Volume 93  ·   Issue 18  ·  2013

To summarize the clinicopathological manifestations of Wilson disease (WD) so as to improve its recognition.

A total of 29 WD cases were retrospectively analyzed, including clinical presentations, liver function test, serum ceruloplasmin, 24 hour urinary copper excretion,ATP7B gene analysis and liver histology.All cases were diagnosed from January 2007 to October 2012 at Third Hospital of Hebei Medical University and China-Japan Friendship Hospital.

There were 18 males and 11 females with an average age of 25.9 years.The major clinical symptoms included fatigue (n=18, 62.1%), abdominal distension (n=4,13.8%) and pruritus (n=4, 13.8%).The common physical signs were hepatomegaly (n=11, 37.9%), splenomegaly (n=15, 51.7%) and ascites (n=4, 13.8%).The laboratory examinations included abnormal liver function (n=29, 100%), high level of 24-hour urinary copper excretion (n=29, 100.0%), low serum ceruloplasmin (n=24, 82.8%) and Kayser-Fleischer ring (n=8, 27.6%).ATP7B gene mutations were at exons 5, 8, 11, 12, 16 and 18.The earliest histologic abnormalities of liver included steatosis (both microvesicular and macrovesicular). Timm′s stain showed positive or negative staining.There was no or focal hepatocellular necrosis in liver.During chronic hepatitis phase, the major changes included inflammatory cells infiltration in portal area with biliary epithelium degeneration.The periportal area hepatic cells were swollen, cytoplasm slightly stained and accompanied with some copper particles deposition and cholestic changes.There were many spotty or focal lesion of necrosis in liver.During cirrhotic phase, portal area became enlarged by fibrotic tissue, numerous copper particles deposited in wide fibrous septa and small bile ducts were damaged and became proliferative.Hepatocytes around fibrous interval showed cholestatic changes and contained many copper particles.They diagnosed on the basis of clinical presentation (n=6), clinical presentation and liver histology (n=4) and clinical presentation, liver histology and gene analysis (n=19).

There is a high misdiagnosis rate of WD based solely on clinical presentation.Cholestic changes around fibrous interval are common histologic features.The most common ATP7B gene mutations are compound heterozygotes in exons 16.Comprehensive evaluations of clinical presentation, liver histology and gene analysis are helpful for early diagnosis and timely treatment so that it helps to reduce the misdiagnosis and missed diagnosis rate sof WD.

To evaluate the effectiveness and complications of an ultrasound-aided biodegradable osteosynthesis system in the treatment of midfacial fractures.

From January 1,2010 to March 1, 2013, a total of 193 midfacial fractures patients were recruited.There were 120 males and 73 females.Among them, 93 patients were treated with SonicWeld Rx system (KLS Martin, Tuttlingen, Germany) while 100 patients FIXSORB MX (Takiron Co., Ltd, Osaka, Japan).The effectiveness, shortterm and long-term complications were assessed by clinical examinations and computed tomography during an average follow-up period of 18 months.

All fractures healed well without dislocation, malunion, delayed union or nonunion.Pin insertion was completed with a total success rate of 99% in SonicWeld Rx group versus 98% in FIXSORB MX group.Three patients in SonicWeld Rx group and 2 in FIXSORB MX group developed postoperative local inflammation and healed with antibiotics therapy.Hardware visibility or palpability occurred in 3 and 8 patients in two groups respectively.One patient in SonicWeld Rx group and 4 in FIXSORB MX group experienced sterile abscess at Months 12-15 postoperatively and resolved by the removal of biodegradable materials.Two cases of implant looseness were observed in FIXSORB MX group.No other procedure-related complication was noted in either group.

The ultrasound-aided biodegradable osteosynthesis of SonicWeld Rx system is both effective and safe in the treatment of midfacial fractures.And its complication rate is equal to that of traditional biodegradable fixation.

To explore the clinicopathological characteristics of rectal gastrointestinal stromal tumors (GISTs) and elucidate their associated prognostic factors.

The clinicopathological data were collected for 27 patients with rectal gastrointestinal stromal tumors at our hospital from January 2000 to December 2011.Univariate analyses were performed to evaluate the prognostic factors.

Changed habit of discharge and hematochezia were the most common symptoms.Most GISTs were localized in lower rectum.The 1, 3 and 5-year progression-free survival (PFS) rates were 85.19%, 65.04% and 52.04% respectively.Overall survival (OS) and PFS rates were significantly correlated with incisional margin and invasion of surrounding organs.There was no significant difference in PFS and OS between different resection procedures.Due to the limitation of cases multivariate survival analysis can not be pertormed.

Incisional margin and invasion of surrounding organs are two important prognostic factors.And transanal excision is both safe and effective for those properly indicated patients.

To analyze the clinicopathologic characteristics of gastroenteropancreatic neuroendocrine neoplasm (GEP-NET) and explore the prognostic factors for patients with GEPNET.

Retrospectively reviews were conducted for the charts of 68 patients diagnosed pathologically with GEP-NET and treated at Sichuan Cancer Hospital during January 2001 to June 2012.The information of prognostic factors was retrieved and analyzed.Kaplan-Meier method was used to estimate survival rates and plot patient survival curves of patients at different levels of predictive factors.The association between clinicopathologic characteristic and prognosis in GEP-NET patients was assessed with Log-rank test.Meanwhile Cox proportional hazard model was used to select independent risk factors of patient survival.

Stomach (20/68,29.41%) and cardia (16/68,23.53%) were mostly involved.Frequent tumor sites for males were stomach and cardia (34/52,65.38%) while the most common site was intestinal canal for female (12/16).Ages of disease onset were different significantly among patient groups of different sites (P=0.023).The average age of intestinal NET was the highest while gastric NET had the lowest.During a median follow-up duration of 49 (3-120) months, there were 37 deaths (54.41%), including 30 from postoperative relapses.Postoperative survival time ranged from 4-115 months.The mean survival periods were (46±7) months respectively.The 1, 3, and 5-year survival rates were 65.1%, 41.5% and 28.7% respectively.Univariate analyses showed that the risk factors of survival time were patient age over 60 years,tumor size>2 cm, T_2-4 stage of tumor, vascular invasion, lymph node metastasis, distant metastasis, positive surgical margin and pathological grades of neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC).Multivariate analysis indicated independent risk factors were tumor size>2 cm and pathological grades of NEC and MANEC.

GEP-NET may occur at multiple sites of digestive system and lack specific clinical manifestations.Tumor size, distant metastasis and pathological grades were independent prognostic factors for GEP-NET patients.

To explore the anti-apoptotic mechanism of p21^waf1in human basal like breast cancer cell line HCC1937.

There were 3 groups, i.e.experimental group HCC1937 with lentivirus-p21^waf1-shRNA-RFP, control group 1 HCC1937 without lentivirus and control group 2 HCC1937 with lentivirus-RFP.The p21^waf1and bim mRNA and protein expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.And apoptosis of HCC1937 in different groups was assayed by terminal deoxynucleotidyl transferase mediated C-d UTP nick end labeling (TUNEL).

After interference with letivirus-p21^waf1-sh RNA-RFP, p21^waf1mRNA and protein expressions declined significantly in the experimental group versus the control groups (experiment group:0.260±0.004, 0.293±0.006, control group 1:0.879±0.028, 0.483±0.071, control group 2: 0.870±0.025, 0.469±0.047, all P<0.01).The bim mRNA and protein expressions increased.And there was significant difference between the experiment and control groups (experiment group: 0.420±0.013, 0.355±0.007, control group 1: 0.258±0.005, 0.142±0.012, control group 2: 0.259±0.002, 0.147±0.013, all P<0.001); apoptotic index increased (experiment group:0.279±0.012, control group 1:0.145±0.008, control group 2: 0.148±0.012, both P<0.001).

In human basal-like breast cancer cell line HCC1937, p21^waf1exerts anti-apoptotic activity by inhibiting the expression of bim, a mediator of mitochondrial apoptosis.

To evaluate the efficacy and safety of vitamin D (VD) for patients with type 2 diabetes mellitus.

Randomized controlled trials (RCT) were identified from CBM (1978.1—2012.9), CNKI (1979.1—2012.9), Pubmed (1950.1—2012.9), EMbase (1970.1—2012.9) and Cochrane library (issue 4, 2012).Publications of the RCT on the treatment of type 2 diabetes mellitus with VD were included and analyzed according to the criteria of Cochrane handbook.

Six RCT involving 328 patients were included.Meta-analysis indicated that VD caused a reduction in glycosylated hemoglobin A 1c (HbA 1c)(P=0.05) but not in fasting plasma glucose (FPG), homeostasis model assessment index of insulin resistance (HOMA-IR) and failed to improve quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment index of β cell function (HOMA-β)(P>0.05).As reported in a trial, the side effect of VD was hypercalcemia.

VD may have positive effects on patients with type 2 diabetes mellitus.However, the evidence is weak due to the general low methodological quality.Thus we have not made a reliable conclusion about the effects of VD for type 2 diabetes mellitus at the moment.Further larger, randomized, double-blind, placebo-controlled and multicenter trials are warranted.

To assess the efficacy of docetaxel plus capecitabine versus docetaxel plus epirubicin as first-line treatment in women with HER-2 negative advanced breast cancer.

A paired study was conducted for 92 cases with HER-2 negative advanced breast cancer.They received 3 weekly cycles of either TX (docetaxel 75 mg/m², day 1; capecitabine 1000 mg/m²orally twice daily, days 1-14) or TE (docetaxel 75 mg/m², day 1; epirubicin 75 mg/m², day 1).The objective was to compare 6-month non-progression rate, time to progression (TTP), overall response rate (ORR) and toxicities.

The 6-month non-progression rates were 78% with TX versus 70% with TE (P=0.477).Medium TTP was 10.2 versus 8.7 months (P=0.128) and ORR was 72% and 63% respectively (P=0.505).Severe toxicities included hand-foot syndrome (37% vs 4%, P<0.001), grade 3-4 neutropenia (30% vs 70%, P<0.001) and febrile neutropenia (2% vs 11%,P=0.004) respectively.No relevant differences in other toxicities were observed in two arms.

Both regimens of TX and TE have similar efficacy and are well-tolerated as the first-line therapy for HER-2 negative advanced breast cancer.

To explore the antimicrobial resistance of nosocomial Gram-negative bacilli across China.

A total of 1247 consecutive and non-repetitive Gram-negative bacilli were isolated from 13 Chinese teaching hospitals from March to August 2012.All isolates were sent to a central laboratory for reidentification and susceptibility testing.The minimal inhibitory concentration (MICs) of meropenem and other antibacterial agents were determined by agar dilution method.And the data were analyzed with WHONET-5.6 software.

The activity of antimicrobial agents against Enterobacteriaceae was in the following descending order of susceptibility rate: meropenem (97.5%, 849/871), amikacin (94.5%, 823/871),imipenem (93.6%,815/871),ertapenem (92.9%,809/871), piperacillin/tazobactam (89.9%,783/871), cefoperazone/sulbactam (83.5%, 727/871), cefepime (78.1%, 680/871), polymyxin B (77.0%, 670/871), cefiazidime (69.6%, 606/871), levofloxacin (69.2%, 603/871), ciprofloxacin (63.6%, 554/871), minocyline (63.1%, 550/871), ceftriaxone (55.7%, 485/871), cefotaxime (54.2%, 472/871) and cefoxitin (51.4%, 448/871).The prevalence of extended-spectrum beta-lactamase (ESBL) was 64.3% (117/182) in Escherichia coli (E.coli) and 32.1% (60/187) in Klebsiella pneumonia (K.pneumoniae).The sensitivities of E.coli to meropenem and imipenem were 100%.And over 90% of E.coli was sensitive to ertapenem,amikacin, piperacillin/tazobactam and polymyxin B.However,over 60% of E.coli was resistant to ciprofloxacin, levofloxacin, ceftriaxone and cefotaxime.The susceptibility of K.pneumoniae to meropenem,imipenem,amikacin and polymyxin B maintained at over 90%.The activities of antimicrobial agents against E.cloacae, E.aerogenes and Citrobacter freundii were in the following descending order of susceptibility rate: meropenem (96.0%-100%), imipenem (96.0%-100%), polymyxin B (95.8%-100%), amikacin (92.2%- 100%), ertapenem (85.6%-93.3%), cefepime (77.8%-93.3%), cefoperazone/sulbactam (78.4%-90.0%) and piperacillin/tazobactam (65.0%-89.8%).The most susceptible agent against Acinetobacter baumannii (A.baumannii) was polymyxin B (100%).The susceptibilities of A.baumannii to imipenem, meropenem and minocyline were 37.8% (65/172),36.0% (62/172) and 62.8% (108/172) respectively.The most active agents against Pseudomonas aeruginosa (P.aeruginosa) were polymyxin B (97.2%,173/178),followed by amikacin (89.3%,159/178) and cefiazidime (83.7%, 149/178).Clinical and Laboratory Standards Institute revised P.aeruginosa susceptibility standard in 2012.The sensitivity of piperacillin/tazobactam changed from 83.7% (149/178) to 77.5% (138/178).The sensitivity of meropenem decreased from 78.1% (139/178) to 71.3% (127/178) while that of imipenem declined from 69.7% (124/178) to 59.6% (106/178).The prevalence of multidrug resistant A.baumannii and P.aeruginosa were 65.7% (113/172) and 9.0% (16/178) respectively.

Carbapenems remain highly active against Enterobacteriaceae.Increasing resistance of A.baumanni to all antimicrobial agents is noted.New breakpoint to P.aeruginosa has obvious effects on antimicrobial sensitivity.

To survey the prevalence rate of bronchial asthma in Beijing area among residents aged over 14 years.

In accordance with stratified cluster random sampling, epidemiological questionnaires were performed in Beijing residents aged over 14 years during household visits from Febuary 2010 to August 2011.Asthma was diagnosed on the basis of case history, clinical signs and lung function test.The statistical software SAS 9.2 was employed to analyze the epidemiological status of asthma.

In a sampling population of 61 107,57 647 questionnaires were effective.Among 687 asthmatics, there were 296 males and 391 females.The overall prevalence rate of asthma was 1.19% (687/57 647).The asthma prevalence rates were 1.09% (418/38 468) and 1.40% (269/19 179) in urban and suburb Beijing respectively and the prevalence rate of asthma in suburb area was significantly higher than that of urban area (χ²=10.850, P=0.001).The prevalence rates of males and females were 1.06% (296/27 947) and 1.32% (391/29 700) respectively and the prevalence rate of asthma in females was much higher than that of males (χ²=8.098,P=0.004).Significant differences existed among different age groups (χ²=404.874, P=0.000) and residents aged at or over 71 years had the highest prevalence rate.The prevalence rates in urban and suburb Beijing area increased by 1.12 and 2.26 folds respectively than that of 2002.And 198 asthmatics were first diagnosed in this survey and accounted for 28.8% (198/687) in all asthma diagnosed asthmatics.

The prevalence rate of asthma in Beijing area among residents aged over 14 years increased greatly from 2010 to 2011.And the epidemiological data may reflect the current distribution status of asthma in Beijing area.

To explore the role of platelet factor 4 (PF4) andβ-thromboglobulin (β-TG) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

A total of 71 AECOPD patients and 50 chronic obstructive pulmonary disease (COPD) patients within a stable stage were admitted into Beijing Chaoyang Hospital from January 2008 to June 2010.And another 40 healthy volunteers were selected as control group.The data of demographics, arterial blood gas analysis and pulmonary function parameters was collected and analyzed.The plasma levels of PF4 and β-TG were measured by enzyme-linked immunosorbent assay (ELISA).Platelet count was measured by hematology analyzer.Statistical analysis was used for PF4,β-TGand platelet count.Spearman rank correlation was used for correlation analysis.

No differences in age and gender existed among the AECOPD, stable and control groups.The plasma level of PF4 in the AECOPD group (2.28μg/L) was significantly higher than that of the stable group (2.01μg/L) and control group (1.57μg/L) (both P<0.05).The level ofβ-TG in AECOPD was 2.32μg/L and it was significantly higher than that of the stable group (1.85μg/L) and control group (1.29μg/L) (both P<0.05).The differences in platelet counts were insignificant between the AECOPD group ((196±67)×10⁹/L), stable group ((194±50)×10⁹/L) and control group ((190±48)×10⁹/L).AECOPD group was divided into moderate, severe and very severe groups by pulmonary function parameters.The levels of PF4 and β-TG in very severe group were significantly higher than those in moderate and severe groups (P<0.05).A significant positive correlation was observed between PF4 and β-TG (r=0.518, P<0.01).The levels of PF4 and β-TG were negatively correlated with FEV₁%, FEV₁/FVC and PaO₂ (all P<0.05).

Abnormal platelet activation exists in AECOPD.And the levels of PF4 and β-TG may reflect the severity of AECOPD and can be used as the markers of estimating prethrombotic state.

To observe the effects of leptin on activity of GSK-3β and explore its mechanism.

C2C12 myoblasts differentiated for 3 days into myotubes in differentiation medium.Myotubes were stimulated by leptin (100 nmol/L) for 0, 5, 15 or 30 min respectively.Western blot was used to detect the expression levels of GSK-3β and phospho-GSK-3β (ser-9).Coimmunoprecipitation (CO-IP) was performed to determine the relationship among APPL1, leptin receptor and GSK-3β in the presence or absence of leptin.The expression level of GSK-3β at phospho-GSK-3β (ser-9) was detected in APPL1-suppressed C2C12 myotube while that of APPL1 at phospho-APPL1 (ser-401) determined in GSK-3β overexpressed/inhibited C2C12 cell.

Leptin timedependently increased the phosphorylation level of GSK-3β at ser-9 in C2C12 cell, and the pGSK-3β level in cells incubated by leptin for 30 min was as 4.08 times as which in control cells (P<0.01).The triple complex of APPL1, leptin receptor and GSK-3β, in the presence of leptin, the binding capacity between APPL1 and GSK-3βwas stronger.The level of phospho-GSK-3β was significantly lower in APPL1-suppressed C2C12 cell compared with that in control cells.And the phosphorylation of APPL1 at ser-401 could be induced by GSK-3β.

Leptin promotes muscle glycogen synthesis by inducing phosphorylation of GSK-3β in C2C12 cell.Such a function may be mediated by the triple complex of APPL1, leptin receptor and GSK-3β.Meanwhile, GSK-3β can also increase the phosphorylation of APPL1 at ser-401.

To explore the role and mechanism of microRNA185 (miR-185) on proliferation, migration and invasion of esophageal squamous cell carcinoma (ESCC).

Samples were obtained from 23 ESCC patients undergoing surgery whose were confirmed by pathological diagnosis of esophageal carcinoma from 2002 to 2012,at Department of Thoracic Surgery,Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.Real-time PCR was used to measure the expression of miR-185.The xCELLigence RTCA MP system and Transwell assay were performed to detect the effect of miR-185 on proliferation, migration and invasion of ESCC respectively.After transfectiing of miR-185 mimic into KYSE150, the expression of Six1′s downstream gene cyclin A1 was evaluated by real-time PCR.After transfection of miR-185 inhibitor into KYSE30,the expression of Ecadherin, a downstream protein of Six1, was observed under confocal microscope.

The expression level of miR-185 was down-regulated in ESCC compared with adjacent normal tissue (0.006 vs 0.039,P=0.016). After transfection of miR-185 mimic, miR-185 significantly inhibited proliferation, migration and invasion of ESCC. Transwell assay showed, in comparison with the control group, the number of KYSE150 metastatic and invasive cells was respectively decreased (146±15 vs 64±11,110±12 vs 67±5, both P<0.05).And the expression level of cyclin A1 decreased.After transfection of miR-185 inhibitor,the expression level of E-cadherin decreased.

miR-185 may inhibit proliferation, migration and invasion of ESCC through its target gene Six1.