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The incidence of each of the rare disease is very low. The complexity and diagnosis difficulty of the rare disease lead to the difficulties in the clinical research and development (R&D) of drugs for rare diseases. There is an urgent clinical need for the drug development of rare diseases in China. Encouraging R&D of new drugs, particularly the innovative drugs with China's own independent intellectural property is the basis for solving the predicament in drug shortage in China.. In order to further improve the efficiency of clinical R&D of drugs for rare diseases, the National Medical Products Administration (NMPA), Center for Drug Evaluation (CDE) issued Technical Guidance for Clinical Research and Development of Drugs for Rare Diseases. This is the first guidance for rare diseases in China that is drafted from the standpoint of the clinical technology research and development.The guidance is the scientifitc thinking and framework for the drug developing enterprises to research and develop drugs for rare disease efficiently and appropriately by following drug developing protocols and relating to the special features of rare disease.This paper presents the concepts and rationale in the guidance for the appraisal of rare disease drug research and development.
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In the present study, the safety of Haemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.
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Humans , Infant , Bacterial Capsules , China , Haemophilus Vaccines , IncidenceABSTRACT
ObjectiveTo summarize the initial experience of transumbilical laparoendoscopic single-site surgery of urology.MethodsFrom February 2010 to March 2011,21 patients underwent laparoendoscopic single-site surgery using transumbilical single-site and common surgical instruments of laparoendoscopic.Nine patients underwent single-site laparoscopic ureterolithotomy,5 underwent transumbilical single-site laparoscopic ureteral stricture resection and anastomosis,5 underwent transumbilical single-site laparoscopic renalcyst unroofing and 2 had a nephrectomy.All of the cases were definitely diagnosed.A single umbilical incision of 1.5 cm to 2.5 cm was made for Triport.The procedures were performed according to the methods used in classical laparoscope methods using general instruments.ResultsAll the operations were successfully completed without conversion to open surgery.The mean operative time of ureterolithotomy was 143 (120-230) min,the mean operative time of ureteral stricture resection and anastomosis was 157 (120 -180) min,the mean operative time of unroofing of renal cysts was 110 (95 -132) min,and the operative time of the nephrectomy was from 95 to 120 min.The intestinal tract function recovered within 1 -2 d,the drainage tube was removed within 2 -3 d and the postoperative hospitalization duration was 4 -7 d.The symptoms were reduced or disappeared and no major intraoperative or postoperative complications occurred within 4 - 6 months.Conclusions Transumbilical laparoendoscopic single-site surgery represents a safe and feasible operation for urologic patients.With more clinical practice,laparoendoscopic single-site surgery could be generally applied.
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ObjectiveTo investigate the diagnosis,differential diagnosis,treatment and prognosis of multilocular cystic renal cell carcinoma (MCRCC).MethodsA total of 398 patients with renal carcinoma were hospitalized from January 1999 to October 2010,and there were 18 patients with MCRCC.The data of clinical diagnosis and treatment of these cases were analyzed retrospectively.ResultsMCRCC accoumted forrenal carcinoma in the same period was 4.52％( 18/398 ).According to TNM staging,5 cases were in stage pT1N0M0,13 cases in stage pT2N0M0.There were 8 cases in G1 phase,10 cases in G2 phase.Conclusions The preoperative diagnosis of MCRCC is difficult to differentiate,and mainly based on CT,especially spiral CT.It should be treated mainly with radical nephrectomy,and nephron sparing surgery in some cases.
