1.Evaluation of Simulated Weightlessness Model of Hindlimb Unloading Miniature Pigs and Their Tissue Damage
Yingxin TU ; Yilan JI ; Fei WANG ; Dongming YANG ; Dongdong WANG ; Zhixin SUN ; Yuexin DAI ; Yanji WANG ; KAN GUANGHAN ; Bin WU ; Deming ZHAO ; Lifeng YANG
Laboratory Animal and Comparative Medicine 2024;44(5):475-486
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.
2.Effects of Brucea javanica oil emulsion injection on the expression of PDL-1 and the sensitivity of PD-1 monoclonal antibody in lung adenocarcinoma tumor-bearing mice
Wenjing YANG ; Qian ZHANG ; Chunjiang LI ; Lihong ZHOU ; Xin JIN ; Deming MENG ; Jiang JIA
Immunological Journal 2024;40(5):458-463,484
The study was aimed to assess the impact of Brucea javanica oil emulsion(BJOE)on the responsiveness of programmed death receptor-1(PD-1)monoclonal antibody to lung adenocarcinoma in mice.The experimental approach involved subcutaneously inoculating Lewis's lung adenocarcinoma(LLC)cells into C57BL/6 mice,which were then divided into four groups:model group,25 ml·kg-1 BJOE group,10 mg·kg-1 PD-1 group,and combination group(25 ml·kg-1 BJOE and 10 mg·kg-1 PD-1).Tumor volume,mass,and inhibition rate were evaluated;the apoptosis within tumor tissue was detected by TUNEL staining;CD4+and CD8+T cell proportions within tumor tissues were analyzed by flow cytometry;the levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and granzyme B in tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA).Additionally,LLC cells were categorized into a control group and three BJOE treatment groups(10,30,50 μl·ml-1),and programmed death ligand 1(PD-L1)expression in tumor tissues and LLC cells were assessed by Western blotting.Data showed that as compared with the model group,PD-1 monoclonal antibody alone did not significantly alter tumor volume,tumor mass,CD4+and CD8+T cell proportions,cytokine levels(IFN-γ,TNF-α,Granzyme B),or apoptosis in lung cancer-bearing mice.However,BJOE treatment reduced tumor volume and mass,enhanced CD4+and CD8+T cell proportions,increased cytokine levels,and augmented apoptosis(all P<0.05).Furthermore,the combination therapy of BJOE and PD-1 monoclonal antibody yielded significantly greater reductions in tumor volume and mass,with heightened CD4+and CD8+T cell proportions,cytokine levels,and apoptosis compared to either treatment alone(all P<0.05).Both BJOE treatment and the combination therapy significantly upregulated PD-L1 protein expression in tumor tissues compared to the model or PD-1 monoclonal antibody groups(P<0.05).Similarly,BJOE treatment at all tested concentrations significantly increased PD-L1 protein expression in LLC cells as compared to the control group(P<0.05).In conclusion,BJOE could upregulate PD-L1 expression in LLC cells and enhance the sensitivity of lung adenocarcinoma-bearing mice to PD-1 monoclonal antibodies.
3.Genetic analysis of two families with abnormal findings upon prenatal diagnosis
Wenjing WANG ; Chenchun REN ; Weiwei YANG ; Mingyan JU ; Haixia ZHANG ; Deming LI ; Yuexiang ZHANG
Chinese Journal of Medical Genetics 2024;41(6):753-757
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.
4.Analysis of risk factors and construction of prediction model for infectious stones in western Fujian Province
Quanfang HE ; Peichang WANG ; Huaxu YANG ; Hua TANG ; Qifu CHEN ; Deming WANG ; Jinsong LIN ; Yefu LIN
Journal of Clinical Medicine in Practice 2024;28(10):24-28
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 (
5.Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors.
Xinyu LI ; Weining MA ; Hui LIU ; Deming WANG ; Lixin SU ; Xitao YANG
Chinese Medical Journal 2023;136(21):2621-2631
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
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Female
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Genomics
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Carcinogenesis
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Carcinoma
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Breast Neoplasms
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Cell Transformation, Neoplastic
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Nucleotides
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Tumor Microenvironment
6.Assessment of Radiation Shielding Requirements in Room of Radiotherapy Installations—Part 1: General Principle (GBZ/T 201.1—2007): A survey of relevant personnel in technical service institutions
Hezheng ZHAI ; Quan WU ; Yunfu YANG ; Wei LI ; Xiaojun CHENG ; Chuanpeng HU ; Hailiang LI ; Zechen FENG ; Ribala HA ; Xiao XU ; Deming LIU ; Chuanwen WANG ; Chunyong YANG
Chinese Journal of Radiological Health 2023;32(5):479-483
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.
7.Epidemiological characteristics of influenza in Fuling district of Chongqing of China in 2010-2019
Xiaoli KANG ; Yu XIANG ; Lei FENG ; Yiyao CHEN ; Hong PAN ; Qiaolei LIU ; Deming YANG
Chinese Journal of Primary Medicine and Pharmacy 2022;29(4):584-589
Objective:To investigate the characteristics and change law of influenza in Fuling District of Chongqing in 2010-2019, and to provide a scientific basis for the pre-control of influenza.Methods:We performed an epidemiological analysis on the data of influenza-like illness reported by Fuling District influenza surveillance sentinel hospitals in Chongqing in 2010-2019.Results:In 2010-2019, a total of 42 169 cases of influenza-like illness were reported in Fuling District, with an average treatment rate of 1.22%. The activity of influenza-like illness peaked in winter, spring, and summer. There were 22 788 cases in the group of cases aged < 5 years, accounting for 50.4%. In 2010-2019, a total of 8049 pharyngeal swabs were collected to screen for influenza-like illness, with a positive rate of 14.52%. Influenza virus A H3 positive rate was highest, accounting for 37.98%, followed by influenza virus B BV positive rate, accounting for 30.80%. The highest influenza virus-positive rate was reported in January (26.34%), followed by November (24.85%).Conclusion:Influenza in the Fuling district of Chongqing mainly occurs in winter, spring, and summer. Influenza virus A H3 is the dominant strain. Children and school students are prone to develop influenza-like illnesses. We should continue to strengthen the monitoring of influenza strains, greatly promote vaccination, and strengthen the monitoring and prevention of influenza-like illness among susceptible populations.
8.Embolization of congenital arteriovenous fistula in the parotid region using coils and absolute ethanol
Deming WANG ; Lixin SU ; Zhenfeng WANG ; Lianzhou ZHENG ; Xitao YANG ; Mingzhe WEN ; Xindong FAN
Chinese Journal of Plastic Surgery 2021;37(8):907-911
Objective:To evaluate the clinical effect of embolization of congenital parotid arteriovenous fistula(AVF) using coils and absolute ethanol.Methods:From January 2015 to December 2019, 8 patients with congenital AVF in parotid region were admitted to the Department of Interventional Radiology Shanghai Ninth People’s Hospital. AVF was confirmed by angiography of common carotid artery and vertebral artery through femoral artery puncture with Seldinger technique. Using coaxial microcatheter to reach the fistula via artery or using direct percutaneous puncture to reach the dilated vein and introduced microcatheter to the fistula via puncture needle. Combined detachable coils with fiber coils, and used absolute ethanol to occlude the fistula. Then the outcome was evaluated.Results:There were 7 males and 1 female involved in this study. The average age was 28.5 years (3-58 years). All of the 8 patients were confirmed AVF in parotid region by angiography, five on the right and three on the left. The feeder artery was external carotid artery, and the outflow vein was external jugular vein. Among them, 6 patients used coaxial microcatheter to reach the fistula via artery, 2 patients used direct percutaneous puncture after failure via transarteral approach. All the 8 patients were treated with absolute ethanol, the total amount of which was 17.4 ml on average. After embolization, the external carotid angiography demonstrated that the fistula was completely occluded, the branches of the external carotid artery at the distal end of the fistula were normal, and there was no obvious reflux vein. After the operation, all the patients had no pulsation and tremor. The external jugular vein dilation disappeared in 4 patients. One patient had temporary facial paralysis on the same side of the operation area. The symptoms disappeared three days after treatment. This patient had undergone coils exposed three months after operation. After local debridement, the exposed coils were removed and the wound healed. The 8 patients were followed up for 6-12 months without recurrence.Conclusions:Embolization with coils combined with absolute ethanol is safe and affective treatment for congenital parotid AVF.
9.Embolization of congenital arteriovenous fistula in the parotid region using coils and absolute ethanol
Deming WANG ; Lixin SU ; Zhenfeng WANG ; Lianzhou ZHENG ; Xitao YANG ; Mingzhe WEN ; Xindong FAN
Chinese Journal of Plastic Surgery 2021;37(8):907-911
Objective:To evaluate the clinical effect of embolization of congenital parotid arteriovenous fistula(AVF) using coils and absolute ethanol.Methods:From January 2015 to December 2019, 8 patients with congenital AVF in parotid region were admitted to the Department of Interventional Radiology Shanghai Ninth People’s Hospital. AVF was confirmed by angiography of common carotid artery and vertebral artery through femoral artery puncture with Seldinger technique. Using coaxial microcatheter to reach the fistula via artery or using direct percutaneous puncture to reach the dilated vein and introduced microcatheter to the fistula via puncture needle. Combined detachable coils with fiber coils, and used absolute ethanol to occlude the fistula. Then the outcome was evaluated.Results:There were 7 males and 1 female involved in this study. The average age was 28.5 years (3-58 years). All of the 8 patients were confirmed AVF in parotid region by angiography, five on the right and three on the left. The feeder artery was external carotid artery, and the outflow vein was external jugular vein. Among them, 6 patients used coaxial microcatheter to reach the fistula via artery, 2 patients used direct percutaneous puncture after failure via transarteral approach. All the 8 patients were treated with absolute ethanol, the total amount of which was 17.4 ml on average. After embolization, the external carotid angiography demonstrated that the fistula was completely occluded, the branches of the external carotid artery at the distal end of the fistula were normal, and there was no obvious reflux vein. After the operation, all the patients had no pulsation and tremor. The external jugular vein dilation disappeared in 4 patients. One patient had temporary facial paralysis on the same side of the operation area. The symptoms disappeared three days after treatment. This patient had undergone coils exposed three months after operation. After local debridement, the exposed coils were removed and the wound healed. The 8 patients were followed up for 6-12 months without recurrence.Conclusions:Embolization with coils combined with absolute ethanol is safe and affective treatment for congenital parotid AVF.
10.Animal experimental study of endoscopic cholecystolithotomy after lumen-apposing metal stent implantation (with video)
Junjie YANG ; Xiongchang LIU ; Xiaoqin CHEN ; Tianrang LIU ; Qiyong ZHANG ; Deming WU ; Chengpeng DONG ; Dacheng JIN ; Yunjiu GOU
Chinese Journal of Digestive Endoscopy 2020;37(3):200-204
Objective:To investigate the safety and feasibility of endoscopic cholecystolithotomy after endoscopic ultrasonography (EUS)-guided lumen-apposing metal stent (LAMS) implantation in animals.Methods:Six miniature pigs of 30-35 kg were selected to laparotomy under intravenous anesthesia. Two to four sterile human stones with diameter of 0.8-2.0 cm were implanted in their gallbladder. After successful modeling, LAMS was implanted between the stomach and gallbladder under the guidance of EUS. Ultrafine endoscope was used to search and remove stones after passing the gastric stent into the gallbladder. Endoscopic sphincterotomy (EST) and endoscopic retrograde biliary drainage (ERBD) was performed to prevent bile leakage. And then ordinary endoscope was used to remove LAMS and close the wound. The success rate, operation time, and incidence of complications were analyzed.Results:Five pigs were successfully implanted with LAMS, and the ultrafine endoscope entered the gallbladder smoothly. Small stones were removed from the stone basket, and large stones were completely removed after laser lithotripsy. The total operation time was 87-128 min. No postoperative complications such as bleeding, perforation, infection, or biliary fistula were observed. Failure in 1 pig was due to the first EST plus ERBD, resulting in rapid reduction of gallbladder volume and away from the gastric cavity leading to puncture difficulties.Conclusion:Endoscopic cholecystolithotomy after EUS-guided LAMS implantation is safe and feasible, and may provide animal experimental evidence for potential therapeutic approach for patients with difficulty in cholecystectomy.


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