Objective To investigate the effect of human interferon-beta (IFN-β) gene engineered human mesenchymal stem cells (hMSC) in the treatment of human prostate cancer xenograft in nude mice.Methods An adenovirus vector containing human IFN-β gene was constructed and transfected into hMSC in vitro.IFN-β-expressing mesenchymal stem cells (IFN-β-hMSC) were labeled with 4,6-diamidino-2-phenylindole (DAPI).The human prostate cancer cell line PC-3 were injected into the flank or axillary of severe combined immunodeficiency (SCID) mice subcutaneously to establish human prostate cancer xenograft models.IFN-β-hMSC were injected into the tail vein of mice bearing human prostate cancer xenografts.The tumors,livers,lungs,spleens and kidneys were harvested.Frozen sections and paraffin sections were used to observe the distribution of IFN-β-hMSC in vivo by fluorescence microscope.Mice were divided into seven groups of six animals randomly,IFN-β-hMSC (2 × 106,2 × 105 ) as treatment group,Ad-hMSC,unmodified hMSC,Ad-IFN-β,Recombinant IFN-β,and NS as control group.The weight of the tumor and the survival time of mice were observed to evaluate the experimental efficacies of IFN-β-hMSC in the treatment of prostate cancer. Results IFN-β-hMSC with blue nuclei were distributed extensively in the tumors,but no blue nucleus was seen in the livers,lungs,spleens and kidneys.After treating,the weights of the tumour masses from mice were (1.35 ±0.28) g,(1.43±0.41) g,(3.49 ±0.25)g,(3.58±0.30)g,(3.30 ±0.24) g,(3.32 ±0.25) g,(3.32 ±0.47) g in the IFN-β-hMSC (2 ×106),IFN-β-hMSC (2 ×105),Ad-hMSC,unmodified hMSC,Ad-IFN-β,Recombinant IFN-β,and NS group,the median survival time from mice were 91 d,87 d,57 d,59 d,62 d,61 d,61 d in the IFN-β-hMSC (2 × 106),IFN-β-hMSC (2 × 105),Ad-hMSC,unmodified hMSCs,Ad-IFN-β,Recombinant IFN-β,and NS group,respectively.Injection of IFN-β-MSC can significantly reduce tumor weight and increase animal survival compared with controls ( P ＜ 0.05 ). Conclusion IFN-β-hMSC can migrate to prostate cancer microenviroment in vivo,and injection of IFN-β-MSC can significantly reduce tumor weight and increase animal survival.

Objective The aim of this study was to investigate the co-operative role of HGF and IL-1ra in metastatic processes by interactions between colon cancer cells and stromal cells in their microenvironment.Methods Expression of IL-1α,HGF and c-Met mRNA and proteins were determined by RT-PCR and Western blot.The effect of HGF on metastatic potential was evaluated by proliferation,invasion,and angiogenesis assays using an in vitro system consisting of co-cultured tumor cells and stromal cells.Results IL-1α expression was closely correlated with metastatic potential,and cancer cell-derived IL-1α significantly promoted HGF expression by fibroblasts (P ＜ 0.01).HGF enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs),and angiogenesis (P ＜ 0.01).The high liver-metastatic colon cancer cell line (HT-29),which secretes IL-1 α,significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2),which does not produce IL-1 α (P ＜ 0.01).IL-1 ra significantly inhibit migration,proliferation and angiogenesis (P ＜ 0.01).Conclusions Autocrine IL-1α and paracrine HGF enhance the metastatic potential of colon cancer cells;IL-1ra inhibit the metastatic potential of colon cancer cells by blocking IL-1α and HGF signaling pathways.

Objective:To analyze the law of distant metastasis in patients with small lung adenocarcinoma with different CT findings, and to explore the feasibility of different preoperative examination methods for small lung adenocarcinoma with different imaging characteristics.Methods:Clinicopathological data of cT1a-cN0 lung adenocarcinoma patients admitted to the respiratory center of China-Japan Hospital from January 2017 to December 2018 were retrospectively collected. A total number of 785 patients were included, including 289 males and 496 females. SPSS 22.0 was used for statistical analysis.Results:A total number of 785 patients were included in this study, including 287 pure ground-glass nodule (GGN) patients, 111 GGN predominant patients, 221 solid predominant patients and 166 solid nodule patients. Among the included patients, 8 had distant metastasis, including 6 with bone metastasis, 1 with brain metastasis and 1 with brain and adrenal metastasis. No distant metastasis was observed in the patients with pure GGN and GGN predominant nodule, while 1 solid predominant patients had distant metastasis, and 7 patients with solid nodules had distant metastasis. The probability of distant metastasis was 0.5% for the solid predominant patients and 4.2% for the solid nodule patients. Univariate analysis results showed that CEA level ( P=0.030), the largest diameter of the lung window tumor ( P=0.003), the largest diameter of the solid component of the lung window tumor ( P<0.001), the largest area of the lung window tumor ( P=0.002), mediastinal window tumor maximum area ( P<0.001), CTR ( P<0.001), TDR ( P<0.001), and pleural indentation sign ( P=0.037) were risk factors for distant metastases. Multivariate analysis showed that CEA ( OR=1.019, 95% CI: 1.002-1.037, P=0.028) and TDR ( OR=0.000, 95% CI: 0.000-0.310, P=0.001) were independent risk factors of distant metastasis. Conclusion:For patients with pure GGN and GGN predominant nodule, preoperative examination could not be required, but for pure solid nodules, it is necessary to perform relevant preoperative examination including skull MRI before surgery to exclude distant metastasis.

In recent years, with the in-depth study of PD-1 and PD-L1 and the development of immunotherapy, the first problem is how to screen the beneficiaries. Recent clinical studies have shown that the expression level of PD-L1 in circulating tumor cells (CTC) can be used as a potential biomarker to play a guiding role in immunotherapy of malignant tumors. This article reviews the latest clinical research progress on the expression of PD-L1 in circulating tumor cells in various solid tumors.

Objective:Based on experience of robotic gastrointestinal surgery at the Department of General Surgery, Clinical Medicine Center of Gansu Provincial Hospital, this study explored the principles and methods of trocar layout for robotic "3+2" mode gastrointestinal surgery, suitable for beginners.Methods:From Apr 2017 to Oct 2022, the robotic gastrointestinal surgery team of Gansu Provincial Hospital completed 998 cases of robotic "3+2" mode gastrointestinal surgery, including 600 cases of gastric cancer, 100 cases of rectal cancer, 98 cases of descending colon and sigmoid colon cancer, 20 cases of transverse colon cancer, and 180 cases of right colon cancer. Through the continuous optimization and improvement of the problems encountered during the operation, combined with the operator's experience, and taking into account various aspects, we developed the robotic "3+2" mode trocar layout for gastrointestinal surgery.Results:Four principles of trocar layout were developed, namely, the principle of lens placement around the navel, the principle of symmetry in the main operation, the principle of 8-10cm distance between trocar holes, and the principle of symmetry in the auxiliary hole lens. Three trocar layout methods and principles applicable to robotic gastric surgery, and four applicable to robotic colorectal surgery were developed.Conclusion:The trocar layout method of robotic "3+2" mode gastrointestinal surgery is established based on a large number of robotic gastrointestinal surgery experiences. This method is simple and easy to learn, with strong repeatability and operability.

Objective:To investigate the efficacy and safety of modified early unclamping technique in robot-assisted laparoscopic partial nephrectomy (RAPN) for patients with renal tumors.Methods:A total of 32 renal tumor patients undergoing RAPN with modified early unclamping technique between January 2019 and August 2020 were retrospectively collected, including 18 males and 14 females. The average age was (48.5±11.2) years old, average BMI was (23.8±3.7) kg/m 2, average tumor size was (4.2±1.4)cm with 18 left tumors and 14 right tumors, average R. E.N.A.L. score was 7.6±0.4, and average preoperative eGFR was (84.0±18.6)ml/(min·1.73 m 2). The control group included 66 renal tumor patients undergoing RAPN with standard unclamping technique during the same period by the same surgeon, including 42 males and 24 females. The average age was (50.2±13.8) years old, average BMI was (24.0±4.5)kg/m 2, average tumor size was (4.1±1.6)cm with 35 left tumors and 31 right tumors, average R. E.N.A.L. score was 7.5±0.5, and average preoperative eGFR was (82.8±20.2) ml/(min·1.73 m 2). There was no significant difference in above variables between two groups. Modified early unclamping technique used barbed wire to continually suture 2-3 needles in a short time to close the large space at the outer after the inner suture, and then loosen the blocking clip to restore renal blood supply. The operative time, warm ischemia time, blood loss, postoperative tube removal time, postoperative hospital stay and 3 months postoperative renal function of two groups were compared. Results:All of the 98 RAPN were performed successfully and no patient was converted to radical nephrectomy or open surgery. There was no significant difference in operation time [(120.9±22.8)vs.(111.6±25.0)min, P=0.079], postoperative tube removal time [(4.0±0.6)day vs.(3.8±0.8) day, P=0.214] and postoperative hospital stay [(5.1±0.7)day vs.(5.2±0.5) day, P=0.419] between the two groups. Compared with the standard unclamping group, the modified early unclamping group had obvious less warm ischemia time [(13.5±3.6)min vs.(21.2±4.4) min, P<0.001]. There was no difference in intraoperative estimated blood loss between two groups (110 ml vs. 100 ml, P=0.480). No blood transfusion, urine leakage, postoperative hemorrhage occurred in either group. The 3 months postoperative renal function decline of modified early unclamping group was slightly less than standard unclamping group [(10.5±7.6)ml/(min·1.73m 2)vs.(13.2±6.4) ml/(min·1.73m 2)], but did not reach statistical significance ( P=0.069). The median follow-up period was 12.4 months(4-24 months) without any recurrence or metastasis. Conclusions:The modified early unclamping technique in RAPN for patients with renal tumors is safe and feasible. Compared with the standard unclamping technique, the modified early unclamping technique could shorten the warm ischemia time without increasing blood loss and complications, and might protect the postoperative renal function, which has high value in clinical practice.

Objective:To compare the efficacy and safety of robot-assisted laparoscopic and laparoscopic partial nephrectomy (RAPN and LPN) for patients with completely endophytic renal tumor.Methods:A total of 73 patients with completely endophytic renal tumor receiving RAPN (n=29) or LPN (n=44) in our center between January 2015 and June 2021 were retrospectively collected. There were 21 males and 8 females in RAPN group. The average age was 48.6±13.7 years old, average tumor size was 2.9±0.9 cm with 13 left tumors and 16 right tumors, average R. E.N.A.L. score was 9.2±1.0, and average preoperative eGFR was 82.6±10.7 ml/(min·1.73 m 2). There were 27 males and 17 females in LPN group. The average age was 50.1±12.3 years old, average tumor size was 2.9±0.9 cm with 24 left tumors and 20 right tumors, average R. E.N.A.L. score was 9.1±1.3, and average preoperative eGFR was 81.7±9.6 ml/(min·1.73 m 2). There was no significant difference in above variables between two groups. The operative time, warm ischemia time, blood loss, postoperative complication, postoperative hospital stay and postoperative 3 months renal function of two groups were compared. Results:All 73 patients successfully underwent RAPN or LPN and no patient converted to radical nephrectomy or open surgery. There was no significant difference in operation time [140(80, 160) min vs. 150 (90, 180) min, P=0.264], intraoperative estimated blood loss[150 (100, 200)vs. 180 (120, 200) ml, P=0.576]and postoperative hospital stay (7.0±2.7 vs. 7.4±2.1 days, P=0.480) between two groups. Compared with LPN group, RAPN group had obvious less warm ischemia time (23.1±3.3 vs. 27.6±4.7 min, P<0.001). No obvious complication occurred in RAPN group and one case with postoperative hemorrhage occurred in LPN group. No positive margin occurred in either group. There was no difference in renal function 3 months after operation between the two groups [73.2±6.3 vs.70.5±7.6ml/(min·1.73 m 2), P=0.117]. The median follow-up period was 22.6 months with no tumor recurrence or metastasis. Conclusions:For experienced surgeons, both RAPN and LPN are safe and feasible for patients with completely endophytic renal tumor. Compared with LPN, RAPN has advantages of perioperative curative effect, which could reduce the operating difficulty and shorten the warm ischemia time.

Objective    To investigate the predictive value of preoperative radiological features on spread through air spaces (STAS) in stage cⅠA lung adenocarcinoma with predominant ground-glass opacity, and to provide a basis for the selection of surgical methods for these patients. Methods    The clinical data of 768 patients with stage cⅠA lung adenocarcinoma undergoing operation in our hospital from 2017 to 2018 were reviewed, and 333 early stage lung adenocarcinoma patients with predominant ground-glass opacity were selected. There were 92 males and 241 females, with an average age of 57.0±10.0 years. Statistical analysis was performed using SPSS 22.0. Results    STAS-positive patients were mostly invasive adenocarcinoma (P=0.037), and had more micropapillary component (P<0.001) and more  epidermal growth factor receptor (EGFR) gene mutations (P=0.020). There were no statistically significant differences between the STAS-positive and STAS-negative patients in other clinicopathological features. Univariate analysis showed that the maximum diameter of tumor in lung window (P=0.029), roundness (P=0.035), maximum diameter of solid tumor component in lung window (P<0.001), consolidation/tumor ratio (CTR, P<0.001), maximum area of the tumor in mediastinum window (P=0.001), tumor disappearance ratio (TDR, P<0.001), average CT value (P=0.001) and lobulation sign (P=0.038) were risk factors for STAS positive. Multivariate logistic regression analysis showed that the CTR was an independent predictor of STAS (OR=1.05, 95%CI 1.02 to 1.07, P<0.001), and the area under the receiver operating characteristic (ROC) curve was 0.71 (95%CI 0.58 to 0.85, P=0.002). When the cutoff value was 19%, the sensitivity of predicting STAS was 66.7%, and the specificity was 75.2%. Conclusion    CTR is a good radiological feature to predict the occurrence of STAS in early lung adenocarcinoma with predominant ground-glass opacity. For the stage cⅠA lung adenocarcinoma with predominant ground-glass opacity and CTR ≥19%, the possibility of STAS positive is greater, and sublobar resection needs to be carefully considered.

Objective: To explore the safety, feasibility and advantages of Da Vinci robot "3+ 2" mode in radical gastrectomy. Methods: Clinical data of 30 patients received radical gastrectomy at our department under the "3+ 2" mode of Da Vinci robot from Jan. 2018 to Oct. 2018 were retrospectively analyzed. 30 patients who received classical robot mode in the same period were randomly selected as control group. Results: Compared with the control group, the observation group had a shorter operative time (174±16)min vs.(197±19)min, t=-3.275, P<0.01) , a lower operation costs[(22 794±3 660)yuan vs.(29 307±3 220)yuan, t=-3.316, P<0.01; and inhospital costs (70 910±6 399)yuan vs.(78 180±6 636)yuan), t=-7.316, P<0.01]. Conclusion The "3+ 2" mode of Da Vinci robot in radical gastrectomy is beneficial to enhance the exposure of the surgical field, improve the cooperation of assistants, reduce the costs of surgery, shorten the operative time and the learning curves. In addition, it has similar clinical efficacy to radical gastrectomy under the classical robot mode.

Objective    To investigate the mediastinal lymph node metastasis of cT1a-cN0M0 lung adenocarcinoma, so as to provide a theoretical basis for intraoperative lymph node dissection in patients with early stage lung adenocarcinoma. Methods    Clinicopathological features of lung adenocarcinoma patients who received operation in our hospital from 2017 to 2018 were collected. A total of 667 patients including 241 male and 426 female patients at age of 59 (16, 87) years were included. There were 234 patients with pure ground glass nodules, 98 patients with ground glass-predominant tumor, 199 patients with consolidation-predominant tumor and 136 patinets with solid tumor in the study. Postoperative N1 lymph node metastasis occurred in 30 patients and N2 lymph node metastasis occurred in 52 patients. Results    The result of univariate analysis showed that male (P=0.014), higher carcino-embryonic antigen levels (P<0.001), larger nodal diameter (P<0.001), larger consolidation tumor ratio (P<0.001), smaller tumor disappearance ratio (P<0.001), solid nodules (P<0.001), cavitary sign (P=0.005), lobulation sign (P=0.002), spicule sign (P=0.003), pleural indentation sign (P=0.001), bronchus sign (P=0.025) were risk factors for mediastinal lymph node metastasis. In terms of pathology, the N2 positive group had larger size of pathological tissue (P<0.001), more N1 lymph node metastasis (P<0.001), higher pathology T stage (P<0.001), more spread through air space (P=0.001), more pleural invasion (P<0.001), and more lymphovascular invasion (P<0.001). Multivariate analysis showed that lymphovascular invasion (OR=6.9, 95%CI 2.3-20.7, P=0.001), larger consolidation tumor ratio (OR=109.6, 95%CI 3.8-3 124.3, P=0.006), cavitary sign (OR=3.1, 95%CI 1.1-8.3, P=0.028) and N1 lymph node metastasis (OR=15.7, 95%CI 6.7-36.4, P<0.001) were independent risk factors for mediastinal lymph node metastasis. Conclusion    For lung adenocarcinoma, mediastinal lymph node metastasis will not occur in ground glass nodule and ground glass-predominant tumor patients. The probability of mediastinal lymph node metastasis increases with the increase of solid components and presence of cavitary sign. Therefore, different types of lymph node resection can be considered for patients with different imaging findings.