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Objective To develop and evaluate a porcine model for training the single needle running suture method of laparoscopie urethrovesical anastomosis(LUA). Methods Twenty minipigs with mean weight of 30kg were general anaesthetized with Sumianxin solution 0. 1 ml/kg intramuscularly. Pneumoperitoneum was created by insufflation of carbon dioxide by a veress needle inserted through the umbilicus. One 10mm port and two 5mm ports were positioned after the establishment of pneumoperitoneum. The intestine was used as "bladder". The procedures were completed with the single needle running suture method of laparoscopic urethrovesical anastomosis. Six trainees performed the LUA procedure based on the models during a laparoscopic training course, following the technique used in the operation room. The learning curve was analyzed by operative time. Results The porcine model for laparoscopic training was established successfully and 3 LUAs could be performed on each pig. Each trainee performed 10 LUAs based on the models during the training course of laparoscopic urology. The operative time declined from (55.3±10. 4)min initially to (22.4±4.8)min (P＜0. 01) after the training course. At the end of training, all trainees could accomplish a watertight LUR procedure on the model. Conclusions The establishment of the training model is feasible. The trainees could acquire the skills necessary to perform LUA in vivo based on this model. The model provides a platform for training the basic techniques of LUA procedures.
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Objective To discuss the diagnosis and management of metastatic adrenal carcinoma. Methods Forty-seven cases with metastatic tumor in the adrenal glands were analyzed retrospectively from December 1996 to April 2010. Lung was the most common primary tumor site (51.1 %, 24 cases), followed by the renal cell carcinoma (12.8%, 6 cases), liver cancer (10.6%,5 cases), breast cancer (8.5%, 4 cases), melanoma (4.2%, 2 cases), and other carcinoma (12.8%,6 cases). Most patients with metastatic adrenal carcinoma had no special clinic manifestation. Lesions of 36 cases were surgically removed and 11 cases gave up operation. Results The mean survival time were 33.8±4.5 months for 31 cases underwent adrenalectomy and 6.3±2.7 months for 6 cases without operation. Patients with surgically removed adrenal metastases had better survival than those without surgical resection. Conclusions Adrenal gland is a common site of metastatic carcinoma.Ultrasonographic and CT scans are important diagnosis methods for metastatic adrenal carcinoma. Operation is still effective and long-term survival may be achieved for those well selected patients, but surgical indication must be strictly monitored.
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<p><b>OBJECTIVE</b>To study the effect on promoter de-methylation, expression of ALDH1a2 gene and cell apoptosis by treated with 5-Aza-dC and TSA in five human bladder cancer cell lines.</p><p><b>METHODS</b>Human bladder cancer cell lines RT-4, 253J, 5637, BIU-87 and T24 were cultured and treated with 5-Aza-dC and(or) TSA. The expression of the ALDH1a2 gene was detected by RT-PCR and Western blot. The methylation status of gene promoter was determined by MSP, and the cell cycle profile was established by flow cytometry.</p><p><b>RESULTS</b>ALDH1a2 was silenced in five human bladder cancer cell lines. Re-expression of ALDH1a2 was detected after treated with 5-Aza-dC alone or TSA in combination. ALDH1a2 transcript was marked in each cell lines combined with 5-Aza-dC and TSA treatment which showed a synergistic effect on expression of ALDH1a2 transcript. Early apoptotic was the main mode of apoptosis and death of human bladder cancer cell lines induced by 5-Aza-dC and TSA. The percentage of early apoptotic cells was 1.4% in control group and 2.8% in TSA group, however, 20.2% in 5-Aza-dC group and 33.8% in 5-Aza-dC + TSA group, respectively. The groups of TSA, 5-Aza-dC and 5-Aza-dC + TSA were significantly different from control group (P < 0.05).</p><p><b>CONCLUSIONS</b>Aberrant methylation of ALDH1a2 gene is the main cause for gene transcriptional inactivation. Re-expression of ALDH1a2 gene and cell apoptosis are detected after either treatment with 5-Aza-dC alone or in combination with TSA.</p>
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Humans , Apoptosis , Azacitidine , Pharmacology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Hydroxamic Acids , Pharmacology , Retinal Dehydrogenase , Metabolism , Urinary Bladder Neoplasms , Metabolism , PathologyABSTRACT
The single needle method for urethrovesical anastomosis with strengthened posterior fixation during laparoscopic radical prostatectomy was explored. The method was initiated by performing a fixing suture with a knot at 4 o'clock of the posterior lip of bladder neck, and another suture at nearby position was performed to leave the knot outside. From 5 o'clock to 8 o'clock, sutures were performed every one o'clock to secure posterior approximation, then every two o'clock a suture. To avoid a loose anastomosis, lock sutures were performed every 3 sutures. The needle was always driven full-thickness outside-in in the bladder neck and inside-out on the urethra. After completing the full circumference, the needle was drawn near the 4 o'clock and tied at the tail end. Any leakage could be closed with additional interrupted sutures. The clinical data of 89 patients who underwent this method were retrospectively compared with those of 23 patients who underwent the single knot method. The results showed that the anastomosis, operative and catheterization time was 17.6+/-4.7 min, 134.0+/-10.7 min and 6.5+1.6 days respectively. There were 3 temporal urinary leakages identified in 89 cases requiring prolonged catheterization. No urinary leak and anastomotic stricture was confirmed, and 95.2% patients had total urinary control. It was concluded that this method was simple and safe for urethrovesical anastomosis.
