This article presents the treatment of a complex solitary kidney stone(＞2.5 cm)with infection.The operation proceeded successfully with a tip-bendable ureteral access sheath combined with flexible ureteroscopic lithotripsy,there were no serious complications and no residual stones.

This article presents the treatment of a complex solitary kidney stone(＞2.5 cm)with infection.The operation proceeded successfully with a tip-bendable ureteral access sheath combined with flexible ureteroscopic lithotripsy,there were no serious complications and no residual stones.

Objective:To develop and evaluate a deep learning-based automatic measurement model for panoramic ultrasound biomicroscopy (UBM) images.Methods:A diagnostic test study was conducted.Preoperative UBM examination results of 372 patients who underwent implantable collamer lens (ICL) implantation were collected at the Eye Center of Renmin Hospital of Wuhan University between February 2021 and March 2023.A total of 1 368 panoramic UBM images were obtained to establish an image database.The dataset was divided into a training set (760 images), a validation set (86 images) and an internal test set (522 images).An expert panel consisting of three ophthalmologists annotated the images.The UNet+ + network was used to automatically segment anterior segment tissues, such as the cornea, lens and iris.In addition, image processing techniques and geometric localization algorithms were developed to automatically identify the anatomical landmarks of pupil diameter (PD), anterior chamber depth (ACD), angle-to-angle distance (ATA) and sulcus-to-sulcus distance (STS) to complete the measurement of these parameters.Additionally, 480 panoramic UBM images of 135 patients (240 eyes) from Aier Eye Hospital of Wuhan University were used as an external test set to further evaluate the performance of the model in different centers.The consistency between the measurements from the model and expert panel, the Pentacam system was assessed.Finally, 150 images were randomly selected from the external test set for a human-machine comparison to further evaluate the model's performance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109) and Aier eye Hospital of Wuhan University (No.2023IRBKY120903).Written informed consent was obtained from each subject.Results:In the internal test dataset and external test dataset, with manual labeling as the reference standard, the model achieved a mean Dice coefficient of not less than 0.882.At least 95.65% of the anatomical landmark localization results had Euclidean distance differences within 250 μm.The intraclass correlation coefficients (ICCs) for the measurements of PD, ACD, angle-to-angle ATA, and STS were at least 0.958, with mean relative errors not exceeding 2.407%.With the Pentacam measurements as the reference standard, the ICCs for PD in the internal and external test sets were 0.540 and 0.466, respectively, while the ICCs for ACD were 0.946 and 0.908, respectively.In the human-machine comparison, the ICCs between the model's measurements and those of senior experts were all not lower than 0.969.Conclusions:The deep learning-based model can automatically measure anterior segment parameters from preoperative panoramic UBM images of patients undergoing ICL surgery.The model demonstrates a consistency comparable to that of senior experts, while providing higher efficiency.In terms of ACD measurement, the model shows good agreement between the measurements obtained from the model and Pentacam system.

Objective:To develop and evaluate a deep learning-based automatic measurement model for panoramic ultrasound biomicroscopy (UBM) images.Methods:A diagnostic test study was conducted.Preoperative UBM examination results of 372 patients who underwent implantable collamer lens (ICL) implantation were collected at the Eye Center of Renmin Hospital of Wuhan University between February 2021 and March 2023.A total of 1 368 panoramic UBM images were obtained to establish an image database.The dataset was divided into a training set (760 images), a validation set (86 images) and an internal test set (522 images).An expert panel consisting of three ophthalmologists annotated the images.The UNet+ + network was used to automatically segment anterior segment tissues, such as the cornea, lens and iris.In addition, image processing techniques and geometric localization algorithms were developed to automatically identify the anatomical landmarks of pupil diameter (PD), anterior chamber depth (ACD), angle-to-angle distance (ATA) and sulcus-to-sulcus distance (STS) to complete the measurement of these parameters.Additionally, 480 panoramic UBM images of 135 patients (240 eyes) from Aier Eye Hospital of Wuhan University were used as an external test set to further evaluate the performance of the model in different centers.The consistency between the measurements from the model and expert panel, the Pentacam system was assessed.Finally, 150 images were randomly selected from the external test set for a human-machine comparison to further evaluate the model's performance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109) and Aier eye Hospital of Wuhan University (No.2023IRBKY120903).Written informed consent was obtained from each subject.Results:In the internal test dataset and external test dataset, with manual labeling as the reference standard, the model achieved a mean Dice coefficient of not less than 0.882.At least 95.65% of the anatomical landmark localization results had Euclidean distance differences within 250 μm.The intraclass correlation coefficients (ICCs) for the measurements of PD, ACD, angle-to-angle ATA, and STS were at least 0.958, with mean relative errors not exceeding 2.407%.With the Pentacam measurements as the reference standard, the ICCs for PD in the internal and external test sets were 0.540 and 0.466, respectively, while the ICCs for ACD were 0.946 and 0.908, respectively.In the human-machine comparison, the ICCs between the model's measurements and those of senior experts were all not lower than 0.969.Conclusions:The deep learning-based model can automatically measure anterior segment parameters from preoperative panoramic UBM images of patients undergoing ICL surgery.The model demonstrates a consistency comparable to that of senior experts, while providing higher efficiency.In terms of ACD measurement, the model shows good agreement between the measurements obtained from the model and Pentacam system.

Objective:To investigate personal exposures to nitrogen oxides(NOX)and nitrogen di-oxide(NO2)and the influence of baseline personal characteristics,living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai.Methods:In this panel study,91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study.The study was conducted in summer and winter.The participants were followed for three times with an interval of at least two weeks.Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic.Twenty-seven participants completed follow-up visits in both seasons.We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity in-formation through questionnaire/diary.The linear mixed model was used to analyze the associations be-tween potential influencing factors and personal NOX and NO2 exposure levels.Results:There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities.The ave-rage 24 h personal exposures to NO2 and NOX(volume fraction)in Tianjin participants were 18.0 x 10-9 and 26.2 × 10-9 in summer,and 31.0 x 10-9 and 54.9 x 10-9in winter,respectively;and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7 x 10-9and 100.0x10-9in summer,and 45.5 x10-9 and 139.2 x 10-9 in winter,respectively.The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city,season,gender,average daily cooking times,and ambient NO2 concentrations measured at fixed-site monitoring stations.In addition to the above factors,the personal NOX exposure levels were also significantly associ-ated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking,average daily home time,cooking energy type,residential distance from main traffic road,and use of kitchen ventilators.Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai,were significantly lower in summer than that in winter,and were significantly and positively associated with ambient NO2 concen-trations measured at fixed-site monitoring stations.In addition,personal NOX exposure levels were signifi-cantly lower in females than in males,and personal NO2 exposure levels were significantly positively asso-ciated with average daily cooking times and significantly inversely associated with average daily home time.For every interquartile range(IQR)increase(12.7 × 10-9)in ambient NO2,the personal NO2 exposure levels increased by 27.5％(95％CI:17.0％-38.9％),and personal NOX exposure levels in-creased by 16.1％(95％CI:7.1％-25.8％).Conclusion:Season,city and ambient NO2 concentra-tions are significant influencing factors of personal exposure levels of NO2and NOX At the same time,the personal exposures levels of NO2 are also affected by lifestyle factors.Our study provides scientific evi-dence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Objective To mine and analyze the adverse drug event(ADE)signals of trastuzumab emtansine(T-DM1)and trastuzumab deruxtecan(T-DXd)using the Japanese Adverse Drug Event Reporting(JADER)database,and to provide reference for safe clinical use of the two drugs in Asian populations.Methods The ADEs reported for T-DM1 and T-DXd from the Japanese JADER database from January 2014 to June 2024 were mined and analyzed using the reporting odds ratio method,Medicines and Healthcare products Regulatory Agency method,and information component method.Results A total of 1 013 ADE reports were extracted for T-DM1,involving 733 patients.38 ADE signals were detected,and 18 ADE signals were not documented in package inserts in China.Similarly,1 224 ADE reports were obtained for T-DXd,involving 732 patients.A total of 25 ADE signals were detected,and 10 ADE signals not documented in package inserts in China.The ADE signals of T-DM1 were involved in the system organ class(SOC)with unique conditions such as cardiac disorders,nervous system disorders,and ocular organ diseases.The ADE signals of T-DXd were involved in the SOC with unique conditions such as infections and infestations,general disorders and administration site conditions.Conclusion T-DM1 and T-DXd exhibit differences in terms of high-frequency ADE,SOC distribution,and overall safety profiles.In clinical practice,it is important to enhance our understanding of the primary ADEs and differential ADEs associated with T-DM1 and T-DXd.Additionally,close monitoring of patients'parameters,including blood routine,pulmonary function,hepatic function,and cardiac function,should be carried out throughout the treatment period to enable timely intervention when necessary.

【Objective】 To investigate the safety and efficacy of flexible ureteroscope (FU) combined with retrograde ureteroscope (URS) in the treatment of lower ureteral calculi with ureteral atresia. 【Methods】 Clinical data of 7 patients treated during Jan.2018 and Jun.2021 were retrospectively analyzed. 【Results】 Ureteral calculi and ureteral atresia were successfully treated, without serious complications. Six to eight weeks after operation, CT examination showed that hydronephrosis was relieved to varying degrees and the ureteral stents were in good position, without residual stones. Six months after operation, there was no significant exacerbation of hydronephrosis and the renal function remained stable. 【Conclusion】 Anterograde FU combined with retrograde URS has high stone-clearance rate, small trauma and high safety in the treatment of ureteral stricture and ureteral calculi.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M₃) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10⁹/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients’ partner genes weren’t identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.