Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis.

Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses. Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis. Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets-human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)-were identified as pivotal players in pathways such as "Antigen processing and presentation" and "Phagosome," which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets. Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis.

[Characteristics，Sources，and Ozone-sensitive Species of VOCs in Four Seasons in Yuncheng].

Based on the one-year observational data of volatile organic compounds （VOCs） in an urban area of Yuncheng in 2021， the concentration， composition， sources， and ozone-sensitive species of VOCs in four seasons were analyzed. The results showed that the average annual concentration of VOCs was （32.1 ±24.2）×10-9， i.e.， at the national middle level. The seasonal concentrations of VOCs were in the order of： winter （46.3×10-9）> autumn （35.5×10-9）> spring （25.6×10-9）> summer （21.2×10-9）. Alkanes and OVOCs were the most dominant VOCs compounds， accounting for 69.0%-80.4% of TVOCs in Yuncheng. Affected by changes in source emissions， the proportion of OVOCs was higher in spring and summer （41%-43%）， whereas the proportion of alkanes was higher in autumn and winter （42%-43%）. Vehicle exhaust， LPG/NG， industrial production， and combustion sources were identified as the main sources of VOCs in Yuncheng. The largest contributors in the four seasons were vehicle exhaust （28.5% in spring）， secondary + combustion sources （29.0% in summer）， LPG/NG sources （30.4% in autumn）， and coal combustion （27.3% in winter）. The ozone formation was located in the transitional regime in summer and in the VOC-limited regime in other seasons. Ozone production was more sensitive to alkenes （isoprene， ethylene， and propene）， OVOCs （acetaldehyde and propanal）， and aromatics （xylene， toluene， and benzene）. Winter was more sensitive to ethylene， and the other seasons were more sensitive to isoprene. The primary emission sources related to these sensitive species should be reduced to achieve the goal of air quality improvement.

Effect of transcutaneous electrical acupoint stimulation based on the theory of "qi ascending and descending movement" on autonomic nervous system and gastrointestinal function in patients after general anesthesia laparoscopic cholecystectomy. / 基于"气机升降"ç†è®ºç»çš®ç©´ä½ç”µåˆºæ¿€å¯¹å ¨éº»è ¹è ”é•œèƒ†å›Šåˆ‡é™¤æœ¯åŽæ‚£è€ è‡ªä¸»ç¥žç»å’Œèƒƒè‚ åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) based on the theory of "qi ascending and descending movement" in patients after general anesthesia laparoscopic cholecystectomy, so as to explore the impact of TEAS on the autonomic nervous system and gastrointestinal function of patients. METHODS: A total of 204 patients scheduled to undergo general anesthesia laparoscopic cholecystectomy were selected and randomly divided into control, double acupoints and multiple acupoints groups, with 68 cases in each group. For patients in the multiple acupoints group, TEAS was applied at Zusanli (ST36), Tiantu (CV22), Danzhong (CV17), Zhongwan (CV12), Taichong (LR3), and Neiguan (PC6) 30 min before anesthesia induction until the end of the surgery. In the double acupoints group, TEAS was applied only at ST36 and PC6. No electrical stimulation was applied in the control group. The postoperative bloating, bowel sound recovery time, first farting time, first defecation time, length of hospital stay, nausea and vomiting were compared among the three groups. Heart rate variability was monitored by twelve-lead electrocardiogram to evaluate the autonomic nervous function of the patients, including the low frequency power/high frequency power ratio (LF/HF), the standard deviation of all sinus RR intervals (SDNN), and the root mean square of difference between successive normal RR intervals (RMSSD). RESULTS: At 6 h and 24 h after surgery, the symptoms of bloating, nausea and vomiting in the multiple acupoints group and double acupoints group were significantly improved compared to the control group (P<0.05), and the multiple acupoints group was superior to the double acupoints group (P<0.05). Compared with the control group, the bowel sound recovery time, first farting time, first defecation time, and length of hospital stay were significantly shorter (P<0.05) in the multiple acupoints group and double acupoints group, and the multiple acupoints group was superior to the double acupoints group (P<0.05). At 1 d and 2 d after surgery, compared with the control group, LF/HF was decreased (P<0.05) while SDNN and RMSSD were increased (P<0.05) in the multiple acupoints group and double acupoints group, and there was a significant difference between the two groups (P<0.05). CONCLUSIONS: TEAS treatment based on the theory of "qi ascending and descending movement" can relieve gastrointestinal dysfunction, reduce early postoperative sympathetic nerve excitement and maintain parasympathetic nerve tension in patients after general anesthesia laparoscopic cholecystectomy, thereby promoting gastrointestinal function recovery.

