0.817, 0.838, 0.809, respectively, and that of the combination of four indicators was 0.952. CONCLUSIONS: CRP, PCT, HMGB-1, and CRP/Alb ratio resulted as effective indicators for early diagnosis and evaluation of childhood sepsis, having a higher value in combined diagnosis.

[Clinical application of serum Golgi protein 73 in patients with chronic liver diseases].

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

[Progress on the mechanism and application of adipose-derived stem cells in promoting wound repair].

Chronic refractory wounds and scars caused by abnormal wound repair seriously damage the health of patients and affect their quality of life. At present, there is a lack of simple but effective and economical treatment methods. Adipose-derived stem cells (ASCs), as a kind of mesenchymal stem cells with multi-directional differentiation potential, have been confirmed by several in vivo and in vitro studies to promote wound healing by promoting epithelialization, angiogenesis, immunoregulation, antioxidant properties, and other mechanisms. ASCs and their derivatives have been used in the treatment of refractory wounds caused by burns, diabetic, and radiation injuries with good results achieved. Their potential to become new materials for wound repair has also been confirmed. This paper reviewed the mechanism and clinical application of ASCs in promoting wound repair, and looked into its research direction and prospects.

[Factors associated with identification of lymph node detected by axillary reverse mapping for breast cancer].

Objective: To investigate the different tracer materials in identifying the axillary reverse mapping(ARM) lymph nodes. Methods: A retrospective analysis of clinical and pathological data of 478 breast cancer female patients(mean age: 50.5±8.0) under axillary lymph node dissection(ALND) with ARM technique was conducted between March 2019 and November 2020 in Wuhan University Zhongnan Hospital. Of the 478 patients, methylene blue was applied in 147 patients, indocyanine green in 119, and indocyanine green plus methylene blue in 212 patients. Wilcoxon rank-sum test, Chi-squire test or Fisher test, and binary logistic regression were carried out to identify the factors associated with identifying ARM lymph nodes. Results: The recognition rates of ARM lymph nodes were 73.5%, 79.0%, and 83.0%(P=0.091), and the recognition rate of ARM lymphatic vessels was 62.6%, 92.4%, 89.6%(P<0.001), respectively. The coincidence rate of ARM lymph node and SLN was 8.1%(12/148), and the metastasis rate was 16.1%(61/378). Supplemental injection of 1 ml of methylene blue or indocyanine green can improve the identification of ARM lymph nodes. The larger BMI and the performance of neoadjuvant therapy were associated with the lower recognition rate of ARM lymph nodes. Neoadjuvant therapy was an independent factor for the identification rate of ARM lymph nodes. Conclusions: Indocyanine green combined with methylene blue can improve the recognition rate of ARM lymph nodes. Obese patients have a lower recognition rate of ARM lymph nodes, and the supplemental injection tracer can be injected to improve the recognition rate. In breast cancer patients whose ARM lymph nodes are not successfully identified during operation, it may be that the ARM lymph nodes are not located in the axilla.

[Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation].

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

MiR-133b inhibits MPP+-induced apoptosis in Parkinson's disease model by inhibiting the ERK1/2 signaling pathway.

OBJECTIVE: The aim of this study was to explore the effect of micro ribonucleic acid (miR)-133b on 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis in the Parkinson's disease (PD) model. MATERIALS AND METHODS: PC12 cells were induced by different concentrations of MPP+ to establish the PD cell model. Subsequently, the survival rate of PC12 cells was detected using Cell Counting Kit-8 (CCK-8) assay. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of miR-133b in the PD model induced by different concentrations of MPP+. Next, PC12 cells were transfected with miR-133b mimic and miR-negative control (NC), and divided into MPP+ group, MPP+ + miR-NC group and MPP+ + miR-133b mimic group. Transfection efficiency was verified using qRT-PCR. The apoptosis of cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the expressions of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated (p)-ERK1/2 were determined using Western blotting. RESULTS: After MPP+ treatment, the survival rate of PC12 cells significantly declined (p<0.05). MPP+ exhibited toxicity against PC12 cells in a concentration-dependent manner. Meanwhile, cell survival rate decreased remarkably with the increase of MPP+ concentration (p<0.05). With increased concentration of MPP+, the expression of miR-133b in the PD cell model declined significantly (p<0.05). The apoptosis of PC12 cells was remarkably inhibited by overexpression of miR-133b in the PD cell model (p<0.05). In addition, the protein expression of p-ERK1/2 in PC12 cells was notably reduced after overexpression of miR-133b in the PD cell model (p<0.05). CONCLUSIONS: MiR-133b is lowly expressed in the PD cell model. Furthermore, overexpression of miR-133b inhibits cell apoptosis in the PD cell model by regulating the ERK1/2 signaling pathway.

[Diagnostic value of liver stiffness measurement for the evaluation of liver fibrosis in nonalcoholic fatty liver].

Objective: To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD). Methods: 103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established. Results: Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis (f ≥ 2), and advanced liver fibrosis (f ≥ 3). Conclusion: LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.

Transinguinal preperitoneal repair of giant inguinoscrotal hernias using Kugel mesh.

