Tumor immunotherapy occupies a pivotal position in the field of hematological malignancies.Chimeric antigen receptor(CAR)T-cell therapy has established a new therapeutic pattern for hematological immunotherapy and achieved satisfactory clinical results in the treatment of B-lineage hematological malignancies.However,CAR T-cell therapy has some limitations in the treatment of T-cell acute lymphoblastic leukemia because of the presence of CAR T-cell fratricide,tumor cell contamination,T-cell aplasia,and other clinically relevant problems.Therefore,the current major challenge is overcoming the existing bottlenecks to optimize CAR-T therapy and improve its efficacy against T-ALL while improving the prognosis of patients.

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.
Adolescent ; Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; China ; Humans ; Immunogenicity, Vaccine ; Middle Aged ; SARS-CoV-2 ; Vaccination ; Young Adult

Objective:To construct a serine protease inhibitor Kazal type-5 (Spink5) conditional knockout mouse model, and to identify its phenotype.Methods:B cell-specific Spink5 conditional knockout mice of genotype Mb1 cre/+Spink5 floxp/floxp were constructed by using clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR-associated protein 9 (Cas9) technology, and served as the knockout group. Mice of genotype Mb1 +/+Spink5 floxp/floxp served as the control group. The mice of genotype Mb1 cre/+Spink5 floxp/floxp or Mb1 +/+Spink5 floxp/floxp were sacrificed when they were 4 to 6 weeks old, splenic mononuclear cells were isolated, and B lymphocytes and non-B lymphocytes were sorted by flow cytometry and fluorescence-activated cell sorting. Genotype identification was performed by PCR, and protein expression of lymphoepithelial Kazal-type-related inhibitor (LEKTI) was determined by Western blot analysis. Skin tissues were resected from the mice, and subjected to hematoxylin-eosin staining for measuring the epidermal thickness. Immunofluorescence staining was performed to determine fluorescence intensity of LEKTI protein in the mouse skin tissues. Paired t test or two-independent-sample t test was used for comparisons between groups. Results:Genotype identification results demonstrated that the stable B lymphocyte-specific Spink5 conditional knockout mouse model was successfully constructed. Western blot analysis revealed that the relative protein expression of LEKTI in the B lymphocytes in the knockout group was 0.01 ± 0.02, which was significantly lower than that in the non-B lymphocytes in the knockout group (0.66 ± 0.11, t = 9.99, P < 0.001) , and that in the B lymphocytes in the control group (1.08 ± 0.13, t = 13.78, P < 0.001) . Among 39 mice in the knockout group, 4 presented with dry skin and scattered scaly hypertrophic maculopapules. The epidermal thickness of the lesional skin tissues in the knockout group was 90.42 ± 21.31 μm, significantly higher than that of the non-lesional skin tissues in the knockout group (29.71 ± 3.63 μm, t = 5.05, P = 0.002) and that of normal skin tissues in the control group (12.42 ± 2.21 μm, t = 6.74, P < 0.001) . Immunofluorescence staining showed no significant difference in the fluorescence intensity of LEKTI protein among the lesional skin tissues (46.21 ± 1.21) , non-lesional skin tissues (46.62 ± 2.13) in the knockout group and normal skin tissues in the control group (47.69 ± 1.71, P > 0.05) . Conclusion:The B lymphocyte-specific Spink5 conditional knockout mouse model was successfully constructed, which provides a basis for further exploring mechanisms underlying skin barrier defects and immune dysfunction in Netherton syndrome.

Abstract： With the increasing rise in antidepressant consumption, more and more antidepressants and their metabolic products enter into water and soil environments. This will cause toxicity to animals living in these environments, and antidepressants may be transferred to humans via food chain, leading to human health risks. Based on national and international publications pertaining to environmental pollution and toxic effects of antidepressants during the period between 2005 and 2021, this review summarizes the biological accumulation, acute toxicity, reproductive and developmental toxicity, metabolic effects and biological behavior changes of antidepressants, so as to provide insights into the elucidation of the impact of antidepressants on human health risks.

