1.Biological and genetic characteristics of three hypervirulent Klebsiella pneumoniae strains causing liver abscess
Yuqi ZHANG ; Juan WANG ; Lei HAN ; Pu LI ; Wentao MA ; Chun ZHANG ; Yali LI ; Jing YUAN ; Jin’e LEI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):885-894
[Objective] To understand the resistance mechanisms, virulence characteristics, and pathogenicity of hypervirulent Klebsiella pneumoniae (hvKp), which causes pyogenic liver abscess (PLA), and to provide related data for clinical treatment of infection caused by this type of bacteria. [Methods] We collected three strains of Klebsiella pneumoniae isolated from the liver abscess fluid of patients with liver abscesses in various departments of The First Affiliated Hospital of Xi’an Jiaotong University. The hypervirulent phenotypes were determined by the wire test, and drug sensitivity was assessed using the VITEK 2 compact automatic microbiological analyzer. Molecular characteristics such as podocarp serotypes, multi-locus sequence typing (MLST), virulence genes, and drug resistance genes were identified through whole-genome sequencing. Additionally, a mouse infection model was established to evaluate pathogenicity. [Results] The isolates were sticky, with mucous thread pulling length >5 mm, all of which exhibited high viscosity phenotypes. Except 146007, which is a multidrug-resistant bacterium, the other two strains had higher antibiotic sensitivity. Whole genome sequencing revealed that the isolates were of high-virulence type, carrying the toxin plasmid rmpADC/rmpA2, iron uptake system, bacterial hairs, secretion system, and other virulence factors. All the three isolates tested positive for rmpA/rmpA2 combined with iucA/iutA, indicating they could be classified as hvKp. Multiple resistance genes were detected, such as β-lactamase like bla
2.Simultaneous determination of gefitinib,erlotinib,nilotinib and imatinib concentrations in plasma by HPLC-MS/MS
Tian-Lun ZHENG ; Jing-Pu XU ; Zhu-Hang HAN ; Wen-Li LI ; Wei-Chong DONG ; Zhi-Qing ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):899-903
Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)for the simultaneous determination of gefitinib,erlotinib,nillotinib and imatinib plasma concentrations and analyze the results.Methods The plasma samples were treated with acetonitrile precipitation and separated by Diamonsil C18 column(150 mm ×4.6 mm,3.5 μm)with mobile phase of 0.1%formic acid water(A)-0.1%formic acid acetonitrile(B).The flow rate of gradient elution was 0.7 mL·min-1,and the column temperature was 40 ℃ and the injection volume was 3 μL.Using arotinib as the internal standard,the scanning was carried out by using electrospray ionization source in positive ionization mode with multi-reaction monitoring.The specificity,standard curve,lower limit of quantitation,precision,accuracy,recovery rate,matrix effect and stability of the method were investigated.The concentrations of imatinib and erlotinib in 20 patients with chronic myelogenous leukemia(CML)and gefitinib and erlotinib in 3 patients with non-small cell lung cancer were measured.Results The standard curves of the four drugs were as follows,gefitinib:y=2.536 × 10-3x+9.362 × 10-3(linear range 20-2 000 ng·mL-1,R2=0.996 6);erlotinib:y=3.575× 10-3x+7.406 × 10-3(linear range 50-5 000 ng·mL-1,R2=0.994 9);nilotinib:y=1.945 x 10-3x+0.015 643(linear range 50-5 000 ng·mL-1,R2=0.990 6);imatinib:y=4.56 x 10-3x+0.010 451(linear range 100~104 ng·mL-1,R2=0.9963).RSD of intra-day and inter-day were less than 10%,and the accuracy ranged from 90%to 110%,and the recovery rates were 91.35%to 98.93%(RSD<10%);the matrix effect ranged from 91.64%to 107.50%(RSD<10%).Determination of 23 patients showed that the blood concentration of nilotinib ranged from 623.76 to 2 934.13 ng·mL-1,and the blood concentration of imatinib ranged from 757.77 to 2 637.71 ng·mL-1,and the blood concentration of gefitinib ranged from 214.76 to 387.40 ng·mL-1.The serum concentration of erlotinib was 569.57 ng·mL-1.Conclusion The method of this research is simple,fast,sensitive and dedicated,which can be monitored by the concentration of clinical blood.
3.Analysis on the quality of wild and different cultivation methods of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai
Chenchen WU ; Lu YAN ; Jingzhe PU ; Yazhong ZHANG ; Lan HAN
International Journal of Traditional Chinese Medicine 2024;46(2):209-214
Objective:To compare and evaluate the quality of wild and different cultivation methods of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai through analysis on UPLC characteristic atlas and multi-component content determination results. Methods:UPLC was used to establish the characteristic chromatogram and multi-component content determination method of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai, and clustering analysis, orthogonal partial least squares - discriminant analysis method were used for chemical pattern recognition analysis. Results:The results showed that there were 10 common peaks in 18 batches of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai. Five components were identified, erythrothioneine(peak 1), protocatechuic acid (peak 2), protocatechualdehyde (peak 3), caffeic acid (peak 4) and Hispidin (peak 5). HCA and OPLS-DA could distinguish Sanghuang porus vaninii (Ljub.) with different cultivation methods. Conclusion:Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai in wood is closer to wild Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai than in substitute cultivation. The UPLC characteristic atlas and multi-component content determination method established in this study can provide reference for the quality evaluation of Sanghuang porus vaninii (Ljub.) L.W. Zhou & Y.C. Dai.
4.Research progress in regulation and mechanism of transcription factors on tanshinones
Yan-hong BAI ; Lin-lin XIN ; Ting ZENG ; Feng-xia HAN ; Yong-qing ZHANG ; Gao-bin PU ; Xue CHEN ; Qian LIU
Acta Pharmaceutica Sinica 2024;59(5):1218-1228
italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of
5.Expression and significance of ubiquitin-specific proteases 20 and hypoxia inducible factor-1α in breast cancer
Lingyu FANG ; Jinghua HU ; Junfeng WEN ; Shiqi HAN ; Yali WANG ; Lulan PU ; Jingjia LI ; Yi YANG ; Shishan DENG ; Lingmi HOU ; Fangfang ZHOU
The Journal of Practical Medicine 2024;40(16):2270-2276
Objective To explore the changes and significane of USP20 and HIF-α expression in breast cancer.Methods Following transfection of shRNA-USP20 lentivirus into breast cancer MDA-MB-231 cells,the gene and protein expression levels of USP20 were detected using fluorescence quantitative PCR and Western Blot.Subsequently,the overexpression of USP20 was observed to determine its effect on HIF-α expression.Similarly,siRNA-USP20 was used to knock down USP20 in breast cancer MDA-MB-231 cells,followed by detection of gene and protein expression levels using fluorescence quantitative PCR and Western Blot.The subsequent changes in HIF-α expression were then examined.Rusults The positive expression rates of USP20 and HIF-α in breast cancer tissues were 69.6%and 46.83%,respectively,while they were negatively expressed in the adjacent normal tissues,with statistically significant differences(P<0.01).The positive expressions of USP20 and HIF-α were predomi-nantly observed in the cytoplasm of breast cancer tissue,with a smaller amount present in the nucleus.There was a significant positive correlation between USP20 and HIF-α in breast cancer.Following transfection of shRNA-USP20 lentivirus into MDA-MB-231 cells,both the protein and gene expression levels of USP20 significantly increased(P<0.01).Over-expression of USP20 did not affect HIF-α mRNA levels but led to a significant increase in HIF-α protein expression(P<0.01).Conversely,siRNA-USP20 interference resulted in a significant decrease in both the protein and gene expression levels of USP20(P<0.01),without affecting HIF-α mRNA levels;however,it caused a notable reduction in HIF-α protein expression(P<0.01).Conclusion The expression of USP20 exhib-ited a significant positive correlation with HIF-α in breast cancer.Overexpression of USP20 led to a substantial increase in HIF-α protein expression,while knock-down of the USP20 gene resulted in a significant decrease in HIF-α protein levels.Therefore,it can be inferred that USP20 may exert its influence on the development of breast cancer through modulation of HIF-α expression,thereby providing crucial experimental evidence for clinical treat-ment,prognosis,and further investigations.
6.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.
