1.Natural killer cell-derived granzyme B as a therapeutic target for alleviating graft injury during liver transplantation.
Kai WANG ; Zhoucheng WANG ; Xin SHAO ; Lijun MENG ; Chuanjun LIU ; Nasha QIU ; Wenwen GE ; Yutong CHEN ; Xiao TANG ; Xiaodong WANG ; Zhengxing LIAN ; Ruhong ZHOU ; Shusen ZHENG ; Xiaohui FAN ; Xiao XU
Acta Pharmaceutica Sinica B 2025;15(10):5277-5293
Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB+ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg -/- Rag2 -/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.
2.Epidemiological surveillance and molecular profiling of brucellosis in Bozhou city, Anhui province
Xiaodong Kang ; Jun Wang ; Shusheng Qian ; Xiangying Wang ; Yunfei Tang ; Xuefei Huai ; Dongdong Jiang ; Yan Liu
Acta Universitatis Medicinalis Anhui 2025;60(5):964-970
Objective :
To illuminate the distribution of brucellosis patients and the epidemic typologies as well as the genetic attributes of brucellosis in Bozhou City,Anhui Province,thereby furnishing a substantive foundation for formulating efficacious prevention and control strategies for this disease within the region.
Methods :
The rose bengal plate agglutination test(RBPT) and the tube agglutination test(TAT) were conducted on a total of 698 blood samples that had been collected.Epidemiological data of the tested subjects were meticulously collected,followed by statistical analyses of the obtained results.The genomic DNA of positive bacterial strains was cultured and extracted.Molecular identification and typing of the isolated strains were executed through 16 S rRNA sequencing.Sequence alignment was conducted employing Clustal W and MEGA 7,with comparisons made against the outcomes of AMOS-PCR and BCSP31-PCR.
Results :
A total of 66 positive samples were detected through serological assays,with a positive rate of 9.46%.The demographic cohort demonstrating the highest detection rate primarily comprised individuals engaged in live sheep slaughtering.The 1 6 S rRNA gene sequencing on ten positive strains disclosed close phylogenetic affinities with Brucella melitensis.Moreover,the phylogenetic tree analysis indicated that these strains coalesced within the same branch,the findings were in alignment with the results obtained from BCSP31-PCR and AMOS-PCR assays.
Conclusion
Brucella melitensis assumes a predominant position in the transmission dynamics within this area,identifying individuals involved in sheep breeding,slaughtering,vending,and related occupations as high-risk groups.The outcomes of this study offer molecular biological substantiation for the distribution of brucellosis patients in this region,contribute to genotyping endeavors and tracing studies associated with the pathogen,and concurrently verify the efficacy of 16S rRNA molecular tracing.
3.Increasing pressure ulcer burden in China:Age and gender differences based on GBD data
Zhenjia HUANG ; Li WU ; Yong TANG ; Dan LI ; Xiaodong LAN
Journal of Army Medical University 2025;47(20):2548-2557
Objective To analyze the burden of pressure ulcers and its changing trends among the general population(all age groups)and the elderly aged 65 years and above in China based on the global burden of disease(GBD)data from 1990 to 2021,predict the burden trends from 2022 to 2035,and address the public health issues of its unclear medium-and long-term trends and insufficient precise interventions in its prevention and control in order to provide support for formulating targeted prevention and control strategies.Methods The GBD database was used to extract the incidence,mortality and disability-adjusted life years(DALYs)of pressure ulcers in the general population and in the elderly aged 65 years and above in China from 1990 to 2021.Meanwhile,the age-standardized incidence rate(ASIR),mortality rate(ASMR),and disability-adjusted life rate(ASDR)of the general population were also extracted,and the age-standardized rate(ASRs)corresponding to the elderly population aged 65 years and above were estimated based on the GBD 2021 standard population.The average annual percentage changes(EAPCs)of ASRs were calculated to assess the trends.Bayesian age-period-cohort(BAPC)model was adopted to predict the ASRs and their changing trends of the general and elderly population from 2022 to 2035,respectively.Results From 1990 to 2021,the number of pressure ulcer cases in the general population of China increased from 163 508.67(95%CI:142 891.48~184 055.10)cases to 397 312.27(95%CI:360 058.44~444 875.78)cases,the number of deaths soared from 242.51(95%CI:125.26~702.84)cases to 3 131.54(95%CI:1 562.60~4 126.85)cases,and DALYs increased from 11 965.10(95%CI:7 820.54~21 703.78)to 61 933.91(95%CI:36 313.26~77 402.42).During the same period,the EAPCs of ASIR,ASMR and ASDR were 1.06(95%CI:0.84~1.28),3.63(95%CI:3.45~3.81),and 2.76(95%CI:2.60~2.92),respectively.In 2021,the number of male cases and DALYs were both higher than those of females,while the number of deaths was similar.The ASIR,ASMR and ASDR of the males were all higher than those of the females,and the growth rates of both genders were relatively fast.All indicators were increased significantly with age.It is predicted that by 2035,the ASIR,ASMR,and ASDR in the general Chinese population will continue to rise significantly.From 1990 to 2021,the number of pressure ulcer cases among the elderly(≥65 years old)in China increased from 42 334.95(95%CI:35 739.05~48 930.84)to 238 431.65(95%CI:212 539.53~264 323.77).The number of deaths rose from 204.97(95%CI:93.33~316.60)to 2 871.02(95%CI:2 334.39~3 407.66),and DALYs increased from 4 619.74(95%CI:2 990.73~6 248.76)to 43 968.28(95%CI:37 542.85~50 393.70).The EAPCs of ASIR,ASMR,and ASDR were 2.62(95%CI:2.44~2.80),3.54(95%CI:3.38~3.70),and 3.28(95%CI:3.14~3.42),all of which increased significantly.In 2021,the number of cases,deaths and DALYs among elderly men and women were similar,but the ASIR,ASMR and ASDR of men were all higher than those of women,and their growth rates were faster.It is projected that by 2035,the ASIR of the elderly population will significantly decline to 146.24(95%CI:140.35~152.14),with an EAPC of-0.57(95%CI:-0.64~-0.50),while the ASMR and ASDR will continue to rise and remain higher in males than in females.Conclusion From 1990 to 2021,the number of pressure ulcer cases,deaths and DALYs among the general population and the elderly in China increased significantly,and the ASRs rose rapidly.The burden of pressure ulcers increases significantly with age and is higher in men than in women.Predictions show that ASIR in the general population will continue to rise,while that in the elderly will slightly decline.However,the ASMR and ASDR will continue to increase.Countermeasures Continuously strengthen the prevention and control of pressure ulcers,implement precise intervention for the elderly,especially older men,promote standardized nursing guidelines,enhance training and resource input in primary medical care,and establish a national pressure ulcer monitoring system.
4.Investigation of the impact and mechanism of IRF2BP2 knockdown on the proliferation in acute myeloid leukemia cells
Bi Zhou ; Xiaodong Tang ; Ying Li ; Yongping Zhang ; Shaoyan Hu
Acta Universitatis Medicinalis Anhui 2025;60(9):1682-1688
Objective:
To explore the effect of interferon regulatory factor 2 binding protein 2 ( IRF2BP2) on the proliferation of acute myeloid leukemia ( AML) cells and its molecular mechanism.
Methods:
The CRISPR-Cas9 gene editing technology was used to knock out IRF2BP2 in human AML cell lines Kasumi-1 and U937,and West- ern blot was performed to detect the knockout efficiency of IRF2BP2 protein.Cell morphology was observed using a microscope.Cell phenotypes were analyzed by CCK-8 assay,colony formation experiments,and flow cytometry. RNA-Seq was performed to identify differentially expressed genes between the IRF2BP2 knockout group and the control group in the U937 cell line.Gene Set Enrichment Analysis ( GSEA) was conducted to explore the down- stream molecular mechanisms.Western blot was used to detect the expression of downstream differentially expressed genes.The Cleavage Under Targets and Tagmentation ( CUT&Tag) technique was applied to identify the direct tar- gets of the IRF2BP2 protein,and the corresponding binding signals were visualized using the Integrated Genomics Viewer ( IGV) .
Results:
Compared with the control group,after knocking out IRF2BP2,the CCK-8 experiment showed that AML cell proliferation was inhibited ( P <0. 05) ; the number of colonies in the IRF2BP2 knockout group decreased ( P<0. 05) ,and the proportion of G1 phase was prolonged ( P<0. 05) ; in U937 cell lines,knoc- king out IRF2BP2 resulted in significant enrichment of differential genes in myelocytomatosis oncogene ( MYC) -re- lated signaling pathways,and the protein expression levels of pathway molecules MYC,cyclin-dependent kinase 4 ( CDK4) ,and cyclin - dependent kinase 2 ( CDK2 ) decreased with the downregulation of IRF2BP2; using IRF2BP2 antibodies in U937 cell lines for CUT&Tag experiments,IGV visualization analysis showed a significant increase in signal peaks in the MYC promoter region.
Conclusion
IRF2BP2 protein affects the cell cycle and pro- liferation of AML cells by targeting and regulating MYC.
5.Dosimetric comparison between abdominal deep inspiration breath hold and free breath in intensity modulated radiotherapy for left breast cancer
Yan ZHANG ; Yun TENG ; Luoyong TANG ; Baoqin XU ; Xiaodong LIN ; Wangyuan HU
Chongqing Medicine 2024;53(4):576-581
Objective To explore the dosimetric differences between abdominal deep inspiration breath hold(ADIBH)mode and free breath(FB)mode in intensity modulated radiation therapy(IMRT)for left breast cancer.Methods From July 2022 to May 2023,a total of 22 patients who needed adjuvant radiation therapy after left breast cancer surgery in the hospital were selected as the research objects.The simulated computed tomography(CT)positioning images of ADIBH and FB modes were collected,the planned target volume(PTV)and endangered organs were outlined,the IMRT plan was designed,and the dosimetric param-eters of the two modes were compared.Results There was no significant difference in the mean dose(Dmean),homogeneity index(HI)and conformity index(CI)of PTV between the ADIBH and the FB modes(P>0.05).Compared with the FB mode,the heart Dmean,V5,V10,V20,V30 and V40 in the ADIBH mode decreased by 2.95 Gy,12.21%,8.26%,6.56%,5.41%and 3.48%,respectively,and the left anterior descending(LAD)coronary artery Dmean,maximum dose(Dmax),minimum dose(Dmin)and V40 decreased by 15.99 Gy,16.10 Gy,0.82 Gy and 13.73%,respectively,with statistical significance(P<0.05).Compared with the FB mode,the dose and volume of heart irradiation in the ADIBH mode at the same level were significantly reduced.Pearson correlation analysis showed that there was a positive correlation between heart Dmean and LAD Dmean in the ADIBH mode(r=0.72),and between heart Dmean and LAD Dmean in the FB mode(r=0.69).Compared with the FB mode,the left lung Dmean of the ADIBH mode decreased by 0.99 Gy,and the difference was statistically significant(P<0.05).However,there was no significant difference in left lung V5,right lung Dmean and right breast Dmean between the two breathing modes(P>0.05).Conclusion ADIBH mode can effectively reduce the dose to the heart and LAD,and play a good protective role.
6.Trans-nasal biliary drainage tube water-injection ultrasound: a new method for detecting residual stones after endoscopic extraction of bile duct stones
Xiaodong WU ; Shaoshan TANG ; Shuodong WU
Chinese Journal of Digestion 2024;44(1):44-49
Objective:To observe the ability of abdominal ultrasonography (hereinafter referred to as water-injection ultrasonography) after injection of 0.9% sodium chloride solution via endoscopic nasobiliary drainage tube in the detection of residual stones in bile duct after stone extraction by endoscopic retrograde cholangiopancreatography (ERCP).Methods:From January 2015 to June 2023, at the Second Department of General Surgery, Shengjing Hospital, China Medical University, 342 patients, who were diagnosed with choledochal stones and received stone extraction by ERCP and at the same time placed endoscopic nasobiliary drainage tube, were enrolled.After stone extraction by ERCP, all the patients underwent cholangiography, conventional abdominal ultrasound, and water-injection ultrasonography. The patients with stones removed by the secondary ERCP were positive. The ability to detect residual stones in bile duct by cholangiography, conventional abdominal ultrasound and water-injection ultrasonography were compared. Chi-square test was performed for statistical analysis.Results:The results of cholangiography showed that 35 patients were suspected with residual stones in bile duct, among them 28 were confirmed to be true-positive, the sensitivity was 50.9% and specificity was 97.6%; the results of conventional abdominal ultrasound showed that 15 patients were suspected with residual stones in bile duct, among them 13 were confirmed to be true positive with a sensitivity of 23.6% and a specificity of 99.3%; and the results of water-injection ultrasonography showed that 56 patients were suspected with residual stones in bile duct, among them 50 were confirmed as true positive, with a sensitivity of 90.9% and a specificity of 97.9%. The number of true-positive patients detected by water-injection ultrasonography was greater than those determined by cholangiography and conventional abdominal ultrasonography, and the sensitivity was higher than that of cholangiography and conventional abdominal ultrasonography, and the differences were statistically significant ( χ2=21.33, 50.85, 38.77 and 92.53, all P<0.001). There was no statistically significant difference in the specificity among water-injection ultrasonography, cholangiography and conventional abdominal ultrasonography (both P>0.05). Conclusion:Water-injection ultrasonography can effectively improve the detection rate of residual stones in bile duct after ERCP.
