Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Pancreatic Neoplasms ; Pancreas ; Needles

OBJECTIVE: Our study aimed to conduct genomic characterization of Salmonella strains carrying the bla _NDM-1 gene in the intestinal tract of healthy individuals. The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations, and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes. METHODS: We performed antimicrobial susceptibility testing and employed second- and third-generation sequencing techniques to analyze Salmonella strains harboring the bla _NDM-1 gene, to surveil drug-resistant bacteria in the intestines of healthy subjects. Sequence comparison was conducted using both core- and pan-genome approaches. Concurrently, conjugation experiments were carried out to assess the efficiency of plasmid transfer. RESULTS: We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China. This strain harbored an IncHI2/IncHI2A plasmid carrying bla _NDM-1 along with multiple antibiotic resistance genes (ARGs). Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs. Pan-genomic analysis revealed that bla _NDM-1-positive plasmids could traverse bacterial species barriers, facilitating cross-host transmission. CONCLUSION This study marks the first detection of bla _NDM-1 in Salmonella strains isolated from healthy individuals. We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying bla _NDM-1, which have the potential to be harbored and transmitted among healthy individuals. Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
beta-Lactamases/genetics* ; Plasmids/genetics* ; Humans ; Anti-Bacterial Agents/pharmacology* ; China ; Microbial Sensitivity Tests ; Salmonella typhimurium/isolation & purification* ; Salmonella/isolation & purification* ; Salmonella Infections/microbiology*

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Background::Joint dislocations significantly impact public health. However, a comprehensive study on the incidence, distribution, and risk factors for joint dislocations in China is lacking. We conducted the China National Joint Dislocation Study, which is a part of the China National Fracture Study conducted to obtain the national incidence and risk factors for traumatic fractures, and to investigate the incidence and risk factors for joint dislocations.Methods::For this national retrospective epidemiological study, 512,187 participants were recruited using stratified random sampling and probability-proportional-to-size method from January 19 to May 16, 2015. Participants who sustained joint dislocations of the trunk, arms, or legs (skull, sternum, and ribs being excluded) in 2014 were personally interviewed to obtain data on age, educational background, ethnic origin, occupation, geographic region, and urbanization degree. The joint-dislocation incidence was calculated based on age, sex, body site, and demographic factors. The risk factors for different groups were examined using multiple logistic regression.Results::One hundred and nineteen participants sustained 121 joint dislocations in 2014. The population-weighted incidence rate of joint dislocations of the trunk, arms, or legs was 0.22 (95% confidence interval [CI]: 0.16, 0.27) per 1000 population in 2014 (men, 0.27 [0.20, 0.34]; women, 0.16 [0.10, 0.23]). For all ages, previous dislocation history (male: OR 42.33, 95% confidence interval [CI]: 12.03–148.90; female: OR 54.43, 95% CI: 17.37–170.50) and alcohol consumption (male: OR 3.50, 95% CI: 1.49–8.22; female: OR 2.65, 95% CI: 1.08–6.50) were risk factors for joint dislocation. Sleeping less than 7 h/day was a risk factor for men. Compared with children, women aged ≥15 years (female 15–64 years: OR 0.16, 95% CI: 0.04–0.61; female ≥65 years: OR 0.06, 95% CI: 0.01–0.41) were less likely to sustain joint dislocations. Women with more than three children were at higher dislocation risk than women without children (OR 6.92, 95% CI: 1.18–40.78).Conclusions::The up-to-date data on joint dislocation incidence, distribution, and risk factors can be used as a reference for national healthcare, prevention, and management in China. Specific strategies for decreasing alcohol consumption and encouraging adequate sleeping hours should be developed to prevent or reduce dislocation incidents.Trial Registration::Chinese Clinical Trial Registry, ChiCTR-EPR-15005878.

Purpose: This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods: From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA). Results: Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness. Conclusion Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Objective To explore the CT dominant phase and optimal classification model in differenting clear cell renal cell carcinoma (ccRCC) from fat‐poor angiomyolipoma (fpAML) through quantitative multiple‐phase CT radiomic features analysis. Methods Clinical and imaging data of 195 cases pathologically confirmed ccRCC (n=131) and fpAML (n=64) were retrospectively studied. All the patients underwent non‐contrast enhanced CT scans and dynamic multi‐phase (corticomedullary phase, medullary phase and excretion phase) contrast‐enhanced CT scans. Regions of interest (ROIs) were manually delineated based on the selected image slices with the maximal diameter of the lesion using ITK‐SNAP software, followed by the acquisition of candidate CT radiomic feature sets from each phase with statistically significant differences by using Mann‐Whitney U test. Then, using the synthetic minority oversampling technique (SMOTE), 232 classification models which are composed of 29 different feature selection algorithms (top 10 features were chosen by the backward elimination method) and 8 different classifiers were constructed. Employing the 5‐fold cross‐validation method, the performance of each classification models for each phase was evaluated using accuracy (ACC), sensitivity (SEN), specificity (SPE) and area under receiver operating characteristic curve (AUC), to acquire dominant CT phases and the optimal classification models for distingushing ccRCC and fpAML, along with the key imaging radiomic features. Results In this study, the mean maximal diameter of ccRCC and fpAML lesions were (3.9±1.4) cm, and (3.5±1.7) cm, respectively, and there was no statistically significant difference in the size of the tumor between two groups (P>0.05). From 102 initial imaging feature sets, the total number of candidate imaging feature sets (P<0.05) were:non‐enhanced phase (n=26), corticomedullary phase (n=71), medullary phase (n=68), excretion phase (n=62). Among the 232 classification models through different combination of classifiers and feature selectors, the amount of classification models which achieved the maximum of AUC value (AUCmax) from different CT phases were: non‐enhanced phase (n=106, 45.7%), corticomedullary phase (n=94, 40.5%), medullary phase (n=23, 9.9%), excretion phase (n=9, 3.9%). Imaging features from non‐enhanced phase and corticomedullary phase yielded higher performance compared with medullary phase and excretion phase, with the corresponding optimal prediction models were SVM‐fisher_score (AUC: 0.897, ACC: 83%, SEN: 84%, SPE:80%) and Logistic Regression‐RFS (AUC: 0.891, ACC: 83%, SEN: 81%, SPE: 89%), respectively. Conclusions The quantitative imaging features from non‐enhanced and corticomedullary phase have better performance among proposed classification models than that from medullary phase and excretion phase. Furthermore, it is feasible to acquire proper combination of feature selection and classifiers to achieve high performance in identifying ccRCC and fpAML.

Objective To compare and analyze the epidemiological features of adult patients with scapular fracture between eastern and western areas in China from 2010 to 2011. Methods The data of adult patients with scapular fracture who had been treated from January 2010 to December 2011 in 63 hospitals in the eastern and western areas in China were collected through the PACS system and case reports checking system. The data from the eastern 35 hospitals were classified as group A and those from the 28 western hospitals as group B. The analytic items included gender, age and AO classification. Results A total of 2, 063 cases were collected. The median age was 44 years ( interquartile range, from 33 to 56 years ) and gender ratio 3. 50:1 in Group A of 1, 376 cases; the median age was 41 years ( interquartile range, from 31 to 51 years ) and gender ratio 3. 09:1 in Group B of 687 cases. There was a significant difference between the 2 groups in median age ( Z= -3. 798, P=0. 000 ) . There was no significant difference between the 2 groups in gender ratio or constituent ratio of fracture peak age ( P > 0. 05 ) . The proportions of patients from 16 to 20 and from 31 to 40 years old in group A were significantly lower than in group B ( P <0. 05 ) . The proportion of middle-aged patients was significantly higher and that of young patients significantly lower in group A than in group B. The proportion of AO type 14-A fractures in group A ( 66. 49％) was significantly higher than in group B ( 55. 60％) while the proportion of AO type 14-C fractures was significantly lower ( 21. 37％) in group A than in group B ( 29. 55％) . Conclusions Most scapular fractures occurred in male patients. The proportion of young patients in the eastern area was lower than in the western area, but the proportion of middle-aged patients was higher in the eastern area than in the western area. The proportion of AO type 14-A fractures in the eastern area was significantly higher than in the western area while the proportion of AO type 14-C fractures in the eastern area significantly lower than in the western area.

