Objective To investigate the correlation between the anatomical structure of patent foramen ovale(PFO)observed by transesophageal echocardiography(TEE)and the right to left shunt(RLS)grade of contrast-enhanced transthoracic echocardiography(c-TTE).Methods Ninety cases in which the presence of PFO was suggested by TEE examination as a diagnostic criterion from November 2021 to December 2022 in the First Hospital of Nanchang were retrospectively analysed.According to the c-TTE results of patients,the RLS was divided into 4 levels,and the correlation between PFO structural characteristics and RLS grading was analyzed.Results There was a positive correlation between PFO diameter size and RLS grading in resting state(r=0.381,P<0.05);The PFO diameter of patients with hypermobile interatrial septum(HIS)was larger and the difference was statistically significant(P<0.05);The PFO diameter of patients with persistent RLS was larger than that of excited phase patients,and the difference was statistically significant(P<0.05);There was no significant difference in RLS shunt degree between patients with long tunnel and those without long tunnel;There was no significant difference in RLS grade and PFO diameter size under Valsalva state.Conclusion Research has shown that certain anatomical structures of PFO interact with RLS grading,and PFO anatomical structures can also interact with each other(the opening diameter of the foramen ovale with HIS is larger);At the same time,TEE can clearly show the morphological characteristics of PFO and predict the degree of RLS,so as to further evaluate the possibility of ischemic stroke in patients with PFO,and provide more evidence for the indications for foramen ovale closure.

Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P＜0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.

Cell therapy refers to an innovative approach, in which autologous or allogeneic stem cells or differentiated somatic cells are reinfused back into the body through venous blood circulation or tissue in situ colonization after in vitro dedifferentiation or induced differentiation, culture amplification and genetic modification to achieve the goal of treating diseases by repairing or reconstructing tissues and organs, or by activating immune responses. Cell therapy leads an important paradigm shift in medical biology and marks the arrival of a new era in the history of pharmacological intervention. Compared with traditional small molecule chemical drugs and biological products, living cells are a complex organic whole involved in the body fine regulatory network and have shown great advantages and potential in clinical treatment for some complex and intractable diseases. Currently, preclinical and clinical researches on multiple innovative therapeutic strategies based on stem and immune cells are being actively optimized and explored, and have achieved many impressive results. This article reviewed the significant articles published in the field of cell therapy in 2022 from the aspects of both basic research and clinical application, summarized recent advances and major breakthroughs in stem cell therapy and immune cell therapy for the treatment of human diseases, and analyzed the challenges, hopefully powering the rapid progress in this field.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC. METHODS: We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25. RESULTS: USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo . CONCLUSIONS In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.
Animals ; Mice ; beta Catenin/genetics* ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; Liver Neoplasms/pathology* ; Ubiquitin Thiolesterase/metabolism* ; Wnt Signaling Pathway/genetics*

Objective:To understand the clinical characteristics of empyema caused by Streptococcus pneumoniae in children. Methods:The clinical manifestations, imaging characteristics, treatment and prognosis of 49 children with pneumococcal empyema admitted to Beijing Children′s Hospital, Capital Medical University from March 2007 to February 2018 were retrospectively analyzed.Results:Among the 49 children, 26 were male and 23 were female, with a median age of 2.63 years old.All the cases had cough and fever, 46 cases of them had high fever, 2 cases had moderate fever and 1 case had ultrahyperpyrexia.The course of disease before admission was 2-90 days, with a median of 10 days.All cases had toxic symptoms and signs of pleural effusion; 26 patients had dyspnea; 23 patients had moist rales, while 8 cases of whom had wheezing sounds.Eleven cases had extrapulmonary complications, including purulent meningitis in 6 cases, purulent pericarditis 1 case, 2 cases of hemophagocytic syndrome and hemolytic uremic syndrome respectively.The medians of leukocytes in the whole blood, white blood cells in pleural effusion and multinuclear cell percentage were 26.97×10 9/L, 32×10 9/L and 0.85, respectively.The average C-reactive protein (CRP) was 177.79 mg/L.The drug sensitivity test of Streptococcus pneumoniae showed that 68.89% strains were insensitive to Penicillin and all strains were resistant against Erythromycin.Chest image showed bilateral consolidation in 32 cases and pneumothorax in 31 cases.Besides antimicrobial therapy, 34 patients were treated with chest drainage, and 7 cases underwent surgery.Ten of the 49 cases were treated with nasal continuous positive airway pressure, tracheal intubated was used in 6 cases, and 1 case was given cardiopulmonary resuscitation.Forty-five cases discharged with improvement, 3 cases were not cured and 1 case died. Conclusions:Pneumococcal empyema is more common in children under 5 years old.Children with pneumococcal empyema usually have poor mental status, high fever, cough accompanied by dyspnea, high peripheral white blood cells and CRP.Their radiographic findings are usually serious, and the insensitive rate to Penicillin is high.The main treatment is anti-infection therapy and closed thoracic drainage.The prognosis of most patients is good, but there are still dead cases.

