1.Genetic analysis and prenatal diagnosis of structural brain abnormalities associated with TUBB gene c.155A>G variant.
Yifan LIU ; Wei SONG ; Xinlian WANG ; Yan RUAN ; Meng ZHANG ; Yujiao CHEN ; Yan LIU ; Puqing ZHANG ; Li WANG ; Yousheng YAN
Chinese Journal of Medical Genetics 2026;43(2):136-142
OBJECTIVE:
To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene.
METHODS:
A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01).
RESULTS:
Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3).
CONCLUSION
The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans
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Female
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Pregnancy
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Prenatal Diagnosis
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Tubulin/genetics*
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Adult
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Brain/diagnostic imaging*
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Male
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Pedigree
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DNA Copy Number Variations/genetics*
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Exome Sequencing
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Genetic Association Studies
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Magnetic Resonance Imaging
2.Relationship between RNase3 Gene Polymorphism and Its Expression Level with Airway Inflammation and Glucocorticoid Efficacy in Children with Bronchial Asthma
Huimin MA ; Xiaojing ZHOU ; Donge LU ; Yujiao YAN
Journal of Modern Laboratory Medicine 2025;40(2):164-168
Objective To explore the relationship between ribonuclease A3(RNase3)gene polymorphism and its expression level with airway inflammation and glucocorticoid efficacy in children with bronchial asthma(BA).Methods A total of 110 children with bronchial asthma admitted to Handan Maternal and Child Health Hospital June 2022 to June 2024 were selected as the study objects.According to the severity of the condition at admission,they were divided into mild group(n=64),moderate to severe group(n=46),and children who underwent physical examination in the hospital during the same period were selected as the control group(n=82).Molecular weight array gene analysis(MassArray)was used to detect the genotyping of RNase3 gene rs2073342 locus.Quantitative real-time PCR(RT-PCR)was used to detect the expression level of RNase3 mRNA.The clinical data of the children were collected,and the differences of genotype and allele frequency were compared.The relationship between RNase3 gene polymorphism and BA susceptibility was analyzed by unconditioned Logistic regression.Results Compared with the mild group,IL-6(21.49±3.01ng/L vs 13.21±2.84ng/L)and PCT(19.16±4.02μg/L vs 9.94±3.15μg/L)in the moderate and severe group were significantly increased(t=-14.568,-12.952),while FVC,PEF and FEV1 were significantly decreased(t=2.534,3.304,2.011),and the differences were statistically significant(all P<0.05).The genotype distribution of RNase3 gene rs2073342 in both control and study groups was consistent with Hardy-Weinberg balance law(χ2=0.402,0.689,all P>0.05),indicating population representation.Compared with the control group and the mild group,the CC,CA genotype frequencies were higher in moderate to severe group(χ2=35.008,23.079),Compared with the control group,the frequency of CC and CA genotypes in mild group was higher(χ2=7.325),the differences were statistically significant(all P<0.05).Compared with mild group,RNase3 mRNA expression in peripheral blood mononuclear cells of children with C gene BA at rs2073342 in moderate to severe group was higher,and the difference was statistically significant(t=-19.622,P<0.05).In the same group,the mRNA expression level of RNase3 in peripheral blood mononuclear cells of the children with C gene BA at rs2073342 was higher than that of the children without C gene(t=4.169,22.608,all P<0.05).Unconditional Logistic regression results showed that RNase3 gene carrying allele C or dominant model(CC vs CA+AA)was a risk factor for severe disease in BA children(P<0.05).The total effective rate of genotype AA carriers was the highest after glucocorticoid therapy,and the therapeutic effect of genotype AA carriers was significantly better than that of genotype AC and CC,and the difference was statistically significant(χ2=11.858,P<0.05).Conclusion The expression of RNase3 mRNA in peripheral blood of BA children increased significantly with the exacerbation of the disease.Carrier of allele C or dominant model(CC vs CA+AA)is a risk factor for severe disease in BA children.Genotype AA carriers had better therapeutic effect.
3.Establishment and evaluation of method for rapid detection of Bacillus cereus cytK and nhe toxin genes by dual nucleic acid test strips
Jifei YANG ; Beizhen PAN ; Yan LIU ; Yujiao ZHOU ; Jianyu YANG ; Xianyu ZHANG ; Wenbo DING ; Haoyu LI ; Liyuan SUN
Journal of Jilin University(Medicine Edition) 2025;51(2):516-525
Objective:To establish a method of dual nueleic acid test strips for rapid detection of Bacillus cereus cytK and nhe toxin genes based on polymerase chain reaction(PCR)and colloidal gold technique,and to evaluate its specificity,sensitivity,repeatability and stability.Methods:Bacillus cereus DNA was extracted by boiling method.Specific primers were designed with Bacillus cereus cytK and nhe as the target genes.Clonal transformation was used to identify the PCR products.The optimal labeling amounts of colloidal gold-labeled streptavidin,quality control line(C line),cytK detection line(T1)and nhe detection line(T2)were determined.The nucleic acid test strips were assembled and its specificity,sensitivity,reproducibility and stability were evaluated.Results:The DNA concentration of Bacillus cereus was 248 mg·L-1,and the purities were 1.8-2.0.After cloning and plasmid sequencing,the similarities between the PCR products and the sequences of cytK and nhe registered in the GenBank database were 100%.Under the condition of pH 7.0,the optimal amount of streptavidin labeling per 200 μL of colloidal gold solution was 6.0 μL;the optimal marking amount was 2.00 g·L-1 for the quality control line(C line),0.550 g·L-1 for cytK gene detection line(T1)and 0.2 g·L-1 for nhe gene detection line(T2).In the specificity test,positive result on the test strips was seen only for Bacillus cereus,and no cross-reactivity was observed for Staphylococcus aureus,Escherichia coli,Pseudomonas aeruginosa and Bacillus subtilis,which were consistent with the electrophoresis results.Sensitivity assay showed that even when DNA concentration was reduced to 10-2 mg·L-1,three bands(C line,T1 line and T2 line)could be observed,and the detection limit of the test strip was one-tenth of agarose gel electrophoresis(10-1 mg·L-1).The nucleic acid test strips were verified by different operators in different laboratories,and the results were consistent.The stability of the test strips was verified at the 6th,9th and 12th months,and the results showed good stability.Conclusion:The dual nucleic acid test strip method established in this study can simutaneously detect the cytK and nhe toxin genes of Bacillus cereus with high sensitivity and specificity,achieving short-term visual detection.
4.Establishment of LAMP combined with CRISPR/Cas12a system for detecting tlh gene of Vibrio parahaemolyticus and its evaluation
Yujiao ZHOU ; Jifei YANG ; Yan LIU ; Wenbo DING ; Xianyu ZHANG ; Jianyu YANG ; Linran GAO ; Yundong ZHAO ; Liyuan SUN
Journal of Jilin University(Medicine Edition) 2025;51(5):1399-1406
Objective:To establish a rapid detection method for pathogenic microorganisms by combining loop-mediated isothermal amplification(LAMP)and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 12a(Cas12a)(CRISPR-Cas12a)system,and to evaluate its efficacy for detecting the thermolabile hemolysin(tlh)gene of Vibrio parahaemolyticus(Vp).Methods:Using the tlh gene of Vp as the target gene,LAMP primers and CRISPR RNA(crRNA)were designed to construct and optimize the optimal concentration ratio of each component in the LAMP-CRISPR detection system.Bacillus cereus,Staphylococcus aureus,and Escherichia coli were used as control groups,and the specificity,sensitivity,reproducibility and positive conformity rate were verified to establish a rapid LAMP-CRISPR/Cas12a method for detecting the tlh gene of Vp.Results:The method specifically detected Vp,while Bacillus cereus,Staphylococcus aureus,and Escherichia coli yielded negative results.The DNA extraction concentration of Vp was 190.67 mg·L-1 with an A(260)/(A280)ratio of 1.84.Under the reaction conditions of 37℃ with 80 cycles for 40 min using quantitative PCR(qPCR)method,when the concentrations of Cas12a protein and crRNA in the LAMP-CRISPR/Cas12a system were 50 nmol·L-1,the visual brightness and relative fluorescence intensity peaks were high.The sensitivity of LAMP CRISPR/Cas12a for detecting Vp DNA concentration could reach 10-6 mg·L-1.The reproducibility test results showed that different experimenters had consistent results in different experimental environments and times.Conclusion:The established LAMP-CRISPR/Cas12a method can rapidly detect the tlh gene of Vp with high sensitivity and specificity,and can achieve short-term visual detection in the field.
5.Clinical significance of corrected serum calcium level in newly-diagnosed multiple myeloma patients and analysis of influencing factors of concomitant hypercalcemia
Yujiao FENG ; Caili PEI ; Yan KANG
Journal of Leukemia & Lymphoma 2025;34(7):416-421
Objective:To explore the relationship between corrected serum calcium level and clinical characteristics in patients with newly-diagnosed multiple myeloma (MM), as well as the influencing factors of concomitant hypercalcemia.Methods:A retrospective case cohort study was conducted. The clinical data of newly-diagnosed MM patients who were admitted to Shanxi Province Cancer Hospital from January 2020 to December 2023 were collected. When serum albumin (ALB) was less than 40 g/L, the serum calcium level was corrected. The hypercalcemia group was defined as the corrected serum calcium level >2.60 mmol/L, the normal blood calcium group was defined as 2.20-2.60 mmol/L, and the hypocalcemia group was defined as <2.20 mmol/L; the combination of normal blood calcium group and hypocalcemia group was the non-hypercalcemia group. The age, gender, immune typing, ALB, blood urea nitrogen (BUN), serum creatinine (Scr), β 2-microglobulin (β 2-MG), and alkaline phosphatase (ALP) of patients in the hypercalcemia group and the non-hypercalcemia group were compared. Pearson correlation analysis was used for the correlation analysis. The logistic regression model was used to conduct multivariate analysis on the influencing factors of hypercalcemia. Results:Before correction, there were 31 cases (26.5%), 48 cases (40.0%) and 38 cases (32.5%) of MM patients in the hypocalcemia group, normal blood calcium group and hypercalcemia group, respectively. After correction, there were 17 cases (14.5%), 58 cases (49.6%) and 42 cases (35.9%), respectively. The corrected serum calcium level for male MM patients was (2.58± 0.41) mmol/L, while for females it was (2.53±0.38) mmol/L, and there was no statistically significant difference between the two groups ( t = 0.79, P > 0.05). The corrected serum calcium levels for patients in stage Ⅰ, stage Ⅱ and stage Ⅲ of the International Staging System (ISS) were (2.31±0.15) mmol/L, (2.52±0.37) mmol/L and (2.65±0.42) mmol/L, respectively, and the difference between the three groups was statistically significant ( F = 53.62, P < 0.01). Corrected serum calcium showed a negative correlation with patients' serum ALB ( r = -0.201, P < 0.05), and positive correlations with Scr, BUN and β 2-MG levels ( r values were 0.470, 0.247 and 0.469, respectively, all P < 0.01), but it had no correlation with age or ALP ( r values were -0.013 and 0.078, respectively, both P > 0.05). There were 15 cases (17.1%), 48 cases (54.5%) and 25 cases (28.4%) of patients with normal renal function in the hypocalcemia group, normal blood calcium group and hypercalcemia group, respectively; there were 2 cases (6.9%), 10 cases (34.5%) and 17 cases (58.6%) of patients with impaired renal function in the hypocalcemia group, normal blood calcium group and hypercalcemia group, respectively; there were statistically significant differences between the hypocalcemia group and the hypercalcemia group, as well as between the normal blood calcium group and the hypercalcemia group ( χ2 = 4.57, P < 0.05; χ2 = 6.67, P < 0.05), but there was no statistically significant difference between the hypocalcemia group and the normal calcium group ( χ2 = 0.29, P>0.05). The patients with approximately normal bone status in the hypocalcemia group, normal blood calcium group and hypercalcemia group were 3 cases (13.0%), 17 cases (74.0%) and 3 cases (13.0%), respectively, and the patients with bone damage were 14 cases (14.9%), 41 cases (43.6%), and 39 cases (41.5%), respectively, and there was a statistically significant difference between the normal blood calcium group and the hypercalcemia group ( χ2 = 7.48, P < 0.01), while there was no statistically significant difference between the hypocalcemia group and the hypercalcemia group ( χ2 = 1.46, P > 0.05). The proportions of patients with Scr > 177 μmol/L and β 2-MG > 3.5 mg/L in the hypercalcemia group were higher than those in the non-hypercalcemia group, and the differences were statistically significant (both P < 0.05). The results of logistic regression multivariate analysis showed that β 2-MG >3.5 mg/L was an independent risk factor for hypercalcemia in newly-diagnosed MM patients ( OR = 1.178, 95% CI: 1.058-1.311, P = 0.003). Conclusions:Corrected serum calcium level may be an important indicator for evaluating the severity of disease, renal function and bone status in newly-diagnosed MM patients.
