Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective To evaluate the predictors of gleason score pathological downgrading after radical prostatectomy in patients with biopsy-proven level 2 of grading groups (Gleason Score 3 + 4 =7).Methods Data of 252 patients,diagnosed with level 2 of grading groups(Gleason score 3 + 4 =7) prostate cancer by biopsy,with subsequent laparoscopic radical prostatectomy,were retrospectively analyzed.The mean age was 64.3,ranged from 46 to 82 years.The average body mass index (BMI) was 23.2 kg/m2,ranged from 15.2 to 30.4 kg/m2.The median prostate volume,transition zone volume(TZV) and transition zone index(TZI) were 48.9 ml (30.3-73.1 ml),21.4 ml(13.5-31.2 ml) and 0.46％ (0.37％-0.58％),respectively.The median value of tPSA,fPSA and PSAD were 1.53 ng/ml(0.67-3.92 ng/ml),9.65 ng/ml (4.13-18.68 ng/ml) and 0.18 ng/(ml · cm3) [0.09-0.50 ng/ (ml · cm3)],respectively.Clinical T stage was also evaluated,including 153 (60.7％) diagnosed as T1e stage,78 (3 1.0％) diagnosed as T2 stage,and 21 (8.3％) diagnosed as T3 stage.There were 58(23.0％) with extracapsular extension,47 (18.7％) patients with seminal vesicle invasion,and 2(0.8％) with lymph node metastasis.Pathological T stage includes 112 (44.4％) diagnosed as T2 stage,55 (21.8％) diagnosed as T3a stage,35 (13.9％) diagnosed as T3b stage,and 50(19.8％) diagnosed as T4 stage.The patients were assigned Prostate ImagingReporting and Data System version 2 scores of 1,2,3,4,and 5 were 45 (17.9％),36 (14.3％),51 (20.2％),68(27.0％)and 52(20.6％),respectively.The patients were categorized into 2 groups with and without pathological downgrading,including downgrade and no downgrade group.Univariate and multivariate logistic regression analysis were done to determine the predictors of pathological downgrading.Results The patients were categorized into downgrade(n =31) and no downgrade group(n =221) of 252 patients.The pathological downgrading was identified in 31 (12.3％).The tPSA,PSAD and PI-RADS scores in patients with downgrade group which were lower than those in without downgrade group (P ＜ 0.05).The logistic regression analysis revealed PI-RADS score was the independent predictor of downgrading(OR =0.364,95％ CI 0.253-0.522,P ＜ 0.01).The area under the ROC curve of PI-RADS score was 0.810 and the diagnostic value was the best.Conclusions These findings suggested that PI-RADS scores was predictor for pathological downgrading after radical prostatectomy in patients with biopsy-proven level 2 of grading groups,reduced PI-RADS score (PI-RADS score ≤ 3) is correlated with increased pathological downgrading after radical prostatectomy.

Objective: To explore the effects of various forms of prostatic apex on positive apical margin rate (PAM) and biochemical recurrence (BCR) after laparoscopic radical prostatectomy. Methods: A retrospective analysis of 309 patients (aging (65±6) years) who were experienced laparoscopic radical prostatectomy from January 2010 to December 2016 at the Department of Urology, First Affiliated Hospital of Fujian Medical University. According to the relationship between prostate apex and membrane urethra at the mid-sagittal plane of preoperative MRI, all patients were classified into 4 categories. There were 31 patients for type 1, apex covering both anterior and posterior aspects of membranous urethra, 139 patients for type 2, apex covering anterior side of membranous urethra, 63 patients for type 3, apex covering posterior aspect of membranous urethra, 76 patients for type 4, apex not covering membranous urethra. PAM and BCR after operation were compared between this four groups respectively. The χ² test was used to compare PAM among the 4 types. Logistic regression analysis were undertaken to analyze the factors affecting PAM. Cox′s proportional hazards regression model was undertaken to identify the variables influencing BCR. Results: There was no significant difference in the 4 groups concerning age, body mass index, prostate volume, preoperative prostate-specific antigen (PSA) value, postoperative Gleason score and pathological stage (P>0.05).The median follow-up time was 32 months (ranged from 12 to 60 months).The data showed that the apical type 3 patients has the highest PAM. There was statistical difference among the 4 groups in PAM (χ²=15.592, P=0.001). Preoperative level of PSA (OR=20.356, 95% CI: 2.440 to 169.810, P=0.005), postoperative Gleason score (OR=4.113, 95% CI: 1.911 to 8.849, P=0.001), pathological stage (OR=3.422, 95% CI: 1.600 to 7.319, P=0.002) and apical type 3 (OR=6.134, 95% CI: 2.196 to 17.132, P=0.001) were independent relactive factors of PAM. Preoperative level of PSA (HR=1.362, 95% CI: 1.006 to 1.843, P=0.045), postoperative Gleason score (HR=1.920, 95% CI: 1.384 to 2.665, P=0.001), pathological stage (HR=1.476, 95% CI: 1.098 to 1.983, P=0.010), PAM (HR=3.497, 95% CI: 2.407 to 5.081, P=0.001)and apical type 3 (HR=1.828, 95% CI: 1.266 to 2.639, P=0.001) were independent prognosis factors of BCR. Conclusion Prostate apical type 3 could be a significant independent predictor of PAM, and an independent prognosis factor for BCR.

