Effects of cholesterol metabolism on prostate cancer progression / 现代泌尿外科杂志

Cholesterol metabolism is vital for the progression of prostate cancer (PCa), especially in the occurrence and development. Statins can affect the progression of PCa by reducing cholesterol. This paper will review how cholesterol metabolism affects the progression of PCa.

Preliminary evaluation of the safety and efficacy of oral human antimicrobial peptide LL-37 in the treatment of patients of COVID-19, a small-scale, single-arm, exploratory safety study

Background& AimsThe Coronavirus Disease 2019 (COVID-19) has become a global epidemic and has caused a lasting and huge loss of life security, economic development and social stability in more than 180 countries around the world. Unfortunately, there is still no specific treatment for COVID-19 till now, therefore, at this point, all potential therapies need to be critically considered. LL-37 is one of the best-studied human antimicrobial peptide (AMPs) that has a broad-spectrum activity against bacteria and viruses. The use of living, genetically modified organisms (GMOs) is an effective approach for delivery of therapeutic proteins. The aim of this study was to determine the safety and efficacy of the Lactococcus lactis which has been genetically modified to produce the therapeutic human antimicrobial peptide LL-37 (herein after referred to cas001) in the patients of COVID-19. MethodsFirstly we constructed genetically modified food-grade probiotic, Lactococcus lactis, with sequence of seven tandem repeats of mature human LL-37 under control of the nisin-inducible nisA promoter to produce the cas001. A total of 20 healthy SD rats, half male and half female (There were five male and five female in the control group, the same in treatment group) were used to observe the acute toxic reaction and death after daily administration of cas001 for three weeks, which helps to provide necessary reference basis for clinical dose selection, verificaition of toxic reaction and possible target organs. According to the estimated clinical dosage of 1 x 108CFU /kg/day, considering the conversion of body surface area, the dose for rats should be multiplied by 6.17 to 6 x 108 CFU/kg/day. We administrated 100 times higher dose at 6 x 1010 CFU/ /kg/day to rats. In order to investigate the pharmacokinetics of cas001, male SD rats (body weight 250-300g, 1 x 1010 /animal, n=3) were given oral administration of LL-37 bacteria powder. The concentration of LL-37 in the blood before and after gavage was detected by ELISA kit (Hycult biotechnology Cat# HK321). Human clinical study was approved by Ethics committee of Chinese PLA General Hospital (S2020-074-04) and a total of 11 patients with mild symptoms were enrolled in Wuhan hankou hospital and Huoshenshan hospital. They were enrolled voluntarily and all patients signed informed consent. Among them, there were 5 males and 6 females, aged 55 {+/-} 12 (36-70) years old, and the duration from onset to medication enrollment was 35 {+/-} 19 (5-68) days. 6 patients were nucleic acid positive and 5 patients were nucleic acid negative when they were enrolled. All patients received the oral drug cas001 treatment according to requirement(1 x 109 CFU/capsule, 3 capsules/time, three times a day for 3weeks), with an average follow-up time of 33 {+/-} 15 days (see table 1 for the results). O_TBL View this table: org.highwire.dtl.DTLVardef@1845d29org.highwire.dtl.DTLVardef@1004b38org.highwire.dtl.DTLVardef@4a741aorg.highwire.dtl.DTLVardef@c73d5org.highwire.dtl.DTLVardef@188b563_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSerum biochemical detection in rats two weeks after gavage Serum biochemistry detection of rats at the end of two weeks (Vehicle[male] v.s. LL-37[male], n=5; Vehicle[female] v.s. LL-37[female], n=5). *represent p value<0.05. C_TABLECAPTION C_TBL FindingsWestern blot analysis shows that reasonable amount of LL-37 were induced by different concentrations of nisin, which means we have successfully constructed cas001. In the pre-clinical safety evaluation test, after three weeks administration of cas001, no adverse effects were observed on the rats body weight, food and water intake, hematological or serum biochemical parameters. The results showed that the LD50 of cas001 was higher than that of the 100 times of the expected clinical dose of 6 x 1010 CFU/day. These results showed that cas001 could be safe in animal experiments. In addition, rat pharmacokinetics results showed that the serum concentration of LL-37 reached peak 2 hours after gavage of cas001 and returned to basal level 6 hours after gavage. During study period, the volunteers did not feel any discomfort while taking the cas001 capsules, and two hours after oral administration, the concentration of LL-37 were increased in healthy volunteers. cas001 shows definite effect in the improvement of gastrointestinal symptoms and is possible to have effects in improving the systemic symptoms and respiratory symptoms and may play a role in the improvement of results of nucleic acid test and lung CT test. 11 patients enrolled showed good compliance, tolerance, subjective feeling and actively interacted with the doctors. None of the patients had any adverse reactions. ConclusionsBased on above observations, we conclude here that as an oral anti-viral agent, cas001 displayed good safety profiles. It is very hard to reach conclusion of clinical outcomes related to the cas001, although changes of several symptoms indicate encouraging findings.

Establishment and predictive efficiency of model for the effect and safety of endoscopic lithotripsy on pediatric upper urinary tract calculi / 中华泌尿外科杂志

Objective:To establish a predictive model that can predict the effectiveness and safety of endoscopic surgery for pediatric upper urinary tract calculi, and evaluate its diagnostic efficacy through internal validation.Methods:The data was selected from the prospective database of pediatric upper tract calculi constructed by Beijing Friendship Hospital Affiliated to Capital Medical University from June 2014 to April 2019. A total of 348 children were recruited in this investigation including 250 boys and 98 girls, with a median age of 3.0 years(Interquartile Range 1.4, 7.0 years). Totally 375 endoscopic surgeries were performed, with an overall stone free rate (SFR) of 88.0% (330/375) and complication rate (CR) of 23.2% (87/375). This research used univariate and multivariate logistic regression analysis to evaluate and screen the predictors of SFR and CR. The nomogram of SFR and CR was established by using the selected predictive factors. The differentiation degree of the model was evaluated by the area under the curve (AUC), the consistency between the prediction probability and the actual risk was evaluated by the calibration curve, and the clinical benefits of the model application were assessed by the decision curve.Results:The results of multivariate analysis demonstrated that stone burden, operation duration, intraoperative perfusion, stone location and operative options were the postoperative predictors of SFR and CR for children. Besides, BMI was also a predictor of postoperative CR. The AUC of the model (model 1: SFR; model 2: CR) based on the above predictive factors was 0.81 and 0.73, respectively. The predictive probability of the calibration curve showed that the model had a good consistency with the actual value. The decision curve showed that the application of model 1 to predict SFR had significant clinical benefits when the threshold value was greater than 20%, and the application of model 2 to predict the postoperative CR had a significant clinical benefit when the threshold was greater than 10%.Conclusions:Nomogram based on stone burden, operation time, intraoperative perfusion, stone location and operative options was validated internally with preferable predictive power on the effectiveness and safety of pediatric endoscopic surgery. This model can be used to predict the clinical effects of pediatric endoscopic lithotripsy. BMI was also an important factor for the safety of pediatric endoscopic procedures.

Progress in the diagnosis and treatment of adrenal metastatic carcinoma / 国际外科学杂志

Adrenal gland is one of the most common metastases from malignant tumors. Most adrenal metastases have not completely destroyed adrenal tissue, so most patients have no clinical symptoms. The main methods for the diagnosis of adrenal metastases are CT, magnetic resonance imaging and positron emission tomography. At present, there is still controversy about the treatment of adrenal metastasis of all kinds of adrenal metastases. Non-surgical treatment mainly includes chemical drug therapy, radiotherapy, interventional therapy and so on. With the development of cognition and technology, the mode and indication of surgical treatment have also changed. In this paper, the diagnosis and treatment of adrenal metastases in recent years are reviewed.

