Long-term burden of illness and associated medication usage make osteoporosis(OP) a common complication of respiratory diseases. The pathogenic risk factors and treatment strategies for respiratory diseases related OP are similar to primary OP. However, due to differences in the pathogenesis of each disease, there are distinctions in the characteristics of bone loss and treatment approaches. Therefore, targeted diagnostic and therapeutic plans need to be formulated. This article provides a comprehensive review of secondary OP caused by common respiratory diseases in terms of epidemiological characteristics, related risk factors or possible mechanisms, changes in bone metabolic indexes or characteristics of bone damage, and progress in diagnosis and treatment. The aim of this review is to offer insights into the prevention and treatment of secondary OP related to respiratory diseases and promote the development of a multidisciplinary collaborative approach.

【Objective】 To evaluate the clinical implications of ARL5B in esophageal cancer and its underlying mechanisms by using bioinformatics methods. 【Methods】 ARL5B transcriptomic expression data were obtained from The Cancer Genome Atlas (TCGA), R software was employed to detect the differential expression mRNAs, and related clinical information was collected for survival analysis. To validate the bioinformatics results, Real-time quantitative PCR (qRT-PCR) and Western blotting were carried out for clinical specimens of esophageal cancer tumor tissues and adjacent tissues. Immunohistochemistry was used to evaluate the expression of ARL5B and its associated clinicopathologic features. The underlying mechanisms of ARL5B in esophageal cancer were preliminarily explored by bioinformatics and qRT-PCR. 【Results】 Bioinformatics method showed that the expression of ARL5B in human esophageal cancer tissues was significantly higher than in adjacent tissues and correlated with poor prognosis. Clinical specimens were detected, the expressions of ARL5B mRNA and protein were the highest in metastases lymph node, followed by esophageal cancer tissues and adjacent tissues, which corresponded with bioinformatics results. The expression of ARL5B was strongly correlated with lymph node metastases and advanced clinical stage. Kaplan-Meier analysis results denoted high ARL5B level, indicating poor prognosis. Enrichment analysis showed that ARL5B was associated the biological processes such as vacuolar transport, late endosome to lysosome transport, and organelle localization. Protein-protein interaction analysis (PPI) suggested that ARL5B might interact with VPS16, KIF1A and TOM1, whose expressions were verified by qRT-PCR and positively correlated with ARL5B expression. 【Conclusion】 ARL5B was highly expressed in esophageal cancer and associated with lymph node metastases, advanced clinical stage, and poor prognosis. ARL5B may be involved in the progression of esophageal cancer with several molecular mechanisms.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

Objective:To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome,and to lay the foundation for the development of anti-Staphylococcus aureus drugs.Methods:The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information(NCBI)Database with Staphylococcus aureus as the keyword;BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus;subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes.These potential antibacterial targets were used as the receptors;LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration(FDA)-approved drug library;molecular docking technology was used to analyze the binding abilities of the drugs and targets.Results:There were 14 379 gene families in the 50 Staphylococcus aureus genomes,of which 1 620 were the core genes.The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target.LibDock software screened out nine compounds,including balofloxacin,tenofovir disoproxil fumarate,and adefovir,that may exert anti-Staphylococcus aureus effects on this target protein.The molecular docking results showed there was good binding abilities between the targets and the compounds.Conclusion:Tyrosine autokinase may be the potential target for antii-Staphylococcus aureus.

Gene-knockout technology is increasingly used as a powerful tool for establishing animal models of hyperuricemia(HUA).HUA gene-knockout animal models are not only helpful in revealing the molecular mechanisms of uric acid metabolism but are also of great value for evaluating potential therapeutic strategies.In this paper,the application of gene-knockout technology in HUA animal models is discussed in detail by reviewing the domestic and foreign literature,focusing on the knockout of urate oxidase,glucose transporter 9,and ATP-binding cassette transporter G2.The review provides a reference and guidance for the further establishment of HUA animal models by gene knockout technology.

Objective:To establish a hyperuricemia rat model through the high temperature-humidity treatment, and monitor its vital signs and biochemical indicator characteristics, as well as observe the changes of renal histomorphology and ultrastructure.Methods:Male SD rats were randomly divided into control(CON) group, potassium oxonate(PO) group and high temperature-humidity(HTH) group, 6 rats each. The experiment lasted for 6 consecutive weeks. Rats from PO group was given 250 mg/kg PO by gavage every day. The rats from HTH group were treated with a special thermostatic incubator for one hour each day after gavaging 250 mg/kg PO. Serum uric acid, creatinine and other indicators were detected every 2 weeks. After 6 weeks, the kidney tissues were collected. The morphological changes and urate crystal deposition of kidney tissues were observed by hematoxylin-eosin staining, Masson′s trichrome staining and gomori staining, while the ultramicrostructural changes of kidney were observed by transmission electron microscope.Results:Two weeks after the experiment, the average serum uric acid values of PO group and HTH group increased significantly, HTH group was higher than PO and CON groups[(133.9±17.8), (107.6±12.4), and (85.7±4.1) μmol/L, P=0.001]. And after 6 weeks, the HTH group was still higher than the other two groups[(115.1±27.8), (82.7±13.9), and (72.9±17.8) μmol/L, P=0.008). The average serum creatinine in HTH group was slightly higher than that in PO group and CON group at 6 weeks[(46.2±4.7), (38.1±6.0), and (28.3±6.3) μmol/L, P=0.001]. Light microscope showed partial renal tubular dilatation in PO group, but renal tubular epithelial cells swelling and inflammatory cells infiltration were more significant in HTH group. The ultrastructural changes such as glomerular podocyte swelling were found in HTH group by transmission electron microscope. Conclusion:In this study, we had successfully established a hyperuricemia rat model by simulating the high temperature-humidity environment combined with potassium oxyzinate after 2 weeks of experiment. After 6 weeks of modeling, it was found that the high temperature-humidity induced rat models possessed a relatively higher and stabler serum uric acid level than that of the traditional chemical medicine induced rats. The method can be applied to the research of pathogenesis and pharmacotherapy of hyperuricemia caused by high temperature-humidity environment.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

OBJECTIVE: To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age. METHODS: A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed. RESULTS: One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria. CONCLUSION This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.
Asians/genetics* ; China ; Exome ; Female ; Humans ; Infant, Newborn ; Metabolic Diseases/genetics* ; Mitochondrial Membrane Transport Proteins/genetics* ; Oxidoreductases/genetics* ; Whole Exome Sequencing

【Objective】 To investigate the effect of Qingkailing injection on platelet function preserved in vitro. 【Methods】 A total of 15 bags of plateletpheresis (≥250 mL/bag), adding Qingkailing injection(1.25 mL/bag) at the final concentration of 1%, were stored at 22 ℃ with gentle agitation as the experimental group, and samples were collected on day 1, 3, 5, 8, 10 and 14 to detect the thromboelastogram (TEG), CD62p expression rate and mitochondrial membrane potential (JC-1). The control group was set up synchronously, with the same volume and storage conditions as the experimental groups, and samples were taken on day 1, 3 and 5 after preservation to undertake the same test items as the experimental groups. The differences of detection indexes between the two groups were compared. 【Results】 1) In the experimental group, there was no significant change in K and α during day 1 to 14(P>0.05). The R value (min) increased from 6.12±1.58 to 11.02±2.26, and the CI value changed from 0.27±1.24 to -10.47±3.51 (P<0.05). The MA value (mm) had no significant change within 5 days (P>0.05), but decreased to 53.18±2.71 on day 8 and 22.88±3.45 on day 14 (P<0.05). In the control group during day 1 to 5, K(min) and α showed no significant change, while R(min) was significantly prolonged, MA (mm) decreased and CI increased significantly (P<0.05). 2) The expression rate of CD62p (%) was 70.50±9.12 in the experimental group on day 5 (vs 83.16±5.33 in the control groups, P<0.05) and 82.77±7.17 on day 14 (P<0.05). 3) There was no significant change in JC-1 (%) during regular preservation period between the experimental group and control group (P>0.05), but JC-1 (%) was 86.75±3.88 vs 70.36±19.8 on day 5 (P<0.05). In the experimental group, JC-1(%) was 81.04±9.50 vs 71.38±8.77 vs 82.77±7.17 on day 8, 10 and 14, respectively. 【Conclusion】 The activation and aggregation as well as anti-apoptosis function of plateletpheresis, adding Qingkailing injection at the final concentration of 1%, are similar to those of routine preservation.

OBJECTIVE: To summarize the genetic characteristics of 671 Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: Clinical data of the pedigrees were collected. Multiplex PCR, multiple ligation dependent probe amplification (MLPA), next generation sequencing (NGS), Sanger sequencing and long read sequencing were used to detect the variant of DMD gene in the probands and their mothers, and prenatal diagnosis was provided for high risk pregnant women. RESULTS: Among 178 pedigrees analyzed by multiplex PCR, 44 variants of the DMD gene were detected, with the genetic diagnosis attained in 110 pedigrees. Among 493 pedigrees analyzed by MLPA in combination with NGS or Sanger sequencing, 294 pathogenic/possible pathogenic variants were identified, among which 45 were unreported previously, and the genetic diagnosis attained in 484 pedigrees. Structural variants of the DMD gene were identified in two pedigrees by long-read sequencing. Among 444 probands, 341 have inherited the DMD gene variant from their mothers (76.8%). Among 390 women with a high-risk, 339 have opted to have natural pregnancy and 51 chose preimplantation genetic testing for monogenetic disease (PGT-M). The detection rate of neonatal patients and carriers following natural pregnancy was significantly higher than that for PGT-M. CONCLUSION Combined application of MLPA, NGS, Sanger sequencing and long-read sequencing is an effective strategy to detect DMD/BMD. PGT-M can effectively reduce the risk of fetuses. Above finding has expanded the spectrum of DMD gene variants and provided a basis for reproductive intervention for pregnancies with a high risk for DMD/BMD.
China ; Dystrophin/genetics* ; Exons ; Female ; Genetic Testing ; Humans ; Infant, Newborn ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis