Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective:To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi-square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval ( CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them ( χ2=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non-smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them ( χ2=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC ( odds ratio=4.18, 7.62, 4.23, 4.08, 95% CI as 1.60?11.60, 2.00?31.70, 1.71?10.90, 1.60?10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring-like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95% CI as 0.80?0.92), 79.7% (95% CI as 69.2%?87.3%), 80.0% (95% CI as 69.6%?87.5%) and 79.9% (95% CI as 72.7%?85.5%), respectively. Results of Hosmer-Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status ( P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26?35)months. The time to tumor recurrence and 2-year cumulative tumor recurrence rate of 149 patients were 29(range, 24?33)months and 43.0%, respectively. The 2-year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between ( χ2=3.90, P<0.05). The 2-year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between ( χ2=4.20, P<0.05). Conclusions:Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.

Objective:To investigate the value of machine learning-based computed tomography (CT) images radiomics analysis in preoperative evaluation of surgical portal vein-superior mesenteric vein (PV-SMV) invasion in patients with pancreatic ductal adenocarcinoma (PDAC).Methods:The retrospective study was conducted with 156 consecutive PDAC patients who were underwent surgery at the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University between January 2010 and July 2021. There were 95 males and 61 females, with the age of (65.7±8.2) years. Patients were randomly split into training set and validation set by a ratio of 3∶2. Minimum redundancy maximum relevance was used to select radiomic features, which were extracted from contrast-enhanced CT images. Five machine learning classifiers were developed, and those models' area under the curve (AUC) values were compared with the conventional radiologic-feature-based evaluation.Results:Ninety-four and 52 patients were included into the training set and validation set, respectively. Their PV-SMV invasion rates were confirmed by intraoperative exploration with 31.9%(30/94) and 40.3%(25/61), respectively. Five models: LASSO regression, random forest, support vector machine, k-nearest neighbor and Naive Bayesian, were established based on ten features from CT images radiomics, and LASSO regression model achieved the highest AUC value compared with the other four models (all P<0.05). Compared with the conventional radiologic evaluation, the LASSO regression model had higher AUC (0.920 vs. 0.752) and sensitivity (92.0% vs. 86.5%)(both P<0.05). Conclusion:Machine learning-based CT images radiomics analysis can be used to evaluate PV-SMV invasion status preoperatively in PDAC. The LASSO regression model showed better performance than the conventional radiologic evaluation.

Objective:To study the protective effects of various doses of Glycyrrhizin on hippocampus of young rats with status epilepticus (SE).Methods:Lithium chloride and pilocarpine were injected intraperitoneally into male Sprague-Dawley (SD) rats (with a postnatal age of 18-21 days), so as to induce SE in rats.The rats were divided into 5 groups according to the random number table method: control group, SE group, SE+ low dose Glycyrrhizin group, SE+ medium dose Glycyrrhizin group and SE+ high dose Glycyrrhizin group.Three different doses of Glycyrrhizin (20 mg/kg, 40 mg/kg and 60 mg/kg) were injected intraperitoneally into the rats.The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in serum of SE rats were determined by enzyme linked immunosorbent assay.Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression levels of TNF- α, IL-1β and IL-6 in hippocampus of SE rats.The expression levels of Bax, Bcl-2 and Caspase-3 in hippocampus were detected by Western blot.The damage of neurons was measured by hematoxylin and eosin (HE) staining and Nissl staining.Neurons apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The mitochondrial changes were observed under transmission electron microscopy.One-way ANOVA followed by Tukey post-hoc test was used for statistical analysis. Results:Compared to the control group, TNF-α[(369.69±58.07) ng/L vs. (75.46±14.64) ng/L], IL-1β[(242.27±25.23) ng/L vs. (45.29±5.90) ng/L] and IL-6[(288.15±24.60) ng/L vs. (46.59±8.80) ng/L] in the serum of SE rats were significantly up-regulated(all P<0.05). Compared to SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of TNF-α[(216.67±8.31) ng/L, (158.81±5.03) ng/L and (113.69±12.54) ng/L vs. (369.69±58.07) ng/L], IL-1β[(131.21±5.50) ng/L, (86.60±7.79) ng/L and (65.06±4.39) ng/L vs. (242.27±25.23) ng/L] and IL-6[(150.24±9.48) ng/L, (101.70±5.85) ng/L and (91.60±2.81) ng/L vs. (288.15±24.60) ng/L] released in serum after SE occurred (all P<0.05). The neuronal damage, loss, apoptosis and mitochondrial damage were found in the hippocampus of SE rats.Glycyrrhizin could ameliorate these symptoms.Compared to the control group, Bax levels(0.57±0.01 vs. 0.14±0.01)and Caspase-3 levels(0.54±0.00 vs. 0.11±0.01)in the hippocampus of SE rats were markedly increased, while Bcl-2 levels(0.27±0.01 vs. 0.57±0.02)were decreased(all P<0.05). Compared to the SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of Bax(0.51±0.02, 0.45±0.03 and 0.40±0.02 vs. 0.57±0.01)and Caspase-3(0.47±0.02, 0.42±0.02 and 0.37±0.01 vs. 0.54±0.00), and increase the levels of Bcl-2(0.41±0.02, 0.45±0.02 and 0.51±0.01 vs. 0.27±0.01)(all P<0.05). Conclusions:Glycyrrhizin can effectively protect the hippocampus of young rats with SE.

Objective:To explore the clinical outcome of measured resection combined with gap balancing technique in total knee arthroplasty (TKA).Methods:From January 2016 to October 2017, 61 cases of varus knee joint flexion deformity were applied the procedure of measured resection combined with gap balancing technique in primary total knee arthroplasty, including 24 male and 37 female; the average age was 66.80±8.2 years old (range from 60 to 78 years old). All patients underwent antero-medial incision of knee joint,medial parapatellar approach and posterior stabilized prosthesis. Measurement osteotomy technique was used to localize osteotomy. Gap balancing technique was vitrificated flexion and extension. Operation time, surgical blood loss and osteotomy volume were recorded. Radiographic evaluation included alignment of lower extremity, knee joint linedistance, tibiofemoral joint angle, rotation angle of femoral prothesis and posterior condylar offset (PCO). Joint functions were assessed including KSS scores, ROM and patient satisfaction.Results:The average operation time was 54±12 min (range from 45 to 65 min). The average postoperative drainage was 140±26 ml (range from 120 to 180 ml). The difference in hemoglobin values were 22±8.5 g/L(range from 20 to 30 g/L) between preoperative and postoperative 5 days. The lateral proximal tibial bone mass was 10.2±1.5 mm (range from 9.2 to 11.5 mm). The lateral distal femoral bone mass was 9.1±1.5 mm (range from 8.8 to 10 mm). The bone mass of posterior lateral condyle of femur was 8.6±1.5 mm (range from 7.8 to 10 mm). The bone mass of posterior medial condyle of femur was 9.2±1.2 mm (range from 8.6 to 10 mm), compared with the bone mass of posterior lateral condyle of femur, and the difference was statistically significant ( t=2.44, P=0.006). The intraoperative angle between osteotomy line of gap balanced osteotomy technique (line B) and connecting line of screw hole in measure osteotomy (line A) was 1.15°±0.47° (range from 1.02° to 2°). The external rotation angle was27.8%, the internal rotation angle was72.2%. There was no significant difference between preoperative knee joint line distance 40.55±4.32 mm and postoperative knee prosthesis joint line distance 40.99±3.86 mm. Postoperative knee straight and bent-knee 90° stress X-ray demonstrated that medial-lateral tibiofemoral joint angle showed no significant difference ( P >0.05). Cross-sectional CT of knee joint post operation, rotation angle of femoral prosthesis ≤±2°. Most of them were mainly concentrated in the internal rotation angle. There was no significant difference between preoperative PCO 31.55±3.18 mm and postoperative PCO 31.55±3.18 mm ( P>0.05). The KSS score and patient satisfaction score post operationwere significantly higher than those preoperation. The KSS score and patient satisfaction score at 3 months after operation were 89.2±9.4 points and 7.2±2.6 points, which were higher than that at 1 month after operation (78.0±3.5 points and 5.2±1.8 points), with statistically significant differences ( t=1.897, P=0.026; t=1.753, P=0.038). The KSS score was above 90 at 6 months after operation. The knee ROM after 1 month (94.7°±10.6°) had no statistical significance compared with that preoperation (91.9°±12.5°) ( t=1.286, P=0.245). The knee ROM at 3 months after surgery (105.8°±14.7°) was significantly higher than that before operation (91.9°±12.5°) ( t=1.924, P=0.041). There was no significant difference between the scores of the follow-up time points and those of 3 months after operation ( P >0.05). Conclusion:TKA were performed by using measured resection combined with gap balancing technique. Not only can good alignment of lower extremity be restored, but also flexion-extension gap balance can be obtained. Equal osteotomy with less soft tissue release. There are better ROM of knee and KSS functional scores in the early postoperative period. However, it is easy to cause femoral pseudointernal rotation.

Objective: This study aims to explore the relationships of family functioning, general well-being, and exercise with psychological distress.Furthermore, we investigated the special roles of general well-being and exercise on the association between family functioningand psychological distress. Methods: Of 769 end-stage renal disease (ESRD) patients participated in the cross-sectional study which consisted of the 12-item GeneralHealth Questionnaire (GHQ-12), the Family APGAR Scales, and the General Well-Being Schedule. The collected data were analyzedusing multiple linear regression analysis and path analysis. Results: The prevalence of psychological distress was 72.3%. Family functioning, general well-being and exercise were associated factorsof psychological distress (p<0.05). The indirect effect of family functioning on psychological distress was partially mediated by generalwell-being (Effect=-0.08, 95% CI=-0.11, -0.04). In addition, the effect of family functioning on general well-being was moderated byexercise (Index=-0.092, SE=0.033, 95% CI=-0.159, -0.029). Conclusion The prevalence of psychological distress among ESRD patients was high. Family functioning, general well-being and exercisewere associated with psychological distress. Family functioning could affect psychological distress partially by affecting general wellbeing.Furthermore, exercise had a significant moderating effect on the relationship between family functioning and general well-being.Psychiatry Investig 2020;17(4):356-365

Objective To investigate the role of COOH-terminus tensin like molecule (CTEN) in epithelial-mesenchymal transformation of gastric cancer and its prognostic factors.Methods The expressions of CTEN,E-cadherin and Vimentin in 220 patients with gastric cancer were detected by immunohistochemical staining.Results The positive expression rate of CTEN was 61.8％ (136/220) in gastric cancer specimens,higher than 15％ (3/20) in adjacent tissues (x2 =16.488,P ＜0.01);the positive expression rate of E-cadherin in gastric cancer specimens was 25.5％ (56/220),lower than 85％ (17/20) in adjacent tissues (x2 =30.713,P ＜0.01);and the positive expression rate of Vimentin in gastric cancer specimens was 35.0％ (77/220),higher than 10％ (2/20) in adjacent tissues.There was no significant difference in the expression of CTEN between different genders,ages,size of tumors and histopathological types (P ＞ 0.05).In different infiltration depth,the CTEN expression difference were statistically significant (x2 =54.058,P ＜0.01),CTEN expression rate in lymph node metastasis group was obviously higher than without lymph node metastasis group (x2 =15.989,P ＜0.01),and CTEN expression rate in distant metastasis group was obviously higher than without distant metastasis group (x2 =4.143,P ＜0.01).CTEN and E-cadherin expression in gastric cancer tissue showed a negative correlation (r =0.357,P ＜ 0.01),while CTEN and Vimentin expression were positively correlated (r =0.498,P ＜0.01).220 cases of patients with gastric cancer received follow-up.Median survival time of CTEN negative express group was 48.2 months (95％ confidence interal,44.0-52.5 months),69.0％ for the 5-year cumulative survival rate.The survival analysis showed median survival time of CTEN positive expression group was 41.8 months (95％ confidence interal,38.3-45.3 months),48.5 ％ for the 5-year cumulative survival rate,which were lower than that in negative group (x2 =4.884,P ＜ 0.05).Multifactor analysis showed CTEN expression,lymph node metastasis and distant metastasis were independent risk factors for the prognosis of gastric cancer patients (P ＜ 0.05).Conclusions CTEN was positively correlated with gastric cancer invasion and metastasis,and played an important role in gastric cancer epithelial mesenchymal transformation.CTEN is independent risk factor for prognosis of gastric cancer,detection of CTEN gene mutation has important significance to evaluate the treatment and prognosis of gastric cancer.