[Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion].

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

[Co-exposure of carbon black and cadmium induces autophagy and inflammation in human bronchial epithelial cells via PERK pathway].

Objective: To investigate the effects of carbon black and cadmium (Cd) combined exposure on autophagy and inflammatory response mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in human bronchial epithelial (16HBE) cells. Methods: In January 2022, human bronchial epithelial (16HBE) cells were resuscitated and cultured. Carbon black nanoparticles (CBNPs) were oxidized to adsorb Cd ions to construct "CBNPs-Cd" complexes. CCK-8 assay was used to detect the effects of different concentrations and time combinations of CBNPs and Cd on the viability of 16HBE cells. The subsequent dose groups were exposed to 2 µg/ml Cd, 100 µg/ml CBNPs, 100 µg/ml CBNPs+2 µg/ml Cd for 24 h. The number of autophagosomes and autolysosomes was detected by transmission electron microscopy. Western blotting was used to detect the protein expressions of PERK, eukaryotic initiation factor 2α (eIf2α), activating transcription factor 4 (ATF4), sequestosome 1 (SQSTM1/P62), and microtubule-associated protein 1 light chain 3 (LC3). After PERK gene was silenced by siRNA technology, the changes of autophagy marker proteins P62 and LC3 were detected, and the expressions of inflammatory factors interleukin-6 (IL6) and interleukin-8 (IL8) were detected by fluorescence quantitative PCR technique. One-way ANOVA analysis was used to compare three groups or more. LSD test was used for comparison between two groups. Factorial analysis was used for multivariate component analysis. Results: There was no significant change in cell viability of 16HBE after 24 h exposure to CBNPs and Cd alone or combined (P>0.05). Compared with the control group, the expressions of P62 and LC3 in 16HBE cells were significantly increased in the CBNPs and Cd alone/combined exposure group (P<0.05), and the number of autophagosomes and autophagolysosomes in the combined exposure group was increased compared with other groups. Compared with the control group, CBNPs and Cd alone exposure group had no significant effects on p-PERK/PERK and p-eIf2α/eIf2α protein expression (P>0.05). However, the protein expressions of p-PERK/PERK and p-eIf2α/eIf2α and ATF4 were all increased in the combined exposure group (P<0.05), and the levels of IL6 and IL8 in 16HBE cells in the combined exposure group of CBNPs and Cd were significantly higher than those in the control group (P<0.05). The levels of LC3 protein, IL6 and IL8 were decreased in the CBNPs-Cd combined exposure group after knockdown of PERK gene (P<0.05). The results of factorial analysis showed that exposure to CBNPs and Cd had significant effects on the expression of P62, LC3 and IL6 (P<0.05), but the interaction between the two chemicals had no statistical significance (P>0.05) . Conclusion: CBNPs-Cd combined exposure may inhibit autophagy and increase inflammation in human bronchial epithelial cells through activation of PERK-eIf2α-ATF4 pathway.

[Fibrocartilaginous lipoma: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.

[Uniportal thoracoscopic thorough debridement for tubercular empyema with abscess of the chest wall].

Objective: To examine the feasibility and technical considerations of thorough debridement using uniportal thoracoscopic surgery for tuberculous empyema complicated by chest wall tuberculosis. Methods: A retrospective analysis was conducted on 38 patients who underwent comprehensive uniportal thoracoscopy debridement for empyema complicated by chest wall tuberculosis in the Department of Thoracic Surgery, Shanghai Pulmonary Hospital, from March 2019 to August 2021. There were 23 males and 15 females, aged (M(IQR)) 30 (25) years (range: 18 to 78 years). The patients were cleared of chest wall tuberculosis under general anesthesia and underwent an incision through the intercostal sinus, followed by the whole fiberboard decortication method. Chest tube drainage was used for pleural cavity disease and negative pressure drainage for chest wall tuberculosis with SB tube, and without muscle flap filling and pressure bandaging. If there was no air leakage, the chest tube was removed first, followed by the removal of the SB tube after 2 to 7 days if there was no obvious residual cavity on the CT scan. The patients were followed up in outpatient clinics and by telephone until October 2022. Results: The operation time was 2.0 (1.5) h (range: 1 to 5 h), and blood loss during the operation was 100 (175) ml (range: 100 to 1 200 ml). The most common postoperative complication was prolonged air leak, with an incidence rate of 81.6% (31/38). The postoperative drainage time of the chest tube was 14 (12) days (range: 2 to 31 days) and the postoperative drainage time of the SB tube was 21 (14) days (range: 4 to 40 days). The follow-up time was 25 (11) months (range: 13 to 42 months). All patients had primary healing of their incisions and there was no tuberculosis recurrence during the follow-up period. Conclusion: Uniportal thoracoscopic thorough debridement combined with postoperative standardized antituberculosis treatment is safe and feasible for the treatment of tuberculous empyema with chest wall tuberculosis, which could achieve a good long-term recovery effect.