An elastic competitive and discriminative collaborative representation method for image classification.

Collaborative representation-based (CR) methods have become prevalent for pattern classification tasks, achieving formidable performance. Theoretically, we expect the learned class-specific representation of the correct class to be discriminative against others, with the representation of the correct class contributing dominantly in CR. However, most existing CR methods focus on improving discrimination while having a limited impact on enhancing the representation contribution of the correct category. In this work, we propose a novel CR approach for image classification called the elastic competitive and discriminative collaborative representation-based classifier (ECDCRC) to simultaneously strengthen representation contribution and discrimination of the correct class. The ECDCRC objective function penalizes two key terms by fully incorporating label information. The competitive term integrates the nearest subspace representation with corresponding elastic factors into the model, allowing each class to have varying competition intensities based on similarity with the query sample. This enhances the representation contribution of the correct class in CR. To further improve discrimination, the discriminative term introduces an elastic factor as a weight in the model to represent the gap between the query sample and the representation of each class. Moreover, instead of focusing on representation coefficients, the designed ECDCRC weights associated with representation components directly relate to the representation of each class, enabling more direct and precise discrimination improvement. Concurrently, sparsity is also enhanced through the two terms, further boosting model performance. Additionally, we propose a robust ECDCRC (R-ECDCRC) to handle image classification with noise. Extensive experiments on seven public databases demonstrate the proposed method's superior performance over related state-of-the-art CR methods.

Comprehensive effects of thiamethoxam from contaminated soil on lettuce growth and metabolism.

The second-generation neonicotinoid thiamethoxam, is prevalent in soils because of its extensive application and persistence. However, the comprehensive effects of thiamethoxam residue in soils on cultivated plants are still poorly understood. This study examined variations of growth state, physiological parameters, antioxidant activity, and metabolites in lettuce after thiamethoxam exposure; the removal effects of different washing procedures were also investigated. The results indicated that thiamethoxam in soils significantly increased the fresh weight, seedling height and chlorophyll content in lettuce, and also altered its lipid, carbohydrate, nucleotide and amino acids composition based on untargeted metabolomics. KEGG pathway analysis uncovered a disruption of lipid pathways in lettuce exposed to both low and high concentrations of thiamethoxam treatments. In addition, the terminal residues of thiamethoxam in lettuce were below the corresponding maximum residue limits stipulated for China. The thiamethoxam removal rates achieved by common washing procedures in lettuce ranged from 26.9% to 42.6%. This study thus promotes the understanding of the potential food safety risk caused by residual thiamethoxam in soils.

Enhanced secondary organic aerosol formation during dust episodes by photochemical reactions in the winter in Wuhan.

To investigate the effect of frequently occurring mineral dust on the formation of secondary organic aerosol (SOA), 106 volatile organic compounds (VOCs), trace gas pollutants and chemical components of PM2.5 were measured continuously in January 2021 in Wuhan, Central China. The observation period was divided into two stages that included a haze period and a following dust period, based on the ratio of PM2.5 and PM10 concentrations. The average ratio of secondary organic carbon (SOC) to elemental carbon (EC) was 1.98 during the dust period, which was higher than that during the haze period (0.69). The contribution of SOA to PM2.5 also increased from 2.75% to 8.64%. The analysis of the relationships between the SOA and relative humidity (RH) and the odd oxygen (e.g., OX = O3 + NO2) levels suggested that photochemical reactions played a more important role in the enhancement of SOA production during the dust period than the aqueous-phase reactions. The heterogeneous photochemical production of OH radicals in the presence of metal oxides during the dust period was believed to be enhanced. Meanwhile, the ratios of trans-2-butene to cis-2-butene and m-/p-xylene to ethylbenzene (X/E) dropped significantly, confirming that stronger photochemical reactions occurred and SOA precursors formed efficiently. These results verified the laboratory findings that metal oxides in mineral dust could catalyse the oxidation of VOCs and induce higher SOA production.

Translocation and dissipation of thiamethoxam applied by root irrigation in tomato plant-soil system.

Thiamethoxam (TMX) has been registered for use on a wide range of crops due to its versatile application methods, however, there is limited literature evaluating the residue behaviors of TMX applied through root irrigation. In this study, the uptake and translocation of TMX, its degradation to clothianidin (CLO), and dissipation in the tomato plant-soil system were conducted. TMX applied by root irrigation was transferable within the tomato plant, including stems, leaves, and fruits at different heights. TMX concentrations in the four sections of stems were ordered as Clower > Cmid > Cupper > Ctop, while in the leaves were ordered as Ctop > Cupper > Cmid > Clower. The degradation product CLO was detected in the tomato plant, and concentrations of CLO were even higher than those of TMX in the leaves. The translocation factor (TF) of TMX in the same section generally followed the order of TFleaf > TFstem > TFfruit. Residues of TMX and CLO in tomato on 7 days after application were below maximum residue limits (MRLs) in China and Codex Alimentarius Commission (CAC). This study promotes the evaluation of TMX applied through root irrigation for use in the tomato system from a dietary safety perspective.

Clinical features and molecular characterization of Chinese patients with FKBP10 variants.

BACKGROUND: Osteogenesis imperfecta (OI) is a group of rare skeletal dysplasia. Long bone deformity and scoliosis are often associated with progressively deforming types of OI. FKBP65 (encoded by FKBP10, OMIM *607063) plays a crucial role in the processing of type I procollagen. Autosomal recessive variants in FKBP10 result in type XI osteogenesis imperfecta. METHODS: Patients diagnosed with OI were recruited for a genetic test. RT-PCR and Sanger sequencing were applied to confirm the splicing defect in FKBP10 mRNA with the splice-site variant. The bone structure was characterized by Goldner's trichrome staining. Bioinformatic analyses of bulk RNA sequencing data were performed to examine the effect of the FKBP10 variant on gene expression. RESULTS: Here we reported three children from a consanguineous family harboured a homozygous splice-site variant (c.918-3C > G) in FKBP10 intron and developed long bone deformity and early onset of scoliosis. We also observed frequent long bone fractures and spinal deformity in another 3 OI patients with different FKBP10 variants. The homozygous splicing variant identified in the fifth intron of FKBP10 (c.918-3C > G) led to abnormal RNA processing and loss of FKBP65 protein and consequently resulted in aberrant collagen alignment and porous bone morphology. Analysis of transcriptomic data indicated that genes involved in protein processing and osteoblast differentiation were significantly affected in the patient-derived osteoblasts. CONCLUSION: Our study characterized the clinical features of OI patients with FKBP10 variants and revealed the pathogenesis of the c.918-3C > G variant. The molecular analyses helped to gain insight into the deleterious effects of FKBP10 variants on collagen processing and osteoblast differentiation.

Retrospective analyses of clinical features in 28 Chinese patients with type V osteogenesis imperfecta: new perspectives in an old issue.

Type V osteogenesis imperfecta (OI) is a form of OI characterized by radial head dislocation (RHD), calcification of interosseous membrane (CIM), and hyperplastic callus (HPC). In this study, we characterized the clinical features of 28 type V OI patients. We presented that dysfunctions of elbow, hip joint, and abnormal epiphyseal growth plate were associated with ectopic calcification and summarized the history of HPC progression and treatment. INTRODUCTION: The current study aims to systematically characterize the skeletal phenotypes of patients with type V OI and suggested possible surgical solutions. METHODS: A total of 28 patients were admitted for inpatient care at The Hong Kong University-Shenzhen Hospital diagnosed with type V OI (either clinically diagnosed or genetically confirmed with the IFITM5 c.-14C > T mutation). RESULTS: Prevalence of type V radiological features was comparable to previous literatures (RHD, 100%; CIM, 100%; HPC, 44%; and scoliosis, 50%). Novel skeletal phenotypes were presented including extension of coronoid process, acetabular labrum, acetabular protrusion, spontaneous autofusion of the hip, bulbous epiphysis, and popcorn calcification. Significant increase in BMD was observed in patients with bisphosphonate treatment. Twenty-five percent (3/12) of patients with preoperative use of indomethacin developed HPC postoperatively, and HPCs were absorbed in 2 young patients 2 years later. CONCLUSION: This retrospective study summarized the clinical features and highlighted the abnormalities in elbow, hip joint, and growth plate in type V OI patients. Our study contributed to a more comprehensive clinical spectrum of type V OI. We also characterized the natural progression of HPC formation and resorption in patients in different ages. The use of bisphosphonate treatment is effective in improving bone mineral density in type V OI patients, and whether indomethacin can reduce incidence of HPC formation deserves further investigation.

