Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To address the quality problems caused by high porosity in the preparation of dental cobalt-chrome alloy prosthetics based on selective laser melting(SLM)technology,we investigated the influence mechanism of different forming process parameters on the microstructure and properties of the materials.Moreover,the range of form-ing process parameters that can effectively reduce defects was precisely defined.Methods The effects of laser power,scanning speed,and scanning distance on the pore properties,surface roughness,and hardness of dental cobalt-chrome al-loy were investigated by adjusting the printing parame-ters in the process of SLM.Through metallographic anal-ysis,image analysis,and molten pool simulation,the pore formation mechanism was revealed,and the relation-ship between the porosity and energy density of SLM dental cobalt-chrome alloy was elucidated.Results When the linear energy density was higher than 0.18 J/mm,the po-rosity defect easily appeared at the bottom of the molten pool.When the laser energy density was lower than 0.13 J/mm,defects occurred in the gap of the molten pool due to insufficient melting of powder.In particular,when the linear energy density exceeded the threshold of 0.30 J/mm or was below 0.12 J/mm,the porosity increased significantly to more than 1%.In addition,we observed a negative correlation between free surface roughness and energy density and an inverse re-lationship between macroscopic hardness and porosity.Conclusion On the basis of the conditions of raw materials and molding equipment used in this study,the key process parameters of SLM of molding parts with porosity lower than 1%were successfully determined.Specifically,these key parameters included the line energy density,which ranged from 0.13 J/mm to 0.30 J/mm,and the scan spacing should be strictly controlled below 90 μm.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective: To examine the safety and effectiveness of inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE). Methods: Totally 269 patients admitted to the Anhui Provincial Hospital of Anhui Medical University who underwent IVMTE (IVMTE group, n=47) or thoracoscopy combined with minimally invasive Mckeown esophageal cancer resection (MIME group, n=222) from September 2017 to December 2021 were analyzed retrospectively. There were 31 males and 16 females in IVMTE group, aged (68.6±7.5) years (range: 54 to 87 years). There were 159 males and 63 females in MIME group, aged (66.8±8.8) years (range: 42 to 93 years). A 1∶1 match was performed on both groups by propensity score matching, with 38 cases in each group. The intraoperative conditions and postoperative complication rates of the two groups were compared by t test, Wilcoxon rank, χ² test, or Fisher exact probability method. Results: Patients in IVMTE group had less intraoperative bleeding ((96.0±39.2) ml vs. (123.8±49.3) ml, t=-2.627, P=0.011), shorter operation time ((239.1±47.3) minutes vs. (264.2±57.2) minutes, t=-2.086, P=0.040), and less drainage 3 days after surgery (85(89) ml vs. 675(573) ml, Z=-7.575, P<0.01) compared with that of MIME group. There were no statistically significant differences between the two groups in terms of drainage tube-belt time, postoperative hospital stay, and lymph node dissection stations and numbers (all P>0.05). The incidence of Clavien-Dindo grade 1 to 2 pulmonary infection (7.9%(3/38) vs. 31.6%(12/38), χ²=6.728, P=0.009), total complications (21.1%(8/38) vs. 47.4%(18/38), χ²=5.846, P=0.016) and total lung complications (13.2%(5/38) vs. 42.1%(16/38), χ²=7.962, P=0.005) in the IVMTE group were significantly lower. Conclusion: Inflatable video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopic esophagectomy is safe and feasible, which can reach the same range of oncology as thoracoscopic surgery.
Male ; Female ; Humans ; Retrospective Studies ; Esophagectomy/methods* ; Treatment Outcome ; Laparoscopy ; Thoracoscopy ; Lymph Node Excision/methods* ; Esophageal Neoplasms/surgery* ; Postoperative Complications

OBJECTIVE To investigated the anti-de-pressant effects of the fruit Areca catechu L.(ACL)and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress(CUMS).METHODS CUMS was induced in rats to establish a depression animal model for 28 d.According to the baseline sucrose preference,the male rats were divided into six different groups.They were treated with parox-etine hydrochloride,ACL,and water once a day until the behavioral tests were performed.The levels of corticoste-rone(CORT),malondialdehyde(MDA),catalase(CAT),and total superoxide dismutase(T-SOD)in serum were de-tected using a commercial kit,and the concentrations of 5-hydroxytryptamine(5-HT)and dopamine(DA)mono-amine neurotransmitters in the brain tissues were detect-ed by liquid chromatography-tandem mass spectrometry.Doublecortin(DCX)expression in the hippocampal den-tate gyrus(DG)was determined by immunofluorescence,and the relative abundance of brain-derived neurotrophic factor(BDNF),TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β of brain tissues were assayed by West-ern blotting.RESULTS ACL markedly increased sucrose preference,decreased the immobility time,and short-ened the feeding latency of CUMS-induced rats.CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters(5-HT and DA)in the hippocampus and cortex of brain tissues and the levels of CORT,MDA,CAT,and T-SOD in serum,whereas ACL administration alleviated these considerable changes.ACL promoted DCX expression in DG and increased the protein levels of BDNF,TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.CONCLUSION Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis,stimulating hippo-campal neurogenesis,and activating the BDNF signaling pathway.

Objective:To evaluate the accuracy of the domestic "Skywalker" surgical robot in implementing personalized lower limb alignment reconstruction scheme in total knee arthroplasty (TKA) and the short-term clinical outcome of robotic assisted TKA.Methods:From September 2020 to January 2021, the data of patients who received surgical robot assisted TKA in 5 clinical centers in China (Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Southwest Hospital affiliated to Third Military Medical University, The Affiliated Hospital of Qingdao University, The First Affiliated Hospital of Chongqing Medical University and Yantai Yuhuangding Hospital, and Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine was the group leader) were prospectively collected and retrospectively analyzed. There were 24 males and 82 females with an average age of 67.6±7.3 years, (range 45-80 years); Average body mass index 26.42±4.31 kg/m 2, all the operation were performed by "Skywalker" surgical robot system according to preoperative design based on CT. The operation time, intraoperative blood loss, hospitalization days and postoperative complications were recorded, and the imaging indexes including hip-knee-ankle (HKA), lateral distal angle of femur (LDFA) and medial proximal angle of tibia (MPTA) measured before and after the operation, implant model indexes (preoperative planning implant model and postoperative implant model) and short-term clinical efficacy indexes [Western Ontario and McMaster Universities (WOMAC) osteoarthritis index] pain score, stiffness score, joint function score, total score and SF-12 score before and 3 months after the operation) were compared. Results:The average follow-up period was 109.60±9.80 d, (range 95-143 d). The average operation time of 106 patients was 105.30±23.22 min; The average intraoperative blood loss was 141.70±58.33 ml; The average length of hospitalization was 5.82±2.80 d. One patient had ischemic stroke after operation, and one patient had abnormal liver function after operation. According to the judgment of the investigator, all of them were not related to the operation. The actual angle error is the difference between the preoperative planning angle and the postoperative measurement angle. The absolute error of 99.1% (105/106) of the HKA angle was within 3°, 90.8% (69/76) of LDFA, 98.7% (75/76) of the MPTA. In 45 patients in one center where data were available, the actual implant models used in all patients were consistent with the preoperative planning size, and there were only differences in version selection such as Asian condyle. WOMAC pain score, joint function score, total score was improved from 7.34±2.85, 25.10±9.85, 34.75±13.02 to 3.34±2.66, 14.68±9.64, 18.66±13.49 before and after operation, respectively, which were statistically significant ( P<0.001) and SF-12 physiological score and psychological score were improved form 27.24±6.42, 30.68±8.26 to 38.83±5.74, 39.36±7.85 before and after operation, respectively, which were statistically significant ( t=7.33, P<0.001; t=4.53, P=0.043). Conclusion:Domestic surgical robot system "Skywalker" can assist the surgeon to achieve accurate and personalized reconstruction of lower limb alignment and achieve satisfactory short-term clinical outcomes. The long-term clinical outcomes of personalized reconstruction and survival rate of implant still need to be further studied.

Oxidative Phosphorylation ; Acetylglucosamine ; Uridine Diphosphate N-Acetylglucosamine/metabolism*

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.
Humans ; Atrial Fibrillation/drug therapy* ; Cardiovascular Diseases ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Atherosclerosis ; Dyslipidemias/drug therapy*