Objective: To evaluate the efficacy of cognitive-behavioral therapy (CBT) combined with mirtazapine for patients with functional dyspepsia (FD). Methods: Totally 121 patients with FD who met Rome Ⅳ diagnostic criteria in clinic of clinical psychiatry of a general hospital were collected.They were randomly divided into combined treatment group(n=61) and single drug group(n=60). The treatment period was 8 weeks.All patients with FD were given mirtazapine.The combined treatment group received 8 times systemic CBT treatments at the same time.Symptom checklist-90 (SCL-90) and gastrointestinal integral scale (GIS) were evaluated in all patients before and after 8-week intervention. Results: After 8 weeks of intervention, the total score of SCL-90 scale, somatization, compulsion, depression, paranoia and other factors in the combined treatment group were lower than those in the single group(130.26±36.18 vs 147.95±45.55, 1.34±0.44 vs 1.51±0.5, 1.66±0.50 vs 1.90±0.66, 1.47±0.52 vs 1.69±0.63, 1.48±0.49 vs 1.70±0.61, 1.47±0.50 vs 1.73±0.68, respectively)(all P<0.05). After 8 weeks of intervention, the total score of the GIS scale in the combined treatment group (6.77±5.05 vs 9.49±5.24), vomiting (0.57±0.77 vs 0.88±0.91), spastic upper abdominal pain (0.43±0.74 vs 0.90±1.08) and post-sternal discomfort (0.57±0.89 vs 1.05±1.19) were significantly lower than that of the simple drug group after intervention(6.77±5.05 vs 9.49±5.24, 0.57±0.77 vs 0.88 ±0.91, 0.43±0.74 vs 0.90±1.08 and 0.57±0.89 vs 1.05±1.19, respectively), and the differences were statistically significant (all P<0.05). Conclusion CBT combined with mirtazapine in the treatment of FD is superior to drug therapy alone.CBT combined with mirtazapine can improve the emotional problems in the treatment of FD and further improving the digestive function.

The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.
China ; Humans ; Program Evaluation ; Space Flight ; Weightlessness ; Weightlessness Simulation

Objective To explore the folate receptor alpha(FRA)expression in different types and stages of in endometrial carcinoma(EC). The sensitivity and specificity of FRA testing were compared with CA125 to evaluate its diagnostic performance.Methods Serum from 50 cases of EC patients and 30 cases of normal patients was collected.Tissue from 83 cases of typeⅠEC and 30 cases of normal endometrium and typeⅡEC were collected. The expression of serum FRA was detected by ELISA.The expression ofserum CA125 was detected by electrochemi-luminescence.The expression of FRA and CA125 in tissues was detected by immunohistochemistry. Results The rate of elevated FRA expression of in typeⅠEC tissue was higher than that in typeⅡEC(P < 0.05). The rate of elevated FRA expression in type I EC was higher than that in the early stage(P < 0.05). The ROC curve showed that the sensitivity and specificity of FRA was higher than these of CA125′s. Further,they are higher in the com-bined serum FRA and CA125.Conclusions This study shows that the FRA expression level in endometrial carci-noma varies in different subtypes,indicating the potential different pathogeneses. The rate of elevated FRA expression in type I endometrial carcinoma was higher than that in the early stage. This provides the possibility for the application of FRA targeted fluorescent developer in advanced endometrial carcinoma meticulous surgery. Combination of FRA and CA125 have better diagnostic value in detecting EC.

Objective To type Streptococcus pneumoniae(S.pneumoniae) isolated from children, and provide scientific basis for the correct selection of S.pneumoniae vaccine.Methods 182 strains of S.pneumoniae were collected from Children's Hospital of Hebei Province in 2014, species of strains were identified by polymerase chain reaction (PCR), types of strains were analyzed with multiplex PCR.Results PCR detection showed that cpsA gene amplification of 182 strains were all positive;multiplex PCR detection revealed that except 8 strains were not typed, the main types of the remaining 174 strains were 19 F (n=68, 37.36%), 19A(n=33, 18.13%), and 6A/6B (n=26,14.28%), the other types were 35B, 14, 6C/6D, 23F, 15B/15C, and so on.Conclusion The main types of 182 strains of S.pneumoniae are 19 F, 19A, and 6A/6B, which provide scientific basis for the correct selection of S.pneumoniae vaccine for this province.