[MRI manifestations of 40 cases with the hepatic epithelioid hemangioendothelioma classification based on the morphology and size].

Objective: To explore the MRI characteristics of the hepatic epithelioid hemangioendothelioma (HEHE) classification according to morphology and size. Methods: The clinical, pathological, and MRI imaging data of 40 cases with HEHE confirmed pathologically from December 2009 to September 2021 were retrospectively analyzed. A paired sample t-test was used for comparison between the two groups. Results: There were 40 cases (5 solitary, 24 multifocal, 9 local fusion, and 2 diffuse fusion) and 214 lesions (163 nodules, 31 masses, and 20 fusion foci). The most common features of lesions were subcapsular growth and capsular depression. The signal intensity of lesions ≤1cm was usually uniform with whole or ring enhancement. Nodules and mass-like lesions ≥1cm on a T1-weighted image had slightly reduced signal intensity or manifested as a halo sign. Target signs on a T2-weighted image were characterized by: target or centripetal enhancement; fusion-type lesions; irregular growth and hepatic capsular retraction, with ring or target-like enhancement in the early stage of fusion and patchy irregular enhancement in the late stage; blood vessels traversing or accompanied by malformed blood vessels; focal bleeding; an increasing proportion of extrahepatic metastases and abnormal liver function with the type of classified manifestation; primarily portal vein branches traversing; and reduced overall intralesional bleeding rate (17%). Lollipop signs were presented in 19 cases, with a high expression rate in mass-type lesions (42%). The fusion lesions were expressed, but the morphological manifestation was atypical. The diffusion-weighted imaging mostly showed high signal or target-like high signal. An average apparent diffusion coefficient of lesions was (1.56±0.36) ×10(-3)mm(2)/s, which was statistically significantly different compared with that of adjacent normal liver parenchyma (t=8.28, P<0.001). Conclusion: The MRI manifestations for the HEHE classification are closely related to the morphology and size of the lesions and have certain differences and characteristics that are helpful for the diagnosis of the disease when combined with clinical and laboratory examinations.

[The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Jing Xiao Chan Bao collected by the Waseda university library].

The current version of Jing Xiao Chan Bao is believed to be the earliest medical book on gynecology remaining in China. It has three problems: formulae missing, lack of fluency in the text, and thus difficulties in proofreading and editing. These problems are still there because there are very few versions of Jing Xiao Chan Bao left in China and so it is difficult to do further studies to make comparisons. The Waseda University Library announced that the version they held was a handwritten. It provides a new version for further research of this book. This version was believed to be compiled and edited by Japanese scholars based on Medical Prescription Analogues (Yi Fang Lei Ju) and therefore appears to be similar to the South Song Dynasty version. Using archival research, it was found that in the version at Waseda University Library, the content organisation, the number of formulas, and the use of taboo words is different from those in the current version in China. In this sense, it is believed that this version is valuable and meaningful for archival and clinical research for traditional Chinese medicine.

[Application value of folate receptor-positive circulating tumor cells in the diagnosis of head and neck squamous cell carcinoma].

A total of 82 patients and healthy subjects in the First Affiliated Hospital of Sun Yat-sen University from March to August 2023 were recruited. The cohort consisted of 43 patients with head and neck squamous cell carcinoma (HNSCC) and 39 non-cancer patients or healthy subjects. There were 63 males and 19 females, with a median age of 62 (46, 67) years. The levels of folate receptor-positive circulating tumor cells (FR+CTCs) in the blood of HNSCC patients and non-cancer/healthy subjects were 12.4 (8.5, 17.8) floate unit (FU)/3 ml and 5.0 (3.8, 6.6) FU/3 ml, respectively, with a statistically significant difference (P<0.001). The area under the receiver operating characteristic (ROC) curve for FR+CTCs levels was 0.937 (95%CI: 0.888-0.986, P<0.001), with a cut-off value of 7.4 FU/3 ml determined by the maximum Youden index. At this cut-off value, the sensitivity and specificity of FR+CTCs for diagnosing HNSCC were 90.70% and 89.74%, respectively. The current study suggests that FR+CTCs could be used as a liquid biopsy marker for the screening and diagnosis of HNSCC.

