Clinical Features of Traditional Chinese Medicine Syndrome Elements in Patients with Multi-Drug Resistant Bacterial Pneumonia:A Retrospective Analysis of 126 Cases / 广州中医药大学学报

Objective To explore the distribution of traditional Chinese medicine(TCM)syndrome elements in patients with multi-drug resistant bacteria-infected pneumonia.Methods Clinical data of 126 patients with multi-drug resistant bacteria-infected pneumonia admitted to the intensive care unit of Lung Disease Centre of Qingdao Hospital of Traditional Chinese Medicine from May 2020 to July 2022 were retrospectively collected.The clinical data included the patients'gender,age,underlying diseases,history of bad additions of smoking and alcohol,multi-drug resistant bacteria,and the information of four diagnostic methods of TCM,etc.The disease-nature syndrome elements in patients with drug-resistance to various strains of drug-resistant bacteria were extracted,and then deficiency-excess syndrome differentiation was carried out.Results(1)A total of 201 strains of multi-drug resistant bacteria were detected in 126 patients with multi-drug resistant bacterial pneumonia.The main pathogenic species were Gram-negative bacteria,and the proportion accounted for 95.52%(192/201),which was significantly higher than that of Gram-positive bacteria[4.48%(9/201)],with a statistically significant difference(χ2 = 166.612,P＜0.001).Klebsiella pneumoniae accounted for the highest percentage of 23.38%in the gram-negative bacterium.(2)A total of 12 syndrome elements were extracted from the 126 patients.The excess syndrome elements were predominated by phlegm and heat,and the deficiency syndrome elements were predominated by yin deficiency.There was no statistically significant difference in the distribution of yin deficiency,blood deficiency,heat,phlegm,fluid-retention and damp syndrome elements among patients with different strains of drug-resistant bacterial infection(P＞0.05).(3)Of the 126 patients,62 cases(49.21%)had simple excess syndrome,one case(0.79%)had simple deficiency syndrome,and 63 cases(50.00%)had concurrent deficiency-excess syndrome.Among the 126 patients,there were 19 cases of single syndrome element,41 cases of concurrent two-syndrome element,49 cases of concurrent three-syndrome element,16 cases of concurrent four-syndrome element,and one case of concurrent five-syndrome element.And the combined syndrome element of phlegm-heat-yin deficiency occurred most frequently for 26 times.Conclusion Gram-negative bacteria are the primary infectious pathogens for the patients with multi-drug resistant bacterial infections,and the TCM syndrome elements of the patients are characterized by the concurrence of deficiency and excess and simple excess syndrome,mainly manifesting as phlegm,heat,and yin deficiency.

Research progress of extra-genitourinary system infections caused by Mycoplasma hominis and Ureaplasma urealyticum / 中华临床感染病杂志

It is generally accepted that Mycoplasma hominis and Ureaplasma urealyticum are primarily found in the genitourinary tract and rarely enter the tissues and bloodstream. In recent years，cases of extra-genitourinary system infections caused by Mycoplasma hominis and Ureaplasma urealyticum have been increasing with a trend of multi-drug resistance，while detection and diagnosis are difficult，leading to treatment delay clinically. This article reviews the latest research progress on the pathogenic characteristics，laboratory diagnosis，infection types，and treatment options of extra-genitourinary system infections caused by Mycoplasma hominis and Ureaplasma urealyticum，in order to provide reference for etiological diagnosis and treatment of the infection.

Drug resistance and homology of diarrheagenic Escherichia coli in sentinel hospital of Fengxian District of Shanghai， 2019‒2022 / 上海预防医学

