OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.

Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.

Objective:To investigate the clinical features of patients with local recurrence and secondary operation after partial nephrectomy for renal cancer.Methods:The clinical data of 14 patients who underwent secondary operation for local recurrence of renal cancer after partial nephrectomy in the First Affiliated Hospital and the Second Affiliated Hospital of Naval Medical University from January 2000 to January 2022 were retrospectively analyzed. There were 12 males and 2 females. Nine patients had a body mass index ≥24 kg/m 2. At first diagnosis of renal cancer, nine patients’ R. E.N.A.L. score of renal mass were at least 7. Partial nephrectomy was performed in the first operation of each patient, including 4 cases of open surgery, 6 cases of laparoscopic surgery, and 4 cases of robot-assisted laparoscopic surgery. The pathological stage of nine patients was pT 1aN 0M 0 and that of five patients was pT 1bN 0M 0. Twelve cases were clear cell carcinoma, 1 case was sarcomatoid carcinoma and 1 case was chromophobe cell carcinoma. The mean time from the first operation to local recurrence was (29.3±16.8) months. All recurrence lesions were found by abdominal CT or MRI. Thirteen patients had no clinical symptom at the time of tumor recurrence. The location of recurrence was clear. No sign of invasion of peripheral organs and tissues was observed. There was no other suspicious lesion. The tumor was considered to be completely resectable in all patients. All 14 cases underwent secondary operation. Ten patients underwent radical nephrectomy [tumor size was (2.8±0.9) cm]. Partial nephrectomy was performed in 4 cases [tumor size was (1.8±0.9) cm]after full evaluation by surgeons, including 2 cases of anatomic solitary kidney, and 2 cases of recurrent tumor less than 2 cm with clear tumor margin. Results:Eleven of the 14 cases underwent minimally invasive surgery, and no cases were converted to open surgery. The other 3 cases underwent open surgery. Seven patients had severe adhesions in the operation area. The blood loss in the partial nephrectomy group and the radical nephrectomy group was (100.0±70.7) ml and (143.0±81.2) ml, respectively. According to the Clavien-Dindo classification of surgical complications, Grade Ⅰ and Grade Ⅱ complication occurred in 1 patient respectively, and no patient had Grade Ⅲ or above complication. No tumor cell was found at the surgical margin. The pathological type and nuclear grade were the same as those in the first operation. There were 10 cases of pT 1aN 0M 0 stage, 3 cases of pT 3aN 0M 0 stage and 1 case of pT 3aN 1M 0stage. The follow-up time of 13 patients with complete follow-up data was (21.4±14.9) months after local recurrence resection. The tumor recurred in 3 patients and metastasized in 2 patients. The disease-free survival time of the above 5 patients was (13.2±8.8) months. Of the 4 patients who underwent partial nephrectomy, 3 had recurrence or metastasis. Among the 9 patients who underwent radical nephrectomy, 2 had postoperative recurrence or metastasis, and 7 patients survived without tumor until the last follow-up. Conclusions:For patients with local recurrence after partial nephrectomy who are in good condition and the recurrent lesions can be completely resected, the second operation is safe, feasible and effective. Patients with secondary radical nephrectomy have better prognosis. If the patient has a solitary kidney, the recurrent tumor is small and the margin is clear, partial nephrectomy can also be selected for the second operation. But the postoperative follow-up should be emphasized, and the adjuvant drug therapy should be given if necessary.

Objective:To investigate the safety and prognosis of partial nephrectomy (PN) in the treatment of highly malignant non-clear renal cell carcinoma (nccRCC).Methods:Clinical data of 47 patients with cT 1N 0M 0 high malignant nccRCC treated in Changhai Hospital from March 2016 to March 2022 were retrospectively analyzed. All patients received PN. There were 34(72.3%) males and 13(27.7%) females. The mean age was (53.5±15.0) years, and average BMI, was(23.7±3.4)kg/m 2.The maximum tumor diameter was (29.8±12.6) mm, and R. E.N.A.L. score was 7(5-9), with 37(78.7%) cases of T 1a and 10(21.3%) cases of T 1b. The mean estimated glomerular filtration rate (eGFR) before surgery was (96.3±25.5) ml/ (min·1.73m 2). All patients underwent PN, including 1 patient (2.1%) undergoing open surgery, 29 patients (61.7%) undergoing laparoscopic surgery, and 17 patients (36.2%) undergoing robotic surgery. There were a total of 22(46.8%) cases of papillary cell carcinoma(pRCC)type Ⅱ, 4(8.5%) cases of collecting duct carcinoma (cdRCC), 9(19.1%) cases of MiT family translocated renal cell carcinoma (tRCC), 5(10.6%) cases of mucoid tubular and spindle cell carcinoma (mtSCC)and 7(14.9%) cases of unclassified renal cell carcinoma (uRCC). The surgical conversion rate, positive margin rate, operative time, intraoperative blood loss, complications, and postoperative hospital stay were analyzed. Preoperative and postoperative eGFR were analyzed, and overall survival (OS) and cancer specific survival (CSS) were calculated. Results:All the operations were successfully completed. No radical operation or open operation was performed, with operation time of(100±60) min and intraoperative blood loss of(100±59) ml. There were no intraoperative complication and 1 case (2.1%) suffered from postoperative complication. Postoperative hospital stay were 5 (4-6) days. The mean eGFR after surgery was (86.5±27.1) ml/(min·1.73m 2), and the difference was statistically significant ( P=0.041). In this study, the mean follow-up time was (45.7±20.9)months, and no adjuvant therapy was used after surgery. During the follow-up period, 2 patients died, who all of them were kidney cancer-related death, and both OS and CSS were 95.7% (45/47). Conclusions:PN is safe, feasible and has a good prognosis in the treatment of high malignant T 1 nccRCC. For tumors with clear imaging boundaries and complete envelope, complete tumor resection is more likely, postoperative follow-up should be strict, and no remedial radical or systemic treatment was required.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective:To investigate the feasibility and safety of a novel single-port robotic surgical system with flexible 3D endoscope and deformable surgical instruments in zero ischemic partial nephrectomy.Methods:From May 2021 to October 2021, a prospective study on patients with renal tumor who plan to receive zero ischemic partial nephrectomy was conducted. Inclusion criteria included over 18 years old, body index between 18.5 to 30.0 kg/m2, American Society of Anesthesiologists Score ranged from 1 to 3 points, cooperation with the follow-up and related examinations, voluntary in participating the clinical trial and signing the informed consent. Exclusion criteria included patients with other co-existed malignant tumors or a medical history of other malignant tumors, the patients who have received the same urological surgery in the past, the patients who underwent or plan to undergo other major operations 3 months before or after the surgery, the patients with active pulmonary tuberculosis or severe systemic diseases, the patients to be considered not suitable to enroll in by the researchers. A novel single-port robotic surgical system was used to perform the surgery. The system consiststed of a remote control console, a surgical equipment cart, a four-arm operation cart and deformable robotic instruments which were reusable. The two-section deformable robotic instruments were able to bend in four directions and carried different surgical instruments such as unipolar scissors, bipolar grasping forceps and needle holders. The deformable robotic instruments entered the body through a special trocar with single hole and multi-channel, and then unfolded in a triangle. By bending instruments, surgeons could perform single-port robotic surgery without the trouble of "chopstick effect" or "reverse direction" . Four cases of single-port partial nephrectomy were carried out. Under general anesthesia, the patients were taken the lateral recumbent position, with elevated waist and lowered head and feet. A 3-4 cm incision was taken layer by layer along the lateral edge of the rectus abdominis at the umbilicus level. A special 2.5 cm robotic trocar was set into the cavity, and a high-definition 3D laparoscopic lens and a snake shaped mechanical arm were then put into the abdominal cavity through the trocar. All operations were performed by transperitoneal approach with an auxiliary port through the same or a different skin incision if necessary. Tumor resection and renal reconstruction were performed by the way of zero ischemia. The perioperative parameters such as tumor size, operation time, intraoperative bleeding and postoperative complications were analyzed.Results:Four patients were involved, including 2 males and 2 females, with 2 of them having a history of hypertension. The ECOG scores were all 0, and KPS score was 100 in 3 cases and 90 in 1 case. Preoperative mean serum creatinine was (76.8±18.8)μmol/L (range 70-104 μmol/L). The tumors were located on the left in 3 cases and on the right in 1 case. The diameter of the tumor ranged from 1.1 to 2.8 cm, with the TNM classification of T 1a. The R. E.N.A.L. scores were 4a, 7p, 6p and 4P respectively. The first operation was performed by pure single-port surgery, and the other 3 cases were performed with the help of an auxiliary port to ensure the safety .The operation time ranged from 155 min to 210 min, and the intraoperative bleeding ranged from 20 ml to 170 ml. Postoperative pathology showed 2 cases of renal clear cell carcinoma with negative margin and 2 cases of angiomyolipoma. No severe complications, such as bleeding or urinary leakage, were observed during the perioperative period, and the change of serum creatinine was insignificant before discharge and before operation( P=0.24). Conclusions:A robotic single-port partial nephrectomy can be successfully carried out by using this novel single-port robotic surgical system with flexible 3D endoscope and deformable surgical instruments.

Objective:To analyze the correlation between R. E.N.A.L., PADUA, C-index, DAP scoring system and the efficacy and safety of nephron-sparing surgery (NSS) for T 1b renal tumors, and to construct a nomogram model to predict the efficacy and safety of surgery by combining multiple parameters. Methods:The data of 80 patients with stage T 1b renal tumor who received NSS from March 2020 to July 2021 in Changhai Hospital of Naval Military Medical University were retrospectively analyzed. There were 59 males and 21 females, aged (56.9±10.2) years old. The tumor diameter was (4.7±0.9) cm, with 40 cases on the left and 40 on the right sides. Tumors were located in the upper/lower pole in 46 cases and in the middle in 34 cases. The tumors were located in 59 cases laterally, 21 cases medially, and 74 cases were bulging, 16 cases endogenous. There were 53 round tumors, 18 lobular tumors, and 9 irregular tumors. One case underwent open surgery, 43 cases underwent laparoscopic surgery, and 36 cases underwent robotic surgery.42 cases underwent transperitoneal approach, and 38 cases underwent retroperitoneal approach. The composite outcome (MIC) achieved by all three indicators, including negative surgical margins, warm ischemia time <20 min, and no serious complications, was used as the main indicator to evaluate the efficacy and safety of surgery. Secondary indicators were operation time, intraoperative blood loss, postoperative hospital stay, postoperative creatinine changes and hemoglobin changes. Relevant risk factors were analyzed by logistic regression, and a nomogram model for predicting surgical efficacy and safety was constructed. Receiver operating characteristic(ROC) curves were used to compare the predictive power of the nomogram model with other scoring systems. Results:Univariate logistic regression analysis showed that PADUA and R. E.N.A.L. scores were risk factors for MIC achievement( OR=1.419, P=0.038; OR=1.358, P=0.038). However, C-index and DAP were not risk factors for MIC achievement( P>0.05). The results of correlation analysis showed that R. E.N.A.L. score was significantly correlated with postoperative hemoglobin decrease(R 2=0.197). PADUA score was significantly correlated with postoperative hospital stay(R 2=0.186). C-index was significantly correlated with postoperative creatinine increase(R 2=-0.221). DAP was significantly associated with operation time (R 2=0.192). The results of univariate logistic regression analysis showed that body mass index ( OR=1.257, P=0.025), tumor morphology ( OR=18.741, P=0.005), longitudinal location of tumor ( OR=1.992, P=0.038), the relationship between tumor and collection system ( OR=4.886, P=0.002) were risk factors for MIC attainment. A nomogram prediction model was constructed by combining these indicators with the Mayo adhesive probability (MAP) index. The ROC curve showed that the area under the curve (AUC) of the nomogram model and R. E.N.A.L. score, PADUA score, C-index, and DAP were 0.834, 0.645, 0.643, 0.526, and 0.593, respectively. The nomogram model had the highest predictive power for T 1b renal tumors achieving MIC. Conclusions:In the renal tumor scoring system, PADUA and R. E.N.A.L. scores can predict whether the MIC of T 1b renal tumor NSS is achieved or not. The nomogram model composed of patient body mass index, tumor shape, longitudinal position of tumor, relationship between tumor and collecting system and MAP can better predict whether the MIC of T 1b renal tumor NSS is achieved or not.

Objective:To initially investigate whether simultaneous radiochemotherapy with hyperthermia can prolong the survival of glioblastoma (GBM) patients.Methods:Clinical data of 61 GBM patients undergoing surgery in our hospital from September 2016 to June 2019 were retrospectively analyzed. According to different treatment methods, all patients were divided into the control group ( n=34) and observation group ( n=27). In the control group, three-dimensional radiotherapy with a dose of 60 Gy combined with temoazolamine chemotherapy was delivered. In the observation group, simultaneous radiochemotherapy with 15-20 cycles of hyperthermia at 40-41℃ was supplemented. The survival time was calculated by Kaplan-Meier method, and the survival time was compared with log-rank test between two groups. Results:The median progression-free survival in the observation group was significantly longer than that in the control group (14.33 months vs.9.94 months, P<0.05). The median overall survival in the observation group was also remarkably higher than that in the control group (18 months vs. 14 months, P<0.05). Conclusions:Simultaneous radiochemotherapy with hyperthermia is innovatively applied to treat GBM after surgical resection. Preliminary findings demonstrate that compared with chemoradiotherapy, simultaneous radiochemotherapy with hyperthermia can prolong the survival time of GBM patients.