Abstract Pancreatic cancer is a highly malignant gastrointestinal cancer with a poor prognosis, and early diagnosis remains challenging. The use of reliable biomarkers can significantly enhance the early evaluation and management of this disease. Circulating tumor cells(CTCs) are released into the bloodstream and can be obtained easily through minimally invasive liquid-based biopsy, making them promising candidates for early tumor diagnosis, prognosis assessment, and monitoring therapeutic responses. This paper reviews the advancements in CTCs detection technology and their clinical applications in pancreatic cancer over the past decade, both domestically and internationally, which offer a new perspective on the early diagnosis and prognosis of pancreatic cancer.

Objective:To explore the optimization of the standardized assessment tool for clinical diagnosis of Chinese developmental dyslexia (DD).Methods:A cross-sectional study was conducted from May to December 2023, in which 130 primary school children in grades 1 to 3 with clinical signs of literacy lag and positive screening results on the screening scales were recruited from the outpatient clinic of Child Health Care Medical Division, Shanghai Children′s Hospital, Shanghai Jiao Tong University School of Medicine. Chinese dyslexia screening behavior checklist for primary students (CDSBC) was used as the screening scales, and supplemented by dyslexia checklist for Chinese children. Referring to the standard procedure of the"expert advice on diagnosis and intervention of Chinese developmental dyslexia", the developmental dyslexia scale for standard mandarin (DDSSM) was used to evaluate the children′s literacy-related cognitive abilities and conduct the diagnostic assessment, and divided the children into learning backward group and the DD group. The t-test and χ2 test were used to compare the differences in the distribution of intelligence, literacy and attention deficit hyperactivity disorder between the two groups. Spearman′s correlation was used to analyze the correlation between the scores for each cognitive ability in the DDSSM and the CDSBC. Results:Of the 130 children, 90 were male, aged (8.3±1.0) years; 40 were female, aged (8.1±0.9) years. A final diagnosis of DD was made in 59 cases, of which 41 were males. There was no statistically significant difference in operational intelligence quotient (101±15 vs.100±15, t=0.53, P>0.05) and statistically significant difference in literacy of DDSSM (32±5 vs.21±4, t=11.56, P<0.001) between the learning backward group and the DD group. Eighteen cases (25.4%) of the learning backward group were children with attention deficit subtype attention deficit hyperactivity disorder (ADHD-I), and 16 cases (27.1%) in DD group, the difference in incidence between the two groups was not statistically significant ( χ2=0.05, P>0.05). There were correlations between the DDSSM (for oral vocabulary, morphological awareness and orthographic awareness) and the CDSBC total score ( r=-0.42, -0.32, -0.35, all P<0.01), but the correlations for visuospatial perception and rapid automatized naming with CDSBC total score were not statistically significant ( r=-0.09 and -0.20,both P>0.05). Conclusion:For literacy-related cognitive abilities, screening scales CDSBC are not sufficiently useful for assessment, so the introduction of standardized assessment tools DDSSM is an optimization of the clinical diagnosis of Chinese DD, which is crucial for achieving accurate diagnosis and intervention.

Objectives:To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases.Methods:A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021.Results:①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9–22) days and 13 (10–24) days, respectively ( P=0.834), whereas the median implantation time for platelets was 15 (7–103) days and 14 (8-38) days, respectively ( P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% ( P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% ( P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% –38.1% ) and 28.8% (95% CI 17.2% –41.6% ( P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% –14.0% ) and 9.6% (95% CI 3.5% –19.5% ) ( P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% –44.1% ), respectively ( P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively ( P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% –20.5% ) and 10.0% (95% CI 3.6% –20.2% ), respectively ( P=0.341), and the NRM were 14.7% (95% CI 8.4% –22.6% ) and 16.2% (95% CI 7.4% –28.0% ), respectively ( P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% –90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively ( P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% –79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively ( P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% –79.3% ), respectively ( P=0.284) . Conclusion:The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Objective:To analyze the correlation between Cutibacterium acnes (C. acne) ribotypes (RTs) on the skin surface and epidermal barrier function in patients with acne vulgaris.Methods:Sixty patients with acne vulgaris were enrolled in this prospective study from the Department of Dermatology, the Affiliated Hospital of Southwest Medical University from November 2018 to May 2019, including 23 males and 37 females, aged (21.6±2.6) years. According to the General Acne Grading System (GAGS) score, the patients were divided into three groups: 28 mild cases, 14 moderate cases, and 18 severe or above cases. Twenty healthy controls aged 18 to 30 years were recruited in the same period from the community, including 5 males and 15 females, aged (24.2±2.3) years. The VISIA skin testing device was used to detect the percentage of red areas and porphyrins on the facial skin of all subjects. The hydration of the stratum corneum (SCH), transepidermal water loss (TEWL), PH value and the skin surface sebum level on the facial skin were detected by CK system. The RTs of C. acne were further analyzed based on the 16s rDNA sequences. The correlation between the abundance of each RT and epidermal barrier function was analyzed using Pearson correlation analysis.Results:Compared with the healthy controls, the percentage of porphyrins [(41.69±23.10) % vs (61.33±24.27) %, t=2.98, P<0.01] and the percentage of red area [(26.71±17.13) % vs (67.97±15.22) %, t=10.78, P<0.01] decreased in the acne vulgaris patients. Meanwhile, the patients of different severity levels had decreased SCH ( P<0.01), but increased TEWL, pH value, and the skin surface sebum level ( P<0.05) compared to healthy controls. Six different RTs (RT1, RT2, RT7, RT12, RT13 and RT14) were found in both healthy controls and acne vulgaris patients with varying degrees of severity, while there was no statistically significant difference of C. acne abundance between the mild patients and the controls ( P>0.05). As the severity of disease increased, the abundance of the above RTs showed a changing trend, with the gradually decreasing abundance of RT1 and the gradually increasing abundance of RT2, RT7, RT12, RT13, and RT14 (all P<0.05). The abundance of RT1 was negatively correlated with pH value ( r=-0.33, P=0.04) and GAGS score ( r=-0.39, P=0.01). The abundance of RT2 ( r=0.39, P=0.02) and RT7 ( r=0.39, P=0.01) were positively correlated with GAGS score. The abundance of RT13 was negatively correlated with SCH ( r=-0.34, P=0.02) and positively correlated with TEWL ( r=0.30, P=0.05). Conclusions:As the severity of disease increases, the abundance of various RTs of C. acne on the skin surface of acne vulgaris patients shows a trend of gradually increasing or decreasing, and the abundance of differential RTs of C. acne is closely related to the function of the epidermal barrier.

