Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Objective:To explore the current status of readiness for young and middle-aged maintenance hemodialysis (MHD) patients to return to work and analyze its influencing factors, with the aim of providing reference for the evaluation and intervention of patients returning to work.Methods:From October to December 2022, convenience sampling was used to select 425 patients from six hospitals in the urban area of Yangzhou as the subject. A cross-sectional survey was conducted using the General Information Questionnaire, Readiness for Return-To-Work Scale (RRTWS), Distress Disclosure Index (DDI) and Perceived Social Support Scale (PSSS). Binary Logistic regression was used to analyze the influencing factors of returning to work.Results:Among 425 young and middle-aged patients undergoing MHD, 105 (24.7%) returned to work, of which 79 (75.2%) were in the uncertain maintenance stage and 26 (24.8%) were in the active maintenance stage. 320 did not return to work, including 148 (46.3%) in the pre-intention stage, 86 (26.9%) in the intention stage, 42 (13.1%) in the action preparation self-evaluation stage, and 44 (13.8%) in the action preparation behavior stage. Age, per capita monthly income of the family, number of comorbidities, level of self-disclosure, and level of perceived social support were factors that affected patients' readiness to return to work.Conclusions:The rate of young and middle-aged MHD patients returning to work needs to be improved. The return of patients to work is influenced by multiple factors. Medical and nursing staff should focus on patients who are old, have low per capita monthly income of the family, and have a large number of comorbidities. Targeted interventions and guidance should be provided to patients, such as self-disclosure training and improving their perceived social support, in order to increase the rate of patients returning to work rate.

Objective:To investigate the effects and significance of acute and chronic trauma on brain degree centrality (DC) in patients with post-traumatic stress disorder (PTSD) who lost their only child at resting state.Methods:Retrospectively, the study enrolled a total of 51 parents with PTSD, including 35 PTSD parents whose children was lost in emergencies (acute bereaved PTSD group) and 16 PTSD parents whose children was lost of chronic causes such as diseases (chronic bereaved PTSD group). Fifty local adults were also included as healthy controls (HC group). The clinical administered PTSD scale(CAPS) was used to evaluate the severity of the subjects' clinical symptoms.Resting-state functional magnetic resonance imaging(fMRI) data of all subjects were collected and DC values were calculated.SPSS 22.0 software was used for statistical analysis.Covariance analysis was performed among three groups, while post hoc was performed between any two groups.What's more, correlation analyses were utilized between abnormal brain regions and the scores of CAPS.Results:Significant group effects were found in multiple regions, including the right inferior temporal gyrus (MNI: x, y, z=66, -27, -21), right temporal pole (MNI: x, y, z=54, 15, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15), bilateral medial superior frontal gyri (MNI: right x, y, z=6, 63, 12; left x, y, z=-3, 60, 18), left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with HC group, the DC of two patient groups increased in the right inferior temporal gyrus (MNI: acute x, y, z=63, -27, -21; chronic x, y, z=63, -21, -27); the DC of acute bereaved PTSD group decreased in the right temporal pole (MNI: x, y, z=45, 21, -15) and the right orbital inferior frontal gyrus (MNI: x, y, z=48, 24, -12), while the DC of chronic bereaved PTSD group decreased in the left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with chronic bereaved PTSD group, the DC of acute bereaved PTSD group increased in the left inferior parietal angular gyrus (MNI: x, y, z=-33, -39, 42) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51), while decreased in the right temporal pole (MNI: x, y, z=51, 12, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15) and bilateral medial superior frontal gyri (MNI: left x, y, z=0, 57, 15; right x, y, z=3, 57, 15). In chronic bereaved PTSD group, the DC of the left postcentral gyrus was negatively correlated with C1 (avoid trauma-related thoughts, feelings) score in CAPS ( r=-0.606, P=0.028). In acute bereaved PTSD group, the DC of the left medial superior frontal gyrus was negatively correlated with D4 (high vigilance) score ( r=-0.416, P=0.020). Conclusion:There exist functional abnormalities of multiple brain regions in acute and chronic bereaved parents with PTSD.The high arousal symptoms of the former may be related with the abnormalities of prefrontal-amygdala neural circuit, while the latter show higher avoidance which may be associated with the dysfunction of somatosensory brain regions such as postcentral gyrus.

Objective:To investigate the effect of coping style on the gray matter volume in patients with post-traumatic stress disorder (PTSD) who lost their only child, and the mediating role of gray matter volume in evaluating the influence of coping style in clinical symptoms of these parents.Methods:A total of 57 parents with PTSD (PTSD group) and 162 parents without PTSD (non-PTSD group) who lost their only child from September 2016 to March 2017 were enrolled from Jiangsu Province, China. Brain MRI data at resting state were collected. Voxel-based multiple regression analysis was performed to confirm the brain areas in which coping style main effect, diagnosis main effect and their interaction had significant influences in gray matter volumes. Correlations among gray matter volume of brain areas related to coping style, coping style scale scores, and clinician-administered PTSD scale (CAPS) scores were analyzed. Structural equation modeling was used to analyze the mediating role of gray matter volume in the influence of coping style in clinical symptoms of parents lost their only child.Results:(1) The coping style main effect did not significantly influence the gray matter volume in all subjects, and the diagnosis main effect had significant influence in gray matter volume in the right lingual gyrus; their interaction had significant influence in gray matter volume in the right peritalar fissure cortex and lingual gyrus. The positive coping style in the PTSD group had significant influence in the gray matter volumes of the right peritalar fissure cortex and lingual gyrus. (2) In the PTSD group, the scores of positive coping style were positively correlated with the gray matter volumes of the right talus fissure and the lingual gyrus ( P<0.05); the scores of positive coping style, and the gray matter volumes of the right talus fissure and the lingual gyrus were negatively correlated with scores of CAPS-C 5 and CAPS-C ( P<0.05). (3) In the PTSD group, positive coping style can positively predict the gray matter volumes of the right talus fissure and the lingual gyrus; the gray matter volumes of the right talus fissure and the lingual gyrus can negatively predict the avoidance-related symptoms. Conclusion:Positive coping style has influence in the gray matter volumes of the right talar fissure and lingual gyrus of PTSD patients lost their only child; and less positive coping style may affect the brain areas related to visual information processing, thus aggravating avoidance-related symptoms of PTSD patients.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

Objective To investigate the clinical efficacy of levothyroxine replacement therapy in children with hypothyroidism.Methods 45 children with hypothyroidism admitted from Apr.2015 to Dec.2016 were selected as observation group,and 45 healthy children in the same period were selected as the control group.Children in the control group received regular diet and were paid attention to nutritional balance.Children in the observation group were given levothyroxine sodium on the basis of dietary guidance.The two groups were treated continuously for 6 months.The levels of thyroid function,insulin-like growth factor,indicators for growth and development and inflammatory factors were measured before and after treatment in both groups.Results After treatment for 3 months and 6 months,the levels of FT3,FT4,IGF-1,IGFBP-3 and IGF-1/IGFBP-3 in the observation group increased significantly compared with those before treatment,and the levels of TSH in the observation group decreased significantly(P＜0.05).The levels of FT3,lFT4,TSH,IGF-1,IGFBP-3 and IGF-1/IGFBP-3 in the observation group after treatment for 6 months were (7.17±0.06)pmol/L,(2.74±0.07)mU/L,(207.67±9.06)μg/L,(0.46±0.02) mg/L and(34.59±1.97).The difference was not statistically significant (P＞0.05).After 3 months and 6 months of treatment,the height,body weight,osteocalcin and 25-(OH)2D3 levels in the observation group were significantly higher than those in the control group (P＜0.05),and there was no significant difference between the two groups after 6 months (P＞0.05).The difference was statistically significant (P＜0.05).Conclusion Left thyroid hormone replacement therapy can significantly improve the thyroid function of children with hypothyroidism,increase the level of thyroid-associated hormone and insulin-like growth factor,promote the growth and development of children,which is worthy of clinical application.