7.Early warning value of blood urea nitrogen to albumin ratio combined with soluble growth stimulation expressed gene 2 on sepsis-induced myocardial injury in elderly patients in emergency intensive care unit
Yongyan HAN ; Junli YANG ; Huimin MENG ; Hao YAO ; Pu WANG ; Qingmian XIAO ; Weizhan WANG
Chinese Journal of Geriatrics 2024;43(6):727-732
Objective:To examine the potential of combining the blood urea nitrogen(BUN)/albumin(ALB)ratio(BAR)with soluble growth stimulation expressed gene 2(sST2)as an early warning indicator for myocardial injury in elderly patients with sepsis in the emergency intensive care unit(EICU).Methods:The clinical data of elderly patients with sepsis admitted to the EICU of the Emergency Medicine Department at Harrison International Peace Hospital of Hebei Medical University from August 2018 to August 2022 were prospectively analyzed.The patients were divided into two groups based on the presence or absence of myocardial injury: the myocardial injury group and the non-myocardial injury group.The general clinical data and laboratory indexes of the two groups were compared, and the BAR was calculated.The correlation between BAR and myocardial injury in elderly patients with sepsis was analyzed.Binary Logistic regression analysis was used to identify the risk factors for myocardial injury in elderly patients with sepsis in the EICU.MedCalc software was employed to determine the early warning value of the combined sST2 and BAR for myocardial injury in elderly patients with sepsis in the EICU.Results:A total of 165 cases were analyzed, with 106 cases(64.24%)showing myocardial injury.It was found that elderly sepsis patients with lung and abdominal infection were more likely to experience myocardial injury( P<0.05 for all).In comparison to the group without myocardial injury, the levels of inflammatory markers such as white blood cell count(WBC), neutrophil to lymphocyte ratio(NLR), lactic acid, and procalcitonin(PCT), as well as combined markers BAR and sST2, were higher in elderly sepsis patients with myocardial injury upon admission.Correlation analysis results revealed significant positive correlations between BAR and lactic acid, PCT, and C-reactive protein(CRP)within 24 hours of admission to EICU in elderly sepsis patients with myocardial injury.Among these correlations, the strongest was observed between BAR and PCT( r=0.417, P<0.001).Additionally, BAR exhibited a positive correlation with acute physiology and chronic health evaluation scoring system(APACHEⅡ)scores( r=0.241, P=0.002).Furthermore, BAR showed positive correlations with myocardial injury markers sST2 and cTnI( r=0.327, 0.307, P<0.05 for all).Logistic regression analysis revealed that septic shock( OR=2.406, P=0.008), decreased left ventricular ejection fraction(EF)( OR=0.939, P=0.015), BAR( OR=2.205, P=0.044), lactic acid( OR=1.137, P=0.014), and sST2 elevation( OR=1.016, P=0.020)were identified as independent risk factors for predicting myocardial injury in elderly patients with sepsis.The results of ROC analysis indicated that BAR had a high early warning value for the occurrence of myocardial injury in elderly patients with EICU sepsis[area under curve(AUC)0.651, P<0.05], with an optimal cut-off value of 0.32(sensitivity 77.4%, specificity 60.2%).Furthermore, the combined detection of BAR and sST2 demonstrated a higher early warning value for the occurrence of myocardial injury in elderly patients with sepsis(AUC 0.697, P<0.05).The mortality rate of patients with myocardial injury below a cut-off value of 0.32 was 36.00%(9/25), while the mortality rate of patients with myocardial injury equal to or above 0.32 was 66.67%(54/81).The difference between the two groups was statistically significant( χ2=8.624, P=0.003). Conclusions:Both BAR and sST2 are considered independent risk factors for myocardial injury in elderly patients with sepsis.The combined detection of BAR and sST2 provides a more accurate prediction for the occurrence of myocardial injury in these patients.
8.Dosimetric study of intensity-modulated radiotherapy and volumetric intensity modulated arc therapy based on the inner edge tangent field for radiotherapy after breast-conserving surgery of left-sided breast cancer
Biao ZHAO ; Qin PU ; Meifang YUAN ; Lishuang MA ; Han LI ; Yi YANG ; Chaoxi SUN
Journal of International Oncology 2024;51(7):441-447
Objective:To explore the dosimetry difference between intensity-modulated radiotherapy (IMRT) and volumetric intensity modulated arc therapy (VMAT) based on the inner edge tangent field (IETF) after left-sided breast conserving surgery.Methods:The localization CT and target organ at risk (OAR) data of 35 patients with left-sided breast cancer treated with IMRT after breast conserving surgery at Department of Radiotherapy in Yunnan Cancer Hospital from June 2022 to June 2023 were selected. The IETF-IMRT and the IETF-VMAT plans were designed for the same patient based on IETF, the dosimetry differences of target areas and OAR, as well as the planned execution time were compared between the two groups.Results:Dosimetry of target areas: for IETF-IMRT and IETF-VMAT, the D 98% of the planning target volume were (47.92±0.51) and (48.21±0.33) Gy, respectively, while the D 50% were (52.04±0.22) and (51.91±0.26) Gy, respectively, and the D 2% were (53.93±0.36) and (53.62±0.41) Gy, respectively, the conformity index were 0.84±0.03 and 0.87±0.02, respectively, while the homogeneity index were 0.12±0.01 and 0.10±0.01, respectively, with statistically significant differences ( t=-3.87, P<0.001; t=3.53, P=0.001; t=5.30, P<0.001; t=-13.60, P<0.001; t=6.24, P<0.001). Dosimetry of OAR: for IETF-IMRT and IETF-VMAT, the left lung V 5 were (31.91±6.28) % and (33.99±6.31) %, respectively, and the V 20 were (11.71±2.06) % and (9.73±2.12) %, respectively, with statistically significant differences ( t=-4.18, P<0.001; t=12.40, P<0.001). The right lung V 5 were (0.11±0.08) % and (7.13±3.12) %, respectively, and the D mean were (1.05±0.12) and (2.71±0.27) Gy, respectively, with statistically significant differences ( t=-33.62, P<0.001; t=-13.30, P<0.001). The spinal cord D 2% were (1.08±0.11) and (4.83±1.40) Gy, respectively, with a statistically significant difference ( t=-15.99, P<0.001). The left lung D mean were (7.45±1.08) and (7.37±1.03) Gy, the heart D mean were (4.21±0.96) and (4.41±0.48) Gy, and the right-sided breast D mean were (3.74±1.52) and (3.48±1.11) Gy, respectively, with no statistically significant difference ( t=1.16, P=0.253; t=-1.76, P=0.088; t=1.41, P=0.169). Planned execution time: the execution time of IETF-IMRT and IETF-VMAT was (10.73±1.21) and (2.18±0.17) min, respectively, with a statistically significant difference ( t=44.71, P<0.001) . Conclusion:Both IETF-IMRT and IETF-VMAT can meet clinical requirements, however the two techniques have their own characteristics. IETF-VMAT has better conformity and homogeneity of target region. The planned OAR dosimetry in both plans are significantly lower than the dose limit of postoperative radiotherapy for breast cancer, among which the left lung V 5, the right lung V 5, D mean and spinal cord D 2% of IETF-IMRT are slightly lower, the left lung V 20 of IETF-VMAT is slightly lower. IETF-VMAT significantly reduces the planned execution time compared with IETF-IMRT, thus can greatly reduce the dose deviation caused by patient position change, and significantly improve patients experience and comfort of radiotherapy. Taken together, IETF-VMAT has advantages over IETF-IMRT in radiotherapy after breast conserving surgery of left-sided breast cancer.
9.Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia
Yan PU ; Xiangyue ZHOU ; Yin LIU ; Xin KONG ; Jingjing HAN ; Jian ZHANG ; Zhihong LIN ; Jun CHEN ; Huiying QIU ; Depei WU
Chinese Journal of Hematology 2024;45(4):339-344
Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.
10.EIT-based study of lung ventilation and perfusion regional distribution and ventilation/perfusion matching in different body positions
Ti-Xin HAN ; Yi-Fan LIU ; Meng DAI ; Pu WANG ; Jian-An YE ; Zhi-Bo ZHAO ; Zhan-Qi ZHAO ; Feng FU
Chinese Medical Equipment Journal 2024;45(5):1-7
Objective To compare regional pulmonary ventilation and perfusion and ventilation/perfusion(V/Q)matching in different body positions using electrical impedance tomography(EIT).Methods Ten healthy experimental pigs were selected to collect their EIT lung ventilation and perfusion data in supine,prone,left lateral and right lateral positions.The EIT data underwent analysis and image reconstruction using MATLAB R2022b and EIDORS v3.9.The effective regions with ventilation and perfusion were determined and the V/Q matching regions were computed with the maximum pixel value 20%as the threshold.Comparisons were carried out over the V/Q matching indexes including V/Q match%,dead space%and shunt%and ventilation and perfusion distribution in regions of interest(ROIs)including ROI1,ROI2,ROI3 and ROI4 in different body positions.Results The differences in V/Q match%,dead space%and shunt%of the experimental animals in varied positions were not statistically significant(P>0.05).The regional distribution of pulmonary ventilation and perfusion changed in different positions,and the regional distributions differed in ROIl,ROI2 and ROI3 for ventilation(P<0.05)and in ROI1 and ROI2 for perfusion(P<0.05).The ventilation and perfusion regions were distributed consistently with the gravity-dependent areas in supine and prone positions whereas conversely in the right and left lateral positions.Conclusion The V/Q matching indexes of one subject have high test consistency in different body positions;gravity-dependent areas varied with the changes of the body positions,which affected the distribution of pulmonary ventilation and perfusion regions;EIT can be used for measuring the changed pulmonary ventilation and perfusion due to different positions and determining the influences of position changes on pulmonary ventilation and perfusion and V/Q matching.[Chinese Medical Equipment Journal,2024,45(5):1-7]

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