Objective:To explore the feasibility of cardiac T 2 weighted dark blood sequence (T 2W-DB) based on artificial intelligence assisted compression-sensing(ACS) in clinical cardiac MR examination, compared with the conventional cardiac fast spin-echo T 2W-DB sequence. Methods:A total of 38 patients referred for cardiac MR examination in Tongji Hospital were enrolled prospectively from August to December 2021. The conventional T 2W-DB scan and the single-shot ACS T 2W-DB scan were acquired at continuous short-axial slices covering the whole left ventricle in all patients, and the acquisition time of each scan was recorded. The image quality of the two sequences was evaluated by the objective quantitative parameters and the subjective scoring methods, respectively. The signal to noise ratio (SNR), the contrast to noise ratio of the interventricular septum to blood pool (CNR), and the sharpness of the images were calculated. The subjective scoring was to evaluate the overall image quality, the effect of blood pool suppression, the visibility of right ventricular free wall, left ventricular free wall, and interventricular septum with a 5-point Likert scale. The intraclass correlation coefficient and Kendall W were calculated to evaluate the interobserver agreement of the objective quantitative parameters and subjective scoring. The paired t-test or Wilcoxon test was used to compare the difference in acquisition time, objective quantitative parameters and subjective scoring between the conventional T 2W-DB and the single-shot ACS T 2W-DB. Results:The inter-observer agreement between the single-shot ACS T 2W-DB and conventional T 2W-DB was good in all the objective quantitative parameters and subjective scoring of image quality ( P<0.05 for all). Compared with conventional T 2W-DB, acquisition time of single-shot ACS T 2W-DB was remarkably shortened [(85.8±14.7) s vs. (16.9±3.0) s, t=35.42, P<0.001]. Compared with SNR (66.4±29.0) and CNR(61.8±28.6) of conventional T 2W-DB, single-shot ACS T 2W-DB had significantly higher SNR(110.8±36.8, t=-8.13, P?0.001) and CNR(88.2±31.1, t=-5.89, P?0.001). Compared with conventional T 2W-DB, single-shot ACS T 2W-DB had better blood pool inhibition effect (4.6±0.6 vs. 4.7±0.5, Z=-2.64, P=0.008). There was no significant difference in overall image quality, visibility of right ventricular free wall, left ventricular free wall, and interventricular septum between the two sequences( P>0.05 for all). Conclusions:In cardiac MR examination, compared with the conventional T 2W-DB sequence, the single-shot ACS T 2W-DB sequence can significantly shorten the acquisition time and obtain better image quality.

Signaling pathways in innate and adaptive immunity play vital roles in pathogen recognition and the functions of immune cells. Higher-order assemblies have recently emerged as a central principle that governs immune signaling and, by extension, cellular communication in general. There are mainly two types of higher-order assemblies: 1) ordered, solid-like large supramolecular complexes formed by stable and rigid protein-protein interactions, and 2) liquid-like phase-separated condensates formed by weaker and more dynamic intermolecular interactions. This review covers key examples of both types of higher-order assemblies in major immune pathways. By placing emphasis on the molecular structures of the examples provided, we discuss how their structural organization enables elegant mechanisms of signaling regulation.

Objective:To study the effect of insulin intraperitoneal injection on abnormal blood lipid intype 2 diabetic KKAy mice.Methods:Type 2 diabetic mice model was established by feeding high fat and high sugar diet. KKAy model mice were randomly divided into intraperitoneal injection group ( n=6), subcutaneous injection group ( n=6) and no-treatment group ( n=3). At the same time, healthy C57BL/6J mice were selected as normal group ( n=6), and healthy KKAy mice as disease-free group ( n=6). The treatment process was divided into two stages. The first stage consists of 6 weeks, in which the mice in the intraperitoneal and subcutaneous groups were treated with insulin intraperitoneally and subcutaneously respectively. The second stage consists of 4 weeks, in which the mice in intraperitoneal and subcutaneous groups were subcutaneously injected with insulin. The mice in the remaining 3 groups were not treated. The changes of related indicators were detected every two weeks, including body weight, fasting blood sugar, 2 hours after meal blood sugar, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Results:Changing the injection solution in the medium term of the treatment had no effect on the body mass and blood sugar of KKAy mice with type 2 diabetes. Under this condition, the effect of intraperitoneal injection of insulin on HDL-C and LDL-C is significantly better than that of subcutaneous injection. Besides, both injection solutions are effective in regulating TG, but the effect of reducing total cholesterol is not obvious.Conclusions:The intraperitoneal injection of insulin has a certain effect on the blood lipid abnormality of type 2 diabetic KKAy mice. It can promote the increase of HDL-C, the decrease of LDL-C, and the decrease of TG.

OBJECTIVE: To explore the characteristics of mutations of four common pathogenic genes (GJB2, SLC26A4, GJB3 and 12S rRNA) among patients with nonsyndromic hearing loss (NSHL) from eastern Shandong. METHODS: Peripheral blood samples of 420 NSHL patients were collected, and a hereditary-deafness-gene microarray was used to detect GJB2 c.235delC, c.299-300delAT, c.35delG and c.176del16 mutations, GJB3 c.538C>T mutation, SLC26A4 c.2168A>G and c.IVS7-2A>G mutations, and 12S rRNA c.1555A>C and c.1494C>T mutations. For patients carrying single heterozygous mutations, the coding regions of the above genes were analyzed with Sanger sequencing. RESULTS: The results of the microarray assay and Sanger sequencing showed that 84 patients (20.00%) carried GJB2 mutations, with c.235delC (16.43%) and c.299-300delAT (7.86%) being most common. Seventy-five patients (17.86%) carried SLC26A4 mutations, for which c.IVS7-2A>G accounted for 15.71%. In addition, 5.95% of patients carried 12S rRNA mutations. Only one patient was found to carried GJB3 mutation (c.538C>T). CONCLUSION Common pathogenic mutations for NSHL in eastern Shandong included GJB2 c.235delC and SLC26A4 c.IVS7-2A>G. Of note, 5.95% of patients were due to 12S rRNA m.1555A>G mutation, which gave a frequency greater than other regions of China.
China ; Connexin 26 ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Deafness ; Genes, rRNA ; Hearing Loss ; Humans ; Mutation ; RNA, Ribosomal ; Sulfate Transporters

Objective To compare the effect of storage autologous blood component transfusion versus storage autologous whole blood transfusion on the cellular immune function and hemorheology in the patients undergoing spinal surgery.Methods Forty patients of both sexes,aged 32-60 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elective multilevel spinal surgery,were divided into 2 groups (n =20 each) using a random number table:stored autologous whole blood transfusion group (group A) and stored autologous blood component transfusion group (group B).Before blood sampling (T0),immediately after blood sampling (T1) and at the end of surgery (T2),arterial blood samples were collected for determination of red blood cell count (RBC),hemoglobin (Hb),hematocrit (Hct),erythrocyte aggregation index (EAI) and erythrocyte rigidity index (ERI).Venous blood samples were collected at T0,T2 and on day 6 after surgery (T3),the distribution of T lymphocyte subsets (percentage of CD3+,CD4+ and NK cells) was measured,and CD4+/CD8+ ratio was calculated.Results Compared with the baseline at T0,the percentage of CD3+,CD4+ and NK cells and CD4+/CD8+ ratio were significantly decreased at T2,3 in group A and at T2 in group B,and RBC,Hb and Hct were significantly decreased at T1,and EAI and ERI were decreased at T1,2 in two groups (P＜0.05).Compared with group A,the percentage of CD3+,CD4+ and NK cells and CD4+/CD8+ ratio were significantly increased at T3 (P＜0.05),and no significant change was found in RBC,Hb,Hct,EAI or ERI at each time point in group B (P＞0.05).Conclusion The effect of storage autologous blood component transfusion on cellular immune function is mitigated than that of storage autologous blood transfusion and the effects on hemorheology are comparable in the patients undergoing spinal surgery.