Objective To analyze the trends in the disease burden of pertussis in China from 1990 to 2021, and to provide a basis for the development of effective prevention and control strategies. Methods Using the 2021 Global Burden of Disease Study (GBD) database, the incidence, mortality, and disability-adjusted life years (DALYs), as well as the age-standardized rates of pertussis in China from 1990 to 2021 were analyzed. Descriptive statistical methods were employed to analyze the characteristics of the pertussis disease burden, and the Joinpoint regression model was used to analyze the trends in pertussis disease burden. Results From 1990 to 2021, the incidence, mortality, and DALYs of pertussis in China decreased from 1 503 800 cases, 10 951 deaths, and 954 900 person-years to 65 400 cases, 548 deaths, and 46 500 person-years, representing a decrease of 95.65%, 95.00%, and 95.13%, respectively. The corresponding age-standardized rates also decreased by 93.58%, 92.47%, and 92.53%, respectively. The Joinpoint regression model revealed a significant downward trend in the age-standardized incidence, mortality, and DALYs rates for pertussis (AAPCs were -8.32%, -9.65%, and -9.58%, respectively, P<0.001). The disease burden was slightly higher in females than in males, with the majority of cases occurring in children under 10 years old, particularly in infants under 1 year old, where the burden was the heaviest. As age increased, the disease burden decreased. Conclusion Between 1990 and 2021, the overall disease burden of pertussis in China showed a significant downward trend, with gender and age differences. Special attention should be given on the prevention and control of pertussis in children under 10 years old, especially in infants under 1 year old.

BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.

Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.

Objective To investigate the changes in blood microbiota in patients with high altitude polycythemia(HAPC)and the correlation with the risk of HAPC.Methods A cross-sectional trial was carried out among 41 HAPC patients(HAPC group)and 41 healthy plateau individuals(control group)who took physical examination in the Health Management Department of No.953 Hospital of PLA Army in 2021.High-throughput sequencing technology was used to detect the V3-V4 variable region of the 16S ribosomal RNA(16S rRNA)gene in the blood smaples,and the composition and difference of the blood microbiota were compared and analyzed between the 2 groups.Results All the participants were male and Han people,and there were no significant differences in baseline data such as age,body mass index and plateau migration time between the 2 groups(P＞0.05).The α-diversity of blood microbiota in the HAPC group,including the Simpson index(0.931±0.005 vs 0.907±0.008,P＜0.05),Goods Coverage index(0.998±0.001 vs 0.997±0.001,P＜0.001)and Pielou index(0.597±0.011 vs 0.567±0.009,P＜0.05)were significantly higher than those in the control group.Meanwhile,obvious difference was observed in the β diversity between the 2 groups(P＜0.01).The relative abundance analysis of bacteria showed that Pelomonas(0.046±0.004 vs 0.033±0.003,P＜0.05),Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01),Acidovorax(0.032± 0.003 vs 0.019±0.002,Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01)and Acidovorax(0.032± 0.003 vs 0.019±0.002,P＜0.05)were statistically higher in the HAPC group than the control group.LEfSe analysis showed that the characteristic blood microbiota of the HAPC group were α-Proteobacteria,and those of control group were Trichospiridae.Conclusion Significant changes are found in diversity,relative abundance and characteristic bacteria of the blood microbiota between the HAPC patients and healthy people at the high altitude,which might be closely associated with the occurrence and development of HAPC.

Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.