Objective To evaluate the therapeutic effects of thymectomy in myasthenia gravis (MG) patients with thymoma.Methods A total of 178 MG patients with thymectomy between July 2008 and December 2010 were included.All the subjects were received either cyclophosphamide alone or in combination with radiotherapeutic treatment after surgery.The MG absolute and relative clinical scores were used to assess the effectiveness of long-term trcatments.Clinical evaluations were conducted before,and at 1,6,12 and 24 months after operation.A comparative analysis on the inter-relationships among MG clinical presentation,WHO histology aud Masaoka stage was also conducted.Results (1) Of the 178 thymomapatients,103 were male and 75 were female,with a mean age of (43.7 ± 12.5)-years old.One hundred and twelve cases were taken cyclophosphamide,and 58 cases with invasive thymoma (stages Ⅱ,Ⅲ and Ⅳ or WHO type B3) were taken cyclophosphamide in combination with radiotherapy.Five patients refused cyclophosphamide or radiotherapy and 3 did not finish treatment.(2) The muscular strength improved obviously in 32.8％ (58/177) of the patients after 1 month after thymectomy,and 59.8％ (101/169),69.7％ (115/165) and 81.5％ (132/162) after 6 months,1 year and 2 years,respectively with MG score for disease severity decreased significantly with time.(3) No significant differences of the improvement rates were observed in patients within different WHO histology category.However,the rates were much higher in patients with Masaoka stage Ⅰ (91.4％) and stage Ⅱ (89.8％) than those in patients with stage Ⅲ (45.5％) and Ⅳ(28.6％) (all P＜0.001).Conclusions The remission rate of MG patients with thymomas increase after thymectomy plus cyclophosphamide or in combination with radiotherapy and reached 81.5％ after 2 years.The remission rate is associated with Masaoka stagc,but not with WHO histology.

Objective To research the relationship between the serum level of cystatin C (CysC),N-terminal pro brain natriuretic peptide (NT-proBNP) and the cardiovascular (CV) events in maintenance hemodialysis (MHD) patients,looking for a new and effective biological prediction method for cardiovascular disease (CVD).Methods According to the excluded criteria and included criteria,a total of 126 patients [male 67(53.2％),female 59 (46.8％)] were included in this study,screening out of 452 MHD patients from 3 blood purification centre,no secondary hyperparathyroidism,blood pressure controlled,hemoglobin standard,no lipid abnormalities,and without history of coronary heart disease,heart failure and arrhythmia.Participants adopted 3 dialysis treatment,including hemodialysis,hemoperfusion and hemodiafiltration.Every 3 months before the dialysis,the Cys-C,NT-proBNP,serum phosphorus,serum intact parathyroid hormone (iPTH),hemoglobin and electrocardiogram were detected.The heartbeat ultrasound was examined every 6 months,observed for 24 months and followed up for 3 years,recording the incidence and the inspection results.The correlation and the occurrence of CVD were analyzed by conducting a multiple factor logistic regression analysis.The forecast performance of Cys-C,NT-proBNP was evaluated by using receiver operating characteristic (ROC) curves and area under curves (AUC).Results Eighteen episodes of CV events occurred in 126 patients during the experiment and follow-up,including 8 episodes of heart failure,4 episodes of myocardial infarction,6 episodes of arrhythmia.Detection indexes had no statistically significant correlation (P ＞ 0.05),and the results of ECG and ultrasound heartbeat graph showed that no significant difference in cardiac structure and function before treatment (P ＞ 0.05).After 24 months duration,the research showed that the level of serum calcemia was lower,and the levels of phosphorus and iPTH were higher in hemodialysis group compared with that in the other 2 groups,and the differences had statistical significance (P ＜ 0.05).The median levels of Cys-C and NT-proBNP were 8.59 (9.74,7.10) mg/L and 7 739 (9 887,6 736) ng/L in the patients CV events occurred.Non conditional multivariate logistic regression analysis demonstrated that the increasing interdialytic weight,Cys-C,NT-proBNP,iPTH,dialysis hypotension were the independent risk factors of CV occurrence.AUCs to predict CVD occurrence in MHD patients was 0.64 (95％CI 0.53-0.71,P ＜ 0.05) and 0.79 (95％CI 0.72-0.89,P＜ 0.01) using Cys-C and NT-proBNP respectively.The cut-off values of serum Cys-C and NT-proBNP for CVD occurrence were 8.59 mg/L and 7 739 ng/L,with a sensitivity of 84.3％ and a specificity of 92.7％.Conclusions Cys-C,NT-proBNP can be used to predict the risk of CV events in dialysis patients.

