Objective:To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED).Methods:Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed.Results:Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases.Conclusions:CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Objective:To explore the relationship between blood urea nitrogen to creatinine ratio and frailty in the elderly aged ≥65 years in 8 longevity areas in China.Methods:Participants were recruited from the Healthy Aging and Biomarkers Cohort Study. Based on baseline information about blood urea nitrogen and risk for frailty obtained at follow-up of the participants, blood urea nitrogen to creatinine ratio was classified according to quintiles, Cox proportional hazard regression models were used to analyze the association between blood urea nitrogen to creatinine ratio and frailty.Results:A total of 1 562 participants aged (81.0±17.0) years were included, in whom 814 (52.1%) were men, and 258 frailty events occurred during a mean follow-up of (3.73±1.43) years. Cox proportional hazards model showed that after adjusting for relevant confounders, compared with the participants in the lowest quintile group ( Q1), the risk for frailty decreased by 36%, 44%, and 40% in the participants in the third quintile group ( Q3), the fourth quintile group ( Q4) and the highest quintile group ( Q5) respectively [hazard ratio ( HR)=0.64, 95% CI: 0.43-0.94; HR=0.56, 95% CI: 0.38-0.84; HR=0.60, 95% CI: 0.41-0.88]. The risk for frailty decreased by 20% for every unit standard deviation increase in blood urea nitrogen to creatinine ratio ( HR=0.80, 95% CI: 0.70-0.91). Moreover, blood urea nitrogen to creatinine ratio and the risk for frailty showed a nearly linear dose-response relationship. Conclusions:The increase in blood urea nitrogen to creatinine ratio was associated with higher risk for frailty. Maintaining high blood urea nitrogen to creatinine ratio is important for the prevention of frailty in the elderly.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To compare the therapeutic effects of modified plantar skin grafting and thigh skin grafting on the deep burn wounds of the back and buttocks.Methods:A retrospective cohort study was conducted to analyze the clinical data of 30 patients with deep burn wounds on their back and buttocks who were admitted to the 910th Hospital of Joint Logistic Support Force of PLA from January 2021 to April 2023, including 26 males and 4 females, aged 21-72 years [(49.9±14.0)years]. The total burn size was 50%-97% of the total body surface area (TBSA), with the third-degree burn on the back and buttocks 6%-16% TBSA. The burn wounds on the back and buttocks were repaired using plantar skin grafts alone, thigh skin grafts alone or plantar skin grafts combined with the grafts from other body parts. The patients were grouped according to the skin graft donor sites and the times of harvesting skin grafts: there were 20 patients undergone plantar skin grafting including 10 patient with plantar skin graft harvested once (group of plantar skin graft harvested once) and 10 patients with plantar skin graft harvested twice or three times (group of plantar skin graft harvested more than once), and 10 patients undergone thigh skin grafting harvested once (group of thigh skin graft harvested once). The areas of plantar skin grafts harvested at the last time and the wound areas on the back and butts that could be repaired each time were calculated. After the last harvest, the thickness of the stratum corneum, 7-day survival rate of the skin grafts, proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month Vancouver Scar Scale (VSS) scores of the donor sites in the group of plantar skin graft harvested once were compared with those in the group of thigh skin graft harvested once and the group of plantar skin graft harvested more than once. The appearance and texture of the skin graft, patients′ walking patterns and complications were observed at 6 months after the last skin harvest.Results:All the patients were followed up for 6-18 months [(7.8±1.6)months]. In the 20 patients with plantar skin grafts harvested, the areas of skin grafts harvested at the last time were 2.5%-4.5% TBSA [(3.4±0.6)% TBSA] and the wound areas that could be repaired each time were 3%-8% TBSA [(5.5±1.5)% TBSA]. After the last harvest, the thickness of the stratum corneum in the group of plantar skin graft harvested once was (190.4±8.9)μm, which was significantly thicker than that in the group of thigh skin graft harvested once [(50.0±6.6)μm] and that in the group of plantar skin graft harvested more than once [(166.8±21.9)μm] ( P<0.01); the 7-day survival rate of the skin grafts, proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month VSS scores of the donor sites were (93.6±2.3)%, 2.0 (0.1, 3.5)%, (9.9±1.8)days and (1.7±0.7)points in the group of plantar skin graft harvested once, (78.0±6.6)%, 5.3 (4.0, 5.8)%, (14.0±1.4)days and (4.9±2.3)points in the group of thigh skin graft harvested once, and (93.4±2.6) %, 2.0 (0.1, 3.8)%, (10.0±1.2)days and (1.8±0.8)points in the group of plantar skin graft harvested more than once. The group of plantar skin graft harvested once showed a significant increase in the 7-day survival rate and a significant decrease in the proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month VSS scores of the donor sites in comparison with the group of thigh skin graft harvested once ( P<0.05 or 0.01), while there were no significant differences in above mentioned indices between the group of plantar skin graft harvested once and the group of plantar skin graft harvested more than once ( P>0.05). At 6 months after the last skin harvest, the skin graft areas on the back and buttocks were flat, hard and firm and all the patients in the three groups could walk normally, with no complications such as severe itching, pain or folliculitis in the skin graft area. Conclusions:In the treatment of burn wounds on the back and buttocks, compared with thigh skin grafting, modified plantar skin grafting has advantages of thicker stratum corneum, better wear resistance and pressure resistance in the skin graft areas, a higher survival rate of skin grafts, rapid healing, mild scar, and undisturbed walking pattern after surgery and no common complications. Moreover, skin grafts can be harvested repeatedly from the donor sites, with no impact on the therapeutic effects.

Purpose To explore the value of the new generation tau PET tracer 18F-Florzolotau in Alzheimer's disease(AD)at different stages.Materials and Methods Twenty-five MCI patients and sixty-one AD patients with positive β-amyloid status in Huashan Hospital,Fudan University from February 2020 to January 2022 were retrospectively enrolled with 18F-Florzolotau PET imaging and demographic and clinical data.The pre-processed PET images were analyzed by SPM two-sample t-test between MCI and AD groups,and the standardized uptake value ratios(SUVR)were extracted from the region of interest defined by SPM analysis(P＜0.001);scaled subprofile model/principal component analysis was used to construct the different tau related patterns(MCItauRP,ADtauRP)and calculate the corresponding expression values.The classification efficiency of SUVR and MCItauRP,ADtauRP expression values was evaluated by receiver operating characteristic curve.Results Compared with MCI patients,tau protein deposition of AD patients was increased mainly in the bilateral temporal,occipital lobe(P＜0.001),and the SUVR of these brain region in the AD group was higher than that in the MCI group(Z=-3.164,P＜0.00l);the expression values of MCItauRP and ADtauRP were significantly different between the AD group and MCI group(t=3.72,Z=-3.51;both P＜0.001),and these expression values of AD patients were higher than those in the MCI group;the accuracy of tauRP expression values and SUVR for the differentiation between the AD and MCI group were 61.63％,65.12％and 65.12％,respectively;the sensitivity was 88.00％,96.00％and 100.00％,respectively;the specificity was 50.82％,52.46％and 50.82％,respectively.Conclusion The new tau PET can identify and distinguish the differences in tau protein deposition between AD and MCI patients.However,the classification and diagnosis efficiency is not high.In the future,it is necessary to find a more ideal analysis method.

Objective:To compare the localization accuracy of interictal 18F-FDG and 18F-flumazenil (FMZ) PET/CT imaging for focal cortical dysplasia (FCD). Methods:A retrospective analysis was conducted on 22 patients (12 males, 10 females; age 8-36 years) with pathologically confirmed FCD who underwent surgical resection at Huashan Hospital, Fudan University from July 2021 to June 2023. All patients underwent 18F-FDG and 18F-FMZ PET/CT scans before surgery. Surgical pathological diagnosis was used as the gold standard. Visual scoring was used to analyze the images. The accuracy of the two imaging methods in the localization of FCD was compared, and subgroup analysis (FCD Ⅱa, FCD Ⅱb) of different pathological type was further performed. Paired- t test, χ2 test or Fisher′s exact test was used to analyze the data. Results:The visual score of 18F-FMZ PET/CT was higher than that of 18F-FDG (3.00±0.82 vs 2.27±0.92; t=4.17, P=0.020). The accuracy of interictal 18F-FMZ PET/CT was 77.27%(17/22), which was higher than that of 18F-FDG PET/CT (36.36%, 8/22; χ2=7.50, P=0.006). Subgroup analysis showed that within the cohort of patients diagnosed with FCD Ⅱa ( n=18), 18F-FMZ PET/CT outperformed 18F-FDG in terms of accuracy for localization (15/18 vs 6/18; P=0.006). Conclusion:Compared to 18F-FDG, 18F-FMZ PET/CT demonstrates clearer and more accurate identification of lesion borders, and exhibits higher precision, which provides valuable guidance for preoperative localization.

The determination of kinship requires the probability calculation among a set of individuals in a population supposed in a certain relationship.To make the method of kinship estimation easier to understand and for reasonable application,a general algorithm for parentage testing is presented in this paper.Furthermore,we discussed the reasons for the controversy of disputed-parent cases and proposed suggestions for it.In conclusion,all kinds of parentage testing can be easily solved based on the genetic rule and general algorithm.

