AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

The incidence of cancer is closely correlated with age,as 75％of non-small cell lung cancer(NSCLC)patients are aged at least 65 years.The availability of immune checkpoint inhibitors(ICIs)has altered the available NSCLC therapeutic pattern.Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial ben-efits for patients aged 65-75 years,showing no significant difference compared to younger patients.This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy.For individuals older than 75 years,the survival effect was not evident,though.Immune-related adverse events(irAEs)with ICIs alone were similar in incidence across age catego-ries.Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone,and patients ≥75 years of age were more likely to experience higher-grade irAEs.Besides the fact that immunosenescence in older patients influ-ences the immune milieu in a multifaceted manner,which in turn impacts the effectiveness of immunotherapy,the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status(ECOG PS)score,among other factors.For certain individuals aged ≥75 years or in poor physical health,immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option.However,there are fewer related studies,so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment op-tions.To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new thera-peutic perspectives in combination with their characteristics,this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors in these patients.

Purpose: Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy,which is associated with the progression of carcinoma. Yet, it is still unclear whetherLC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aimto explore the predictive value of LC3B on prognosis of ICC, and to establish a novel andavailable nomogram to predict relapse-free survival (RFS) and overall survival (OS) for thesepatients after curative-intent hepatectomy. Materials and Methods: From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the ThirdAffiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolledpatients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. Results: The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariateCox regression analysis, independent risk factors for 5-year OS were cancer antigen 125,microvascular invasion, LC3B expression and lymph node metastasis. Except for the above4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factorsfor 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and0.747, respectively. Conclusion The nomograms based on LC3B can be considered as effective models to predict postoperativesurvival for ICC patients.

BACKGROUND: Our previous findings indicate that inflammation-activated bone marrow mesenchymal stem cell conditioned medium (MSC-CM) contribute to repairing the structure and function of the small intestine after radiation-induced acute intestinal injury. However, it is unclear whether the repair effect can be achieved by regulating small intestinal stem cells. OBJECTIVE: To investigate the effects of inflammation-activated bone marrow MSC-CM on the small intestinal epithelial stem cells after acute radiation-induced intestinal injury and to further discuss the repairing mechanism. METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were separated, cultured and identified. Then, the bone marrow mesenchymal stem cells were co-cultured with normal or radiation-induced IEC-6 cell lines in the Transwell system for 24 hours. Inflammation-activated bone marrow mesenchymal stem cells were cultured alone for 48 hours. Non-activated MSC-CM (MSC-CMNOR) and MSC-CM under radiation-induced inflammatory condition (MSC-CMIR) were collected. Adult Sprague-Dawley rats (provided by the Experimental Center of Sun Yat-Sen University North Campus) were randomly divided into four groups with 20 rats in each group: control group, radiation group, radiation+MSC-CMNOR group and radiation+MSC-CMIR group. The rats in the latter three groups were exposed to one-off 14 Gy whole abdominal radiation to make a rat model of acute radiation-induced small intestinal injury. Three-day continuous administration beginning within 4 hours after successful modeling was given via the tail vein and intraperitoneal implantation of Alzet micro-osmotic pumps: EMEM-F12 (200 μL/d) for the radiation group, MSC-CMNOR for radiation+MSC-CMNOR group and MSC-CMIR for radiation+MSC-CMIR group. There was 2 mL of concentrated conditioned medium in the pump which was released at a constant rate of 10 μL/h into the abdominal cavity after implantation. Intestinal samples were collected at 1, 3, 5, 7 days after radiation for immunochemistry staining, western blot and qRT-PCR detection. RESULTS AND CONCLUSION: (1) On the 3rd day after radiation, Lgr5 positive cells, which were actively proliferating on the base of crypts, became significantly reduced compared with the normal control group, and there was nearly no existing Lgr5 positive cells. However, after infusion of MSC-CMIR, Lgr5 positive intestinal stem cells were significantly increased compared with the radiation group, while in the radiation+MSCNOR group, there was no significant increase in Lgr5 positive intestinal stem cells. (2) On the 3rd day after radiation injury, Bmi1 positive intestinal stem cells were almost invisible. After infusion of MSC-CMIR, Bmi1 positive intestinal stem cells increased significantly, and it was observed not only in the +4 cell position but also in the common position used to be Lgr5 stem cells, indicating that Bmi1 stem cells could differentiate into Lgr5 positive cells to act its repairing effect. (3) Western blot and qRT-PCR further confirmed that the radiation+MSC-CMIR group was significantly higher on the Lgr5 expression level than the radiation group and the radiation+MSC-CMNOR group, and it returned to the normal level on the 7th day after the continuous high expression level. The repair effect of radiation+MSC-CMNOR group was weaker, and only on the 7th day, the expression level of Lgr5 was statistically different from the radiation group. To conclude, inflammation-activated bone marrow MSC-CM exert a protective effect on the small intestinal epithelial stem cells after acute radiation-induced intestinal injury

Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.

Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS) and the IMS-localized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.
Cell Line ; Humans ; Mitochondrial Membranes ; metabolism ; Protein Transport ; RNA ; biosynthesis ; chemistry ; metabolism ; RNA Stability ; RNA, Mitochondrial ; Ribonucleases ; metabolism ; Tumor Suppressor Proteins ; metabolism

Objective To compare the clinical effect of penehyclidine hydrochloride and atropine in the treatment of acute organophosphorus pesticide poisoning.Methods 86 patients with organophosphorus pesticide poisoning were selected and randomly assigned to the observation group and the control group according to the digital table,43 cases in each group.The two groups were given conventional treatment,while the control group was treated with atropine,the observation group was given penehyclidine hydrochloride.The disappearance time of main symptoms, rescue success rate and adverse reactions of the two groups were observed.Results After salvage treatment, the rescue success rate of the observation group was 97.8%,which of the control group was 88.4%,the difference was statistically significant (x2=1.433,P<0.05).The disappear time of M like symptoms,N like symptoms and central nervous system symptoms in the observation group was significantly shorter compared with the control group (all P<0.05).The number of drugs,dosage,cholinesterase recovery time and hospitalization time between the two groups had statistically significant differences (P<0.05).The incidence rates of blurred vision,restlessness,heart rate and urinary retention in the control group were significantly higher than those in the observation group (all P<0.05).Conclusion Penehyclidine hydrochloride for acute organophosphorus pesticide poisoning can significantly reduce the incidence of symptoms,shorten the disappearance time of symptoms,reduce hospitalization time,improve the efficacy of rescue,reduce the incidence of adverse reactions, it is safe,effective and has great clinical significance.

Objective To explore the risk and treatment of laparoscopic cholecystectomy(LC) in patients with liver cirrhosis and cholelithiasis.Methods To summarize the clinical data of 28 patients with liver cirrhosis and cholelithiasis.The patients were repeated right upper quadrant pain,including 4 cases of gallbladder neck stones incarcerated,gallbladder effusion.Among them,there were 20 cases of hepatitis B cirrhosis,5 cases of schistosomiasis cirrhosis,3 cases of alcohol.Results There were 6 patients with hemorrhage during operation.Among them,5 patients were treated with gelatin sponge,hemostatic gauze and bio-glue spray to stop bleeding,1 case was transferred to open surgery because of bleeding.The remaining 27 cases of LC were successful.Complications occurred in 8 patients,3 cases of increased liver function abnormalities,1 case of upper gastrointestinal bleeding,1 case of mild hepatic encephalopathy,2 cases of significant ascites formation,1 patient underwent subtotal resection of the gallbladder with Hartmanns bag,and bile was found in the ascites after surgery,but the bile disappeared after five days.All patients with complications after symptomatic treatment were cured,no death,no major bleeding and liver failure,bile duct injury,severe biliary fistula and other serious complications.Conclusion Although the risk of LC in patients with liver cirrhosis is higher than that in the general population,with the help of current high-tech surgical instruments,we can safely accomplish this with an improved surgical procedure.As these patients require high technical requirements of surgery,surgeons must have a wealth of experience and familiar laparoscopic liver and gallbladder anatomy.

Cystic echinococcosis (CE) treatment urgently requires a novel drug. The p38 mitogen-activated protein kinases (MAPKs) are a family of Ser/Thr protein kinases, but still have to be characterized in Echinococcus granulosus. We identified a 1,107 bp cDNA encoding a 368 amino acid MAPK protein (Egp38) in E. granulosus. Egp38 exhibits 2 distinguishing features of p38-like kinases: a highly conserved T-X-Y motif and an activation loop segment. Structural homology modeling indicated a conserved structure among Egp38, EmMPK2, and H. sapiens p38α, implying a common binding mechanism for the ligand domain and downstream signal transduction processing similar to that described for p38α. Egp38 and its phosphorylated form are expressed in the E. granulosus larval stages vesicle and protoscolices during intermediate host infection of an intermediate host. Treatment of in vitro cultivated protoscolices with the p38-MAPK inhibitor ML3403 effectively suppressed Egp38 activity and led to significant protoscolices death within 5 days. Treatment of in vitro-cultivated protoscolices with TGF-β1 effectively induced Egp38 phosphorylation. In summary, the MAPK, Egp38, was identified in E. granulosus, as an anti-CE drug target and participates in the interplay between the host and E. granulosus via human TGF-β1.
Cloning, Molecular* ; DNA, Complementary ; Echinococcosis ; Echinococcus granulosus* ; Echinococcus* ; Humans ; In Vitro Techniques ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Phosphotransferases ; Protein Kinases* ; Signal Transduction

Aim Toinvestigatewhetherexposureto Sanguinarine (SAN ) can inhibit cell proliferation in human mammary adenocarcinoma cells (MCF-7 ) and thepossiblemechanism.Methods WeexposedMCF-7 to anticancer compound SAN,cell viability was as-sessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT ) reduction assay. ROS was measured using confocal microscopy,expres-sion of caspase-3 ,caspase-8 and caspase-9 were calcu-latedusingchemiluminescencemethod.Results SAN remarkably inhibited growth of human mammary adeno-carcinoma MCF-7 cells by decreasing cell proliferation. ROS release and caspase-3,caspase-8,caspase-9 ex-pression were stimulated by SAN in MCF-7 ,and these changes were abolished by the antioxidant,N-acetyl-cysteine(NAC).Conclusion Regulationofcaspases expression and release from MCF-7 cells are possibly e-voked by SAN through reactive oxygen species.