[Ureteral stenosis following hematopoietic stem cell transplantation: A case report].

Ureteral stenosis is a comparatively rare complication following hematopoietic stem cell transplantation (HSCT). The etiology is still unclear and most believe that this may be due to the reactivation of BK virus in a state of immunodeficiency. In the later stages of ureteral stenosis with scarring, invasive interventions must be taken to relieve the hydronephrosis. Common treatments, such as D-J stent placement and permanent nephrostomy may not only entail the risk of infection, but also seriously affect the quality of life. Few cases of surgical intervention have been reported. In this article, a 25-year-old female was admitted to Peking University First Hospital suffering from recurrent flank pain. Seven years before, she developed hemorrhagic cystitis and bilateral urethritis 40 days after allogeneic HSCT. After continuous bladder irrigation and antiviral therapy, the left-sided hydronephrosis gradually alleviated while the right-sided one did not improve. D-J stents were used for urine drainage for 7 years before percuta-neous nephrostomy. Preoperative antegrade pyelography revealed significant hydronephrosis in the right kidney with long stricture of proximal-middle ureter. After comprehensive decision, she underwent ileal ureter replacement. The operation was successful. The segmental lesion was dissected and the scar tissue was removed. A 25 cm intestinal tube was isolated to connect the pelvis and bladder. An anti-reflux nipple was created at the distal end of ileal ureter to prevent the potential infection. The blood loss was minimal. After surgery, the drainage tube was removed in 2 weeks, the nephrostomy tube and the D-J stent was removed in 3 months. Follow-up mainly included clinical assessment, serologic testing, renal ultrasonography, blood gas analysis and radiological examination. During the follow-up of 6 years, she was symptom-free and no postoperative complications occurred. The serum creatinine level was stable. No hydronephrosis was observed under ultrasonography. Obvious peristaltic waves and ureteral jets of the ileal ureter was confirmed on cine magnetic resonance urography. To sum up, ureteral stenosis after HSCT is relatively rare. Obstruction caused by scarring is usually irreversible and surgical intervention should be designed according to the location and length of the lesion. Ileal ureter replacement can be a safe, feasible and effective method to solve this kind of complex stricture.

[Trends in upper urinary tract reconstruction surgery over a decade based on a multi-center database].

OBJECTIVE: To study the trend of surgical type, surgical procedure and etiological distribution of upper urinary tract repair in recent 10 years. METHODS: The preoperative and perioperative variables and follow-up data of upper urinary tract reconstruction surgery in RECUTTER (Reconstruction of Urinary Tract: Technology, Epidemiology and Result) database from 2010 to 2021 were searched, collected and analyzed. The surgical type, surgical procedure, duration of hospitalization, time of operation, incidence of short-term complications, and proportion of the patients undergoing reoperations were compared between the two groups of 2010-2017 period and 2018-2021 period. RESULTS: A total of 1 072 patients were included in the RECUTTER database. Congenital factors and iatrogenic injuries were the main causes of upper urinary tract repair. Among them, 129 (12.0%) patients had open operation, 403 (37.6%) patients had laparoscopic surgery, 322 (30.0%) patients had robot-assisted laparoscopic surgery and 218 (20.3%) patients had endourological procedure. In the last decade, the total number of surgeries showed a noticeable increasing annual trend and the proportion of robot-assisted laparoscopic surgery in 2018-2021 was significantly higher than that in 2010-2017 (P < 0.001). The 1 072 patients included 124 (11.6%) cases of ileal ureter replacements, 440 (41.1%) cases of pyeloplasty, 229 (21.4%) cases of balloon dilation, 109 (10.2%) cases of ureteral reimplantation, 49 (4.6%) cases of boari flap-Psoas hitch surgery, 60 (5.6%) cases of uretero-ureteral anastomosis, 61 (5.7%) cases of lingual mucosal onlay graft ureteroplasty or appendiceal onlay flap ureteroplasty. Pyeloplasty and balloon dilatation had been the main types of surgery, while the proportion of lingual mucosal onlay graft ureteroplasty plus appendiceal onlay flap ureteroplasty had increased significantly in recent years (P < 0.05). In addition, the time of operation was significantly increased (P < 0.05) after 2018, which was considered to be related to the sharp increase in the proportion of robot-assisted laparoscopic surgery. We found that minimally invasive surgery (endourological procedure and robot-assisted laparoscopic surgery) as an independent risk factor (P=0.050, OR=0.472) could reduce the incidence of short-term post-operative complications. CONCLUSION: We have justified the value of the RECUTTER database, created by the Institute of Urology, Peking University in data support for clinical research work, and provided valuable experience for the construction of other multi-center databases at home and abroad. In recent 10 years, we have observed that, in upper urinary tract reconstruction surgery, the surgery type tends to be minimally invasive and the surgery procedure tends to be complicated, suggesting the superiority of robot-assisted laparoscopic surgery.

[Effects of orlistat and metformin on metabolism and gonadal function in overweight or obese patients with polycystic ovary syndrome].

The aim of this study was to assess the effects of orlistat or metformin treatment on lipid and glucose metabolism, and gonadal function in obese/overweight women with polycystic ovary syndrome (PCOS). A total of 39 patients diagnosed with PCOS were randomly (digital table method) divided into orlistat treatment group (20 cases) and metformin treatment group (19 cases). Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months (P<0.05). No significant differences could be viewed between orlistat and metformin treated subjects. Moreover, orlistat treatment significantly lowered the levels of low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) (P<0.05), while there were no significant changes in above parameters with metformin treatment. The improvement of menstrual cycle was observed after 6-month treatment in both groups (P<0.05). However, changes in polycystic ovarian morphology by ultrasound were only observed in orlistat treated group. In conclusion, orlistat is comparable with metformin in weight loss and improvement of insulin resistance and menstrual cycle, and is superior to metformin in improvement of lipid metabolism in overweight/obese PCOS patients.

[Changes in platelet related parameters in obese patients after sleeve gastrectomy].

To compare changes in platelet related parameters in obese patients before and after sleeve gastrectomy (SG), we retrospectively analyzed the clinical data of 31 obese patients who underwent SG in Peking Union Medical College Hospital from December 2012 to September 2020. Results showed that compared with those before surgery, platelet count (PLT) decreased significantly at 2-12 weeks of follow-up (P=0.009), while platelet distribution width (PDW), mean platelet volume (MPV), and large platelet ratio (P-LCR) increased significantly at the same periods of follow-up after operation (P<0.001). However, the levels of PDW, MPV, and P-LCR began to decrease at 16-55 weeks when compared with those at 2-12 weeks of follow-up (P<0.01). PLT was positively correlated with white blood cells and neutrophils at 2-12 weeks of follow-up and positively correlated with high sensitivity C-reactive protein at 16-55 weeks of follow-up after operation (P<0.05).

[Updated key points of Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021 edition)].

Led by the China Pituitary Adenoma Specialist Council, the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021 Edition) is developed combined with the research progress of pituitary growth hormone (GH)-secreting adenoma both at home and abroad, evidence-based evidence of the diagnosis and treatment of acromegaly, and China's national conditions. Based on the guideline for acromegaly (2013 Edition), the new version of consensus emphasizes the importance of multidisciplinary team (MDT) and individual therapy. The criteria for control of acromegaly is discussed. Pathological criteria for the diagnosis of pituitary GH-secreting adenoma is updated. New developments in surgery, drug and radiotherapy are introduced. Meanwhile, the diagnosis and treatment of acromegaly patients concurrent with other particular scenarios, including pregnancy and refractory pituitary GH-secreting adenoma is suggested. This article aims to describe the updated key points of the new version of the consensus, and thus facilitate the clinical implementation of standardized diagnosis and treatment for acromegaly patients.

[Association of sleep duration with cognitive impairment among older adults aged 65 years and older in China].