7.Bacterial community diversity in human Demodex mites
Renren HAN ; Dacun ZHANG ; Lan WANG ; Feifan TANG ; Jiacheng CAO ; Jingxuan WANG ; Xiaodong ZHAN ; Shengli GU
Chinese Journal of Schistosomiasis Control 2024;36(2):174-178
Objective To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. Methods From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. Results A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. Conclusions There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.
8.Analysis of active components of Acorus tatarinowii extracts and its activity against dust mites
Huiyong WANG ; Meiqing WANG ; Feifan TANG ; Lan WANG ; Renren HAN ; Feng JIANG ; Xiaodong ZHAN
Chinese Journal of Schistosomiasis Control 2024;36(2):179-183
Objective To investigate the activity of Acorus tatarinowii extracts against dust mites, and to isolate and characterize active ingredient of A. tatarinowii extracts. Methods The essential oil components were extracted from A. tatarinowii rhizome powder by rotary evaporation with methanol as solvents, followed by petroleum ether extraction and rotary evaporation. The essential oil was mixed with Tween-80 at a ratio of 1:1 and diluted into concentrations of 1.000 00%, 0.500 00%, 0.250 00%, 0.125 00%, 0.062 50% and 0.031 25%, while diluted Tween-80 served as controls. A. tatarinowii essential oil at each concentration (200 μL) was transferred evenly to filter papers containing 100 adult mites, with each test repeated in triplicate, and controls were assigned for each concentration. Following treatment at 25 °C and 75% relative humidity for 24 h, the mean corrected mortality of mites was calculated. The essential oil components were separated by silica gel column chromatography, and the essential oil was prepared in the positive column of medium pressure; and then, each component was collected. Silica gel column chromatography was run with the mobile phase that consisted of petroleum ether solution containing 10% ethyl acetate and pure ethyl acetate, detection wavelength of 254 nm, positive silica gel column as the chromatography column, and room temperature as the column temperature. Each component of the purified A. tatarinowii essential oil was diluted into 1.000 00% for acaricidal tests. The components with less than 100% acaricidal activity were discarded, and the remaining components were diluted into 50% of the previous-round tests for subsequent acaricidal tests. The components with acaricidal activity were subjected to high-performance liquid chromatography, liquid chromatography-mass spectrometry and pulsed-Fourier transform nuclear magnetic resonance spectroscopy. The structure of active monomer compounds was determined by standard spectral library retrieval and literature review. Results A. tatarinowii essential oil at concentrations of 1.000 00%, 0.500 00%, 0.250 00% and 0.125 00% killed all dust mites, and the corrected mortality was all 100%. Exposure to A. tatarinowii extracts at an effective concentration of 0.062 50% for 24 hours resulted in 94.33% mortality of dust mites. Six components (A to F) were separated using gel column chromatography, and components D and E both showed a 100% acaricidal activity against dust mites at a concentration of 0.50000%. In addition, Component D was identified as isoeugenol methyl ether, and Component E as β-asarinol. Conclusion The extract of A. tatarinowii essential oil has acaricidal activity, and the isoeugenol methyl ether shows a remarkable acaricidal activity against dust mites.
