Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.

Objective To investigate whether norepinephrine (NE) regulates the oxidative stress in human endom-etrial epithelial cells (hEECs) by activating nuclear factor E2-related factor 2(Nrf2)/ heme oxygenase -1(HO-1) signal pathway.Methods Cultured hEECs were used.The expression of α and β adrenergic receptors was detec-ted by reverse transcription-polymerase chain reaction (RT-PCR).Cell counting kit-8(CCK-8) assay was applied to test the effect of NE on cell viability, then the cells were divided into Control group and NE treatment group, and the appropriate concentrations were chosen.The expression of tight junction proteins Occludin and zona occludens-1(ZO-1), apoptosis-related proteins apoptosis-related protein B-cell lymphoma-2 protein(Bcl-2) and Bcl-2 associ-ated X protein(Bax) , antioxidant proteins Nrf2 and HO-1 were examined by Western blot.The apoptosis was de-tected by flow cytometry.The malonaldehyde (MDA) and superoxide dismutase(SOD) in the cell culture medium were detected by enzyme-linked immunosorbent assays kit (ELISA).Results The mRNA expression of α1 a,α1 b,α2 a,α2 b,α2 c,β1, β3 was detected in the hEECs.After the NE treatment, no significant change in cell viability was observed in low concentration (5 μmol/L and 10 μmol/L) groups, while 15 μmol/L and 20μmol/L NE treatments for 6 h or 24 h promoted the cell viability significantly.The expression of ZO-1 and Occlu-din increased significantly in 15 μmol/L group after 24 h treatment, the expression of ZO-1 decreased in 6 h treat-ment group, significant down regulation was observed after 15 μmol/L NE application, the expression of Occludin increased in 6 h group.The cell apoptosis increased compared with the control group after NE stimulation, espe-cially a significantly increase in 6 h 15 μmol/L group was detected,while the fall in increased apoptosis was ob-served after 24 h treatment.The ration of Bcl-2/Bax>1.The expression of Nrf2 and HO-1 was elevated by NE.There was no obvious change in MDA level while significant elevation in SOD was detected in cell culture medium.Conclusion Nrf2/HO-1 signal is activated after application of NE to the hEECs, which may responsible for the upregulation of SOD, antioxidant and anti-apoptotic effect in the hEECs.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Ferroptosis is a way of cell death with lipid peroxides as the core.Cells can reduce ferroptosis sensitivity by relying on glutathione peroxidase 4(GPX4)/glutathione(GSH)antioxidant systems.Triple-negative breast cancer(TNBC)cells are more dependent on the intracellular antioxidant mechanism than normal cells,thus induction of ferroptosis based on the GPX4/GSH system has shown bright anti-TNBC prospects.This paper reviews the recent research on TNBC treatment with ferroptosis in the background of GPX4/GSH,in order to provide references for the clinical treatment of TNBC.

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.

【Objective】 To investigate the effect of Qingkailing injection on platelet function preserved in vitro. 【Methods】 A total of 15 bags of plateletpheresis (≥250 mL/bag), adding Qingkailing injection(1.25 mL/bag) at the final concentration of 1%, were stored at 22 ℃ with gentle agitation as the experimental group, and samples were collected on day 1, 3, 5, 8, 10 and 14 to detect the thromboelastogram (TEG), CD62p expression rate and mitochondrial membrane potential (JC-1). The control group was set up synchronously, with the same volume and storage conditions as the experimental groups, and samples were taken on day 1, 3 and 5 after preservation to undertake the same test items as the experimental groups. The differences of detection indexes between the two groups were compared. 【Results】 1) In the experimental group, there was no significant change in K and α during day 1 to 14(P>0.05). The R value (min) increased from 6.12±1.58 to 11.02±2.26, and the CI value changed from 0.27±1.24 to -10.47±3.51 (P<0.05). The MA value (mm) had no significant change within 5 days (P>0.05), but decreased to 53.18±2.71 on day 8 and 22.88±3.45 on day 14 (P<0.05). In the control group during day 1 to 5, K(min) and α showed no significant change, while R(min) was significantly prolonged, MA (mm) decreased and CI increased significantly (P<0.05). 2) The expression rate of CD62p (%) was 70.50±9.12 in the experimental group on day 5 (vs 83.16±5.33 in the control groups, P<0.05) and 82.77±7.17 on day 14 (P<0.05). 3) There was no significant change in JC-1 (%) during regular preservation period between the experimental group and control group (P>0.05), but JC-1 (%) was 86.75±3.88 vs 70.36±19.8 on day 5 (P<0.05). In the experimental group, JC-1(%) was 81.04±9.50 vs 71.38±8.77 vs 82.77±7.17 on day 8, 10 and 14, respectively. 【Conclusion】 The activation and aggregation as well as anti-apoptosis function of plateletpheresis, adding Qingkailing injection at the final concentration of 1%, are similar to those of routine preservation.