Objective To explore the successful breastfeeding experience of primiparous women with natural childbirth during the first 6 months postpartum. Methods A phenomenological methodology was used. Semi-structured in depth interviews were conducted among 11 primiparous women of natural childbirth. The data were transcribed, collated, summarized and analyzed using Colaizzi′s method. Results The primiparous women who sustained exclusive breastfeeding for six months after natural delivery experienced three stages which were:anxiety of breastfeeding,gradual adaption of breastfeeding, and coexistence of puzzles and insistence. The first stage was anxiety of breastfeeding including three themes: lack of experience in breastfeeding, conflict of breastfeeding, and noticeable fatigue during feeding.The second stage was gradual adaption of breastfeeding including four themes:family and social support, presenting regular feeding schedules, identification of mother role, and establishing a good mother-child relationship.The last stage was coexistence of puzzles and insistence which containing three themes: coexistence of confusion and perseverance, fear of returning back to work, suffering of maternal separation,and commitment of breastfeed. Conclusions In order to release the anxiety and improve the confidence of breastfeeding of primiparous women, it is vital to rely on the conjoint efforts of the family members,healthcare institutions,communities,enterprises,society and other aspects to improve the rate and duration of exclusive breastfeeding.

Objective To explore the application effect of health-care failure mode and effect analysis (HFMEA) in infection control among hemodialysis patients.Methods In October 2014,Northern Jiangsu People′s Hospital hemodialysis unit established a management group for HFMEA. We assessed the susceptible failure of hemodialysis patients and analyzed the causes to propose corrective measures. We compared the control group and the intervention group in following aspects:the occurrence of infection (vascular access infection, respiratory infection,urinary system infection and other infections),risk priority number (RPN) of HFMEA and patient′s satisfaction.Results The incidence rate of infection in hemodialysis patients was significantly decreased after the application of HFMEA mode. RPN value of failure mode easy to cause infection dropped to 605 points′s from 1470 points,and the total scores reduced by 58.8%;the patient′s satisfaction increased from (81.31±6.74) to (91.70±5.02)(t=23.935,P<0.05).Conclusions By using HFMEA mode,the failure can be forecasted in hemodialysis procedure and the potential danger can be quantized through RPN. In addition, the projects that need to be focusd on can be identified. So as to effectively reduce the incidence of infection in hemodialysis patients and improve patient′s satisfaction.

Objective To compare the diagnostic efficiency of the thyroid imaging reporting and data system (TIRADS), the Bethesda system for reporting thyroid cytopathology(BSRTC) and BRAFV600E detection, and their combined use in the differentiation between benign and malignant thyroid nodules. Methods One hundred and twenty eight patients with 128 thyroid nodules who were scheduled for ultrasound-guided fine-needle aspiration biopsy (FNAB) were recruited for the study. All of them underwent ultrasound, fine-needle aspiration cytology(FNAC) examination, and BRAFV600E detection. TIRADS and BSRTC systems were adopted to judge the ultrasound and FNAC results. The receiver operating characteristic curve was established to assess the diagnostic value of each method. Results The sensitivity, specificity, and AUC of TIRADS were 74. 3%, 84. 5%, and 0. 794, respectively. BSRTC had higher specificity(98. 3%) and equal sensitivity compared to TIRADS. The sensitivity, specificity, and AUC of BRAFV600E detection were the highest ones among the three methods. Combinations of different methods could increase the diagnostic sensitivity and accuracy. The combination of FNAC and BRAFV600E detection significantly increased the diagnostic efficiency(AUC=0. 984), with sensitivity 98. 6% and specificity 98. 3%. Conclusions The diagnostic value of BRAFV600E detection in the differentiation of benign and malignant thyroid nodules is better than both TIRADS and BSRTC, and the combination of FNAC and BRAFV600E detection reaches the best diagnostic efficiency.