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1.  The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia 
Scientific Reports  2016;6:36823.
Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia.
PMCID: PMC5103295  PMID: 27830735
2.  White light, autofluorescence and narrow-band imaging bronchoscopy for diagnosing airway pre-cancerous and early cancer lesions: a systematic review and meta-analysis 
Journal of Thoracic Disease  2016;8(11):3205-3216.
We aimed to summarize the diagnostic accuracy of white light bronchoscopy (WLB) and advanced techniques for airway pre-cancerous lesions and early cancer, such as autofluorescence bronchoscopy (AFB), AFB combined with WLB (AFB + WLB) and narrow-band imaging (NBI) bronchoscopy.
We searched for eligible studies in seven electronic databases from their date of inception to Mar 20, 2015. In eligible studies, detected lesions should be confirmed by histopathology. We extracted and calculated the 2×2 data based on the pathological criteria of lung tumor, including high-grade lesions from moderate dysplasia (MOD) to invasive carcinoma (INV). Random-effect model was used to pool sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the receiver-operating characteristic curve (AUC).
In 53 eligible studies (39 WLB, 39 AFB, 17 AFB + WLB, 6 NBI), diagnostic performance for high-grade lesions was analyzed based on twelve studies (10 WLB, 7 AFB, 7 AFB + WLB, 1 NBI), involving with totally 2,880 patients and 8,830 biopsy specimens. The sensitivity, specificity, DOR and AUC of WLB were 51% (95% CI, 34–68%), 86% (95% CI, 73–84%), 6 (95% CI, 3–13) and 77% (95% CI, 73–81%). Those of AFB and AFB + WLB were 93% (95% CI, 77–98%) and 86% (95% CI, 75–97%), 52% (95% CI, 37–67%) and 71% (95% CI, 56–87%), 15 (95% CI, 4–57) and 16 (95% CI, 6–41), and 76% (95% CI, 72–79%) and 82% (95% CI, 78–85%), respectively. NBI presented 100% sensitivity and 43% specificity.
With higher sensitivity, advanced bronchoscopy could be valuable to avoid missed diagnosis. Combining strategy of AFB and WLB may contribute preferable diagnosis rather than their alone use for high-grade lesions. Studies of NBI warrants further investigation for precancerous lesions.
PMCID: PMC5179382  PMID: 28066600
Advanced bronchoscopy; lung cancer; white light bronchoscopy (WLB); autofluorescence bronchoscopy (AFB); narrow-band imaging bronchoscopy
3.  Effect of preservation of Denonvilliers’ fascia during laparoscopic resection for mid-low rectal cancer on protection of male urinary and sexual functions 
Medicine  2016;95(24):e3925.
The aim of this study was to investigate the effect of preservation of Denonvilliers’ fascia (DF) during laparoscopic resection for mid-low rectal cancer on protection of male urogenital function. Whether preservation of DF during TME is effective for protection of urogenital function is largely elusive.
Seventy-four cases of male mid-low rectal cancer were included. Radical laparoscopic proctectomy was performed, containing 38 cases of preservation of DF (P-group) and 36 cases of resection of DF (R-group) intraoperatively. Intraoperative electrical nerve stimulation (INS) on pelvic autonomic nerve was performed and intravesical pressure was measured manometrically. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS), and quality of life (QoL). Sexual function was evaluated using the International Index of Erectile Function (IIEF) scale and ejaculation function classification.
Compared with performing INS on the surfaces of prostate and seminal vesicles in the R-group, INS on DF in the P-group exhibited higher increasing intravesical pressure (7.3 ± 1.5 vs 5.9 ± 2.4 cmH2O, P = 0.008). In addtion, the P-group exhibited lower RUV (34.3 ± 27.2 vs 57.1 ± 50.7 mL, P = 0.020), lower IPSS and QoL scores (7 days: 6.1 ± 2.4 vs 9.5 ± 5.9, P = 0.002 and 2.2 ± 1.1 vs 2.9 ± 1.1, P = 0.005; 1 month: 5.1 ± 2.4 vs 6.6 ± 2.2, P = 0.006 and 1.6 ± 0.7 vs 2.1 ± 0.6, P = 0.003, respectively), higher IIEF score (3 months: 10.7 ± 2.1 vs 8.9 ± 2.0, P = 0.000; 6 months: 14.8 ± 2.2 vs 12.9 ± 2.2, P = 0.001) and lower incidence of ejaculation dysfunction (3 months: 28.9% vs 52.8%, P = 0.037; 6 months: 18.4% vs 44.4%, P = 0.016) postoperatively.
Preservation of DF during laparoscopic resection for selective male mid-low rectal cancer is effective for protection of urogenital function.
PMCID: PMC4998490  PMID: 27311004
Denonvilliers’ fascia; rectal cancer; sexual dysfunction; total mesorectal excision; urinary dysfunction
4.  Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals 
PLoS ONE  2016;11(3):e0151259.
In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs).
PubMed, Embase and Clinical were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted.
Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents.
Our results indirectly suggest that BP-stainless DESs may offer more benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is better.
PMCID: PMC4816558  PMID: 27032086
5.  Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents 
Breast cancer susceptibility gene 1 (BRCA1) expression has been suggested as a predictor in anti-neoplastic treatment with anti-microtubule agents. However, the existing evidence is conflicting. Consulting the literature, we sought to examine the true impact of BRCA1 expression on the efficacy of anti-microtubule agents.
Medline by PubMed and Embase databases were searched for eligible studies. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Additional subgroup analyses stratified for detection methods, regimen, and patient origin were also performed.
A total of 13 relevant studies involving a total of 1,490 cases were enrolled. Involved agents included paclitaxel, docetaxel and vinorelbine; Malignancies included non-small cell lung cancer, gastric cancer, esophageal carcinoma, ovarian carcinoma, malignant pleural mesothelioma, breast cancer, and small cell lung cancer. Through meta-analyses, we observed a potentially greater ORR in the population with high BRCA1 expression vs. low BRCA1 expression (OR 1.63, 95% CI: 0.92 to 2.88, P=0.09) but the heterogeneity is severe (P=0.01; I2=61%). Similar results were observed in PFS (high vs. low expression, HR 0.93, 95% CI: 0.75 to 1.15, P=0.49; heterogeneity, P<0.01, I2=75%). After stratification by testing methods, a significantly higher ORR in the population with high BRCA1 expression was shown in the subgroup using mRNA as a quantitative method (OR 2.90, 95% CI: 1.92 to 4.39, P<0.01; I2=0) whereas the difference in the subgroup using immunohistochemistry (IHC) was not significant (OR 0.60, 95% CI: 0.33 to 1.10, P=0.10; I2=0). Stratification by regimen (platinum-based vs. non platinum-based) and patient origin (Asian vs. Caucasian) did not reduce the heterogeneity.
Although the predictive value of BRCA1 expression on the anti-microtubule chemotherapy remained uncertain based on overall results, our exploratory analyses suggested that detection using mRNA might be a preferred technique, however, further validation is required to substantiate our findings.
PMCID: PMC4828752  PMID: 27127763
Breast cancer susceptibility gene 1 (BRCA1); anti-microtubule agents; meta-analysis
7.  Modified inflammation-based score as an independent malignant predictor in patients with pulmonary focal ground-glass opacity: a propensity score matching analysis 
Scientific Reports  2016;6:19105.
Pulmonary focal Ground-glass Opacities (fGGOs) would frequently be identified after widely implementation of low-dose computed tomography (LDCT) screening. Because of the high false-positive rate of LDCT, antibiotics should be regarded as advocates in clinical management for detected fGGOs. Retrospectively review consecutive patients with fGGOs between August 2006 and August 2012. Then, relative Glasgow prognostic score (GPS) were constructed in three different systems, traditional GPS system (tGPS), modified GPS system 1 (m1GPS), and modified GPS system 2 (m2GPS). Moreover, propensity score matching (PSM) was employed in balancing baseline covariates. After PSM, patients were matched and included in benign and malignant groups as 1:1 ratio. All reported parameters were balanced in both groups and no statistical differences could be detected. Finally, m1GPS exhibited remarkable different distribution between benign and malignant fGGOs. In detail, m1GPS 1 was more frequently observed in benign fGGOs nodules, while m1GPS 2 in malignant fGGOs nodules. Modified inflammation-based score was identified as an independent predictor of malignancies in patients with pulmonary fGGOs. Patients with m1GPS 1 were more likely to be benign fGGOs, while victims with m1GPS 2 more likely to be malignant.
PMCID: PMC4707538  PMID: 26752624
8.  Carbon Monoxide Improves Neurologic Outcomes by Mitochondrial Biogenesis after Global Cerebral Ischemia Induced by Cardiac Arrest in Rats 
Mitochondrial dysfunction contributes to brain injury following global cerebral ischemia after cardiac arrest. Carbon monoxide treatment has shown potent cytoprotective effects in ischemia/reperfusion injury. This study aimed to investigate the effects of carbon monoxide-releasing molecules on brain mitochondrial dysfunction and brain injury following resuscitation after cardiac arrest in rats. A rat model of cardiac arrest was established by asphyxia. The animals were randomly divided into the following 3 groups: cardiac arrest and resuscitation group, cardiac arrest and resuscitation plus carbon monoxide intervention group, and sham control group (no cardiac arrest). After the return of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the rats. This treatment also decreased the number of damaged neurons in the hippocampus CA1 area and increased the brain mitochondrial activity. In addition, it increased mitochondrial biogenesis by increasing the expression of biogenesis factors including peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, nuclear respiratory factor-2 and mitochondrial transcription factor A. Thus, this study showed that carbon monoxide treatment alleviated brain injury after cardiac arrest in rats by increased brain mitochondrial biogenesis.
PMCID: PMC4971738  PMID: 27489503
carbon monoxide; brain injury; cardiac arrest; mitochondria biogenesis
10.  The distribution and characteristics of LDL receptor mutations in China: A systematic review 
Scientific Reports  2015;5:17272.
Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese), and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: “familial hypercholesterolemia”, “Chinese”, “China”, “Hong Kong”, and “Taiwan”. A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y, and A606T, and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database.
PMCID: PMC4660303  PMID: 26608663
11.  Nomogram to Predict Occult N2 Lymph Nodes Metastases in Patients With Squamous Nonsmall Cell Lung Cancer 
Medicine  2015;94(46):e2054.
For nonsmall cell lung cancer (NSCLC) patients without distant metastases, occult involvement of N2 lymph nodes would be of the utmost importance in determining both treatment and survival. The key to optimal treatment strategies relied on accurate diagnosis, in particular accurate clinical tumor staging. Patients with clinical N0 or N1 staging preoperatively had a sizeable risk to have occult N2 lymph nodes metastases.
From November 2004 to March 2007, the entire database in a tertiary hospital of all patients with a pathologic diagnosis of squamous NSCLC underwent anatomical pulmonary resection and systematic mediastinal lymph node dissection were retrospectively collected and reviewed. A nomogram was developed on the basis of a multivariable logistic regression model with a combination of all potential variables. In order to surmount the potential of overestimating predictive performance, both bootstrapping for internal validation and an independent external validation set were employed.
A nomogram incorporating the significant risk factors was created to predict the probability of occult N2 lymph nodes metastases. The calibration plot for the probability of occult N2 lymph nodes metastases showed an optimal agreement between the predicted probabilities by nomogram and actual observed probabilities. An objective and accurate nomogram predictive model for occult N2 lymph nodes metastases was drawn up and validated internally and externally in patients with squamous NSCLC.
The nomogram model, as a robust tool in predicting occult N2 lymph nodes involvement, could be involved in a cost-effective application of specific diagnostic and therapeutic strategies.
PMCID: PMC4652824  PMID: 26579815
12.  Prognosis and status of lymph node involvement in patients with adenocarcinoma in situ and minimally invasive adenocarcinoma—a systematic literature review and pooled-data analysis 
Journal of Thoracic Disease  2015;7(11):2003-2009.
Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have been brought up that substitute for bronchioloalveolar carcinoma (BAC), according to the new classification of lung adenocarcinoma. There has been increasing opinions that argues for the adjustment of lymph node disposition in patients with such early stage tumors. Therefore, we sought to overview the prognosis and status of lymph node involvement in AIS/MIA patients.
PubMed, Springer and Ovid databases were searched for relevant studies. Data was extracted and results summarized to demonstrate the disposition of lymph nodes in AIS/MIA.
Twenty-three studies consisting of 6,137 lung adenocarcinoma were included. AIS/MIA accounted for 821 of the total 6,137. All included patients received curative surgery. After a review of the summarized data we found that only one patient (with MIA) had N1 node metastasis, N2 disease was not found in any of the included patients. In concordance with this, studies that reported 5-year disease free survival (5-year DFS) have almost 100% rate.
Our findings indicated that patients with AIS/MIA have good survival prognosis after surgical resection, and that recurrence and lymph node metastasis in these patients is rare. Therefore, we strongly encouraged further studies to determine the role of different lymph node disposition strategies.
PMCID: PMC4669280  PMID: 26716039
Adenocarcinoma in situ (AIS); minimally invasive adenocarcinoma (MIA); lymph node involvement
13.  Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls 
Nature Communications  2015;6:8355.
Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS.
The authors perform a genome-wide association study of adolescent idiopathic scoliosis patients of Han Chinese descent, and identify 3 new loci for disease susceptibility.
PMCID: PMC4595747  PMID: 26394188
14.  Combination of body mass index and oxidized low density lipoprotein receptor 1 in prognosis prediction of patients with squamous non-small cell lung cancer 
Oncotarget  2015;6(26):22072-22080.
Lung cancer, especially non-small cell lung cancer (NSCLC), represents enormous challenges in continuously achieving treatment improvements. Besides cancer, obesity is becoming ever more prevalent. Obesity is increasingly acknowledged as a major risk factor for several types of common cancers. Significant mechanisms overlap in the pathobiology of obesity and tumorigenesis. One of these mechanisms involves oxidized low density lipoprotein receptor 1 (OLR1), as a link between obesity and cancer. Additionally, body mass index (BMI) has been widely used in exploiting the role of obesity on a series of diseases, including cancer. Significantly, squamous NSCLC revealed to be divergent clinical and molecular phenotypes compared with non-squamous NSCLC. Consequently, OLR1 immunostaining score and BMI were assessed by Fisher's linear discriminant analysis to discriminate if progression-free survival (PFS) would exceed 2 years. In addition, the final model was utilized to calculate the discriminant score in each study participant. Finally, 131 patients with squamous NCSLC were eligible for analysis. And a prediction model was established for PFS based on these 2 markers and validated in a second set of squamous NCSLC patients. The model offers a novel tool for survival prediction and could establish a framework for future individualized therapy for patients with squamous NCSLC.
PMCID: PMC4673147  PMID: 26061746
squamous non-small cell lung cancer; oxidized low density lipoprotein receptor 1; body mass index; prediction model
15.  Correlation between epidermal growth factor receptor mutations and nuclear expression of female hormone receptors in non-small cell lung cancer: a meta-analysis 
Journal of Thoracic Disease  2015;7(9):1588-1594.
Compared with male, female non-small cell lung cancer (NSCLC) patients have better response when treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), suggesting a potential association between female hormones and EGFR mutation. However, the results provided by previous studies were inconclusive and controversial. We sought to examine the link between the expression of nuclear female hormone receptors and EGFR mutations in NSCLC.
Electronic databases were used to search the relevant articles. The involved hormone receptors included estrogen receptor (ER) and progesterone receptor (PR). The primary endpoint was the occurrence of ER/PR expression and EGFR mutation in NSCLC patients.
Five studies fulfilled the criteria and were included in our analysis. Patients with high ER-β expression had higher positive EGFR mutation than low ER-β patients (44.2% vs. 23.7%), and there was a significant difference between the two groups [odds radio (OR) 3.44, 95% confidence interval (CI): 2.40-4.93, Z=6.72, P<0.001]. However, there is no significant correlation between EGFR mutations and ER-α (when included ER-α3, OR 1.20, 95% CI: 0.62-2.33, Z=0.55, P=0.58; and when included ER-α4, OR 1.18, 95% CI: 0.62-2.25, Z=0.51, P=0.61) or PR (OR 1.29, 95% CI: 0.40-4.10, Z=0.43, P=0.67). No significant publication bias was observed.
High nuclear expression of ER-β, but not ER-α or PR is correlated with EGFR mutations in NSCLC. The underlying mechanism and potential translational relevance warrant further investigation.
PMCID: PMC4598494  PMID: 26543606
Non-small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR) mutation; estrogen receptor (ER); progesterone receptor (PR); meta-analysis
17.  Laparoscopic resection for rectal cancer and cholecystectomy for patient with situs inversus totalis 
Journal of Minimal Access Surgery  2015;11(3):210-212.
Situs inversus totalis (SIT) is a rare congenital anomaly presenting with complete transposition of thoracic and abdominal viscera. Laparoscopic surgery for either rectal cancer or gallbladder diseases with SIT is rarely reported in the literature. A 39-year-old woman was admitted to hospital owing to rectal cancer. She was diagnosed with SIT by performing radiography and abdominal computed tomography scan as a routine preoperative investigation. We performed laparoscopic resection for rectal cancer successfully in spite of technical difficulties caused by abnormal anatomy. One year later, she was diagnosed with cholecysticpolyp, and we performed laparoscopic cholecystectomy for her uneventfully. With this case, we believe that performance by an experienced laparoscopic surgeon, either laparoscopic resection for rectal cancer or cholecystectomy with SIT is safe and feasible.
PMCID: PMC4499930  PMID: 26195883
Laparoscopic cholecystectomy; laparoscopy; rectal neoplasms; situs inversus totalis
18.  Identification of the gene defect responsible for severe hypercholesterolaemia using whole-exome sequencing 
Scientific Reports  2015;5:11380.
Familial hypercholesterolaemia (FH) is a serious genetic metabolic disease. We identified a specific family in which the proband had typical homozygous phenotype of FH, but couldn’t detect any mutations in usual pathogenic genes using traditional sequencing. This study is the first attempt to use whole exome sequencing (WES) to identify the pathogenic genes in Chinese FH. The routine examinations were performed on all parentage members, and WES on 5 members. We used bioinformatics methods to splice and filter out the pathogenic gene. Finally, Sanger sequencing and cDNA sequencing were used to verify the candidate genes. Half of parentage members had got hypercholesterolaemia. WES identified LDLR IVS8[−10] as a candidate mutation from 222,267 variations. The Sanger sequencing showed proband had a homozygous mutation inherited from his parents, and this loci were cosegregated with FH phenotype. The cDNA sequencing revealed that this mutations caused abnormal shearing. This mutation was first identified in Chinese patients, and this homozygous mutation is a new genetic type of FH. This is the first time that WES was used in Chinese FH patients. We detected a novel genetic type of LDLR homozygous mutation. WES is powerful tools to identify specific FH families with potentially pathogenic gene mutations.
PMCID: PMC4468422  PMID: 26077743
19.  Laparoscopic total colectomy and proctocolectomy for the treatment of familial adenomatous polyposis 
Objective: To evaluate the safety, feasibility and efficacy of Laparoscopic prophylactic treatment of familial adenomatous polyposis (FAP). Methods: Perioperative data and surgical outcomes of 11 FAP patients who underwent laparoscopic surgery between January 2012 and June 2014 in our hospital were analyzed retrospectively. Results 2: Patients had laparoscopic total proctocolectomy with ileostomy, and 9 patients had laparoscopic total colectomy with ileorectal anastomosis. The median number of harvested lymph nodes was 36 (range, 21~46). The mean operating time was 330 minutes with a range of 240 to 380 minutes. Blood loss ranged from 90 to 200 ml with a median being 150 ml. The median incision length was 4 (3-5) cm. The bowel function recovered by the third (range from 2~4 day) postoperatively. The follow-up time of these patients were 3~32 months (median 20 months) respectively and no local recurrence or distant metastases were found. Conclusion: Laparoscopic prophylactic treatment for FAP can be performed safely and effectively with the advantage of minimal invasion by experienced surgeons.
PMCID: PMC4537952  PMID: 26309575
Laparoscopic surgical procedures; familial adenomatous polyposis; total colectomy; proctocolectomy
20.  Adjuvant Chemotherapy for the Completely Resected Stage IB Nonsmall Cell Lung Cancer 
Medicine  2015;94(22):e903.
Supplemental Digital Content is available in the text
Adjuvant chemotherapy is recommended for postoperative stage II-IIIB nonsmall cell lung cancer patients. However, its effect remains controversial in stage IB patients. We, therefore, performed a meta-analysis to compare the efficacy of adjuvant chemotherapy versus surgery alone in stage IB patients.
Six electronic databases were searched for relevant articles. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS). The time-to-event outcomes were compared by hazard ratio using log-rank test.
Sixteen eligible trials were identified. A total of 4656 patients were included and divided into 2 groups: 2338 in the chemotherapy group and 2318 in the control group (surgery only). Patients received platinum-based therapy, uracil-tegafur, or a combination of them. Our results demonstrated that patients can benefit from the adjuvant chemotherapy in terms of OS (HR 0.74 95% CI 0.63–0.88) and DFS (HR 0.64 95% CI 0.46–0.89). Patients who received 6-cycle platinum-based therapy (HR 0.45 95% CI 0.29–0.69), uracil-tegafur (HR 0.71 95% CI 0.56–0.90), or a combination of them (HR 0.51 95% CI 0.36–0.74) had better OS, but patients who received 4 or fewer cycles platinum-based therapy (HR 0.97 95% CI 0.85–1.11) did not. Moreover, 6-cycle platinum-based therapy (HR 0.29 95% CI 0.13–0.63) alone or in combination with uracil-tegafur (HR 0.44 95% CI 0.30–0.66) had advantages in DFS. However, 4 or fewer cycles of platinum-based therapy (HR 0.89 95% CI 0.76–1.04) or uracil-tegafur alone (HR 1.19 95% CI 0.79–1.80) were not beneficial.
Six-cycle platinum-based chemotherapy can improve OS and DFS in stage IB NSCLC patients. Uracil-tegafur alone or in combination with platinum-based therapy is beneficial to the patients in terms of OS, but uracil-tegafur seems to have no advantage in prolonging DFS, unless it is administered with platinum-based therapy.
PMCID: PMC4616365  PMID: 26039122
21.  Significance of local treatment in patients with metastatic soft tissue sarcoma 
American Journal of Cancer Research  2015;5(6):2075-2082.
Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago, although surgery, radiotherapy and radiofrequency ablation has been accepted in the treatment of metastatic STS. Moreover, STS varies between elderly and younger victims in the aspect of diagnoses, prognosis, and treatment strategies. In order to evaluate the role of local treatment in improving prognosis for patients with metastatic STS and select the proper candidates who will benefit from local therapy, a single-institution nearly 50-year experience were collected and reviewed. Finally, we found that local treatments could improve treatment response and survival, but overall survival advantage could not be seen in elderly patients. This conclusion from a single institution could serve as a basis for future prospective multi-institutional large-scale studies.
PMCID: PMC4529626  PMID: 26269766
Soft tissue sarcoma; metastasis; local treatment; prognosis
22.  Prognostic value of monocyte and neutrophils to lymphocytes ratio in patients with metastatic soft tissue sarcoma 
Oncotarget  2015;6(11):9542-9550.
Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago. Prognosis of cancer patients are based not only on tumor-related factors but also on host-related factors, particularly systemic inflammatory response. We evaluated the association among possible risk factors and survival for metastatic STS by reviewed a single-institution nearly 50-year experience. We found that both monocyte ratio and NLR ratio were significant prognostic predictors for OS and PFS of metastatic STS. And patients with monocyte ratio or NLR ratio > 1 should be screened out as candidates for more intensive or aggressive multimodality treatments and more aggressive follow-up. For this reason, this result could serve as a basis for future prospective study.
PMCID: PMC4496237  PMID: 25865224
soft tissue sarcoma; metastasis; immunity; prognosis
23.  Evaluation of the efficacy and safety of anti-PD-1 and anti-PD-L1 antibody in the treatment of non-small cell lung cancer (NSCLC): a meta-analysis 
Journal of Thoracic Disease  2015;7(3):455-461.
Currently, blockade of the programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway has been proved one of the most promising immunotherapeutic strategies against cancer. Several antibodies have been developed to either block the PD-1 or its ligand PD-L1 are under development. So far, a series of phase I trials on PD-1/PD-L1 antibodies for non-small cell lung cancer (NSCLC) have been completed, without reports of results from phase II studies. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of PD-1 or PD-L1 inhibition therapy.
Electronic databases were searched for eligible literatures. Data of objective respond rate (ORR) and rate of adverse effects (AEs) with 95% confidence interval (CI) evaluated by immunohistochemistry (IHC) was extracted. The outcomes were synthesized based on random-effect model. Subgroup analyses were proposed.
In overall, ORR in the whole population with PD-1 blockage treatment is 22.5% (95% CI: 17.6% to 28.2%). Additionally, the rate of Grade 3-4 AEs is 16.7% (95% CI: 6.5% to 36.8%) and drug-related death rate is 2.5% (95% CI: 1.3% to 4.6%). As for patients with PD-L1 inhibition therapy, an overall ORR is 19.5% (95% CI: 13.2% to 27.7%). A higher rate of Grade 3-4 AEs (31.7%, 95% CI: 14.2% to 56.5%) is observed with a lower drug-related death rate (1.8%, 95% CI: 0.4% to 8.3%). In exploratory analyses of anti-PD-1 agents, we observed that greater ORR was presented in the median-dose cohort (3 mg/kg) than that of both low-dose (1 mg/kg) and high-dose (10 mg/kg) cohort (low-dose vs. median-dose: OR =0.12, P=0.0002; median-dose vs. high-dose: OR =1.47, P=0.18).
Anti-PD-1 and anti PD-L1 antibodies showed objective responses in approximately one fourth NSCLC patients with a tolerable adverse-effect profile. In addition, median-dose (3 mg/kg) might be a preferential dosage of anti-PD-1 agents.
PMCID: PMC4387409  PMID: 25922725
Anti-programmed cell death-1 (anti-PD-1); anti-programmed cell death-ligand 1 (anti-PD-L1); non-small cell lung cancer (NSCLC)
24.  Prognostic Significance of Programmed Cell Death 1 (PD-1) or PD-1 Ligand 1 (PD-L1) Expression in Epithelial-Originated Cancer 
Medicine  2015;94(6):e515.
Supplemental Digital Content is available in the text
The expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients’ survival remains controversial.
Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed.
Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33–2.46, P < 0.001). Similarly, patients with PD-1 positive expression on TILs had significantly shorter OS than the PD-1 negative group (HR 2.53, 95% CI 1.22–5.21, P = 0.012). In analyses of PD-L1, all subgroups showed consistent trends toward unfavorable prognoses of patients with positive PD-L1 expression, regardless of antibodies and evaluation cutoffs. Subgroup analyses on PD-1 were not available due to limited data.
PD-L1 or PD-1 expression status is a significant prognostic factor in epithelial-originated malignancies.
PMCID: PMC4602735  PMID: 25674748
25.  Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells 
Cancer Cell International  2015;15(1):12.
Malignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest.
The anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student’s t-test was used to compare differences between treated groups and their controls.
We found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice.
In summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.
PMCID: PMC4326453  PMID: 25685066
Glioma cells; Schisandrin B; Proliferation; Cell cycle; Apoptosis

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