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 construct a mouse asthma model induced by mugwort pollen and to explore endotyping,providing methods for subsequent precision treatment.Methods:BALB/c mice were intraperitoneally injected with mugwort pollen extract(MPE)to sensitize,following MPE intranasal challenge to construct MPE allergic asthma murine model.Mice were randomly divided into PBS sensitization and PBS challenge(P-P),MPE sensitization and PBS challenge(M-P),MPE sensitization and MPE challenge model(M-M)groups.24 h after final challenge,mice were performed to examine airway responsiveness;bronchoalveolar lavage fluid(BALF)was harvested for cell counting and statistical classification of inflammatory cells through flow cytometry analysis.Pulmonary slides were collected for pathological examination,including HE,PAS,Masson and α-SMA immunohistochemical staining.ELISA was used to detect levels of IFN-γ,IL-4,IL-5,IL-13,IL-17A in lung tissue and serum,as well as serum total IgE and MPE-specific IgE,IgG1,IgG2a levels.Results:Pathological examination showed higher airway reactivity,more inflammatory cells infiltration around airway,obvious goblet metaplasia,thickening of airway smooth muscles and dramatical fibrin deposition around airway in model group.Total cell numbers of BALF were increased from<1×105 cells/ml in P-P group to>5×105 cells/ml in model group,in which eosinophils were predominant cellular type,levels of IL-4,IL-13,IL-17A in lung and IL-5,IL-13 levels in serum were significantly increased,as well as significant increasing levels of total IgE and MPE-specific IgE,IgG1,IgG2a.Conclusion:MPE-sensitized and challenged mice induces typical eosinophilic asthma featured with elevated eosinophils,as well as secretion of inflammatory factors of type 2 and type 17,IgE,IgG1 and IgG2a subtypes soars to high levels.

Objective To examine the effect of patient-centered care services on compliance to treatment among patients with multidrug-resistant (MDR) or rifampicin-resistant (RR) pulmonary tuberculosis (PTB), so as to provide the scientific evidence for promoting the widespread application of the appropriate nursing process of MDR/RR-PTB patients in the hospital. Methods The MDR/RR-PTB patients that were definitely diagnosed at the Sixth People’s Hospital of Nantong City during the period from January 2017 to October 2020 were enrolled. The patients with confirmed diagnosis of MDR/RR-PTB during the period January 2017 to December 2018 served as controls, who were given routine care in the hospital, and those with confirmed diagnosis of MDR/RR-PTB during the period January 2019 to October 2020 served as the care group, who were given patient-centered personalized care services, including one-to-one consultations, periodic group activities, informatization case management, and personal reminder for return visits. The proportion of inclusion into treatment, loss to follow-up, return visits and sputum examinations were compared between the care and control groups. Results A total of 104 MDR/RR-PTB patients were included, including 54 cases in the control group and 50 cases in the care group. There was no significant difference in gender and age distribution between the two groups (χ² = 3.013, 1.336, P > 0.05). The proportion of inclusion into treatment was higher in the care group (100.00%, 50/50) than in the control group (87.04%, 47/54) (P = 0.013), and the proportion of loss to follow-up was lower in the care group (0, 0/43) than in the control group (19.05%, 8/42) (P = 0.002). In addition, the overall proportion of return visits was higher in the care group (93.09%, 377/405) than in the control group (83.56%, 371/444) (χ² = 18.345, P < 0.001), and the proportion of sputum examinations was higher in the care group was (83.70%, 339/405) than in the control group (79.28%, 352/444) (χ² = 2.737, P = 0.098). Conclusion Patient-centered care services facilitate the improvements in the proportion of inclusion into treatment and compliance to treatment and reduction in the proportion of loss to follow-up among MDR/RR-PTB patients, which deserves widespread applications.

Objective:Radiotherapy is the primary treatment for nasopharyngeal carcinoma,but it frequently leads to radiotherapy-induced temporal lobe injury(RTLI).Magnetic resonance imaging(MRI)is the main diagnostic method for RTLI after radiotherapy for nasopharyngeal carcinoma,but it is prone to missed diagnoses.This study aims to investigate the causes of missed diagnoses of RTLI in nasopharyngeal carcinoma patients undergoing MRI after radiotherapy. Methods:Clinical and MRI data from nasopharyngeal carcinoma patients diagnosed and treated with radiotherapy at Xiangya Hospital of Central South University,from January 2010 to April 2021,were collected.Two radiologists reviewed all head and neck MRIs(including nasopharyngeal and brain MRIs)before and after radiotherapy of identify cases of late delayed response-type RTLI for the first time.If the original diagnosis of the initial RTLI in nasopharyngeal carcinoma patients did not report temporal lobe lesions,it was defined as a missed diagnosis.The first diagnosis of RTLI cases was divided into a missed diagnosis group and a non-missed diagnosis group.Clinical and imaging data were compared between the 2 groups,and multivariate logistic regression analysis was used to identify independent risk factors for MRI missed diagnoses of initial RTLI. Results:A total of 187 nasopharyngeal carcinoma with post-radiotherapy RTLI were included.The original diagnostic reports missed 120 cases and accurately diagnosed 67 cases,with an initial RTLI diagnosis accuracy rate of 35.8%and a missed diagnosis rate of 64.2%.There were statistically significant differences between the missed diagnosis group and the non-missed diagnosis group in terms of lesion size,location,presence of contralateral temporal lobe lesions,white matter high signal,cystic degeneration,hemorrhage,fluid attenuated inversion recovery(FLAIR),and examination site(all P<0.05).Multivariate logistic regression analysis showed that lesions≤25 mm,non-enhancing lesions,lesions without cystic degeneration or hemorrhage,lesions located only in the medial temporal lobe,and MRI examination only of the nasopharynx were independent risk factors for missed MRI diagnosis of initial RTLI(all P<0.05). Conclusion:The missed diagnosis of initial RTLI on MRI is mainly related to lesion size and location,imaging characteristics,and MRI examination site.