9.Effectiveness analysis of life support equipment in clinical assisted decision-making under the background of intelligent intensive care unit construction
Xiaodong WANG ; Jun YANG ; Jie TANG ; Yali WU
China Medical Equipment 2024;21(2):132-137
Objective:Based on the construction of intelligent intensive care unit(ICU)in hospital,to analyze the effectiveness of intelligent ICU life support equipment in clinical decision-making assistance.Methods:The functional modules of the ICU ward interaction system,equipment management system,risk response system and intelligent ward round system were designed to collect information and data of life support equipment in diagnosis and treatment,nursing,operation and technical support in real time to provide medical auxiliary decision-making basis for the improvement of diagnosis,treatment and nursing measures for critically ill patients.115 life-support equipment in clinical use in 3 hospitals including Zhujiajiao People's Hospital of Qingpu District,Shanghai from July 1,2018 to December 31,2022 were selected,the traditional assisted decision-making management mode(referred to as traditional mode,83 sets)and intelligent assisted decision-making management mode(referred to as intelligent mode,89 sets,including 57 units of the traditional mode and 32 newly added units)were adopted respectively.The management level and management effect of life support equipment of the two management modes were compared.Results:The data collection time of the equipment of intelligent mode was(5.67±2.80)min,which was less than that of the traditional mode,the accuracy and completeness of data acquisition,as well as the effective resolution rate of equipment deployment and use,monitoring and alarm,equipment failure and emergency response were(99.02±1.14)%,(94.35±3.46)%,(98.78±0.90)%,(98.99±0.91)%,(88.26±5.31)% and(90.23±5.54)%,respectively,which were higher than those of the traditional mode,the difference between was statistically significant(t=6.504,6.474,3.574,7.620,6.784,4.522,3.719,P<0.05).The effective utilization rates of diagnostic decisions for treatment,care and rehabilitation of intelligent mode equipment were(93.83±3.12)%,(94.99±2.47)% and(91.44±4.62)%,respectively,the comprehensive scores of respiratory function support equipment,circulatory function support equipment,blood purification support equipment and emergency monitoring support equipment were(92.97±4.35)points,(94.34±2.95)points,(93.01±2.44)points and(94.11±1.89)points,respectively,which were higher than those of the traditional mode,the difference was statistically significant(t=4.169,4.875,5.159,4.069,3.033,2.757,6.893,P<0.05).Conclusion:Based on the construction of intelligent ICU,it can improve the quality of life support equipment operation data collection,solve the equipment operation problems in a timely manner,provide an effective basis for the decision-making of diagnosis and treatment,nursing and rehabilitation of critically ill patients,and improve the clinical service level of equipment.
10.Application of shear wave elastography in T restaging for locally advanced rectal cancer after neoadjuvant chemoradiotherapy
Qingfu QIAN ; Minling ZHUO ; Yi TANG ; Xiaodong LIN ; Ensheng XUE ; Zhikui CHEN
Chinese Journal of Ultrasonography 2024;33(1):71-76
Objective:To investigate the application value of shear wave elastography (SWE) in the evaluation of T re-staging after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer.Methods:Clinical, endorectal ultrasound (ERUS) and SWE data of 271 patients with locally advanced rectal cancer who underwent nCRT and total mesorectal excision in Fujian Medical University Union Hospital from October 2021 to March 2023 were prospectively collected. The independent predictors for low T staging were analyzed and screened, and the Logistic regression model was constructed. An independent test set was used to validate the prediction performance of the models and compare them with the diagnostic results of sonographers.Results:Binary multivariate Logistic regression analysis showed that Emean of the mesentery around the lesion, thickness, and enlarged lymph nodes around the rectum were the independent predictors for low T staging, and the odds ratios were 1.089, 1.214, 0.183, respectively. The Logistic regression model A established by Emean, thickness and enlarged lymph nodes around the lesion and the Logistic regression model B established by Emean around the lesion had high diagnostic efficiencies (area under the ROC curve were 0.931, 0.918, respectively, the accuracy were 0.888 and 0.887, respectively). There was no significant difference in diagnostic accuracy between the two models ( P=1.000), and both models were significantly higher than that of sonographers (all P<0.001). Conclusions:SWE can effectively predict whether the tumor is of low T staging after nCRT in locally advanced rectal cancer, and can be used as an important supplement to ERUS in evaluating the T re-staging of rectal cancer after nCRT.


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