Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

Objective To observe and evaluate the protective effect of desflurane post-conditioning on myocardial injury during cardiopulmonary bypass and its influence on patients'postoperative recovery.Methods A total of 200 patients in need of cardiac surgery were selected as the experimental subjects,who were aged from 20 to 65 years old,and divided into ASA Ⅱ-Ⅲ and NYHA Ⅱ-Ⅲ by endotracheal intubation and extracorporeal circulation method under general anesthesia.The patients were randomly divided into desflurane post-treatment group(experi-mental group,group D)and control group(group C)after selection.With the successive opening of the aorta and superior vena cava,group D were given 5%desflurane by inhalation with mechanical ventilation.While group C inhaled pure oxygen without inhaling desflurane.The depth of intraoperative anesthesia was maintained between 40～50 during the operation.Radial artery blood was collected from patients in 24 h before surgery(T0),immediately after intubation(T1),and 1 h(T2),6 h(T3),12 h(T4)and 24 h(T5)after aortic opening to achieve the determi-nation of troponin I(cTnI)and creatine kinase isoenzyme MB(CK-MB).On the premise of obtaining the informed consent of the patient,about 50 mg of right atrial appendage tissue was collected before aortic intubation(T1.5)and 1 hour after aortic opening(T2)to determine the apoptosis rate.Results(1)cTnI in group C at the time of T2,T3,T4 and T5 was apparently higher than group D(P<0.05).(2)CK-MB in group C at the time of T3 was apparently higher than group D(P<0.05).(3)The myocardial tissue results showed that there was a lower apoptosis rate in experimental group at the time of T2(P<0.05).Conclusion Desflurane post-conditioning has a myocardial protec-tive effect during cardiac surgery under cardiopulmonary bypass.

Objective:To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice.Methods:Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People′s Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group ( n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group ( n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results:The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35, P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81, P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion:Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.

Objective:To carry out genetic analysis on two families with carriers of small terminal translocations using karyotyping analysis and genomic copy number variation sequencing (CNV-seq).Methods:Two couples undergoing prenatal diagnosis at the Tianjin Central Hospital of Obstetrics and Gynecology respectively on April 12, 2020 and December 17, 2021 were selected as the study subjects. With informed consent, amniotic fluid and peripheral blood samples were collected and subjected to conventional karyotyping and CNV-seq analysis for the detection of chromosomal microdeletion/duplications.Results:Both couples had given births to children with chromosomal aberrations previously, and both fetuses were found to have abnormal karyotypes. CNV-seq showed that they had harbored microdeletion/duplications, and their mothers had both carried balanced translocations involving terminal fragments of chromosomes.Conclusion:For fetuses with small chromosomal segmental abnormalities, their parental origin should be traced, and the diagnosis should be confirmed with combined genetic techniques.

Objective To investigate the risk factors for the formation of infectious stones among residents in western Fujian Province and construct a nomogram model for preoperative prediction of the risk of infectious stones. Methods Clinical data of 204 patients who received treatment for urinary tract stones at Longyan People′s Hospital Affiliated to Xiamen Medical University from October 2021 to November 2023 were analyzed. All patients underwent stone composition analysis. Univariate and multivariate Logistic regression analysis were used to screen independent risk factors for infectious stones, construct a nomogram model for predicting the risk of infectious stones, and the discriminative power and accuracy of the model was evaluated. Results Based on the results of stone composition analysis, 204 patients were divided into infectious stone group(56 cases) and non-infectious stone group(148 cases). Univariate and multivariate Logistic regression analysis showed that female (OR=2.602, 95%CI, 0.766 to 8.842, P=0.039), diabetes (OR=9.751, 95%CI, 2.547 to 17.332, P=0.001), long diameter of stones (OR=1.123, 95%CI, 1.046 to 4.207, P=0.031), moderate to severe hydronephrosis (OR=4.173, 95%CI, 1.256 to 13.865, P=0.020), high urine pH value (OR=6.078, 95%CI, 1.922 to 19.216, P=0.002), and positive urine culture (OR=6.060, 95%CI, 1.398 to 16.262, P=0.016) were independent risk factors for infectious stones. A nomogram model for predicting the risk of infectious stones was constructed based on independent risk factors. The area under the curve of this model for predicting infectious stones was 0.860, which was significantly larger than the area under the curve predicted by gender, diabetes, stone long diameter, degree of hydronephrosis, urine pH value, and urine culture results (P < 0.05). The model was validated by 1 000 internal resampling, with an average absolute error of 1.8%, indicating a high consistency between the predicted risk of infectious stones and the actual situation. Conclusion Female, diabetes, long diameter of stones, moderate to severe hydronephrosis, high urine pH value, and positive urine culture are independent risk factors for infectious stones among residents in western Fujian Province. The nomogram model constructed based on these factors can predict the risk of infectious stones preoperatively with high predictive efficiency.

Vascular malformations, which mainly occur in the head and neck region, are a group of congenital disorders that cannot involute and dilate gradually as patients grow. Traditional therapeutic strategies for vascular malformations include laser therapy, sclerotherapy, interventional embolization, surgical resection, etc. However, for some cases with a relatively larger range of lesions, traditional therapeutic strategies might fall short of the goals. With the development of molecular genetics, gene mutations are currently recognized as the root cause of the occurrence of vascular malformations. The progression of vascular malformation lesions is further promoted by the activation of related pathways. Low-flow vascular malformations mainly involve activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, whereas high-flow vascular malformations mainly involve activation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MAPKK)/extracellular-signal regulated protein kinase (ERK) pathway. Targeted drugs against relevant gene mutations and signaling pathways have also been applied in the treatment of vascular malformations, and previous studies have shown that the mTOR inhibitor rapamycin is effective and now widely used in the treatment of low-flow vascular malformations. The PI3K inhibitor alpelisib is also promising in the treatment of venous malformations, and the MAPKK inhibitor trametinib has shown good results in the treatment of arteriovenous malformations. Therefore, traditional therapies supplemented by targeted drugs may bring new breakthroughs to the treatment of vascular malformations.

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i^-/-) arrested tooth root formation, indicated by truncated Hertwig's epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i^-/- mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i^-/- mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i^-/- odontoblasts. Through treating pulp precursor cells with Atp6i^-/- or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i^-/- OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i^-/- mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.
Female ; Animals ; Mice ; Transforming Growth Factor beta1 ; Odontoblasts ; Culture Media, Conditioned ; Cell Differentiation ; Signal Transduction ; Disease Models, Animal ; Tooth Root

Objective　 : To evaluate the implementation, application, and problems and suggestions of the Radiation Shield- ing Requirements in Room of Radiotherapy Installations—Part 1: General Principle (GBZ/T 201.1—2007) through a survey of relevant personnel in radiation health technical service institutions, and to provide a scientific basis for further revision and implementation of this standard. Methods: A questionnaire survey was conducted among randomly selected per- sonnel in radiation health technical services across China, which mainly investigated the awareness, training, application, and revision suggestions related to the GBZ/T 201.1—2007. The results were aggregated and analyzed. Results: A total of 184 evaluation questionnaires on the GBZ/T 201.1—2007 were collected from technical service staff in 25 provinces. Among the responders, 64.1% thought that the standard had been widely applied; 91.8% thought that the standard could meet work needs; only 54.3% ever received relevant training on the standard; 68.5% used the standard once or more per year; 33.7% thought that the standard needed to be revised. Conclusion The personnel in radiation health technical services have a high awareness rate of the GBZ/T 201.1—2007 and its contents, but their familiarity with and application of the standard need to be improved. Relevant departments should strengthen the training and promotion of the standard, and part of the standard should be revised.

BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
Humans ; Female ; Genomics ; Carcinogenesis ; Carcinoma ; Breast Neoplasms ; Cell Transformation, Neoplastic ; Nucleotides ; Tumor Microenvironment