Volume 93  ·   Issue 48  ·  2013

50% ~75% of patients with chronic kidney disease (CKD) have hypertension. Studies have confirmed that the blood pressure status of patients with CKD is closely related to their long-term prognosis. At present, calcium channel blocker (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensin Ⅱ receptor blocker (ARB), β-adrenergic receptor blocker (β-receptor blocker), diuretics, etc. are the main drugs for clinical treatment of hypertension in patients with CKD. However, clinical practice has found that it is still difficult for some patients with CKD to reach the blood pressure standard after sufficient doses and combined use of antihypertensive drugs. Therefore, new therapeutic approaches should be sought for refractory hypertension that is still difficult to control after more than 2 weeks of treatment with sufficient doses and combined application of more than 3 antihypertensive drugs.

To explore the value of altered serum level of Ghrelin for severity assessment in patients with acute pancreatitis (AP).

Peripheral blood samples were collected from 47 AP patients at admission, 48 hours post-admission and at discharge.According to the criteria of APACHEⅡscore≥8, RANSON≥3, CT≥4, they were divided into mild (n=17) and severe (n=30) groups.Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of Ghrelin.And correlation analysis was made with the score of APACHEⅡand the level of C reactive protein (CRP).Also the serum level of Ghrelin was analyzed with receiver operating characteristic (ROC) curve.

The serum levels of Ghrelin after 24 h were 358.6±119.3 vs 212.1±42.7 ng/L (P<0.001); after 48 hours, 253.1±71.2 vs 275.5±73.6 ng/L (P=0.572); at discharge,327.8±103.8 vs 319.4±87.1 ng/L respectively (P=0.816).And serum level of Ghrelin was positively correlated with APACHEⅡand CRP.ROC area under curve was 0.841±0.057 and 95% confidence interval 0.729-0.952 (P<0.001).

The serum level of Ghrelin during early-stage AP has significant differences between two groups.And it may become an early predictor of pancreatic necrosis and a degree marker of clinical severity.

To evaluate the safety and feasibility of intraoperative radiotherapy during breast-conserving surgery instead of whole breast radiotherapy in early breast cancer patients.

From July 2008 to December 2012, 36 early breast cancer patients underwent breast-conserving surgery plus interoperative radiotherapy on a Mobetron 1000 mobile electron accelerator.Postoperative recurrence and metastases, complications and cosmetic outcomes were recorded and analyzed.

During a median follow-up period of 27.9 months, 2 patients (5.56%) underwent mastectomy after local relapses.There was no occurrence of distant metastasis or mortality.Their average wound healing time was 17 days and 2 of them (5.56%) developed infection while another 2 (5.56%) had delayed wound healing.And 1 patient (2.78%) showed wound edema and neither lyponecrosis nor hematoma was found.The evaluation of cosmetic outcome shows 32 patients (88.89%) were graded as excellent or good while another 4 (11.11%) fair or poor.None had radiotherapy-related acute hemotological toxicity and 2 patients (5.56%) developed skin pigmentation.

Intraoperative radiotherapy during breast-conserving surgery instead of whole breast radiotherapy in early breast cancer patients is both safe and reliable with better cosmetic outcomes.

To evaluate the long-term efficacies and complications of thulium laser resection of prostate-tangerine technique (Tm LRP-TT) in the treatment of benign prostatic hyperplasia (BPH).

From November 2004 to December 2009, a total of 348 BPH patients undergoing Tm LRP-TT at our hospital were evaluated retrospectively for long-term efficacies and complications.The follow-up data included international prostate symptom score (IPSS), quality of life score (QOL), maximum urinary flow (Q_max) and postvoid urinary residual (PVR).

After 4 years, IPSS decreased 70% (22.7±7.7 vs 6.8±5.1), QOL decreased 65% (4.3±0.7 vs 1.5±1.0), Q_max increased 212% (6.0±2.6 ml/s vs 18.7±4.6 ml/s) and PVR decreased 83% (104.7±34.3 ml vs 17.7±10.7 ml).Cumulative incidences of long-term complications was 6.0% (n=21), including a second Tm LRP-TT due to BPH recurrence (n=4, 1.2%), urethral stricture (n=8, 2.3%) and bladder neck contracture (n=9, 2.6%).Overall, 93% were satisfied with surgical outcomes.

Tm LRP-TT has excellent efficacies with a low rate of long-term complications.Most patients are satisfied with surgical outcomes.

To explore the clinical values of detecting drug related molecules excision repair cross complementing 1 (ERCC1) and top-oisomeraseⅠ (TOPOⅠ) in individualized therapies of metastatic colorectal cancer.

From June 2009 to December 2011, 90 patients at Huadong Hospital with metastatic colorectal cancer were randomly separated into 2 groups after operation.Each group had 45 patients without difference in gender, age or TNM stage.The expressions of ERCC1 and TOPOⅠin cancer tissues were detected by immunehistochemical staining.The testing group received individualized chemotherapies following the expression results while the control group had random chemotherapies.The survival difference between two groups was analyzed by log-rank test and Kaplan-Meier analysis.And curative effect was analyzed by χ² or Fisher′s analysis.

The expressions of ERCC1 and TOPOⅠ had no statistical significance between two groups (both P>0.05).In the testing group, the median survival time was 281 days and the beneficial ratio 51.1% (23/45) versus 246 days and 44.4% (20/45) respectively in the control group.The inter-group comparisons of survival (P=0.235) and curative effect (χ²=0.04, P>0.05) showed no statistical significance.In the estimated drug tolerated group (ERCC1 high expression or TOPOⅠ low expression), the median survival time was 196 days and the beneficial ratio 4/14 versus 304 days and 51.3% (39/76) in the estimated drug sensitive group.The inter-group comparisons of survival and curative effect (both P<0.05) had statistical significance.The median survival time and beneficial ratio significantly increased in estimated drug sensitive group than those in estimated drug tolerated group.

The expression of drug related molecule in colorectal cancer tissue is significantly associated with curative effect in patients.Patients with down-regulated ERCC1 on Oxaliplatin or upregulated TOPOⅠon Irinotecan have longer survival and better curative effect.And chemotherapies guided by drug related molecule detection may boost curative effects in metastatic colorectal cancer.

To explore the risk factors and prognostic impact of duodenohepatic ligamentous lymph node (No.12 LN) metastasis in cases with curable advanced distal gastric cancer.

The data of 379 cases with advanced distal gastric cancer undergoing radical resection were screened from the Database of Gastric Cancer Center of Sun Yat-sen University from January 1997 to December 2010.According to No.12 LN metastasis, they were divided into negative (n=339) and positive (n=40) groups.Their clinicopathological parameters and surgical regimens were compared.And the risk factors and prognostic impact of No.12 LN metastasis were analyzed.

No significant inter-group difference existed in gender, age, infiltration depth or differentiation degree (all P>0.05).In negative and positive groups, the percent of tumor size≥5 cm was 30.1% (102/339) vs 55.0% (22/40), lymph node metastasis N₃ stage 8.3% (28/339) vs 42.5% (17/40), other lymph nodes except for No.12 metastasis 70.2% (238/339) vs 92.5% (37/40), distal metastasis M₁ 10.9% (37/339) vs 32.5% (13/40), TNM stage Ⅳ 18.6% (63/339) vs 65.0% (26/40), infiltration Borrmann type 74.3% (252/339) vs 92.5% (37/40), non-adenocarcinoma 15.9% (54/339) vs 35.0% (14/40) and positive serum-carcinoembryonic antigen (S-CEA) 12.7% (43/339) vs 32.5% (13/40).There were all with significant difference (all P<0.01).Logistic regression analysis showed tumor size≥5 cm, lymph node (except for No.12) metastasis, distal metastasis and positive S-CEA were independent risk factors of No.12 LN metastasis (OR=2.144, 3.581, 2.597, 2.552| P=0.035, 0.042, 0.019,0.022 respectively).Cox regression analysis showed lymph nodes (except for No.12) and No.12 metastasis, distal metastasis and Borrmann type were independent prognostic factors for all cases.In negative and positive groups, median survival time was 63.0 versus 12.0 months with significant difference (P=0.000).

For cases with curable advanced distal gastric cancer, No.12 LN metastasis was an independent prognostic factor.No.12 LN should be dissected thoroughly in cases with tumor size≥5 cm, lymph nodes (except No.12) metastasis, distal metastasis and positive S-CEA.

To establish a formula for estimating area under the concentration-versustime curve (AUC) of mycophenolate sodium in Chinese renal allograft recipients with a limited sampling model.

A total of 35 renal allograft recipients were recruited from 2010 to 2013 to receive enteric-coated mycophenolate sodium (EC-MPS), calcineurin (CNI) and prednisone as immunosuppressive triple therapy.The serum concentration of mycophenolic acid (MPA) was assayed by enzyme multiplied immunoassay technique (EMIT) at pre-dose (C₀), 0.5 (C_0.5), 1.0 (C₁), 1.5 (C_1.5), 2.0 (C₂), 3.0 (C₃), 4.0 (C₄), 6.0 (C₆), 8.0 (C₈) and 12.0 (C₁₂) h post-dose respectively.Pharmacokinetic parameters of MPA (C₀, C₁₂, C_max, T_max, AUC_{0-12 h}) were calculated by software WINNOLIN.Simplified formulae for estimation of MPA-AUC in tacrolimus (Tac) group or cyclosporin A (CsA) group were established by multiple stepwise regression analysis.

There were variable MPA AUC_{0-12 h}levels between 14 and 67 mg·h/L (mean:37±14).The MPA trough level (C₀) had no correlations with MPA AUC_{0-12 h} (r²=0.090).The simplified MPA AUC formula for Tac group was AUC=5.678+1.718×C₄+2.853×C₆+1.812×C₈+3.413×C₁₂with four sampling points (C₄, C₆, C₈, C₁₂).Estimated AUC with the formula had correlations with AUC_{0-12 h} (r²=0.890).The mean absolute predict error (APE) was 3.45% (0.41%-24.71%) and the proportion of APE above 15% stood at 11.1% (2/18).In Cs A group, the simplified MPA AUC formula was AUC=7.072+1.525×C₃+1.558×C₄+1.573×C₆+2.285×C₈.The correlation was r²=0.952, mean APE was 6.50% (0.02%-12.91%) and proportion of APE above 15% stood at 0.The above formulae were observed to have agreement with AUC_{0-12 h}by Bland-Altman analysis.

The simplified MPA AUC formulae with 4-point sampling provide an effective approach for estimating full MPA AUC_{0-12 h}in Chinese renal recipients on EC-MPS plus tacrolimus or cyclosporin A.

To detect the status of methylation in promoter region of MEIS1 gene and its expression in cell lines and patients with HOX11⁺ T-cell acute lymphoblastic leukemia (TALL) and explore the relationship between the expression level of MEIS1 gene and methylation of Cp G island in promoter region.

The methylation pattern in MEIS1 gene was detected with bisulfite sequencing PCR, DNA methylation immunoprecipitation and promoter oligonucleotide microarray.And the expression level of MEIS1 mRNA was detected with reverse transcription PCR in 3 T-ALL cell lines: sil-ALL, DND41 and RPMI as well as in 75 clinical bone marrow samples including 38 de novo T-ALL patients, 29 complete remission T-ALL patients and 8 normal samples from January 2009 to December 2011.

The expressions of HOX11 mRNA in the patients were classified into high expression (HOX11⁺) groups (n=14) and low expression (HOX11^-) groups (n=24).There was hypermethylation of Cp G island in promoter region of MEIS1 gene in patients with HOX11⁺T-ALL.The methylation rate of promoter CpG islands of MEIS1 gene in HOX11⁺T-ALL (76.8%) was significantly higher than that of HOX11^-T-ALL (29.5%)(P<0.01).The expression MEIS1 in complete remission T-ALL patients and normal samples was significantly lower than that in de novo T-ALL patients (both P<0.05).The expression MEIS1 in HOX11⁺ cell lines was significantly lower than that in HOX11^- cell lines (0.392±0.226,0.378±0.317 vs 1.059±0.533, both P<0.05) and the expression level of MEIS1 in HOX11⁺ T-ALL patients (0.462±0.281) significantly lower than that in HOX11^- T-ALL patients (0.916±0.437)(P<0.01).The relationship between MEIS1 and HOX11 mRNA expression level had a negative correlation (r_s=-0.416, P<0.01).The expression level of MEIS1 gene was negatively correlated with the methylation of CpG island in promoter region in T-ALL (r_s=-0.383, P<0.01).

The expression of MEIS1 becomes down-regulated or even lost by promoter methylation in T-ALL.HOX11 maybe a negative regulator of MEIS1 gene.

To evaluate the clinical value of PVE (portal vein embolism) prior to surgery in primary liver cancer (PLC) patients and the effect of liver cirrhosis on liver lobe hyperplasia after PVE.

13 patients with primary liver cancer non-suitable for curative hepatectomy underwent k sequential transcatheter arterial chemoembolization (TACE)(1-3 times) and percutaneous selective portal vein embolization (PVE) when the remnant liver volumes were predicted to be insufficient.All patients were divided into non-cirrhosis (n=7) and cirrhosis group (n=6).Left liver remnant volumes were assessed by computed tomography (CT) before and after PVE.Right liver resection was performed when the remnant liver volume was sufficient.

All patients underwent TACE treatment was successful.The frequency of TACE was 1-3.PVE was all successfully performed at weeks 2-4 after final TACE, all PVE patients subsequently underwent hepatic lobectomy.Left liver volume increased from (457.0±121.0) cm³ pre-PVE to (633.6±120.2) cmcm³ post-PVE.Hepatic lobe volume increased (44.4±39.7) %.Statistical difference existed in left hepatic lobe volume before and weeks 4-6 after PVE (P=0.000).The mean volume of left liver, calculated before and 4-6 weeks after PVE, increased from (442.0±96.8) to (652.3±115.8) cm³ in non-cirrhotic group and from (474.5±152.4) to (611.7±132.3) cm³ in cirrhotic group.Hepatic lobe volume increased (54.5±50.7)% and (32.7±19.9)% respectively.Statistical differences were both detected in left hepatic lobe volume before and 4-6 weeks after PVE (P=0.011, P=0.003).However, no significant inter-group difference existed at Weeks 4-6 weeks (P=0.295).Liver function damage was minimal after PVE and no serious complications occurred.

Sequential transcatheter arterial chemoembolization, TACE and percutaneous selective PVE before surgery may cause ramnant liver compensatory hypertrophy and increase the resection rate of primary liver cancer.Liver cirrhosis has no significant effect on liver lobe hyperplasia after PVE.

To explore the related factors of remission and relapse in lupus nephritis (LN) patients.

A retrospective study was conducted for proliferation and membrane LN patients diagnosed from 2003 to 2010.Their clinical, laboratory and pathological parameters were collected.According to the response to treatment, they were divided into 3 groups of complete remission (CR), partial remission (PR) and no response (NR).Those in remission were divided into 2 groups of relapsing and non-relapsing during maintenance period.Associated factors for remission and relapse were analyzed.

(1) Among a total of 105 patients, there were 99 females and 6 males with an average follow-up period of (51±30) months.Eighty-six patients achieved remission after 6-month treatment. (2) The outcomes were CR (n=36), PR (n=50) and NR (n=19).Proteinuria in PR group was higher than that in CR group (4.7 (3.1-7.6) vs 1.7 (1.4-3.8), P<0.01) while proteinuria of CR group was lower than that of NR group (1.7 (1.4-3.8) vs 3.0 (2.3-5.9),P<0.01).Serum albumin level of CR group was significantly higher than those of PR (30.6 (27.8-34.6) vs 22.4 (19.3-29.4), P<0.01) and NR groups (30.6 (27.8-34.6) vs 23.1 (18.9-28.6), P<0.01).Serum creatinine was significantly higher in NR group than those of CR (128.9 (69.9-184.3) vs 58.1 (53.0-70.9), P<0.01) and PR group (128.9 (69.9-184.3) vs 67.5 (53.5-129.1), P<0.05).Acute index (AI) and chronic index (CI) were lower in CR group than those of PR and NR groups. (3) A total of 86 cases achieved remission (CR/PR) while 20 cases (23.3%) had relapse.During the maintenance period, the relapse rate was higher in the group on prednisone alone than those on combined therapy of prednisone plus immunosuppressant (P<0.05).Sixty patients (90.9%) in non-relapse group and 12 cases (60.0%) in recurrence group had good compliance.

Initial proteinuria, serum creatinine, serum albumin, estimated glomerular filtration rate and AI were related with remission of induction period.Prednisone-alone therapy is an independent risk factor for relapse during maintenance period.Poor compliance of patients may be one of the risk factors for relapse during maintenance period.It may be useful to maintain sustained remission and reduce relapse in LN patients by improving their compliance and using steroids plus immunosuppressant during maintenance period.

To explore the protein expressions of DNMT1, DNMT3a and DNMT3b in sera of lung cancer patients.

Enzyme-linked immunosorbent assay (ELISA) method was used to measure the protein expressions of DNMT1, DNMT3a and DNMT3b in 136 lung cancer patients hospitalized at Department of Respiratory Diseases, First Affiliated Hospital, Zhengzhou University during September 2012 to June 2013.And 147 healthy controls were selected from a population of physical examination at Sixth People′s Hospital of Zhengzhou.And the relationship was analyzed between protein expressions of DNMT1, DNMT3a and DNMT3b and clinic characteristics of lung cancer.

The protein expressions of DNMT1, DNMT3a and DNMT3b in patients with lung cancer (15±10, 997±76,302±25) were higher than those of the controls (13±10, 344±93, 108±22).And there were statistical significance (t=3.28, 62.51, 37.27; P=0.021, 0.000, 0.000).The results of Logistic regression show that the protein expressions DNMT1, DNMT3a and DNMT3b increased morbidity for lung cancer (χ²=14.811, 26.768, 12.057; P=0.000, 0.000 0.001), especially so for DNMT1 (OR=1.545, 95% CI: 1.238-1.928).No correlation existed between the protein expressions of DNMT1, DNMT3a, DNMT3b and histological types or stages (P>0.05).

The high protein expressions of serum DNMT1, DNMT3a and DNMT3b increase morbidity for lung cancer.And these markers may predict the early occurrence of lung cancer.

To explore the phenotypes and genotypes of Staphylococcus aureus (S.aureus) hetero-resistant to erythromycin and clindamycin and compare their detection methods so as to report results accurately to guide clinical rational use of antibiotics.

D test was used to detect the phenotypes of S.aureus hetero-resistant to erythromycin.And then the results of two methods (automated instrument and disk diffusion) were analyzed.All strains were continuously passaged for 50 generations to verify the phenotypic and genotypic stability of hetero-resistance.Erm A, ermC and msr A genes were amplified by multiplex polymerase chain reaction (PCR).

Among 95 erythromycin-sensitive strains, there were 70 strains hetero-resistant to erythromycin (73.7%).The primary 70 strains were all susceptive to erythromycin (MIC≤0.25μg/ml) and clindamycin (MIC≤0.25μg/ml) with the cards of GP-67 of VITEK2 Compact.With D tests, the results were difficult to observe.The passaged 70 strains were all resistant to erythromycin (MIC>8μg/ml) and susceptible to clindamycin (MIC≤0.25μg/ml) and D test positive with the cards of GP-67 of VITEK2 Compact.The primary and 50^th generation of herero-erythromycin resistant strains were stable in susceptibility test results.The primary and the 50^th generation strains were all ermA gene positive, ermC and msrA negative with PCR results.

The phenotypes and genotypes of hetreo-erythromycin resistant S.aureus strains were stable.Missed detection with VITEK2 Compact may affect the proper use of erythromycin and clindamycin.Laboratory technicians should identify the erythromycin-susceptible strains by disk diffusion method.