[Prevalence of hypertension, blood pressure control and influencing factors in residents aged 35-75 years in Jiangsu Province].

Objective: To understand the prevalence, blood pressure control, and influencing factors of hypertension in residents aged 35-75 years in Jiangsu Province, and provide data support and basis for hypertension prevention and treatment. Methods: A stratified cluster sampling method was adopted to conduct community population surveys in 22 districts and counties in 12 prefectures in Jiangsu from 2021 to 2022. A total of 123 531 permanent residents aged 35-75 years were included in the study. The questionnaire survey collected the information about the demographic characteristics, disease history, lifestyle, and control of hypertension of study subjects. Statistical software SPSS 23.0 was used for χ2 test and multivariate logistic regression analysis, and Joinpoint 4.9.1.0 software was used to evaluate the trend of age change. Results: The standardized prevalence of hypertension in study subjects was 46.60%, the prevalence was higher in men than in women, and in rural residents than in urban residents, and the standardized blood pressure control rate was 11.24%, and it was lower in men than in women and in rural residents than in urban residents. The hypertension prevalence and control rates showed increasing trends with age (both P<0.001). The multivariate analysis results showed that being man, older age, being rural resident, higher frequency of alcohol consumption, marital status of being separated and widowed, overweight and obese, abdominal obesity and stroke, diabetes mellitus and dyslipidaemic diseases histories, and family history of hypertension were risk factors for hypertension, and being man, being rural resident, living north area, higher frequency of alcohol consumption, and obesity were risk factors for blood pressure control. Conclusions: The prevalence of hypertension in residents aged 35-75 years in Jiangsu was high, and the rate of blood pressure control was low. It is suggested to take integrated intervention measures, especially in in rural residents and people with low levels of education to reduce the disease burden of the patients.

[Prospective association study of sleep status and risk of coronary heart disease in adults in Suzhou].

Objective: To investigate the association between sleep status and the risk for coronary heart disease in adults in Suzhou. Methods: Using the baseline and follow up information of 53 269 local residents aged 30-79 years in China Kadoorie Biobank conducted in Wuzhong District, Suzhou, 51 929 subjects were included in this study after excluding those reporting coronary heart disease, stroke and cancer at the baseline survey. A Cox proportional hazards regression model was used to analyze the association of healthy sleep score (0-3 points) and sleep factors (snoring, insomnia, long sleep duration and nap) with the risk for coronary heart disease. Results: The median follow-up time was 11.12 years, and 1 304 individuals were diagnosed with coronary heart disease during the follow-up. After adjusting for potential confounders, occasional snoring (HR=1.20, 95%CI: 1.04-1.38), usual snoring (HR=1.17, 95%CI: 1.02-1.33), insomnia disorder (HR=1.41, 95%CI: 1.12-1.78), daytime dysfunction (HR=1.56, 95%CI: 1.20-2.03) and perennial nap (HR=1.37, 95%CI: 1.19-1.59) were associated with increased risk of coronary heart disease. Compared with those with sleep score of 0 - 1 (low sleep quality), the people with sleep score of 3 had reduced risk of coronary heart disease by 26% (HR=0.74, 95%CI: 0.63-0.87). Stratified analysis showed that the association of healthy sleep score 3 with risk of coronary heart disease was stronger in low physically active individuals (interaction P<0.05). Conclusions: Snoring, insomnia disorders, daytime dysfunction, and perennial napping were all associated with increased risk for coronary heart disease, and keep healthy sleep mode might reduce the risk for coronary heart disease in adults.

[Rethinking the scope of lymphadenectomy after neoadjuvant immunotherapy for locally advanced gastric cancer].

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

[Identification of potential biomarkers and immunoregulatory mechanisms of rheumatoid arthritis based on multichip co-analysis of GEO database].