ObjectiveWe conducted a drug resistance and homology analysis of diarrheagenic Escherichia coli （DEC） in Fengxian District of Shanghai in order to provide a basis for clinical rational drug use， risk monitoring and early warning. MethodsDEC were isolated from diarrheal patients in Fengxian District， Shanghai from 2019 to 2022. The minimum inhibitory concentrations （MIC） of 21 drugs to the DEC were determined. Genotyping and homology analysis were conducted with pulsed-field gel electrophoresis （PFGE）. ResultsThe DEC detection rate of diarrhea cases was 18.99% （131/690）， including enteroaggregative E.coli （EAEC） 64.89% （85/131）， enterotoxigenic E.coli （ETEC） 22.14% （29/131）， enteropathogenic E.coli （EPEC） 12.21% （16/131）， and enterohemorrhagic E.coli （EHEC） 0.76%（1/131）. The DEC detection showed obvious seasonal characteristics with a high incidence in summer. The DEC multidrug resistance rate was 66.41% with a total of 65 drug resistance profiles. The five antimicrobial drugs with the highest resistance rate were ampicillin （60.31%）， nalidixic acid （51.91%）， cefazolin （50.38%）， tetracycline （44.27%）， and cotrimoxazole （35.11%）. The rate of DEC resistance to levofloxacin was significantly increased from 2019 to 2022. Cluster analysis showed that the similarity of 85 EAEC cluster was 58.4%‒100.0%， and 69 band patterns were obtained. The similarity of 29 ETEC cluster was 58.5%‒100.0%， and 13 band patterns were obtained， including 2 dominant band types. The similarity of 16 EAEC clusters was 53.9%‒100.0%， and 15 band patterns were obtained. Five groups of homologous strains were found， consistent with the resistance phenotypes. ConclusionAmong the diarrhea cases， the DEC epidemic intensity is high， the drug resistance situation is severe， and the risk of outbreak infection is high in Fengxian District， Shanghai. Therefore， health monitoring and prevention need to be strengthened.

Drug resistance and molecular typing characteristics of Klebsiella pneumoniae in meat food and diarrhea samples in a local area / 上海预防医学

ObjectiveTo determine the drug sensitivity and molecular typing characteristics of Klebsiella pneumoniae isolated from meat and diarrhea samples in a local area. MethodsSeventy-one strains of K.pneumoniae were isolated from 118 meat food （chicken and pork） randomly sampled in the markets in Jinshan District， Shanghai， 2020‒2021， and 1 499 diarrhea samples from outpatient diarrhoea patients in hospitals in the same district. Then drug susceptibility testing was conducted by micro-broth dilution method， and sequence identity was determined by pulsed field gel electrophoresis（PFGE）. ResultsThe overall detection rate of K.pneumoniae in meat was 11.86% （14/118）， with detection rate 20.93% （9/43） in chicken and 6.67% （5/75） in pork. The difference in detection between meats was statistically significant （χ2=5.317，P<0.05）. The detection rate of K.pneumoniae in diarrhea samples was 3.80% （57/1 499）. Furthermore， the isolated strains showed the highest resistance to ampicillin at 76.06%. The multi-drug resistant strains included 5 of human origin （8.77%） and 2 of foodborne origin （14.28%）. Additionally， 1 foodborne imipenem-resistant strain was detected. A total of 71 strains of K.pneumoniae were found to have 70 banding types， with similarity ranging from 39.4% to 100%， suggesting genetic diversity. ConclusionK.pneumoniae isolated from foodborne and diarrhea samples showed multi-drug resistance in Jinshan District， . with scattered PFGE banding patterns. It is recommended to strengthen the monitoring of this pathogen in the population and animal food， and be alert to the emerging multi-drug resistant strains and risk of food chain transmission.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Detection mecA gene and Staphylococcus aureus resistance to several antibiotics isolated from cat ear swabs at a veterinary hospital located at Surabaya ­ Indonesia / Detecção do gene mecA e resistência a diversos antibióticos em Staphylococcus aureus isolados do ouvido de gatos em um hospital localizado em Surabaya ­ Indonesia

Cats are susceptible to S. aureus, which mainly colonizes the nose and ears of these feline species. Otitis externa in cat ears is one of the illnesses produced by S. aureus in animals. Antibiotic therapy for affected animals is the conventional treatment for infections by S. aureus. Antibiotic use during prolonged treatment and given at the wrong doses can cause germs to become resistant. Given this context, research on S. aureus isolated from cat ears and tests for antibiotic resistance and the mecA gene is required. Samples of cat ears were obtained from the Amies media using a sterile cotton swab. Bacterial isolation was done on MSA media, and then the catalase and coagulase assays were used to identify the bacteria. S. aureus isolates were evaluated for sensitivity using disks of the antibiotics cefoxitin, tetracycline, erythromycin, gentamicin, and chloramphenicol connected to MHA media. All positive isolates of S. aureus underwent MRSA testing, and then the mecA gene was detected. The sample investigation revealed that 91% (91/100) were positive for S. aureus, and 3.30% (3/91) were confirmed to be multidrug-resistant (MDR) because they are resistant to 3­4 antibiotic classes. Out of the 12 MRSA isolates analyzed, the mecA gene was detected in one isolate. Inappropriate antibiotic use causes bacterial resistance in pets. Additionally, excessive antibiotic use in a population might develop acquired bacterial resistance to an antibiotic. Antibiotic use in animals must be assessed to administer medication and prevent the development of antibiotic resistance appropriately.(AU)