ObjectiveTo explore the effects of negative life events on suicidal ideation in adolescents with depressive disorder and the mediating role of mother-child attachment， so as to provide references for reducing suicidal ideation in adolescents with depression. MethodsA total of 145 adolescents underwent psychiatric inpatient and outpatient treatment in the First Affiliated Hospital of Chongqing Medical University From May 2020 to April 2021 and met the International Classification of Diseases， tenth edition （ICD-10） criteria for depressive episode were enrolled， and all selected individuals were assessed using the Adolescent Self-rating Life Events Checklist （ASLEC）， the Inventory of Parent and Peer Attachment （IPPA） and Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）. Then Bootstrap method was used to test the mediating effect. ResultsBSI-CV score in adolescents with depressive disorder was positively correlated with ASLEC score （r=0.453， P<0.01）， and negatively correlated with mother-child attachment score in IPPA （r=-0.165， P<0.01）. The partial mediating effect of mother-child attachment between negative life events and suicidal ideation was significant， with a mediating effect value of 0.008， accounting for 14.55% of the total effect value （0.055）. ConclusionSuicidal ideation in adolescents with depressive disorder may be related to loads of negative life events and poor mother-child attachment， moreover， mother-child attachment plays a mediating role in the relationship between negative life events and suicidal ideation.

【Objective】 To study the metabolism and morphology changes of platelets in vitro using traditional Chinese medicine named Qingkailing injection as the additive solution, and to explore the viability of Qingkailing in the extension of platelet storage. 【Methods】 Apheresis platelets, adding 1% final concentration of Qingkailing injection, were taken as experiment groups, and sampled on 1, 3, 5, 8, 10 and 14 days(6 time points)of storage. Apheresis platelets without adding Qingkailing injection were taken as the control, and sampled on 1, 3 and 5 days(3 time points)of storage. The platelet count, morphology scores, biochemical parameters, pH and response rate of hypotonic shock during agitated storage(22 ℃) were tested. 【Results】 1) No significant change in platelet count was noticed in both experimental group(within 14 days) and the control(within 5 days)(P>0.05). The MPV and PDW of both groups increased at any sampling time within 5 days(P<0.05). 2) The morphology score of experimental groups and the control all decreased within the storage period(P<0.05), but its decrease of the control was greater than that of the experimental groups, especially on day 8(P<0.05). 3)Glucose, lactate dehydrogenase, lactate, Na⁺, and K⁺ values increased or decreased in varying degrees(P<0.05), while Cl^- value stayed almost the same during 14 days(P>0.05). Glucose, lactate dehydrogenase, lactate and Na⁺ value changed significantly in the control within 5 days(P<0.05), while K⁺ and Cl^- value did not(P>0.05). Within 5-day storage, the glucose consumption, lactate dehydrogenase and lactate generation in the control were significantly greater than those in experimental groups(P<0.05), but the added value of Na⁺, K⁺ and Cl^- showed no significant difference(P>0.05). 4) pH value, relative to the baseline of day 1, decreased in both groups within 5 days, and its decreasing trend was significant in the control (P<0.05), but not in the experimental group(P>0.05). No significant difference was noticed in the response rate of hypotonic shock in experimental groups within 8 days, while significant decrease was noticed in the control within 5days(P<0.05). The response rate of hypotonic shock in experimental groups were significantly higher than that in the control on day 3 and day 5(P<0.05). 【Conclusion】 The comparison of apheresis platelets, stored in vitro, in terms of platelet count, morphology scores, biochemical parameters, pH and response rate of hypotonic shock showed that platelets, adding 1% final concentration of Qingkailing injection, could prolong the platelet storage to at least 10 days in vitro.

【Objective】 To study the feasibility of whole blood thromboelastogram (WB-TEG) and its correlative kit for plasma thromboelastogram (P-TEG) detection and the characteristics of P-TEG in healthy subjects. 【Methods】 17 healthy volunteers were detected by WB-TEG instrument and its correlative kit, and the results were compared with those by P-TEG. The P-TEG characteristics of 17 healthy volunteers were analyzed. Three groups (7 cases/group)of plasma samples with different platelet (Plt) count and the other three groups of plasma(7, 6 and 4 cases, respectively) with different fibrinogen(Fib) concentration were tested for P-TEG. The effects of Plt and Fib on P-TEG detection were observed. 【Results】 There was no significant difference in R and MA value (P>0.05)as WB-TEG was compared with P-TEG in healthy subjects, while in K(min) (1.71±0.47 vs 1.07±0.45), A(°) (66.1±5.41 vs 75.59±5.77), and CI value (0.9±1.8 vs 2.52±2.58)(all P <0.05). Various parameters of healthy individuals were basically within the range of 95% CI of WB-TEG, but there were significant diffferences in K, A and CI value(P<0.05). When Plt count (×10¹¹/L) was≥2.5 in plasma, the MA value of P-TEG was significantly extended than that of normal individuals(P<0.05); when Plt count (×10¹¹/L) was 6.0 ~12.0, the MA and CI value of P-TEG significantly decreased(P<0.05). When Fib(g/L) was 6.4~6.91 in plasma, the R and K value of P-TEG were prolonged, but A, MA and CI value all decreased(P <0.05); when Fib(g/L) <1, the A and MA value significantly decreased(P<0.05), and K and CI value could not be detected. 【Conclusion】 The WB-TEG and its correlative kit can be used in P-TEG detection, and corresponding reference values of TEG parameters should be established in combination with the conditions of laboratories.