Objective Nude mice xenograft model with aberrant activation of the PI3K/AKT pathway was established based on PIK3CA-overexpressing non-small cell lung cancer(NSCLC)cell lines PC-9,to observe the effect of Qingkailing injection combined with gefitinib on the growth of xenograft tumor in nude mice and explore its effects on ROS levels,mTOR pathway and STAT3 pathway.Methods After the xenografttumor model of BALB/c nude mice was established successfully,the mice were randomly divided into control group,Qingkailing injection group(10 mL·kg-1),gefitinib group(2.5 mg·kg-1),and Qingkailing combined with gefitinib group,with 5 mice in each group.They were administered for 32 days and then sacrificed.The tumor weight of each group was weighed and the tumor suppression rate was calculated;the level of ROS in the tumor tissues of each group was detected by flow cytometry;the protein levels of PI3K p110α,p-AKT and p-STAT3 in the xenograft tumor tissues of each group were detected by immunohistochemistry;the protein levels of the PI3K/AKT/mTOR pathway and the STAT3 pathway in the xenografttumor tissues of each group were detected by protein western blotting.Results Compared with the control group,Qingkailing injection could slow the tumor growth,significantly reduce the tumor weight,increase the level of ROS,and could significantly down-regulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in the tumor tissues(P<0.05);compared with the gefitinib single-agent group,the tumor growth of the Qingkailing combined with gefitinib group was slow,the weight of the tumors was significantly lower,and it also could significantly elevate the ROS level and downregulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in tumor tissues(P<0.05).Conclusion Qingkailing injection combined with gefitinib inhibited the growth of gefitinib-resistant xenograft in nude mice caused by abnormal activation of the PI3K/AKT pathway.Qingkailing injection may inhibit the PI3K/AKT pathway,its downstream mTOR pathway and STAT3 signaling pathway by up-regulating ROS levels,thereby enhancing the inhibitory effect of gefitinib on the proliferation of xenograft tumors of lung cancer xenografts in nude mice.

Objective Nude mice xenograft model with aberrant activation of the PI3K/AKT pathway was established based on PIK3CA-overexpressing non-small cell lung cancer(NSCLC)cell lines PC-9,to observe the effect of Qingkailing injection combined with gefitinib on the growth of xenograft tumor in nude mice and explore its effects on ROS levels,mTOR pathway and STAT3 pathway.Methods After the xenografttumor model of BALB/c nude mice was established successfully,the mice were randomly divided into control group,Qingkailing injection group(10 mL·kg-1),gefitinib group(2.5 mg·kg-1),and Qingkailing combined with gefitinib group,with 5 mice in each group.They were administered for 32 days and then sacrificed.The tumor weight of each group was weighed and the tumor suppression rate was calculated;the level of ROS in the tumor tissues of each group was detected by flow cytometry;the protein levels of PI3K p110α,p-AKT and p-STAT3 in the xenograft tumor tissues of each group were detected by immunohistochemistry;the protein levels of the PI3K/AKT/mTOR pathway and the STAT3 pathway in the xenografttumor tissues of each group were detected by protein western blotting.Results Compared with the control group,Qingkailing injection could slow the tumor growth,significantly reduce the tumor weight,increase the level of ROS,and could significantly down-regulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in the tumor tissues(P<0.05);compared with the gefitinib single-agent group,the tumor growth of the Qingkailing combined with gefitinib group was slow,the weight of the tumors was significantly lower,and it also could significantly elevate the ROS level and downregulate the levels of PI3K p110α,AKT,mTOR,and STAT3 proteins in tumor tissues(P<0.05).Conclusion Qingkailing injection combined with gefitinib inhibited the growth of gefitinib-resistant xenograft in nude mice caused by abnormal activation of the PI3K/AKT pathway.Qingkailing injection may inhibit the PI3K/AKT pathway,its downstream mTOR pathway and STAT3 signaling pathway by up-regulating ROS levels,thereby enhancing the inhibitory effect of gefitinib on the proliferation of xenograft tumors of lung cancer xenografts in nude mice.

Objective:To investigate the status of vitamin D deficiency in middle aged and elderly patients at an orthopedic department.Methods:The data of 25-hydroxy vitamin D[25(OH)D]in patients aged over 55 years at an orthopedic department in Beijing Hospital from November 2014 to January 2020 were collected.The differences in serum 25(OH)D status were compared in different gender and age.Results:A total of 3004 subjects were included with 725 males and 2279 females, ranged from 55 to 102 years old with an average of(71.1±9.7)years.The average serum 25(OH)D level was(17.77±9.92)ng/ml, which was diagnosed as vitamin D deficiency status.Serum 25(OH)D levels were(19.66±9.77)μg/L, (18.34±9.78)μg/L, (16.19±9.51)μg/L and (14.74±10.49)μg/L, at different age groups of 55-64, 65-74, 75-84, 85 years and over, respectively, with statistically significant differences( F=29.357, P<0.05). Serum(OH)D levels of patients were severely deficient, deficient, insufficient and sufficient, with their proportion of 21.3%, 44.6%, 23.3% and 10.8%, respectively.The proportion of patients achieving from vitamin D levels severe deficiency to deficiency to insufficient to sufficient were 18.2%, 44.8%, 25.1% and 11.9% in men, and 22.2%, 44.6%, 22.7% and 10.5% in women, respectively. Conclusions:The deficiency of vitamin D is prevalent in elderly patients visiting at orthopedic department.Serum 25-hydroxy vitamin D has a decreased trend along with age increasing, showing an increased trend of vitamin D deficiency.Patients with severe vitamin D deficiency are the focus for the intervention.

Objective:To investigate the surgical indications of gallbladder polyps.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 272 patients with gallbladder polyps who underwent cholecystectomy in 11 medical centers from January 2015 to December 2019 were collected, including 585 in the First Affiliated Hospital of Xi′an Jiaotong University, 352 in No. 215 Hospital of Shaanxi Nuclear Industry, 332 in the First People′s Hospital of Xianyang, 233 in Shaanxi Provincial People′s Hospital, 152 in the Second Affiliated Hospital of Xi′an Jiaotong University, 138 in Xianyang Hospital of Yan′an University, 137 in People′s Hospital of Baoji, 125 in Hanzhong Central Hospital, 95 in Baoji Central Hospital, 72 in Ankang Central Hospital, 51 in Yulin No.2 Hospital. There were 887 males and 1 385 females, aged (48±12)years, with a range from 12 to 86 years. Observation indicators: (1) surgical treatment, pathological examination and hospitalization; (2) follow-up and complications; (3) comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps; (4) comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis; (5) analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis; (6) construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Follow-up using outpatient examination or telephone interview was conducted to detect complications and survival of patients up to April 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the rank-sum test. Ordinal data was analyzed using the rank-sum test of multi-samples. Analysis of influence factors for the incidence of neoplastic polyps was conducted after excluding missing data of CEA and CA19-9. Univariate analysis was conducted using the chi-square test or rank-sum test of multi-samples, and multivariate analysis was conducted using Logistic regression model. Based on Logistic regression model multivariate analysis, the nomogram prediction model was constructed using the R 3.6.0 version software. Results:(1) Surgical treatment, pathological examination and hospitalization: of the 2 272 patients, 2 199 cases underwent laparoscopic cholecystectomy, 43 cases underwent open cholecystectomy, 28 cases underwent radical resection for gallbladder carcinoma, and 2 cases underwent laparoscopic gallbladder preservation and polypectomy. There were 1 050 of the 2 272 patients undergoing intraoperative frozen section examination. Results of pathological examination showed that 1 953 of the 2 272 patients had non-neoplastic polyps including 1 681 cases with cholesterol polyps and 272 cases with inflammatory polyps; 319 cases had neoplastic polyps including 274 with benign polyps (93 cases with adenoma, 66 cases with adenomyoma, 81 cases with adenoma-like hyperplasia, 34 cases with adenoma combined with intraepithelial neoplasia); and 45 cases had malignant polyps including 43 cases with adenocarcinoma, 1 case with adenosquamous carcinoma and 1 case with sarcomatoid carcinoma. The duration of postoperative hospital stay of 2 272 patients was 3 days(range, 1 to 27 days). (2) Follow-up and complications: of the 2 272 patients, 1 932 were followed up for 3.5 to 63.5 months, with a median follow-up time of 31.0 months. During the follow-up, 180 patients had short-term complications and 170 patients had long-term complications. (3) Comparison of clinicopathological data between patients with non-neoplastic polyps and neoplastic polyps: cases with age ≤50 years or >50 years, cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, CA125, cases with single or multiple polyps in preoperative ultrasonography examination, cases with diameter of polyps in preoperative ultrasonography examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasono-graphy examination as nodular, papillary, globular or mulberry-like, cases undergoing or not undergoing intraoperative frozen section examination, cases with diameter of polyps in postoperative pathological examination as 1-6 mm, 7-9 mm, 10-12 mm or ≥13 mm, cases with gallbladder wall thickness in postoperative pathological examination as ≤4 mm or >4 mm of the 1 953 patients with non-neoplastic polyps were 1 118, 835, 1 027, 422, 230, 274, 2.0 mg/L(range, 0.2-8.6 mg/L), 14.5 U/mL(range, 2.6-116.4 U/mL), 10.5 U/mL(range, 1.2-58.7 U/mL), 658, 1 295, 674, 741, 413, 125, 1 389, 564, 407, 1 119, 292, 135, 832, 1 121, 698, 774, 385, 96, 1 719, 234, respectively. The above indicators of the 319 patients with neoplastic polyps were 160, 159, 204, 55, 26, 34, 2.9 mg/L(range, 0.2-28.8 mg/L), 19.7 U/mL(range, 3.5-437.1 U/mL), 15.0 U/mL(range, 1.0-945.0 U/mL), 203, 116, 49, 59, 100, 111, 154, 165, 92, 153, 49, 25, 218, 101, 53, 85, 90, 91, 263, 56, respectively. There were significant differences in the above indicators between the non-neoplastic polyps and neoplastic polyps patients ( χ2=5.599, Z=-3.668, -2.407, -3.023, -3.403, χ2=104.474, Z=-13.367, χ2=65.676, 12.622, 73.075, Z=-11.874, χ2=7.649, P<0.05). (4) Comparison of clinicopathological data among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥13 mm without cholecystolithiasis: after excluding 311 of the 2 272 patients with cholecystolithiasis, there were 706 cases with gallbladder polyp diameter of 7 to 9 mm, 459 cases with gallbladder polyp diameter of 10 to 12 mm, and 205 cases with gallbladder polyp diameter ≥13 mm, respectively. Cases with time from first discovery of polyp to operation <1 year, 1-3 years, >3 years and ≤5 years or >5 years, CEA, CA19-9, cases with single or multiple polyps in preoperative ultrasonography examination, cases with pedicled or broad based polyp wall in preoperative ultrasonography examination, cases with polyp morphology in preoperative ultrasonography examination as nodular, papillary, globular or mulberry-like, cases with echo intensity of preoperative ultrasonography examination as slightly strong, medium or weak, cases undergoing or not undergoing intraoperative frozen section examination, and cases with pathological types of polyps as non-neoplastic polyps, benign polyps or malignant polyps of the 706 patients with gallbladder polyp diameter of 7 to 9 mm were 291, 170, 107, 138, 2.2 mg/L(range, 0.5-8.6 mg/L), 21.0 U/mL(range, 2.8-116.4 U/mL), 207, 499, 620, 86, 118, 463, 75, 50, 252, 410, 44, 379, 327, 657, 49, 0, respectively. The above indicators of the 459 patients with gallbladder polyp diameter of 10 to 12 mm were 267, 85, 43, 64, 1.6 mg/L(range, 0.4-9.3 mg/L), 10.4 U/mL(range, 3.3-354.0 U/mL), 205, 254, 237, 222, 158, 223, 51, 27, 222, 213, 24, 263, 196, 373, 79, 7, respectively. The above indicators of the 205 patients with gallbladder polyp diameter ≥13 mm were 128, 38, 20, 19, 2.1 mg/L(range, 0.6-28.8 mg/L), 10.2 U/mL(range, 3.6-307.0 U/mL), 120, 85, 75, 130, 68, 97, 22, 18, 98, 95, 12, 148, 57, 113, 71, 21, respectively. There were significant differences in the above indicators among patients who had gallbladder polyp diameter of 7 to 9 mm, 10 to 12 mm, or ≥ 13 mm ( χ2=46.482, 8.093, 39.504, 66.971, 277.043, 60.945, 19.672, 22.340, 197.854, P<0.05). (5) Analysis of influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: of the 459 patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis, there were 373 cases with non-neoplastic polyps, and 86 cases with neoplastic polyps, respectively. Results of univariate analysis showed that CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were influence factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( χ2=10.342, 5.616, 20.009, Z=-4.352, χ2=6.203, P<0.05). Results of multivariate analysis showed that CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis ( odds ratio=8.423, 0.082, 0.337, 3.694, 2.318, 95% confidence interval: 1.547-45.843, 0.015-0.443, 0.198-0.575, 1.987-6.866, 1.372-3.916, P<0.05). (6) Construction and evaluation of nomogram prediction model for neoplastic polyps of patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis: CEA, CA19-9, the number of polyps in preoperative ultrasonography examination, diameter of polyps in preoperative ultrasonography examination, polyp wall in preoperative ultrasonography examination were imported into R 3.6.0 version software to establish the nomogram prediction model for neoplastic polyps. The results showed the score for CEA>5.0 mg/L, CA19-9>39.0 U/mL, cases with single polyp in preoperative ultrasonography examination, cases with polyp diameter of 10 mm in preoperative ultrasonography examination, cases with polyp diameter of 11 mm in preoperative ultrasonography examination, cases with polyp diameter of 12 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination were 25, 27, 100, 0, 26, 72, 98 in the nomogram prediction model, respectively. The C-index of nomogram prediction model was 0.768. Result of nomogram prediction model showed that the incidence of tumor polyps was 0, 6% and 10% in patients with multiple and pedicled gallbladder polyps with diameter of 10, 11, 12 mm and with CEA ≤5.0 mg/L and CA19-9 ≤39.0 U/mL, the incidence of tumor polyps was 43%, 53% and 70% in patients with single and broad base gallbladder polyps with diameter of 10, 11, 12 mm. The calibration curve showed that the probability of the nomogram prediction model predicting neoplastic polyps was nearly consistent with the actual probability. Conclusions:CEA>5.0 mg/L, CA19-9>39.0 U/mL, single polyp in preoperative ultrasonography examination, polyp diameter of 11 mm in preoperative ultrasonography examination, polyps of broad base in preoperative ultrasonography examination are independent risk factors for the incidence of neoplastic polyps in patients who had gallbladder polyp diameter of 10 to 12 mm without cholecystolithiasis. Cholecystectomy should be performed in time for patients with single and broad based gallbladder polyps with diameter of 10, 11, 12 mm.

Objective To investigate the clinical feasibility and effectiveness of 3-D printing (3DP) combined with 3-D laparoscopic nephron-sparing surgery (LNSS) for partial endogenous renal cell carcinoma.Methods A retrospective analysis was made of the clinical data of 79 patients with partial endogenous renal cell carcinoma who were admitted to our department from July 2015 to October 2018.There were 46 males and 33 females.Their average age was (50.9 ± 7.9) years old,ranged from 33 to 68 years old.Tumor stages were T1aN0M0 in 53 cases and T1bN0M0 in 26 cases.The preoperative serum creatinine ranged from 40 to 107 μmol/L,with an average of (72.4 ± 14.2) μmol/L.The preoperative GFR ranged from 19 to 54 ml/min,with an average of (40.2 ± 6.2) ml/min.Thirty-four patients underwent 2-D laparoscopic nephron-sparing surgery (2DLNSS) based on preoperative enhanced CT scans.Forty-five patients underwent 3-D printing (3DP) based on three-dimensional reconstruction of renal CT scans.Seventeen patients underwent 2-D laparoscopic nephron-sparing surgery guided by 3-D printing model(3DP-2DLNSS),and 28 patients underwent 3-D laparoscopic nephron-sparing surgery guided by 3-D printing (3DP-3DLNSS).Serum creatinine levels ranged from 42 to 122 μmol/L with an average of (86.3 ± 14.8) μmol/L,and creatinine levels ranged from 8 to 66 μmol/L with an average of (19.1 ± 14.1) μmol/L.Six months after operation,the GFR of the kidney was 9-36 ml/min with an average of (21.4 ± 6.4)ml/min,and the fluctuation range was 6-40 ml/min with an average of (19.2 ± 8.8) ml/min.There was no statistical difference in the incidence of complications and pathological types after operation.Results There was no statistical difference in general data of preoperative patients.In intraoperative and post-operative statistics,the time of exploring renal artery was shorter than that of 2DLNSS (33.7 ± 7.5) min in 3DP-2DLNSS (28.3 ± 8.2,P =0.015) min and 3DP-3DLNSS (27.8 ± 6.5,P =0.002) min.In tumor detection time,3 DP-2DLNSS was shorter than 2DLNSS group (41.2 ± 6.6 vs.46.5 ± 6.9 min,P =0.012),and 3 DP-3DLNSS was shorter than 3DP-2DLNSS (35.4 ± 7.3 vs.41.2 ± 6.6 min,P =0.009).In warm ischemia time,3DP-2DLNSS min was shorter than 2DLNSS (23.5 ±9.7 vs.33.9 ±7.5 min P ＜0.001),and 3DP-3DLNSS was shorter than 3DP-2DLNSS (18.3 ± 4.6 vs.23.5 ± 9.7,P =0.023).In surgical time,3DP-2DLNSS (115.7 ± 23.0) min and 3DP-3DLNSS (103.3 ± 22.8) min were shorter than 2DLNSS (132.4 ± 28.9) min (P =0.031,P ＜ 0.001).In intraoperative bleeding volume,3 DP-3 DLNSS was less than 2DLNSS (117.9 ± 17.9 vs.130.6 ± 16.8,P =0.009) ml.Fasting for 1 to 4 days after operation,with an average of (1.7 ± 0.8) days.The indwelling catheterization ranged from 1 to 8 days after operation,with an average of (3.9 ± 1.3) days.Negative pressure drainage was removed 2-9 days after operation,with an average of (4.9 ± 1.4) days.And the hospitalization 5-11 days after operation,with an average of (7.3 ± 1.5) days.Conclusions Preoperative 3D printing combined with intraoperative 3D laparoscopic nephron sparing surgery for partial endogenous renal tumors is safe and effective,which is superior to the previous CT scan alone and intraoperative 2D laparoscopic treatment.

Objective To investigate the early diagnostic ability of conventional imaging methods in micro-hepatocellular carcinoma(M HCC) in order to improve the imaging diagnostic procedure for M HCC.Methods The data of 40 cases of M HCC(52 lesions)and 21 cases of regenerative nodules(35 lesions)confirmed by clinical results were collected continuously.All the patients were examined with ultrasonography (US),plain CT combined with multi-phase enhancement scans,and plain MRI combined with diffusion weighted imaging(DWI).To compare the diagnostic efficacy of three different imaging methods,the imaging data were analyzed retrospectively by χ2test and receiver operating characteristic curve(ROC).Results There was a significant difference in the M HCC detection rate between US and CT,and between US and MRI,respectively(P<0.05).There was no significant difference in the MHCC detection rate between CT and MRI(P>0.05).The sensitivity of US,CT and MRI in the detection of MHCC was 61.5%,80.8% and 92.3%,specificity was 88.6%,91.4% and 97.1%,positive predictive value was 88.9%,93.3% and 98.0%,and area under the ROC curve was 0.751, 0.861 and 0.947,respectively.Plain MRI combined with DWI had the highest diagnostic efficacy,among the three imaging methods. Conclusion US can be used as a primary screening method for M HCC in high risk population,and plain CT combined with multi-phase enhancement scans can be the first choice for early diagnosis of MHCC.For highly suspected the cases with positive AFP but negative findings on US and CT,plain MRI combined with DWI are recommended to rule out the possibility.

Objective To explore the therapeutic efficacy of Stone Cone under ureteroscopic lithotripsy and its clinical value in the treatment of ureteral stone.Methods A retrospective analysis of the clinical data of 30 cases of ureteral stone was made in the patients treated with ureteroscopic lithotripsy combined with Stone Cone,and holmium laser or EMS from June 2014 to June 2015 in our hospital.Results The mean surgical time for all the patients that underwent surgery was (20 ± 11) min.Ureteral stone was successfully removed in 29 cases,with the stone removal rate of 96.7％.There was 1 case of stone migration to renal pelvis following ureteroscopic lithotripsy.No cases of ureteral laceration or perforation or other complications were found in all the patients following treatment.Conclusions In ureteroscopic lithotripsy,Stone Cone could obviously decrease the rate of stone migration of ureteral stone and increase stone-free rate.

Objective To explore the therapeutic efficacy of Stone Cone under ureteroscopic lithotripsy and its clinical value in the treatment of ureteral stone.Methods A retrospective analysis of the clinical data of 30 cases of ureteral stone was made in the patients treated with ureteroscopic lithotripsy combined with Stone Cone,and holmium laser or EMS from June 2014 to June 2015 in our hospital.Results The mean surgical time for all the patients that underwent surgery was (20 ± 11) min.Ureteral stone was successfully removed in 29 cases,with the stone removal rate of 96.7％.There was 1 case of stone migration to renal pelvis following ureteroscopic lithotripsy.No cases of ureteral laceration or perforation or other complications were found in all the patients following treatment.Conclusions In ureteroscopic lithotripsy,Stone Cone could obviously decrease the rate of stone migration of ureteral stone and increase stone-free rate.

Objective To investigate the effecacy of open reduction internal fixation in cases with rib fracture. Methods The pain scores,respiratory related clinical indicators change of 81 rib fractuure cases underwent open reduction internal fixation surgery were ob-served. A comparison was made between the surgical group and the non-surgical group of 37 cases on pain scores trend and hospital stay. Re-sults All operations were successfully completed and postoperative recovery was good. Postoperative pain scores and respiratory rate was sig-nificantly lower(P=0. 000),Oxygen saturation was significantly higher(P=0. 002),the proportion of expectoration difficult,dyspnea and ac-tivities inconvenience were significantly lower(P<0. 05). Pain scores of surgical group significantly decreased after surgery peak hours that was the fourth day hospitalized,but the overall decline of pain scores in non-surgical group was slow. The hospital stay between the surgical group and the non-surgical group was not significantly different(P=0. 084). Conclusion The efficacy of open reduction internal fixation is significant to rib fracture with exact surgery indications,and appropriate timing of surgery is the fourth day after admission.