Purpose To investigate the changes of interhemispheric functional connectivity and functional connectivity between the selected region of interest(ROI)and other brain areas of the whole brain in resting state in early-blind adolescents(EBAs)via the voxel-mirrored homotopic connectivity(VMHC)and seed-based functional connectivity methods.Materials and Methods A total of 23 EBAs in the Guangdong Province Blind School and 21 age-and gender-matched normal-sighted controls were recruited from June to August 2015.Brain resting-state magnetic resonance imaging scans were performed on all participants.The VMHC were calculated and compared between these two groups.And take the most significant brain area of VMHC as the ROI,the functional connectivity between it and all voxels in the whole brain were calculated and compared,respectively.Results Compared with the control groups,the EBAs groups showed decreased VMHC values in the occipital visual cortex with bilateral calcarine as peak point,bilateral cerebellum and right inferior temporal gyrus(FDR corrected,P<0.05).The EBAs group showed a decreased functional connectivity between bilateral calcarine(brain areas with significantly reduced VMHC),set as ROI and the right cuneus and middle cingulum gyrus,while the enhanced functional connectivity between the bilateral calcarine and the right cerebellum-Crus1 when compared with normal-sighted controls(false discovery rate,FDR corrected,P<0.05).Conclusion The visual cortex interhemispheres mainly in the primary visual cortex of EBAs and its functional connections with multiple brain regions are abnormal,which may indicate abnormal coordination between the primary visual center and other perceptual cortex,and may be related to the brain structure and function remodeling caused by visual loss.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To assess the differences in multidimensional clinical manifestations between patients with irritable bowel syndrome (IBS) matching the Rome Ⅲ criteria but not matching Rome Ⅳ and IBS patients matching the Rome Ⅳ criteria, among patients diagnosed with IBS according to Rome Ⅲ criteria.Methods:From November 2016 to October 2017, a total of 472 IBS patients admitted to six hospitals were selected, which included Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (139 cases), Sir Run Run Shaw Hospital, School of Medicine of Zhejiang University (95 cases), the First Affiliated Hospital of Dalian Medical University (96 cases), the Affiliated Hospital of Guizhou Medical University (90 cases), the People′s Hospital of Guangxi Zhuang Autonomous Region (20 cases), and the Second Affiliated Hospital of Xi′an Jiaotong University (32 cases). The 472 IBS patients were divided into the group that matching the Rome Ⅳ criteria (Rome Ⅳ group), and the group that matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria (Rome Ⅲ group). The basic characteristics (IBS course, post-infectious IBS, history of smoking or drinking, etc.), abdominal symptoms, and defecation-related symptoms of two groups were compared and analyzed by face-to-face questionnaires. Multi-dimensional clinical manifestations assessment was completed by questionnaires, which included gastrointestinal symptom rating scale (GSRS), irritable bowel syndrome-severity scoring system (IBS-SSS), irritable bowel syndrome-quality of life (IBS-QOL), and hospital anxiety and depression scale (HADS). Independent sample t-test, rank sum test, and chi-square test were used for statistical analysis. Results:There were 344 patients (72.9%) in Rome Ⅳ group and 128 patients (27.1%) in Rome Ⅲ group. The IBS course of patients in Rome Ⅳ group was longer than that in Rome Ⅲ group (3.0 years (7.0 years) vs. 2.0 years (5.7 years)), and the difference was statistically significant ( Z=-2.73, P=0.006). The GSRS scores of loose stools and abdominal pain of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group, and the GSRS scores of increased exhaust and abdominal distension of IBS patients in Rome Ⅳ group were lower than those in Rome Ⅲ group (3.0(2.0) vs. 2.0(4.0), 3.0(2.0) vs.1.0(2.0), 1.5(3.0) vs. 2.0(3.0), 1.0 (3.0) vs. 2.0(3.0)), and the differences were statistically significant ( Z=-2.48, -9.90, -2.11 and -2.06, P=0.013, <0.001, =0.035 and =0.040). The proportions of fatigue and dizziness of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (58.4% (201/344) vs. 43.0% (55/128), 30.8% (106/344) vs. 29.7% (38/128)), and the differences were statistically significant ( χ2=8.37 and 12.36, P=0.004 and <0.001). The scores of anxiety and depression subscales of the HADS of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (6.5 (6.8) vs. 6.0 (6.0), 5.0 (6.0) vs. 3.0 (5.0)), and the differences were statistically significant ( Z=-2.58 and -2.40, P=0.010 and 0.017). The scores of IBS-SSS scale, abdominal pain severity, abdominal pain frequency, and impact on quality of life of IBS patients in Rome Ⅳ group were all higher than those in Rome Ⅲ group (249.5 (108.0) vs. 177.0 (111.8), 50.0 (25.0) vs. 20.0 (30.0), 50.0 (70.0) vs. 10.0 (30.0), 66.0 (42.0) vs. 42.5 (34.0)), and the differences were statistically significant ( Z=-7.79, -9.64, -10.65 and -2.48, P<0.001, <0.001, <0.001 and =0.013). The score of IBS-QOL for behavioral disorder of IBS patients in Rome Ⅳ group was lower than that in Rome Ⅲ group (74.5±21.6 vs. 79.2±17.7), and the difference was statistically significant ( t=-2.22, P=0.027). Conclusion:The clinical symptoms of patients mathching the Rome Ⅳ criteria are more typical and severe, as compared with those of IBS patients matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria.

High Altitude Military Hygiene is the professional core course of high-altitude medicine, which is significant to the cultivation of military medical talents urgently needed by plateau troops. Under the background of "golden course" construction and army curriculum reform, aiming at the problems such as outdated content of course materials, single teaching mode and insufficient capacity of practical courses, we actively explored the effective path of "golden course" construction, including the renovation of the curriculum-construction concept, the optimization and reorganization of the teaching content, the expansion of case teaching and equipment teaching methods, and the implementation of curriculum ideological and political education and examination reforms. The reform has further improved the learning effect of students and the level of curriculum construction, and also provided beneficial reference for the construction of similar courses in military colleges and universities.

Objective To explore the predictive value of artificial intelligence(AI)quantitative model for pathological subtypes of stage Ⅰ invasive lung adenocarcinoma with ground glass nodule(GGN).Methods A total of 118 cases(124 lesions)of GGN patients with stage Ⅰ invasive lung adenocarcinoma confirmed by surgery and pathology were analyzed retrospectively,and they were divided into lepidic predominant adenocarcinoma(LPA)group(46 lesions)and non-lepidic predominant adenocarcinoma(n-LPA)group(78 lesions)according to the pathological subtype results.Some relevant AI quantitative parameters were recorded,including the longest diameter,total volume,the percentage of solid volume,total mass,the percentage of solid mass,maximum CT value,minimum CT value,and average CT value.The independent predictors of n-LPA were screened by univariate and multivariate logistic regression analysis,the independent risk factors were quantified by Nomogram,and the diagnostic efficiency of the model was evaluated by using receiver operating characteristic(ROC)curve.Results Binomial logistic regression analysis showed that the percentage of solid mass[odds ratio(OR)=1.965,95％confidence interval(CI)1.515-2.549]and average CT value(OR=1.020,95％CI 1.004-1.036)were independent predictors of n-LPA(P＜0.05).The Nomogram to quantify the independent risk factors showed that the above prediction model was in good agreement with the actual results,and the C-index value was 0.872(95％CI 0.791-0.953).ROC curve analysis showed that the diagnostic performance of the combination of the above two indexes[area under the curve(AUC)=0.829]was better than that of the solid mass percentage(AUC=0.788)and the average CT value(AUC=0.765)of the single indexes,and the corresponding sensitivity and specificity were 87.2％and 84.8％,respectively,which were consistent with the pathological results(Kappa=0.667).Conclusion The percentage of solid mass and the average CT value in the AI quantitative model can effectively help predict the pathological subtypes of GGN stage Ⅰ invasive lung adenocarcinoma,and the combination of the above two indicators can improve the differential diagnosis efficiency of CT between LPA and n-LPA.