Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Objective : To explore the role and mechanism of plasmalemma vesicle-associated protein(PLVAP) in the progression of hepatocellular carcinoma(HCC). Methods : Bioinformatic analysis, quantitative real-time PCR, Western blot and immunohistochemistry were used to analyze the expression level of PLVAP in HCC and paracancerous tissues, and its correlation with clinicopathological characteristics. Stable HCC cell lines with knockdown and overexpression of PLVAP were constructed, then cell proliferation, migration and invasion of HCC cells were examined by CCK-8, foci formation assays, wound-healing assays and Transwell assays. Western blot was used to detect the protein levels of phosphatidylinositol 3-kinase PI3K, phosphorylated phosphatidylinositol 3-kinase p-PI3K, protein kinase B AKT and phosphorylated protein kinase B p-AKT in the PI3K/AKT pathway after PLVAP knockdown and overexpression. Cell proliferation, migration and invasion were also examined in PLVAP-overexpressed cells after treatment of LY294002, an inhibitor of the PI3K/AKT pathway. Results : The expression of PLVAP was significantly higher in HCC tissues than that in adjacent non-tumor tissues(P<0.05), and was positive correlated with tumor stage, T stage, M stage, and microvascular invasion(P<0.05). Knockdown of PLVAP significantly reduced the proliferation, migration and invasion of HCC cells(P<0.001), while overexpression of PLVAP significantly increased the proliferation, migration and invasion of HCC cells(P<0.01). Western blot analysis revealed that knockdown of PLVAP decreased the protein expression levels of p-PI3K and p-AKT, overexpression of PLVAP increased the protein expression levels of p-PI3K and p-AKT, whereas the PI3K/AKT inhibitor LY294002 eliminated the effects of PLVAP on cell proliferation, migration and invasion(P<0.01). Conclusion PLVAP is highly expressed in HCC and may promote HCC progression by activating the PI3K/AKT signaling pathway.

Diabetic kidney disease is one of the complications of diabetes,which can progress to end-stage renal disease.In recent years,it has been found that miRNAs have become a research hotspot,with miRNA-21 regulating transforming growth factor β1(TGF-β1)/Smads,phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT),Wnt/β-catenin and other signaling pathways to promote the progress of diabetic kidney disease.Studies have showed that traditional Chinese medicine has a regulatory effect on the expression of miRNA-21 and can target miRNA-21 to regulate TGF-β1/Smads,phosphatase and tensin homolog/PI3K/AKT/mammalian target of rapamycin(mTOR),peroxisome proliferator activated receptors and other signal transduction pathways to trigger signal cascade reactions,which intervene in pathological processes such as fibrosis,inflammation,oxidative stress and autophagy.In this article,the role of miRNA-21 in diabetic kidney disease and the intervention of traditional Chinese medicine were summarized,in order to provide some reference for the treatment of diabetic kidney disease and the development of new drugs.

Objective    To investigate the clinical manifestations of patients with cardiac myxoma and the factors affecting the occurrence of embolic events. Methods     A retrospective study of 38 patients with cardiac myxoma diagnosed and surgically removed from January 2010 to December 2017 was performed. There were 11 males and 27 females at age of 32-75 (50.00±16.12) years. The patients were divided into a non-embolized group and an embolized group. The clinical manifestations of the patients were summarized and the factors leading to embolism were analyzed. Rseults    Of the 26 patients in the non-embolized group, 22 patients (84.62%) had dyspnea, 14 patients (53.85%) had palpitations, 4 patients (15.38%) had angina pectoris, and 1 patient (3.85%) had heart failure. Of the 12 patients in the embolized group, 4 patients (33.33%) had dyspnea, 3 patients (25%) had palpitations, and 1 patient (8.33%) had angina pectoris. The mean diameter of the non-embolized group was 5.71±1.63 cm, and the maximum diameter of the tumor in the embolized group was 4.52±1.88 cm. There was no significant difference between the maximum diameter of the tumor in the embolized group and the maximum diameter of the non-embolized group (P>0.05). Atrial fibrillation occurred in 2 patients in the non-embolized group before operation. Atrial fibrillation occurred in 5 patients in the embolized group. Atrial fibrillation was more likely to occur in the embolized group (P<0.05). Conclusion     Atrial fibrillation in the patients with cardiac myxoma is closely related to embolic events. The size of myxoma is not related to the occurrence of embolic events.

Objective: To investigate the correlation between clinical phenotype, electroencephalogram (EEG) characteristics and genotype in children with Angelman syndrome(AS). Methods: A total of 103 children with AS at Department of Neurology, Children′s Hospital of Fudan University from June 2017 to June 2018, were included in this study.The information of clinical characteristics, EEG manifestations, genotypes as well as the epileptic outcome were collected retrospectively.The correlations between clinical phenotype, genotype, and epileptic outcome were evaluated. Results: (1) Of the 103 cases, 48 were male (46.6%) and 55 were female (53.4%). (2) Genotypes on AS critical region were maternal chromosome 15q11.2-q13 [86.4%(89/103 cases)], paternal uniparental disomy [3.9%(4/103 cases)], imprinting defects [1.9%(2/103 cases)], and mutations in the maternal copy of UBE3A [7.8%(8/103 cases)]. (3) Apparent happy demeanor or smile and general developmental delay were observed in all AS children.Dyskinesia accounted for 98.1% (101/103 cases), followed by oral movement or suck disorders [97.1%(100/103 cases)] and abnormal posture [67.0%(69/103 cases)]. The proportion of acquired small head circumfe-rence or microcephaly, flat occiput or occipital groove and wide-spaced teeth were 61.2%(63/103 cases), 85.4%(88/103 cases) and 44.7%(46/103 cases), respectively.(4) Behavioral problems like fascination with water, sleep problems and feeding difficulties were found in 86.4%(89/103 cases), 89.3%(92/103 cases) and 85.5%(88/103 cases) of the children, respectively.Sleep disorders [94.4%(84/89 cases) vs.57.1%(8/14 cases)] and feeding difficulties [93.3%(83/89 cases) vs.35.7%(5/14 cases)] were more frequently seen in children with maternal absence group, compared those with no absence, and the differences were statistically significant (all P<0.05). (5) Epilepsy was present in 77.7% (80/103 cases) of children with onset age varying from 8 to 72 months and 80.8% (59/73 cases) were developing seizures prior to 3 years old.Children with maternal absence showed more multiple seizure types than those with no absence[41.7%(32/68 cases) vs.0(0 case)], and the difference was statistically significant(P<0.05). Children with well-controlled epilepsy had more atonic seizure, compared with those with poorly controlled seizure [48.3%(14/29 cases) vs.18.5%(4/27 cases)], and the difference was statistically significant(P<0.05). Conclusions Sleep disorders, feeding difficulties in infancy and multiple seizure types are more commonly seen in AS children with maternal absence.Atonic seizure is easier to be controlled over other types of seizures.

This paper summarizes the research situation of the treatment for the periarthritis of shoulder using fire-needle, and summarizes the effective treatment of shoulder periarthritis by using fire-needle method, including the fire-needle with acupuncture or with the cupping therapy, the fire needle combing other methods.Meanwhile. This paper puts forward the problems in the treatment and the clinical study of shoulder arthropoditis.

OBJECTIVETo compare the effect difference for stroke between meridian-collateral diagnosis and therapy byand conventional acupuncture with syndrome differentiation.

METHODSTotally 148 patients were assigned into an observation group(72 cases) and a control group(76 cases) by random number table,with 10 cases dropping out in the observation group. In the observation group,meridians were examined and differentiated and then the treating meridians and acupoints were defined. Corresponding acupuncture was used according to them. In the control group,acupuncture was applied at acupoints by internal differentiation and experience. Treatment was given once a day and five times a week,with total 20 times. The motion function of limbs and coloboma degree of nerve function were assessed by Fugl-Meyer score and National Institutes of Health Stroke Score(NIHSS) before and after treatment as well as at three-month follow-up.

RESULTSAfter treatment,the Fugl-Meyer scores increased and the NIHSS scores decreased in the two groups compared with those before treatment(all<0.05). At follow-up three months after treatment,Fugl-Meyer score upgraded in the observation group (<0.05) and NIHSS score declined in the two groups (both<0.01) than those before treatment,and NIHSS scores were statistically different between the two groups(<0.05).

CONCLUSIONSMeridian-collateral diagnosis and therapy byhas better long-term efficacy when it is compared with conventional acupuncture with syndrome differentiation for motion function of limbs and nerve function of stroke.

This study was to investigate the inhibitory effects of single-chain variable fragment of alpha fetopro-tein (scFv-AFP)in combination with doxorubicin on the proliferation of human hepatocellular carcinoma cell lines Huh7.Huh7 cells were treated with different concentration of scFv-AFP or doxorubcin alone or their combi-nation.The inhibitory effects were detected by MTT assay,and cycle arrest and apoptosis of Huh7 cells were ana-lyzed by flow cytometry in different groups using PI and Annexin V /PI-staining respectively.Results showed that scFv-AFP,doxorubicin alone or in combinations dose-dependently inhibited the proliferation of Huh7,and a syn-ergistic effect was observed in their combined action.The combination treatment resulted in significantly higher apoptosis than those in other groups (P <0.05).scFv-AFP (40 μg/mL)markedly blocked the Huh7 cell pro-gression by arresting the cells in the G0 /G1 phase,and the percentage of cells in S phase decreased dramatically (P <0.05);and scFv-AFP combined with doxorubicin blocked the Huh7 cell progression by arresting the cells in G2 /Mphase (P <0.01).

OBJECTIVEThe aim of this study was to compare the safety and efficacy profiles of R-CHOP and R-fCHOP regimes in the treatment of primary gastric diffuse large B cell lymphoma (PG-DLBCL).

METHODSData of PG-DLBCL patients admitted in our hospital from March 2010 to March 2014 were collected retrospectively. Differences in gastrointestinal bleeding and perforation between the R-CHOP group and R-fCHOP group were compared. The influence of the gastrointestinal complication on subsequent treatment was also analyzed. Treatment outcome of the two groups was also compared.

RESULTSA total of 50 patients were included in this retrospective study. Forty of them were in the R-CHOP group, another ten were in the R-fCHOP group. Patients in the R-fCHOP group had a higher rate of Lugano late stage disease, and a relatively high rate of a deeper/larger ulcer. Fence occult blood test (FOBT) was positive in one (10.0%) patient in the R-fCHOP group, and 11 (31.4%) patients in the R-CHOP group, among them one had hematemesis and had to give up the subsequent chemotherapy. No perforation was observed in both groups. The response rate (RR) was 92.5% in the R-CHOP group and 90.0% in the R-fCHOP group (P > 0.05). The PFS was also comparable between the two groups (P > 0.05).

CONCLUSIONSR-fCHOP regimen has a good safety profile in patients with Lugano late stage and deep/large ulcers, who are of high risk of gastrointestinal bleeding or perforation, and also has a comparable efficacy profile when compared with the R-CHOP regimen in short-term follow-up.

Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; Doxorubicin ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Lymphoma, Non-Hodgkin ; Male ; Middle Aged ; Prednisone ; Retrospective Studies ; Rituximab ; Stomach Neoplasms ; Treatment Outcome ; Vincristine