Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective To explore the effects and mechanism of Baitouweng Decoction in intestinal mucosal healing in mice with ulcerative colitis(UC)based on RIPK1/RIPK3/MLKL signaling pathway.Methods Totally 30 C57BL/6 male mice were randomly divided into control group,model group,Baitouweng Decoction group,infliximab group and combination group(Baitouweng Decoction+infliximab),with 6 mice in each group.A mouse model of UC was established by free administration of 3.5%sodium gluconate sulfate solution for 7 days.After modeling,Baitouweng Decoction group was given 8 g/kg Baitouweng Decoction solution by gavage daily,while the infliximab group was given 5 mg/kg infliximab intraperitoneal injection,the combination group was given synchronous gastric and intraperitoneal injection,while the control group and model group were given equal volume of normal saline by gavage for 7 consecutive days.The body mass of mice was recorded daily,fecal characteristics were observed,and disease activity index(DAI)score was performed,colon length was measured after intervention,ELISA was used to detect the contents of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),RT-qPCR was used to detect mRNA expressions of RIPK1,RIPK3 and MLKL in colon tissue,Western blot and immunofluorescence staining were used to detect the expressions of RIPK1,RIPK3 and MLKL protein in colon tissue.Results Compared with the control group,the model group mice showed a decrease in body mass(P<0.01),an increase in DAI score(P<0.01),a shortened colon length(P<0.01),and an increase in serum IL-6 and TNF-α content(P<0.01);colonic mucosal was destructed,with disappearance of crypts and glandular structures,extensive infiltration of inflammatory cells,and increased pathological score of colon tissue(P<0.01);the mRNA and protein expressions of RIPK1,RIPK3 and MLKL in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the body mass of mice in each treatment group increased(P<0.01),and the DAI score decreased(P<0.01),colon length increased(P<0.01),and the contents of serum IL-6 and TNF-α decreased(P<0.05,P<0.01);the destruction of the colonic mucosal barrier was reduced,the pathological score of colon tissue was reduced(P<0.05);the expressions of RIPK1,RIPK3 and MLKL mRNA and protein in colon tissue decreased(P<0.05,P<0.01).Conclusion Baitouweng Decoction can alleviate intestinal mucosal damage and inflammation in UC mice,and its mechanism may be related to the inhibition of the RIPK1/RIPK3/MLKL signaling pathway.

Perianal Paget's disease (PPD) is a rare malignant cutaneous tumor. This paper reported a case of PPD complicated by lung adenocarcinoma and anal canal cancer. The patient, a 76-year-old female, had been experiencing recurrent lower abdominal pain and perianal pruritus for the past 5 years. Upon physical examination, a cauliflower-like neoplasm in size of 5 cm×6 cm was observed on the right perianal skin, with local skin ulceration and a small amount of fluid discharge. The left perianal skin was also involved. In thoracoknee position, a hard mass was palpable in the rectal submucosa at 5-6 points 2 cm from the anal verge. Chest CT revealed multiple lesions in both lungs, indication of metastatic tumors. Further evaluation with fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) indicated multiple hypermetabolic nodules in the lungs, hypermetabolic lymph nodes throughout the body, early FDG uptake in a small patch of skin on the left hip, and increased FDG uptake in the anorectal region. Histopathological examination confirmed the diagnosis of lung adenocarcinoma. This resulted in the patient being diagnosed with PPD, lung adenocarcinoma, anal canal cancer, and systemic multiple lymph node metastasis. The combination of PPD with gastrointestinal tumors and other metachronous malignant tumors is highly prevalent. Colonoscopy, FDG-PET/CT, histopathology, and immunohistochemistry play crucial roles in early identification of local lymph node and distant involvement, facilitating the evaluation of potential malignant tumors and differential diagnosis. Treating methods for PPD are currently diverse, including postoperative combined or single chemotherapy, radiotherapy, targeted therapy, and photodynamic therapy. As trerapeutical options continue to develop, the extent and efficacy of surgery need to be reassessed.
Female ; Humans ; Aged ; Paget Disease, Extramammary/pathology* ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Adenocarcinoma of Lung/complications* ; Lung Neoplasms/complications*

Ulcerative colitis(UC)is a chronic non-specific inflammatory disease of the intestine.With the application of biological agents,more and more UC patients have achieved endoscopic healing,but about one-third of UC patients achieving endoscopic healing still have histological activity,and this sustained histological activity may be associated with disease recurrence.Therefore,histological remission of UC has received increasing attention in clinical practice.In 2020,European Crohn's and Colitis Organization(ECCO)proposed histological remission as an important therapeutic target for UC.In 2021,the International Organization for the Study of Inflammatory Bowel Disease(IOIBD)in its latest program on standard treatment pointed out that histological remission will be used as a measure of deep remission.This article reviewed the progress of research on clinical application of histological remission assessment in UC.

Objective: To explore the role of the new regulator pseudogene phosphatase and tensin homolog pseudogene 1 (PTENp1) in the regulation of PTEN mRNA and gene expression in oral squamous cell carcinoma (OSCC) so as to provide a new target for the prevention, treatment and outcome of OSCC. Methods: First, we collected 42 specimens of OSCC and normal tissues, extracted RNA, detected the expressions of PTENp1, PTEN and miR-21 by qRT-PCR, and studied their correlation by Pearson correlation analysis. HEK293 cells were cultured and transfected with luciferase plasmid of 3'UTR of PTEN and mimic or inhibitor of miR-21 or full-length PTENp1 3'UTR plasmid, respectively. The regulatory role of PTENp1 in PTEN-miR-21 axis and its cancer promoting function were verified by luciferase activity test. Results: qRT-PCR showed that the expressions of PTEN (85.7%) and PTENp1 (90.4%) were significantly repressed in the OSCC tissues while miR-21 expression (76.2%) was remarkably increased. Pearson correlation analysis showed that PTEN expression was negatively correlated with miR-21 expression (R=0.123 5, P<0.001) but positively correlated with PTENp1 expression (R=0.051 8, P=0.01). The results of luciferase activity showed that PTEN expression was significantly up-regulated by overexpression of PTENp1, suggesting that PTENp1 could target competitive binding miR-21 to regulate PTEN expression. Results: PTENp1, as the ceRNA of PTEN, competitively binds the miR-21, which provides a new idea for predicting the early marker and targeting therapy of OSCC in the future.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3⁺, CD4⁺, and CD8⁺ cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.
Animals ; Apoptosis ; Aquaporin 4 ; Astrocytes ; Brain ; Brain Ischemia ; Cisterna Magna ; Drainage ; Edema ; Hippocampus ; Lymph Nodes ; Mice ; Neuroglia ; Neurons ; Prognosis ; Spasm ; Subarachnoid Hemorrhage ; tau Proteins

Objective To investigate the clinical and radiological features of children with first attack of inflammatory central nervous system disorders and seropositivity to myelin-oligodendrocyte glycoprotein (MOG).Methods The clinical course,cerebrospinal fluid (CSF),MRI studies,MOG status and outcomes were retrospectively analyzed in children with first attack of inflammatory central nervous system disorders and seropositivity to MOG who were hospitalized in Children's Hospital of Fudan University from January 2016 to April 2017.Results Thirteen patients including 8 males and 5 females were included in this study,the ratio of male/female was 1.6∶ 1,and the median age was six years.Ten patients were diagnosed with acute disseminating encephalomyelitis,and three with clinically isolated syndromes.Seven patients had elevated CSF lymphocyte cells,and five patients had elevated CSF protein.All the patients' sera were tested for the anti-MOG IgG,which ranged from 1∶10 to 1∶100 with cell-based assay.MRI results showed that multiple anatomical areas were involved.Twelve patients had brain lesions,in which 10 patients had multiple lobes involved and four had tumefactive demyelinating lesions.The affected anatomical areas included white matters in 11 cases,thalamus/basal ganglias in nine,corpus callosums in three,brainstems in 10,spinal cord in five.The MRI features were characterized by hazy,bilateral lesions without clear boundaries.Clinical symptoms were fully restored in all the patients after treated with intravenous globulin and methyl prednisone.The average follow-up time was 8.9 months,and none of the patients had clinical recurrence.Conclusions MOG was associated with many kinds of inflammatory demyelinating diseases of central nervous system in children.Most of them were diagnosed with acute disseminating encephalomyelitis which has an acute or sub acute clinical course.The clinical manifestations of patients showed diversity.Multiple anatomical areas were involved,and treatment with intravenous globulin and methyl prednisone was effective in the acute phase.All of the patients had a favorable outcome.

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks). Among them, five cases had no effect and two cases were seizure free recently. A case with GABRB3 (C.905A>G) had seizure controlled for 3 mouths. A case with ARX (C.700G>A) had seizure controlled for 6 mouths. Conclusion The early onset epileptic spasm with unknown reason is highly related to genetic disorders. A variety of genetic mutations, especially new mutations were found. Genetic heterogeneity of epileptic spasm is obvious.

Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutations. Method: The clinical data of a patient with novel TBC1D24 compound heterozygous mutations from Children′s Hospital of Fudan University were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to April 2016) by using search terms "TBC1D24" "epilepsy" . The clinical features, electroencephalogram (EEG) and prognosis of the patients with TBC1D24 gene mutations were studied. Result: The patient was a boy with non-consanguineous healthy parents.He had an acute episode of focal continuous myoclonus lasting a few hours with consciousness preserved at the age of 3 months.Myoclonic jerks alternatively affected the eyelids, either the right or left limbs, sometimes triggered by fever or fatigue.The frequency was once 3-7 days.At the age of 6 months he was found to have myoclonus seizures with onset from a unilateral eyes lid and limb lasting 10 more minutes and subsequently affected four extremities or the trunk.They occurred once 3-4 months with perserved consciousness and lasted from several hours to up to ten more hours.They mostly disappeared during sleep.He had ataxia and mild mental retarding.Paroxysmal anomalies were not found on ictal traces.A novel compound heterozygous mutation of TBC1D24 gene, c. 730G>A, p.A244T and c. 1571G>C, p.R524P were found in the patient.Further study showed that c. 730G>A mutation was inherited from his father and c. 1571G>C from his mother. These two were not reported in public databases and predicted deleterious by Mutation Taster and polyphen-2.Literature relevant to TBC1D24 published all around the world was reviewed, no Chinese cases with TBC1D24 gene mutations had been reported. The total of 24 cases including the present case with TBC1D24 gene mutation were reported.Among them, 11 cases had compound heterozygous mutations and 13 cases had homozygous mutations.Ten mutations were identified, including 1 termination mutation, 1 frameshift mutation and 8 missense mutations. Conclusion TBC1D24 gene mutational analysis should be performed on patients with early-onset focal continuous myoclonus, if the etiology was unclear.

Alzheimer′s patients bring heavy burden to their family and society, causing potential safety prob-lems unable to escort for a long time with the family, physical constraints between protection and between self-es-teem and the mental health law,the quality of life and life values produce a series of contradiction and ethical is-sues,also make close contact with their nursing staff have to face the moral and ethical dilemma.The suggestions are:Hospital provides professional full-time, professional pension caregivers of alzheimer′s patients for long-term care, Strengthen the communication of nursing staff and patients′families, Reasonable and legitimate use tools, Perfect medical system construction, buildMedical support combinedcare system, Carry out the comprehensive rehabilitation nursing intervention, improve the patients quality of life, Change service concept, strengthening the study of ethical knowledge and application to promote the doctor-patient relationship.