Objective:To investigate the preliminary efficacy of 3D printed individualized genioglossus advancement (GA) for the treatment of obstructive sleep apnea (OSA) in adults with micrognathia.Methods:The OSA patients with retropalatal and retroglossal collapses due to micrognathia underwent 3D printed individualized GA combined with Uvulopalatopharyngoplasty(UPPP) in Department of Otolaryngology, Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Clinical data including pre-and post-operative polysomnography (PSG), cephalometric measurements of genioglossus advancement, patient-reported symptom and surgical complications were collected. A comparison of pre-and post-operative data was conducted using paired t-tests. Results:Nineteen OSA patients with micrognathia successfully underwent 3D printed individualized GA combined with UPPP, and achieved an actual mean genioglossus advancement distance of (9.0±1.4) mm compared to the planned distance of (9.4±1.0) mm preoperatively ( t=0.81, P=0.427). Among the 14 patients followed up for more than 6 months, the mean AHI reduced by 60.4% at 6 months postoperatively, with 5 cases (5/14) cured and 5 cases (5/14) showing significant improvement, resulting in an overall surgical response rate of 10/14. All patients expressed satisfaction with their postoperative facial appearance, with 13 cases perceiving an improvement in attractiveness. Two patients reported temporary genial numbness, and one patient experienced temporary mandibular occlusal asthenia. Conclusion:The 3D printed individualized GA combined with UPPP effectively reduces AHI in adult OSA patients with micrognathia, accompanied by a low incidence of surgical complications and high patient satisfaction regarding postoperative facial appearance.

Objective:To investigate the value of aspartate aminotransferase/lymphocyte ratio (ALR), γ-glutamyltranspeptidase/lymphocyte ratio (GLR) and aspartate aminotransferase/alanine aminotransferase ratio (AAR) in predicting the recurrence of hepatocellular carcinoma after liver transplantation.Methods:The retrospective cohort study was conducted. The clinicopathological data of 178 patients with hepatocellular carcinoma who underwent liver transplantation in Tianjin First Central Hospital from July 2014 to June 2018 were collected. There were 156 males and 22 females, aged (54±9)years. All patients received the first time of orthotopic liver transplantation. Observation indicators: (1) follow-up; (2) the predictive value and cutoff value of each index for tumor recur-rence of patients with hepatocellular carcinoma after liver transplantation; (3) analysis of risk factors for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation; (4) cons-truction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and the Log-rank test was used for survival analysis. Factors with P<0.05 in univariate analysis were included in multivariate analysis. Univariate analysis and multivariate analysis were performed by COX proportional risk regression model with forward method. The regression coefficient was used to build the prediction model. The receiver operating characteristic curve was drawn, and the area under curve (AUC) was used to evaluate the predictive ability of prediction model. Results:(1) Follow-up. All 178 patients with hepatocellular carcinoma were followed up for 36(range, 1?74)months after liver transplantation. During the follow-up, there were 41 patients died, 61 patients with tumor recurrence and 117 cases without tumor recurrence. The 3-, 5-year overall survival rates and 3-, 5-year tumor recurrence free survival rates of patients after liver transplantation were 72.8%, 69.9% and 57.3%, 52.8%, respectively. (2) The predictive value and cutoff value of each index for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. The AUC of preoperative serum alpha fetoprotein (AFP), tumor diameter, ALR, GLR, neutrophil to lymphocyte ratio, AAR in recipients were 0.76, 0.70, 0.69, 0.65, 0.64, 0.65 (95% confidence interval as 0.68?0.83, 0.61?0.79, 0.61?0.77, 0.57?0.74, 0.56?0.73, 0.56?0.74, P<0.05), and the corresponding best cutoff value of each index were 228.00 μg/L, 5.25 cm, 92.90, 122.40, 3.00, 2.42. (3) Analysis of risk factors for tumor recurrence of patients with hepato-cellular carcinoma after liver transplantation. Results of multivariate analysis showed the preoperative serum AFP >228.88 μg/L, number of tumor as multiple, tumor diameter >5.25 cm, ALR >92.90, AAR >2.42 were indepen-dent risk factors for tumor recurrence of hepatocellular carcinoma after liver transplantation ( hazard ratio=3.13, 1.90, 2.66, 2.40, 2.75, 95% confidence interval as 1.81?5.41, 1.08?3.35, 1.49?4.74, 1.40?4.11, 1.54?4.91, P<0.05). (4) Construction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. According to the results of multivariate analysis, the preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR were used to construct the predictive model for tumor recurrence of hepatocellular carcinoma after liver transplantation. The AUC, best cutoff value, specificity and sensitivity of the predictive model were 0.83 (95% confidence interval as 0.76?0.89, P<0.05), 5.5, 80.3% and 73.8%. Of the 178 patients, there were 110 patients with low risk of tumor recurrence (scoring as 0?5) and 68 patients with high risk of tumor recurrence (scoring as 6?16) after liver transplantation. The 1-, 3-, 5-year tumor recurrence free survival rates and 1-, 3-, 5-year overall survival rates of patients with high risk of tumor recurrence were 27.7%, 18.2%, 18.2% and 63.7%, 48.9%, 48.9%, respectively. The above indicators of patients with low risk of tumor recurrence were 92.3%, 82.4%, 74.6% and 90.4%, 87.7%, 83.6%, respectively. There were significant differences of the above indicators between patients with high risk of tumor recurrence and low risk of tumor recurrence ( χ2=67.83, 21.95, P<0.05). Conclusions:The preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR are independent influencing factors for tumor recurrence of hepato-cellular carcinoma after liver transplantation. The predictive model constructed based on the above indexes has a good prediction efficiency.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells