Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

Real-time acquisition of pulmonary ventilation and perfusion information through thoracic electrical impedance tomography (EIT) holds significant clinical value. This study proposes a novel method based on the rime (RIME) algorithm-optimized variational mode decomposition (VMD) to separate lung ventilation and perfusion signals directly from raw voltage data prior to EIT image reconstruction, enabling independent imaging of both parameters. To validate this approach, EIT data were collected from 16 healthy volunteers under normal breathing and inspiratory breath-holding conditions. The RIME algorithm was employed to optimize VMD parameters by minimizing envelope entropy as the fitness function. The optimized VMD was then applied to separate raw data across all measurement channels in EIT, with spectral analysis identifying relevant components to reconstruct ventilation and perfusion signals. Results demonstrated that the structural similarity index (SSIM) between perfusion images derived from normal breathing and breath-holding states averaged approximately 84% across all 16 subjects, significantly outperforming traditional frequency-domain filtering methods in perfusion imaging accuracy. This method offers a promising technical advancement for real-time monitoring of pulmonary ventilation and perfusion, holding significant value for advancing the clinical application of EIT in the diagnosis and treatment of respiratory diseases.
Humans ; Electric Impedance ; Algorithms ; Tomography/methods* ; Pulmonary Ventilation/physiology* ; Lung/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Adult

Objective:To systematically evaluate the differences in CT values between virtual non-contrast (VNC) images and true non-contrast (TNC) images generated from dual-energy CT (DECT), and to validate the feasibility of VNC images replacing TNC images in dose calculations for photon and proton radiotherapy plans.Methods:A retrospective analysis was conducted on the imaging data of 40 patients with solid tumors (20 cranial, 10 thoracic and 10 abdominal cases) who underwent DECT scans at Cancer Hospital of Shandong First Medical University from February 2022 to May 2023. VNC and TNC images were registered slice-by-slice. The differences in CT values of anatomical structures were compared, and Pearson correlation analysis was used to evaluate the correlation of CT values of different anatomical structures in VNC and TNC images. For structures with significant differences, linear regression models (TNC=β×VNC+α) were established using the least squares method. In the Varian Eclipse 15.5 treatment planning system, photon and proton radiotherapy plans based on TNC images and VNC images, as well as the proton radiotherapy plan based on the VNC images corrected by the regression models, were respectively designed. Dose differences of radiotherapy plans designed based on the two images were evaluated. To evaluate dose variations in regions adjacent to the clinical target volume (CTV), two 2-mm-thick annular reference structures were generated on the axial slice containing the largest cross-section of the CTV, extending cranially and caudally from the CTV. These structures were designated as Ring_p and Ring_d, respectively.Results:The differences in CT values between VNC and TNC images were mainly concentrated in the bony structure. The CT values difference between TNC and VNC images was (409.07±53.38) HU for the skull in 20 cranial tumor patients ( t=13.88, P<0.001), and (118.66±20.90) HU for the vertebral bone in 10 thoracic and 10 abdominal tumor patients ( t=10.43, P<0.001). The CT values of the skull and spine showed high correlation between TNC and VNC images ( r=0.98, P<0.001; r=0.99, P<0.001). The regression models established respectively were: TNC=1.859×VNC+33.896 (skull), and TNC=1.827×VNC+5.491 (spine). For photon radiotherapy plans based on TNC and VNC images, the D mean of the CTV were (60.00±0.00) and (60.00±0.00) Gy respectively, with D mean of Ring_p were (61.17±1.69) and (61.01±1.67) Gy, and Ring_d were (55.26±2.06) and (55.20±1.94) Gy, respectively. The relative dose differences in D mean between the two image types were 0 ( t<0.01, P>0.999), 0.33% ( t=0.30, P=0.766), and 0.19% ( t=0.07, P=0.947), all with no statistically significant differences. For proton radiotherapy plans based on TNC and VNC images, the D mean of the CTV were (61.73±0.32) and (61.67±0.26) Gy (RBE), respectively, with D mean of Ring_p were (61.19±0.44) and (60.53±1.22) Gy (RBE), and Ring_d were (60.97±0.67) and (59.80±4.26) Gy (RBE), respectively. The relative dose differences in D mean between the two image types were 0.24% ( t=0.63, P=0.530), 1.80% ( t=1.45, P=0.156), and 3.56% ( t=2.26, P=0.030), with a statistically significant difference in the Ring_d region. In the proton radiotherapy plan designed based on the corrected VNC images, the D mean of the CTV was (61.75±0.32) Gy (RBE), Ring_p was (61.43±0.71) Gy (RBE), and Ring_d was (59.96±2.80) Gy (RBE). The relative dose differences in D mean between TNC images and corrected VNC images were 0.16% ( t=0.19, P=0.850), 0.76% ( t=1.32, P=0.196), and 2.22% ( t=1.93, P=0.061), respectively, with no statistically significant differences. Conclusions:The differences in CT values between VNC and TNC images in DECT mainly exist in bony structures, particularly in the skull and vertebrae. For patients with cranial tumors, VNC images can be directly used in photon radiotherapy planning. In contrast, for proton therapy, after being corrected by the regression model, VNC images can effectively replace TNC images for the dose calculations of radiotherapy plan.

Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.

Among the current curricula of medical teaching in China, most courses focus on the integrated teaching of a single organ-system combination, while there are relatively a few integrated courses that focus on the multiple dimensions between different organs and systems and between medical sciences and social sciences. In 2016, Chongqing Medical University started to cooperate with University of Leicester to establish the clinical medicine major and introduced the course of Integration for Clinical Application (ICA) that had been run well in University of Leicester for years. With reference to the education goal of our university, the curriculum group adopted a series of actions for the localization of this course from the aspects of teaching objectives, contents, teaching model, education resources, and quality of faculty. After the completion of the first round of this course, the passing rate reached 86.96%(100/115) in the quantified evaluation of accomplishment, which was higher than the passing rate of other courses introduced from University of Leicester. The quantitative expert assessment of this course also ranked among the top courses in our university, and student assessment showed that the ability indicators were improved by 25.00%- 38.00%. The above data show that good results have been achieved for the curriculum localization of ICA.

Objective:To explore the suitable prostate cancer screening mode under the medical community for primary hospitals.Methods:From April 2021 to April 2022, a total of 16007 male population ≥50 years from 9 branches of the medical community of the second hospital of Yinzhou participated in this study. They were divided into four groups according to age with group 1 of 50-59 years old, group 2 of 60-69 years old, group 3 of 70-79 years old, and group 4 of 80 years old and above. Serum tPSA was added to the routine physical examination, and the screening positive patients were referred to the referral hospital for further diagnosis and treatment under the mode of medical community. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 ng/ml and suspicious lesions should be scored according to PI-RADS V2. The ultrasound-guided transperineal targeted prostate biopsy was performed for those with PI-RADS ≥3 and those with PI-RADS < 3 but tPSA ≥10 ng/ml. The tPSA follow-up examinations were performed every 6 months for tPSA < 10 ng/ml and PI-RADS < 3 points and once a year for tPSA < 4 ng/ml.Results:Among the 16 007 male population ≥50 years, 2 007(12.54%) were found serum PSA ≥4 ng/ml, and 634(31.59%)were referred to the referral hospital through the medical community system. Combining tPSA and mpMRI, 271 patients underwent ultrasound-guided transperineal targeted prostate biopsy. Among them, 162 were finally diagnosed with PCa, with a biopsy positive rate of 59.78%. The detection rate of PCa in all the subjects was 1.01%. According to the pathological grade, 5(3.08%) were in ISUP group 1, 95(58.64%) in ISUP group 2-3, and 62(38.27%) in ISUP group 4-5. There were 102(62.96%), 39(24.07%) and 21(12.96%) with localized, locally advanced or metastatic PCa, respectively. The levels of tPSA in the four groups were (1.13±1.44)ng/ml, (1.77±3.45)ng/ml, (3.27±17.58)ng/ml, and (4.26±11.48)ng/ml, respectively, with statistically significant differences ( P<0.01). The positive number of biopsy in each group was 1 case(0.06%), 56 cases(0.79%), 81 cases(1.36%) and 24 cases(1.82%) respectively, with statistically significant differences ( P<0.01). The number of ISUP 4-5 grades in each group was 0, 17(30.35%), 29(35.80%), and 16(66.67%) respectively, with statistically significant differences ( P<0.01). Conclusions:Based on the medical community system, according to the tPSA screening results of the primary hospitals, it is feasible and effective to refer suspicious patients to the referral hospitals for mpMRI examination, and screen prostate cancer by ultrasound-guided transperineal prostate fusion biopsy.

