Distribution and Drug Resistance Analysis of 2287 Strains of Pathogenic Bacteria in Children’s Blood Culture

Background: Bloodstream infection is a serious infectious disease. In recent years, the drug resistance of pathogenic bacteria to commonly used anti-infective drugs has been widely concerned, which also makes the treatment of bloodstream infection face severe challenges. Objective: To explore the distribution characteristics of blood culture-positive pathogens and the resistance to antibacterial drugs, so as to provide clinicians with accurate laboratory evidence, so as to guide clinicians to rationally apply antibiotics, improve clinical treatment effects, and reduce the emergence of drug-resistant strains. Methods: From January 2019 to June 2022, 2287 positive blood culture specimens of patients in Guangzhou Women and Children’s Medical Center were retrospectively analyzed, and the proportion of different pathogenic bacteria, the distribution of pathogenic bacteria in different departments, and the multi-drug resistance of different pathogenic bacteria were counted. Results: Among the 2287 blood culture positive samples, 1560 strains (68.20%) of gram-positive bacteria and 727 strains (31.80%) of gram-negative bacteria were strained. The top three departments in the distribution of pathogenic bacteria were pediatric intensive care unit (600 strains), pediatric internal medicine (514 strains), and pediatric emergency comprehensive ward (400 strains). The pathogens with high detection rates were: Staphylococcus epidermidis (24.09%), Staphylococcus humans (23.74%), Escherichia coli (13.21%) and Klebsiella pneumoniae (8.71%). The pathogens with high multi-drug resistance rates were: Streptococcus pneumoniae (93%), Staphylococcus epidermidis (83.76%), Enterobacter cloacae (75.61%) and Staphylococcus humans (62.43%). Conclusion: In our hospital, gram-positive bacteria were the main pathogenic bacteria in the blood culture of children patients. The children’s intensive care unit was the department with the largest distribution of pathogenic bacteria, and the multiple drug resistance rate of Streptococcus pneumoniae was the highest.

Distribution and drug resistance of pathogenic bacteria isolated from cancer hospital in 2013

Objective： To understand distribution and drug resistance of pathogenic bacteria from a specialized cancer hospital in 2013 in order to provide a basis for rational clinical antimicrobial agents. Methods： Pathogenic bacteria identification and drug sensitivity tests were performed with a VITEK 2 compact automatic identification system and data were analyzed using WHONET5.6 software.Results： Of the 1,378 strains tested, 980 were Gram-negative bacilli, accounting for 71.1%, in which Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa were the dominant strains. We found 328 Gram-positive coccus, accounting for 23.8%, in which the amount of Staphylococcus aureus was the highest. We identified 46 fungi, accounting for 4.1%. According to the departmental distribution within the hospital, the surgical departments isolated the major strains, accounting for 49.7%. According to disease types, lung cancer, intestinal cancer and esophagus cancer were the top three, accounting for 20.9%, 17.3% and 14.2%, respectively. No strains were resistant to imipenem, ertapenem or vancomycin.Conclusions： Pathogenic bacteria isolated from the specialized cancer hospital have different resistance rates compared to commonly used antimicrobial agents; therefore antimicrobial agents to reduce the morbidity and mortality of infections should be used.

Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review

To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODSA literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: “spontaneous” AND “peritonitis”. RESULTSThe initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSIONN-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.

Analysis on Distribution and Drug Resistance of Pathogenic Bacteria in ICU Patients with Nosocomial Infection from 2019 to 2021

Objective:To understand the pathogenic bacteria isolated from patients and their drug resistance changes in general ICU of the Affiliated Hospital of Hebei University,so as to provide reference for appropriate selection of antibiotics in clinical practice.Methods:A retrospective investigation was conducted to analyze the bacteriological distribution and drug resistance of nosocomial pathogens isolated from the specimens of hospitalized patients in the comprehensive ICU of the hospital from 2019 to 2021.The US technology BD Phoenix 100 automatic bacterial identification analyzer was used for bacterial identification of the pathogen samples,disk diffusion method was used for drug susceptibility test,and SPSS 22.0 software was used to analyze the trend of drug resistance.Results:A total of 970 strains of nosocomial pathogens were detected in the three years.The main pathogens were Acinetobacter baumannii(133 strains,13.71%),Klebsiella pneumoniae(106 strains,10.93%),Pseudomonas aeruginosa(83 strains,8.56%),Escherichia coli(76 strains,7.84%)and Enterococcus faecium(69 strains,7.11%).The resistance rate of Acinetobacter baumannii to antibiotics was high.Klebsiella pneumoniae,Pseudomonas aeruginosa and Escherichia coli had low resistance rates to carbapenems.The situation of bacterial drug resistance is still serious.Conclusion:The drug resistance of pathogenic bacteria collected from Class III Grade A Hospital’s patients to antibiotics was generally high.Therefore,clinical departments should strengthen the inspection of specimens of infection and drug sensitivity test in order to grasp the resistance mechanisms and drug resistance of pathogenic bacteria changes,and select appropriate antimicrobial agents according to the test results.Besides,the formation of drug-resistant strains also needs to be prevented,and the treatment of patients with severe infection needs to be improved.