Analysis of clinical features and related prognosis in chromophobe renal cell carcinoma / 国际外科学杂志

Objective@#To investigate the clinical features of chromophobe renal cell carcinoma (chRCC) and analyze the factors affecting its prognosis.@*Methods@#Retrospectively analyze the case data of 66 patients with chRCC admitted to Beijing Friendship Hospital, Capital Medical University from October 2003 to September 2018, including 32 males and 34 females; the average age was (53.9±13.9) years and the age range was 24-85 years. To analyze the clinical symptoms, whether have hypertension, diabetes, tumor characteristics (size, side, location), surgical methods, TNM staging and other clinical features of patients, with disease-free survival (DFS) as the study endpoint. The survival curve was drawed by the kaplan-Meier method. Survival analysis was performed using Log-rank test, and the clinical features of prognosis were analyzed by Cox regression models.@*Results@#Among the 66 patients, the mean diameter of the tumor was (5.4±3.5) cm, 17 cases were ≥7 cm, 49 cases were <7 cm; 48 cases were asymptomatic, and 18 cases were symptomatic; 45 cases in T1, 15 cases in T2, 6 cases in T3; 33 cases were underwent radical nephrectomy, 32 cases were underwent nephron sparing surgery, 1 case was under the therapy of watchful waiting. The median follow-up time was 61 months, and the DFS in 1, 5, and 10 years were 94.6%, 91.3%, and 82.2%, respectively. Log-rank results showed that the maximum diameter of the tumor was related to the T stage and the survival time of the patients (P<0.05). Cox multivariate analysis showed that T stage was an independent risk factor for DFS (HR=8.102, P=0.027).@*Conclusions@#ChRCC is a type of kidney cancer with a good prognosis. Tumor staging is more common in T1 and T2 phases, patients with higher DFS in 5 and 10 years, and T staging is an independent risk factor for DFS in patients.

Analysis of clinical features and related prognosis in chromophobe renal cell carcinoma / 国际外科学杂志

Objective To investigate the clinical features of chromophobe renal cell carcinoma (chRCC) and analyze the factors affecting its prognosis.Methods Retrospectively analyze the case data of 66 patients with chRCC admitted to Beijing Friendship Hospital,Capital Medical University from October 2003 to September 2018,including 32 males and 34 females;the average age was (53.9 ± 13.9) years and the age range was 24-85 years.To analyze the clinical symptoms,whether have hypertension,diabetes,tumor characteristics (size,side,location),surgical methods,TNM staging and other clinical features of patients,with disease-free survival (DFS)as the study endpoint.The survival curve was drawed by the kaplan-Meier method.Survival analysis was performed using Log-rank test,and the clinical features of prognosis were analyzed by Cox regression models.Results Among the 66 patients,the mean diameter of the tumor was (5.4 ±3.5) cm,17 cases were ≥7 cm,49 cases were ＜7 cm;48 cases were asymptomatic,and 18 cases were symptomatic;45 cases in T1,15 cases in T2,6 cases in T3;33 cases were underwent radical nephrectomy,32 cases were underwent nephron sparing surgery,1 case was under the therapy of watchful waiting.The median follow-up time was 61 months,and the DFS in 1,5,and 10 years were 94.6％,91.3％,and 82.2％,respectively.Log-rank results showed that the maximum diameter of the tumor was related to the T stage and the survival time of the patients (P ＜ 0.05).Cox multivariate analysis showed that T stage was an independent risk factor for DFS (HR =8.102,P =0.027).Conclusions ChRCC is a type of kidney cancer with a good prognosis.Tumor staging is more common in T1 and T2 phases,patients with higher DFS in 5and 10 years,and T staging is an independent risk factor for DFS in patients.

Direct lineage conversion: induced neuronal cells and induced neural stem cells

Cellular reprogramming to neural cells is an area of ongoing study in developmental neuroscience, and recent research has generated remarkable achievements. Several studies have shown that the ectopic expression of specific neural transcription factors can convert terminally differentiated cells into neural cells. Here, we review the most recent progress in the field of induced neuronal (iN) cells and induced neural stem (iNS) cells and their potential clinical applications.

THE EFFECT OF rAAV-hGDNF ON PROTECTING RAT SPINAL CORD NEURONS FROM DEATH INDUCED BY GLUTAMATE / 解剖学报

Objective In this experiment,we explored the effects of rAAV\|hGDNF on protecting spinal neurons From death. Methods rAAV\|hGDNF particals were produced by recombinant virus technolgy,and infected the culture spinal neurons which were exposed to glutamate.We counted the mortality rate and detected the expression of NOS mRNA by RT\|PCR. Results In the group transfering rAAV\|hGDNF the death rate was inhibited(50%?0^02,control 59^25%?0^023, P