Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells（BMSC-exos） modified with Bushen Yisui capsule（BSYS）-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups， including the normal（NC） group， BMSC-exos group， BSYS-BMSC-exos group， BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group， and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay（CCK-8）. Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos， and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR） detection of miR-15b-5p. The expressions of 2′，3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） and myelin proteolipid protein（PLP） in OLN-93 cells were detected by immunocytochemistry（ICC） and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR， and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells， including glycogen synthase kinase（GSK）-3β， β-catenin， and T-cell specific transcription factor 4/transcription factor 7-like 2（TCF4/TCF7L2）， were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L^-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability（P<0.01） and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs， Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs（P<0.01）， and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos（P<0.01）. ICC analysis further revealed an increase in the number of differentiated， mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment（P<0.01）. Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment（P<0.01）. Additionally， BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells， while decreased the mRNA and protein expressions of Wnt3a， as well as the mRNA expressions of β-catenin and TCF4/TCF7L2， and the protein expression level of p-GSK-3β（Ser9） was significantly reduced（P<0.05， P<0.01）. After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos， the above effects were significantly diminished（P<0.05， P<0.01）. ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells， and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells， which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.

Objective To investigate the changes of OAT expression in bone cells in chronic renal failure(CRF)and involved mechanism,and to explore the effect of OAT expression on bone metabolism.Methods Ra-ndomly divide the rats into a control group(n=6)and a model group(n=6).The model group established a rat chronic renal failure model using"single nephrectomy+adenine gavage"method,and the red blood cell(RBC)and hemoglobin(HGB)of the rat body were measured using a blood routine analyzer;Measure indicators such as creatinine(Cr),urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),and blood phosphorus(P3+)using a fully automated biochemical analyzer;Pathological examination of rat kidneys;X-ray examination of rat tibia;Immunohistochemical examination of bone tissue OAT1 level.Results The bone density of the model group rats is lower than that of the control group;The calcium and phosphorus metabolism of rats in the model group was in metabolic disorder,and the OAT1 value of bone tissue binding was much lower than that of the control group(P= 0.0018),which was statistically significant.(P=0.0018)Conclusion Chronic renal failure affected the binding ability of OAT1 in bone tissue,leading to the metabolic disorder for calcium absorption and phosphorus metabolism,thus aggravating renal osteodystrophy(P<0.05).

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

Objective:To explore the expression and clinical significance of heme oxygenase-1 (HO-1) and quinone oxidoreductase (NQO-1) in children with different severity levels of mycoplasma pneumoniae (MP) infection.Methods:A total of 140 children with MP infection who were treated at the Affiliated Hospital of Jining Medical University from January to June 2022 were selected as the observation group, while 100 healthy children who underwent physical examination were selected as the control group. The serum levels of interleukin-2 (IL-2), IL-6, IL-10, IL-1β, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), HO-1, and relative expression of NQO-1 protein were compared between the control group and the observation group, as well as between children with different degrees of MP infection, Forced vital capacity (FVC), maximum expiratory volume in the first second (FEV 1), peak expiratory flow rate (PEF), 50% forced expiratory flow rate and maximum mid expiratory flow rate (MEF 25-70), 50% forced expiratory flow rate (MEF 50), and 25% forced expiratory flow rate (MEF 25). Pearson correlation method was used to analyze the correlation between the expression of HO-1 and NQO-1 with inflammatory factors and lung function indicators. The receiver operating characteristic (ROC) curve was used to analyze the value of HO-1 and NQO-1 expression in predicting severe MP. Results:The serum levels of IL-2, IL-6, IL-10, IL-1β, TNF-α, IFN-γ, and HO-1 in the observation group were significantly higher than those in the control group (all P<0.05), while the relative expression level of NQO-1 protein was significantly lower than that in the control group ( P<0.05). The FVC, FEV 1, PEF, MEF 25-70, MEF 50, and MEF 25 in the observation group were significantly lower than those in the control group (all P<0.05). The serum levels of IL-2, IL-6, IL-10, IL-1β, TNF-α, IFN-γ, and HO-1 in the observation group of severe children were significantly higher than those in mild children (all P<0.05), while the relative expression of NQO-1 protein, FVC, FEV 1, PEF, MEF 25-70, MEF 50, and MEF 25 were significantly lower than those in mild children (all P<0.05). HO-1 in children with MP infection is positively correlated with IL-6, IL-1β, and IFN-γ, while the relative expression level of NQO-1 protein is negatively correlated with IL-6, IL-1β, and IFN-γ (all P<0.05); HO-1 was negatively correlated with MEF 50 and MEF 25, while the relative expression level of NQO-1 protein was positively correlated with MEF 50 (all P<0.05). The area under the ROC curve for predicting the relative expression levels of HO-1 and NQO-1 proteins in severe MP was 0.871 and 0.934, respectively (all P<0.05). Conclusions:The expression of serum HO-1 and NQO-1 in children with MP infection is correlated with cytokines and lung function indicators, and has certain application value in predicting severe illness.

Objective To understand the current status and influencing factors of patient perception for humanistic care in China hospitals,and to provide a basis for developing nursing humanistic care measures and improving the quality of nursing humanistic care services.Methods A total of 30,099 outpatients and inpatients from 107 hospitals in 30 provinces(autonomous regions and municipalities)from July to August 2022 as survey subjects.A general information questionnaire and the Relational Caring Questionnaire-Patient Form were used for a cross-sectional survey,and a single-factor analysis was used to analyze the influencing factors of patient relationship care.Results Finally,29 108 valid questionnaires were collected,and the effective questionnaire recovery rate was 96.7％.The patient evaluation of relationship care was(65.72±8.61)points.Single-factor analysis showed that gender,age,marital status,children's situation,education level,occupation,place of residence,average family income,medical insurance type,visiting department,and location of the visiting hospital,and whether or not surgery were influencing factors of patient relationship care(P＜0.05).Conclusion The evaluation score of caregiver-patient relationship care among Chinese hospital patients is above average,but there is still room for improvement in western and rural regions,seriously ill and outpatient patients,low-income and low-medical insurance reimbursement populations,and non-surgical patients.Medical institutions at all levels should optimize and improve nursing humanistic care services based on influencing factors,and further enhance patients'perception of nursing humanistic care.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To evaluate the effect of different operation methods on the early swallowing function in the patients with laryngocarcinoma.Methods A total of 138 patients with the first time of open laryngectomy in this hospital from January 2021 to December 2022 were selected as the research subjects by convenience sampling method.The patients were divided into the vertical laryngeal resection group(vertical group,n=34),horizontal laryngeal partial resection(horizontal group,26 cases),suprachloroid laryngeal par-tial resection annular hyoid epiglottis fixation group(SCPL-CHEP group,n=26)and total laryngeal resection group(total laryngeal group,n=52)according to the operation methods.The Anderson Dysphagia Scale,Syd-ney Dysphagia Scale and modified swale drinking water test were used to evaluate the swallowing function on the first day of postoperative oral feeding in the patients.Results The total scores and scores of various di-mensions of the Chinese version of Anderson Dysphagia Scale,total scores and scores of various dimensions of Sydney Swallowing Scale and the results of the modified swale drinking water test had statistical differences a-mong the various groups(P＜0.01);the above indexes had statistical difference between the total laryngeal group and the other groups(P＜0.01),but the above indexes had no statistical difference between the two groups in the horizontal group,vertical group and SCPL-CHEP group(P＞0.05).Conclusion In the patients with laryngeal cancer undergoing open laryngectomy,the dysphagia is less severe during early eating after to-tal laryngectomy,which has little impact on life.

