Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Objective This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells(CNCs)in mice.Methods The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day(E)8.0-E9.25 were collected for histological observation.We per-formed immunostaining to compare green fluorescent pro-tein(GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5.Single-cell RNA sequencing(scRNA-seq)was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5.Real time fluorescence quantitative polymerase chain reaction(q-PCR)was performed to val-idate the differential genes.Results Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch,respectively,at E8.0.Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues,the former had higher expression in palate and tongue.The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentia-tion and ossification,while Wnt1-Cre-marked CNCs participated in limb development,cell migration,and ossification.The q-PCR data also confirmed the results of gene ontology analysis.Conclusion Pax2-Cre mice are perfect experimen-tal animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.

Objective To propose a Q factor-based fatigue vibration evaluation method of the ultrasonic knife tip.Methods Firstly,an ultrasonic cutter fatigue testing table was established to realize repeated cutting,which was composed of a power supply module,a three-axis moving module,an ultrasonic cutter clamping module and a control module.Secondly,10 ultrasonic knives of some brand underwent fatigue testing with the table,during which non-contact measurement of the ultrasonic knife tip vibration was carried out and the Q factors were calculated at the five periods of the fatigue test,including the periods before cutting,after 500 times of cutting,after 1 000 times of cutting,after 2 000 times of cutting and after 3 000 times of cutting.Finally,the average cutting speed and burst pressure for coagulated vessels were computed at each period to validata the effectiveness of the method proposed.Results It's indicated that Q factor could effectively reflect the fatigue degradation of the ultrasonic knife tip,while the average cutting speed and burst pressure for coagulated vessels were difficult to efficiently evaluate the fatigue degradation level of the ultrasonic knife tip due to the uncertainty factors in the measurement process.Conclusion The proposed Q factor-based evaluation method can directly evaluate fatigue vibration of the ultrasonic knife tip in an accurate and quantitative manner.[Chinese Medical Equipment Journal,2024,45(6):17-22]

Objective To carry out accurate quantative evaluation of MRI scanning noise based on laser vibrometry technology.Methods Skull and spine MRI was performed with mute and conventional sequences.A laser vibrometry device was used to sample the surface vibration noise at the outer edge of the inspection hole of MRI system according to GB/T 16539-1996 Acoustics—Determination of sound power levels of noise sources using vibration velocity—Measurement for seal machinery,and the indicators of sound power level,sound pressure level and perceived noise level obtained by the three calculation methods(LPN1,LPN2 and LPN3)were analyzed with some dedicated MRI noise analysis software.Results The peak sound pressure levels for conventional and mute sequences of skull scanning were 81 and 63 dB(A),respectively,and mute sequence reduced the noise level significantly;the peak sound pressure levels for conventional and mute sequences of spine scanning were 79 and 75 dB(A),respectively,and the noise reduction level was significantly lower than that of skull scanning.Significant differences in noise reduction were not found in spine scanning sequences,while were found in skull scanning sequences.During spine and skull scanning LPN1,LPN2 and LPN3 obtained by the three calculation methods of conventional and mute sequences were all higher than the overall sound power and overall pressure levels obviously.Conclusion Mute sequence can not realize linear noise reduction for the whole frequency band,the perceived noise of the human ear during MRI scanning is related directly to the scanning sequence,and there may be some bias when only one physical indicator is involved in the noise evaluation of MRI system.[Chinese Medical Equipment Journal,2024,45(10):20-24]

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.
Phylogeny ; Genome, Chloroplast ; Codon ; Molecular Sequence Annotation ; Thymelaeaceae/genetics*

Objective:To explore the pathogenesis of gallbladder cholesteryl polyps (GCP) and gallbladder cholesterol calculus (GCC) by studying the different changes of mucin (MUC) expression and reverse cholesterol transporter (RCT) in gallbladder mucosa epithelium.Methods:The data of 10 GCP patients (GCP group), 10 GCC patients (GCC group) and 5 patients with normal gallbladder resection (control group) were retrospectively analyzed, who underwent cholecystectomy in the Department of General Surgery, Xuanwu Hospital, Capital Medical University from January to December 2021. Among the 10 patients in the GCP group, there were 5 males and 5 females, aged (43.40±9.59) years old. Among the 10 patients in the GCC group, 5 males and 5 female, aged (45.00±8.13) years old. Among the 5 patients in the control group, there were 3 males and 2 females, aged (43.80±6.01) years old. Immunohistochemical analysis was used to investigate the expression differences of various subtypes of MUC and RCT [ATP binding cassette transporter G1 (ABCG1) and B group type I scavenger receptor (SR-BI)] among each group.Results:Compared with the control group, the expression of MUC1 (3.40±0.70 vs. 0), MUC5AC (1.50±0.53 vs. 0), MUC6 (4.70±0.48 vs. 0), and ABCG1 (3.50±0.53 vs. 1.60±0.55) in the gallbladder mucosa of the GCP group increased, while the expression score of SR-BI decreased (1.70±0.48 vs. 3.40±0.55), with statistical significance (all P<0.001). Compared with the control group, the expression of MUC1 (4.80±0.42 vs. 0), MUC5AC (4.70±0.48 vs. 0), MUC6 (3.30±0.67 vs. 0), and ABCG1 (3.40±0.52 vs. 1.60±0.55) in the gallbladder mucosa of the GCC group increased, while the expression score of SR-BI decreased (0 vs. 3.40±0.55), with statistically significant differences (all P<0.001). Conclusion:The different expression levels of MUC1, MUC5AC, MUC6, and RCT proteins lead to the differential formation of GCP and GCC on the basis of the co-pathogenesis in high cholesterol in bile.

Objective:To investigate the metabolic profile of fatty acids in elderly frail patients, and its value as a biomarker of frailty.Methods:Forty-nine older adults were recruited, of whom 19 were non-frail while 15 were in the pre-frail or frail phase.Targeted metabolomics was used to detect the serum levels of fatty acids, concerning 38 short-, medium-and long-chain fatty acids.Results:Metabolomics indicated elevated levels of 9 long-chain fatty acids in the serum of the elderly frail patients, with a 1.056-fold increase in the risk of fatigue for every 1 unit increase in the level of HOMO-γ-linolenic acid( OR=2.056, P=0.016). No metabolic differences were found between the pre-frail and non-frail groups.Three and seven long-chain fatty acids were negatively correlated with the grip strength and gait speed, respectively.The γ-linolenic acid was positively correlated with body mass index(BMI), percent body fat, visceral fat area and other indicators reflecting adipose tissue.However, no correlation was found between skeletal muscle, laboratory indicators or fatty acids.Five metabolic pathways were correlated with frailty, namely fatty acid biosynthesis, fatty acid metabolism, fatty acid elongation in mitochondria, linoleic acid metabolism and α-linolenic acid metabolism. Conclusions:Nine unsaturated fatty acids, including HOMO-γ-linolenic acid and γ-linolenic acid, may be potential biomarkers of frailty in the elderly.However, the value of fatty acid metabolomics for identifying pre-frail elderly people needs to be further investigated.