Quantification of left atrial strain in patients with idiopathic inflammatory myopathy using cardiovascular magnetic resonance feature tracking.

BACKGROUND: Left atrial (LA) dysfunction is involved in idiopathic inflammatory myopathy (IIM). Multiparametric cardiovascular magnetic resonance (CMR) strain imaging is a feasible and reproducible tool for examining global and regional LA functions, as well as left ventricular (LV) function in IIM patients. AIM: The aim of this study was to evaluate the feasibility and reproducibility of LA strain occurrence and strain rate for LA function assessment using CMR in IIM cases. MATERIALS AND METHODS: A total of 36 IIM and 42 healthy control cases were included. Baseline ventricular function was comparatively assessed in both groups. LA strain occurrence and strain rate were examined by cine cardiac magnetic resonance imaging [MRI] utilizing an in-house semiautomated technique. LA global function indexes were quantitated, including reservoir, conduit, and booster-pump functions. RESULTS: A total of 78 participants were enrolled in this study. There was no significant difference in left/right ventricular routine functions between IIM patients and control individuals (p>0.05); the same results (p>0.05) was also observed between patients with high hs-cTnI and normal. However, LV mass index had significant difference (p1=0.003, p2<0.01). Compared with IIM patients and control individuals, only total strain (εs) (p4=0.046) and passive strain (εe) (p4=0.002) showed significant difference, and in cases with high hs-cTnI and normal hs-cTnI, there are differences for εs (p3=0.012) and εe (p4=0.047). The strongest association was found between εe and LV ejection fraction (LVEF) (r=0.581, p<0.01). CONCLUSION: IIM cases have altered LA reservoir and conduit functions, and LA strain could reflect LA function.

[Effect of SHP-1 knockout in airway epithelial cells on emphysema phenotype in chronic obstructive pulmonary disease in mice].

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER+/+), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1flox/floxCC10-CreER+/-, SHP-1Δ/Δ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

Seedlings of Poncirus trifoliata exhibit tissue-specific detoxification in response to NH4 + toxicity.

Ammonium nitrogen (NH4 +-N) is essential for fruit tree growth, but the impact of excess NH4 +-N from fertilizer on evergreen citrus trees is unclear. In a climate chamber, 8-month-old citrus plants were exposed to five different hydroponic NH4 +-N concentrations (0, 5, 10, 15 and 20 mm) for 1 month to study effects of NH4 +-N on growth characteristics, N uptake, metabolism, antioxidant enzymes and osmotic regulatory substances. Application of 10 mm NH4 +-N adversely affected root plasma membrane integrity, root physiological functions, and plant biomass. MDA, CAT, POD, APX and SOD content were significantly correlated with leaf N metabolic enzyme activity (GOGAT, GDH, GS and NR). GDH was the primary enzyme involved in NH4 +-N assimilation in leaves, while the primary pathway involved in roots was GS-GOGAT. Under comparatively high NH4 + addition, roots were the main organs involved in NH4 + utilization in citrus seedlings. Our results demonstrated that variations in NH4 + concentration and enzyme activity in various organs are associated with more effective N metabolism in roots than in leaves to prevent NH4 + toxicity in evergreen woody citrus plants. These results provide insight into the N forms used by citrus plants that are important for N fertilizer management.

[Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

[Current status of local treatment for multifocal / multicentric breast cancer].

The detection rate of multifocal / multicentric breast cancer (MMBC) is increasing, and the local treatment of MMBC is attracting more attention. Relevant research focuses on the selection of surgical methods, the application of radiotherapy, and the feasibility of local ablation. Currently, due to the high rate of local recurrence in breast conserving surgery, most Chinese doctors recommend mastectomy to patients with MMBC. Recent studies have shown that with the development of imaging technology, surgical techniques, accurate judgment of the resection margin, the emergence of new therapeutic drugs and the improvement of the accuracy of radiotherapy, for eligible patients with MMBC, breast conserving surgery did not increase the local recurrence rate while ensuring negative margin and cosmetic results. Whether patients with MMBC must receive adjuvant radiotherapy after mastectomy is controversial, with some evidence suggesting that MMBC may increase the risk of local recurrence and should be an important consideration for radiotherapy, and there is also evidence that the local recurrence rate of MMBC was higher regardless of the type of surgery. In general, the local treatment modality for MMBC is essentially the same as that for unifocal breast cancer, but more prospective studies are needed for further evaluation.

