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.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ²=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ²=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ²=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ²=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.
Child ; Female ; Male ; Humans ; Hodgkin Disease ; Retrospective Studies ; Neoplasm Recurrence, Local ; China ; Antineoplastic Combined Chemotherapy Protocols ; Prognosis ; Disease-Free Survival

BACKGROUNDKnee osteoarthritis (KOA) is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling, stiffness, and movement disorders. The therapeutic goal is to alleviate or eliminate pain, correct deformities, improve or restore joint functions, and improve the quality of life. This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA.

METHODSThis multi-center, randomized, double-blind, double-dummy, parallel controlled trial, started from December 2011 to May 2014, was carried out in 6 cities, including Beijing, Shanghai, Chongqing, Changchun, Chengdu, and Nanjing. A total of 432 patients with KOA were divided into three groups (144 cases in each group). The groups were treated, respectively, with Zhuanggu joint capsules combined with celecoxib capsule simulants, Zhuanggu joint capsules combined with celecoxib capsules, and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively. The improvement of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment. Intergroup and intragroup comparisons of quantitative indices were performed. Statistically significant differences were evaluated with pairwise comparisons using Chi-square test (or Fisher's exact test) and an inspection level of α = 0.0167.

RESULTSFour weeks after treatment, the total efficacies of Zhuanggu group, combination group, and celecoxib group were 65%, 80%, and 64%, respectively, with statistically significant differences among the three groups (P = 0.005). Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu (P = 0.005) and celecoxib (P = 0.003) groups. The difference between the latter two groups was not statistically significant (P > 0.0167). Four weeks after discontinuation, the efficacies of the three groups were 78%, 95%, and 65%, respectively, with statistically significant differences (P < 0.0001). Intergroup pairwise comparisons revealed that the efficacy of the combination group was significantly better than that of the Zhuanggu and the celecoxib groups (P < 0.0001). The difference between the latter two groups was not statistically significant (P > 0.0167). The incidences of adverse events in Zhuanggu group, combination group, and celecoxib group were 8.5%, 8.5%, and 11.1%, respectively, with insignificant differences (P > 0.05).

CONCLUSIONSZhuanggu joint capsules alone or combined with celecoxib showed clinical efficacy in the treatment of KOA. The safety of Zhuanggu joint capsules alone or combined with celecoxib was acceptable.

TRIAL REGISTRATIONChinese Clinical Trial Registry, ChiCTR-IPR-15007267; http://www.medresman.org/uc/project/projectedit.aspx?proj=1364.

Adult ; Aged ; Celecoxib ; administration & dosage ; adverse effects ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy

PURPOSE: The aim of this study was to determine the relationship of hypoxia-inducible factor-2 (HIF-2α) and vascular endothelial growth factor (VEGF) with radiographic severity in primary osteoarthritis (OA) of the knee. Expression of these two factors in cartilage samples from OA knee joints was examined at mRNA and protein levels. MATERIALS AND METHODS: Knee joints were examined using plain radiographs, and OA severity was assessed using the Kellgren and Lawrence (KL) grading system. Specimens were collected from 29 patients (31 knees) who underwent total knee replacement because of severe medial OA of the knee (KL grades 3 and 4), 16 patients who underwent knee arthroscopy (KL grade 2), and 5 patients with traumatic knees (KL grade 0). HIF-2α and VEGF expression was quantified by real-time polymerase chain reaction and western blotting. RESULTS: Cartilage degeneration correlated with the radiographic severity grade. OA severity, determined using the Mankin scale, correlated positively with the KL grade (r=0.8790, p<0.01), and HIF-2α and VEGF levels with the radiographic severity of knee OA (r=0.7001, p<0.05; r=0.6647, p<0.05). CONCLUSION: In OA cartilage, HIF-2α and VEGF mRNA and protein levels were significantly and positively correlated. The expression of both factors correlated positively with the KL grade. HIF-2α and VEGF, therefore, may serve as biochemical markers as well as potential therapeutic targets in knee OA.
Adult ; Aged ; Arthroplasty, Replacement, Knee ; Arthroscopy ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Biomarkers/*blood ; Cartilage/*metabolism ; Female ; Humans ; Knee Joint/*diagnostic imaging ; Male ; Middle Aged ; Osteoarthritis, Knee/*blood/diagnostic imaging/physiopathology ; RNA, Messenger ; Radiography ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Vascular Endothelial Growth Factor A/*metabolism

Human carnitine/organic cation transporter 1 and 2(hOCTN1 and hOCTN2) mediate transport of endogenous and exogenous compounds. The present study aimed to establish cell models with stable expression of hOCTN1 or hOCTN2 to study interactions with compounds and transporters. MDCK cells were transfected with pcDNA3.1(+) plasmid vector containing hOCTN1 or hOCTN2(pcDNA3.1(+)-hOCTN1/2), several stable transfected clones were obtained after G418 screening. hOCTN1 and hOCTN2 clones were screened with ergothioneine and mildronate respectively as substrates to identify the best candidates. We explored interactions of endogenous substances, alkaloids, flavonoids and ACEIs with hOCTN1/2. As a result, the cellular accumulation of ergothioneine in MDCK-hOCTN1 or mildronate in MDCK-hOCTN2 was 122 and 108 folds of the control cells, respectively. The kinetic parameters, K_m and V_max of ergothioneine, mediated by MDCK-hOCTN1, were 8.19±0.61 μmol·L^-1 and 1427±49 pmol·mg^-1(protein)·min^-1; while K_m and V_max of mildronate by MDCKhOCTN2 were 52.3±4.3 μmol·L^-1 and 2454±64 pmol·mg^-1(protein)·min^-1. Dopamine, glutamine, piperine, berberine, nuciferine, lisinopril and fosinopril could inhibit ergothioneine or mildronate uptake by MDCKhOCTN1/2. In conclusion, cell models with good stable hOCTN1 and hOCTN2 functions have been established successfully, which can be applied to the study of interactions between compounds and transporters of hOCTN1 and hOCTN2.

OBJECTIVETo assess the operative technique and results with the usage of cementless prosthesis in hip revision.

METHODSRetrospective study was done on revision of total hip arthroplasty with cementless prosthesis in 72 patients (41 males and 31 females) with an average age of 65.7 years (28-82 years) from January 2004 to December 2009. The reason for revision was 2 infection, 54 aseptic loosening, 4 periprosthetic fractures, 5 fracture of femoral stems and 7 cases of acetabular abrasion after hemi-arthroplasty. The operation time, bleeding loss, complications of infection, dislocation, periprosthetic fractures and loosening were evaluated. The Harris score were used for hip function evaluation.

RESULTSThe average operation time was (146±47) minutes (70-280 minutes) and bleeding loss during the operation was (970±540) ml (200-2500 ml). Bacterium cultivation during operation demonstrated infection in 2 patients. Bone windows at the lateral femoral were opened in 4 patients and extend trochanteric osteotomy was done in 7 patients. Fracture of the proximal femur occurred in 8 cases. Twenty-nine patients were treated with bone graft including 18 autografts and 11 allografts. Sixty-seven patients were followed up for an average time of 66 months (20-92 months). Additional revisions were performed in 3 cases including 2 dislocations and 1 infection. There were no death, no damage of major blood vessels and nerves. The bone graft healed during 3-5 months. The survival rates of the femoral prosthesis and the acetabulum prostheses were 95.5% and 98.4%. The mean Harris score was 86±8 (55-95 points). Osteolysis were seen in 13 hips but migration was seen in only 1 patient.

CONCLUSIONSThe cementless prosthesis is useful in revision total hip arthroplasty and the perfect clinical results are related to the reliable primary fixation.

Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; instrumentation ; Bioprosthesis ; Bone Transplantation ; Female ; Follow-Up Studies ; Hip Prosthesis ; Humans ; Male ; Middle Aged ; Retrospective Studies

Persistent baculovirus infection is observed frequently in insect populations. Persistent infection can be transformed to a replicative and infective state caused by stress factors and plays an important role in regulating the size of insect population and in epizoology of baculoviruses. The aim of this study is to establish a persistently baculovirus-infected cell system to explore the molecular mechanisms of baculoviral persistence. Spodoptera exigua nucleopolyhedrovirus (SeMNPV) was serially undiluted passaged in Se301 cells to reduce virulence. Upon infection of Se301 cells with the SeMNPV up to passage 8, a few cells survived even if most of cells died due to virus infection. The surviving cells were passaged and designated as P8-Se301 cell strain. P8-Se301 cells had a population doubling time of 58-65 hours and grew slower than Se301 cells. Light microscopy and electron microscopy observation showed symptom of baculovirus infection, such as virogenic stroma, viral particles and occlusion bodies, in some of P8-Se301 cells. End-point dilution assay and infectious center assay showed that 4.14% +/- 0.99% cells continually released infectious progeny virus which replicated slower than SeMNPV in Se301 cells. The result indicated that P8-Se301 cells show a typical character trait of baculovirus persistent infection.
Animals ; Cells, Cultured ; Nucleopolyhedrovirus ; growth & development ; physiology ; Spodoptera ; virology ; Virus Cultivation ; methods

Objective To investigate the limitation of quantitative measurement of cerebral blood flow (CBF) of normal white matter by using a single subtraction with thin-slice TI1 periodic saturation (Q2TIPS Ⅱ ) pulsed arterial spin labeling (PASL)technique. Methods Thirty-one patients with brain tumors were examined at 3.0 T MRI system . A second version of quantitative imaging of perfusion using a single subtraction with additional thin-section periodic saturation after inversion and a time delay (Q2TIPS) technique of pulsed arterial spin labeling in the multisection mode and T2* dynamic susceptibility-weighted contrast-enhanced (T2* DSC)MR imaging were both implemented. Cerebral blood flow map obtained from PASL and DSC were reviewed. The regions of interest( ROI )were placed in the region of normal white matter contralateral to the lesion in the proximal and distal slices. In regions of interest, the signal intensity (SI)was measured from the maps of cerebral blood flow map obtained from PASL and DSC. Pair-t test was performed to determine if there were significant signal differences between proximal and distal slices. Pearson linear correlation analysis of signal intensity was performed for values from the same slices of PASL-CBF and DSC-CBF maps. Results In the deep white matter of distal slice, PASL-CBF map showed perfusion deficit while DSC-CBF map showed low CBF in the corresponding brain area. With the increased inversion time,the PASL-CBF map showed obviously improved perfusion signal in deep white matter (but still some perfusion deficit)and slightly decreased perfusion signal in grey matter. The mean signal of normal white matter measured from distal slices of PASL-CBF maps was( -22.1 ±55.5) ml· 100 g-1 · min-1 while it was (89.5 ±45.5) ml. 100 g-1 · min-1 in proximal slices. There was a significant difference of signal intensity from PASL-CBF maps between distal and proximal slices ( t = - 9. 512, P ＜ 0. 01 ＝, while no difference of signal intensity between distal[ (62. 8 ± 29.9) ml · 100 g-1 · min-1] and proximal slices [(57. 1 ±29.6) ml · 100 g-1 · min-1 ]was obtained from DSC-CBF maps(t= -1.607,P＞0.05). There was no significant correlation between PASL-CBF and DSC-CBF in both distal ( r = 0. 093, P ＞ 0. 05 ) and proximal slices ( r = - 0. 234, P ＞ 0. 05). ConclusionsPASL has limitation in the accurate quantification of cerebral blood flow of normal white matter. The quantification of CBF was affected by the limitations of the technique itself and the different parameters chosen..

Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Osteochondrodysplasias ; diagnosis ; diagnostic imaging ; surgery ; Radiography ; Young Adult