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*

Objective: Toestablish and verify the method of genetic polymorphisms using time-of-flight mass spectrometry as a polygene testing platform. Methods: 998 cases of DNA samples and 20 cases of whole blood samples were collected from Fuwai hospital of Chinese academy of medical sciencesduring September 2017 to October 2018, including 512 cases of males and 506 cases of females.280 patients aged 18-30, 442 patients aged 31-64, and 296 patients aged ≥65.11 cardiovascular drugsrelatedgenes in 998 DNA samples were detected by time-of-flight mass spectrometry to evaluate the compliance rate compared with identifiedresults. 20whole blood samples were selected to detect 11 genes using both time-of-flight mass spectrometry and Sanger sequencing. The results were compared twice, and accuracy was evaluated according to Sanger sequencing as the gold standard. Ten cases of genomic DNA with wild-type loci were selected for specific evaluation by time-of-flight mass spectrometry. Samples containing all heterozygous genotypes were measured after gradient dilution to evaluate the detection sensitivity of the new method. Samples containing all 49 genotypes (two genotypes were not found because they are rare in Chinese population) were used in order to do the inter-assay and intra-assay precision evaluation. An anti-interference study was performed by selecting wild and homozygous mutant samples of represented heterozygous peak shape. Results: The results showed that the compliancerate of the single retrospective sample was over 99.5%. The resultsof time-of-flight mass spectrometry and Sanger sequencing was the same. The minimum detection limit of DNA was 0.4 ng, the inter-assay and intra-assay precision were 100%, and the degradation ability of the UNG enzyme was 10⁵ copies/μl in aerosol.The reaction system has a strong anti-interference ability to the genome and intermediate aerosol, and no cross-contamination between different matrices of the chip. Conclusions The time-of-flight mass spectrometry as a polygene detection system shows agood detection performance and can be applied to clinical detection. In addition, this paper established a performance verification research scheme based on the time-of-flight mass spectrometry platform polygene detection system.

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.

Objective To summarize the etiological,clinical and imaging characteristics of cerebral venous sinus thrombosis (CVST) in children so as to provide the basis for early diagnosis and prompt treatment.Methods All the medical records including clinical manifestations,laboratory data,neuroimaging changes,treatment and short-term prognosis were analyzed retrospectively in 12 cases of CVST hospitalized in Children' s Hospital of Fudan University from Aug 2008 to May 2012.Results (1) Regarding the etiology:of the 12 cases,the causes of CVST were infection (2/12),intracranial tumor (1/12),nephrotic syndrome (2/12),cryptogenic disease (7/12).Seven out of all 12 cases without definite cause were presented subacute or chronic headache associated with progressive or acute exacerbation.Seven cases had been misdiagnosed.(2)Diagnosis:All 12 cases were made a definite diagnosis as CVST after neuroimaging examination of brain magnetic resonance imaging combined with magnetic angiography venography.(3) Short-term prognosis:all the patients were treated with anticoagulation,and 11 cases improved.Four of 7 cases with cryptogenic disease had different degrees of visual impairment,and no improvement were found after the treatment; One patient died although accepted digital subtraction angiography and balloon catheter technique.Conclusions Cerebral venous sinus thrombosis has no specific clinical manifestations and a high rate of misdiagnosis.Increased consideration and prompt magnetic angiography venography play a key role in the accurate diagnosis.Anticoagulation is safe and effective.

Objective To set up a method for the determination of ginsenoside Rg1 in Changyu Granules. Methods The content of ginsenoside Rg1 was determined by RP-HPLC on C18 column (4.6 mm?250 mm, 5 ?m). The mobile phase consisted of ethane nitrile and water (80:20). The flow rate was 1.0 mL/min. The detection wavelength was at 210 nm. Results Ginsenoside Rg1 showed a good linear relationship at the range of 0.125～4 ?g, r =0.999 7. The average recovery rate was 97.30%, RSD=1.31%. Conclusion The method is simple with good reproducibility, and can be used for the quality control of Changyu Granules.