[ ABSTRACT] AIM:To investigate the effects of BARF1 down-regulation on EBV-positive gastric carcinoma cell apoptosis, and the molecular mechanisms by BARF1 silencing-mediated apoptosis.METHODS: After NUGC3 and SNU719 cells were transfected with NCsiRNA and siRNA, respectively, the protein levels of BARF1, Bcl-2, Bax, cyto-chrome C, caspase 3 and capase 9 were detected by Western blot, and the mRNA expression of BARF1, Bcl-2 and Bax was determined by RT-PCR.The cell viability was measured by the method of Trypan blue exclusion and the cell apoptosis was analyzed by flow cytometry analysis with Annexin V-FITC/PI staining.The expression of the apoptosis-related proteins in the cells transfected with siRNA and NCsiRNA was examined by human apoptosis antibody arrays.Mitochondrial mem-brane potential was determined by flow cytometry.The interaction between Apaf-1 and caspase 9 was confirmed by immuno-precipitation.RESULTS: Compared with untreated and NCsiRNA groups, BARF1 gene silencing significantly inhibited the cell viability, induced apoptosis, and reduced the mitochondrial membrane potential in the NUGC3 and SNU719 cells transfected with siRNA.BARF1 gene silencing up-regulated the expression of pro-apoptotic proteins and down-regulated the expression of anti-apoptotic proteins, and the Bcl-2/Bax ratio was significantly decreased.In BARF1 gene silencing cells, the caspase inhibitor z-VAD-fmk inhibited BARF1 silencing-mediated apoptosis, and significantly increased the levels of cleaved caspase 3 and caspase 9.The concentration of cytochrome C significantly increased as compared with NCsiRNA group, and Apaf-1 interacted with caspase 9 in the cytoplasm.CONCLUSION:BARF1 silencing induces apoptosis via the mitochondrial pathway through regulating the expression of Bcl-2 and Bax proteins in a caspase-dependent manner in the NUGC3 and SNU719 cells.

Aim To study the growth inhibitory effect of the conjugate ( ovarian cancer specific targeting peptide and cisplatin, OSTP-DDP ) that targeting ovarian cancer cells A2780. Methods Using chemical method to syn-thesize OSTP-DDP, ovarian cancer cells A2780 were cul-tured in vitro, using CCK-8 method ( Cell Counting Kit-8) to detect the growth inhibitory effect of ovarian cancer A2780 cells, which were disposed by OSTP-DDP and DDP. Annexin V-FITC was used to detect the cycle and apoptosis effect of ovarian cancer A2780 cells which were disposed by OSTP-DDP and DDP. Results According to the mass spectrometry and the high performance liquid chromatography ( HPLC ) analysis, OSTP-DDP was proved to synthesize successfully. CCK-8 assay showed that both OSTP-DDP and DDP could play the growth in-hibitory effect and showed a concentration-dependent manner when cells were treated in different concentrations (10,20,40,80,160,320μmol·L-1 ) respectively after 24 h, 48 h, 72 h. And the effect of OSTP-DDP was stronger than DDP (P<0. 05), indicated OSTP-DDP had targeted cytostatic effect. The result of the flow cytometry showed that cell cycle was mostly arrested in G1 phase after 72h treated by OSTP-DDP and DDP, the inhibitory effect of OSTP-DDP was stronger than DDP (P<0. 05). The apop-tosis effect of OSTP-DDP was stronger than DDP ( P <0. 01),suggested that OSTP-DDP had a stronger targeting apoptosis-inducing effect. Conclusion OSTP-DDP has the targeting growth inhibitory effect on the ovarian cancer cell A2780, OSTP as a chemotherapeutic drug targeting vector has a great prospect to treat ovarian cancer.

Objective To elucidate the imaging characteristics of spongiform leukoencephalopathy induced by heroin and the diagnostic value of MRI examination.Methods Eleven cases of heroin addiction were examined by MRI.The sequences included T1-weighted imaging(T1WI),T2-weighted imaging(T2WI)and fast fluid-attenuated inversion recovery pulse sequence(Flair).Results Bilateral symmetrical lesions were located in the white matter of the cerebrum and cerebellum,the internal capsule in all cases,and the callosum in 6 cases.Elliptical lesions in the mesencephalon were found in two cases.These lesions were shown as hypointense signals on T1WI and hyperintense signals on T2WI and Flair's imaging.Cerebellar white matter suffered more severely,but the dentate nuclei were not invaded.Conclusion Heroin-induced spongiform leukoencephalopathy has characteristic patterns in MRI,which are very specific to this form of the disease.

Objective To explore the etiopathogenisis of Reinke's edema. Methods To detect 15 samples of Reinke's edema of vocal cord mucosal and 5 samples of common vocal cord mucosal with S-P immunohistochemical method. Then to observe the effect of immunity class under the light microscope. To detect the expression of the VEGF and the production of the blood capillary in the sample of Reinke's edema of vocal cord mucosal with immunohisto-chemical method. Results There are 12 effects of sex in the 15 samples of Reinke's edema of vocal cord mucosal. There are effects of feminine in the 5 samples of common. Conclusion The main etiopathogenisis of Reinke's edema is that blood vessel grew ad libitum, the permeability of blood vessel increase and oxygen lack partly.

BACKGROUNDAt present, little is known about the correlation between osteopontin (OPN) and P21 in primary non-small cell lung cancer (NSCLC). The aim of this study is to investigate the expression of OPN and P21 and their correlation in NSCLC.

METHODSThe expression of OPN and P21 was detected in 58 NSCLC tissues and 18 pulmonary inflammatory pseudotumor (PIP) as controls by immunohistochemical technique.

RESULTSThe positive rate of OPN and P21 in NSCLC was 58.6% and 70.7% respectively, which was significantly higher than those in PIP (11.1% and 16.7%) (P=0.0008, P < 0.0001). There was a positive correlation between OPN and P21 expression (P < 0.0001). Lymph node metastasis was closely related to OPN expression (P=0.0367), but not to P21 expression (P=0.4898).

CONCLUSIONSThe abnormal expression of OPN and P21 in NSCLC may act in a synergistic way. Immunopositivity of OPN may suggest a potential risk of metastasis in NSCLC.

OBJECTIVE To study clinical manifestations and characteristics of adverse drug reactions （ADRs）induced by roxadustat，and to provide reference for rational use of it in clinic . METHODS Retrieved from PubMed ，Web of Science ，Wanfang Med，VIP and CNKI ，clinical trials and case reports （including series studies and case reports ）of ADRs induced by roxadustat were collected ；descriptive method was used to analyze patients ’basic information ，involved systems/organs and main clinical manifestations. The incidence of ADR was compared between roxadustat group and erythropoietin （EPO）group. RESULTS & CONCLUSIONS A total of 17 articles were included ，including 14 clinical trials and 3 case reports . In the clinical trial studies ， there were 4 033 patients using roxadustat ，including 1 972 males（48.9%）and 2 061 females（51.1%），aged from 36 to 80 years. The type of patients in one clinical trial was low -risk myelodysplastic syndrome ，and the others were renal anemia ；they received relevant drugs with dosage of 40-120 mg，mostly three times a week . Roxadustat-induced ADR （1-2 grade）involved systems/ organs mainly included cardiovascular system ，respiratory and thoracic system ，digestive system ，infection and infestation . The major systems/organs involved in serious adverse drug reaction （sADR）were cardiovascular system ，infection and infestation ； there was no statistically significant difference in the incidence of ADR between roxadustat group and EPO group （P＞0.05），but the incidence of sADR in roxadustat group was significantly higher than that in EPO group （P＜0.05）. In the case reports ， pulmonary hypertension ，rhabdomyolysis and fatigue were the clinical manifestations of ADRs induced by roxadustat . During clinical medication ，attention should be paid to the changes in relevant systems/organs of patients . If ADR is found ，timely intervention should be carried out .

OBJECTIVE To carry out data mining on the prescriptions of traditional Chinese medicine （TCM） for the treatment of renal anemia， and to explore the medication rules of TCM in the treatment of renal anemia. METHODS The Chinese and English databases including PubMed， the Cochrane Library， Web of Science， CNKI， Wanfang， VIP and CBM were searched by computer to screen the related literature about TCM in the treatment of renal anemia. Excel software was used to extract prescription information， including frequency of use， property and flavor， meridian tropism and efficacy of single TCM. Association rule analysis and hierarchical clustering analysis were performed for each ingredient of TCM with R language. RESULTS A total of 268 literature were included， involving 169 ingredients with a total use frequency of 3 919 times. Among them， Astragalus memeranaceus， Angelica sinensis， Atractylodes macrocephala， Rheum officinale， Poria cocos， Radix Rehmanniae Praeparata， Radix Codonopsis， Salvia miltiorrhiza and Ligusticum chuanxiong were used more than 100 times. The properties and flavors of the drugs were mainly warm and sweet； meridian tropism mainly targeted spleen， liver and kidney； the function was mainly in replenishing qi， nourishing blood， promoting blood circulation and removing blood stasis， and clearing damp and promoting diuresis， purgation. The result of association rule analysis showed that the core ingredients were A. memeranaceus， A. sinensis， A. macrocephala， P. cocos and S. miltiorrhiza. Hierarchical cluster analysis showed that the clustering results were divided into grade 1， 2 and 3， and the cluster classification of A. memeranaceus and A. sinensis was always the same. CONCLUSIONS The core prescription for treating renal anemia includes A. memeranaceus， A. sinensis， A. macrocephala， P. cocos and S. miltiorrhiza； among them， A. memeranaceus and A. sinensis are at the center of the core prescription and indispensable. The medication rule is mainly guided by drugs for invigorating qi， nourishing blood， strengthening spleen， and removing dampness. According to the characteristics of different symptoms of patients， dialectical treatment is made， and other TCM is added or subtracted on the basis of the core prescription.

