ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

[Objective]To construct a prediction model for brucellosis by using a deep neural network algorithm to improve the early detection.[Methods]We collected the clinical data of 202 brucellosis patients and 319 non-brucellosis patients admitted to Hohhot Occupational Disease Prevention and Treatment Hospital in 2023,and analyzed data such as gender,age,blood routine indices and clinical diagnosis.A prediction model for brucellosis was constructed by using a deep neural network algorithm and optimized through 10-fold cross-validation.Performance metrics included sensitivity,false negative rate,specificity,false positive rate,accuracy,positive predictive value,negative predictive value,F1 score,and area under the receiver operating characteristic curve(AUC).The optimal model was interpreted by using SHapley Additive exPlanations(SHAP)to clarify decision-making logic and feature influencing mechanisms.[Results]Data visualization analysis revealed no significant difference between brucellosis and non-brucellosis groups.The optimal model demonstrated good performance:sensitivity(85.3%),specificity(92.1%),accuracy(89.5%),AUC(96.6%),95%CI(0.937,0.977).SHAP analysis identified age,platelet count,mean platelet volume,basophil ratio,red blood cell distribution width,and absolute basophil count as significant predictors of brucellosis.[Conclusions]The deep neural network prediction model constructed in this study has good performance and can provide reliable support for the early diagnosis,prevention and control of brucellosis.Identification of key brucellosis-related influencing features will help further understand the pathogenesis of the disease,and this model holds promise for broad clinical application in the future.

[Objective]To construct a prediction model for brucellosis by using a deep neural network algorithm to improve the early detection.[Methods]We collected the clinical data of 202 brucellosis patients and 319 non-brucellosis patients admitted to Hohhot Occupational Disease Prevention and Treatment Hospital in 2023,and analyzed data such as gender,age,blood routine indices and clinical diagnosis.A prediction model for brucellosis was constructed by using a deep neural network algorithm and optimized through 10-fold cross-validation.Performance metrics included sensitivity,false negative rate,specificity,false positive rate,accuracy,positive predictive value,negative predictive value,F1 score,and area under the receiver operating characteristic curve(AUC).The optimal model was interpreted by using SHapley Additive exPlanations(SHAP)to clarify decision-making logic and feature influencing mechanisms.[Results]Data visualization analysis revealed no significant difference between brucellosis and non-brucellosis groups.The optimal model demonstrated good performance:sensitivity(85.3%),specificity(92.1%),accuracy(89.5%),AUC(96.6%),95%CI(0.937,0.977).SHAP analysis identified age,platelet count,mean platelet volume,basophil ratio,red blood cell distribution width,and absolute basophil count as significant predictors of brucellosis.[Conclusions]The deep neural network prediction model constructed in this study has good performance and can provide reliable support for the early diagnosis,prevention and control of brucellosis.Identification of key brucellosis-related influencing features will help further understand the pathogenesis of the disease,and this model holds promise for broad clinical application in the future.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

Objective To analyze the expression of serum microRNA(miR)-145 and miR-195 in patients with oral squamous cell carcinoma(OSCC)and their relationship with cervical lymph node metastasis.Methods A total of 102 patients diagnosed with OSCC in the hospital from January 2020 to June 2022 were selected as OSCC group.Clinicopathological parameters of OSCC patients were collected and sorted.According to whether cervical lymph node metastasis occurred,the patients were divided into a cervical lymph node me-tastasis group(43 cases)and a non-cervical lymph node metastasis group(59 cases).In the same period,79 patients with precancerous lesion were selected as the precancerous lesion group,and 86 healthy subjects with-out oral disease were selected as the healthy control group.Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of serum miR-145 and miR-195.The evaluation value of relative expression levels of serum miR-145 and miR-195 in cervical lymph node metastasis in OSCC patients was examined by receiver operating characteristic curve analysis.Results The relative expression lev-els of serum miR-145 and miR-195 in OSCC group were lower than those in precancerous lesion group and healthy control group,and the difference was statistically significant(P＜0.05).The relative expression levels of serum miR-145 and miR-195 in precancerous lesion group were lower than those in healthy control group,and the difference was statistically significant(P＜0.05).The relative expression levels of serum miR-145 and miR-195 in OSCC patients with low tumor differentiation and TNM stage Ⅲ+Ⅳ were lower than those in OSCC patients with medium/high tumor differentiation and TNM stage Ⅰ+Ⅱ,with statistical significance(P＜0.05).The relative expression levels of serum miR-145 and miR-195 in cervical lymph node metastasis group were lower than those in non-cervical lymph node metastasis group,and the difference was statistically significant(P＜0.05).The relative expression levels of serum miR-145 and miR-195 were 0.840(95％CI:0.765-0.915),0.832(95％CI:0.754-0.910)and 0.898(95％CI:0.754-0.910)of cervical lymph node metastasis in OSCC patients respectively.The specificity was 79.1％,88.4％and 77.5％,and the sensitivity was 74.6％,67.8％and 87.4％,respectively.Conclusion Serum miR-145 and miR-195 are low expressed in OSCC patients,and are related to cervical lymph node metastasis,tumor differentiation,and TNM stage in OSCC patients,which can be used as an important indicator to evaluate cervical lymph node metastasis in OS-CC patients.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.