Nature’s Pharmacy under Siege: Investigating Antibiotic Resistance Pattern in Endophytic Bacteria of Medicinal Plants

Antibiotic resistance poses a significant global health threat, necessitating a thorough understanding of its prevalence in various ecological contexts. Medicinal plants, renowned for their therapeutic properties, host endophytic bacteria that produce bioactive compounds. Understanding antibiotic resistance dynamics in these bacteria is vital for human health and antibiotic efficacy preservation. In this study, we investigated antibiotic resistance profiles in endophytic bacteria from five medicinal plants: Thankuni, Neem, Aparajita, Joba, and Snake plant. We isolated and characterized 113 endophytic bacteria, with varying resistance patterns observed against multiple antibiotics. Notably, 53 strains were multidrug-resistant (MDR), with 14 exhibiting extensive drug resistance (XDR). Thankuni-associated bacteria displayed 44% MDR and 11% XDR, while Neem-associated bacteria showed higher resistance (60% MDR, 13% XDR). Aparajita-associated bacteria had lower resistance (22% MDR, 6% XDR), whereas Joba-associated bacteria exhibited substantial resistance (54% MDR, 14% XDR). Snake plant-associated bacteria showed 7% MDR and 4% XDR. Genus-specific distribution revealed Bacillus (47%), Staphylococcus (21%), and Klebsiella (11%) as major contributors to MDR. Our findings highlight diverse drug resistance patterns among plant-associated bacteria and underscore the complexity of antibiotic resistance dynamics in diverse plant environments. Identification of XDR strains emphasizes the severity of the antibiotic resistance problem, warranting further investigation into contributing factors.

Distribution and drug resistance of pathogenic bacteria in emergency patients

BACKGROUND Antibiotic resistance has become a global threat for human health,calling for rational use of antibiotics.AIM To analyze the distribution and drug resistance of the bacteria,providing the prerequisite for use of antibiotics in emergency patients.METHODS A total of 2048 emergency patients from 2013 to 2017 were enrolled.Their clinical examination specimens were collected,followed by isolation of bacteria.The bacterial identification and drug susceptibility testing were carried out.RESULTS A total of 3387 pathogens were isolated.The top six pathogens were Acinetobacter baumannii(660 strains),Staphylococcus aureus(436 strains),Klebsiella pneumoniae(347 strains),Pseudomonas aeruginosa(338 strains),Escherichia coli(237 strains),and Candida albicans(207 strains).The isolation rates of these pathogens decreased year by year except Klebsiella pneumoniae,which increased from 7.1%to 12.1%.Acinetobacter baumannii is a widely-resistant strain,with multiple resistances to imipenem,ciprofloxacin,minocycline and tigecycline.The Staphylococcus aureus had high resistance rates to levofloxacin,penicillin G,and tetracycline.But the susceptibility of it to vancomycin and tigecycline were 100%.Klebsiella pneumoniae had high resistance rates to imipenem,cefoperazone/sulbactam,amikacin,and ciprofloxacin,with the lowest resistance rate to tigecycline.The resistance rates of Pseudomonas aeruginosa to cefoperazone/sulbactam and imipenem were higher,with the resistance rate to amikacin below 10%.Besides,Escherichia coli had high resistance rates to ciprofloxacin and cefoperazone/sulbactam and low resistance rates to imipenem,amikacin,and tigecycline.CONCLUSION The pathogenic bacteria isolated from the emergency patients were mainly Acinetobacter baumannii,Staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginosa,Escherichia coli,and Candida albicans.The detection rates of drugresistant bacteria were high,with different bacteria having multiple drug resistances to commonly used antimicrobial agents,guiding the rational use of drugs and reducing the production of multidrug-resistant bacteria.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Multiple drug resistance and bacterial infection

Drug resistance is becoming a great problem in developing countries due to excessive use and misuse of antibiotics. The emergence of new pathogenic strains with resistance developed against most of the antibiotics which may cause,difficult to treat infection.To understand the current scenario in different mode of infection is most important for the clinicians and medical practitioners.This article summarized some common infections and antibiotic resistance pattern found among these pathogens.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

Multi Drug Resistance Bacterial Isolates of Surgical Site Infection

Multi drug resistance microorganism is considered to be one of the major health problems. The aim of this study was to determine antibiotic susceptibility pattern of bacterial pathogens of surgical site infection. A total 250 samples were included, out of which 62.4% showed significant bacterial growth. Gram negative bacteria were 85.25% and gram positive bacteria were 14.75%;among them 65.38% of the total isolates were multi drug resistance (MDR). The age group between 31 - 40 found the highest number of isolates 22.4%. Among gram negative bacilli, the highest production of MDR was found in Acinetobacter spp. followed by Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. In gram positive cocci, the highest production of MDR was found in Staphylococcus aureus. Acinetobacter spp. was found highly susceptible to amikacin and gentamycin 20.1% followed by ofloxacin and ciprofloxacin 18.6% and 16.2% respectively. Staphylococcus aureus showed 100% sensitive to clindamycin whereas penicillin showed 100% resistance followed by amoxycillin (93.75%). Amikacine and clindamycin were drugs of choice for gram negative and gram positive bacteria respectively. This study showed that alarming increase of infections was caused by multi drug resistance bacterial organisms. It increases length of stay and may produce lasting sequelae and requires extra resources for investigations, management and nursing care. Surveillance of surgical site infection is a useful tool to demonstrate the magnitude of the problem and find out appropriate preventive methods.

Repurposing Loperamide as an Anti-Infection Drug for the Treatment of Intracellular Bacterial Pathogens

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Prox1 Suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1

Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

Diarrheal Diseases: A Review on Gastroenteritis Bacteria Global Burden and Alternative Control of Multidrug-Resistant Strains

Diarrheal diseases represent a significant and pervasive health challenge for humanity. The aetiology of diarrheal diseases is typically associated with the presence of enteropathogens, including viruses, bacteria and parasites. The implementation of preventive measures, including the maintenance of good food hygiene, effective water sanitation, and the development of rotavirus vaccines, has resulted in a notable reduction in the prevalence of the disease. However, the emergence of bacterial multidrug resistance due to the past or present inappropriate use of antibiotics has rendered bacterial infections a significant challenge. The objective of this review is threefold: firstly, to provide an overview of diarrheal diseases associated with bacteria;secondly, to offer a concise analysis of bacterial multidrug resistance on a global scale;and thirdly, to present the potential of filamentous fungi as an alternative solution to the challenge posed by multidrug-resistant strains. Campylobacter spp. is the most dangerous bacteria, followed by Shigella spp. and Vibrio cholerae in all age groups combined. However, Shigella spp. was the deadliest in children under five years of age and, together with E. coli, are the most antibiotic-resistant bacteria. With their highly developed secondary metabolism, fungi are a reservoir of natural bioactive compounds.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.

Distribution of pathogenic bacteria and antimicrobial sensitivity of eye infections in Suzhou

AIM:To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs.METHODS:The clinical data of 155 patients were retrospectively collected in this study,and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed.RESULTS:Among the 155 patients(age from 12 to 87 years old,with an average age of 57,99 males and 56 females)with eye infections(160 eyes:74 in the left eye,76 in the right eye and 5 in both eyes,all of which were exogenous),71(45.81%)strains were gram-positive bacteria,23(14.84%)strains were gram-negative bacteria and 61(39.35%)strains were fungi.Gram-positive bacteria were highly resistant to penicillin and erythromycin(78.87%and 46.48%respectively),but least resistant to vancomycin at 0.Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole(100%and 95.65%respectively),but least resistant to meropenem at 0.Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences(P<0.05)in the resistance of both to cefoxitin,cotrimoxazole,levofloxacin,cefuroxime,ceftriaxone and ceftazidime,and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria.The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva,cornea,aqueous humor or vitreous body and other eye parts.Besides,Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections.CONCLUSION:Gram-positive bacteria are the dominant bacteria in eye infections,followed by gram-negative bacteria and fungi.Considering the resistance of gramnegative bacteria to multiple drugs,monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.