Gatos são suscetíveis a adquirir S.aureus que colonizam principalmente as narinas e os ouvidos de espécies de felinos. A otite externa no ouvido dos gatos é uma das doenças produzidas pelo S.aureus nos animais. A terapia com antibióticos é o tratamento convencional para as infecções produzidas pelo S.aureus. Os antibióticos utilizados durante o prolongado tratamento e o emprego de sub doses podem selecionar microorganismos resistentes. Com base em tais argumentos torna-se necessária a pesquisa de S.aureus isolados do ouvido dos gatos, bem como, a realização de testes para a resistência a antibióticos e do gene mecA. Empregando swabs estéreis de algodão foram obtidas amostras dos ouvidos dos gatos em meio de Amies. O isolamento bacteriano foi efetuado em meio MAS e os testes catalase e coagulase foram realizados para a identificação das bactérias. A sensibilidade dos isolados de S.aureus foi avaliada com o emprego de discos dos antibióticos cefoxitin, tetraxiclina, eritromicina, gentamicina e cloranfenicol, incorporados no meio MHA. Todos os isolados positivos de S.aureus foram submetidos ao test MRSA para a detecção do gene mecA. A amostra investigada revelou 91% (91/100) de positivos para S.aureus, dos quais, 3,30% (3/91) foram resistentes a múltiplas drogas (MDR) pois foram resistentes a 3-4 classes de antibióticos. De 12 MRSA isolados analisados o gene mecA foi detectado em um isolado. O uso inapropriado de antibióticos é a causa da resistência bacteriana em pets. Adicionalmente o emprego excessivo de antibióticos em uma população pode resultar no desenvolvimento de resistência bacteriana adquirida a antibióticos. O uso de antibióticos em animais deve ser ordenado por uma administração de medicamentos apropriada para prevenir o desenvolvimento da resistência.(AU)

Value of rifampicin-resistant real-time fluorescence quantitative nucleic acid amplification detection technology in the fast diagnosis of pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To evaluate the value and significance of rifampicin-resistant real-time fluorescence quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in the diagnosis of pulmonary tuberculosis. 　　Methods　The clinical data of 228 patients with suspected pulmonary tuberculosis, who admitted to Hebei Chest Hospital from January 2018 to December 2019, were analyzed retrospectively. The sputum was collected for GeneXpert MTB/RIF, sandwich cup liquid-based bacterial acid-fast staining smear microscopy (referred to as “sandwich cup method”) and Loop-Mediated isothermal amplification (referred to as “LAMP method”) and the results were statistically analyzed by SPSS 17.0 software. Results　Among the 228 patients with suspected cases, 200 cases were clinically diagnosed as pulmonary tuberculosis and 28 were non-tuberculosis. The positive detection rate of GeneXpert MTB/RIF (81.0%, 162/200) was significantly higher than that of sandwich cup method (62.5%, 125/200) and LAMP method (72.5%,145/200) (χ2=16.885, 4.049, P<0.05). Taking clinical diagnosis as gold standard, the sensitivity of GeneXpert MTB/RIF (80.00%,160/200) was significantly higher than that of sandwich cup method (60.00%, 120/200) and LAMP method (70.50%, 141/200) (χ2=19.048, 4.846, P<0.05). The diagnostic consistency of GeneXpert MTB/RIF (K=0.73) was higher than that of sandwich cup method (K=0.39) and LAMP method (K=0.56). Conclusions The GeneXpert MTB/RIF detection method is rapid and simple, and can diagnose pulmonary tuberculosis rapidly and simultaneously detect rifampicin resistance of Mycobacterium tuberculosis with high sensitivity. It has high clinical value for early diagnosis of pulmonary tuberculosis and guidance of treatment in general and specialized hospitals.

Advances in genomics of multi-drug resistant Stenotrophomonas / 生物工程学报

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.

Green synthesis of gold nanoparticles from Sophora flavescens extract and their antibacterial effect against some pathogenic bacteria

Aims@#The current study was aimed to evaluate the antibacterial activity of biogenic synthesized golden nanoparticles from Sophora flavescens Aiton roots aqueous extract against multidrug-resistant (MDR) clinical bacterial isolates.@*Methodology and results@#The green synthesis of gold nanoparticles (AuNPs) was accomplished using S. flavescens roots aqueous extract and examined using many accepted techniques. The antibacterial activity of S. flavescens extract and the aqueous AuNPs at concentrations (7% and 9%) ppm were investigated against two clinical MDR bacteria, including Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa). The findings demonstrate inhibitory activity against the selected MDR bacterial isolates for the aqueous extract of S. flavescens and the aqueous AuNPs noted by the significant decrease in the number of bacteria after treatment with highly significant differences (P≤0.01) compared to the untreated control.@*Conclusion, significance and impact of study@#Sophora flavescens root extracts and their biosynthesized AuNPs with antibacterial activity may find broad applications in fighting MDR pathogenic bacteria and therapeutic manufacturing.

Prevalence of new defined extensive drug resistant tuberculosis in Xi'an / 中国热带医学

@#Abstract: Objective　To collect extensively drug-resistant tuberculosis (XDR-TB) Mycobacterium tuberculosis strains isolated from Xi'an City between 2019 and 2020, and analyze the drug resistance patterns of XDR-TB strains to second-line anti-tuberculosis drugs and the occurrence of new defined extensively drug-resistant tuberculosis in Xi'an, in order to provide evidence for guiding clinical drug use of multidrug-resistant tuberculosis (MDR-TB) patients. Methods A total of 3 088 strains of Mycobacterium tuberculosis that underwent phenotypic drug susceptibility testing at Xi'an Chest Hospital from January 2019 to December 2020 were retrospectively selected to analyze the resistance of anti-tuberculosis drug. Among the stored MDR-TB strains, 114 strains of preserved multidrug-resistant Mycobacterium tuberculosis were randomly selected for bedaquiline and linezolid susceptibility testing. Combined with the results of previous second-line drug susceptibility testing, the incidence of newly defined extensive drug resistance was analyzed. Results Among the 3 088 Mycobacterium tuberculosis strains analyzed, 411 strains (14.3%) showed resistance to isoniazid, 347 strains (11.2%) showed resistance to rifampicin, 142 strains (4.6%) showed resistance to ethambutol, 550 strains (17.8%) showed resistance to streptomycin, and 237 strains (7.6%) exhibited multidrug resistance. Of 237 MDR-TB strains, the resistance rates of ethambutol, moxifloxacin, rifampicin, sodium para-aminosalicylate, prothioconazole, capreomycin, amikacin, and clofazimine were 44.3%, 26.6%, 33.3%, 24.1%, 5.1%, 4.2%, 3.0%, and 2.5%, respectively. Among the randomly selected 114 MDR-TB strains, none showed resistance to bedaquiline, three showed resistance to linezolid, and one strain met the new definition for extensively drug-resistant tuberculosis. Conclusion In Xi'an City, high rates of resistance among MDR-TB strains are observed for ethambutol, quinolone and sodium para-aminosalicylate, and the drug susceptibility tests should be obtained as much as possible when using these drugs. The incidence of new definition extensively drug-resistant tuberculosis is low, and bedaquiline and linezolid remain effective drugs for the treatment of multidrug-resistant tuberculosis even without drug susceptibility testing results.

Efficacy of perioperative use of tigecycline in preventing infection and incidence of hypofibrinogenemia in liver transplant recipients / 器官移植

Objective To evaluate the efficacy of perioperative use of tigecycline in preventing infection and the incidence of hypofibrinogenemia in liver transplant recipients. Methods Clinical data of 40 liver transplant recipients given with tigecycline to prevent infection were retrospectively analyzed. The incidence of infection in recipients and donor-derived infection were analyzed. The changes of clinical indexes in recipients during, upon the completion and (7±2) d after tigecycline treatment were analyzed, respectively. The incidence and treatment of hypofibrinogenemia were summarized. Results Among 40 liver transplant recipients, 2 cases were infected by aspergillus niger and cytomegalovirus, out of the antibacterial spectrum of tigecycline. After adjusting the anti-infection regimen, the infection was properly controlled. Liver allografts were positive for relevant culture in 9 cases, whereas none of them progressed into donor-derived infection. Approximately at postoperative 2 weeks, all 40 recipients restored liver function and were discharged from hospital. Among them, 6 recipients developed hypofibrinogenemia complicated with coagulation disorder at postoperative 2-4 d, whereas transaminase level, bilirubin level and infection-related indexes were gradually decreased after liver transplantation, and albumin level was stable. After supplemented with human fibrinogen and prothrombin complex, coagulation function was improved, but fibrinogen level persistently declined. After terminating use of tigecycline, fibrinogen level was gradually restored to normal range, which might be an adverse drug reaction induced by tigecycline. Conclusions Perioperative anti-infection regimen including tigecycline may reduce the incidence of infection caused by sensitive bacteria in liver transplant recipients. Nevertheless, the incidence of hypofibrinogenemia should be intimately monitored throughout the use of tigecycline.

Distribution and drug resistance characteristics of pathogens in recipients undergoing simultaneous pancreas-kidney transplantation / 器官移植

Objective To investigate the distribution and drug resistance characteristics of pathogens in donors and recipients undergoing simultaneous pancreas-kidney transplantation (SPK). Methods Clinical data of 231 pairs of donors and recipients undergoing SPK were analyzed retrospectively. The pathogens of samples from donors and recipients were identified by VITEK-2 analyzer, and drug sensitivity test was performed by K-B method. The source distribution and composition ratio of pathogens in donor and recipient samples, distribution characteristics of multi-drug resistant organism, infection of recipients and drug resistance characteristics of pathogens were analyzed. Results A total of 395 strains of pathogens were cultured from 1 294 donor samples, and the detection rate was 30.53%. Gram-negative bacteria mainly consisted of klebsiella pneumoniae, Gram-positive bacteria mainly comprised staphylococcus aureus, and fungi primarily included candida albicans, respectively. In total, 2 690 strains of pathogens were cultured from 10 507 recipient samples, and the detection rate was 25.60%. Gram-negative bacteria mainly consisted of pseudomonas maltophilia, Gram-positive bacteria primarily comprised enterococcus faecalis, and fungi mainly included candida albicans, respectively. Among 395 pathogens of donors, 15 strains of methicillin-resistant staphylococcus aureus (MRSA), 16 strains of extended-spectrum β-lactamase (ESBL) positive drug-resistant bacteria, 8 strains of carbapenem-resistant pseudomonas aeruginosa (CR-PA), 21 strains of carbapenem-resistant acinetobacter baumannii (CR-AB), 2 strains of carbapenem-resistant enterobacteriaceae (CRE) and 1 strain of multiple-drug/pan-drug resistant pseudomonas aeruginosa (MDR/PDR-PA) were identified. Among 2 690 strains of recipient pathogens, 73 strains of ESBL positive drug-resistant bacteria, 44 strains of CR-PA, 31 strains of CR-AB and 3 strains of MDR/PDR-PA were detected. One recipient developed donor-derived infection, 69 cases of pneumonia, 52 cases of urinary tract infection, 35 cases of abdominal infection and 2 cases of hematogenous infection were reported within postoperative 1 year. Gram-negative bacteria were resistant to certain antibiotics. Gram-positive bacteria were sensitive to vancomycin. Fungi were sensitive to amphotericin B. Conclusions Gram-negative bacteria are the main pathogens of SPK recipients, which are resistant to certain antibiotics. Empirical use of antibiotics can be delivered before culture results are obtained. Subsequently, sensitive antibiotics should be chosen according to the culture results to improve the survival rate of SPK recipients.

Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children.@*METHODS@#The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared.@*RESULTS@#A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011).@*CONCLUSIONS@#The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.

Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.@*METHODS@#Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.@*RESULTS@#Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.@*CONCLUSION@#Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.

