Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Objective:To study the expressions of bronchoalveolar lavage fluid(BALF), C-reactive protein (C reactive protein, CRP), procalcitonin (PCT) and Interleukin 6 (IL-6) in mechanically ventilated patients with chronic obstructive pulmonary diseases (COPD) and their clinical significance.Methods:A total of 128 COPD patients with mechanical ventilation admitted to the Third People's Hospital of Chengdu from September 2022 to September 2023 were selected as the study subjects. They were divided into VAP group and non-VAP group according to the occurrence of ventilator associated pneumonia (VAP). Comparison of general data between the two groups, measurement data in line with normal distribution were expressed xˉ± s, and independent sample t test was used to compare the mean between groups. Enumeration data were expressed as constituent ratio, and χ2 test was used to compare between groups. Multivariate Cox regression was used to analyze the influencing factors of VAP in COPD patients. The diagnostic value of CRP, procalcitonin and IL-6 in BALF and serum for VAP was evaluated by receiver operating characteristic (ROC) curve. Results:There were 32 cases of VAP and 96 cases of non-VAP in 128 COPD patients with mechanical ventilation. In the VAP group, the duration of mechanical ventilation was (5.12±0.48) days, and 13 patients (40.63%) had used antibiotics within 3 months, while in the non-VAP group, the duration of mechanical ventilation was (4.79±0.69) days, and 56 patients (61.46%) had used antibiotics within 3 months, respectively. There were significant differences between the two groups ( t=2.51, χ2=4.23, all P<0.05). The levels of CRP, procalcitonin and IL-6 in BALF of VAP group were (26.46±6.78) mg/L, (2.47±0.69) ng/L and (751.46±126.44), and in the non-VAP group, they were (20.47±6.26) mg/L, (1.12±0.32) ng/L and (447.89±68.69) μg/L, respectively. There were significant differences between the two groups ( t=4.59, 15.00, 17.18, all P<0.001). The serum levels of CRP, procalcitonin and IL-6 in VAP group were (124.78±26.32) mg/L, (10.53±2.20) ng/L and (221.69±45.46). The non-VAP group was (96.78±24.96) mg/L, (6.46±1.89) ng/L and (146.36±42.34) μg/L, respectively ( t=5.42, 10.12, 8.56; all P<0.001). Multivariate Cox regression analysis showed that mechanical ventilation time, BALF and serum CRP, procalcitonin and IL-6 were independent factors affecting the occurrence of VAP in COPD patients ( OR values were 1.578, 1.687, 1.669, 1.844,1.645, 1.775 and 1.659, respectively). 95% CI were 1.017-2.447, 1.066-2.669, 1.076-2.588, 1.148-2.963, 1.086-2.493, 1.172-2.690 and 1.084-2.538, all P<0.05). ROC curve showed that the AUC of CRP, procalcitonin and IL-6 in BALF and serum were 0.758/0.792, 0.965/0.930 and 0.977/0.900 respectively ( P values were 0.049/0.046, 0.030/0.030 and 0.021/0.033, respectively). Conclusion:The expressions of CRP, procalcitonin and IL-6 in BALF and serum of COPD patients with mechanical ventilation have high clinical diagnostic value, which can assist the diagnosis of early VAP.

AIM To study the protective effects and mechanism of pueraria isoflavones on myocardial injury in ovariectomized rats.METHODS Thirty-six rats were randomly divided into the sham operation group,the model group,the estradiol valerate group(0.1 mg/kg)and the low,medium and high dose pueraria isoflavones groups(55,110,220 mg/kg).In contrast to the rats of the sham operation group having their small pieces of adipose tissue removal around the ovaries,rats of the other groups had their bilateral ovaries excised,followed by the 16-week corresponding oral drug administration 2 weeks later at a once daily frequency for,6 days a week.At the end of the 16th week,the rats had their hemodynamics[systolic pressure(SBP),diastolic pressure(DBP),mean pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVMP),and the maximum rate of increase and decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)]detected by PowerLab;their cardiac pathological changes observed by HE staining;their levels of creatine kinase(CK),lactate dehydrogenase(LDH),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and glucose(Glu)in plasma detected by biochemical analyzer;their myocardial level of adenosine triphosphate(ATP)detected by colorimetry;their mRNA expressions of glucose transporter 4(GLUT4),lactate dehydrogenase A(LDHA),carnitine palmitoyl transferase-1(CPT-1α),acyl coenzyme A carboxylase(ACC),liver kinase B1(LKB1),adenylate-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor γ coactivator factor 1α(PGC-1α)detected by RT-qPCR;and their myocardial expressions of energy metabolism related proteins LKB1,p-AMPK/AMPK and PGC-1α detected by Western blot.RESULTS Compared with the model group,the pueraria isoflavones groups displayed decreased levels of SBP,DBP,MBP,LVSP,LVMP(P＜0.05,P＜0.01);increased-dp/dtmax(P＜0.05,P＜0.01);improved myocardial fibrinolysis,gap widening and inflammatory infiltration caused by ovariectomy;decreased activities of LDH and CK(P＜0.05);increased myocardial ATP level(P＜0.05,P＜0.01);decreased levels of TC,TG,LDL-C and Glu(P＜0.05,P＜0.01);increased HDL-C level(P＜0.05,P＜0.01);increased myocardial mRNA expressions of GLUT4,LDHA,CPT-1α,ACC,LKB1,AMPK and PGC-1α(P＜0.05,P＜0.01);and increased protein expressions of myocardial LKB1,p-AMPK/AMPK and PGC-1α(P＜0.05,P＜0.01).CONCLUSION Pueraria isoflavones are protective to myocardial injury in ovariectomized rats,and the mechanism may lie in the improvement of energy metabolism-related myocardial proteins via LKB1/AMPK/PGC-1α signaling pathway.

Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quantitative CT(QCT)BMD examination were retrospectively enrolled and divided into training set(n=304)and test set(n=76)at a ratio of 8∶2.The mean BMD of L1-L3 vertebrae were measured based on QCT.Spongy bones of T5-T10 vertebrae were segmented as RO1,radiomics(Rad)features were extracted,and machine learning(ML),Rad and deep learning(DL)models were constructed for classification of osteoporosis(OP)and evaluating BMD,respectively.Receiver operating characteristic curves were drawn,and area under the curves(AUC)were calculated to evaluate the efficacy of each model for classification of OP.Bland-Altman analysis and Pearson correlation analysis were performed to explore the consistency and correlation of each model with QCT for measuring BMD.Results Among ML and Rad models,MLBagging OP and RadBagging-OP had the best performances for classification of OP.In test set,AUC of MLBagging-OP,RadBagging-op and DLOP for classification of OP was 0.943,0.944 and 0.947,respectively,with no significant difference(all P＞0.05).BMD obtained with all the above models had good consistency with those measured with QCT(most of the differences were within the range of(x)±1.96s),which were highly positively correlated(r=0.910-0.974,all P＜0.001).Conclusion AI models based on non-contrast chest CT had high efficacy for classification of OP,and good consistency of BMD measurements were found between AI models and QCT.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.
Fertilizers ; Rhizosphere ; Angelica/chemistry* ; Fungi/genetics* ; Phosphorus

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.
Humans ; Salmonella enterica/genetics* ; Serogroup ; Anti-Bacterial Agents/pharmacology* ; Multilocus Sequence Typing ; Cities ; London ; Clonidine ; Phylogeny ; Genomics ; Drug Resistance ; Electrophoresis, Gel, Pulsed-Field ; Microbial Sensitivity Tests

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.
Young Adult ; Humans ; Female ; Male ; Beijing/epidemiology* ; Tuberculosis ; Tuberculosis, Pulmonary/epidemiology* ; Tuberculosis, Multidrug-Resistant/epidemiology* ; Drug Resistance