Objective: The study is to examine association of sleep duration and cognitive impairment in the older adults aged 65 years and older in China. Methods: We analyzed data from 2017-2018 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 14 966 participants were included in the analysis. Data with respect to socioeconomic status, community involvement, behavior pattern, diet, life style, family structure, disease condition, mental health and cognitive function were collected. Cognitive function was measured with Mini-mental State Examination (MMSE). We conducted generalized linear mixed models to examine associations of sleep duration with cognitive impairment, and subgroup analyses of sex and age were conducted. Results: Among 14 966 participants, the percentage of participants aged 65 to 79 years, 80 to 89 years, 90 to 99 years and 100 years and older was 5 148 (4.40%), 3 777 (25.24%), 3 322 (22.20%) and 2 719 (18.16%), respectively. A total of 2 704 participants reported sleep duration of 5 h and less, and 3 883 reported 9 h and more, accounting for 18.94% and 27.19%, respectively. In total, 3 748 were defined with cognitive impairment, accounting for 25.04%. The results of generalized linear mixed models showed that both short (≤5 h) and long (≥ 9 h) sleep duration were associated with cognitive impairment compared with sleep duration of 7 h, with OR(95%CI) of 1.35(1.09-1.68) and 1.70(1.39-2.07), respectively. The association of sleep duration with cognitive impairment was more obvious in males and individuals aged 65 to 79 years old. Conclusion: Short or long sleep duration was responsible for increased risk of cognitive impairment in older Chinese.

[Risk factors for postoperative intestinal obstruction in patients undergoing robot-assisted laparoscopic radical prostatectomy].

Objective: To analyze the risk factors of postoperative intestinal obstruction (POI) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RARP). Methods: The clinical data of 573 patients receiving RARP from January to December 2019 in Nanjing Drum Tower Hospital were analyzed retrospectively. According to the occurrence of POI, the cases were divided into the occurrence group and the non-occurrence group. The clinical data of the two groups were compared and the risk factors of POI were investigated by multivariate logistic regression. Results: Forty-five of 573 patients (7.9%) had POI. Between the two groups, preoperative underlying diseases (cardiopathy, COPD, hypoalbuminemia), preoperative chemotherapy, preoperative WBC, operation time, blood loss, blood transfusion rate, postoperative early fever, length of stay were statistically significant (P<0.05). Multivariable logistic regression analysis showed that heart disease (OR=2.331, P=0.036), COPD (OR=4.285, P=0.001), hypoalbuminemia(OR=2.142, P=0.026), blood loss (≥4.26 ml/kg) (OR=2.388, P=0.010), operative time (≥225 min) (OR=4.200, P<0.001), and postoperative early fever (OR=2.773, P=0.004) were independent risk factors for POI after RARP. Conclusions: The incidence of POI following RARP is related to multiple perioperative factors. Improving the preoperative heart and lung function, correcting hypoalbuminemia, reducing intraoperative bleeding, shortening the operation time, and preventing early postoperative infection may be important measures to reduce the risk of POI in RARP patients.

[Etiology and clinical features of primary adrenal insufficiency].

Objective: To summarize the etiology of primary adrenal insufficiency (PAI) and analyze its clinical features. Methods: A retrospective analysis was performed in the Department of Endocrinology, Peking Union Medical College Hospital from October 1981 to June 2019. Patients with PAI as the first symptom were enrolled. The etiology of PAI was analyzed and the clinical characteristics was also summarized. Results: A total of 131 patients with PAI were enrolled, including 87 males and 44 females (57 adolescents, and 74 adults). The age ranged from 0 to 73 years. The primary cause of PAI in adolescents was genetic defects (52.6%, 30/57), in which congenital adrenal dysplasia caused by DAX1 gene deficiency accounted for 50.0% (15/30), followed by autoimmunity (22.8%, 13/57). The primary cause of adult PAI was infection (58.1%, 43/74), of which tuberculosis accounted for the majority (93.0%, 40/43), and autoimmune adrenalitis accounted for 19.0% (14/74). Compared with the tuberculosis group, female patients were more common, and the onset age was younger, the plasma cortisol, serum sodium, fasting blood glucose, creatinine and aldosterone were lower (all P<0.05), and serum potassium and renin levels were higher in the autoimmune adrenalitis group (both P<0.05). Conclusions: In the current study, the proportion of PAI caused by infection in the adult group was higher than that in the adolescent group. The most common cause of adult PAI was tuberculosis infection. The most common cause of childhood PAI was genetic defects. Autoimmune damage to the adrenal glands may be more severe than tuberculosis infection.

[Relationship between C-reactive protein level and incidence of left atrial spontaneous echocardiographic contrast in patients with nonvalvular atrial fibrillation].