Objective The objective of this study was to investigate the effects of propofol on glycolysis of lung cancer,and to further explore its potential mechanism of inhibiting glycolysis in lung cancer through glucose transporter 4(GLUT4).Methods Human lung cancer A549 cells and mouse lung cancer LLC cells were cultured,and the experimental groups were set as the blank control group(Control group)and propofol(10μmol/L)group(Propofol group).The CCK-8 assay was used to detect cell viability;Immunofluorescence(IF)was used to detect the expression of Ki-67 in lung cancer cells and A549 cell xenografts.Extracellular acidi-fication rate(ECAR)and mitochondrial oxygen consumption(OCR)assays were used to detect the cellular metabolic levels;ELISA was used to detect the cell lactate and pyruvate content;Molecular docking experiments were used to detect the binding ability of GLUT4 with propofol using CB-Dock online tool;The glucose uptake kit was used to detect glucose uptake;Western blot was used to detect the expression of GLUT4,HK2,and PFK1 proteins in lung cancer cells.Results The cell viability of A549 cells(0.661±0.052)and LLC cells(0.632±0.033)in the propofol group was significantly inhibited by 10 μmol/L of propofol in lung cancer cells(P＜0.001).Compared with the control group,the average fluorescence intensity of Ki-67 in A549 and LLC positive cells(0.663±0.064 and 0.540±0.070)was significantly suppressed(P＜0.001).The ELISA results showed that compared with the control group,the levels of lactate and pyruvate in the propofol group decreased(P＜0.001),and under the action of propofol,the glucose uptake ability of cells decreased(P＜0.001).Molecular docking experiments using the CB-Dock online tool showed that GLUT4 had the strongest binding force with propofol.The results of Western blot showed a decrease in the expression of GLUT4 and its downstream HK2 and PFK1 pro-teins.After transient transfection and knockdown of GLUT4,cellular lactate(P＜0.001)and pyruvate content(P＜0.01)decreased,glu-cose uptake capacity reduced,and the inhibitory effect of propofol on glycolysis disappeared.In A549 cell xenografts,the weight of xenografts in the propofol group was significantly smaller than that of the model group(P＜0.001).Compared with the model group,the lactate content and pyruvate content decreased in the propofol group(P＜0.001).Conclusion Propofol can inhibit the proliferation of lung cancer cells and the progression of A549 cell xenografts in bearing mice by inhibiting the glycolysis of lung cancer cells,and its mechanism may be related to the targeted effect of GLUT4 on the glycolysis of lung cancer cells.

Objective:To establish a Plaque-reduction Neutralization Test (PRNT) for the detection of neutralizing antibody titers of Human Respiratory Syncytial Virus (HRSV) and optimize the conditions for preliminary application.Methods:The CHO expression system was used to produce palivizumab monoclonal antibody (palivizumab) and the influencing factors such as cell type, cell culture duration, fixation and permeabilization protocols, and blocking agents. The reproducibility of the method was verified and its correlation was verified with conventional PRNT. Finally, the optimized PRNT assay was further used to determine neutralizing antibody titers against HRSV subtypes A and B in BALB/c mouse serum (immunized by intramuscular injection of HRSV fusion proteins).Results:Palivizumab was expressed at approximately 50 mg/L. The optimal working conditions for PRNT were as follows: culturing HEp-2 cells for 2 days, fixing with 4% (V/V) paraformaldehyde at room temperature for 15 min followed by 0.2% (V/V) Triton X-100 permeabilization for 15 minutes as the optimal fixation-permeabilization and removing the blocking step. The overall coefficient of variation (CV) for the reproducibility validation of this method was <15%, showing a good linear relationship with the conventional PRNT. The Spearman correlation coefficient r s was 0.983. This method was used to detect neutralizing antibody titers in mouse sera against HRSV subtype A strain long and subtype B strain 9320, and the fusion proteins combined with AlOH and CpG adjuvant induced the highest neutralizing antibody titers in mice. Conclusion:The HRSV neutralizing antibody assay established in this study is rapid, reproducible, high-throughput, and can be used to detect neutralizing antibodies to HRSV subtypes A and B.