OBJECTIVE: To identify the biomarkers for early rheumatoid arthritis (RA) diagnosis and explore the possible immune regulatory mechanisms. METHODS: The differentially expressed genesin RA were screened and functionally annotated using the limma, RRA, batch correction, and clusterProfiler. The protein-protein interaction network was retrieved from the STRING database, and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms. ROC curves was used to validate the accuracy of diagnostic models based on the key genes. The disease-specific immune cells were selected via machine learning, and their correlation with the key genes were analyzed using Corrplot package. Biological functions of the key genes were explored using GSEA method. The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis (CIA). RESULTS: We identified 9 core key genes in RA (CD3G, CD8A, SYK, LCK, IL2RG, STAT1, CCR5, ITGB2, and ITGAL), which regulate synovial inflammation primarily through cytokines-related pathways. ROC curve analysis showed a high predictive accuracy of the 9 core genes, among which STAT1 had the highest AUC (0.909). Correlation analysis revealed strong correlations of CD3G, ITGAL, LCK, CD8A, and STAT1 with disease-specific immune cells, and STAT1 showed the strongest correlation with M1-type macrophages (R=0.68, P=2.9e-08). The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts. The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment. CONCLUSION: CD3G, CD8A, SYK, LCK, IL2RG, STAT1, CCR5, ITGB2, and ITGAL may serve as biomarkers for early diagnosis of RA. Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells, ITGAL-Tfh cells, and STAT1-M1-type macrophages may be closely related with the development of RA.

Variations in water use efficiency and carbon and nitrogen concentrations in red heart Chinese fir.

Temperature can significantly (P < 0.05) affect plant growth by modifying water use strategies, which are determined by intrinsic water use efficiency (WUEi). Red Heart Chinese Fir (Cunninghamia lanceolata) is one of the most important ecological and economic plantation species in China. However, the C. lanceolata water use strategy in response to increased temperatures and uneven temporal distribution of precipitation during the growing season is rarely reported. In a 7-year-old C. lanceolata plantation, differences in WUEi and C and N concentrations in different organs were analysed by anova, and the δ13C stable isotope, C, and N concentrations in stems determined at different tree heights. Stepwise regression and variance inflation factor were used to remove autocorrelated factors, and structural equation modelling was then used to explore relationships between WUEi and climate and biological factors. WUEi differed significantly between leaf and branch at different standardized precipitation evapotranspiration indices (SPEI). WUEi and N concentration decreased with age. The highest WUEi in branches and leaves were 92.7 and 88.4 µmol·mol-1 in 2020 (SPEI = 0.00), respectively. δ13C increased with relative tree height but N concentration and C/N ratio were not affected. Air temperatures has increased in between 2014 and 2020. WUEi and N concentration decreased with increasing branch and leaf age, but C concentration increased. SPEI significantly positively affected WUEi (P < 0.05), and WUEi was significantly negatively related to C concentration, which is consistent with the trade-off between C and water.

Polarization self-compensation in a laser-driven interferometric fiber optic gyroscope with high long-term stability.

We present a laser-driven interferometric fiber optic gyroscope (IFOG) with polarization self-compensation to achieve high scale-factor stability, sensitivity, and long-term stability. Coherent light with 200kHz linewidth is employed to keep the scale factor stable. The optical scheme ensures polarization reciprocity as well as the optimal working point for good sensitivity. Furthermore, a hybrid machine learning loop (MLL) method, combining the advantages of PID fast response and artificial neural network (ANN) dynamic search, can control a liquid crystal rotator (LCR) to dynamically compensate for slow drift induced by polarization coupling. In open environment, when the sensitivity is 0.005 ∘/h, the bias instability (BI) is significantly optimized from 0.6723°/h at 60s (PID) to 0.3869°/h at 200s (MLL), which is close to the Sagnac interferometric limit (SIL). Such IFOG can meet the real-time and robust requirements for inertial navigation systems in long-term measurement.