Objective: To investigate the relationship between high sensitivity C-reactive protein (hs-CRP) level and incidence of left atrial spontaneous echocardiographic contrast (LASEC) in the patients with nonvalvular atrial fibrillation (AF). Methods: Four hundred and ninety consecutive patients with nonvalvular atrial fibrillation who underwent radiofrequency ablation for the first time from January 1, 2018 to June 30, 2018 in the Department of Cardiology, Beijing Anzhen Hospital were enrolled. According to the results of transesophageal echocardiography before radiofrequency ablation, patients were divided into the group without LASEC (n=338) and the group with LASEC (n=152). hs-CRP was determined by latex enhanced immunoturbidimetry. The relationship between hs-CRP and LASEC in patients with nonvalvular atrial fibrillation was investigated by univariate and multivariate logistic analysis. Results: LASEC was detected in 152 (31%) of 490 patients. Significant differences in age, type of atrial fibrillation, previous embolic events, fibrinogen, D-dimer, the left atrial anteroposterior diameter and CHA(2)DS(2)-VASc scores were found between patients with and without LASEC (all P<0.05). Compared with the group without LASEC, the serum hs-CRP level was significantly higher in the group with LASEC (3.16 (1.30, 5.23) mg/L vs. 0.67 (0.37, 1.48) mg/L, P<0.001). Multivariate logistic regression analysis showed that hs-CRP (OR=1.136, 95%CI 1.060 - 1.217, P<0.001) and D-dimer (OR=1.040, 95%CI 1.011 - 1.070, P=0.007) were independent determinants for LASEC in this patient cohort. Conclusions: hs-CRP is an independent determinant for LASEC in patients with nonvalvular atrial fibrillation. Inflammation may thus be involved in the formation of prethrombotic state in patients with nonvalvular atrial fibrillation.

[Impact of history of hypertension and blood pressure levels on the risk of thromboembolism in nonvalvular atrial fibrillation patients].

Objective: To investigate the impact of history of hypertension and blood pressure levels on the thromboembolism risk in the setting of nonvalvular atrial fibrillation (NVAF). Methods: China Atrial Fibrillation Registry Study prospectively enrolled 25 512 atrial fibrillation (AF) patients between August 2011 and December 2018. After exclusion of patients with valvular AF, hypertrophic cardiomyopathy, receiving anticoagulation or ablation therapy at the enrollment, 7 757 patients were included in analysis. The primary endpoint was the time to the first occurrence of ischemic stroke or systemic embolism. Cox proportional hazards models were performed to evaluate whether a history of hypertension or blood pressure levels were independently associated with thromboembolism. Results: During a mean follow up of (35±25) months, 455 （5.9%）thromboembolic events occurred. The crude incidence rate of thromboembolism in patients with a history of hypertension was higher than that in patients without hypertension (2.38 vs. 1.35 per 100 patient-years, χ²=16.8，Log-rank P<0.001). Patients were further divided into 4 groups according to systolic blood pressure (SBP) levels at baseline, the crude incidence rate of thromboembolism significantly increased in proportion to the elevation of SBP levels (χ²=17.9，Log-rank P<0.001). However, there was no significant difference in thromboembolism risk among 4 groups stratified by diastolic blood pressure (DBP) levels (χ²=0.6，Log-rank P=0.907). Multivariable regression analysis showed that history of hypertension was independently associated with a 27% higher risk of thromboembolism (HR=1.27, 95%CI 1.01-1.61, P=0.045). Patients with SBP≥140 mmHg (1 mmHg=0.133 kPa) was associated with 36% higher risk of thromboembolism than patients with SBP<120 mmHg (HR=1.36, 95%CI 1.02-1.82, P=0.036). However, patients with SBP 120-129 mmHg or 130-139 mmHg were not at a higher risk of thromboembolism as compared to the patients with SBP<120 mmHg (SBP 120-129 mmHg: HR=1.23, 95%CI 0.90-1.67, P=0.193; SBP 130-139 mmHg: HR=1.30, 95%CI 0.95-1.77, P=0.098). In addition, DBP levels were not independently associated with the increased thromboembolism risk. Conclusion: A history of hypertension and SBP≥140 mmHg are independent predictors of thromboembolism risk in patients with NVAF. These results indicate that intensive efforts to lower SBP below 140 mmHg might be an important strategy to reduce the risk of stroke in patients with NVAF.