INTRODUCTION: Giant inguinoscrotal hernias are rarely encountered in clinical settings, and their repair is technically challenging. The aim of this study is to evaluate the efficacy of transinguinal preperitoneal repair (TIPP) of giant inguinoscrotal hernias using Kugel mesh. METHODS: A retrospective analysis was conducted on 9 patients with 11 giant inguinoscrotal hernias who underwent TIPP repair using Kugel mesh between December 2008 and January 2019. Demographics and perioperative and postoperative data were collected, and the operative experience was summarized. RESULTS: The patients underwent a successful repair procedure with simultaneous omentectomy but without resection of the other abdominal organs. The median operation time was 120min, the median intraoperative blood loss was 75mL and the median defect area was 72 cm2. The median duration for diet restoration was 4 days, and the median postoperative hospital stay was 6 days. The drainage tube placed in the preperitoneal space was removed after a median duration of 5 days, and the drainage tube placed in the distal hernia sac was removed after a median duration of 6 days. Three patients suffered from a postoperative increase in intra-abdominal pressure, while one patient deteriorated into abdominal compartment syndrome accompanied by respiratory dysfunction. No haematomas, seromas, incisional or mesh infections, recurrence or chronic pain occurred during the follow-up period. CONCLUSIONS: TIPP repair using Kugel mesh is a feasible and effective method for giant inguinoscrotal hernias.

[Establishment and preliminary application of serum Golgi protein 73 based noninvasive diagnostic model for compensated stage hepatitis B cirrhosis].

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.

[Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis].

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ(2)=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ(2)=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ(2)=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ(2)=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ(2)=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion: The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

MiR-223-5p inhibitor suppresses microglia inflammation and promotes Nrg-1 in rats of spinal cord injury.

OBJECTIVE: The aim of this study was to investigate the role of microRNA-233-5p (miR-233-5p) in spinal cord injury (SCI), and to explore the possible underlying mechanism. MATERIALS AND METHODS: Microglia were first isolated from neonate rats and cultured in a suitable environment in vitro. Lipopolysaccharide (LPS) and interleukin-4 (IL-4) were used to activate microglia. The expressions of miR-223-5p, inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) were measured by qRT-PCR, respectively. After transfection of miR-233-5p inhibitor, the expression levels of miR-223-5p, iNOS and Arg-1 in cells were detected as well. A moderate SCI model was successfully established in rats (10 g fallen on T10 spinal cord at the height of 5 cm). Subsequently, inflammation indexes at miR-223-5p peak moment were observed. Meanwhile, its neuro-protective effect at 28 days after SCI was estimated. Finally, Basso, Beattie, and Bresnahan (BBB) rating scale was applied to evaluate the hindlimb locomotor function of rats at 1, 3, 7, 14, 21, 28 days after SCI. RESULTS: MiR-223-5p inhibitor significantly promoted M2 microglia expression and degenerated M1 microglia expression in vitro. SCI elevated the level of miR-223-5p in injured spinal cord tissues within one week, which reached a peak at 5 days after injury. Meanwhile, miR-223-5p inhibitor remarkably reduced the expressions of inflammatory factors, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at 3 days after SCI, as well as increased neuregulin1 (NRG-1) expression. However, miR-223-5p inhibitor significantly declined the levels of apoptosis key enzyme-caspase-3 and glia reaction marker-glial fibrillary acidic protein (GFAP) at 7 and 28 days after SCI, respectively. As a result, BBB rating scale demonstrated that hindlimb locomotor function was significantly recovered in miR-223-5p injection group. CONCLUSIONS: MiR-223-5p was up-regulated in M1 microglia, whereas down-regulated in M2 microglia. MiR-223-5p inhibitor could significantly increase M2 microglia expression, while decrease M1 microglia expression in vitro. In vivo, miR-223-5p inhibitor suppressed the inflammatory response and reinforced NRG-1 level to reduce glia reaction and neuron apoptosis. Thereby, its treatment promoted the hindlimb locomotor function of rats.

MiR-203 regulates DJ-1 expression and affects proliferation, apoptosis and DDP resistance of pancreatic cancer cells.

OBJECTIVE: DJ-1 is a negative regulator of PTEN and plays a role in tumorigenesis. Abnormal miR-203 expression is associated with pancreatic cancer. Bioinformatics analysis showed a targeted relationship between miR-203 and DJ-1 3'-UTR. This study investigated whether miR-203 regulates DJ-1 expression and its role in pancreatic cancer cell proliferation, apoptosis, and cisplatin (DDP) resistance. MATERIALS AND METHODS: The Dual-Luciferase reporter gene assay validated the targeted regulation between miR-203 and DJ-1. The DDP-resistant cell line SW1990/DDP was established and divided into miR-NC group and miR-203 mimic group followed by analysis of the expression of DJ-1, PTEN and p-AKT, cell apoptosis, and proliferation. RESULTS: There was a targeted relationship between miR-203 and DJ-1 mRNA. The expression of miR-203 in SW1990/DDP cells was significantly lower than that in SW1990 cells, while the expression of DJ-1 mRNA and protein was significantly higher than that in SW1990 cells. Compared with miR-NC group, the expression of DJ-1 and p-AKT protein in SW1990/DDP cells was significantly decreased in miR-203 mimic transfection group, while the expression of PTEN was significantly increased with increased cell apoptosis and decreased cell proliferation, as well as reduced DDP resistance. CONCLUSIONS: The decreased expression of miR-203 and the increased expression of DJ-1 is associated with drug resistance in pancreatic cancer cells. Elevated miR-203 can inhibit the expression of DJ-1, affect the activity of PTEN-PI3K/AKT pathway, inhibit the proliferation of pancreatic cancer cells, induce cell apoptosis, and reduce DDP resistance of pancreatic cancer cells.