Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Hepatic fibrosis(HF)is a pathophysiological outcome of chronic liver injury and is characterized by excessive accumulation of extracellular matrix protein.A number of studies have confirmed that the signaling pathways formed by transforming growth factor-β1(TGF-β1)and its downstream Smad family play an important role in the occurrence and development of HF,and the traditional Chinese medicine(TCM)research targeting this pathway is currently a hot spot in the reversal of HF.Therefore,taking TGF-β1/Smads signaling pathway as the entry point,this paper reviewed the mechanism of action of TCM compound formula and single drug extract in intervening TGF-β1/Smad pathway and related factors upstream and downstream of the pathway to reverse HF in recent years,revealed the targeted therapeutic effect of TCM,and provided new strategies for clarifying the mechanism of TCM.

Objective To establish a method for the determination of lorlatinib in human plasma by two-dimensional high performance liquid chromatography.Methods In the two-dimensional high performance liquid chromatography method,one-dimensional column SX1E-1A(50 mm × 3.5 mm,5 μm)and two-dimensional column SCB-C18(125 mm × 4.6 mm,5 μm)were used with flow rates of 0.8 mL·min-1 and 1.0 mL·min-1,respectively.The column temperature was 40 ℃,The UV detection wavelength was 317 nm,and the sample size was 500 μL.This study investigated the specificity,standard curve and minimum quantification limit,precision and recovery rate,as well as stability of the method.Results The concentration of lolatinib in human plasma showed a good linear relationship in the range of 11.72-1 018.98 ng·mL-1,and the regression equation was y=944.50x-588.90(R2=0.999 7).The minimum limit of quantification was 11.72 ng·mL-1.The extraction recovery rates of the three quality control samples were 97.61％-99.86％,and the intra-day and inter-day precisions were less than 5.29％,indicating that the detection performance of the method was good.Conclusion The method has the characteristics of good stability,high sensitivity and strong anti-interference ability,and is suitable for the determination of loratinib in human plasma.

Infrared spectroscopy technology has many advantages such as high efficiency and non-destructiveness,and has an important research and application value in the field of petroleum pollutant classification and detection.In this study,a petroleum pollutant classification method by combing the discrete wavelet transform(DWT)algorithm and a one-dimensional convolutional neural network based on the Inception module(Inception-1D-CNN)was proposed.Firstly,the DWT algorithm was used to denoise the original infrared spectral data to eliminate the interference information caused by experimental environment,instrument error and manual operation.Then,the inception-1D-CNN model was used to obtain multi-scale infrared spectroscopy feature information,and then classify the petroleum pollutants.Experimental results showed that compared with preprocessing methods such as standard normal variable(SNV),adaptive iteratively reweighted penalized least squares(AirPLS),and Savitzky-Golay smoothing(S-G),the prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 3×1 was 86.6%,which was 6.6%,6.6%and 3.3%higher,respectively.The prediction accuracy of DWT algorithm combined with 1D-CNN model with a convolutional kernel size of 5×1 was 93.3%,which was 10.0%,7.0%and 3.3%higher,respectively.The prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 7×1 was 90.0%,which was 6.7%,10.0%and 3.4%higher,respectively.The prediction accuracy of the DWT algorithm combined with the inception-1D-CNN model was 100.0%,which was 10.0%,10.0%and 3.4%higher,respectively.Therefore,the DWT algorithm combined with the inception-1D-CNN model could accurately classify and predict petroleum pollutants,and provided a certain basis for the subsequent treatment of oil spills on the sea surface.

Objective To explore the effects of antenatal corticosteroids(ACS)on the outcomes of very premature infants(VPIs)and neurodevelopment during infancy.Methods A retrospective study was conducted on 190 VPIs admitted to the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University from January 2020 to December 2022.The infants were categorized into four groups based on ACS usage and dosage:no ACS group(n=18),single-course group(n=88),multi-course group(n=40),and partial-course group(n=44).The clinical outcomes,Neonatal Behavioral and Neurological Assessment(NBNA)scores at 40 weeks of corrected age,and Gesell Developmental Schedule(Gesell)scores at 1 year of corrected age were compared among the four groups.The impact of timing of ACS use on the Gesell scores of infants at 1 year of corrected age in VPIs with specific gestational ages was analyzed.Results The incidence rates of neonatal respiratory distress syndrome,bronchopulmonary dysplasia,transient tachypnea of the newborn,and neonatal pneumonia were significantly lower in the partial-course,single-course,and multiple-course groups compared with the no ACS group(P<0.008).However,there was no significant difference among the partial-course,single-course,and multiple-course groups(P>0.008).The NBNA scores(behavioral ability,active muscle tone,primitive reflexes,and general assessment)at 40 weeks of corrected age were significantly higher in the no ACS,partial-course,and single-course groups than in the multiple-course group(P<0.008).The proportion of VPIs with normal neurodevelopment at 1 year of corrected age was significantly higher in the no ACS,partial-course,and single-course groups than in the multiple-course group(P<0.008).The timing of ACS use had no significant effect on neurodevelopment at a corrected age of 1 year in infants with various gestational ages(P>0.05).Conclusions ACS is crucial for the development of the respiratory system in VPIs,but multiple courses of ACS may cause neurodevelopmental abnormalities.The impact of ACS use on neurodevelopment is independent of gestational age and the timing of ACS use.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.