Objective:To investigate the factors associated with the occurrence of coccoid forms in clinical isolates of Helicobacter pylori ( H. pylori) and its relationship with the pathological changes of gastric mucosa. Methods:A total of 66 H. pylori-infected patients admitted to People′s Hospital of Ningxia Hui Autonomous Region from January 2020 to June 2021 were included.The clinical data of the patients were collected. Immunohistochemical staining was performed on gastric mucosal biopsy specimen to observe the occurrence of coccoid forms of H. pylori and pathological changes of gastric mucosa. Chi-square test was used for statistical analysis. Results:After immunohistochemical staining of 66 gastric mucosa biopsy specimens from H. pylori-infected patients, the co-existence of helical and coccoid forms of H. pylori was found in 26(39.39%) specimens, and no simple coccoid H. pylori change was found. Among them, the patients with a history of eradication therapy had a coccoid forms rate of 52.63%(20/38), and those without a history of eradication therapy had a coccoid forms rate of 21.43%(6/28), and the difference was statistically significant ( χ2=6.57, P=0.012). There were no significant differences in the coccoid forms rates between patients with different gender, ethnicity, age and gastric mucosal pathological changes (including atrophy, gastric intestinal metaplasia, inflammation, activity)(all P>0.050). Seventeen (73.9%) of the 23 patients whose endoscopy was more than one to three months from the last eradication therapy developed coccoid forms, while three of 15 patients whose endoscopy was more than three months from the last eradication therapy had coccoid forms, and the difference was statistically significant ( χ2=10.59, P=0.002). Conclusions:The transformation of H. pylori coccoid forms is related to the previous eradication therapy. The coccoid forms of H. pylori is equally pathogenic relative to the helical forms of H. pylori.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective:To investigate the value of the size-specific dose estimate (SSDE) on dose estimations of children's head CT scans.Methods:A retrospective study was conducted on plain head CT scans of 252 patients with the 64-row detector CT device of Discovery 750HD in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to September in 2019. The volume CT dose index (CTDI vol)values were recorded. The head circumference (HC), area, and CT value were measured using a self-developed computer program, and the water equivalent diameter (WED), size-specific conversion factors ( f293 and f220), and absorbed dose (SSDE 293 and SSDE 220) were calculated according to the AAPM reports 293 and 220.The patients were divided into three groups by the quartering meth odaccording to their HC(<47.8 cm, 47.8-52.7 cm, >52.7 cm)and four groups based on their ages(0-2, 3-6, 7-10 and 11-14 years old). The difference between parameters ( f220 and f293, SSDE 220 and SSDE 293、SSDE 293 and CTDI vol) were compared for different groups, and the correlation of HC with f293 and SSDE 293 was analyzed. Results:There was an overestimation of f220 by 11.11% ( t=252.61, P<0.05) compared with f293. SSDE 220 was overestimated by 10.31% ( t=228.21, P<0.05) compared with SSDE 293, and SSDE 293 was underestimated by 9.60% ( t=-31.34, P<0.05)compared with CTDI vol. For the three HC groups, SSDE 220 was overestimated by 8.54%, 10.37%, and 11.57% ( t=73.73, 438.58, 275.52, P<0.05)compared with SSDE 293, and SSDE 293 was underestimated by 1.30%, 9.79%, and 14.61% ( t=-1.91, -60.95, -47.64, P<0.05)compared with CTDI vol. For the four age groups SSDE 220 was overestimated by 8.45%, 10.00%, 10.57%, and 11.36% ( t=63.58, 232.29, 247.84, 302.95, P< 0.05)compared with SSDE 293, and SSDE 293 was underestimated by 1.49%, 8.27%, 10.63%, and 13.78% ( t=-1.83, -28.27, -37.30, -49.80, P< 0.05)compared with CTDI vol. Furthermore, HC was highly correlated with f293 and SSDE 293 ( r2=0.88 and 0.76, respectively, P< 0.05). Conclusions:The radiation dose in children′s head CT scanning can be more accurately estimated according to the AAPM Report 293, while it can be overestimated by CTDI vol. Meanwhile, the CT radiation dose can be patently overestimated with the AAPM Report 220 compared with Report 293.HC is closely correlated with f293 and SSDE 293 and it can be used to estimatee more accurately for SSDE and the radiation dose received by children during head CT scanning.

