Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E

Objective: To summarize clinical features and our experience of the diagnosis and treatment of laryngocele. Methods: Clinical data of 11 laryngocele patients in department of Otorhinolaryngology Head and Neck Surgery of the Second Affiliated Hospital of Shanxi Medical University from January 2012 to December 2021 were retrospectively reviewed, including 9 men and 2 women, aged from 12 to 75 years, with median age of 56 years. Electronic laryngoscope was performed in 10 of all patients, laryngeal CT in 10 and cervical color ultrasound in 5 before operation.All the operations were performed under general anesthesia, and the external cervical approach was used for external and combined laryngocele. The internal laryngocele was resected by low temperature plasma through transoral endoscopy. Patients were followed up regularly after operation to evaluate the effect. Clinical feature, types of lesions, imaging findings, surgical approaches and follow-up results were analyzed through descriptive statistical method. Results: Eleven laryngocele patients were divided into mixed type (n=6), internal type (n=4) and external type (n=1).Nine patients presented with hoarseness or dysphonia, 7 with cervical mass and 1 with airway obstruction. Surgical resections were done through external cervical approach (n=7)or transoral endoscopic approach (n=4). All the operations were successful and no complication occurred. All cases were followed up from 17 to 110 months. No recurrence was encountered. Conclusions: Laryngocele is a rare lesion with atypical clinical presentation. Preoperative imaging including CT scan and electronic laryngoscope is essential to evaluate the location, and extent of the lesion, and to make the surgical plan.Complete surgical excision is required. Surgical resection is the only effective method for the treatment of laryngocele.
Male ; Humans ; Female ; Middle Aged ; Child ; Adolescent ; Young Adult ; Adult ; Aged ; Laryngocele/pathology* ; Retrospective Studies ; Larynx/pathology* ; Laryngoscopy/methods* ; Hoarseness

Objective: To assess the level and trend of varicella-zoster virus (VZV) antibody among healthy population in Beijing in 2017, after the five-year implementation of the two doses varicella vaccination strategy in 2012, and to provide evidence for scientific evaluation of immunization strategy. Methods: A total of 2 144 subjects in ten age groups from 8 districts of Beijing city were recruited in this study using cross-sectional survey based on multi-stage cluster random sampling method. Serum samples were collected and VZV antibody was detected by ELISA. The influencing factors of antibody concentration and positive rate were analyzed and compared with the study in 2012. The antibody concentration and antibody positive rate were analyzed by nonparametric test and χ² test respectively. Results: The ratio of subjects with registered residence in Beijing city to other provinces was 1∶1. The ratio of male to female was 1∶1.08. The median concentration of VZV antibody was 341.4 (78.6, 1 497.8) mIU/ml, and the total antibody positive rate was 71.1% (1 524/2 144). There were significant differences in antibody positive rate (χ²=736.39, P<0.01) and antibody concentration (χ²=740.34, P<0.01) among different age groups. The antibody positive rate generally increased with age (χ²_trend=7.32, P_trend<0.01). Among 862 children under 14 years old, the antibody positive rate of two doses vaccination 72.8% (182/250) was significantly higher than that of one dose vaccination 51.9% (154/297) (χ²=25.14, P<0.01). There was significant difference between 1-4 years old group (χ²=11.71, P<0.01) and 10-14 years old group (χ²=5.95, P=0.02), but not in 5-9 years old group (χ²=3.00, P=0.07). Compared with the study in 2012, the antibody positive rate increased in 5-9 years old group (χ²=14.35, P<0.01) and decreased in 1-4 years old group (χ²=11.51, P=0.01) in 2017. Conclusion: The recommended varicella booster vaccination has significantly improved the VZV antibody level of children in Beijing city. In the future, it is necessary to explore a more optimized two doses varicella vaccination schedule for children in combination with epidemiological evidence.
Adolescent ; Antibodies, Viral ; Chickenpox/prevention & control* ; Chickenpox Vaccine ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Herpesvirus 3, Human ; Humans ; Infant ; Male ; Vaccination

Objective: To diagnose a large family of patients with hereditary angioedema, and to study its inheritance pattern and gene locus. Methods: A retrospective analysis was carried out from August 2021 to February 2022 in a proband (female, 48 years old) and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery, the Second Hospital of Shanxi Medical University. The clinical data of members and non-affected members [including 7 males and 5 females, aged 12-78 (median 24) years old], were drawn a family map while confirming the diagnosis. Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation. Results: The inheritance pattern of the family was autosomal dominant, and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination, including 7 cases of type I and 1 case of type Ⅱ. Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes, and it was found that they both carried the same pathogenic mutation locus, which was c.890-2A>G. The family members were verified by next-generation sequencing, and it was found that all members of the family who had a history of edema contained this mutation site, while the younger brother of the proband who had no history of edema did not have this mutation. Conclusion: Both type Ⅰ and type Ⅱ phenotypes are present in this hereditary angioedema family, and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.
Angioedemas, Hereditary/genetics* ; Asian People ; Female ; Humans ; Male ; Mutation ; Pedigree ; Retrospective Studies

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

Objective:To investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.

italic>Dendrobium officinale Kimura et Migo is a rare Chinese herbal medicine, while Dendrobium crepidatum Lindl is a local medicine in Yunnan, both of which have the function of nourishing yin and stomach. To reveal the differences in chemical composition between the two species, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze the chemical composition of stems and leaves of D. officinale and D. crepidatum. Principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) were used to determine the differences in metabolites between species and parts of Dendrobium. Fifty-eight chemical compounds were identified in the two species. Analysis indicated that the side ring of alkaloids connected with nitrogen was readily cleaved during analysis. The results of PCA analysis showed that the stems and leaves of D. officinale and D. crepidatum could be easily differentiated, and the chemical constituents of D. officinale and D. crepidatum were significantly different. OPLS-DA analysis showed that there were 16 metabolite differences between the stems and 22 differences in metabolites between the leaves of D. officinale and D. crepidatum. The main metabolite differences in components between the two Dendrobium species were dendrocrepidine B, dendrocrepidine C and dendrocrepine. There were 14 differences in metabolites between the stems and leaves of D. crepidatum. In conclusion, the chemical compositions of D. officinale and D. crepidatum are quite different; the small molecular compounds of D. officinale are mainly terpenoids and flavonoids, and the content of alkaloids is low. There is no significant difference between stem and leaf. In contrast, D. crepidatum is mainly composed of alkaloids and terpenoids, with crepidamine and dendrocrepine as its unique components, and there are great differences in the components between stems and leaves. This study provides a theoretical basis for the development and utilization of Dendrobium resources.