6.Clinical observation and insights on pathological changes during "deep cervical lymphaticovenous anastomosis+" in elderly patients with cognitive impairment
Xiaoju ZHENG ; Haijun LI ; Jinming ZHANG ; Fang LI ; Baoshan WANG ; Yuqi ZHENG ; Wenbin SONG ; Yan WANG ; Xinhong WANG ; Qian LIN ; Shuang DU ; Dengwen ZHANG ; Rongguo YANG ; Peng HE ; Zhe CHANG ; Yujiao LI ; Linjuan WU
Chinese Journal of Microsurgery 2025;48(3):268-276
Objective:To investigate intraoperative pathological findings and the interventional effects of "deep cervical lymphaticovenous anastomosis+" (dcLVA+) on deep cervical lymphatic drainage as well as the blood flow of carotid artery and jugular vein in elderly patients with cognitive impairment, and to put forward the thoughts based on the findings from the surgery.Methods:Between May 2024 and December 2024, retrospective analysis of Microsurgery Hospital, Fengcheng Hospital, Xi'an Medical College performed dcLVA+ between the deep cervical lymphatics or lymph nodes and jugular veins in 50 elderly patients with cognitive impairment (19 males and 31 females, aged 55-88 years with 69.94 years in average). Nine patients were found with Clinical Dementia Rating (CDR) score at 1 (mild), 7 with CDR score at 2 (moderate) and 34 with CDR score at 3 (severe). Intraoperative observations based on literature reviews had identified anatomical relationships between the lymphatic sacs containing cervical lymphatic chain and the carotid sheath. The lymph node count, size, distribution, thickness of fat tissue and conditions of lymphatic vessels were documented. Ultrasound was used to compare the blood flow of carotid artery and jugular vein as well as the cross-sectional areas at the planes of hyoid and cricoid cartilage before and after the closure of incisions under anaesthesia in 39 patients. Correlation analyses for Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Activities of Daily Living (ADL) and Agitation behavior score before and 1 week after surgery were performed using Spearman's correlation and Wilcoxon paired tests. P<0.05 was considered statistically significant. Postoperative follow-ups were conducted via the visit of outpatient clinic and WeChat and telephone interviews. Results:In surgery, the cervical lymphatic chain was found running within an almost enclosed sac surrounding the carotid sheath. There were enlarged lymph nodes, increased fat deposition, lymphatic dilation or fibrosis in the sac. The preoperative blood flow in the carotid artery at the planes of hyoid and cricoid cartilage in the 39 patients was recorded at 150.52 ml/min±40.33 ml/min and 358.29 ml/min±129.30 ml/min, while that in the jugular vein was at 172.50 ml/min±63.94 ml/min and 317.00 ml/min±105.21 ml/min, respectively, both were far lower than the normal blood flow. There were statistically significant differences in the blood flow of carotid artery and jugular vein before and after surgery ( P<0.01). It was found that the preoperative blood flow of the internal carotid artery at the plane of hyoid was positively correlated with the preoperative scores of MMSE ( P<0.01), MoCa ( P<0.05) and ADL ( P<0.01). The blood flow of the common carotid artery at the plane of cricoid cartilage was found significantly and positively correlated with the preoperative scores of MMSE ( P<0.05). It was also noted that the blood flow of the internal carotid artery at the plane of hyoid was significantly and positively correlated with the postoperative ADL ( P<0.01) but negatively correlated with the Agitation behavior score ( P<0.05). The blood flow of the common carotid artery at the plane of cricoid cartilage was significantly and positively correlated with the postoperative scores of MMSE and MoCa ( P<0.05). The blood flow of the internal jugular vein at the plane of hyoid was negatively correlated with the Agitation behavior score ( P<0.01). The cross-sectional area of carotid artery at the plane of left hyoid was significantly and positively correlated with the MMSE score ( P<0.05). Statistically significant differences were observed in MMSE, MoCa, ADL and Agitation behavior score before and after surgery ( P<0.01). Conclusion:dcLVA+ shows a certain therapeutic benefit to the elderly patients with cognitive impairment. The intraoperatively observed pathological changes in cervical lymphatic sacs affect deep cervical lymphatic drainage and the blood flow of carotid artery and jugular vein. Further studies are necessary to find out whether the findings from this study would be the specific pathological changes and the morbidity mechanisms among the elderly patients with cognitive impairment.