Objective To investigate the distribution and antimicrobial susceptibility of clinically isolated bacteria from intensive care units(ICUs)in hospitals of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to China Antimicrobial Resistance Surveillance System,data of clinically isolated bacterial strains and antimicrobial susceptibility testing results of bacteria from ICUs reported by all member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed with WHONET 2022 software.Results From 2012 to 2021,the total number of bacteria isolated from ICUs of member units of the Hunan Province Antimi-crobial Resistance Surveillance System was 5 777-22 369,with Gram-negative bacteria accounting for 76.1％-78.0％annually.Staphylococcus aureus ranked first among isolated Gram-positive bacteria each year.The top 5 bacteria among Gram-negative bacteria were Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli,Pseudo-monas aeruginosa,and Stenotrophomonas maltophilia.Detection rate of methicillin-resistant Staphylococcus aureus showed a downward trend year by year.No Staphylococcus spp.were found to be resistant to vancomycin,teico-planin and linezolid.Detection rates of vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Entero-coccus faecium were 0.6-1.1％and 0.6％-2.2％,respectively.Resistance rates of Escherichia coli and Kleb-siella pneumoniae to imipenem were 3.1％-5.7％and 7.7％-20.9％,respectively.Resistance rates of Pseudo-monasaeruginosa and Acinetobacter baumannii to imipenem were 24.6％-40.1％and 76.1％-80.9％,respective-ly.Detection rates of carbapenem-resistant Pseudomonas aeruginosa declined year by year.Acinetobacter baumannii maintained high susceptibility to polymyxin B,with resistance rate＜10％.Conclusion Antimicrobial resistance of bacteria from ICUs is serious.Carbapenem-resistant Enterobacteriales has an upward trend after 2019.It is nece-ssary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary collaboration.

Objective To understand the antimicrobial resistance of clinically isolated Enterococcus spp.in Hunan Province.Methods Surveillance data of Enterococcus spp.resistance from member units of Hunan Provincial Anti-microbial Resistance Surveillance System from 2012 to 2021 were collected.Data were cleaned according to a unified method,and WHONET 5.6 software was adopted for statistical analysis.Results From 2012 to 2021,a total of 110 652 non-repetitive Enterococcus spp.strains were included in the analysis,mainly Enterococcus faecalis and Enterococcus faecium,accounting for 46.9％(n=37 774)and 45.9％(n=36 968),respectively,followed by En-terococcus avium(2.5％,n=1 982),Enterococcus gallinarum(1.8％,n=1 428),and Enterococcus casseliflavus(1.5％,n=1 185).The main specimen sources of Enterococcus spp.was urine(51.8％,n=57 350),followed by secretions(9.6％,n=10 660)and bile(8.5％,n=9 377).From 2012 to 2021,the resistance rates of Enteroco-ccus faecalis to ampicillin,teicoplanin,and vancomycin were 5.5％-12.0％,1.3％-2.0％,and 0.6％-1.4％,respectively.The resistance rates of Enterococcus faecium to ampicillin,teicoplanin,and vancomycin were 69.2％-85.0％,1.5％-2.8％,and 0.7％-2.5％,respectively.Except for linezolid and minocycline,the resistance rates of Enterococcus faecium to tested antimicrobial agents were all higher than those of Enterococcus faecalis.The re-sistance rates of Enterococcus faecalis and Enterococcus faecium to vancomycin decreased from 1.4％and 2.1％in 2012 to 0.6％and 0.7％in 2021,respectively,presenting a decreased trend.Conclusion Clinically isolated En-terococcus spp.maintain high antimicrobial susceptibility to vancomycin and teicoplanin.Resistance rates of Entero-coccus faecalis and Enterococcus faecium to vancomycin present decreased trends.