Primary biliary cholangitis and Sjogren's syndrome: bi-directional Mendelian randomization analysis.

OBJECTIVE: Observational studies have shown a higher prevalence of Sjogren's syndrome (SjS) in patients with primary biliary cholangitis (PBC) than in the healthy population, but whether this correlation is causal needs further confirmation. This study aimed to investigate the bidirectional causal relationship between PBC and SjS using Mendelian randomization (MR) analysis. MATERIALS AND METHODS: We used pooled data from a large-scale genome-wide association study (GWAS) to select mutually independent genetic loci associated with PBC and SjS in people of European ancestry as instrumental variables (IVs). The causal association between PBC and SjS was analyzed by MR analysis using inverse variance weighting (IVW) and weighted median methods, and the ratio of ratios (OR) was used as an evaluation index. In addition, sensitivity analyses, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and leave-one-out test, were performed to ensure the stability of the results. RESULTS: A total of 20 validated IVs were selected for PBC, and the number of IVs for SjS was seven. Positive MR analysis showed that genetically predicted PBC was significantly associated with the risk of SjS (IVW OR=1.174, 95% CI: 1.107-1.246, p<0.001). The weighted median method further confirmed this result (OR=1.146, 95% CI: 1.053-1.247, p=0.016). Inverse MR analysis showed that genetic susceptibility to SjS also increased the risk of PBC (IVW OR=1.737, 95% CI: 1.280-2.357, p<0.001), and this result was also confirmed by the weighted median method (OR=1.398, 95% CI: 1.120-1.746, p=0.003). CONCLUSIONS: Our study found that genetically predicted SjS increased the risk of PBC and vice versa in a European population. This may shed light on the etiology of PBC and the management of patients with SjS.

Single-Atom Verification of the Optimal Trade-Off between Speed and Cost in Shortcuts to Adiabaticity.

The approach of shortcuts to adiabaticity enables the effective execution of adiabatic dynamics in quantum information processing with enhanced speed. Owing to the inherent trade-off between dynamical speed and the cost associated with the transitionless driving field, executing arbitrarily fast operations becomes impractical. To understand the accurate interplay between speed and energetic cost in this process, we propose theoretically and verify experimentally a new trade-off, which is characterized by a tightly optimized bound within s-parametrized phase spaces. Our experiment is carried out in a single ultracold ^{40}Ca^{+} ion trapped in a harmonic potential. By exactly operating the quantum states of the ion, we execute the Landau-Zener model as an example, where the quantum speed limit as well as the cost are governed by the spectral gap. We witness that our proposed trade-off is indeed tight in scenarios involving both initially eigenstates and initially thermal equilibrium states. Our work helps understanding the fundamental constraints in shortcuts to adiabaticity and illuminates the potential of underutilized phase spaces that have been traditionally overlooked.

SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

[Application of PRAME immunohistochemistry in the differential diagnosis of primary endometrial and endocervical adenocarcinomas].

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) immunohistochemical staining in differential diagnosis of primary endometrial and endocervical adenocarcinomas. Methods: Eighty-seven cases of endometrial adenocarcinoma and sixty-three cases of cervical adenocarcinoma were collected from May 2018 to November 2023 in the Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and all the cases were subject to PRAME immunohistochemical staining. The difference of PRAME expression between endometrial and endocervical adenocarcinomas was analyzed. Results: In 87 cases of endometrial adenocarcinoma, patients' age ranged from 35 to 71 years (average 59 years, median 59 years); in 63 cases of cervical adenocarcinoma patients' age ranged from 28 to 80 years (average 49 years, median 47 years). Seventy-eight cases (78/87, 89.7%) of endometrial adenocarcinoma; 2 cases (2/63, 3.2%) of cervical adenocarcinoma showed positive PRAME staining, and both cases of cervical adenocarcinoma were clear cell carcinoma. The sensitivity and specificity of PRAME in distinguishing between endometrial and cervical adenocarcinoma in the cohort were 89.7% and 96.8%, while those in differentiating non-clear cell carcinoma of the uterus from that of the cervix reached up to 91% and 100%, respectively. Conclusions: Immunohistochemical staining for PRAME demonstrates statistically significant differences between endometrial and cervical carcinomas, making it a useful auxiliary diagnostic marker for differentiating cervical and endometrial adenocarcinoma, especially non-clear cell carcinoma.