Objective:To investigate the effects of surgery with the Yeung endoscopic spine system (YESS) technique on lumbar range of motion and limb function in patients with lumbar disc herniation.Methods:A total of 148 patients with lumbar intervertebral disc herniation admitted to Liaocheng Second Hospital Affiliated to Shandong First Medical University from April 2018 to April 2021 were included in this study. They were randomly divided into control and observation groups ( n = 74/group). The control group was treated with laminectomy, and the observation group was treated with an intervertebral foramen mirror YESS. The lumbar range of motion, Oswestry disability index score, and incidence of surgical complications were compared between the two groups. Results:At postoperative 7 days, ranges of motion in lumbar flexion, lumbar extension, left lumbar lateral flexion, and right lumbar lateral flexion in the observation group were (87.45 ± 7.38)°, (26.87 ± 3.41)°, (28.58 ± 3.41)°, (28.39 ± 3.41)°, which were significantly higher than (68.98 ± 6.51)°, (15.69 ± 3.23)°, (18.69 ± 2.32)°, (14.56 ± 2.96)° in the control group ( t = 16.15, 20.48, 20.63, 26.35, all P < 0.001). At postoperative 7 days, the Oswestry Disability Index in each group was significantly decreased compared with before treatment (both P < 0.05). At postoperative 7 days, the score of each dimension of the Oswestry Disability Index in the observation group was significantly lower compared with the control group ( t = 49.13, 50.20, 54.78, 37.79, 32.04, 36.68, 43.69, 28.92, 39.31, 64.12, all P < 0.001). There were no significant differences in the incidences of perioperative incision infection, nerve injury, cerebrospinal fluid leaks, lumbar spondylolisthesis, and foot drop between the two groups (all P > 0.05). Conclusion:Treatment of lumbar intervertebral disc herniation with the YESS technique is helpful to improve lumbar mobility and reduce lumbar dysfunction and is highly safe.

Objective To investigate the role of miR-125b on hepatic angiogenesis,with the hope of providing new targets for the prevention and treatment of liver fibrosis.Methods The human hepatic sinusoidal endothelial cells were transfected with miR-125b mimics and inhibitors,and the mRNA and protein expression of vascular endotheli-al growth factor(VEGF),cluster of differentiation antigens 31(CD31),von Willebrand factor(vWF),collagenⅣ,and laminin(LN)were detected by qRT-PCR and ELISA,and the expression of nitric oxide(NO)was detec-ted by fluorescent probe,scanning electron microscopy detected the alteration of the window holes on the surface of human hepatic sinusoidal endothelial cells,angiogenesis assay was performed to observe the neovascularization of each group,and dual luciferase reporter gene assay was performed to validate the targeting relationship between miR-125b and VEGF.Results qRT-PCR and ELISA showed that compared with the negative control group,the mRNA and protein expressions of VEGF,CD31,vWF,Collagen Ⅳ,and LN significantly decreased after miR-125b mimic transfection(P＜0.05),while the mRNA and protein expressions of VEGF,CD31,vWF,CollagenⅣ,and LN were significantly increased after transfection with miR-125 b mimics(P＜0.05);fluorescent probe detection showed that compared with the negative control group,the average fluorescence of intensity expression NO decreased significantly(P＜0.05),while the average fluorescence intensity expression of NO increased significant-ly after miR-125b inhibitor transfection(P＜0.05);the number of fenestrations on the surface of human liver sinu-soidal endothelial cells significantly increased after miR-125b mimic transfection(P＜0.05),while the number of fenestrations on the surface of human liver sinusoidal endothelial cells decreased significantly after miR-125 b inhibi-tor transfection(P＜0.05);angiogenesis assay showed that compared with the negative control group,the number of angiogenesis significantly decreased after miR-125b mimic transfection(P＜0.05),while the number of angio-genesis significantly increased after miR-125b inhibitor transfection(P＜0.05);dual luciferase reporter gene assay showed that compared with negative control group,the expression of relative fluorescence intensity after transfection of miR-125b mimics in VEGF wild-typ significantly decreased(P＜0.05),while the expression of relative fluores-cence intensity after transfection of miR-125b mimics in VEGF mutant significantly decreased(P＞0.05).Con-clusion miR-125b can inhibit liver angiogenesis and thus play an anti-fibrosis role,which can provide a new ref-erence for the prevention and treatment of chronic liver disease and the development of new drugs.

Diffuse large B cell lymphoma （DLBCL） is a malignant tumor derived from mature B cells. Currently， chemotherapy is still the main clinical treatment. However， some patients experience recurrence or refractory conditions after treatment. On June 15， 2023， the FDA approved the marketing of glofitamab， a CD3/CD20 bispecific monoclonal antibody， to provide the new treatment plan for patients with recurrent or refractory DLBCL after receiving 2-line or above systemic treatment. This article reviews pharmacological effects， clinical studies， safety， usage and dosage of glofitamab. Glofitamab mainly plays a therapeutic role in DLBCL by promoting the activation and proliferation of T cells，activating T cells to release tumor cell-killing proteins， and mediating the lysis of B cells. Clinical studies have shown that glofitamab has a better complete and objective response rate for recurrent or refractory DLBCL. Common adverse reactions caused by glofitamab include mild/moderate cytokine release syndrome， musculoskeletal pain， rash， fatigue， and so on，without significant drug interactions.