AIM:The study aimed to explore the effect of curcumin(Cur)on lipopolysaccharide(LPS)-in-duced RAW264.7 cell-derived osteoclasts,together with its underlying mechanism.METHODS:An osteoclast model was established by treating RAW264.7 cells with LPS.The viability of the cells was assessed by CCK-8 assays and osteo-clast formation was evaluated by tartrate-resistant acid phosphatase(TRAP)activity.The levels of reactive oxygen species(ROS),Fe2+,glutathione(GSH),and malondialdehyde(MDA)were examined by biochemical assays.Mitochondrial morphology was assessed by transmission electron microscopy.The mRNA and protein levels of p53,glutathione peroxi-dase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)were determined by RT-qPCR and Western blot,re-spectively.RESULTS:Treatment with LPS successfully induced osteoclasts formation in RAW264.7 cells.The TRAP results showed that compared with the LPS-treated group,the number of osteoclasts and TRAP activity in the curcumin-treated group decreased dose-dependently(P<0.01).Compared with the control group,the LPS+Erastin group showed significantly increased TRAP activity(P<0.01),while after curcumin treatment,the TRAP activity declined in a dose-de-pendent manner(P<0.01).The results of the biochemical tests showed that compared with the control group,the LPS+Erastin group had significantly elevated levels of ROS,Fe2+,and MDA,while the GSH level was significantly reduced(P<0.01),and compared with the LPS+Erastin group,the ROS,Fe2+,and MDA levels in the curcumin group decreased(P<0.01)and GSH levels increased(P<0.01).These effects were all dose-dependent.Transmission electron microscopy showed that compared with the LPS group,the LPS+Erastin group had reduced mitochondrial cristae and increased mem-brane density,while after treatment with curcumin,both these effects were reversed.The RT-qPCR and Western blot re-sults showed that compared with the control group,the mRNA and protein levels of p53 in the LPS+Erastin group were sig-nificantly increased,while those of of SLC7A11 and GPX4 were significantly reduced(P<0.01).After curcumin treat-ment,the p53 mRNA and protein levels were reduced while the levels of SLC7A11 and GPX4 were increased(P<0.01).CONCLUSION:Curcumin can inhibit lipopolysaccharide-induced differentiation of RAW264.7 cells into osteoclasts,and its mechanism may be related to the inhibition of the p53/SLC7A11/GPX4 signaling pathway.

Objective To investigate the clinical characteristics of empyema caused by Streptococcus anginosus (SA).Methods The clinical data in 9 cases of SA caused empyema admitted and treated in the First Affiliated Hospital of Xi'an Medical University from January 2016 to September 2023 were analyzed ret-rospectively,summarized the clinical characteristics of empyema caused by SA.Results Among 9 patients,there were 8 males and 1 female,with a mean age of (60.8±12.8)years old.All patients had the underlying diseases,meanwhile were accompanied by fever,expectoration,chest pain and dyspnea.The onset time was (6.1±2.2)d.The hospitalization time was (19.33±7.48)d.All patients showed the increase in white blood cells (WBC),C reactive protein (CRP),procalcitonin (PCT),D-dimer (D-D) and pleural effusion lactic dehy-drogenase (LDH),and decrease in blood albumin (ALB) and pleural effusion glucose (GLU).Most of the pa-tients had elevation of adenosine deaminase (ADA) in pleural fluid.Four patients had respiratory failure.The drug sensitivity test results of pleural effusion culture suggested five patients were resistant to erythromycin and clindamycin.One patient was resistant to ceftriaxone.Nine patients were improved after symptomatic treatment such as anti-infection,closed thoracic drainage and nutritional support.Conclusion The patients with SA caused empye-ma are more common in elderly patients with underlying diseases.The incubation period is short,the hospital stay is long,the infection indexes are high,malnutrition exists,and the resistance rate to erythromycin and clindamycin is high.

Objective To observe the clinical effect of hypomethylating agents (HMAs) in the treatment of patients with intermediate- and high-risk myelodysplastic syndrome (MDS). Methods A retrospective study was conducted in 58 patients with intermediate-and high-risk MDS. The study group(25 patients) received azacitidine or decitabine for hypomethylating treatment, while the control group(33 patients) received routine symptomatic supportive treatment. The clinical efficacy, hematologic parameters, quality of life, and adverse events were observed and compared between the two groups. Results After treatment, the complete remission rate, objective response rate, and disease control rate were higher in the study group than in the control group, while the disease progression rate was lower (P < 0.05). The 1-year survival rate was 92.00% in the study group, which was higher than 75.76% in the control group, but the difference showed no statistically significant (P>0.05). After treatment, hemoglobin, white blood cell, and platelet levels were higher in both groups than before treatment, and were higher in the study group than in the control group (P < 0.05). The total incidence of adverse events was lower in the study group than that in the control group (P < 0.05). After treatment, the quality of life scores (physical function, cognitive function, emotional function, role function, and social function) were higher in the study group than those in the control group (P < 0.05). Conclusion HMAs treatment is superior to routine symptomatic supportive treatment in patients with intermediate-and high-risk MDS, and not only improves the quality of life but also has good safety.