Expression of water-soluble nucleocapsid protein of SARS-CoV-2 and analysis of its immunogenicity.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major public health concern. Nucleocapsid (N) protein is the most abundant structural protein on SARS-CoV-2 virions and induces the production of antibodies at the early stage of infection. Large-scale preparation of N protein is essential for the development of immunoassays to detect antibodies to SARS-CoV-2 and the control of virus transmission. In this study, expression of water-soluble N protein was achieved through inducing protein expression at 25°C with 0.5 mM IPTG for 12 h. Western blot and ELISA showed that recombinant N protein could be recognized by sera collected from subjects immunized with Sinovac inactivated SARS-CoV-2 vaccine. Four monoclonal antibodies namely 2B1B1, 4D3A3, 5G1F8, and 7C6F5 were produced using hybridoma technology. Titers of all four monoclonal antibodies in ELISA reached more than 1.28×10 6.0. Moreover, all monoclonal antibodies could react specifically with N protein expressed by transfection of pcDNA3.1-N into BHK-21 cells in IPMA and IFA. These results indicated that water-soluble N protein retained high immunogenicity and possessed the same epitopes as that of native N protein on virions. In addition, the preparation of water-soluble N protein and its monoclonal antibodies laid the basis for the development of immunoassays for COVID-19 detection.

Detection and isolation of infectious SARS-CoV-2 omicron subvariants collected from residential settings.

Airborne transmission of infectious (viable) SARS-CoV-2 is increasingly accepted as the primary manner by which the virus is spread from person to person. Risk of exposure to airborne virus is higher in enclosed and poorly ventilated spaces. We present a study focused on air sampling within residences occupied by individuals with COVID-19. Air samplers (BioSpot-VIVAS, VIVAS, and BC-251) were positioned in primary- and secondary-occupancy regions in seven homes. Swab samples were collected from high-touch surfaces. Isolation of SARS-CoV-2 was attempted for samples with virus detectable by RT-qPCR. Viable virus was quantified by plaque assay, and complete virus genome sequences were obtained for selected samples from each sampling day. SARS-CoV-2 was detected in 24 of 125 samples (19.2%) by RT-qPCR and isolated from 14 (11.2%) in cell cultures. It was detected in 80.9% (17/21) and cultured from 61.9% (13/21) of air samples collected using water condensation samplers, compared to swab samples which had a RT-qPCR detection rate of 10.5% (4/38) and virus isolation rate of 2.63% (1/38). No statistically significant differences existed in the likelihood of virus detection by RT-qPCR or amount of infectious virus in the air between areas of primary and secondary occupancy within residences. Our work provides information about the presence of SARS-CoV-2 in the air within homes of individuals with COVID-19. Information herein can help individuals make informed decisions about personal exposure risks when sharing indoor spaces with infected individuals isolating at home and further inform health departments and the public about SARS-CoV-2 exposure risks within residences.

Specific role of NAD+ biosynthesis reduction mediated mitochondrial dysfunction in vascular endothelial injury induced by chronic intermittent hypoxia.

OBJECTIVE: Cardiovascular diseases (CVD) are prevalent among those with obstructive sleep apnea (OSA) and are the leading cause of death in these individuals. However, due to clinical confounders, the mechanism by which OSA induces CVD is still unclear. Previous studies have shown that chronic intermittent hypoxia (CIH) and high cholesterol diet (HCD) induce distinct characteristics of atherosclerotic plaques, highlighting the specific mechanisms involved in CIH-induced vascular endothelial injury. MATERIALS AND METHODS: This study aims to investigate whether nicotinamide adenine dinucleotide (NAD+) biosynthesis reduction-mediated mitochondrial dysfunction is responsible for vascular endothelial injury induced by CIH and to elucidate its specific role in this process. Models were established to stimulate human umbilical vein endothelial cells (HUVECs) with CIH and oxidized low-density lipoprotein (ox-LDL), and the NAD+ biosynthesis-related indicators, such as NAD+ levels and nicotinamide phosphoribosyltransferase (NAMPT) enzyme activity, were measured in this model. Additionally, interventions were performed by supplementing NAD+ levels with nicotinamide mononucleotide (NMN), inhibiting NAD+ synthesis with FK866, and evaluating mitochondrial function, oxidative stress status, vascular constriction and dilation function, and endothelial adhesion function in these models. A comparative study was conducted to assess the effects of these interventions. RESULTS: We found that under CIH conditions, NAMPT enzyme activity was inhibited, leading to a reduction in NAD+ biosynthesis and a decrease in NAD+/NADH ratio. At the same time, CIH caused mitochondrial dysfunction in HUVECs, including a decrease in adenosine triphosphate (ATP) content and mitochondrial membrane potential, as well as the activity of respiratory chain complex I and III, induced an increase in oxidative stress levels in endothelial cells, impaired vascular constriction and dilation function, and significantly increased expression of adhesion factors. The impact of CIH on endothelial cell-related mitochondrial function and endothelial function was restored by supplementing NMN. Although ox-LDL also causes multi-level endothelial injury, it does not involve the NAD+ pathway, as there were no significant changes in the related indicators, and the impaired endothelial function under ox-LDL conditions was not restored by supplementing NMN. CONCLUSIONS: CIH-induced vascular endothelial injury may be associated with NAD+ biosynthesis reduction-mediated mitochondrial dysfunction. Supplementing NAD+ precursors to increase its levels may be a potential intervention to ameliorate CIH-induced vascular endothelial injury, while it does not have a significant effect on endothelial injury caused by ox-LDL.

[Evaluation of the efficacy of TIPS in 27 patients with hepatic sinus obstruction syndrome in the near and medium term].

Objective: intrahepatic portocaval shunt (TIPS) in the treatment of hepatic sinusoidal obstruction syndrome (HSOS). Methods: A retrospective analysis was performed on 27 patients with HSOS who were treated with TIPS in our center from July 2018 to July 2020. The changes of portal vein pressure (PVP), portal vein pressure gradient (PPG) and liver function were observed, so as to evaluate the efficacy. Paired t test was adopted to evaluate the quantitative parameters, while χ (2) test was used to analyze qualitative parameters, with P < 0.05 as statistical difference. Results: PVP decreased from (4.41 ± 0.18) kPa before shunt to (2.69 ± 0.11) kPa after shunt (t = 82.41, P < 0.001), PPG decreased from (3.23 ± 0.18) kPa before shunt to (1.46 ± 0.23) kPa after shunt (t = 32.41, P < 0.001). The liver function improved significantly after operation. After 24 months of follow-up, 3 patients developed stent restenosis and recanalized after balloon dilation. Three patients developed hepatic encephalopathy, which was improved after drug treatment. One patient underwent liver transplantation due to liver failure. Conclusion: TIPS is effective in the treatment of HSOS in the short and medium term, and can provide time for liver transplantation patients to wait for liver source.

[Screening and validation of pivotal genes in hepatitis B virus-associated hepatocellular carcinoma].

Objective: To screen the pivotal genes involved in the occurrence and development of HBV-associated HCC. Additionally, perform validation and biological function analysis to evaluate changes in the expression of pivotal genes and their prognostic value in patients with hepatocellular carcinoma. Methods: The GSE121248 gene expression profile data of HBV-HCC patients were searched and downloaded from the GEO database. The R language was used to compare the differences in gene expression between hepatocellular carcinoma and paracancerous tissues. KEGG and GO function enrichment analyses were performed on the differential genes. PPI plots and pivotal gene screening were carried out through online tools like STRING and Cytoscape software. 369 cases of hepatocellular carcinoma and 160 healthy controls in TCGA and GTEx were used as validation cohorts to verify the expression levels of the pivotal genes. A Kaplan-Meier plot was drawn to evaluate the prognostic value of the pivotal gene. Results: A total of 120 differentially expressed genes were screened, of which 89 were up-regulated and 31 were down-regulated. Differential genes were mainly enriched in the metabolic pathways related to retinol metabolism, cytochrome P450 metabolism, and the p53 signaling pathway. The top 10 differential genes were selected as pivotal genes by the Cytoscape plug-in cytoHubba. There were significant differences in the expression levels of four types of CCNB1, CDK1, RRM2, and TOP2A genes in the validation cohort. All four types of genes were up-regulated. Survival analysis showed that patients with elevated expression levels of four genes had a poorer prognosis, with statistical differences in results. Conclusion: Four types of genes, CCNB1, CDK1, RRM2, and TOP2A, have high expression levels in patients with HBV-HCC and are correlated to shorter survival times, making them a potential target for diagnosis, prognosis, and treatment.

[Application of novel non-endoscopic device in the screening and early diagnosis of esophageal cancer].

Esophageal cancer (EC) is a dreadful disease with a poor prognosis and poses heavy health burden worldwide. Developing effective methods to identify high-risk individuals is urgently needed for preliminary screening before endoscopy. The novel non-endoscopic device has the potential advantages of low cost, simple operation, and minimal invasiveness. Approximately 90% of participants can swallow the device successfully with high safety profiles, and sufficient esophageal exfoliated cells can be collected for cytological examination and biomarker detection. Cytological examination based on the device combined with trefoil factor 3 (TFF3) protein or DNA methylation examinations could effectively screen Barrett's esophagus-associated dysplasia and early esophageal adenocarcinoma, but large prospective studies are needed to further validate the diagnostic value of this device to improve the quality of evidence. Although the device-based cytological examination in combination with biomarker detection holds promise in the early screening of esophageal squamous dysplasia and early esophageal squamous cell carcinoma, related research is still in its infancy, and there is still a lack of sufficient evidence for population screening in China. Active research into the application of this novel non-endoscopic device in EC screening and early diagnosis is of great significance for optimizing EC screening strategies and improving the early diagnosis of EC.

[Expert consensus on the biobank development of oral genetic diseases and rare diseases and storage codes of related biological samples from craniofacial and oral region].

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies].

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Fibulin-1 Regulates Initiation of Successional Dental Lamina.

In humans, teeth are replaced only once, and the successional dental lamina (SDL) of the permanent tooth is maintained in a quiescent state until adolescence. Recently, we showed that biomechanical stress generated by the rapid growth of the deciduous tooth inhibits SDL development via integrin ß1-RUNX2 signaling at embryonic day 60 (E60) in miniature pigs. However, the mechanism by which RUNX2 regulates SDL initiation within the SDL stem cell niche remains unclear. In the current study, we transcriptionally profiled single cells from SDL and surrounding mesenchyme at E60 and identified the landscape of cellular heterogeneity. We then identified a specific fibroblast subtype in the dental follicle mesenchyme between the deciduous tooth and the SDL of the permanent tooth (DFDP), which constitutes the inner part of the niche (deciduous tooth side). Compared with traditional dental follicle cells, the specific expression profile of DFDP was identified and found to be related to biomechanical stress. Subsequently, we found that RUNX2 could bind to the enhancer regions of Fbln1 (gene of fibulin-1), one of the marker genes for DFDP. Through gain- and loss-of-function experiments, we proved that the biomechanical stress-mediated RUNX2-fibulin-1 axis inhibits the initiation of SDL by maintaining SDL niche homeostasis.

[Characteristics of responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency].

Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.