Clinical Application of the Next Generation Sequencing for Molecular Classification in Endometrial Carcinomas / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing （NGS）. MethodsTotally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected. All of them were tested by hybridized-capture second-generation sequencing based on 1，021 gene panel. The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed. ResultsThe cases were distributed as follows： 8 （7.1%） POLE mutation， 34 （30.4%） mismatch repair deficient， 26 （23.2%） TP53 mutation， 44 （39.3%） non-specific molecular profile. The median tumor mutation burden was respectively 252.0， 38.4， 5.8 and 5.4 Muts/Mb. There were no significantly differences among four subtypes in clinicopathological features such as age， histological grade， lymph node metastasis and clinical stage. PTEN （75.5%）， PIK3CA （66.7%）， ARID1A （55.9%）， TP53 （40.2%）， NF1 （29.4%） were the most common mutations in endometrial cancers. ConclusionsThe utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups， screen Lynch syndrome and obtain molecular variation spectrum， which can provide guidance for immunotherapy and targeted therapy， contribute to further accumulation and exploration of molecular genetic characteristics.

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. @*Materials and Methods@#TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. @*Results@#The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. @*Conclusion@#Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

Application of Standardized Wheelchair Skills Training Program in Rehabilitation Therapeutic Clinical Teaching / 中国康复理论与实践

Objective:To introduce the standardized wheelchair skills training program into clinical teaching for the rehabilitation therapeutics students. Methods:From May, 2017 to April, 2018, 48 undergraduate interns of rehabilitation therapeutics were randomly divided into control group (n = 24) and experimental group (n = 24). Both groups accepted the regular practice, and the experimental group accepted standardized wheelchair skills training for five hours. They were tested with Wheelchair Skills Test (WST) 4.3 before, post training and four-week follow-up. The experimental group completed a questionnaire related to the wheelchair skills training. Results:The score of WST was more in the experimental group than in the control group both post training and four-week follow-up (|t| > 9.330, P < 0.001). The rate of improvement of WST scores was also more in the experimental group than in the control group (|t| = 11.214, P < 0.001). The experimental group suggested that the standardized wheelchair skills training was necessary, and should be a compulsory subject of the occupational therapy. Conclusion:The standardized wheelchair skills training is effective to improve the students' wheelchair-skills performance and understand the needs of the wheelchair users, which may be included in the curriculum program.

Predictors of Short-term Outcomes of Patients with Peritoneal Dialysis-associated Peritonitis / 中国医学科学院学报

Objective To investigate the risk factors predicting the short-term outcomes of patients with peritoneal dialysis(PD)-associated peritonitis (PDAP). Methods In this retrospective cohort study,the clinical data at baseline and 0-3 months before peritonitis onset (peritonitis-free period) were collected from end-stage renal disease patients who started PD and suffered from PDAP between January 1,2004 and March 31,2017 in Peking Union Medical College Hospital. After 4 weeks of follow-up,these patients were divided into two groups according to the clinical outcomes,namely poor outcome group and good outcome group. Characteristics at baseline and before peritonitis were compared. Risk factors associated with short-term outcomes were also analyzed. Results Totally 162 PDAP patients were enrolled,among whom 55 (34.0%) experienced adverse outcomes and 107 (66.0%) had good outcome. At baseline,the proportion of clinical atherosclerotic vascular disease was significantly higher in poor outcome group than in good outcome group (49.1% vs. 31.8%;χ=4.639,P=0.031),whereas indicators were comparable (all P>0.05). During the peritonitis-free period,significantly higher level of high-sensitivity C-reactive protein (hsCRP) [9.3(2.2,16.3)mg/dl vs. 3.6(1.4,9.5)mg/dl,Z=-2.879,P=0.004],higher proportion of low transport type of peritoneum function (8.7% vs. 1.0%;Z=4.879,P=0.027),and lower creatinine clearance rate [56.7 (45.7,71.1) ml/(min·w·1.73 m)vs. 61.4 (54.5,76.4) ml/(min·w·1.73 m);Z=-2.084,P=0.037] were observed in poor outcome group. Univariate Logistic regression analysis showed the combination of clinical atherosclerotic vascular disease (OR=2.070,95%CI:1.062-4.034,P=0.033) and higher hsCRP before peritonitis (OR=1.032,95%CI:1.001-1.059,P=0.015) were the risk factors of short-term poor outcome in PDAP patients. Multivariate Logistic regression analysis showed that,after the gender,age at peritonitis,PD duration,diabetes,and serum albumin before peritonitis were adjusted,higher hsCRP before peritonitis (OR=1.026,95%CI:1.000-1.052,P=0.046) and comorbidity of clinical atherosclerotic vascular disease (OR=2.105,95% CI:1.014-4.367,P=0.046) were the independent risk factors for the poor outcomes in PDAP patients. Conclusion Higher pre-peritonitis hsCRP and comorbidity of clinical atherosclerotic vascular disease at baseline may predict poor short-term outcomes in PDAP patients.

Effectiveness of Peritoneal Dialysis in Treating Adult End Stage Renal Disease Patients with Polycystic Kidney Disease / 中国医学科学院学报

Objective To observe the clinical characteristics,dialysis modalities,and outcomes of end stage renal disease(ESRD)patients with polycystic kidney disease(PKD)and to evaluate the feasibility of peritoneal dialysis in these population. Methods The clinical data of ESRD patient whose primary diagnosis was PKD in Peking Union Medical College Hospital were retrospectively collected from January 1993 to December 2015.PKD patients were divided into two groups according to dialysis modality,namely peritoneal dialysis group(PKD-PD)group and hemodialysis(PKD-HD)group.In addition,we randomly chose non-PKD patients from 622 peritoneal dialysis patients who were matched with PKD-PD patients in age,gender and dialysis time.The primary end point was death.The survival rate was calculated by Kaplan-Meier analysis and the risk factors for suivival were analyzed by Cox regression model. Results Totally 47 PKD patients were enrolled,including 33 patients in PKD-PD group and 14 patients in PKD-HD group,and 42 non-PKD patients as the control group.The average age of PKD patients was(53±11)years,of which 38.3% were women.When compared with PKD-HD group,no significant difference in age,gender,comorbidities,kidney size,and residual glomerular filtration rate were observed in PKD-PD patients at baseline(all P>0.05).The average time on dialysis of PKD-PD patients was(36.2±33.1)months.The weekly urea clearance index(Kt/V)and weekly creatinine clearance were similar to non-PKD-PD group at 3 months,1 year,3 years,and 5 years(all P>0.05).The peritonitis rate was 1 episode/84.5 months.The survival rates at 1 year,3 years,and 5 years of PKD-PD group were 85.7%,78.6%,and 78.6%,which were similar to non-PKD-PD group and PKD-HD group respectively(all P>0.05).Multivariate Cox regression analysis showed that neither PKD nor PD independently predicted the mortality. Conclusion PD can be an option for ESRD patients with PKD.

Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement / 癌症

<p><b>INTRODUCTION</b>The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%-6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.</p><p><b>METHODS</b>A total of 487 lung cancer patients who underwent testing for ALK rearrangement in our department were included in this study. ALK rearrangement was examined by using fluorescence in situ hybridization (FISH) assay.</p><p><b>RESULTS</b>Among the 487 patients, 44 (9.0%) were diagnosed with ALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non-smokers and of a young age (≤ 58 years old), the frequency of ALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non-adenocarcinoma tumor type (P = 0.006), poorly differentiated tumors (P = 0.001), advanced-stage tumors (P < 0.001), smoking history (P = 0.008), and wild-type epidermal growth factor receptor (EGFR) (P = 0.008). Moreover, patients with poorly differentiated and advanced-stage tumors had a shorter time to cancer progression compared with those with well differentiated (P = 0.023) and early-stage tumors (P = 0.001), respectively.</p><p><b>CONCLUSIONS</b>ALK-rearranged NSCLC tends to occur in younger individuals who are either non-smokers or light smokers with adenocarcinoma. Patients with ALK rearrangement might benefit from ALK inhibitor therapy.</p>