Analysis of VOC emissions and O3 control strategies in the Fenhe Plain cities, China.

Long-term continuous hourly measurements of ambient volatile organic compounds (VOCs) are scarce at the regional scale. In this study, a one-year hourly measurement campaign of VOCs was performed in Lvliang, Linfen, and Yuncheng in the heavily polluted Fenhe Plain region in China. The VOC average (±standard deviation, std) concentrations in Lvliang, Linfen, and Yuncheng were 44.4 ± 24.9, 45.7 ± 24.9, and 37.5 ± 25.0 ppbv, respectively. Compared to published data from the past two decades in China, the observed VOCs were at high concentration levels. VOCs in the Fenhe Plain cities were significantly impacted by industrial sources according to calculated emission ratios but were less affected by liquefied petroleum gas and natural gas (LPG/NG) and traffic emissions than those in megacities abroad. The emission inventories and observation data were combined for verification and identification of the key VOC species and sources controlling ozone (O3). Industrial emissions were the largest source of VOCs, accounting for 65%-79% of the total VOC emissions, while the coking industry accounted for 45.2%-66.0%. The emission inventories significantly underestimated oxygenated VOC (OVOC) emissions through the verification of VOC emission ratios. O3 control scenarios were analyzed by changing VOC/NOX reduction ratios through a photochemical box model. O3 control strategies were formulated considering local pollution control plans, emission inventories, and O3 formation regimes. The O3 reduction of reactivity-control measures was comparable with emission-control measures, ranging from 16% to 41%, which was contrary to the general perception that ozone formation potential (OFP)-based measures were more efficient for O3 reduction. Sources with high VOC emissions are accompanied by high OFP on the Fenhe Plain, indicating that the control of high-emission sources can effectively mitigate O3 pollution on this region.

Ferroptosis-related long non-coding RNA signature predicts the prognosis of hepatocellular carcinoma: A Review.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a liver cancer. In contrast, ferroptosis is a novel iron-dependent and ROS reliant type of cell death that is observed under various disease conditions. METHODS AND ANALYSIS: RNA sequencing data from HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Ferroptosis-related long non-coding RNAs (lncRNAs) were screened by Pearson correlation analysis. Patients were randomized into training or testing sets in a 1:1 ratio. They were constructed in the training set using univariate-Lasso and multivariate Cox regression analysis and further tested for prognostic values in the testing set. Four lncRNAs were identified. Kaplan-Meier analysis showed that patients in the high-risk group had a worse prognosis than those in the low-risk group. Following differentially expressed genes analysis of these two groups. Functional analysis showed association with oxidative stress response. Cox regression analyses showed that risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) and decision curve analysis demonstrated the accuracy of prediction. Four ferroptosis-related lncRNAs based on differential expression of HCC were screened by bioinformatic methods to construct a prognostic risk model and accurately predict the prognosis of HCC patients. Four lncRNAs may have a potential role in the anti-tumor immune process and serve as therapeutic targets for HCC. To lay the foundation for subsequent studies.

Quantification of enhanced VOC emissions from fireworks.

Fireworks are widely used in celebrations worldwide. The effects of fireworks on the physicochemical characteristics of atmospheric particles are well documented. However, the influence of firework burning on ambient volatile organic compound (VOC) emissions remains unclear. To determine the impact of firework-burning events on VOC emissions, ambient VOCs were measured at a receptor site on the Fenwei Plain during the Chinese Spring Festival period. Firework-burning plumes were identified by using potassium ions (K+) as tracers, and twenty VOC species were obtained as firework tracers. The emission ratios of the VOC species relative to K+ were in a range of 5.40 × 10-3-1.41 µg m-3/µg m-3 and were first estimated through the linear fitting method and source-tracer-ratio method. The VOC contributions of firework burning during the Lantern Festival (31.7 ± 8.3%) were higher than the levels during the Chinese New Year (28.6 ± 7.5%). The daytime net ozone (O3) formation rates during the Spring Festival and Lantern Festival increased by 11.4% and 15.2%, respectively, on average due to firework emissions. Secondary organic aerosol formation potential (SOAP) increased by 18.2% and 34.1% on average, respectively. These results can provide the source tracers of fireworks, and can subsequently help assess their impact on regional air quality and public health.

Patient-reported outcomes in a Chinese cohort of osteogenesis imperfecta unveil psycho-physical stratifications associated with clinical manifestations.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare congenital disorder of the skeletal system, inflicting debilitating physical and psychological distress on patients and caregivers. Over the decades, much effort has been channeled towards understanding molecular mechanisms and developing new treatments. It has recently become more apparent that patient-reported outcome measurements (PROM) during treatment, healing and rehabilitation are helpful in facilitating smoother communication, refining intervention strategies and achieving higher quality of life. To date, systematic analyses of PROM in OI patients remain scarce. RESULTS: Here, utilizing a PROM Information System, we report a cross-sectional and longitudinal study in a southern Chinese cohort of 90 OI patients, covering both the child and adult age-groups. In the child group where both self and parental surveys were obtained, we identified two clusters of comparable sizes showing different outlooks in physical mobility and emotional experiences. One cluster (Cluster 1) is more negative about themselves than the other (Cluster 2). A concordance of 84.7% between self and parental assessments was recorded, suggesting the stability and validity of PROM-based stratification. Clinical subtyping, deformity, leg length discrepancy, and limited joint mobility were significantly associated with this stratification, with Cluster 1 showing higher percentages of severe phenotypes than Cluster 2. Since OI is a genetic disorder, we performed genetic testing on 72 of the 90 patients, but found no obvious association between genotypes and the PROM stratification. Analyses of longitudinal data suggested that patients tended to stay in the same psychological state, in both clusters. Adult patients also showed a continuous spectrum of self-evaluation that matches their clinical manifestations. CONCLUSION: By systematically analyzing patient-reported outcomes, our study demonstrated the link between the sociopsychological wellbeing of OI patients, and their clinical manifestations, which may serve as the basis for evaluating clinical interventions and help achieve better patient-centric medical practices. The lack of genotype-PROM association may be due to the diverse mutational spectrum in OI, which warrants further investigation when a larger sample size is available.

Genome-wide identification, molecular characterization, and gene expression analyses of honeysuckle NHX antiporters suggest their involvement in salt stress adaptation.

Background: Ion homeostasis is an essential process for the survival of plants under salt stress. Na+/H+ antiporters (NHXs) are secondary ion transporters that regulate Na+ compartmentalization or efflux reduce Na+ toxicity and play a critical role during plant development and stress responses. Methods and Results: To gain insight into the functional divergence of NHX genes in honeysuckle, a total of seven LjNHX genes were identified on the whole genome level and were renamed according to their chromosomal positions. All LjNHXs possessed the Na+/H+ exchanger domain and the amiloride-binding site was presented in all NHX proteins except LjNHX4. The phylogenetic analysis divided the seven NHX genes into Vac-clade (LjNHX1/2/3/4/5/7) and PM-clade (LjNHX6) based on their subcellular localization and validated by the distribution of conserved protein motifs and exon/intron organization analysis. The protein-protein interaction network showed that LjNHX4/5/6/7 shared the same putatively interactive proteins, including SOS2, SOS3, HKT1, and AVP1. Cis-acting elements and gene ontology (GO) analysis suggested that most LjNHXs involve in the response to salt stress through ion transmembrane transport. The expression profile analysis revealed that the expression levels of LjNHX3/7 were remarkably affected by salinity. These results suggested that LjNHXs play significant roles in honeysuckle development and response to salt stresses. Conclusions: The theoretical foundation was established in the present study for the further functional characterization of the NHX gene family in honeysuckle.

Comprehensive risk assessments and anesthetic management for children with osteogenesis imperfecta: A retrospective review of 252 orthopedic procedures over 5 years.

BACKGROUND: Major anesthetic risks arise in orthopedic surgeries for children with osteogenesis imperfecta, a rare genetically inherited condition presenting diverse skeletal issues. AIM: We aimed to investigate anesthetic risks, including difficult airway, hypo- and hyperthermia, blood loss, and pain, in connection with patient, anesthetic, and surgical factors. METHODS: Both descriptive and inferential statistics were employed to study the anesthetic risks and their predictors. Data of 252 surgeries for 132 Chinese osteogenesis imperfecta patients aged 18 or below were retrieved from the authors' hospital between 2015 and 2019. RESULTS: Two thirds of the cohort were Sillence type IV patients, with types I, III, and V accounting for 7.6%, 14.4%, and 11.4%, respectively. Video and direct laryngoscopy were used. No case of difficult airway was identified. Due to a careful management strategy, intraoperative temperature varied on average between -0.38°C and +0.89°C from the initial temperature. Fifty-two and 18 cases of hyper- and hypothermia were encountered, respectively. The use of sevoflurane for maintenance resulted in a mean increase of +0.24°C [95% CI 0.05 ~ 0.42] in the maximum temperature. Massive blood losses (>20% of estimated total blood volume) were observed in 18.3% of the cases. Neither intraoperative temperature changes nor blood loss was found to be related to Sillence classification. Regional anesthesia techniques were applied to 72.6% of the cases. Ultrasound guidance was used per the judgment of anesthesiologists or when in case of difficult landmarks. The incidence of difficult regional anesthesia was low (4 out of 252). For postoperative analgesia, 154 neuraxial blocks (including 77 caudal and 77 lumbar epidural) and 29 peripheral nerve blocks were performed. CONCLUSION: Anesthesia for children with osteogenesis imperfecta undergoing complex orthopedic procedures was challenging. Proper anesthesia planning was essential for both intraoperative management and postoperative analgesia. Age, surgical duration, and use of sevoflurane for maintenance impacted the intraoperative temperature most, and massive blood loss was not uncommon. The risks for airway or regional anesthesia difficulties were low. Pain scores could be controlled to be ≤3 via multiple techniques.

Phenotypic Spectrum and Molecular Basis in a Chinese Cohort of Osteogenesis Imperfecta With Mutations in Type I Collagen.

Osteogenesis imperfecta (OI) is a rare inherited connective tissue dysplasia characterized with skeletal fragility, recurrent fractures and bone deformity, predominantly caused by mutations in the genes COL1A1 or COL1A2 that encode the chains of type I collagen. In the present study, clinical manifestations and genetic variants were analysed from 187 Chinese OI patients, majority of whom are of southern Chinese origin. By targeted sequencing, 63 and 58 OI patients were found carrying mutations in COL1A1 and COL1A2 respectively, including 8 novel COL1A1 and 7 novel COL1A2 variants. We validated a novel splicing mutation in COL1A1. A diverse mutational and phenotypic spectrum was observed, coupling with the heterogeneity observed in the transcriptomic data derived from osteoblasts of six patients from our cohort. Missense mutations were significantly associated (χ2 p = 0.0096) with a cluster of patients with more severe clinical phenotypes. Additionally, the severity of OI was more correlated with the quality of bones, rather than the bone mineral density. Bone density is most responsive to bisphosphonate treatment during the juvenile stage (10-15 years old). In contrast, height is not responsive to bisphosphonate treatment. Our findings expand the mutational spectrum of type I collagen genes and the genotype-phenotype correlation in Chinese OI patients. The observation of effective bisphosphonate treatment in an age-specific manner may help to improve OI patient management.

Bioinformatics and systems biology approaches to identify the effects of COVID-19 on neurodegenerative diseases: A review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease (COVID-19), has been devastated by COVID-19 in an increasing number of countries and health care systems around the world since its announcement of a global pandemic on 11 March 2020. During the pandemic, emerging novel viral mutant variants have caused multiple outbreaks of COVID-19 around the world and are prone to genetic evolution, causing serious damage to human health. As confirmed cases of COVID-19 spread rapidly, there is evidence that SARS-CoV-2 infection involves the central nervous system (CNS) and peripheral nervous system (PNS), directly or indirectly damaging neurons and further leading to neurodegenerative diseases (ND), but the molecular mechanisms of ND and CVOID-19 are unknown. We employed transcriptomic profiling to detect several major diseases of ND: Alzheimer 's disease (AD), Parkinson' s disease (PD), and multiple sclerosis (MS) common pathways and molecular biomarkers in association with COVID-19, helping to understand the link between ND and COVID-19. There were 14, 30 and 19 differentially expressed genes (DEGs) between COVID-19 and Alzheimer 's disease (AD), Parkinson' s disease (PD) and multiple sclerosis (MS), respectively; enrichment analysis showed that MAPK, IL-17, PI3K-Akt and other signaling pathways were significantly expressed; the hub genes (HGs) of DEGs between ND and COVID-19 were CRH, SST, TAC1, SLC32A1, GAD2, GAD1, VIP and SYP. Analysis of transcriptome data suggests multiple co-morbid mechanisms between COVID-19 and AD, PD, and MS, providing new ideas and therapeutic strategies for clinical prevention and treatment of COVID-19 and ND.

Effect of Shenfu Injection on Isolated Empty Beating Hearts from Miniature Pigs.

OBJECTIVE: To investigate the effect of Shenfu (SF) injection on donor heart preservation. METHODS: Twelve pigs were randomly divided into SF group (n=6) and control group (n=6). After eight hours of perfusion, the differences in hemoglobin, the expression of Bcl-2 and BAX, and changes in the myocardial ultrastructure were compared to illustrate the effects of SF injection in heart preservation. RESULTS: The differences in free hemoglobin between the SF group and the control group were statistically significant (P=0.001), and there was significant interaction of groups with times (P=0.019), but the perfusion time may not be associated with the hemoglobin concentration (P=0.616). According to Western blotting analysis, the expression of Bcl-2 was higher in the SF group than in the control group, while the expression of BAX was not different between the two groups. As to ultrastructural changes, both groups exhibited mitochondrial swelling and myofilament lysis, but the degree of damage in the SF group was smaller. CONCLUSION: Our study suggests that the application of SF injection for heart preservation may protect against cardiomyocytes and erythrocytes apoptosis, and Bcl-2 protein may play a role in these physiological processes.

Effect of shenfu injection on isolated empty beating hearts from miniature pigs

Abstract Objective: To investigate the effect of Shenfu (SF) injection on donor heart preservation. Methods: Twelve pigs were randomly divided into SF group (n=6) and control group (n=6). After eight hours of perfusion, the differences in hemoglobin, the expression of Bcl-2 and BAX, and changes in the myocardial ultrastructure were compared to illustrate the effects of SF injection in heart preservation. Results: The differences in free hemoglobin between the SF group and the control group were statistically significant (P=0.001), and there was significant interaction of groups with times (P=0.019), but the perfusion time may not be associated with the hemoglobin concentration (P=0.616). According to Western blotting analysis, the expression of Bcl-2 was higher in the SF group than in the control group, while the expression of BAX was not different between the two groups. As to ultrastructural changes, both groups exhibited mitochondrial swelling and myofilament lysis, but the degree of damage in the SF group was smaller. Conclusion: Our study suggests that the application of SF injection for heart preservation may protect against cardiomyocytes and erythrocytes apoptosis, and Bcl-2 protein may play a role in these physiological processes.

In vivo evaluation of porous nanohydroxyapatite/polyamide 66 struts in a goat cervical fusion model.

The hollow cylindrical nanohydroxyapatite/polyamide 66 strut (n-HA/PA66) has been used clinically for anterior cervical reconstruction. However, rates of occurrence of a "radiolucent gap" between the dense strut and adjacent endplates were reported. The aim of this in vivo study was to evaluate the viability and advantages of the novel porous n-HA/PA66 strut. The goat C3/4 partial discectomy and fusion model was built, and two groups of n-HA/PA66 struts were implanted into C3/4: group 1, porous n-HA/PA66 strut; and group 2, hollow cylindrical n-HA/PA66 strut filled with autogenous cancellous bone. CT evaluation was performed to assess the fusion status after 12 and 24 weeks. The cervical spines were harvested. Histomorphological analysis was performed to determine new bone formation. Biomechanical testing was performed to determine range of motion (ROM). CT confirmed the disappearance of the boundary of the porous strut and host bone, while the radiolucent gap remained clearly discernible in the dense strut group. The mean CT fusion scores of the porous group were significantly higher. Histologic evaluation showed that the porous struts promoted better osteointegration. Calcein fluorochrome labelling indicated faster bone ingrowth in the porous struts. Biomechanical tests revealed that the porous struts had significantly reduced micromotion. The porous n-HA/PA66 strut could offer interesting potential for cervical reconstruction after corpectomy.