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Objective To describe the single needle running suture method for the urethrovesi-cal anastomosis during laparoscopic radical prostatectomy(LRP). Methods Forty-five patients of prostate cancer underwent LRP with the single needle running suture method. The technique was initi-ated by performing a fixing suture at the posterior lip of bladder neck at 4 o' clock and tying the first knot. Another suture at the nearby position of the first suture was performed to leave the first knot outside. From 5 o' clock to 8 o' clock, sutures were performed every one o' clock to secure posterior approximation, then every two o'clock a suture. To avoid a loose anastomosis, lock sutures were per-formed every 3 sutures. After completing the full circumference, the needle was drawn at the 2 o' clock for the second knot. The needle was always driven full-thickness outside-in in the bladder neck and inside-out on the urethra. Any remaining leakage could be closed with additional interrupted su-tures. Results All urethrovesical anastomosis were completed successfully. The mean anastomosis time was 16 rain(from 12 to 25 min), and mean operative time was 132 rain (112 to 185 rain). The mean catheterization time was 9 d(7 to 14 d). Three temporal urinary leaks requiring prolonged cathe-terization were identified. Forty-four patients had total urinary control in 1 year postoperatively and no other short-term or persistent complication was found with a mean follow-up of 21 months. Conclu- sion The single needle running suture method could be a simple and safe method for urethrovesical anastomosis during LRP.
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Objective To develop and evaluate a porcine model for laparoscopic ureterovesical reimplantation (LUR) training. Methods Ten female pigs with a mean weight of 30 kg were used and the animals were placed on supine position after anesthesia. One 10 mm port and two 5 mm ports were placed after the establishment of pneumoperitoneum. The horn of uterus was used as "ureter". A model simulating the performance of LUR was then established on the mini-pigs. Four trainees per-formed the LUR procedures on the animal models during an advanced laparoscopic urology training course, following the technique criteria exactly used in LUR. The learning curve was analyzed in terms of operation time. Results The porcine model for laparoscopic training was established suc-cessfully and 4 LUR trainings was performed on each porcine. Each trainee performed 10 LURs on the models during the training course. The operation time declined from 170±10 rain initially to 90±4 rain after the training course (P<0.01). At the end of this training, all trainees could accomplish a watertight LUR procedure on the model. Conclusions The establishment of the training model is feasible. The trainees could acquire skills needed to perform LUR in vivo based on this simple model and to develop dexterity and facility in laparoscopic manipulation of needles and sutures as well. The model provides a platform for basic techniques training of the ureteral reconstruction procedures.
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Objective To investigate the in vitro effects of bladder cancer cell proliferation after silencing Notch1 gene. Methods The siRNA eukaryotic expression vector of Notch1 (psiRNA1)was constructed and transfected into bladder cancer cell lines T24 and BIU-87. Methabensthiazuron (MTT) and flow cytometry (FCM) assays were used to detect bladder cancer cells line growth, cell cycle and apoptosis after the transfection. RT-PCR and Western blotting were used to determine the expression changes of Notch1 in these cell lines. Results After transfection for 72 h, the rate of G0/G1 phase cells inceased from (23.89±1.32) % to (80.13±2.69)% in T24 cell line, and increased from (24.63±1.68)% to (69.44±2.41)% in BIU-87 cell line (both P<0.05). In addition, apop-totic cell index in T24 and BIU-87 cell lines increased from (1.28±0.14)% to (13.75±1.23)%, from (1.01±0.27)% to (8.72±1.01)%, respectively(both P<0.05). The growth of T24 and BIU-87 cell lines was obviously inhibited 24 h after the transfection, and the inhibitory effects lasted until 96 h after the transfection. Notch1 mRNA and protein significantly downregulated after transfection compared to the control(P<0.05). Conclusions Silencing Notch1 expression can inhibit the prolif-eration of bladder cancer cell lines. Notch1 gene might act as a tumor gene in bladder cancer.
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Objective To validate a new standardized training program for urological surgeons to improve their laparoscopic surgical skills. Methods The laparoscopic surgical training program was carried out by using the traditional mechanical simulators and animal models. Thirty-three trainees participated the urological laparoscopic surgical training program. Initially, the novices were assigned to practise basic laparoscopic skills step by step on the simulator with fixed trocar positions. After a period of basic training, they were allowed to practise on animal models for some particular proce-dures. Results All trainees (33/33, 100.0%) participated were able to perform all basic techniques skillfully and completed laparoscopic anastomosis accurately after the training. The time required for performing the partial nephrectomy, dismembered pyeloplasty and ureteral reimplantation on animal models declined from 64.0±18.4, 127.54±17.5 and 75.84±11.6 min at the beginning to 30.94±3.8, 65.2±7. 5 and 37.7±7.2 min after practicing these procedures 8 times (P<0.01). They could un-derstand the crucial procedures of the laparoseopic surgeries after 6 to 8 special trainings on animal models. Fifteen trainees (15/33, 45.5%) had started to carry out laparoscopic surgeries after-finish- ing the training program. Conclusions Our program enables the participants to improve their techniques in complicated laparoscopic surgeries. The challenging parts of reconstructive laparoscopic surgeries such as laparoscopic dismembered pyeloplasty can be taught by using animal models. This program could be incorpo-rated easily by all urological departments developing a laparoscopie surgical training program.
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Objective To study the endoscopic anatomical structures in retroperitoneal space and to share experiences of retroperitoneoscopic radical nephrectomy. Methods Between January 2006 and March 2008, a total of 85 patients underwent retroperitoneoscopic radical nephrectomy. Thirty-eight tumors were on the left kidney and 47 on the right side. The mean tumor size was 5.5± 1.7 cm in diameter (2.5 to 10.5 cm). There were 74 cases in clinical stage T1N0M0 and 11 cases in T2N0M0. Following the principle of radical nephrectomy outside the renal fascia, the whole surgical procedure was performed along "2 spaces" and "2 poles". The ventral attachment of the kidney was dissected in anterior pararenal space between peritoneum and anterior renal fascia. The dorsal attachment was dissected in anterior psoas space between posterior renal fascia and psoas fascia. The cepha-lic attachment was dissected up to the subdiaphragmatic and down to iliac fosse. During the proce-dure, important anatomic structures such as parietal peritoneum and its reflexion, anterior renal fasci-a, lateroeonal fascia, posterior renal fascia, psoas muscles, greatvessels and their branches were care-fully identified. Results One case was converted to open surgery because of severe and extensive ad-hesion of the right kidney to the adjacent tissues. The other 84 procedures were successfully comple-ted. The median operative time was 65 rain (range 50 to 165 min) and median estimated blood loss was 58 ml (range 25 to 600 ml). Of all operations, peritoneum perforation occurred in 5 cases and small vessel injuries around renal pedicles were observed in 6 cases. Major complication such as great vessel injury was not observed. Mean follow-up of all 85 patients was 10 months (range 2 to 25 months). No local recurrence and port site tumor seeding was found. Conclusion During retrope-ritoneoscopic radical nephrectomy, studying anatomical features of renal area and recognizing impor-tant anatomic structures will help to improve the safety of the surgery and reduce morbidities.
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The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P<0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P<0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.
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<p><b>OBJECTIVE</b>To evaluate the effect of combined use of implantation of (125)I seeds with regional arterial infusion chemotherapy on late-staged pancreatic carcinoma.</p><p><b>METHODS</b>During operation, (125)I seeds were implanted into tumor parenchyma or operative beds for 7 patients with pathological diagnosis of late-staged pancreatic carcinoma, then chemotherapy pump was implanted into common hepatic artery or celiac artery through left gastric artery or right epigastric artery. Gemcitabine (1000 mg/m(2)) plus fluorouracil (500 mg/m(2)) was used for postoperative adjuvant chemotherapy once a week for 7 consecutive weeks.</p><p><b>RESULTS</b>The mean number of implanted (125)I seeds was 42 and the mean dose was 29.4 mCi. The mean follow-up time was 245 days. Rate of pain relief was 100%, metastasis foci was reduced in 2 cases. CA-19-9 Antigen level decreased to normal in all patients. Pancreatic fistula occurred in one case and was cured with conservative therapy.</p><p><b>CONCLUSIONS</b>The combination therapy is effective for late-staged pancreatic carcinoma, it brings symptom relief and improvement in quality of life.</p>
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Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Brachytherapy , Methods , Chemotherapy, Adjuvant , Combined Modality Therapy , Follow-Up Studies , Infusions, Intra-Arterial , Iodine Radioisotopes , Therapeutic Uses , Pancreatic Neoplasms , Therapeutics , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P＜0.05), but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P＞0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P＜0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P＜0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.
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Objective To explore a method for establishing stable auditory deprived animal model of mouse.Methods Forty two-month old BALB/c mice with normal auditory brainstem response(ABR) thresholds were divided into two groups randomly.The experimental group underwent an incision inferior to the pinna,and the cochleas were destoried with a drill through the bulla bilaterally.The control group underwent only an incision without cochlea ablation.Mice were tested for ABR thresholds 4 month later to assess hearing sensitivity by comparing the ABR before and after operation.Results In the experimental group,auricle reflection disappeared after operation and ABR waves couldn't be detect.In the control group,the result of hearing test was normal.Conclusion Mouse cochlea ablation is a reliable method for establishing a stable auditory deprived animal model of mouse by the pinna inferior approach.It can be used to the research of auditory centre plasticity induced by auditory deprived.
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Objective To study the effect of magnetic nanoparticles on human cholangiocarcinoma xenograft in nude mice, and compared with otherchemotherapy drugs Methods We established human cholangiocarcinoma xenograft in nude mice with QBC939 cell line.The nude mice were devided into 4 groups randomly.Saline,5-FU, Gemcitabine and magnetic nanoparticles were given to nude mice through tail vein on 20d after implanting QBC939 cell line. Calculations were done at different time after treatment in order to compare tumor volume,inhibition ratio of tumor and tumor growth curve of each group. The nude mice were killed on 35d after treatment to harvest tissue for electron microscopic examination to observe ultra-structural changes. Results The tumor volume of control, 5-FU, magnetic nanoparticles and Gemcitabine groups was (2256.1?267.1) mm3, (2096.5?237.9)mm3,(1392.2?189)mm3, and (1534.9?115 )mm3 respectively.The last two groups have significant difference compared to the first two groups(P