Objective:To investigate whether octyl ester derivative of ginsenoside Rh2(Rh2-O)can induce immunogenic cell death of Huh-7 hepatocellular carcinoma cells and possible mechanism.Methods:Huh-7 cells were cultured in vitro,and divided into control group,Rh2-O group,positive control group(mitoxantrone treatment).Viability and apoptosis of cells were detected by CCK-8 and flow cytometry,respectively.Concentrations of high mobility family protein 1(HMGB1)and adenosine triphosphate(ATP)in supernatant were detected by ELISA and chemiluminescence assay,respectively.Membrane eversion of calreticulin(CRT)was detected by immunofluorescence assay.ROS level in cells was detected by fluorescence probe DCFH-DA,and expressions of proteins associated with endoplasmic reticulum stress signaling pathway were detected by Western blot.Results:Rh2-O treatment significantly reduced cell viability,promoted apoptosis,induced secretion of HMGB1,ATP,membrane eversion of CRT,increased accumulation of ROS in cells,and enhanced expressions of endoplasmic reticulum stress-related proteins PERK,eIF2α,p-eIF2α(all P<0.05).After addition of endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA),membrane eversion of CRT induced by Rh2-O was significantly inhibited(P<0.05).Conclusion:Rh2-O can induce immunogenic cell death in hepatocellular carcinoma cells,whose mechanism may be associated with activation of endoplasmic reticulum stress and promotion of CRT membrane eversion.

Objective:To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement.Methods:From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed.Results:Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement ( P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions:NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.

Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are "undruggable". Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.
Humans ; Proteolysis Targeting Chimera ; Nanostructures ; Neoplasms/drug therapy* ; Proteolysis

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Objective To investigate the display status of ultrasonography imaging check in central nervous system (CNS) in infants of early pregnancy and the diagnostic value of CNS malformation in infants of early pregnancy.Methods Gestational weeks of 2 751 enrolled subjects were divided according to the ultrasonic measurement of the crown rump length (CRL):11-11 +6 weeks group,12-12+6 weeks group,and 13-13 + 6 weeks group,prenatal ultrasound were performed to examine fetal CNS anatomy in infants of early pregnancy,record the display status in each groups of infants and analyze the relationship between the display situation and gestational age.Results Fourteen cases of fetal CNS malformation (20 malformations) in total were found by prenatal ultrasound,and the incidence of CNS malformation was about 5.09％ (14/2 571).Wherein,12 cases of early pregnancy were diagnosed,and 2 cases of middle pregnancy were diagnosed.The sensitivity of ultrasound of early pregnancy in the diagnosis of fetal CNS malformation was 85.71％.In the group of research,the ultrasound display ratios of 11-11+6 weeks group,12-12+6 weeks group and 13-13+6 weeks group were 96.73％,97.94％,98.06％,respectively.There was no significant difference in early pregnancy fetal CNS display ratio among groups (x2 =1.56,v =2,x2＜ x0.05.2 =5.99,P ＞ 0.05).Conclusions The display rate of CNS structure in infants of early pregnancy (11-13+6 weeks)is higher,and is not affected by gestational weeks.Prenatal ultrasound can effectively diagnose CNS severe malformation in infants of early pregnancy.

Objective:To investigate the expression and clinical significance of PD-L1 in colorectal cancer (CRC). Methods:A total of 210 CRC patients who accepted radical surgery in our hospital from January 2015 to January 2016 were divided into three groups, namely, high-frequency microsatellite instability (MSI-H), low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS). The expression of PD-L1 was detected by immunohistochemistry, and the expression characteristics of PD-L1 in different types of CRC were analyzed. Results:CRC cases with low differentiation had a higher expression of PD-L1 than CRC patients with high differ-entiation (P<0.05). PD-L1 had a positive rate of 75.8%in the MSI-H group and a rate of 9.3%in the MSI-L and MSS groups, wherein the difference between the two groups was statistically significant (P<0.05). Conclusion:PD-L1 was positively expressed in some CRC tu-mor tissues, and its positive rate was significantly higher in MSI-H than in MSI-L and MSS. The therapeutic effect of a PD-L1 blocker for patients with MSI-H CRC might be preferable.

Objective To investigate the curative effect of transcatheter arterial chemoembolization (TACE) combined with endovascular 125I seed strip implantation for the treatment of primary hepatocellular carcinoma (PHC) complicated by extensive portal vein tumor thrombus. Methods The clinical data of 72 patients with PHC complicated by extensive portal vein tumor thrombus were retrospectively analyzed. The patients were divided into group A (n=32) and group B (n=40). TACE combined with endovascular 125I seed strip implantation was performed for the patients of group A, while only TACE was employed for the patients of group B. The changes of portal vein tumor thrombus, the survival time and procedure-related adverse events were recorded. The preoperative and postoperative measured values were compared using paired samples t test, the count data were evaluated by χ2 test, and the survival time was analyzed with Kaplan-Meier method. Results Technical success rate of portal vein 125I seed strip implantation was 100%. No serious procedure-related adverse events occurred. The median survival periods of group A and group B were 210 days and 141 days respectively, the difference between the two groups was statistically significant (P=0.012). Conclusion For the treatment of primary hepatocellular carcinoma complicated by extensive portal vein tumor thrombus, TACE combined with endovascular 125I seed strip implantation can significantly improve the patient’s survival time.

Objective To investigate the clinical pathologic features and treatment scheme of primary bronchial carcinoid tumor.Methods Twenty-one cases with primary bronchial carcinoid tumors were selected as our subjects.Clinical information was recorded.Of 21 patients,17 cases were undergone surgery including 12 cases for lobectomy,2 cases for pneumonectomyin,1 case for pulmonary wedge resection and 1 case for egmental resection;Three cases were received adjuvant chemotherapy,1 case for adjuvant and radiation therapy and chemotherapy and 1 case for chemotherapy only.Results Histological classification showed that 7 cases were typical carcinoid,and other 14 cases were atypical carcinoid.Nine cases were TNM stage I,8 cases at stage Ⅱ,1 case at stage Ⅲ,3 cases at stage Ⅳ.All cases were performed follow-up for 5 years.Nineteen cases survived at 1st year and 10 cases survived at 3rd years survival.5 years survival rate was 23.8％ (5/21).Conclusion Surgical operation is proved to be the main method for treating bronchopulmonary carcinoid tumors,and surgical radical operation was recommended.

ObjectiveTo establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT)and examine its growth with MDCT and 3D-MPR. MethodsTumor cell line VX2 was inoculated subcutaneously into rabbit to develop the primary tumor, which was then cut into small strips. Purse-string suture was performed on the anterior wall of IVC after the laparotomy in eighteen New Zealand white rabbits.The tumor strip was injected into IVC through the purse and suspensory fixed on the inner wall of IVC. The general conditions,body weight,and the survival time were monitored after operations.MDCT examinations were performed with plain scan,arterial phase,portal phase and venous phase enhancement every week for all animals and 3D-MPR were acquired.The volumes of IVCTT were calculated.IVC,IVCTT and metastasis were examined with gross and histological pathology. ResultsThe IVCTT was confirmed by MDCT and 3D-MPR images.Collateral varicose veins caused by IVC obstruction and metastasis were also shown in images.IVCTT and metastasis were confirmed by pathological method. The success rate of IVCTT was 100 ％. The mean survival time of operated animals was(49.5±4.4)days. ConclusionsInjecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish the IVCTT animal model. MDCT and 3D-MPR are valuable methods to monitor the growth and metastasis of IVCTT in animal models. The model of implanted IVCTT of rabbits provides a useful tool for the research of treatment of IVCTT.