[The correlation of ganglion cell layer thickness with visual field defect in non-functional pituitary adenoma with chiasm compression].

Objective: To investigate the consequences of the thickness of ganglion cell layer (GCL) and visual field defect of non-functional pituitary adenoma with chiasm compression. Methods: A case control study. The study included 40 (80 eyes) non-functional pituitary adenoma patients in Peking Union Medical College Hospital from March 2015 to February 2017. Twenty patients (no visual field defect group, 40 eyes) of them were detected to be chiasm compressed or touched by the adenoma with no visual field defect detected, and the other 20 patients (visual field defect group, 40 eyes) were the sex-and-age matched pituitary adenoma patients with bitemporal heminopsia. This study also included 20 (control group, 40 eyes) sex-and-age matched healthy controls. The para-papillary retinal nerve fiber layer (RNFL) thickness in 6 quadrants including nasal, temporal, nasal superior, temporal superior, nasal inferior and temporal inferior as well as the macular GCL thickness and ganglion cell-inner plexiform layer (GCIPL) thickness in 4 quadrants including nasal superior, nasal inferior, temporal superior and temporal inferior were measured. The non-parametric test was used to compare the RNFL, GCL and GCIPL thickness among the three groups. Results: The mean age among the three groups was (46±10) years and the difference among the three groups was not significant (P=0.88). The sex ratio of the three groups was 9∶11 (male∶female) and the difference among the three groups was not significant. The mean axial length among the three groups was (23.22±0.90) mm and the difference among the three groups was not significant (P=0.51). The thickness of para-papillary RNFL of temporal superior, temporal, nasal superior, nasal, nasal inferior quadrants and whole circumference was significantly thinner in the visual field defect group than the control group [(129.88±28.64) µm, (63.63±26.84) µm, (88.08±32.16) µm, (50.68±19.99) µm, (92.48±25.06) µm, and (85.00±20.65) µm vs. (141.10±18.95) µm, (79.12±16.78) µm, (113.68±21.28) µm, (69.67±14.23) µm, (117.80±31.32) µm, and (102.80±9.68) µm, t=2.26, 3.06, 4.14, 4.84, 4.25, 4.88, all P<0.05]. In the nasal quadrant, the para-papillary RNFL of the no visual field defect group was significantly thinner compared with the control group [(61.45±9.83) µm vs. (69.67±14.23) µm, t=2.97, P<0.05]. The total GCL thickness was (30.48±5.42) µm in the visual field defect group, (31.35±2.77) µm in the no visual field defect group, thinner than that in the control group [(33.32±2.92) µm, t=2.92, 3.62; both P<0.05]. The total GCIPL thickness showed no significant difference among the three groups (P=0.07). In the superior and inferior temporal quadrants, the GCL and GCIPL thickness showed no significant difference among the three groups (all P>0.05). In the superior and inferior nasal quadrants, the GCL thickness was (29.41±5.97) µm, and (28.47±5.13) µm in the visual field defect group, (31.15±3.27) µm and (30.61±2.96) µm in the no visual field defect group, and (34.23±3.16) µm and (32.97±2.78) µm in the control group. The GCL thickness in the nasal quadrant was thinner in the visual field defect group (t=4.45, 4.82)and the no visual field defect group(t=4.23, 3.63) than in the control group (all P<0.01). However, no significant difference in GCL thickness was detected between the visual field defect group and the no visual field defect group (both P>0.05). In the superior and inferior nasal quadrants, the GCIPL thickness was (54.06±10.50) µm and (51.77±9.18) µm in the visual field defect group, (58.03±4.00) µm and (56.23±5.37) µm in the no visual field defect group, and (62.26±7.11) µm and (59.39±6.64) µm in the control group. The GCIPL thickness was thinner in the nasal quadrant in the visual field defect group than in the control group (t=3.95, 4.20, both P<0.01). Only in the Superior nasal quadrant, the GCIPL was significantly thinner in the no visual field defect group than the control group (t=3.25, P<0.01). Conclusion: The optic GCL may get thinner in pituitary nonfunctional adenoma with chiasm compression patients without the RNFL layer thinning and visual field defect. (Chin J Ophthalmol, 2019, 55: 186-194).

Tacrolimus population pharmacokinetics according to CYP3A5 genotype and clinical factors in Chinese adult kidney transplant recipients.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is characterized by a narrow therapeutic index and a considerable inter- and intraindividual pharmacokinetic variability. The aim of our study was to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant of Chinese patients, identify factors especially CYP3A5*3 genetic polymorphism that explain variability, and determine dosage regimens. METHODS: Pharmacogenomic data obtained from 83 Chinese kidney transplant patients treated with tacrolimus were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Trough blood concentration data were collected from all of the patients during the 12 months of post-transplantation days and were analysed using the nonlinear mixed-effects modelling program. After building the final model, 1000 bootstraps were performed to validate the final model. RESULTS AND DISCUSSION: A one-compartment model with first-order absorption and elimination adequately described the pharmacokinetics of tacrolimus. In this study, we observed that POD, HCT and CYP3A5*3 genotype were determinant factors in CL/F and POD related with V/F of tacrolimus significantly. The final model with the clearance covariates was presented as: Cl/F=THETA(1)*EXP(THETA(4)*(83/POD))*(39.1/HCT)**THETA(5)*EXP(THETA(6)*CYP3A5), and the final model with the volume covariates was presented as: Vd/F=THETA(2)*POD**THETA(3). The Ka was fixed to 4.5 h-1 . WHAT IS NEW AND CONCLUSION: The HCT, CYP3A5*3 genetic polymorphism and POD contributed to the interindividual variability of oral tacrolimus in Chinese adult renal transplant patients.

[Outcome of negative pressure wound therapy on diabetic foot ulcers: an observational study].

Objective: To compare the treatment effects between negative pressure wound therapy (NPWT) and traditional therapy in diabetic patients with foot ulcers. Methods: Diabetic patients with foot ulcers were selected from Endocrinology Ward between January 2015 and December 2016. All the patients were consecutively selected to receive NPWT in addition to the traditional therapy. Each patient receiving NPWT was individually matched with a patient receiving only traditional therapy and selected as the control group. Patients were controlled in both groups for age, sex and history of diabetes, hemoglobin A1c (HbA1c) level, and severity of the ulcer. Each patient received therapy for 3 months and was evaluated at the end of treatment. Treatment efficacy was evaluated by examining the lesion area before and after the therapy. Outcomes were compared between the two groups using the Chi square test. Results: A total of 62 patients were included in the study, with 31 cases in each group.Three months later, in the NPWT group, 26 patients had good therapeutic effects, 5 patients had poor efficacy, and 4 patients underwent the surgical treatment. While in the control group, only 18 patients had good therapeutic effects, 13 patients had poor efficacy, and 6 patients underwent surgical treatment. The effective percentage was significantly higher in NPWT group than that of the control group(P<0.05). Conclusion: NPWT can effectively improve the healing process of patients with diabetic foot ulcers in 3 months.

[Oncolytic property of HSV-1 recombinant viruses carrying the human IL-12].

Objective: Constructed the recombinant HSV-1 deleted ICP47 and inserted human IL-12, and investigate the virus' replication ability and oncolytic property in vitro and vivo. Methods: The recombinant HSV-1 deleting ICP47 (MH1005) and then inserting human IL-12 (MH1006) were obtained with bacterial artificial chromosome technology.The replication ability and the efficiency of inhibiting tumor were detected in several nerve tumor cell lines infected with HSV-wt, MH1005 and MH1006 respectively.The murine tumor model was established by subcutaneous inoculation Neuro-2a cells on both sides of mice back respectively.A dosage of 2×10(6) PFU of HSV-wt, MH1001(recombinant HSV-1 deleted IR), MH1005, MH1006 and Mock were injected 3 times intratumorally on one side of mice back in every 3 days, the tumor volume and survival rate of the mice were measured. Results: The replication abilities of MH1005, MH1006 and HSV-wt in 293FT cells were insignificant (P>0.05); the replication abilities of recombinant HSV-1 in G422 and Neuro-2a were higher than that in SK-N-SH; and the nerve tumor cells could be inhibited significantly by recombinant HSV-1.After 15 days of treatment, on the mouse backside with injection treatment, the tumor volumes of group HSV-wt (6 267±484), MH1001 (5 730±1 071), MH1005 (4 537±538)and MH1006 (4 150±476)mm(3) were smaller than that of group Mock (6 957±722) mm(3) significantly (all P<0.01); on the mouse backside without injection treatment, the tumor volumes of group MH1005 (5 952±607) and MH1006 (5 473±661) mm(3) were smaller than those of HSV-wt (6 785±1 063), MH1001 (6 774±808) and Mock (6 957±190) mm(3) significantly (all P<0.05); after 35 days of treatment, the mice survival rates of group MH1005 (100%) and MH1006 (100%) were higher than those of MH1001 (67%), HSV-wt (50%) and Mock (33%) significantly (all P<0.05). Conclusion: MH1005 and MH1006 can infect nerve tumor cells and replicate at high level, the viruses not only kill tumor cells directly but also induce immunological rejection to tumor, and prolong the survival of mice bearing tumor.