Clinical features and risk factors of multi-drug resistant bacteria infection after liver transplantation / 中华肝胆外科杂志

Objective:To investigate the clinical features and related risk factors of multi-drug resistant organism (MDRO) infection after liver transplantation, so as to guide clinical identification of high-risk patients and reduce the occurrence of MDRO infection.Methods:Of 187 patients undergoing liver transplantation in the First Affiliated Hospital of Nanjing Medical University from February 2019 to September 2020 were enrolled, including 150 males and 37 females, aged (50.6±9.6) years. Data related to MDRO infection were collected, and independent risk factors were identified using univariate analysis and multiple logistic regression analysis.Results:Among the 187 patients, MDRO infection occurred in 39, and 9 patient deaths were directly related to MDRO infection. Lung is the most common infection site, accounting for 82.1% (32/39) of MDRO infection. The most common pathogenic bacteria were Acinetobacter baumannii and Carbapenem-resistant enterobacteriaceae, accounting for 46.8%(36/77) and 41.7%(32/77) of MDRO infection, respectively. Multiple logistic regression analysis showed that postoperative mechanical ventilation ≥ 48 h ( OR=3.430, 95% CI: 1.124-10.467, P=0.030), intensive care unit (ICU) stay ≥7 d ( OR=9.013, 95% CI: 3.054-26.594, P<0.001) were independent risk factors of postoperative MDRO infection. Conclusions:Early removal of endotracheal intubation and discharge from ICU are important to reduce the risk of MDRO infection after liver transplantation.

Characterization of Virulent Bacterial Isolates Associated with Multi-Drug Resistance among Patients with Surgical Site Infections in Selected Specialist Hospitals in Calabar, Nigeria

Aims: Increasing research findings have documented the continuous emergence and threats posed by drug resistant clinical isolates from post-operative wound infections to commonly used antibiotics globally. This hospital-based study investigated virulent bacterial pathogens implicated with post-operative wound infections among surgical site infection (SSI) patients in Calabar, Nigeria and determined their antibiotic resistance pattern. Methodology: A total of 127 bacterial isolates of different genus from 110 SSI patients, were isolated from pus and surgical wound exudates and fully characterized using standard bacteriological procedures. Antimicrobial susceptibility patterns of isolates were determined using Kirby- Bauer disk diffusion method, following the guidelines by Clinical Laboratory Standard Institute (CLSI). Results: Multi-drug resistant bacteria isolated and their percentage frequency were coagulase Negative Staphylococci (21.3%), Staphylococcus aureus (19.7%), Pseudomonas aeruginosa (14.2%), Escherichia coli (11.8%), Klebsiella pneumoniae (9.4%), Enterococcus faecium (6.3), Enterobacter cloacae (4.7%), Proteus mirabilis (4.7%), Acinetobacter baumannii (3.1%), Pseudomonas putida (3.1%) and Aerococcus viridans (1.6%). Among gram-positive bacteria isolated, S. aureus showed highest resistance to several antimicrobials (100% to oxacillin, 96% to ciprofloxacin, 92% to levofloxacin, and 76% resistance to vancomycin). All recovered S. aureus isolates were cefoxitin screen positive indicating possible MRSA isolates. Additionally, among Gram-negative isolates K. pneumoniae was found to possess higher resistance to several antibiotics (66.7% resistance to each of ciprofloxacin, levofloxacin, ceftazidime, trimethoprim /sulfamethoxazole, cefazolin, ampicillin, tobramycin and 58.3% resistance to each of ceftriaxone, gentamicin, and ampicillin/sulbactam). Statistical analysis of categorical variables of study subjects revealed that length of hospital stay, type of surgery, previous admission history, antibiotic use, and age were significant (p<0.05) in SSI outcome of patients, while patients� gender was not significant (p>0.05) in SSI outcome. Conclusion: Adherence to measures of strict infection control, optimal preoperative, intraoperative, and postoperative patient care, including multifaceted approaches involving surveillance, and antimicrobial stewardship, are vital to SSI treatment outcomes.

Review on Drug Resistant Tuberculosis

Introduction: An estimated 9.9 million people fell ill with tuberculosis globally in 2020 with India and China contribu?ng a major percentage to the burden of TB. India is grouped under high TB, high HIV associated TB and MDR TB burden countries and 1.24 lakh fell ill with drug resistant TB out of which 56000 were started on second line treatment in 2020. Annually India accounts for 27% of missing TB cases. Diagnosis: The major forms of drug resistant TB that are of clinical importance are INH monoresistant TB, mul?drug resistant TB, pre- XDR TB and XDR TB.WHO approved newer molecular tests for MTB detec?on and drug suscep?bility tests. Treatment: Few newer drugs and few previously used drugs are showing promise when used in combina?on which have come up in recent years. Bedaquiline based regimens are showing improved cure rates. Conclusion: Guidelines based regimens should be strictly adhered to by both public and private TB case trea?ng physicians.

A study of clinical and treatment profile of tuberculosis patients attending DOTS centre at Primary Health Centre

Introduction: Tuberculosis (TB) is an age-old disease killing significant number of humans over history and one of the major cause of morbidity and mortality, especially in developing and underdeveloped countries. It killed 1.4 million people annually worldwide in the year 2019. India had 2.69 million cases in 2019, according to TB report 2020. Despite the presence of the programme for it's control, TB continues to threaten the population due to emergence of more and more resistance cases challenging it's elimination. This study reflects the annual burden of tuberculosis in an area served by a Primary Health Centre in Urban Delhi and the treatment outcomes. The records of the patients attendingMethods: the DOTS centre was obtained from the treatment register at Primary Health Centre, Palam, Delhi. The records of patients visiting between April 2020 to March 2021 were included. Data analysis was done on Statistical Package for the Social Sciences (SPSS) version 22 and appropriate statistical tests were applied. The total number ofResults & Conclusion: tuberculosis patients registered from April 2020 to March 2021 were 260. Out of these 260 patients, 155 (59.6%) were pulmonary and 105 (40.4%) were extra-pulmonary. A total of 175 (67.3%) were microscopically confirmed and 85 (32.7%) were clinically/radiologically diagnosed.

Anti pathogenic studies of new mixed ligand metal chelates

Drug discovery aimed at the methodical extermination of life-threatening bacterial infection, especially considering the emergence of multi-drug resistance of pathogenic bacteria has remained a challenge for medicinal inorganic chemistry. In this article, the mixed ligand complexes of Cu (II), Co (II), and Ni (II) containing heterocyclic ligands were synthesized and characterized by IR, LC-MS, UV, and TG-DTA. Complexes are screened for Anti-microbial activity against human pathogenic bacteria.

Tratamiento de la tuberculosis drogorresistente en adultos y niños. Revisión narrativa / Treatment of drug-resistant tuberculosis in adults and children. A narrative review

Resumen Desde 2018 han surgido a la luz de la evidencia importantes cambios en el tratamiento de la tuberculosis drogorresistente. El descubrimiento de nuevas drogas antituberculosis, como la bedaquilina y los derivados de nitroimidazopiranos, así como la utilización de drogas repropuestas, llevó a la recomendación de organismos internacionales de nuevos esquemas de tratamiento de la tuberculosis monorresistente y multidro gorresistente que son totalmente orales y así dejan de lado el uso prolongado de inyectables, con su inherente toxicidad e incomodidad. Algunas de las definiciones de tuberculosis drogorresistente han cambiado. También está en revisión el tiempo de su tratamiento y con algunos nuevos esquemas en estudio, como el BpaL (bedaquilina, pretomanid y linezolid), se ha logrado una duración similar a la del tratamiento de la tuberculosis pansensible. En esta revisión bibliográfica narrativa describimos las nuevas definiciones, algunos aspectos diagnósticos básicos, los aspectos farmacológicos y la nueva clasificación de las drogas a utilizar en el tratamiento de la tuberculosis drogorresistente, así como los esquemas actualmente propuestos para tratarla, contextualizados con la realidad nacional. Finalizamos con una breve reseña de los estudios clínicos en curso de nuevos esquemas acortados de tratamiento.

Abstract Since 2018, important changes in the treatment of drug-resistant tuberculosis have been produced in the light of new evidence. The discovery of new anti-tuberculosis drugs, such as bedaquiline and nitroimidazopirane derivatives, as well as the use of repurposed drugs, led to international organizations to recommend new, totally oral, treatment regimens for mono-resistant and multidrug-resistant tuberculosis, leaving aside the prolonged use of injectables, with their inherent toxicity and discomfort. Some definitions of drug-resistant tuberculosis have changed. The duration of treatment is also under review, leading some new regimens under study, such as BPaL (bedaquiline, pretomanid and linezolid), to a duration similar to that for treating susceptible tuberculosis. In this narrative review, we describe the new definitions, some basic diagnostic aspects, the pharmacological aspects, and the new classification of drugs to be used in the treatment of drug-resistant tuberculosis as well as the cur rently proposed schemes to treat it available within the Argentinean context. Finally, we include a brief review of ongoing clinical trials on new shortened treatments.