Initial gastrointestinal endocrine cells (GIECs) likely appear at the proximal and distal sites of abdominal intestines and may take a close topographical relation with neural elements in the gut. We examined immunohistochemically-stained sections from 10 fetuses at approximately 8–18 weeks of gestational age (36–155 mm of crown-rump length). Irrespective of whether physiological herniation was present (early 5 specimens) or absent (the other 5), the duodenum and jejunum had well-developed mucosa with villi containing abundant flask-like chromogranin-positive cells. In the earlier 5 specimens, the rectum, standing up to a level of the umbilicus, had a lumen and villi with a few positive cells, but the colon carried neither the lumen or chromogranin-positive cells. The initial GIECs seemed to appear in the basal payer of the epithelium at the distal and proximal foci depending on double pathways of neural crest cell migration. Less number of the colic chromograninpositive cells, more than 5-times difference in density relative to small intestine, was seen in the larger 5 specimens. The appearance of GIECs was delayed at the anal transitional zone (a border area between the columnar and squamous epithelia).The reactivity of neuronal nitric oxide synthase was restricted in the myenteric plexus, whereas clusters of slender calretininpositive cells existed in the lamina propria or core of villi in the duodenum and colon. Relatively small, round or oval positive cells were also seen in the basal layer of the columnar epithelium. Therefore, calretinin-positive cells might exist closely to GIECs in the developing villi.

Meconium is changed from defoliated intestinal villi with apoptosis. A meconium corpuscle is a limited architecture in the meconium at the light microscopic level. In histological and immunohistochemical sections of the abdomen from 40 fetuses at 20–31 weeks of gestation, we found 12 fetuses with meconium and examined the architecture.A solid or loose meconium was seen depending on sites. The solid meconium in the colon and rectum contained numerous spherical or rugby ball-like corpuscles comprising of a core with tightly-packed atrophied cells and a laminar fibrous sheath.The solid meconium surrounded and incorporated villi that maintained the original architecture. The loose meconium was seen not only in the stomach and duodenum but also, depending on specimens, in the colon and rectum. It was composed of a large mucosal fold, a single small villus and/or fragmented epithelia. Notably, these mucosal tissues still contained chromogranin-positive gastrointestinal cells and cytokeratin-positive epithelia. A large ring-like meconium was composed of the entirely circular mucosa or epithelia that seemed to be detached along the muscularis mucosae or the basal lamina.A sheath-like fibrous structure in meconium seemed to originate from the lamina propria and basal lamina of villi. A defoliation of villi with apoptosis seemed difficult to explain a detachment of the entirely circular mucosa or epithelia in large fetuses examined. The latter event might require a specific mechanism such as an in utero intussusception in which a proximal side of the colon was invaginated into the distal lumen.

Arthroscopic surgery currently faces challenges such as limited intraoperative visibility and high technical demands, resulting in a particularly steep learning curve. However, traditional teaching methods at present also present problems including significant operational risks, high learning costs, and ethical dilemmas associated. This has created an urgent need among surgeons for a more efficient and economical training approach. Recent advancements in virtual reality technology have created high-fidelity virtual environments which allow surgeon users to undergo immersive surgical training within simulated settings, offering novel perspectives for standardised arthroscopic skills training. This review systematically summarises the current application progress, technical challenges, and potential future directions of virtual reality arthroscopy simulators, focusing on their technical architecture, characteristics, and advantages. We aim to provide a theoretical basis for the technical standardisation and clinical translation of virtual reality technology in the field of arthroscopic surgical training.

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.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Arthroscopic surgery currently faces challenges such as limited intraoperative visibility and high technical demands, resulting in a particularly steep learning curve. However, traditional teaching methods at present also present problems including significant operational risks, high learning costs, and ethical dilemmas associated. This has created an urgent need among surgeons for a more efficient and economical training approach. Recent advancements in virtual reality technology have created high-fidelity virtual environments which allow surgeon users to undergo immersive surgical training within simulated settings, offering novel perspectives for standardised arthroscopic skills training. This review systematically summarises the current application progress, technical challenges, and potential future directions of virtual reality arthroscopy simulators, focusing on their technical architecture, characteristics, and advantages. We aim to provide a theoretical basis for the technical standardisation and clinical translation of virtual reality technology in the field of arthroscopic surgical training.

Objective:To investigate the expression, distribution and cellular localization of acylglycerol kinase (AGK) in liver cancer tissues, and the correlation of AGK expression with the prognosis of liver cancer patients.Methods:AGK mRNA expression data and clinical information of hepatocellular carcinoma (HCC) patients were downloaded from The Cancer Genome Atlas (TCGA) database in January 2024. The expression differences of AGK mRNA between HCC tissues and paracancerous tissues were compared, and the high and low expressions of AGK were judged by using the median expression of AGK mRNA in 369 HCC tissues as a cut-off value. A univariate logistic regression model was used to analyze the relationship between clinical pathological characteristics and high expression of AGK. The mRNA expressions in HCC tissues and paracancerous tissues of 9 datasets from the Hepatocellular Carcinoma Molecular Landscape Database (HCCDB) 2.0 were compared. The spatial distribution and cellular localization of AGK were analyzed based on multidimensional data from Bulk transcriptome sequencing (RNA-seq), single-cell sequencing and spatial RNA-seq. The expression of AGK protein in liver cancer tissues was analyzed using the Human Protein Atlas (HPA) database. Kaplan-Meier method and log-rank test were employed to compare the differences in overall survival (OS) among patients with different AGK mRNA expressions in HCCDB25 dataset of HCCDB 2.0 and HPA database. The correlation between expressions of AGK and hepatic stem cell-related markers was analyzed by using Spearman rank test based on Tumor Immune Estimation Resource (TIMER) 2.0 database.Results:Data from both the TCGA and 9 datasets of HCCDB 2.0 showed that AGK mRNA expression in HCC tissues was higher than that in paracancerous non-tumorous tissues and normal liver tissues, and the difference was statistically significant (all P < 0.001). HPA database immunohistochemical testing revealed that AGK protein was primarily localized in the cytoplasm, with positive or strong positive expression in HCC tissues and negative or weak positive expression in normal liver tissues; mass spectrometry data showed that it was upregulated in tumor samples (165 cases) compared to normal liver tissues (165 cases) ( P < 0.001). Univariate logistic regression analysis indicated that tumor family history and tumor pathological differentiation in HCC patients from TCGA database were associated with high AGK expression in tumor tissues ( P values were 0.028 and 0.050), while other factors such as age, gender, body mass index, alpha fetoprotein level, Child-Pugh classification, inflammation degree in paracancerous tissues, Ishak fibrosis score, pathological TNM staging, tumor clinical staging, and tumor vascular infiltration had no impact on AGK expression level in tumor tissues (all P > 0.05). One hundred and fifty-eight patients were divided into high and low KGK mRNA expression groups based on the median expression of AGK mRNA in tissues of HCCDB25 dataset, analysis showed that patients in low AGK mRNA expression group (79 cases) had better overall survival (OS) compared to the high expression group (79 cases) in tumor tissues, and the difference was statistically significant ( P = 0.038), while there was no significant difference in OS between high (79 cases) and low (79 cases) expression groups in paracancerous tissues ( P = 0.760). In HPA database, patients were divided into high and low AGK mRNA expression groups based on AGK mRNA values in liver cancer tissues corresponding to the lowest P value during OS analysis by Kaplan-Meier method; in all stages of HCC patients, low AGK mRNA expression group (279 cases) had better OS than the high expression group (76 cases), and the difference was statistically significant ( P = 0.022). The OS of high AGK mRNA expression group in patients with stages Ⅱ-Ⅲ was worse than that of low expression group, and the difference was statistically significant ( P = 0.007). The UMAP plot obtained through dimensionality reduction and cell clustering analysis based on single-cell sequencing data in HCCDB 2.0 revealed that AGK gene expression in liver cancer tissues was primarily distributed in tumor cells, NK/T cells, stromal cells, and myeloid cells. Spatial transcriptomic analysis of tissue samples from 5 HCC patients using HCCDB 2.0 online tools showed that AGK expression varied across different liver cancer tissue regions (non-tumorous tissue, paracancerous tissue, tumor junction, tumor focus, and portal vein tumor thrombus), with 3 cases showing AGK expression enrichment in tumor cells of the tumor junction, tumor focus and portal vein tumor thrombus, while lower in normal hepatocytes, stromal cells and immune cells. In 2 cases, AGK expression was more widespread. Analysis of 3 patients with significant AGK enrichment showed that in HCC samples with complete fibrous capsule, AGK was mainly localized in tumor cells of the tumor focus and junction areas, with weaker expression in paracancerous normal tissues; while in samples with incomplete capsule, high AGK expression was primarily in tumor cells of the tumor junction, tumor focus and portal vein tumor thrombus. TIMER 2.0 database assessment showed that AGK gene expression in 371 patients of TCGA database was positively correlated with the expressions of liver cancer stem cell-related marker genes, including PROM1 ( rho = 0.250), TYH1 ( rho = 0.188), CD44 ( rho = 0.268), ANPEP ( rho = 0.171), CD47 ( rho = 0.435), EPCAM ( rho = 0.246), KRT19 ( rho = 0.203), TGFB1 ( rho = 0.285), and SOX9 ( rho = 0.328) (all P < 0.001). Conclusions:AGK expression is significantly upregulated at both mRNA and protein levels in tumor tissues of HCC patients, it predominantly localizes in the tumor tissues and the cytoplasm of tumor cells within the junction areas, and its high expression closely associates with poor prognosis of patients. Its expression is positively correlated with the expression of liver cancer stem cell-related markers.

Objective To summarize the clinical and pathological characteristics of Langerhans cell histiocytosis(LCH)involving thyroid gland.Methods We reviewed 5 cases of histologically confirmed LCH with thyroid gland involvement in Huashan Hospital,Fudan University from Jun 2017 to Nov 2022 and analyzed their clinicopathological features.Results There were 1 male and 4 females aged from 29 to 54 years,with a median age of 31 years.Ultrasound showed hypoechoic nodules of thyroid.Morphologically,there were a large number of Langerhans cells,which contained abundant eosinophilic cytoplasm.The nucleus was oval,or had deeply grooved nuclei,which was like coffee beans.The nucleolus was not obvious,accompanied by a variable number of lymphocytes and eosinophils infiltration.The lesional cells were positive for CD1α,S100,Langerin,and Ki67 proliferation index was more than 15%,of which the highest was 70%.The tested 4 cases were all BRAF V600E and MAP2K1 gene mutation negative.Conclusion Cases limited to the thyroid were exceedingly rare.Most cases occurred in patients with multifocal disease.The clinical manifestations were painless enlargement of the thyroid gland.Surgical resection was a common treatment.Pathological manifestations included a large number of Langerhans cells and eosinophils diffused with the destruction of normal thyroid follicular structures.There was a characteristic of low mutation rates in BRAF V600E and MAP2K1 genes.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.