OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

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 explore the compatibility and medication law of Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair in ancient and modern prescriptions.Methods:Ancient prescriptions and Chinese patent medicines containing Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were retrieved from the database of ancient classic famous prescriptions 1.0 and the database of listed Chinese patent medicines 1.0 developed by the Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. Excel 2019 was used to establish a database. The ancient and modern medical record cloud platform V2.3.5 and SPSS Modeler 18.0 software were used to perform frequency statistics, association rule analysis, clustering analysis, etc. on the data.Results:Totally 79 ancient articles with Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were obtained, including 76 ancient prescriptions, involving 250 kinds of Chinese materia medica; 25 kinds of Chinese patent medicine were obtained, involving 186 kinds of Chinese materia medica. The drug properties of ancient prescriptions and modern TCM patent medicines were both mainly warm, cold and neutral. The main tastes of ancient prescriptions and modern Chinese patent medicines were pungent, sweet and bitter. And the drugs mainly belong to spleen, lung, liver and kidney meridians. Correlation analysis suggested the same high-frequency association compatibility of ancient and modern prescriptions, Poria-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Macrocephalae Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma. Both clinical symptoms and diseases associated with medicinal compatibility of ancient prescriptions were intestinal flora, edema and vomiting. The syndrome types included bladder impoundment, dampness trapped in the guardian surface, internal retention of phlegm and morbid fluid. The clinical symptoms associated with medicinal compatibility of modern TCM patent medicine were limb joints pain and edema. The diseases included rheumatic arthritis (RA) and kidney disease. The syndrome types included wind-cold-dampness RA, stagnation of collaterals and kidney yang deficiency. High frequency drug clustering yielded 4 clustered squares.Conclusion:The core indications treated by Cinnamomi Ramulus-Alismatis Rhizoma are exogenous diseases with dampness caused by syndrome types including internal storage of water-dampness, cold-dampness obstruction and so on, which can provide reference for further in-depth research and guidance on clinical medication.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.

Objective:To explore the risk factors for in-hospital mortality in patients with severe trauma and their predictive predictive value.Methods:A retrospective case-control study was used to analyze the data of 509 patients with severe trauma in the trauma database of the Trauma Center of the Second Affiliated Hospital of Soochow University from January 2017 to December 2021, including 377 males and 132 females, aged 18-94 years [53(42, 65)years]. Injury severity score (ISS) was 16-75 points [22(18, 29)points]. Injured parts included the head and neck in 409 patients (80.35%), the chest in 328(64.44%), the abdomen in 193(37.91%), the pelvis in 142(27.90%), the spine in 79(15.52%), and the limb in 247(48.53%). According to the clinical outcome during the hospital stay, the patients were divided into survival group ( n=390) and non-survival group ( n=119). Baseline and clinical data of the two groups were compared, including gender, age, cause of injury (traffic injury, fall from height, sharp instrument injury, etc.), injury site (head and neck, chest, abdomen, pelvis, spine, limb), vital signs on admission (temperature, systolic blood pressure, heart rate, respiratory rate), blood tests on admission [hemoglobin, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (FIB)], Glasgow coma scale (GCS) upon admission to the emergency room, revised trauma score (RTS) upon admission to the emergency room, ISS after whole-body CT examination, quick sequential organ failure assessment (qSOFA) score upon admission to the emergency room, and INR combined with qSOFA score. The baseline and clinical data of the survival group and the non-survival group were first compared with univariate analysis. Then, the independent risk factors of in-hospital mortality in patients with severe trauma were determined by multivariate Logistic stepwise regression (forward and backward). Based on the above data, receiver operating characteristic (ROC) curves were generated with Medcalc statistical software to analyze the efficacy of each risk factor in assessing in-hospital mortality in patients with severe trauma. Results:Univariate analysis showed that there were significant differences in age, injury site, temperature, systolic blood pressure, hemoglobin, platelet, PT, APTT, INR, FIB, GCS, RTS, ISS, qSOFA score, and INR combined with qSOFA score between the two groups ( P<0.05 or 0.01), while there were no significant differences in gender, cause of injury, heart rate, and respiratory rate between the two groups ( P>0.05). Multivariate Logistic stepwise regression analysis showed that age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score were significantly correlated with in-hospital mortality in patients with severe trauma ( P<0.01). ROC curve analysis results showed that the area under the curve (AUC) of in-hospital mortality in patients with severe trauma predicted by age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score were 0.63(95% CI 0.59, 0.68) and 0.60(95% CI 0.55, 0.64), 0.66(95% CI 0.62, 0.70), 0.73(95% CI 0.69, 0.77), and 0.75(95% CI 0.72, 0.80), respectively. Conclusions:Age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score are the independent risk factors for in-hospital mortality in patients with severe trauma. ISS and INR combined qSOFA score can better predict in-hospital mortality of patients with severe trauma than age, systolic blood pressure and APTT.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.