[Uniportal thoracoscopic decortication for stage â ¢ tuberculous empyema of 158 cases].

Objective: To examine the safety and feasibility of uniportal video-assisted thoracoscopic (VATS) decortication in patients presenting with stage Ⅲ tuberculous empyema. Methods: From August 2017 to July 2020, 158 patients of stage Ⅲ tuberculous empyema underwent uniportal VATS decortication with partial rib resection and customized periosteal stripper in Department of Thoracic Surgery, Shanghai Pulmonary Hospital. There were 127 males and 31 females, aged (M(IQR)) 32(28) years (range:14 to 78 years). Follow-up was performed in the outpatient clinic or via social communication applications, at monthly thereafter. If there was no air leak and chest tube drainage was less than 50 ml/day, a chest CT was performed. If the lung was fully re-expanded, chest tubes were removed. All patients received a follow-up chest CT 3 to 6 months following their initial operations which was compared to their preoperative imaging. Results: There was one conversion to open thoracotomy. The operative time was 2.75 (2.50) hours (range: 1.5 to 7.0 hours), and median blood loss was 100 (500) ml (range: 50 to 2 000 ml). There were no perioperative mortalities. There were no major complications except 1 case of redo-VATS for hemostasis due to excessive drainage and 1 case of incision infection, The incidence of prolonged air leaks (>5 days) was 80.3%(126/157). The postoperative hospital stay was 5.00 (2.25) days (range: 2 to 15 days). All patients were discharged with 2 chest tubes, and the median duration drainage was 21.00 (22.50) days (range: 3 to 77 days). Follow-up was completed in all patients over a duration of 20 (14) months (range: 12 to 44 months). At follow-up, 149 patients(94.9%) recovered to grade Ⅰ level, 7 patients to grade Ⅱ level, and 1 patient to grade Ⅲ level. Conclusion: Uniportal VATS decortication involving partial rib resection and a customized periosteal stripper is safe and effective for patients with stage Ⅲ tuberculous empyema.

A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer.

BACKGROUND: HER2-positive (+) breast cancers, defined by HER2 overexpression and/or amplification, are often addicted to HER2 to maintain their malignant phenotype. Yet, some HER2+ tumors do not benefit from anti-HER2 therapy. We hypothesize that HER2 amplification levels and PI3K pathway activation are key determinants of response to HER2-targeted treatments without chemotherapy. PATIENTS AND METHODS: Baseline HER2+ tumors from patients treated with neoadjuvant lapatinib plus trastuzumab [with endocrine therapy for estrogen receptor (ER)+ tumors] in TBCRC006 (NCT00548184) were evaluated in a central laboratory for HER2 amplification by fluorescence in situ hybridization (FISH) (n = 56). HER2 copy number (CN) and FISH ratios, and PI3K pathway status, defined by PIK3CA mutations or PTEN levels by immunohistochemistry were available for 41 tumors. Results were correlated with pathologic complete response (pCR; no residual invasive tumor in breast). RESULTS: Thirteen of the 56 patients (23%) achieved pCR. None of the 11 patients with HER2 ratio <4 and/or CN <10 achieved pCR, whereas 13/45 patients (29%) with HER2 ratio ≥4 and/or CN ≥10 attained pCR (P = 0.0513). Of the 18 patients with tumors expressing high PTEN or wild-type (WT) PIK3CA (intact PI3K pathway), 7 (39%) achieved pCR, compared with 1/23 (4%) with PI3K pathway alterations (P = 0.0133). Seven of the 16 patients (44%) with HER2 ratio ≥4 and intact PI3K pathway achieved pCR, whereas only 1/25 (4%) patients not meeting these criteria achieved pCR (P = 0.0031). CONCLUSIONS: Our findings suggest that there is a clinical subtype in breast cancer with high HER2 amplification and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy. A combination of HER2 FISH ratio and PI3K pathway status warrants validation to identify patients who may be treated with HER2-targeted therapy without chemotherapy.

Deleting the first disulphide bond in an arenicin derivative enhances its expression in Pichia pastoris.

The marine antimicrobial peptide NZ17074, a variant of arenicin-3 from Arenicola marina that has broad antimicrobial activity and high bioavailability, can be designed to treat bacterial and fungal diseases. To reduce the toxicity of NZ17074, N6 was designed by replacing a cysteine in positions 3 and 20 with alanine, fused to the C-terminus of the small ubiquitin-like modifier tag (SUMO), and expressed in yeast. SUMO-N6 yielded as much as 921 mg l-1 at 72 h after induction in a fermentor and increased 1·8-fold over SUMO-NZ17074. After cleavage with 30% formic acid and purification by a Sephadex G-25 column, 9·7 mg of the recombinant peptide N6 (rN6) was obtained from one-litre fermentation broth, increasing 1·4-fold over NZ17074. Compared to NZ17074, rN6 displayed almost identical antimicrobial activity with a minimal inhibitory concentration of 0·5, 0·25-0·5, 4, 0·25-16 and 16 µg ml-1 against Escherichia, Salmonella, Pseudomonas, Staphylococcus and Streptococcus strains. Our results indicate that the first disulphide bond, Cys3-Cys20, in NZ17074 is not necessary for antimicrobial activity and that its deletion might reduce toxicity to host cells. These findings may help design new antimicrobial peptides harbouring fewer disulphide bridges and may have more potent activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Disulphide bond formation is an important step in the protein expression and can also influence protein secretion. A deletion of the first disulphide bond in NZ17074 increased the secreted level of target protein, and its antimicrobial activity was almost unaffected by the deletion of the first disulphide bond. The first disulphide bond in NZ17074 is favourable for correctly forming another disulphide bond during expression but not necessary for its activity. This may help design and produce a novel class of antimicrobial peptides harbouring fewer disulphide bridges to save the cost.

[A new prognostic score system of hepatocellular carcinoma following hepatectomy].

Objective: To establish a new scoring system based on the clinicopathological features of hepatocellular carcinoma (HCC) to predict prognosis of patients who received hepatectomy. Methods: A total of 845 HCC patients who underwent hepatectomy from 1999 to 2010 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. 21 common clinical factors were selected in this analysis. Among these factors, the cut-off values of alpha-fetoprotein (AFP), alkaline phosphatase (ALP) and intraoperative blood loss were evaluated by using a receiver operating characteristic (ROC) curve analysis.The Kaplan-Meier method and Cox regression model were used to evaluate the independent risk factors associated with the prognosis of HCC patients after hepatectomy. HCC postoperatively prognostic scoring system was established according to the minimum weighted method of these independent risk factors, and divided the patients into 3 risk groups, including low-risk, intermediate-risk and high-risk group. The relapse-free survival (RFS) and overall survival (OS) were compared among these groups. Results: The univariate analysis showed that clinical symptoms, preoperative α-fetoprotein (AFP) level, serum alkaline phosphatase (ALP) level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with median RFS of these HCC patients (P<0.05). Alternatively, clinical symptoms, preoperative AFP level, serum ALP level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological lymphocyte invasion, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with the median OS of these HCC patients (P<0.05). The multivariate analysis showed that AFP ≥20 ng/ml, clinical symptoms, tumor diameter ≥5 cm, multiple tumors, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, moderate and severe liver cirrhosis, non- anatomic resection were the independent risk factors of RFS and OS (P<0.05). The independent risk factor of RFS was intraoperative bleeding loss ≥325 ml (P<0.05); The independent risk factors of OS were abdominal lymph node metastasis and pathological tumors thrombus (P<0.05). The respective weight of 11 independent factors was used to establish the scoring system (scores range from 0 to 26). In the score system, 0 to 5 points were defined as the low-risk group (286 cases), 6 to 12 points were determined as the intermediate-risk group (503 cases), more than 13 points were classified as the high-risk group (56 cases). The median RFS of the low-risk, intermediate-risk and high-risk group were 80, 27 and 6 months, respectively. The differences were statistically significant (P<0.001). The median OS of the three groups were 134, 51 and 15 months, respectively, and the differences were statistically significant (P<0.001). Conclusion: This new score system provides effective prediction of postoperative prognosis for HCC patients.

[The effect and comparison of commonly used liver-protection drugs for irradiated HL-7702 by X].

Objective: To investigate the effect of different mechanisms of liver-protection drugs in clinic and compare which one is best for the proliferation of irradiated HL-7702, laying the basis of liver-protection drugs choose in clinic on theory and practice. Methods: Human liver parenchyma cells HL-7702 were given single 6 MV X ray irradiation at a dose of 10Gy, the cells' morphology were detected under an inverted microscope at 24h, 48h and 72h. Then, MTT was used to assess the survival rate of the cells to evaluate the effect of the X ray. The representive medicines which mechanism may relate to RILD were chosen and diluted into various concentrations with culture medium according to clinical and relative reports. Different concentrations of medicines were used to protect the cells damaged by the X ray. Comparing the effect with MTT and measure SOD, MDA for the best one. Further research on its protection of oxidative damage. T-test, F test and non- paramiter test were used for statistical analysis. Results: 2.5 mg/ml and 1 mg/ml of magnesium isoglycyrrhizinate both have an effect on the proliferation of liver cells, especially the concentration of 1 mg/ml. The injection of polyene phosphatidyl choline show trivial effect at the concentrations of 250 µmol/L and reduced glutathione(GSH) did not demonstrate relative functions. Further research on the magnesium isoglycyrrhizinate, found its protection at 48h to oxidative damage (P < 0.05), but the effect is weak at 24h and 48h. Conclusions: In three kinds of representing medicines, magnesium isoglycyrrhizinate has preferable effects on liver parenchyma cells and show a bright future in the treatment of RILD.

[Prognostic analysis of colorectal liver metastases treated by surgery combined with intraoperative radiofrequency ablation].

Objective: To investigate the clinical value of intraoperative radiofrequency ablation (RFA) in the treatment of colorectal liver metastasis (CLM). Methods: A retrospectively analysis of 187 patients with CLM who underwent liver resection with or without RFA from January 2009 to August 2016 in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences was performed. According to whether RFA was used intraoperatively, patients were divided into resection only group and combined treatment group. The clinical and pathological characteristics of the two groups were compared to explore factors influencing survival and recurrence. Imbalance of background characteristics between the two groups was further overcome by propensity score matching method (PSM). Results: The number of liver metastases (267), simultaneous liver metastases (100%), bilobar involvement (73.3%) and preoperative chemotherapy (93.3%) rates were significantly higher in the combined treatment group than those in the resection only group(471, 74.7%, 42.0% and 63.1%)(all P<0.05). In the combined treatment group, median overall survival (OS) was 25.7 months; and 3-year and 5-year OS were 47.9% and 28.8%, respectively. In the resection only group, the median survival time was 46.9 months; and 3-year and 5-year OS rate was 59.1% and 42.4%, respectively (χ(2)=4.579, P=0.034). Median disease-free survival (DFS) was 5.4 months in the combined treatment group, and 10.1 months in the resection only group (χ(2)=5.399, P=0.023). In multivariate analysis, intraoperative RFA was not an independent prognostic factor for OS and DFS (HR=0.98, 95%CI: 0.47-2.08, P=0.965; HR=1.21, 95%CI: 0.71-2.07, P=0.465). After PSM, the median OS of the resection only and the combined treatment groups were 30.2 and 25.7 months (χ(2)=0.876, P=0.350). The median DFS in the two groups was 5.3 and 4.2 months, respectively (χ(2)=0.199, P=0.650). Conclusion: In patients with similar tumor burden, liver resection combined with intraoperative RFA for unresectable CLM can achieve long-term outcomes similar to hepatectomy alone for resectable CLM.

[The Changes of HIF-1α and VEGF-A in Myocardial Tissue of Rats with Arrhythmias].

OBJECTIVES: To observe the expression changes of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor-A （VEGF-A） in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency. METHODS: The arrhythmia was induced by CaCl2, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats. RESULTS: The expression of HIF-1α and VEGF-A showed diffuse in the myocardial tissue of rats died from arrhythmias. Both of them increased in the early arrhythmia, then decreased. Extensive myocardial ischemia happened at the beginning of arrhythmia occurrence and its range didn't expand with time. CONCLUSIONS: The expressions of HIF-1α and VEGF-A in myocardium of the rats with arrhythmia can provide evidence for the differential diagnosis of acute myocardial ischemia caused by fatal arrhythmia and coronary insufficiency.