7.Research on the current status and influencing factors of the multidimensional symptom network in maintenance hemodialysis patients
Li CHENG ; Yujiao ZOU ; Tiantian HU ; Chumin JI ; Yiyang QIU ; Zheng ZHU ; Yongmei ZHANG ; Yan WU
Chinese Journal of Nursing 2025;60(19):2321-2327
Objective To investigate the current symptom status of maintenance hemodialysis(MHD)patients,analyze the influencing factors from the perspective of multidimensional symptom burden,extract symptom groups,and construct a symptom network.Methods A total of 490 patients who received MHD at the blood purification center of a tertiary hospital in Shanghai from March to April 2025 were selected using a convenience sampling method.30 symptoms of MHD patients were investigated using a modified dialysis symptom index table.SPSS and R software were utilized to analyze the influencing factors,extract symptom groups,and construct a multidimensional symptom network.Results A total of 488 valid questionnaires were collected,with a valid questionnaire recovery rate of 99.59%.The median number of symptoms experienced by patients was 6(interquartile range:4,8),with the top 5 symptoms being dry skin(69.88%),fatigue or tiredness(56.97%),itching(56.97%),worry(50.20%),and dry mouth(46.31%).Multidimensional analysis indicated that age,duration of dialysis,education level,and complications were influencing factors of symptom burden scores across different dimensions.6 stable symptom groups were extracted,namely skin discomfort,fatigue and pain,gastrointestinal tract,sleep disorders,water-electrolyte imbalance,and uremia.The results of the symptom network analysis revealed that difficulty of falling asleep had the highest intensity centrality(rs=2.18,2.25,2.12).Conclusion The symptom association is relatively stable,and difficulty of falling asleep is the core symptom.This finding can assist clinical medical staff in achieving efficiency and precision in symptom group management.
8.Study on Functional Substance Basis of Jinhong Tablet Based on GES-1 Cell Model and Mouse Gastric Organoid Model
Lihao XIAO ; Wenjing ZHAO ; Gaoshuang ZHU ; Yujiao YAN ; Xinzhuang ZHANG ; Liang CAO ; Zhenz-hong WANG ; Xiaoxue FAN ; Tong ZHANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):869-880
OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.
9.Clinical and molecular characteristics of myeloproliferative neoplasms patients with NFE2 gene mutations
Songyang ZHAO ; Bing LI ; Zefeng XU ; Tiejun QIN ; Shiqiang QU ; Lijuan PAN ; Meng JIAO ; Qingyan GAO ; Huijun WANG ; Qi SUN ; Yujiao JIA ; Yiru YAN ; Jingye GONG ; Fuhui LI ; Xin WANG ; Zhijian XIAO
Chinese Journal of Hematology 2025;46(10):943-951
Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.
10.Pathogenic Bacteriology and Antimicrobial Treatment of 161 Patients with Biliary Calculi Complicated by Acute Biliary Tract Infection
Dan LIN ; Lindan LIAO ; Zhiqiang LIU ; Kezhang HU ; Yan GAO ; Yujiao LUO ; Wenting CHEN ; Xiaofang XIE ; Bichuan SU ; Lingyan LUO ; Jing TANG
Herald of Medicine 2025;44(5):770-777
Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

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