Nephrocalcinosis is often accompanied by kidney stone disease. In recent years, more and more nephrocalcinosis has been found to be caused by a monogenic disease, and its pathogenesis has not been fully elucidated. With the development of molecular genetics, more than 30 genes have been found to be the causative genes of nephrocalcinosis. At the same time, with the widespread development of genetic testing technology, more patients have received early diagnosis and timely intervention. This article reviews the clinical and basic research progress of monogenic nephrocalcinosis.

Primary hyperoxaluria (PH) are important causes of kidney stone and chronic kidney stone disease in children. Recurrent kidney stone disease and nephrocalcinosis should alter the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition of genotype and phenotype of PH resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. This paper review the characteristics of genotype and phenotype, genotype-phenotype correlation, current treatment and future gene therapy of PH.

Objective To study the short-term clinical efficacy and its possible mechanism of refractory hypertension(RH) treated by continuous veno-venous hemofiltration (CVVH) in maintenance hemodialysis (MHD) patients. Methods Thirty-four MHD patients with RH treated with CVVH enrolled in the treatment group,all these patients were treatment of 2 -3 times,each time 8 - 10 hours. Thirty MHD patients with wellcontroled blood pressure were recruited as control. Changes of blood pressure, dry weight, plasma levels of parathyroid hormone (PTH), renin ( RA), angiotensin Ⅰ , Ⅱ ( AT Ⅰ , AT Ⅱ ), aldosterone ( Ald ) were observed before and after hemodialysis. Results In the treatment group,compared with pre-treatment, the blood pressure decreased significantly with an effective rate of 64.7% and efficient rate of 100. 0%. Before treatment, plasma RA was ([1.10 ±0.25] μg/(L · h)and [0:78 ±0.26] μg/(L · h),AT Ⅰ was [0.89 ±0.21] μg/L and [ 0. 52 ± 0. 14 ] μg/L, AT Ⅱ was [ 177.68 ± 89.46 ] ng/L and [ 89. 25 ± 12. 84 ] ng/L, Ald was [72. 06 ± 11.47 ]ng/L and [ 48.92 ± 8. 65 ] ng/L, PTH was [ 306. 81 ± 69. 37 ] ng/L and [ 248.76 ± 134. 62 ] ng/L in the treatment and control group respectively. All the measurements in the treatment group were significantly higher than those in the control group (P ＜ 0. 05 ). In the treatment group, compared to pre-treatment, plasma RA significantly decreased ( [ 1.10 ± 0. 25 ]μg/ ( L · h) vs [ 0. 76 ± 0. 17 ] μg/( L · h ), as well as AT Ⅰ ( [ 0. 89 ±0.21]μg/L vs [0.50 ±0.12] μg/L),ATⅡ([177.68±89.46]ng/L vs [ 87.13±14.22] ng/L),Ald ([72.06±11.47]ng/Lvs [ 46. 01± 9. 86 ] ng/L ) and PTH ( [ 306. 81 ±69.37]ng/L vs [ 186.53 ±32.93 ] ng/L) ( P ＜ 0. 05 ). However, there was no significant changes in the above mentioned measurements between before and after hemodialysis in the control group (P ＞ 0. 05). Conclusion CVVH may be an effective methods in the treatment of MHD patients with RH, and its antihypertensive mechanisms may be that CVVH can effectively remove the excess water in the body, and reduce plasma RA, AT Ⅰ , AT Ⅱ ,Ald and PTH levels.

Objective To study the efficacy of performing transvaginal Prosima mesh with high uterosacral ligament suspension (HUS) in treatment of severe pelvic organ prolapse (POP).Methods From July 2010 to February 2011,70 patients with severe POP underwent transvaginal prosima mesh with HUS in First Affiliated Hospital,General Hospital of People's Liberation Army.Clinical parameters of perioperation were collected.After 1 month and 2 - 3 months,perineal two-dimensional ultrasound examination was performed to measure mesh length in midsagittal plane.Validated prolapse quality of life questionnaires,pelvic floor distress inventsry short form 20 (PFDI-20) and pelvic floor impact questionnaire short form 7 (PFIQ-7) were used to evaluate the therapeutic effect.The mean results of pre-operative PFIQ-7 and PFDI-20 was 54 and 51,respectively.Results Median operation time was ( 195 ± 47 ) min and median blood loss was (160 ±64) ml.All the patients were followed for a mean time of 13 months (2 - 19 months).Seven cases were found with mesh exposure with less than 1 cm2.The objective cure rate was 100％.The mean score of post-operative PFIQ-7 and PFDI-20 were both 19,which were significantly lower than those of preoperation ( P ＜ 0.05 ).Anterior Prosima mesh was 3.5 cm at 1 month by ultrasound examination,and the second result of ultrasound scans was 2.8 cm at 2 - 3 month,which were both shortened 2.5 cm and 3.2 cm when compared with that of original size.Conclusions Transvaginal Prosima mesh placement with HUS is a safe and efficient surgery with less complication.Although mesh became shorter after 2 - 3 month,it did not affect surgery efficacy.

Objective To study the objective and subjective therapeutic effect of total and partial (LeFort) colpocleisis in treatment of severe pelvic organ prolapsed ( POP) in selected elderly patients.Methods From Oct 2005 to Feb.2010,63 severe POP patients[59-87 years,median age (75 ±6) years]with stage Ⅲ and Ⅳ by POP-Q system underwent total and partial colpocleisis.The mean age was (75 ±6)years (59-87 years).Fifty-eight patients(58/63,92% )present more than one kind of medical disease.There were 53 cases with uterus prolapse,1 case with cervix prolapse and 9 cases with vaginal vault prolapse.Seven patients were recurrent POP from previous surgery.Twenty-three patients(36% ) presentedvoiding difficulty.Seven patients (17%) presented obstructive bowel symptom.Three patients (5%) presented fecal incontinence,and 28 patients(44% )presented either had urinary incontinence or history of that Among 63 patients,48 patients (76% ) underwent total colpoclesis,and 15 (24% ) patients partial colpoclesis.Meanwhile,58 (92% ) patients underwent levator myorrhaphy plus perineorrhaphy and 20 (32% ) patients underwent anti-urinary incontinence procedure ( TVT-0 ),respectively.Patients were followed up to evaluate therapeutic effect at 2 months and 1 year after surgery.Objective evaluation included the POP-Q and the length of vagina,genital hiatus,perineal body.A nonvalidated Body Image and Satisfaction Questionnaire was completed for subjective evaluation.Results The mean operating time of 63 patients was (105 ±48) minutes,which was (128 ±58) in total and (82 ±26) minutes partial procedures,which exhibited significant difference(P<0.05).The mean blood loss was (187 ± 128) ml (50-600 ml),total and partial procedures caused (232 ± 159) and (101 ±54) ml,respectively,which also showed significant difference ( P < 0.05 ).No intraoperative injury or death occurred.The rate of postoperative complications was 5% (3/63).Mean follow-up time of 63 patients was 22.5 months (1-51 months).All patients had POP-Q staging score ≤Ⅰ.No recurrent patient was observed.At 1 year after operation,the mean preoperative total vaginal length (TVL) and genital hiatus (GH) of (7.7 ± 1.1) and (5.5 ± 1.5)cm were decreased to (3.4 ± 1'.l)and (2.3 ±0.5) cm (P<0.01) ;and perineal body (PB) measurements was increased from (2.6±0.9) to (3.4 ±0.9)cm(P <0.01).Three (5%,3/63) patients had mild urinary incontinence after the operation.Twenty-three patients with voiding difficulty presenting the mean postvoid residual volumes (110 ± 38) ml(50-235 ml) were decreased to 12 ml after the operation.Obstructive bowel symptom was improved in 6(54%,6/11) patients,and fecal incontinence improved in 2(2/3).One year after the operation,52 ( 82% ) patients completed the nonvalidated Body Image and Satisfaction Questionnaire.49 (94% ) patients said either 'very satisfied' or 'satisfied' with the outcome of their surgery,while 3 ( 6% ) reported unsatisfied or not at all satisfied.Conclusions The objective and subjective curative rates of colpocleisis in treatment of severe POP are high with lower morbidity and recurrence.Colpocleisis is a safe and effective management in selected elderly patients with severe POP,who no longer desire to maintain vaginal coital function.

Objective To investigate the impact of colpocleisis on body image in women with severe pelvic organ prolapse (POP). Methods From Oct. 2005 to Feb. 2010,60 POP patients with stage Ⅲ and Ⅳ by POP quantitation system underwent total or partial colpocleisis. Patients received body image evaluation before and 1 year after operation. Results One year after operation, 52 (87% , 52/60) patients completed body image evaluation. Before and 1 year after operation, the ratio of answer Not at all of questions such as Have you felt less physically attractive as a result of your vaginal prolapse? , Have you been feeling less feminine as a result of your vaginal prolapse? , Did you find it difficult to look at yourself naked? , Have you been feeling less sexually attractive as a result of your vaginal prolapse?, Have you felt dissatisfied with your body? were 25% and 96% ( P ＜ 0. 01 ) , 21% and 96% ( P ＜ 0. 01) , 37% and 67% (P = 0.018), 29% and 96% (P＜0.01), 12% and 83% (P＜0.01), respectively, indicating significant improvement on body image after operation for patients treated by colpocleisis. Conclusion Women underwent colpocleisis for severe POP could not decrease their body image as a result of the disability of vaginal intercourse.

Objective To assess the long-term effectiveness of the transvaginal high uterosacral ligament suspension (HUS) in women suffering from advanced pelvic organ prolapse (POP).Methods A retrospective review of records identified 118 women who underwent transvaginal HUS with or without additional concomitant anterior and (or) posterior repairs from June 2003 to August 2009 in the First Affiliated Hospital,General Hospital of People's Liberation Army.Of 118 women,104 women completed the follow-up during study period;these 104 women were analysed.Follow-up visits were performed 2,6 and 12 months after surgery and then annually.Anatomic results of POP was established by pelvic examination using pelvic organ prolapse quantitation system (POP-Q) staging.Funtional results were obtained by patient global impression of improvement (PGI-I),pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7).Surgical success required the fulfillment of all 3 criteria:(1) prolapse leading edge of 0 cm or less and apex of 1/2 total vaginal length or less;(2) the absence of pelvic organ prolapse symptoms as reported on the PFDI-20 question No.3 (Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?);and (3) no prolapse reoperations or pessary use during the study period.Results The mean follow-up time was (9.1 ± 1.5) years.The overall surgery success rate was 91.3％ (95/104) according to above all 3 criteria.Prolapse recurrence rates were isolated anterior 6.7％ (7/104),isolated apical 0,isolated posterior 2.9％ (3/104) and multiple compartments 1.0％ (1/104).Five women (4.8％,5/104) developed bothersome vaginal bulge symptoms.None of recurrent women underwent retreatment,including either surgery or use of a pessary at last follow-up.The subjective satisfaction rate was 90.4％ (94/104).PFDI-20 and PFIQ-7 scores showed a statistically significant improvement from preoperative 72 and 65 points to postoperative 17 and 9 points respectively (all P＜0.01).There was a 2.9％ (3/104) rate of intraoperative ureteral kinking and 3.8％ (4/104) rate of postoperative morbidity.Conclusions The transvaginal HUS for vault prolapse offers good long-term anatomical results with excellent vault suspension.With additional concomitant anterior and (or) posterior repairs,it will be a reconstructive surgery for the majority of advanced POP.It is minimal traumatic and appropriate for different type of POP,especially for the eldly patients.It is worthy of being popularized for clinical application.

Background and purpose:Huachansu has been widely used to treat cancer in China.But maximum tolerated dose(MTD) of huachansu is still not well defined.The purpose of this study was to conduct a Phase Ⅰ study to determine the MTD of huachansu in the treatment of patients with hepatocellular carcinoma,non-small cell lung or pancreatic cancer.Toxic profile and efficacy of huachansu were also assessed qualitatively.Methods:Huachansu was intravenously administered to patients with stage Ⅲ/Ⅳ hepatocellular carcinoma,non-small cell lung cancer,or pancreatic cancer.Each cycle consisted of daily huachansu for 14 days with an interval of 7 days between two cycles.2 or more cycles were delivered to the patients if no severe adverse event occurred.The planned dose escalation schedule for huachansu was as follows,10,20,40,60,90 and 120 ml/(m2?d).Results:Fifteen patients(3 at each level) have been recruited to the study(11 with hepatocellular carcinoma,2 with pancreatic cancer,and 2 with lung cancer).There were no dose limiting toxicities found after dose level 5.Among all these patients,the efficacy in 14 patients could be valued,in which,6 were SD(42.9%),8 were PD(57.1%).At dose level 1,there was one patient with hepatocellular carcinoma achieving a 20% reduction in tumor mass that lasted 11 months,6 of 15(42.9%) patients with stable disease and 8 of 15(57.1%) with progress disease after the treatment.Conclusions:To date,dose limiting toxicity has not been seen with doses up to eight times higher than that typically used before.Of interest, several patients had prolonged stable disease or minor tumor shrinkage.

In recent years, multiple monogenic causes of nephrolithiasis have been identified.Monogenic nephrolithiasis can lead to renal calculus, nephrocalcinosis, extrarenal manifestations, renal insufficiency and renal failure.Advances in genetic testing techniques have improved the ability to obtain a definitive diagnosis of monogenic causes of kidney stone diseases efficiently and effectively.Similarly, advances in gene therapy technologies, especially gene editing, promise to change the way to treat patients with monogenic inherited nephrolithiasis.Now, the classification, cha-racteristics of genotype and phenotype, and the treatment of monogenic causes of nephrolithiasis were reviewed.

Some kidney stones are caused by single gene mutations, and monogenic kidney stone diseases associated with purine metabolic disorder mainly including adenine phosphoribosyltransferase(APRT) deficiency, hypoxanthine-guanine phosphoribosyltransferase(HPRT)deficiency, hereditary xanthinuria(HX), and some diseases caused by gene mutations such as PRS1, SLC22A12, SLC2A9 and ABCG2. Such diseases can lead to abnormal metabolism of purine and uric acid, and then form 2, 8-dihydroxyadenine stones, uric acid stones or xanthine stones. This kind of diseases are rare, the genotype and phenotype of different types of monogenic diseases related to purine metabolism have their own characteristics and are not widely recognized. At present, the main treatment is medical therapy. Gene sequencing will make the diagnosis and find more disease-related genes or mutations. Gene editing, such as CRISPR/Cas9 technology, makes it possible to cure monogenic kidney stone diseases associated with purine metabolism disorder in the future.