Objective To investigate the expression and roles of serine/threonine and tyrosine kinases(TTK)and mouse dual microbody 2(MDM2)in cervical lesion tissue.Methods Patients(n=180)who underwent gynecological surgery at the First Affiliated Hospital of Henan University of Science and Technology from June 2022 to January 2024 were evaluated,including 50 patients in the cervical cancer group,50 patients in the high-grade lesion group,40 patients in the low-grade lesion group,and 40 patients in the non-cervical lesion(control)group.The mRNA expression and protein levels of TTK and MDM2 in each group were detected and compared by real-time quantitative PCR and immunohistochemistry,respectively.The diagnostic value of the mRNA expression levels of TTK and MDM2 in cer-vical cancer was analyzed using receiver operating characteristic curves.Results The mRNA levels of TTK and MDM2 significantly dif-fered among the four groups(P＜0.05);with increases in the lesion grade,the mRNA levels of TTK and MDM2 increased gradually and showed significant differences(P＜0.05).Immunohistochemical results showed that TTK was mainly located in the cytoplasm,whereas MDM2 was mainly located in the nucleus,with positive expression rates in cervical cancer tissues of 84.00％and 90.00％,respectively.These values were higher than those in other pathological tissues(P＜0.05).The mRNA levels of TTK and MDM2 were significantly cor-related with the degree of differentiation and lymph node metastasis(P＜0.05).The receiver operating characteristic curve showed that the areas under the curve of TTK and MDM2 mRNA for diagnosing cervical cancer were 0.803 and 0.798,respectively.Additionally,the area under the curve of the combined diagnosis was 0.912,which was higher than that observed for single detection(Z=2.230,2.553,P＜0.05).Conclusion The mRNA expression of TTK and MDM2 and their corresponding protein levels were increased in cervical lesions,demonstrating their potential as biological indicators for the clinical diagnosis of cervical cancer.

The platelets play the important role in tumor angiogenesis,growth,and metastasis,in addition to coagulation.The interaction between tumors and platelets can produce"tumor-induced platelets",which leads various changes of platelet characteristics.In addition,activated platelets can also inhibit the effects of both chemotherapy and immunotherapy,therefore,both inhibiting platelet activation and depleting platelets can effectively improve tumor prognosis.In this review,we intro-duced the key role of platelets in the development of tumors,summarized their application in tumor diagnosis,monitoring,and treatment,and provid-ed our view on how to develop precise delivery strategies based on platelets for achieve efficient and safe tumor treatment.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To establish the method of bacterial endotoxin detection for raw materials and injections of paliperidone palmitate.Methods:Paliperidone palmitate was dissolved with tetrahydrofuran and polysorbate 20 as solvent,and then diluted with BET H2O.According to bacterial endotoxin test in Chinese Pharmacopoeia 2020 Vol general charpters 1143,methodology validation of chromogenic substrate method in bacterial endotoxin test was con-ducted and then the interference experiment of solubilizer was added.Results:Paliperidone palmitate did not pre-cipitate during the experimental process,and then diluted to 0.007 mg·mL-1 with BET H2O.There was no inter-ference for chromogenic substrate method,while the bacterial endotoxin recovery of the solubilizer does not interfere with endotoxin testing.Conclusion:The method established in this paper is suitable for bacteria endotoxin test of raw materials and injections of paliperidone palmitate.

Objective:To establish the method of bacterial endotoxin detection for raw materials and injections of paliperidone palmitate.Methods:Paliperidone palmitate was dissolved with tetrahydrofuran and polysorbate 20 as solvent,and then diluted with BET H2O.According to bacterial endotoxin test in Chinese Pharmacopoeia 2020 Vol general charpters 1143,methodology validation of chromogenic substrate method in bacterial endotoxin test was con-ducted and then the interference experiment of solubilizer was added.Results:Paliperidone palmitate did not pre-cipitate during the experimental process,and then diluted to 0.007 mg·mL-1 with BET H2O.There was no inter-ference for chromogenic substrate method,while the bacterial endotoxin recovery of the solubilizer does not interfere with endotoxin testing.Conclusion:The method established in this paper is suitable for bacteria endotoxin test of raw materials and injections of paliperidone palmitate.

Animal models of TCM syndromes are the important carriers of revealing the basic theory of traditional Chinese medicine(TCM)and promoting the clinical development of TCM,and are indispensable tools to promote the modernization and internationaliza-tion of TCM.At present,the establishment methods of TCM syndrome animal model are varied and the evaluation criteria are different.Based on the main physiological functions of the five viscera,this paper summarized and analyzed the construction and evalu-ation methods of the most commonly used animal models of TCM syndromes in recent years,represented by the common clinical heart-qi deficiency syndrome,liver stagnation syndrome,spleen-qi deficiency syndrome,lung-qi deficiency syndrome and kidney-yang de-ficiency syndrome,in order to provide reference for establishing a more scientific and objective animal model construction method and evaluation system of TCM syndromes.