[Treatment effects analysis of preoperative long-acting somatostatin analogs combined trans-sphenoidal endoscopic surgery for patients with growth hormone secreting pituitary macroadenomas].

Objective: To evaluate the treatment effects of preoperative long-acting somatostatin analogue (SSA) combined trans-sphenoidal endoscopic surgery for patients with growth hormone (GH)-secreting pituitary macroadenomas. Methods: Retrospective analysis was carried out on 20 patients with GH-secreting pituitary macroadenomas who were treated with preoperative SSA and trans-sphenoidal endoscopic surgery in our apartment from January 2010 to January 2016. We also selected 20 patients with only trans-sphenoidal endoscopic surgery treatment and 20 patients with preoperative SSA and non-trans-sphenoidal endoscopic surgery treatment. The changes of tumor imaging, endocrine and blood pressure before and after treatment were analysed. Results: The Gross total resection (GTR) rate of invasive GH-secreting pituitary macroadenomas of preoperative SSA combined trans-sphenoidal endoscopic surgery group (8/13) were higher than that if only trans-sphenoidal endoscopic surgery group (4/16) and preoperative SSA combined non endoscopic surgery group (1/8) (P<0.05). Meanwhile, preoperative SSA combined trans-sphenoidal endoscopic surgery group had significantly improved the GH levels, blood glucose, lipid metabolism and blood pressure levels (P<0.05). Conclusion: The trans-sphenoidal endoscopic surgery on patients with GH-secreting pituitary macroadenomas has a significant improvement on GH levels, blood glucose, lipid metabolism and blood pressure levels. Through the treatment of preoperative long-acting SSA, the gross total resection rate is higher than other two groups.

[The localization diagnosis of patients with adrenocorticotropic hormone-dependent Cushing's syndrome in adolescence].

Objective: To elucidate the clinical characteristics and localization diagnosis of patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) in adolescence. Methods: The clinical data, laboratory examination and localization diagnosis from 35 patients aged less than 18 years old with adolescent CS who were treated at Peking Union Medical College Hospital between January 1990 and March 2012 were analyzed. Results: There were 29 cases of Cushing's disease (CD) and 6 cases of ectopic ACTH syndrome (EAS). Compared to patients with EAS, those with CD were older at diagnosis[(15.2±2.7) vs (12.8±4.4) years], and had longer disease course[(1.9±1.5) vs (0.7±0.3) years]and higher serum potassium[(3.8±0.6) vs (2.5±0.7) mmol/L], however the plasma ACTH level[(15.4±14.9) vs (42.5±22.7) pmol/L]was lower (all P<0.05). If the cut-off of the ratio of 24-hour urine free cortisol (24 h UFC) after low-dose dexamethasone suppression test (LDDST) to before LDDST was 0.65, the sensibility to diagnose CD was 70.8%, and the specificity was 100%. If the cut-off of the 24 h UFC ratio after high-dose dexamethasone suppression test (HDDST) to before HDDST was 0.54, the sensibility to diagnose CD was 91.7%, and the specificity was 100%. If the cut-off of the plasma ACTH ratio of inferior petrosal vein[bilateral inferior petrosal sinus sampling (BIPSS)]to peripheral vein was 2, only 6 CD patients (6/8) met it. Conclusion: The study suggested that HDDST was more meaningful in the localization diagnosis of patients with ACTH-dependent CS in adolescence.

CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors.

The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs.