OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

There are few reports on the study of extraperitoneal robotic single-port laparoscopic radical prostatectomy in China. In this study, patients with localized prostate cancer were treated with extraperitoneal robotic single-port laparoscopic radical prostatectomy extraperitoneal robot-assisted single-port laparoscopic radical prostatectomy(EpRA-spRP)from April 2019 to June 2019.All patients performed EpRA-spRP successfully without adding additional auxiliary port. The operation time and blood loss were controllable, and hospitalization time was short. It is safe and feasible to perform EpRA-spRP for medium and low-risk prostate cancer. The short-term tumor control and functional recovery are satisfactory.However, the long-term effect needs further follow-up and observation.

In order to establish a bone scaffold with good biological properties, two kinds of new gradient triply periodic minimal surfaces (TPMS) scaffolds, i.e., two-way linear gradient G scaffolds (L-G) and D, G fusion scaffold (N-G) were designed based on the gyroid (G) and diamond (D)-type TPMS in this study. The structural mechanical parameters of the two kinds of scaffolds were obtained through the compressive simulation. The flow property parameters were also obtained through the computational fluid dynamics (CFD) simulation in this study, and the permeability of the two kinds of scaffolds were calculated by Darcy's law. The tissue differentiation areas of the two kinds of scaffolds were calculated based on the tissue differentiation theory. The results show that L-G scaffold has a better mechanical property than the N-G scaffold. However, N-G scaffold is better than the L-G scaffold in biological properties such as permeability and cartilage differentiation areas. The modeling processes of L-G and N-G scaffolds provide a new insight for the design of bone scaffold. The simulation in this study can also give reference for the prediction of osseointegration after the implantation of scaffold in the human body.
Bone and Bones ; Humans ; Permeability ; Porosity ; Tissue Engineering ; Tissue Scaffolds

Objective:To investigate the factors related to the prognosis of patients with metastatic renal cell carcinoma after bone metastasectomy and to provide a reference for the clinical treatment of renal cell carcinoma.Methods:The clinical data of 143 patients with metastatic renal cell carcinoma in our center from January 2008 to December 2018 were retrospectively collected. Among 143 patients, 121 were male and 22 were female, with the average age of (54.8±12.5) year-old(from 18 to 85 year-old). The KPS scores of 138 patients were no higher than 80%. According to International Metastatic RCC Database Consortium (IMDC) risk model for metastatic renal cell carcinoma, the patients were divided into intermediate risk group (92 patients) and poor risk group (51 patients). The patients who had received complete resection for both primary lesion and metastatic tumor were regarded as tumor-free (47 patients). Otherwise, the patients with unresectable primary tumor or incomplete resection of the metastatic tumor were defined as the patients surviving conversely bone metastases were the only metastatic site, and the other 57 patients also experienced concomitant metastases comparatively. Sixty-two patients only had solitary bone metastasis lesion and 81 patients had multiple bone metastases. Kaplan-Meier survival analysis was used to calculate the 1-year, 3-year and 5-year survival rate. The impacts of different variables on the prognosis were examined by log-rank test. Univariate analysis and multivariable Cox proportional hazards regression models were used to identify the independent risk factors.Results:The median follow-up time was 49.0 months. The overall survival was 1-115 months, with the median OS was 24.0 months. The 1-year, 3-year and 5-year survival rate were 79.2%, 59.4% and 31.6%, respectively. All the patients underwent bone metastasectomy and 72 of them were treated with targeted therapy. The pathology results of metastasectomy were clear cell carcinoma for 132 patients and non-clear cell carcinoma for the 11 patients. In tumor-free group, the median OS was 30.0 months and in survival with tumor group, the median OS was 19.4 months, with a significant difference between the two groups ( P=0.030). In IMDC intermediate risk group, the prognosis was improved among the patients who received post-surgical targeted therapy after metastasectomy (24.3 months vs. 16.8 months, P=0.027), whereas the difference was not significant for IMDC poor risk group ( P=0.449). Age ≥60 years and multiple bone metastases sites were proved to be the independent risk factors for the prognosis of patients with metastatic renal cell carcinoma after bone metastasectomy. Conclusions:The prognosis of RCC patients with bone metastases was generally poor. Metastasectomy could prolong the OS of the patients who had undergone primary nephrectomy and had solitary bone metastasis. Metastasectomy combined with targeted therapy could significantly improve the prognosis of the IMDC intermediate risk patients. However, the effect of targeted therapy among IMDC poor risk patients remained to be further proved.

Objective:To assess the safety and feasibility of single-port robotic radical cystectomy.Methods:During May 2019 and August 2019, nine patients (8 males, 1 female) received single-port robotic radical cystectomy by the same surgeon. The average age was 65.6(56-78)years. After a 4.5-5.5 cm trans-umbilical incision was made, Lagiport was inserted. Da Vinci Si system 1 #, 2 # arms and 30° lens were applied. Radical cystectomy and bilateral pelvic lymphadenectomy were performed without additional ports. Urinary diversion was completed outside the body. Uterus and vaginal anterior walls were also resected for female patient. Results:All 9 surgeries were successfully conducted without additional ports or conversion to laparoscopic and open surgery. The average operation time was 437.8(280-600)min. Urinary diversion methods included 2 orthotopic ileal neobladder, 5 ideal conduit and 2 cutaneous ureterostomy. Average estimated blood loss was 227.8(100-450)ml, without blood transfusion. Average intestinal recovery time was 3.1(2-4)days, drainage duration was 8.3(3-16) days, and postoperative hospital stays was 7.7(6-13) days. Pathological TNM stage: T 2aN 0M 0 6 cases, T 2bN 0M 0 1 case, T 3aN 3M 0 1 case, T isN 0M 0 1 case. All surgical margins were negative. One bowel obstruction was cured with fasting and indwelling gastric tube. During 9-12 months’ follow-up, no tumor recurrence and metastasis were observed. There was no hydronephrosis or ureterostenosis. All surgical incision healed well. Conclusions:For experienced surgeons, single-port robotic radical cystectomy is safe and feasible with small incision and fast recovery. Short-term clinical result is satisfied.

Objective To compare the perioperative parameters and renal function in patients,whose aged was 65 year-old or above,with clinical T1-2 renal tumors undergoing partial nephrectomy (PN) or radical nephrectomy (RN).Methods A retrospective review of 469 patients,who underwent RN and PN in our center,was conducted from January 2012 to November 2018,icluding 247 in the RN group and 222 in the PN group.The RN group consisted of 170 male and 77 female patients,with the mean age of (70.96 ± 5.21) year-old.126 cases were found that the tumor located on the fight side,with the median diameter of (4.93 ± 2.03) cm.The median BMI,median R.E.N.A.L.score and pre-operation eGFR of the RN group were (24.4 ± 3.1) kg/m2,8.39 ± 1.45) and (80.23 ± 15.14) ml/(min · 1.73 m2),respectively.The PN group consisted of 150 male and 72 female patients,with the mean age of (70.23 ± 4.62) years old.108 patients had tumors on the left side while 114 on the right side,with the median diameter of (3.17 ± 1.41) cm.The median BMI,median R.E.N.A.L score and pre-operation eGFR of the PN group were (23.5 ± 3.2) kg/m2,(6.69 ± 1.81) and (82.83 ± 14.36) ml/(min · 1.73m2),respectively.No statistical difference was noticed in the age,gender,tumor location and BMI between RN group and PN group(P ＞ 0.05).The PN group had smaller tumors and lower R.E.N.A.L.scores than the RN group (P ＜ 0.05).Various parameters were compared between the PN and RN groups,including operative duration,surgical procedure,intraoperative blood loss,perioperative blood transfusion,drainage tube removal time,postoperative duration of hospitalization,pathological results,the renal function immediately after surgery and at 1 month,1 year,2 years,3 years,4 years,5 years after surgery,and the incidence of chronic renal dysfunction.Results Significant differences were found in multiple variables between the two cohorts,such as operative duration [(115.70 ± 39.69) min in RN vs.(132.26 ± 49.02) min in PN],estimated intraoperative blood loss [(45.85 ± 55.93) days in RN vs.(66.60 ± 61.55) ml in PN],drainage tube removal time [(4.38 ± 1.71) days in RN vs.(4.86 ± 1.61) days in PN],duration of postoperative hospitalization [(5.14 ± 1.65) days in RN vs.(5.52 ± 1.32) days in PN] (P ＜ 0.05).Furthermore,higher proportion of RCC was detected in the RN cohort (93.5％ in RN vs.86.5 ％ in PN,P ＜ 0.05).There was no significant difference in perioperative blood transfusion rate between the two cohorts (10.93％ vs.9.01％,P ＞ 0.05).Compared with the RN cohort,the PN cohort had higher eGFR immediately after surgery [(74.08 ± 18.31) ml/(min · 1.73m2) vs.(52.58 ± 14.21) ml/(min · 1.73m2)],1 month after surgery [(76.11 ± 18.34) ml/(min · 1.73m2) vs.(53.78 ± 15.03)ml/(min · 1.73m2)] and at the last follow-up [(73.92 ± 18.59) ml/(min · 1.73m2) vs.(52.35 ± 16.13) ml/(min · 1.73m2)] (P ＜ 0.001).Compared with those of the RN cohort,the incidences of eGFR ＜ 45 ml/(min · 1.73m2) of the PN cohort were lower immediately after surgery [9.01％ (20/222) vs.31.9％ (79/247)],1 month after surgery [7.87％ (14/178) vs.27.31％ (62/227)],1 year after surgery [8.96％ (13/145) vs.38.75％ (62/16 0)],2 years after surgery [9.89％ (9/91) vs.31.57％ (42/133)],3 years after surgery [13.21％ (7/53) vs.30.61％ (30/98)],4 years after surgery [16.21％ (6/37) vs.30.26％ (23/76)] and 5 years after surgery [18.18％ (4/22) vs.31.11％ (14/45)] (P ＜ 0.001).Conclusion The perioperative risk of PN in the treatment of elderly patients aged 65 and above with clinical cT1-2 renal tumor is controllable.PN could better retain renal function for those patients and reduce the risk of postoperative chronic renal insufficiency.

Objective To investigate chromosome abnormality rate and related factors of spontaneous abortion in early pregnancy. Methods A total of 831 tissue samples of spontaneous abortion in early pregnancy were collected from June 2015 to August 2018 in the First Affiliated Hospital of Nanjing Medical University. Chromosomal copy number was analyzed by next generation sequencing (NGS). The relationships between chromosome abnormality and maternal age, in vitro fertilization?embryo transfer (IVF?ET) pregnancy, number of previous spontaneous abortions, history of live birth were analyzed by statistical methods. Results Among 831 tissue samples of spontaneous abortion in early pregnancy, 461 (55.5%, 461/831) were found to have chromosome abnormalities. Maternal age (OR=1.107, 95%CI: 1.070-1.145) and history of live birth ( OR=1.909, 95%CI : 1.182-3.083) were the positive correlative factors of chromosome abnormality. Times of previous spontaneous abortion (OR=0.807, 95%CI: 0.702-0.928) and IVF?ET pregnancy ( OR=0.554, 95%CI : 0.404-0.760) were the negative correlative factors of chromosome abnormality. Conclusions Chromosome abnormality is an important cause of spontaneous abortion in early pregnancy. The rate of chromosome abnormality increases with the increase of maternal age and the history of live birth, and decreases with the increase of number of previous spontaneous abortion and IVF?ET pregnancy.

Objective: To investigate chromosome abnormality rate and related factors of spontaneous abortion in early pregnancy. Methods: A total of 831 tissue samples of spontaneous abortion in early pregnancy were collected from June 2015 to August 2018 in the First Affiliated Hospital of Nanjing Medical University. Chromosomal copy number was analyzed by next generation sequencing (NGS). The relationships between chromosome abnormality and maternal age, in vitro fertilization-embryo transfer (IVF-ET) pregnancy, number of previous spontaneous abortions, history of live birth were analyzed by statistical methods. Results: Among 831 tissue samples of spontaneous abortion in early pregnancy, 461 (55.5%, 461/831) were found to have chromosome abnormalities. Maternal age (OR=1.107, 95%CI: 1.070- 1.145) and history of live birth (OR=1.909, 95%CI: 1.182-3.083) were the positive correlative factors of chromosome abnormality. Times of previous spontaneous abortion (OR=0.807, 95%CI: 0.702-0.928) and IVF-ET pregnancy (OR=0.554, 95%CI: 0.404-0.760) were the negative correlative factors of chromosome abnormality. Conclusions Chromosome abnormality is an important cause of spontaneous abortion in early pregnancy. The rate of chromosome abnormality increases with the increase of maternal age and the history of live birth, and decreases with the increase of number of previous spontaneous abortion and IVF-ET pregnancy.

OBJECTIVETo observe the expression change of mitophagy-related proteins in skeletal muscle in rats with spleen deficiency syndrome and to explain the partial action mechanism of acupuncture at Zusanli (ST 36) for spleen deficiency syndrome.

METHODSForty male SD rats, after normal feeding, were randomly divided into a normal group, a spleen deficiency group, a Zusanli group and a non-acupoint group, ten rats in each group. Except the normal group, the three factors modeling method was used for 14 days to establish the model of spleen deficiency syndrome on the other 3 groups. The rats in the Zusanli group were treated with EA at bilateral "Zusanli" (ST 36), while the rats in the non-acupoint group were treated with EA at bilateral non acupoint (dense-sparse wave, frequency of 2 Hz/100 Hz, 20 min per treatment, once a day for 10 days). The rats in the normal group and spleen deficiency group were treated with immobilization for 20 min per day, and no EA was given. The HPLC method was applied to measure the content of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) in skeletal muscle. The Western blotting method was applied to measure the expression of adenosine monophosphate activated protein kinase (AMPK), p-AMPK, ULK1, p-ULK1，LC3-Ⅰand LC3-Ⅱ in skeletal muscle.

RESULTSThe ATP content in the spleen deficiency group was significantly lower than that in the normal group (<0.01); the ATP content in the Zusanli group was significantly higher than that in the spleen deficiency group (<0.05) but lower than that in the normal group (<0.05), there was no significant difference between the non-acupoint group and the spleen deficiency group (>0.05). Compared with the normal group, the AMP/ATP in the spleen deficiency group and the Zusanli group were significantly up-regulated (<0.01, <0.05). The differences of p-AMPK/AMPK between the spleen deficiency group and the normal group was not significant (>0.05). Compared with the normal group and spleen deficiency group, the p-AMPK/AMPK in the Zusanli group was significantly up-regulated (both <0.05). The p-ULK1/ULK1 and LC3-Ⅱ/LC3-Ⅰin the Zusanli group was higher than those in the normal group and spleen deficiency group (all <0.01).

CONCLUSIONEA at "Zusanli" (ST 36) might activate AMPK and produce stable ULK1/AMPK compound and increase the mitochondrial autophagy, which could regulate spleen-stomach and treat spleen deficiency.

Objective To compare the operative-postoperative outcomes of laparoscopic and robotassisted partial nephrectomy (LPN and RAPN) for patients with T1 b renal masses.Methods A total of 169 T1 b renal mass patients receiving LPN (n =69) or RAPN (n =100) in our center between October 2009 and October 2017 were retrospectively collected.There were 46 males and 23 females in LPN group,with a mean age of (55.0 ± 11.9) years.The mean tumor size was (5.09 ± 0.76) cm,and mean R.E.N.A.L score was 6.36 ± 1.53.49 procedures (71％) were performed via a retroperitoneal approach in LPN group.There were 59 males and 41 females in RAPN group with a mean age of (52.9 ± 11.7) years.The mean tumor size was(4.95 ±0.66) cm,and mean R.E.N.A.L score was 8.17 ± 1.50.31 procedures (31％)were performed via a retroperitoneal approach in RAPN group.There was statistical significance between two groups in R.E.N.A.L score and surgery approach (P ＜ 0.001).The group covariates were balanced through propensity score matching (PSM) using 1∶ 1 nearest neighbor matching method.After PSM,operating time,estimated blood loss,warm ischemia time,incidence of complications,hospital stay and postoperative follow-up status were compared between LPN(n =36)and RAPN(n =36)group.Results After PSM,patient distributions were closely balanced.In the LPN vs the RAPN group,there were significant different in warm ischemia time [(23.9 ± 7.3) min vs.(20.4 ± 6.7) min,P ＜ 0.05],estimated blood loss [(136.9 ± 80.2) ml vs.(136.9 ± 80.2) ml,P ＜ 0.05],incidence of complications (8.7％ vs.1.0％,P ＜0.05),and hospital stay [(11.5 ±3.8)d vs.(9.8 ± 1.80)d].There was no significant differences resulted regarding operating time [(164.5 ± 64.4) min vs.(169.0 ± 42.5) min,P ＞ 0.05],variation of estimated glomerular filtration rate from baseline [(9.97 ± 8.98)％ vs.(9.27 ± 9.19)％,P ＞ 0.05],positive surgical margin rate (1.4％ vs.0,P ＞ 0.05) and rate of recurrence or metastasis (1.4％ vs.1.4％,P ＞ 0.05) between groups.Conclusion Considering operative,functional and oncologic outcomes,both RAPN and LPN performed by an experienced surgeon were acceptable for patients with T1b renal masses.If available,robotic approach may reduce operative trauma and complications.