Objective To investigate the expression and roles of serine/threonine and tyrosine kinases(TTK)and mouse dual microbody 2(MDM2)in cervical lesion tissue.Methods Patients(n=180)who underwent gynecological surgery at the First Affiliated Hospital of Henan University of Science and Technology from June 2022 to January 2024 were evaluated,including 50 patients in the cervical cancer group,50 patients in the high-grade lesion group,40 patients in the low-grade lesion group,and 40 patients in the non-cervical lesion(control)group.The mRNA expression and protein levels of TTK and MDM2 in each group were detected and compared by real-time quantitative PCR and immunohistochemistry,respectively.The diagnostic value of the mRNA expression levels of TTK and MDM2 in cer-vical cancer was analyzed using receiver operating characteristic curves.Results The mRNA levels of TTK and MDM2 significantly dif-fered among the four groups(P＜0.05);with increases in the lesion grade,the mRNA levels of TTK and MDM2 increased gradually and showed significant differences(P＜0.05).Immunohistochemical results showed that TTK was mainly located in the cytoplasm,whereas MDM2 was mainly located in the nucleus,with positive expression rates in cervical cancer tissues of 84.00％and 90.00％,respectively.These values were higher than those in other pathological tissues(P＜0.05).The mRNA levels of TTK and MDM2 were significantly cor-related with the degree of differentiation and lymph node metastasis(P＜0.05).The receiver operating characteristic curve showed that the areas under the curve of TTK and MDM2 mRNA for diagnosing cervical cancer were 0.803 and 0.798,respectively.Additionally,the area under the curve of the combined diagnosis was 0.912,which was higher than that observed for single detection(Z=2.230,2.553,P＜0.05).Conclusion The mRNA expression of TTK and MDM2 and their corresponding protein levels were increased in cervical lesions,demonstrating their potential as biological indicators for the clinical diagnosis of cervical cancer.

Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer.Methods A colitis-cancer model was established in C57BL/6 mice using azoxymethane(AOM)combined with dextran sulfate sodium(DSS).Samples were collected at 7,10,and 14 weeks post-modeling and the spleen index,colon length,mass,and colon mass per unit length were measured.Histopathological changes in the colon were observed by hematoxylin and eosin and Masson staining.Expression levels of the cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b,Lrp5,Axin2,and Znrf3 at different pathological stages were detected by reverse transcription quantitative real time PCR.Cancer-associated fibroblasts(FAP),CD44,the proliferation marker Ki67,and goblet cell MUC2 protein were detected by multiple immunofluorescence histochemistry(mIHC)and immunofluorescence.In addition,colon organoids were isolated from model mice at ten and fourteen weeks and cultured in vitro to observe changes in organoid morphology and marker expression.Results AOM/DSS-induced mice showed reduced,distorted,and branched colon crypt structures with a few collagen fibers at 7 weeks,and varying degrees of colon intraepithelial neoplasia,with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining at ten and fourteen weeks.mRNA levels of CD44 and Wnt2b in the colon were significantly increased(P＜0.05)and Axin2 was decreased(P＜0.01)in model mice compared with control mice at fourteen week,and levels of Wnt2b,Lrp5,and Znrf3 were increased compared with seven-week mice(P＜0.01,P＜0.05,P＜0.01),and Axin2 was decreased(P＜0.01).mIHC staining showed increased expression of FAP and CD44 in the colon in model mice at ten and fourteen weeks,with decreased MUC2 expression.Colon organoids showed cystic dilation,especially at fourteen weeks,with more prominent expression of Ki67 and CD44.Conclusions The AOM/DSS-induced mouse model exhibited chronic colonic inflammation,low-grade intraepithelial neoplasia,and high-grade intraepithelial neoplasia at seven,ten,and fourteen weeks,respectively.The pathological microenvironment was characterized by fibroblast activation and abnormal proliferation of epithelial cells.

The platelets play the important role in tumor angiogenesis,growth,and metastasis,in addition to coagulation.The interaction between tumors and platelets can produce"tumor-induced platelets",which leads various changes of platelet characteristics.In addition,activated platelets can also inhibit the effects of both chemotherapy and immunotherapy,therefore,both inhibiting platelet activation and depleting platelets can effectively improve tumor prognosis.In this review,we intro-duced the key role of platelets in the development of tumors,summarized their application in tumor diagnosis,monitoring,and treatment,and provid-ed our view on how to develop precise delivery strategies based on platelets for achieve efficient and safe tumor treatment.