Association of lipid metabolism disorder with peritoneum transport ability and mortality in peritoneal dialysis patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the features of lipid metabolism disorders of peritoneal dialysis(PD)patients and hemodialysis(HD)patients and explore the association of lipid metabolism disorder with peritoneum transport ability and mortality.</p><p><b>METHODS</b>The clinical data of 127 PD patients and 95 HD patients who had received regular dialysis for more than 3 months in Peking Union Medical College Hospital since March 2009 were retrospectively analyzed.Serum lipid profiles were tested.Serum hypersensitive C reactive protein(hsCRP)was examined by immune turbidimetric method.Serum carbohydrate antigen 125(CA125)and iPTH were detected by electrochemical luminescence method.Peritoneum transport ability was evaluated through peritoneal equilibration test(PET).After a 2-year follow-up,the levels of CA125 and the peritoneum transport abilities were compared between the baseline data and the end point,and the relationship between lipid disorder and the mortality was analyzed.</p><p><b>RESULTS</b>After the 2-year follow-up,25(19.7%)PD patients died.The leading cause of death was congestive heart failure(56.0%),followed by myocardial infarction(12.0%),septic shock(12.0%),respiratory failure(8.0%),asphyxiation(8.0%),and gastrointestinal bleeding(4.0%).Compared with the survivors,the death patients were older(P=0.005),with significant lower albumin level(P=0.000)and pre-albumin level(P=0.001).However,there was no significant difference in other clinical features including body mass index(BMI),blood pressure,dialysis time,nPCR,iPTH,hemoglobin,hsCRP,and serum lipid level(all P>0.05).COX regression analysis showed that diabetes mellitus(P=0.030)and mean SBP(P=0.048)were significantly associated with the mortality of PD patients.At the baseline,the CA125 level in patients with high,high average,and low average transport status of peritoneum was(38.02±64.37),(21.21±19.41),and(17.55±23.2)U/ml,respectively(P=0.09).There was no association between the transport status and lipid(TC,TG and LDL).</p><p><b>CONCLUSIONS</b>Congestive heart failure is the leading cause of death among PD patients.Diabetes and blood pressure are the dependent risk factors of mortality.Lipid disorder is associated with CA125,while its association with peritoneum transport ability or mortality was not found.</p>

Clinical analysis of anti glomerular basement membrane disease with normal renal function / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical and pathologic characteristics of anti-glomerular basement membrane(GBM) disease with normal renal function.</p><p><b>METHODS</b>The clinical and pathologic data of 6 patients with anti-GBM disease and normal renal function in Peking Union Medical College Hospital were reviewed retrospectively. Furthermore, 29 patients with anti-GBM disease and impaired renal function in the same period in the same hospital were enrolled as the control group. Factors that may influence the prognosis were analyzed.</p><p><b>RESULTS</b>Six (17.1%) of all 35 patients maintained normal renal function for 12-133 months during follow-up. Five patients had microhematuria and proteinuria, one had pulmonary hemorrhage only, and three manifested as Goodpasture syndrome. Renal biopsies from 4 patients revealed linear deposition of IgG 2+-3+ along the glomerular capillary walls by immunofluorescence. As shown by normal light microscopy, mild mesangial proliferation and crescentic glomerulonephritis with a large amount of fibrinoid necrosis of glomerular capillary walls were observed in different patients; however, most pathological changes were mild. Five of these six patients were treated with immunosuppressive drugs and/or plasma exchange. Compared with the control group, the 6 patients with normal renal function had significantly higher hemoglobin[(77.97±20.62 vs.(99.67±19.80 g/L P=0.024], lower titers of anti-GBM antibody[(224.34 ± 145.79 vs.(80.23 ± 85.73 EU/ml P=0.027], and lower ratio of glomeruli with crescents[(0.58±0.29 vs.(0.17±0.27 ,P=0.005]. These 6 patients with normal renal function were followed up for 12-133 months, among whom 4 patients achieved complete remission and 2 had mild proteinuria and microhematuria.</p><p><b>CONCLUSION</b>Anti-GBM disease with normal renal function is not uncommon. Most patients have mild pathologic changes and good prognosis.</p>

Status quo and factors influencing smoking cessation in cigarette smoking patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the status quo of smoking cessation and analyze factors influencing smoking cessation in cigarette smoking patients with coronary artery disease (CAD).</p><p><b>METHOD</b>A total of 350 smoking patients with CAD was surveyed by questionnaire, logistic regression analysis was performed to analyze factors influencing smoking cessation.</p><p><b>RESULTS</b>Incidence of smoking cessation was 57.1% (200/350) in this cohort. Patients were divided into two groups, the elderly (> 65 years old, n = 111) and the young group (≤ 65 years old, n = 239). The smoking cessation rate in the elderly group is significantly higher than in the young group (71.2% vs. 50.6%, P < 0.001). Aged patients and patients with high cultural level are easier to give up smoking. Logistic analysis showed that age ≤ 65 years old (OR = 2.336, P = 0.004), low cultural level (OR = 1.310, P = 0.028), PCI (OR = 0.261, P < 0.001), coronary artery bypass graft (OR = 0.107, P = 0.004), total family income > 4000 RMB/month (OR = 1.828, P = 0.003) are risk factors for failed smoking cessation. There are 76 patients smoking again in current smokers, most due to lack of self-control (76.3%). Compared to the elderly group, there is a higher proportion of smoking again due to the need of daily communication and work in the young group.</p><p><b>CONCLUSIONS</b>We still need to raise the awareness of smoking cessation for smoking patients with CAD. Following factors should be focused for tobacco control in CAD patients: younger age, lower cultural level, not treated with PCI or CABG, patients with smoking family members, higher body mass index and higher total family income.</p>

Pulsed Nd:YAG laser-aided debonding for removing the metal brackets / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To explore the possibility of pulsed Nd:YAG laser-aided debonding for removing orthodontic metal brackets and to compare the method with the conventional mechanical debonding method.</p><p><b>METHODS</b>Fifty healthy premolars extracted for orthodontic purpose were randomly divided into five groups (10 teeth in each group). There were four experimental groups and one control group. Every tooth was bonded with bracket. Laser was used to irradiate the teeth in experimental groups with different electric currents (13.0, 13.5, 14.0, 14.5 A). During the irradiation, the brackets received 4.9 N of force until the brackets off. The time needed for debonding and the temperature change of the pulp cavity were recorded. The teeth in control group were debonded using mechanical method. The adhesive remnant index (ARI) was calculated using stereomicroscope and imagetool software. All samples were examined with a scanning electron microscope.</p><p><b>RESULTS</b>The time taken between the four groups were (67.70 ± 7.18), (35.90 ± 4.28), (24.90 ± 3.76), (6.90 ± 2.33) s, highly statistical difference was found in the time needed for debonding (P < 0.01). The temperature in the pulp cavity among the four groups were (20.97 ± 3.10), (12.75 ± 3.14), (8.99 ± 2.47), (2.91 ± 1.88)°C, and statistical differences were found in temperature change of the pulp cavity (P < 0.05). ARI of three experimental groups and the control group were (8.55 ± 5.02)%, (15.42 ± 7.37)%, (5.55 ± 3.79)%, (13.72 ± 6.69)%, and (74.36 ± 29.44)%. The enamel surface of the control group was coarse with deep scratchs. The enamel surface was smooth and clean in the experimental groups.</p><p><b>CONCLUSIONS</b>Pulsed Nd:YAG laser-aided debonding for removing metal brackets was feasible. Laser-aided debonding was better than conventional mechanical debonding method. The method reduced the damage to the enamel surface.</p>

Effects of perindopril and spirolactone on plasma aldosterone and left atrial remodeling in a canine model of atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of perindopril and spirolactone on plasma aldosterone (Ald) and left atrial remodeling and function in a canine model of atrial fibrillation (AF).</p><p><b>METHODS</b>Adult dogs were randomly assigned to receive normal diet (group A), perindopril (group B, 1 mgxkg(-1)xd(-1)) and spironolactone (group C, 10 mgxkg(-1)xd(-1), n = 6 each) and rapid paced (500 beats/min) for 8 weeks. Plasma Ald levels as well as atrial dimension and function at baseline and at 4 and 8 weeks after pacing were measured by RIA and echocardiography, respectively. Incidence of maintained AF and AF duration were recorded when pacing was stopped after 8 weeks of pacing. Left and right atrial tissues were collected for measurements of tissue Ald levels and fibrosis.</p><p><b>RESULTS</b>Plasma Ald was similar among groups at baseline (P > 0.05) and significantly increased post 4 and 8 weeks pacing in group A (P < 0.05) while remained unchanged post pacing in group B and C (P > 0.05) compared to respective baseline level. Atrial Ald was significantly lower in group B and C compared that in group A post 8 weeks pacing (P < 0.05). Left atrial dimension, end-systolic and end-diastolic volume were significantly increased while left atrial ejection fraction (LAEF) was significantly reduced post pacing in group A (all P < 0.05 vs. baseline) and thses changes were significantly attenuated in group B and C (P < 0.05 vs. group A). Incidence of maintained AF and AF duration post pacing as well as interstitial collagen volume fraction were significantly lower in group B and C compared those in group A (P < 0.05).</p><p><b>CONCLUSION</b>Increased Ald might be an important pathogenesis for AF formation and progression, spironolactone and perindopril could attenuate atrial remodeling and improve atrial function by reducing plasma and tissue Ald levels in this model.</p>