Objective To compare the epidemiological characteristics of adult single fractures of the cuneiform between the east and west areas in China from 2010 through 2011.Methods Thirty-five hospitals in the east coast area (group A) and 28 hospitals in the west inland area (group B) were selected for this investigation. The data of adult single fracture of the cuneiform treated between January 2010 and De-cember 2011 at the 63 hospitals were collected through the PACS system and medical records inquiry system. The epidemiological characteristics concerning age, gender and fracture classification were compared between the 2 groups. Results A total of 457 adult single fractures of the cuneiform were collected, involving 384 cases in group A and 73 cases in group B. They accounted respectively for 4.38% (384/8,772) and 3.53% (73/2, 068) of the adult tarsal bone fractures in the same period, showing no significant difference (P >0.05), accounted respectively for 1.71% (384/22, 455) and 1.15% (73/6, 354) of the adult foot frac-tures, showing a significant difference (P <0.05), and accounted respectively for 0.20% (384/192,991) and 0.09% (73/81, 143) of all the adult fractures, showing a significant difference (P <0.05). The median age was 39 years in group A (29, 50) and 36 years in group B (25, 45), showing a significant difference (P <0.05). The male to female ratio was 1.61:1 (237/147) for group A and 1.52:1 (44/29) for group B. The peak age range of the fracture for males was from 21 to 30 years old in both groups, and its proportion was 28.69% (68/237) in group A and 38.64% (17/44) in group B. The peak age range of the fracture for females was from 41 to 50 years old in both groups, and its proportion was 26.53% (39/147)in group A and 27.59% (8/29) in group B. All the above comparisons were statistically insignificant (P> 0.05). The proportion of the age group of≥61 years was significantly larger in group A than in group B (P <0.05). The high risk type of the fracture was type 85-A1 in both groups, and its proportion was 61.98% (238/384) in group A and 52.05% (38/73) in group B. The proportion of type 85-B1 was significantly larger in group B than in group A (P <0.05). Conclusions Adult single fractures of the cuneiform were more common in young and male patients. The proportion of elderly patients (≥61 years old) was significantly larger in the east area. The high risk type of the fracture was simple fracture involving the medial cuneiform bone (type 85-A) in both areas. The proportion of the comminuted fracture of the medial cuneiform (type 85-B1) was significantly larger in the west area.

Objective To investigate the sleep quality of older adults in Shaoxing City and to examine its influencing factors. Methods Based on a cross-sectional questionnaire survey, a cluster sampling method was adopted to collect participants. Five villages were chosen randomly from 20 in the Yuecheng district of Shaoxing. The respondents were adults aged more than 60 years in the 5 villages. In total,1 303 adults participated,including 603 men and 700 women,and the average age was(70.99±7.38). The information related to sociodemographic factors,health status,sleep characteristics,and behavioral and lifestyle factors were collected.A chi-square test and variance analysis were used to compare sleep quality and sleep duration among participants. An ordinal regression model was adopted to examine the factors influencing sleep quality. Results One hundred and ninety-six (15.0%) older adults reported that sleep quality was always bad during the past year, 180(13.8%)reported that sleep quality was bad occasionally, and 927(71.1%)reported that sleep quality was good every day.The average sleep duration of participants was(6.64±1.38)h per night,and sleep durations for older adults who reported that sleep quality was always bad, bad occasionally, and good every day were (4.21 ± 1.13) h, (6.12 ± 1.40) h, and (7.26 ± 1.39) h, respectively,and older adults with poor sleeping quality had a shorter sleep duration(F=421.828,P<0.001). Being a woman, more than 80 years old, not working, and taking sleeping pills were risk factors for poor sleep quality with ORs (95% CI) of 1.492 (1.132-1.964), 1.564 (1.108-2.206), 1.331 (1.015-1.747), and 14.614(7.164-29.844),respectively.Conclusions Elderly individuals in Shaoxing had poor sleep quality. The sleep quality of those who were women, were oldest and took sleeping pills is cause for concern. Encouraging them to engage in work may improve their sleeping status.

Aim To investigate the effect of genistein on apoptosis in triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms.Methods MTT assay was used to detect the inhibition rate on breast cancer MDA-MB-231 cells of genistein.Hoechst 33258 staining was applied to determine the effect of genistein on morphology of MDA-MB-231 cells.qRT-PCR was employed to detect the mRNA expression of EGFR in MDA-MB-231 cells.Western blot was utilized to determine the expression of Bcl-2, Bax, caspase-3, EGFR, Akt, and p-Akt.The expressions of Akt and p-Akt proteins in breast cancer MDA-MB-231 cells were detected after treated with Akt activator insulin, genistein and in combination with insulin.Results Genistein inhibited the viability of breast cancer MDA-MB-231 cells in a time-dependent manner.The results of Hoechst 33258 staining showed a typical apoptotic morphological changes of MDA-MB-231 cells after treatment of genistein for 36 h.qRT-PCR showed that the mRNA expression of EGFR in MDA-MB-231 cells decreased after treated with genistein for 36 h.The expression levels of Bcl-2, EGFR, Akt, p-Akt, ERK, p-ERK were significantly down-regulated(P<0.01) compared with control.While, the expression of Bax, caspase-3 was significantly up-regulated (P<0.01).It was observed that p-Akt was significantly activated after the treatment of Akt activator insulin (P<0.01), however, significantly down-regulated (P<0.01) when treated with genistein.Conclusion Genistein could inhibit the growth of triple-negative breast cancer MDA-MB-231 cells and induce apoptosis, which probably involves regulating EGFR/PI3K/Akt signaling pathway.