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%-85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antineoplastic Agents, Immunological ; pharmacology ; Caco-2 Cells ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; therapy ; ErbB Receptors ; genetics ; immunology ; Female ; HT29 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Mutation ; Xenograft Model Antitumor Assays

Antineoplastic Agents, Immunological ; immunology ; pharmacology ; Cell Line, Tumor ; GPI-Linked Proteins ; antagonists & inhibitors ; immunology ; Humans ; Neoplasm Proteins ; analysis ; immunology ; Pancreatic Neoplasms ; drug therapy ; immunology ; pathology

Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third leading cause of cancer-related mortalities worldwide.In the last few years,treatments for HCC have significantly improved from a mere surgical resection to a series of minimally invasive therapies and targeted drugs.However,recurrence frequently occurs even upon curative therapeutics,and drug therapies generally produce disappointing results,with the overall prognosis dismal.This challenging clinical scenario warrants new effective and life-prolonging strategies for patients with HCC.Compemng evidence suggests that NK cells play a critical role in the immune function of the liver and in the immune defenses against HCC,indicating that HCC might be an ideal target for NK cell-based immunotherapies.To obtain comprehensive insights into the putative influence of NK cells on HCC,this paper summarizes current knowledge on NK cells in HCC and discusses the usefulness and prospects of NK cell-based immunotherapies.Critical issues that require consideration for the successful clinical translation of NK cell-based therapies are also addressed.If appropriately used and further optimized,NK cell-based therapies could dominate important roles in the future immunotherapeutic market of HCC.

Objective To explore the relationship between the immune function of cellin peripheral blood with the virureplication and hepatitiviru(HCV)-cAg expression in the patientwith chronihepatiti(CHC) .MethodPeripheral blood lymphocytesubpopulation ,HCV-Rnand HCV core antigen (HCV-cAg) in 63 healthy people undergoing the physical exami-nation (control group) and 85 caseof CHC(Chgroup) were analyzed by the flow cytometry ,real-time Pcand ELIS,respec-tively .ResultThe percentageof total cell,T4 cell,T8 cell,double negative cell(DN) and double positive cell(DP) in the Chgroup were (67 .37 ± 10 .43)% ,(37 .11 ± 10 .28)% ,(21 .63 ± 8 .87)% ,(7 .80 ± 4 .57)% and (0 .20 ± 0 .29)% , respectively ,the absolute contentwere in turn (0 .70 ± 0 .44) × 109/L ,(0 .37 ± 0 .22) × 109/L ,(0 .22 ± 0 .17) × 109/L ,(0 .08 ± 0.06)×109/Land(0.19±0.68)×107/L,respectively.TheratioofT4/T8was(2.18±1.26)% .Theresultsindicatedthatthe percentage of T8 cellin the Chpatientwadecreased obviously (P＜0 .01) ,which resulted in the ratio of T4/T8 raising(P＜0 .05);meanwhile ,the absolute contentof the total cell,T4 cell,T8 celland Dnwere all decreased obviously (P＜0 .05);moreove,the percentage of T4 celland Dnin the patientwith HCV-Rnpositive and HCV-cAg positive wasignificantly in-creased (P＜0 .05) .Conclusion When HCV replicating in the patientwith CHC,the T lymphocyte subpopulation haobviouab-normity .The low immune function or immune tolerance ofT cells may be the important cause of recurrence and uncurability of CHC.

Objective To detect the effect of chitosan gel on rectal injury which was induced by acetic acid. Methods 36 rats were anesthetized, 4% acetic acid swab was placed into the rectum (3 cm in depth for 1 min) to establish rectum injury model. These rats were divided into model control group, positive control group and drug group with 12 rats each group randomly. Chitosan gel was given to the drug group through anus with the dose of 1 575 mg·kg-1 , and hemorrhoid cream (1 575 mg·kg-1 ) was administered in the positive control group for 6 successive days. At 30 min, 1, 4, 6 day( s) after administration, 3 rats of each group were sacrificed, and were dissected, rectal injury and rectal pathology morphology changing of each group at different time points of administration were compared through visual observation. Results At 30 min, 1, 4, and 6 day(s) after administrating chitosan gel, score of rectum mucosa injury in dury group was lower than those in model control and positive control group. Pathological changes ( including epithelial tissue necrosis, mesenchyme hyperemia, hemorrhage, edema, gland injury, infiltration of inflammatory cells) were significantly slighter in drug group than in model control group and positive control group. Those lesions were restored faster in drug group than in model control group and positive control group, and there was no obvious scar. Conclusion Chitosan gel can obviously alleviate the rectal injury caused by 4% acetic acid and has therapeutic effect.

Objective To study the relationship among the genome mutation,viral protein structures and virus evolution of human Bocavirus 2(HBoV2).Methods A method of PCR was applied to detect HBoV2 genome in 205 fecal specimens collected from children who had diarrhea in Ruian region,Zhejiang province,China.HBoV2-positive specimens were chosen to further amplify the HBoV2 genome.All the tertiary structures were predicted using the Swiss-PdbViewer software,and a phylogenetic analysis was performed by the MEGA software (version 5.1).Result The positive rate of HBoV2 PCR detection in the collected 205 fecal specimens was 5.36％ (11/205).We obtained a sequence of a nearly full-length HBoV2 genome named as Ruian isolate,which is 5196 bases in length.Alignment of the Ruian HBoV2 sequence with other HBoV2 sequences in GenBank revealed that the new HBoV2 shared 99.79％ similarities with the reference genome (GenBank no NC_012042).No mutation was found in the NP1 gene,whereas sense mutation of NS1,VP1 and VP2 gene were found.Residue solvent accessibilities that relates to hydrophobic interactions were changed between the NS1 of the Ruian isolate and the reference isolate.The protein structure and location of H-bonds were different between the NS1 of the Ruian isolate and the reference isolate.The phylogenetic tree shows a clear division of the NS1,which has a potential evolution toward or a closely evolutionary relationship with the NS1 of HBoV4.Conclusion HBoV2 infection was detected in Ruian region,Zhejiang province.We found sense mutations in the HBoV2 genome of Ruian isolate.These mutations may alter HBoV2 protein structures,and may have an evolutionary significance.These findings provide data of HBoV2 genome mutation.