Objective To measure the clinical significance of serum Titin antibody measurement in patients with myasthenia gravis (MG) crisis.Methods Twenty six patients with MG crisis,30 patients with other neurologieal diseases (ONDs) and 30 health controls,collected in our hospital from July 2008 to August 2010,were chosen in our study; the sera level oftitin antibody was deetected by enzyme-linked immunosorbentassay (ELISA); correlations of titin antibody level with the clinical features and prognosis of the patients with MG crisis were analyzed.Results The positive rate of titin antibodies in MG crisis group and ONDs group was 73.1％ and 3.3％,and it was negative in health control group; significant differece was noted (x2=51.922,P=0.000).The positive rate of titin antibodies in patients older than 50 years of the MG crisis group was signifcantly higher than that in patients younger than 50 years (x2=5.052,P=0.014); the positive rate of titin antibodies in MG crisis group was negatively correlated to the gender of the patients,the types of Osserman and the pathological types (P＞0.05).The titin antibody titer after treatment was significantly decreased as compared with that before treatment (P＜0.05).Conclusion Positive titin antibody is mostly found in MG crisis and it's level is related to the severity of MG crisis,indicating that it might be beneficial for evaluating prognosis of MG patients.

Objective To evaluate the efficacy and safety of tacrolimus in patients with generalized myasthenia gravis (MG).Methods A total of 69 cases admitted to our hospital were given 2-6 mg/day tacrolimus (FK506) for 12 months.The MG absolute and relative clinical scores were used to monitor the efficacy of tacrolimus.Clinical evaluation was conducted at month 1,3,6,and 12,while the serum concentration of FK506 was measured at one month after administration of tacromus for one month.Results The therapeutic response presenting as improved muscular strength showed within one month after administration of tacrolimus.The overall response rates (MG relative clinical score≥25％) at month 1,3,6 were 81.2％,87.6％,92.2％ respectively.It reached 93.8％ by the final visit at month 12.MG score to evaluate disease severity decreased significantly as the subjects continued to take tacrolimus.Statistic analysis suggested that the serum concentration of FK506 was correlated with its therapeutic effect.Serum trough levels in remission and response groups [(7.1 ± 3.9) μg/L and (6.3 ± 3.8) pg/L,respectively] were significantly higher than that of no response group [(3.4 ± 1.3) μg/L].The most common adverse effects included hyperglycemia (5 cases),myelosuppression (3 cases),and dizziness tinnitus (3 cases),majority of which were temporary and manageable.Conclusions Our study has shown that tacrolimus significantly improved muscular strength of generalized MG patients.The treatment is well tolerated.The therapeutic effect of tacrolimus is observed within 1 month after initial use.Adverse events were manageable and not common.

In order to investigate the effects of HA whisker and carboxymethyl chitosan-gelatin(CMC-Gel) on the mechanical properties of porous calcium phosphate cement, a series of alpha-tricalcium phosphate (alpha-TCP), HA whisker and L-sodium glutamate porogen with different mass fractions were mixed, and setting liquid was added to them to prepare alpha-TCP/HA whisker composite porous bone cement. Then, the cement was immersed in a series of CMC-Gel solutions which had different weight ratios of CMC to Gel to prepare alpha-TCP/HA whisker/CMC-Gel composite porous bone cement. The compressive strengths and microstructure of cement were characterized by mechanical testing machine and SEM. The results showed that when the mass fraction of HA whisker is 4%, the compressive strength of alpha-TCP/HA whisker composite porous bone cement reaches 2.57MPa, which is 1.81 times that of alpha-TCP bone cement. When the weight ratio of CMC to Gel is 50:50, the compressive strength of alpha-TCP/HA whisker/CMC-Gel composite porous bone cement is 3. 34MPa, which is 2.35 times that of alpha-TCP bone cement, and the toughness of the composite cement is greatly improved as well.
Biocompatible Materials ; chemistry ; pharmacology ; Bone Cements ; chemical synthesis ; Calcium Phosphates ; chemistry ; Chitosan ; analogs & derivatives ; chemical synthesis ; chemistry ; Compressive Strength ; Gelatin ; chemistry ; Hydroxyapatites ; chemical synthesis ; chemistry ; Porosity

Objective To investigate the immunoregulatory role of Th17 cell and the related cytokines in myasthenia gravis.Methods Totally 51 myasthenia gravis (MG) patients were divided into MG with thymomas ( TM group) and the MG with normal thymus ( NT group),as well as 22 healthy subjects as controls.Th17 cells from peripheral blood mononuclear cells were measured by flow cytometry.Th17 related cytokines were detected by ELISA and real-time quantitative-PCR.Results The quantity of Th17 cells in MG patients with thymomas (1.53 ± 0.59 )％ were significantly increased compared with that of healthy control (0.94％±0.32％,P ＜ 0.05 ).There was no significant difference in the number of Th17 cells between healthy controls and NT group.The expression levels of IL-17 mRNA ( 23.7 ± 4.5 ) were upregulated significantly versus those in healthy controls (13.4 ± 3.2,P ＜0.01 ).The levels of mRNA expression of IL-1 β,IL-6 and IL-23 were up-regulated significantly in TM group.The mean concentration of IL-17 was up-regulated significantly in TM group (30.4 ±7.3) ng/L versus healthy controls [ ( 19.2 ±4.9)ng/L,P ＜ 0.05].Serum levels of IL-23 and IL-1β were always increased in TM group versus healthy controls.Conclusion The elevated levels of IL-17 and other Th17 related cytokines in thymomas may aggravate the autoimmunity disorder.

Objective To investigation the clinical characteristics in myasthenia gravis (MG)patients with thymomas.Methods A total of 856 MG patients admitted to the department during 2008.7-2010.12 were reviewed retrospectively.The patients with MG were divided into two groups based on thymic pathology,which were 162 cases with thymoma and 694 cases without thymoma.We compared the different clinical features including the gender,age of onset,MG symptoms and the incidence rate of myasthenia crisis.And the relationship between the WHO types,Maosaoka stages of thymoma and the severe of MG was also studied.Results The percentage of thymoma-associated MG patients was 18.9 percent of hospitalized MG patients at the same period.Of the 162 thymoma-associated patients,94 were male and 68 were female,with a ratio of 1.38∶1 and a mean age of (42.9 ± 12.4)years old.Thymoma was more frequent in middle-old aged patients than in children.Compared with non-thymoma MG,more thymomatous patients showed generalised MG,but not only ocular muscles weakness (90.1％ vs 62.4％,P ＜ 0.001 ).There were significant differences of the incidence rate of myasthenic crisis in the two groups ( 14.8％ vs 2.3％ ).(2)WHO type B2 and Maosaoka Ⅰ,Ⅱ thymoma were the commonest types among all potentially MG-associated thymoma.No differences of Osserman MG classification was found in thymomatous patients with different pathologic changes.Conclusions The thymomatous MG patients had its distinctive clinical features:thymomas occured in about 19.7％ of MG patients with more men than women,more common in generalized,higher incidence of myasthenia crisis,with B2 type thymic pathology and Maosaoka Ⅰ,Ⅱstages.No correlation was found between pathologic and clinical stagcs.