Traditional pig breeding has a long cycle and high cost, and there is an urgent need to use new technologies to revitalize the pig breeding industry. The recently emerged CRISPR/Cas9 genome editing technique shows great potential in pig genetic improvement, and has since become a research hotspot. Base editor is a new base editing technology developed based on the CRISPR/Cas9 system, which can achieve targeted mutation of a single base. CRISPR/Cas9 technology is easy to operate and simple to design, but it can lead to DNA double strand breaks, unstable gene structures, and random insertion and deletion of genes, which greatly restricts the application of this technique. Different from CRISPR/Cas9 technique, the single base editing technique does not produce double strand breaks. Therefore, it has higher accuracy and safety for genome editing, and is expected to advance the pig genetic breeding applications. This review summarized the working principle and shortcomings of CRISPR/Cas9 technique, the development and advantages of single base editing, the principles and application characteristics of different base editors and their applications in pig genetic improvement, with the aim to facilitate genome editing-assisted genetic breeding of pig.
Animals ; Swine/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Breaks, Double-Stranded

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Objective:To investigate the efficacy and safety of thulium laser enucleation of the prostate-pre-transection urethral mucosa at the apex of prostate and traditional three lobe enucleation of the prostate for the treatment of benign prostatic hyperplasia patients.Methods:The data of 270 patients with benign prostatic hyperplasia who were underwent ThuLEP-PAM or ThuLEP in our hospital from May 2020 to September 2021 were analyzed retrospectively. According to the operation methods, the patients were divided into two groups: ThuLEP-PAM group (120 cases) and ThuLEP group (150 cases). There was no significant difference comparing the age [(69.8±7.7) years vs. (71.4±8.0) years], prostate volume [55.5(41.0, 71.0)ml vs. 58.5(45.0, 80.3)ml], the serum PSA [3.0(1.8, 4.6) ng/ml vs. 3.3(2.1, 5.5)ng/ml], international prostate symptom scores (IPSS) [22(17, 28) vs. 22(17, 27)], the quality of life score (QOL)[5(4, 6) vs. 5(4, 6)], the maximum urinary flow rate (Q max)[5.6(3.5, 7.3)ml/s vs. 5.5(4.0, 7.1)ml/s], the residual urine volume [ 31(0, 81)ml vs. 31(0, 102)ml] between the ThuLEP-PAM group and the ThuLEP group. No significant difference was found between the two groups( P>0.05). In the ThuLEP-PAM group, the external sphincter ring was located firstly, and urethral mucosa at the apex of prostate was circumferentially incised at 5 mm proximal of the sphincter ring by laser. Then the urethral mucosa was incised at the left sulcus beside the verumontanum and the prostate surgical capsule gap was exposed. After the middle lobe was removed, the left and right lobes were removed along the urethral mucosa pre-incision line at the prostatic apex. The ThuLEP group was enucleated by traditional three lobes enucleation. Perioperative indicators and postoperative complications during short-term follow-up were compared between the two groups. Results:All patients successfully completed the operation and the symptoms of the lower urinary tract were significantly improved. Comparison the perioperative factors between ThuLEP-PAM group and ThuLEP group included the following: operative time 90(70, 103)min vs. 83(61, 102)min; enucleated tissue weight 27.0(19.3, 36.5)g vs. 27.0(19.0, 39.0)g; decrease of the hemoglobin 9.9(7.4, 12.4)g/L vs. 9.5(7.1, 12.7)g/L; catheterization time 3.5(3.0, 4.0)d vs. 3.5(3.0, 5.0)d; hospital stay 6.0(5.0, 6.0)d vs. 5.0(4.0, 6.0)d. NO significant difference in these parameters was found between the two groups( P>0.05). There also was no significant difference in PSA[1.1(0.8, 1.5) ng/ml vs. 1.0(0.8, 1.6) ng/ml], IPSS score [5(4, 6) min vs. 5(4, 6)min], QOL score [2(1, 3) vs. 2(1, 3)], Q max [20.9(17.5, 22.5) ml/s vs. 20.4(17.8, 22.7) ml/s] and PVR [0 ml vs. 0(0, 6)ml] between the two groups ( P>0.05) after more than 3 months of follow-up. The incidence of incontinence for ThuLEP-PAM(2 cases)were lower than that for ThuLEP(11 cases)( P=0.031), but there was no significant between the two groups in other complications such as blood transfusion, haematuria, post-voidalurinary retention and urethral stricture. Conclusions:ThuLEP-PAM and ThuLEP have similar effect on the improvement of lower urinary tract symptoms in patients with benign prostatic hyperplasia, both of which have good efficacy and high safety. The biggest advantage of ThuLEP-PAM over ThuLEP is that it reduces the incidence of early postoperative stress urinary incontinence.