[Efficacy of alternate mucosa-submucosa clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection].

Objective: To analyze the efficacy of alternate titanium clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection (ESD). Methods: Clinical data of patients with gastric mucosal lesions who underwent ESD in the Department of Gastroenterology, Zhongda Hospital, Southeast University, were retrospectively collected from January 1, 2013 to August 31, 2023. According to the postoperative wound closure status, the patients were divided into completely closed group (complete closure of ESD wounds using alternate titanium clip closure), partially closed group (partial closure of ESD wounds), and unclosed group (without use of clips for treatment of ESD wounds). The incidence of postoperative complications as well as wound healing at 1 month and 3 months after surgery were compared among three groups, and the factors related to delayed bleeding after ESD for gastric mucosal lesions were analyzed through multiple logistic regression analysis. Results: A total of 846 patients were included, 430 cases in the completely closed group, including 300 males and 130 females, age [M (Q1, Q3)] was 65(56, 72) years old; one hundred and nine cases in unclosed group, including 78 males and 31 females, aged 66 (60, 71) years; and 307 cases in the partially closed group, including 214 males and 93 females, aged 66 (59, 71) years. The difference in the rate of delayed postoperative bleeding between the completely closed group [2.1% (9/430)] and the unclosed group [5.5% (6/109)] was not statistically significant (P=0.072), but both were lower than that of the partially closed group [9.4% (29/307), P<0.05)]. Further stratified analysis showed that, for the lesions located in the lower 1/3 of the stomach, the rate of postoperative bleeding was lower in the completely closed group than in the partially closed and unclosed groups [0.9% (2/222) vs 11.4% (4/35) vs 9.5% (7/74), respectively, P<0.001]. For lesions≥50 mm in length, the rate of postoperative bleeding was lower in the completely closed group than that in the partially closed and unclosed group[0 vs 11.8% (2/17) vs 20.5% (15/73), respectively, P=0.004]. The incidence of postoperative abdominal pain in the completely closed group [84.2% (363/430)] was lower than that in the unclosed group [97.2% (106/109)] and the partially closed group [95.4% (293/307), both P<0.001)]. The score of postoperative abdominal pain in the completely closed group [0 (0, 1)], was lower than that in the unclosed group [3 (2, 3)], and that in the partially closed group [2 (1, 3)] (both P<0.001). The wound healing rate of the completely closed group [80% (176/220)] was higher than that of the unclosed group [52.3% (33/63)] and the partially closed group [52.2% (83/159)] at 1 month postoperatively (both P<0.001); the healing rate of all three groups reached 100% at 3 months postoperatively. Multiple logistic regression analysis showed that the presence of ulcers or scars on the surface of the lesion (OR=2.930, 95%CI:1.503-5.712, P=0.002), and the diameter (OR=1.031, 95%CI:1.015-1.047,P<0.001) were related factors for postoperative bleeding. Conclusions: The alternate titanium clip closure surgery can reduce postoperative abdominal pain and shorten wound healing time in patients with gastric mucosal lesions after ESD surgery. The risk of postoperative bleeding can be reduced for lesions with a diameter≥50 mm and located in the lower 1/3 of the stomach.

Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.

[Magnetic resonance imaging features and classification of intraductal papillary neoplasm of the bile duct].

Objective: To explore the magnetic resonance imaging (MRI) features and classification of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Data from 90 patients with intraductal papillary neoplasm of the bile duct confirmed pathologically between June 2010 and January 2023 were retrospectively analyzed. The image analysis included the shape and location of the tumor, whether bile ducts had dilatation and the degree of dilation, whether there was a history of liver disease, whether there was a history of schistosomiasis, whether there was cancerous transformation, whether there were concurrent bile duct stones, whether there was hepatic lobe atrophy, whether there was hilar or abdominal lymph node enlargement, whether there was invasion of the bile duct wall, whether there was invasion of surrounding blood vessels, whether the tumor appears on T1-and T2 weighted imaging (T(1)WI and T(2)WI), whether the diffusion was limited, whether there was concurrent bleeding, enhancement rate, and whether there was abdominal fluid accumulation. Intraductal papillary neoplasms of the bile duct were divided into four types according to the morphological classification standards: type I (local bile duct dilation), type II (cystic), type III (free tumor), and type IV (dilated bile duct). The differences in the clinical and MRI features of the four groups of lesions were analyzed. Statistical analysis was performed with a t-test, an analysis of variance, and an χ(2)-test according to the different data. Results: Among the 90 cases with hepatic IPNB, there were 31 cases of type I, 15 cases of type II, 16 cases of type III, and 28 cases of type IV, 41 cases of liver left lobe, 11 cases of right and left lobe liver span, 7 cases of liver right lobes, 2 cases of liver caudate lobe, and 13 cases of hepatic hilar. There were statistically significant differences between the four groups (P < 0.05) in terms of age, clinical symptoms, direct bilirubin, γ-glutamyltransferase, whether they were cancerous, whether they were combined with bile duct stones, whether the liver lobes were atrophying, whether there was limited diffusion, intrahepatic bile duct diameter, and common bile duct diameter. However, there were no statistically significant differences among the four groups in gender, location, carbohydrate antigen 19-9, history of liver disease, history of schistosomiasis, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, total bilirubin, whether hemorrhage was associated, lesion enhancement rate, whether the hilar/retroperitoneal lymph node was enlarged, whether the bile duct wall was invaded, whether blood vessels were invaded, and whether abdominal fluid was accumulated (P > 0.05). Conclusion: MRI manifestations have certain features for different types of intraductal papillary neoplasm of the bile duct tumors; hence, MRI aids in the diagnosis and differential diagnosis of this disease.

CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair.

BACKGROUND: There is an unmet medical need for effective nonopioid analgesics that can decrease pain while reducing systemic opioid use. CPL-01, an extended-release injectable formulation of ropivacaine, is designed to safely provide analgesia and reduce or eliminate opioid use in the postoperative period. METHODS: Subjects undergoing open inguinal hernia with mesh were prospectively randomized to 1 of 3 doses of CPL-01 (10, 20, or 30 ml of 2% CPL-01, n = 14, 12, and 14, respectively), Naropin (150 mg, n = 40), or saline placebo (n = 13) infiltrated into the surgical site prior to closure. Pain and rescue medication usage was assessed, and Numeric Rating Scale (NRS) pain scores were adjusted for opioid usage using windowed worst observation carried forward (wWOCF) imputation. The primary efficacy endpoint was the mean area under the curve (AUC) of the NRS pain intensity scores with activity. RESULTS: Ninety-three subjects were treated, and 91 subjects completed 72 h of post-operative monitoring. Subjects who received the highest dose of CPL-01 in Cohort 3 showed a clinically meaningful reduction in postoperative pain intensity scores, which was the lowest value for any treatment in all cohorts, showing a trend towards statistical significance as compared to the pooled placebo group (p = 0.08), and numerically better than the 40 subjects who received Naropin. Opioid use through 72 h in subjects who received CPL-01 in Cohort 3 was approximately half of that shown in the placebo and Naropin groups; approximately 2/3 of the CPL-01 subjects (9/14) required no opioids at all through the first 72 h after the operation. More CPL-01 subjects avoided severe pain and were ready for discharge earlier than other groups. CPL-01 was safe and well-tolerated, with no clinically meaningful safety signals, and showed predictable and consistent extended-release pharmacokinetics. CONCLUSION: Results suggest that CPL-01 may be the first long-acting ropivacaine to address postoperative pain while reducing the need for opioids.