Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Objective To analyze the epidemiological characteristics and trends of the incidence and mortality of biliary tract cancer in Shanghai from 2002 to 2020. Methods Data on new cases and deaths of malignant tumors of the gallbladder, extrahepatic bile ducts, and other biliary tract organs from 2002 to 2020 were obtained from the Population-based Cancer Registry and Vital Statistics System of Shanghai Municipal Center for Disease Control and Prevention. Cases or deaths, proportion, crude rate, age-specific rate, age-standardized rate (ASR) and others were calculated stratified by year of diagnosis or death, gender and age-group. ASRs were calculated using Segi′s 1960 world standard population. Trends of the annual percent change (APC) of ASRs, age-specific rates and proportions of new cases with selected diagnostic character of biliary tract cancer stratified by different groups were analyzed by Joinpoint analysis software. Results Annual new cases of biliary tract cancer in Shanghai increased from 963 in 2002 to 1 537 in 2020, with ASR of incidence changing from 3.91/10⁵ to 3.59/10⁵. Annual deaths increased from 830 to 1 225, with ASR of mortality decreased from 3.36/10⁵ to 2.69/10⁵. In 2020, the crude rate of incidence of biliary tract cancer was 10.43/10⁵ (9.54/10⁵ in males and 11.30/10⁵ in females) in Shanghai, and the ASR was 3.59/10⁵ (3.54/10⁵ in males and 3.61/10⁵ in females), with no statistically significant gender difference (P=0.731). The crude rate of mortality was 8.31/10⁵ (7.60/10⁵ in males and 9.00/10⁵ in females), and the ASR was 2.69/10⁵ (2.69/10⁵ in males and 2.66/10⁵ in females), also with no significant gender difference (P=0.874). Age-specific nunbers and rates of incidence and mortality generally increased with aging. Stratified by gender, the trend of ASRs of incidence of biliary tract cancer in Shanghai in males showed no significant change (P=0.179) from 2002 to 2020, nor did that of ASRs of mortality (P=0.738). In females, the ASRs of incidence decreased at an average annual rate of 1.58% (P<0.001), while the trend of ASRs of mortality showed no significant change from 2002 to 2011 (P=0.774), but ASRs decreased at an average annual rate of 3.72% from 2011 to 2020 (P<0.001). Among new cases, the proportions of morphological verification increased, while the proportions of imaging verification decreased. The gallbladder was the most common site, but its proportions decreased significantly, whereas the proportions of extrahepatic bile duct increased from 25.75% to 42.88%. Over 60% of cases were unknown stage at diagnosis, while the combined proportions of stages Ⅰ-Ⅲ remained less than that of stage Ⅳ. Conclusions The ASRs for incidence and mortality of biliary tract cancer in Shanghai remain relatively high, with distinct epidemiological characteristics. The improvement in the diagnosis and treatment of biliary diseases maybe have impact on the incidence patterns of biliary tract cancer in Shanghai, but the effect on increasing survival rates and reducing mortality rates is relatively lagging. It needs a big progress to advance the screening, diagnosis, and survival of biliary tract cancer in Shanghai. This study provides a foundation for further research and prevention strategies for biliary tract cancer.

Objective To construct an automatic segmentation model to segment female urine control anatomy on MRI images based on deep learning methods in order to improve the segmentation efficiency and accuracy.Methods A dataset comprising 49 female pelvic floor muscle MRI images[30 women with varying degrees of pelvic organ prolapse(POP)and 19 healthy individuals],obtained from Faculty of Biomedical Engineering and Medical Imaging in Army Medical University,was used for model training and testing.The dataset was split into a training set(17 normal cases and 22 POP cases)and a testing set(4 normal cases and 6 POP cases)in a ratio of 8∶2.The training set was used to train UNet,UNet+++,Dense UNet,and UNet++models separately,and then input into each network.The model achieving the highest testing accuracy was selected as the backbone network.Results Under the training of UNet,UNet+++,Dense UNet,and UNet++,the 4 models achieved average Dice similarity coefficients of 61.82%,57.94%,57.63%,and 62.76%,respectively,for the segmentation of 5 anatomical structures(compressor urethrae,urethra sphincter body,bladder wall,bladder cavity and urethra submucosa).The corresponding Intersection over Union(IoU)score was 49.74%,46.59%,46.07%,and 49.44%,while the accuracy rate was 61.74%,55.03%,59.23%,and 61.91%,respectively for the 4 models.Notably,UNet++consistently outperformed UNet,UNet+++,and Dense UNet across the 3 metrics,indicating that UNet++achieved the highest overall segmentation accuracy.Conclusion In UNet,UNet++,Dense UNet and UNet++for automatic segmentation of 5 female urine control anatomical elements,UNet++achieves the best overall segmentation accuracy.

Time-of-flight secondary ion mass spectrometer(TOF-SIMS)is a highly sensitive surface analysis instrument with high spatial resolution.Traditional TOF-SIMS instruments for sample targets use high field extraction methods.Although the ion collection efficiency is high,it is prone to issues such as low-energy ion beam defocusing,sample morphology sensitivity,and organic molecule ion dissociation.This study aimed to develope an efficient low-field ion extraction system suitable for TOF-SIMS with a continuous beam source.The SIMION simulation software was used to construct a model of the secondary ion optical extraction system.The key factors affecting the extraction efficiency were studied,and the structural parameters of the extraction cone were optimized.Using an indium target as the sample,an experimental test of the performance of the ion extraction system was carried out on the TOF-SIMS instrument.The influences of the voltages of the ion extraction cone and the single lens on the ion extraction efficiency were consistent with the simulation results.By adopting the technology of deflection and coaxial dynamic compensation,the imaging field of view of the ion extraction system was increased to 500 μm×500 μm.The energy window of the ion extraction system reached 10 eV,and the large imaging depth of field of 400 μm was achieved.In the test of a 5 mg/L cholesterol thin film sample,the signal-to-noise ratio of the characteristic peak[M-OH]+reached 4453.The results showed that this low-field secondary ion extraction system effectively improved the performance of the continuous beam TOF-SIMS instrument.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*