Changes of nucleolin expression and cellular localization during HUVEC apoptosis induced by hydrogen peroxide / 中南大学学报(医学版)

OBJECTIVE@#To investigate the expression and cellular localization of nucleolin C23 during human umbilical vein endothelial cell (HUVEC) apoptosis induced by hydrogen peroxide (H(2)O(2)).@*METHODS@#Apoptosis of HUVEC was induced by exposure to 0.5 mmol/L H(2)O(2) for different periods and detected by flow cytometry and activity of caspase-3. The mRNA and protein expression of nucleolin were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The intracellular distribution of nucleolin was observed by indirect immunofluorescence.@*RESULTS@#The percentage of apoptotic cells was increased significantly after treatment with H(2)O(2) for 12, 24 and 36 hours. The activity of caspase-3 reached the peak after treatment with H(2)O(2) for 4 h. RT-PCR showed that nucleolin C23 mRNA was decreased after 2, 4, and 8 hours treatment with H(2)O(2). Western blot showed that C23 protein level was decreased after 12 hours with an additional cleft band of 80 kD appeared after 8 hours. Density analysis showed that the 80 kD cleft band increased in a time-dependent manner. Immunofluorescence analysis demonstrated that H(2)O(2)-induced C23 redistribution from the nucleus to the cytoplasm.@*CONCLUSION@#H(2)O(2) could induce apoptosis accompanying with C23-cleavage and C23-translocation from the nucleus to the cytoplasm.

Mechanism of isinglass in prevention and treatment of chronic atrophic gastritis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of isinglass in the prevention and treatment of chronic atrophic gastritis (CAG) in rats.</p><p><b>METHOD</b>Animal models of SD rats with CAG were made in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while CAG rat model was being made. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed. Then the length of the proliferation zone of the gastric mucosa and serum epidermal growth factors (EGF) and growth hormones (GH)level were studied.</p><p><b>RESULT</b>In isinglass prevention groups and high dose isinglass reverse group, the length of the proliferation zone of the gastric mucosa was very close to that in normal control group (P > 0.05), much better than model control group (P < 0.01). In low dose isinglass reverse group, it was lower than that in normal control group (P < 0.01), but much better than model control group (P < 0.01). In both prevention and reverse groups, serum EGF level was higher than that in normal (P < 0.01) and model control group (P < 0.05). Serum GH level was the same in every group (P > 0.05).</p><p><b>CONCLUSION</b>The mechanism of isinglass in the prevention and treatment of CAG rats lies in revitalizing and proliferating gastric mucosal cells by stimulating endogenous EGF secretion.</p>

Prevention and treatment of chronic atrophic gastritis in rats with isinglass / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effect of isinglass on the prevention and treatment of chronic atrophic gastritis in rats.</p><p><b>METHOD</b>Animal model of SD rats with CAG was established in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while we were establishing CAG rat model. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed and pathologic changes of the gastric mucosa were studied by gross appearance and microscopy.</p><p><b>RESULT</b>In isinglass prevention groups and reverse groups, inflammation grades of gastric antrum were less than these in model control group (P < 0.01) while the means of ratios of the thickness of gastric mucosal gland and muscularis mucos (L1/L2), the number of gastric glands in 1-mm lengths of mucosal layer were much better than those in model control group (P < 0.01). They were very close to normal control group (P > 0.05).</p><p><b>CONCLUSION</b>Isinglass can prevent the gastric mucosal atrophy in the CAG model and can improve and cure the gastric mucosal atrophy of the SD rats with GAG.</p>