Objective:To clarify the pathogen types, genotypes and molecular biological characteristics of an outbreak in a high school in Yantai city in 2019, and to provide evidence for epidemic prevention and control.Methods:Eleven samples were collected from a high school in Yantai city in 2019. Quantitative PCR was used for primary type identification. RT-PCR and specific primers were used to amplify the target genes, and the sequences of norovirus were compared and analyzed for phylogenetic analysis.Results:The pathogen of this cluster outbreak was norovirus. Five GII-positive samples of norovirus were detected, 4 of which were GII.13 and 1 was GII.17. Sequence analysis of polymerase-capsid region showed that the amino acid sequence of this cluster outbreak was highly conserved.Conclusions:This outbreak is a cluster of diarrhea caused by GII.13 and GII.17 norovirus infection. The analysis of this outbreak is helpful to our general understanding of the evolution, genetic diversity and distribution of norovirus, and the surveillance of norovirus in the jurisdiction should be further strengthened.

Objective:To explore the predictive value of a radiomics model based on preoperative contrast enhanced MRI in the assessment of the isocitrate dedydrogenase 1 (IDH 1) genotype in high-grade glioma.Methods:A retrospective analysis was performed on a dataset including 182 patients with high-grade glioma confirmed by surgical pathology between December 2012 and January 2018 in the Affiliated Hospital of Qingdao University. There were 79 patients with IDH1-mutant glioma (45 cases with WHO grade Ⅲ, 34 with WHO grade Ⅳ) and 103 with IDH 1 wild-type glioma (33 cases with WHO grade Ⅲ, 70 cases with WHO grade Ⅳ). All patients had complete preoperative brain contrast enhanced MRI.The cases were divided into a training dataset and a validation dataset at a ratio of 7∶3 using stratified random sampling. Radiomic features were initially extracted using A.K (Analysis Kit, GE healthcare) software, and were selected and excluded using Kruskal-Wallis and Spearman analyses. Using R softwear " GLM" function, the Lasso-logistic model was finally conducted to obtain the optimized subset of the feature to build the radiomics model, and the model was then tested with cross-validation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of the model in differentiating IDH1-mutant type and wild-type gliomas.Results:The radiomics model showed good performance in IDH genotype differentiation in both the training dataset (AUC 0.870, 95% CI: 0.754 to 0.855, accuracy rate 79.8%, sensitivity 85.5%, specificity 75.4%, positive predictive value 0.734, negative predictive value 0.867) and the validation dataset (AUC 0.860, 95% CI: 0.690 to 0.913, accuracy rate 78.9%, sensitivity 91.3%, specificity 69.0%, positive predictive value 0.700, negative predictive value 0.909).Conclusion:The radiomics model based on the preoperative enhanced MR can provide a way to predict the IDH1 genotype in high-grade gliomas.

Objective To explore the relationship between atrial fibrillation and hip fractures caused by falls in the elderly.Methods All patients aged 65 years or older who underwent surgical treatment for hip fractures caused by falls in our department from January 2015 to December 2017 were enrolled.The relationships of atrial fibrillation as well as chronic medical history with hip fractures were retrospectively analyzed.The control group was matched 1 to 1 by age,sex,and admission time.Chi-square test and Logistic regression analysis were used to calculate the odds ratio (ORvalue) of fractures in patients with atrial fibrillation.Results There was no significant difference in the history of smoking,drinking,diabetes,coronary heart disease,heart failure,chronic kidney disease,chronic obstructive pulmonary disease(COPD),and Parkinson's disease between the two groups.A total of 37 patients had a history of atrial fibrillation in the fracture group,compared to 18 patients with atrial fibrillation in the control group.The incidence of atrial fibrillation in the fracture group and the control group were 9.6％ and 4.7％,respectively,with crude OR=2.18,95％CI(1.32-4.15),P=0.008 and adjusted OR=2.27,95％CI(1.37-5.20),P=0.02.Compared with the control group,the incidence of stroke (x2 =14.06,P ＜ 0.05),osteoporosis (x2 =200.64,P ＜ 0.01) and cognitive impairment(x2 =8.23,P ＜0.01)increased in the fracture group.When classified by age and sex in the fracture group,the incidence of atrial fibrillation had no significant difference between different gender and age subgroups.Conclusions Atrial fibrillation is an independent risk factor for hip fractures caused by falls in the elderly.There is no significant difference in the incidence of atrial fibrillation in hip fracture patients between the different ages(65-74 years,75-84 years,≥of 85 years)and genders.In addition,stroke,osteoporosis,and cognitive impairment increase the risk of hip fractures caused by falls in elderly patients.