Identification of the Lowest T=2, J

Masses of ^{52g,52m}Co were measured for the first time with an accuracy of ∼10 keV, an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous ß-γ measurements of ^{52}Ni, the T=2, J^{π}=0^{+} isobaric analog state (IAS) in ^{52}Co was newly assigned, questioning the conventional identification of IASs from the ß-delayed proton emissions. Using our energy of the IAS in ^{52}Co, the masses of the T=2 multiplet fit well into the isobaric multiplet mass equation. We find that the IAS in ^{52}Co decays predominantly via γ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS.

[Nutritional risk screening in patients with Crohn's disease].

OBJECTIVE: To screen the nutritional risk in patients with Crohn's disease (CD), to explore the prevalence and characteristics of nutritional risk in CD patients, and to identify the possible risk factors. METHOD: A cross-sectional study was performed in 712 patients who was diagnosed as CD in the Center for Inflammatory Bowel Disease of First Affiliated Hospital of Sun Yat-sen University between January 2003 and January 2014. Montreal classification was used to classify CD, Crohn's Disease Activity Index (CDAI) was used to evaluate disease activity, and Nutritional Risk Screening 2002 (NRS2002) was used to assess the nutritional risk in each patient. Reappraisal with NRS 2002 was conducted in patients followed up for 1 year to identify the possible effect of treatment on nutritional risk of the CD patients. RESULTS: The prevalence of nutritional risk was 65.2% (464/712) in the enrolled CD patients. The prevalence of nutritional risk was significantly different among patients with different disease activity (χ(2)=117.169, P<0.001), also significantly different among patients of different age at diagnosis (χ(2)=11.256, P=0.004), with different lesion location (χ(2)=18.841, P=0.001) and different disease behavior (χ(2)=15.793, P<0.001), but not significantly different in patients of different sex (χ(2)=0.601, P=0.245). Multivariate Logistic regression showed that the independent predictive risk factors for nutritional risk included abdominal tenderness (OR=1.895, 95%CI: 1.080-3.324); mild (OR=1.846, 95%CI: 1.179-2.890), moderate (OR=4.410, 95%CI: 2.701-7.200) and severe (OR=14.069, 95%CI: 1.718-115.192) disease activity; B2 (stricturing) (OR=1.620, 95%CI: 1.034-2.538) and B3 (penetrating) (OR=1.920, 95%CI: 1.025-3.596) types of disease behavior; and high level with erythrocyte sedimentation rate (ESR) (OR=1.024, 95%CI: 1.015-1.034). On the other hand, >40 years at diagnosis (A3 type) (OR=0.332, 95%CI: 0.135-0.814) and high albumin level (OR=0.962, 95%CI: 0.934-0.990) were independent protective factors for nutritional risk. After 1-year follow-up, nutritional risk was eliminated in 32.0%(111/347)of the patients, and the rate was higher in patients received surgery than in those treated with medicine alone (42.9%(54/126)vs 25.8%(57/221), χ(2)=10.742, P=0.001). CONCLUSIONS: Two thirds of CD patients may have nutritional risk at diagnosis, which may differ with disease activity and Montreal classification. Abdominal tenderness, disease activity, B2 and B3 types of disease behavior, and high ESR may be independent risk factors for nutritional risk, whereas A3 type of age at diagnosis and high albumin level may be independent protective factors.

Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in patients with chronic hepatitis B: a prospective cohort study in China.

Chronic hepatitis B therapy with nucleos(t)ide analogues, particularly tenofovir or adefovir, may affect renal function. To date, there has not been a head-to-head controlled study to assess estimated glomerular filtration rate (eGFR) fluctuations in nucleos(t)ide-treated CHB patients. We aimed to evaluate the long-term effects of nucleos(t)ide on eGFR in Chinese patients with chronic hepatitis B. This prospective cohort study included 275 patients. Patient subgroups included those treated with lamivudine (n = 50), adefovir (n = 60), telbivudine (n = 68) and entecavir (n = 61); untreated patients (n = 36) served as control. After an average follow-up duration of 23 months, eGFR calculated by Cockcroft-Gault and Modification of Diet in Renal Disease formulas increased by 18.35 mL/min and 19.34 mL/min (P < 0.0001) in the telbivudine group, respectively, and decreased by 10.95 mL/min and 12.17 mL/min (P = 0.0001) in the adefovir group, respectively. Even if renal function was normal or mildly impaired at baseline, eGFR increased significantly more in the telbivudine group than in the other groups (P < 0.001). More patients in the adefovir group (23%) had a ≥20% decrease in eGFR than the other groups (P < 0.0001). More patients in the telbivudine group (31%) had a ≥20% increase in eGFR than the other groups (P < 0.0001). In conclusion, prolonged telbivudine therapy resulted in improved eGFR, while adefovir therapy was associated with decreased eGFR. Lamivudine and entecavir therapy did not significantly influence eGFR.

Serum microRNA-124 is a novel biomarker for liver necroinflammation in patients with chronic hepatitis B virus infection.

Patients with chronic hepatitis B virus (HBV) infection and normal or mildly increased transaminases may have sustained significant liver damage, as verified by liver biopsy. However, no suitable noninvasive method exists for identifying liver necroinflammation in such patients. We aimed to investigate the power of microRNA-124 as a novel biomarker for liver necroinflammation. A total of 131 recruited patients with chronic HBV infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Thirty healthy individuals were included as controls (HCs). Serum microRNA-124 and microRNA-122 levels were measured using qRT-PCR. Forty-five patients from the study population receiving entecavir therapy were monitored for changes in serum microRNA-124 levels in association with improved liver histology. The capacity of serum microRNA-124 levels in discriminating the grade of liver necroinflammation was compared with alanine aminotransferase (ALT) with liver biopsy validation. Serum microRNA-124 levels were significantly higher in patients with chronic HBV infection than in HCs (P < 0.0001). Patients with considerable liver necroinflammation (G ≥ 2) had significantly higher serum miRNA-124 levels than those without or with mild necroinflammation (P < 0.0001). After 48 weeks of antiviral therapy, serum microRNA-124 levels considerably declined in 45 patients (P < 0.0001), which were associated with histological improvement. In patients with normal ALT and a serum HBV DNA load >10(4) copies/mL, receiver operating characteristic (ROC) curve of serum microRNA-124 levels yielded an area under ROC curve (AUC) of 0.840, with 58.3% sensitivity and 91.7% specificity in discriminating between moderate-to-severe liver necroinflammation (G ≥ 2).

Impact of Long-Term Irrigation with Treated Sewage on Soil Magnetic Susceptibility and Organic Matter Content in North China.

This study assessed the effect on magnetic susceptibility and organic matter content of arable soil by irrigation with either treated sewage or groundwater. Results indicated that organic matter and magnetic susceptibility values in the soil irrigated with sewage were increased by 7.1 % and 13.5 %, respectively, compared to agricultural soil that irrigated with groundwater. Both the sewage and groundwater irrigated soils contained a significant fraction of ultrafine superpara magnetic grains, as indicated by high frequency dependent susceptibility (χfd > 6 %). The enhancement of soil magnetic properties was determined to be caused by anthropogenic sewage irrigation and agrochemical use by investigation of vertical soil profiles. Magnetic susceptibility parameters were shown to be significantly correlated with organic matter content (y = 0.0057x + 1.3439, R(2) = 0.09, p < 0.05). This work indicates that measurements of magnetic susceptibility may offer a rapid first step for identifying the potential pollution in arable soils.

Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells.

Hepatitis B virus surface antigen (HBsAg) plays an important role in maintaining the tolerance and may interfere with host innate and adaptive immune responses; therefore, novel therapeutic strategies to reduce HBsAg loads in patients infected with hepatitis B virus (HBV) are emerging as an attractive but challenging issue. Metformin could regulate hepatic metabolism while the latter interacts with HBV infection. We hypothesized that metformin could affect HBsAg expression and HBV replication and may work synergistically when combined with current antivirals. In our study, a notably inhibitory effect on HBsAg production, as well as a moderate inhibition in HBV replication and HBeAg expression was observed following metformin treatment. The 50% effective concentration (EC50) for extracellular HBsAg and intracellular HBsAg in HBV-producing HepG2.2.15 cells was 2.85 mm and 2.75 mm, respectively, with a similarly selective index of about 18. When administered in combination, metformin enhanced the inhibitory effects of interferon-α2b on HBsAg expression and HBV replication and provided a complimentary role in HBsAg expression for lamivudine (LMV). This novel action of metformin derives partially from its inhibition on multiple HBV cis-acting elements. By the virtues of preferably hepatocyte distribution and safety profile, collectively, our results suggest that metformin would be potentially clinically helpful as an HBsAg production inhibitor.