Ultra high performance liquid chromatography coupled with a Q Exactive hybrid quadrupole-orbitrap mass spectrometry ( UPLC-MS/MS) and multivariate statistical analysis was applied to metabonomic
study of drug-induced liver injury. This investigation focused on the liver injury in clinic which was induced by antitumor drug, traditional Chinese medicine, statins and antibiotics. After precipitated by cold acetonitrile, the serum samples were separated on a HSS T3-C18 column using water (containning 0. 01% formic acid) and acetonitrile as mobile phase by gradient elution. Based on metabonomic profiles analysis of the orthogonal projections to latent structures discriminant analysis ( OPLS-DA ) and partial least squares-discriminant analysis ( PLS-DA) , 114 endogenous metabolites had been found to have significant differences between drug-induced liver injury patients and healthy volunteers, 38 endogenous metabolites have significant difference (p<0. 001). According to the results of the OPLS-DA, MS/MS data and human metabolome database ( HMDB) , phenylalanine and dimethylguanosine had been identified as potential biomarkers related to drug-induced liver injury for early discovery and diagnosis.

Objective To establish LC‐MS/MS method for the determination of fluoxetine in human plasma .Methods After protein precipitation of acetonitrile the plasma sample was separated on an Agilent XDB‐C18 column using acetonitrile‐1 mmol/L ammonium formate(containing 0 .1% formic acid) as mobile phase by gradient elution .Detection was carried out by multiple reac‐tion monitoring(MRM) on 3200QTRAP LC‐MS/MS system .Results The assay was linear over the range 0 .30 -50 .0 ng/mL with a lower limit of quantitation of 0 .30 ng/mL .Intra‐and inter‐day precision were less than 15% ,respectively .The relative devia‐tion was in the range -2 .80% -2 .09% .The recovery of fluoxetine was more than 98% with less matrix effects .The stabilities were good .Conclusion It could be a rapid ,sensitive ,selective and reliable method for the determination of fluoxetine in human plas‐ma for therapeutic drug monitoring and pharmacokinetics .

Objective:To investigate the outcomes of the regimen with docetaxel, cisplatin, and 5-fluorouracil (TPF regimen) in chrono-chemotherapy, and evaluate the feasibility of reducing the toxicity and immunological damage in nasopharyngeal carcinoma (NPC) patients with distant metastasis at preliminary diagnosis, then to compare the advantages and disadvantages between chrono-che-motherapy and traditional chemotherapy. Methods:A total of 46 NPC patients with distant metastasis at preliminary diagnosis (UICC 2010 stage IVc) were enrolled in this study. These NPC patients were randomly divided into chrono-chemotherapy and conventional chemotherapy groups, with 23 cases for each group. TPF neo-adjuvant chemotherapy was conducted in both groups for two cycles, with 21 days to 28 days for each cycle. The following regimen was used for the chrono-chemotherapy group:docetaxel 75 mg/m2, infu-sion, d1;cisplatin 75 mg/m2, 10:00 a.m.-10:00 p.m., continuous infusion, d1-d5;and fluorouracil 750 mg/(m2 · d), 10:00 p.m.-10:00 a. m., continuous intravenous infusion, d1-d5. The following regimen was used for the conventional chemotherapy group:docetaxel 75 mg/m2, infusion, d1;cisplatin 75 mg/m2, infusion, d1;and fluorouracil 750 mg/(m2· d), continuous infusion, d1-d5, 120 h. Patients who obtained therapeutic efficacy via induction chemotherapy were provided with intensity-modulated radiotherapy as a concurrent radio-therapy and chemotherapy (DDP 100 mg/m2, infusion, d1-d2, with 21 days each cycle and a total of two courses). One month after con-current chemoradiation, an adjuvant chemotherapy with the same regimen as the induction chemotherapy was employed for a total of two courses. Acute and late toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events v3.0 scor-ing. Tumor response was evaluated using the 2000 Response Evaluation Criteria in Solid Tumors. The effective rates included complete and partial responses. Relevant data were analyzed by SPSS16.0 statistical software. Results:More emesis was observed at Grade 2 or above in the conventional chemotherapy group than in the chrono-chemotherapy group, with statistical significance between the two groups (P=0.035). After chemotherapy, the value of CD4/CD8 increased in the chrono-chemotherapy group and decreased in the con-ventional chemotherapy group, with statistical significance between the two groups (P=0.033). Conclusion:The proposed chrono-che-motherapy outperforms conventional chemotherapy in reducing the occurrence of severe vomiting. This chrono-chemotherapy may be advantageous in reducing severe bone marrow depression and may play a positive role in the immune function of NPC patients.

Objective To investigate serum complement 1q (C1q) levels in the patients with coronary artery disease (CAD),and evaluate its clinical values in predicting and discriminating acute coronary syndrome (ACS) and stable coronary artery disease (SCAD).Methods A total of 52 ACS patients,66 SCAD patients and 54 healthy controls were enrolled in this study.Their serum C1q and oxidized low-density lipoprotein (ox-LDL) levels were detected by an immune turbidimetric method and an enzyme linked immunosorbent assay,respectively.Their serum total cholesterol,triglyceride,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were also determined.Then,the Gensini scores in CAD patients were calculated,and the clinical values of Clq in predicting and discriminating ACS and SCAD were evaluated by stepwise multiple linear regression analysis and Logistic regression analysis.Results Serum C1q and ox-LDL levels in ACS (C1q:t =4.405,P＜0.001;ox-LDL:Z=5.941,P＜0.001) and SCAD (C1q:t =2.320,P=0.022;ox-LDL:Z =4.119,P ＜0.001) patients were significantly higher than those in healthy controls.Moreover,serum C1q (t =2.344,P =0.021) and ox-LDL (Z =2.166,P =0.030) levels in ACS patients were significantly higher than that in SCAD patients.Serum C1 q levels were positively correlated with serum ox-LDL (r =0.246,P =0.028) and TG (r =0.232,P =0.002) levels and Gensini scores (r =0.341,P =0.020) in ACS patients.The stepwise multiple regression analysis showed that serum ox-LDL levels were still independently correlated with serum C1 q levels in ACS patients (β =0.676,P =0.045,adjusted R2 =0.380) after adjusting for age,gender and other biochemical markers.The Logistic regression analysis showed that the increased serum C1q and ox-LDL levels were closely related to the occurrence of ACS (C1q:OR =1.05,95％ CI =1.03-1.08,P ＜ 0.001;ox-LDL:OR =1.18,95％ CI =1.08-1.29,P ＜0.001) and SCAD (C1q:OR =1.04,95％CI=1.01-1.06,P=0.003;ox-LDL:OR=I.11,95％CI=1.03-1.18,P=0.004),and that they could discriminate ACS and SCAD (C 1 q:OR =1.01,95 ％ CI =1.00-1.03,P =0.022;ox-LDL:OR =1.06,95 ％ CI =1.01-1.12,P =0.023).Conclusion Serum C1q levels increase significantly in CAD patients,and that of ACS patients is significantly higher than SCAD patients.In ACS patients,serum C1q levels are independently correlated with ox-LDL levels.Serum C1q levels may be served as a novel biomarker for the prediction and discrimination of ACS and SCAD.

OBJECTIVETo compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).

METHODSSeventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.

RESULTSSixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.

CONCLUSIONSCompared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Drug Chronotherapy ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; methods ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Nausea ; Neoplasm Staging ; Radiotherapy, Intensity-Modulated ; Taxoids ; administration & dosage ; Treatment Outcome

Objective To investigate serum levels of small dense low-density lipoprotein cholesterol (sdLDL-C)in transient ischemic attacks(TIA)patients and assess their predictive values for subsequent stroke risk after TIA.Methods Clinical case-control study.Serum sdLDL-C levels were determined in 96 TIA patients who were admitted to Jinling Hospital from January 2016 to December 2016 and 44 healthy controls who had contemporaneously visited Jinling Hospital For a routine or the routine.ABCD3-I scores in TIA patients were calculated.All TIA patients were classified into three subgroups:high-risk(8≤ABCD3-I≤13,n=23), moderate-risk(4≤ABCD3-I≤7, n=36)and low-risk(0≤ABCD3-I≤3, n=37). Total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other lipid/lipoprotein parameters in TIA patients and controls were also analyzed.Spearman correlation analyses and multivariate linear regression analyses were performed to investigate the association of serum sdLDL-C levels with ABCD3-I scores.Logistic regression analyses were performed to investigate the predictive values of serum sdLDL-C for TIA patients.Results Serum sdLDL-C levels were significantly increased in TIA patients compared with controls(t=-5.202,P<0.001).Furthermore,sdLDL-C levels in high-risk patients were significantly higher than that in moderate-risk(t=3.534, P=0.001)and low-risk(t=4.154,P<0.001)patients.Serum sdLDL-C levels were positively correlated with ABCD 3-I scores(r=0.317,P=0.002)in TIA patients.The stepwise multiple regression analysis showed that only sdLDL-C was a significant independent predictor of ABCD 3-I scores(β=0.481,P=0.032,adjusted R2=0.189), after adjusting for age, gender, blood pressure and other lipid/lipoprotein parameters.Binary Logistic analyses indicated that serum sdLDL-C levels were closely associated with TIA presence(OR=2.84,95%CI =1.42 -5.70, P=0.003), after adjustment with age, gender, blood pressure and other lipid/lipoprotein parameters.Conclusions Serum sdLDL-C levels were increased in TIA patients.The significantly independent associations of sdLDL-C levels with ABCD3-I scores were observed.Serum sdLDL-C levels may contribute to assessing subsequent stroke risk after TIA.(Chin J Lab Med,2018,41:316-320)

Objective To determine the anti-lung cancer effect of koumine(KOU)and total alkaloids of Gelsemium elegans Benth(TAG)and investigate the underlying mechanism.Methods After low,medium and high concentrations(100,150,200 μg/mL)of KOU were used to treat human lung adenocarcinoma cell lines A549 and SPCA1,Live Cell Imaging and Analysis by Sartorius colony formation assay was employed to detect the cell proliferation.The transplanted tumor model of lung cancer cells in mice was constructed and divided into model group(model group),cyclophosphamide group(CTX group,20 mg/kg),KOU group(2 mg/kg)and TAG group(0.5 mg/kg).After the mice of the CTX,KOU and TAG groups were intraperitoneally injected with 0.1 mL/10 g corresponding agents every other day for 10 d,the growth of lung cancer solid tumors was observed grossly and with HE staining,immunohistochemical(IHC)assay and TUNEL staining to and calculate the tumor size and growth inhibitory rate.RNA sequencing analysis was performed on A549 cells treated with TAG for 48 h to screen the differentially expressed genes(DEGs)between the treatment group and the control group,and the obtained DEGs were further analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)functional enrichment analyses.RT-qPCR was applied to further analyze and verify the expression of related genes.Results Live Cell Imaging and Analysis fitted that the confluence of A549 and SPCA1 cells was decreased and the number of cells in the treated groups was observed to decrease,with poor growth.The results of colony formation assay confirmed that KOU reduced the number of cell clones,especially at a dose of 200 μg/mL(P＜0.01).Animal experiments showed that KOU and TAG treatment inhibited the tumor growth by 24.55％and 36.08％,respectively.TAG treatment resulted in significantly decreased tumor size when compared with the model group(P＜0.05).RNA sequencing analysis revealed that there were totally 2 793 DEGs,including 1 433 up-regulated genes and 1 360 down-regulated ones.Enrichment analysis displayed that the DEGs were mainly enriched in IL-17 signaling pathway,tumor necrosis factor signaling pathway and P53 signaling pathway.The results of RT-qPCR were consistent with the results of RNA sequencing analysis.The expression levels of GADD34,ZFP36,GADD45 A,GADD45 B and TP53INP2 genes were significantly increased in the TAG group(P＜0.01).Conclusion Alkaloids of Gelsemium elegans Benth inhibits the proliferation of lung cancer in vivo and in vitro.Transcriptomics find that KOU and TAG inhibit multiple DEGs and pathways of lung cancer.

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children′s Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher′s exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2=0.021, P=0.885). The positive rates of Mp increased with age ( χ 2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

Objective To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5?fluorouracil (5?Fu ) ] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal ( NPC) . Methods Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups:the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21?28?days/cycle. The chronochemotherapy group:DOC:75 mg/m2, i.v. gtt, d1 (03:30?04:30);DDP:75 mg/m2,10 am?10 pm,c.i.v,d1?d5;5?Fu:750 mg·m-2·d-1,10 pm?10 am, c.i.v., d1?d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group:Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5?Fu was given at a dose of 750 mg/m2 for 24 hours from d1?d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose ( GTVnx) was 69. 96 Gy/33 fractions for the T1?T2 nasopharygeal cancer, while 73. 92 Gy/33 fractions nasopharynx lesion dose ( GTVnx) for the T3?T4 nasopharyngeal cancer. The planning target volume ( PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i.v. gtt. d1?d2, and there were two cycles in total and 21 days each cycle. Results Sixty?six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group ( P=0.040) . Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono?chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+/CD8+ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group ( P<0. 05 ) . The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group. Conclusions Compared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.