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Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease that affects multiple organs and systems throughout the body. TSC-associated kidney disease is the leading cause of death in adult TSC patients. This article retrospectively analyzed the characteristics of one TSC-related renal giant angiomyolipoma(RAML)treated with surgery. The patient, 25 years old, was diagnosed with tuberous sclerosis complex in 2000 due to multiple maculopapular rashes on both cheeks. At a regular follow-up in July 2019, imaging examinations revealed a tumor in the left lower quadrant with a maximum cross-sectional area of 16 cm×7 cm. Genetic testing showed a loss of heterozygosity in the EX18_ 41 of TSC2. After the diagnosis was confirmed, open left partial nephrectomy was performed, during which multiple tumors were found on the kidney surface and the largest one was located on the ventral side with a diameter of approximately 20 cm. After the renal artery was occluded, kidney tumors were completely enucleate. Postoperative pathological confirmed the diagnosis of angiomyolipoma. This case provides a reference for the treatment of TSC-related renal giant hamartoma.
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Human-animal chimera technology is increasingly applied to large animals. It is highly possible to cultivate human organs in pigs for transplantation in the future. Chimeric animals contain more and more human materials and are present in their brains and reproductive systems, which may humanize them and give them a higher moral status and even dignity. It raises an important ethical question: should such chimeric animals be created? If so, how they should be treated. It is not convincing to refute the research of human-animal chimera with the arguments of destroying natural order, unnatural and moral chaos. But the non-identity view holds that scientific research makes the lives of chimeric animals more valuable and that they are not actually harmed because their only other options do not exist. The answers to these ethical questions can resolve the ethical risks arising from the research of human-animal chimera.
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The construction of the scientific and technological ethics management system is crucial to ensure the healthy development of scientific research, and is also the premise and foundation for the scientific and technological innovation and "double first-class" construction of colleges and universities. This paper through the investigation of college life science and medical research ethics committees’ relevant situation, concentrated on the comparative analysis of the construction of ethics training system to identify problems and shortcomings, combined with the work example of Peking University and the current development trend of life science and medical research, some suggestions, including take advantage of the combination of medical services, teaching and research at universities, were put forward to provide possible reference for further updating of the science and technology ethics management in colleges and universities.
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Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease that affects multiple organs and systems throughout the body. TSC-associated kidney disease is the leading cause of death in adult TSC patients. This article retrospectively analyzed the characteristics of one TSC-related renal giant angiomyolipoma(RAML)treated with surgery. The patient, 25 years old, was diagnosed with tuberous sclerosis complex in 2000 due to multiple maculopapular rashes on both cheeks. At a regular follow-up in July 2019, imaging examinations revealed a tumor in the left lower quadrant with a maximum cross-sectional area of 16 cm×7 cm. Genetic testing showed a loss of heterozygosity in the EX18_ 41 of TSC2. After the diagnosis was confirmed, open left partial nephrectomy was performed, during which multiple tumors were found on the kidney surface and the largest one was located on the ventral side with a diameter of approximately 20 cm. After the renal artery was occluded, kidney tumors were completely enucleate. Postoperative pathological confirmed the diagnosis of angiomyolipoma. This case provides a reference for the treatment of TSC-related renal giant hamartoma.
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Objective To investigate the effects of microsurgical varicocelectomy on testicular function and sexual function in patients with varicocele.Methods The clinical data of 90 patients with varicocele admitted to our hospital were retrospectively analyzed,and the patients were divided into the laparoscopic group(received laparoscopic varicocelectomy)and the microscopic group(received microsurgical varicocelectomy)according to different surgical methods,with 45 cases in each group.The testicular function and sexual function related indexes including sperm density,normal sperm ratio,rate of sperm motility(grades a+b),forward motility sperm rate,international index of erectile function-5(IIEF-5)score,and the levels of testosterone,follicle-stimulating hormone,luteinizing hormone,and androgen levels before and 6 months after surgery in the two groups were compared.The incidence of complications and recurrence 6 months after surgery in the two groups were counted.Results Compared with those before surgery,the sperm density,forward motility sperm rate,rate of sperm motility(grades a+b),normal sperm ratio,IIEF-5 score,testosterone level,and androgen level 6 months after surgery of patients in the two groups were significantly increased(P<0.05),and the levels of luteinizing hormone and follicle-stimulating hormone were decreased(P<0.05).Compared with the laparoscopic group,the levels of follicle-stimulating hormone and luteinizing hormone,and incidence of complications 6 months after surgery of patients in the microscopic group were decreased(P<0.05),and the levels of testosterone and androgens,and IIEF-5 score 6 months after surgery were increased(P<0.05).There was no significant difference in the recurrence rate between the two groups(P>0.05).Conclusion Microsurgical varicocelectomy can improve the testicular function and sexual function of patients with varicocele,with a low incidence of complications.
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ObjectiveThe scale of microalgae farming industry is huge. During farming, it is easy for microalgae to be affected by miscellaneous bacteria and other contaminants. Because of that, periodic test is necessary to ensure the growth of microalgae. Present microscopy imaging and spectral analysis methods have higher requirements for experiment personnel, equipment and sites, for which it is unable to achieve real-time portable detection. For the purpose of real-time portable microalgae detection, a real-time microalgae detection system of low detection requirement and fast detection speed is needed. MethodsThis study has developed a microalgae detection system based on deep learning. A microscopy imaging device based on bright field was constructed. With imaged captured from the device, a neural network based on YOLOv3 was trained and deployed on microcomputer, thus realizing real-time portable microalgae detection. This study has also improved the feature extraction network by introducing cross-region residual connection and attention mechanism and replacing optimizer with Adam optimizer using multistage and multimethod strategy. ResultsWith cross-region residual connection, the mAP value reached 0.92. Compared with manual result, the detection error was 2.47%. ConclusionThe system could achieve real-time portable microalgae detection and provide relatively accurate detection result, so it can be applied to periodic test in microalgae farming.
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@#The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells (NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells. TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies (mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC) patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.
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Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
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Potassium Channels, Inwardly Rectifying/metabolism , Kidney Tubules, Distal/metabolism , Potassium/metabolism , Epithelial Sodium Channels/metabolism , DietABSTRACT
The chemical compositions of Rodgersia aesculifolia were isolated and purified using a combination of silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography, and semi-preparative HPLC. The structures were determined according to the physicochemical properties and spectroscopic data. The MTT method and the ABTS kit were used to measure the cytotoxicity and antioxidant capacity of all isolates, respectively. Thirty-four compounds were isolated from R. aesculifolia and elucidated as stigmastane-6β-methoxy-3β,5α-diol(1), stigmastane-3β,5α,6β triol(2), β-sitosterol(3), β-daucosterol(4), stigmast-4-en-3-one(5), bergenin(6), 11-β-D-glucopyranosyl-bergenin(7), 11-O-galloybergenin(8), 1,4,6-tri-O-galloyl-β-D-glucose(9), gallic acid(10), 3,4-dihydroxybenzoic acid methyl ester(11), ethyl gallate(12), ethyl 3,4-dihydroxybenzoate(13), caffeic acid ethyl ester(14), p-hydroxybenzeneacetic acid(15), 4-hydroxybenzoic acid(16), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one(17), 3,7-dimethyl-2-octene-1,7-diol(18), crocusatin-B(19), neroplomacrol(20), geniposide(21), 3-hydroxyurs-12-en-27-oic acid(22), 3β-trans-p-coumaroyloxy-olean-12-en-27-oic acid(23), aceriphyllic acid G(24), isolariciresinol(25), trans-rodgersinine B(26), cis-rodgersinine A(27), neo-olivil(28),(7S,8R)-dihydro-3'-hydroxy-8-hydroxy-methyl-7-(4-hydroxy-3-methoxy phenyl)-1'-benzofuranpropanol(29), 5,3',4'-trihydroxy-7-methoxyflavanone(30), quercetin 3-rutinoside(31), catechin-[8,7-e]-4β-(3,4-dihydroxy-phenyl)-dihydro-2(3H)-pyranone(32), ethyl α-L-arabino-furanoside(33), and l-linoleoylglycerol(34). One new compound was discovered(compound 1), 25 compounds were first isolated from R. aesculifolia, and 22 compounds were first isolated from the Rodgersia plant. The results indicated that compounds 22-24 possessed cytotoxicity for HepG2, MCF-7, HCT-116, BGC-823, and RAFLS cell lines(IC_(50) ranged from 5.89 μmol·L~(-1) to 20.5 μmol·L~(-1)). Compounds 8-14 and 30-32 showed good antioxidant capacity, and compound 9 showed the strongest antioxidant activity with IC_(50) of(2.00±0.12) μmol·L~(-1).
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Antioxidants/analysis , Silica Gel/analysis , Plant Roots/chemistryABSTRACT
Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.
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Polyetheretherketone (PEEK) as a new type of thermoplastic engineering plastic, has good biological activity, elastic modulus close to human cortical bone and radiation permeability, and has been widely used in medical field. This study aims to explore the safety and clinical efficacy of using 3D printing personalized PEEK materials to repaire scapular bone defects after bone tumor resection. A total of 6 patients who underwent the implantation of 3D printed PEEK scapular prosthesis from January 2020 to December 2021 in Yunnan Cancer Hospital were retrospectively analyzed. There were 3 males and 3 females, with age ranged from 14 to 52 years. There were 1 case of synovial sarcoma, 1 of Ewing's sarcoma, and 4 of chondrosarcoma. PEEK prosthesis was designed and fabricated based on CT data before surgery. Tumor resection and prosthesis replacement were performed under the premise of ensuring safe surgical boundaries, including 2 cases of total scapular prosthesis replacement and 4 cases of partial scapular prosthesis replacement. The operation time was 90-170 min, and the intraoperative blood loss was 100-400 ml. All 6 patients received satisfactory follow-up, with a tumor progression free survival time of 16-28 months. No tumor recurrence or metastasis was observed, and all patients survived tumor free. At last follow-up, the Constant-Murley shoulder joint score was a minimum of 62 points and a maximum of 68 points. The Japanese Orthopaedic Association's shoulder joint score was 63 points minimum and 78 points maximum. Computer-aided design 3D printing PEEK material prosthesis has certain advantages in the treatment of scapular tumor limb salvage. It has light weight, well adapted, relatively simple installation, good histocompatibility, and can obtain a better appearance and function of the shoulder joint after operation. It can become one of the options for limb salvage treatment of scapular tumor.
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Objective:To introduce a new surgical procedure for harvesting an iliac bone flap with deep iliac circumflex vessels—"retrograde anatomical method", and report the effect of preliminary application with this procedure.Methods:From June 2018 to May 2021, 15 patients who admitted in the Department of Hand and Microsurgery, Xiangya Hospital of Central South University received surgeries of iliac bone flap with deep iliac circumflex artery by "retrograde anatomical method". During the surgery, appropriate cutaneous perforators or muscular branches were found near the medial side of the iliac bone of iliac tubercle. The branches were dissected from surface inwards to the starting point of deep circumflex iliac blood vessel with microsurgery and micro Schlieren forceps. The iliac bone flap was chiselled out, inserted into femoral head, and then anastomosed with the transverse branches of deep circumflex iliac blood vessel and lateral circumflex femoral blood vessel. All patients were included in the postoperative follow-up at the outpatient clinic to evaluate the preliminary effect of this procedure. Harris scores before and after surgery were assessed with paired t test. P<0.05 was considered statistically significant. Results:The length of iliac bone flap was at 3.0-5.0(4.0±0.5) cm, and the length of vascular pedicle was at 4.0-7.0(5.3±1.0) cm. The time of iliac bone flap harvest was 35-55(45.0±6.1) minutes. During the operation, the success rate of harvesting iliac bone flap with deep iliac circumflex artery was 100%, and blood had oozed out of bone surface before the pedicle of all iliac bone flaps was cut-off. The volume of intraoperative autologous blood transfusion was 100-400(226.7±78.2) ml. One patient suffered from traction injury of lateral femoral cutaneous nerve in the operation. The numbness of anterolateral thigh area occurred on the 1st day after the surgery, and relieved 4 months later. Other 14 patients did not suffer from postoperative numbness in the area of anterolateral thigh. The amount of drainage from donor site for the iliac bone flap was 50-70 ml[(62.7±7.5) ml in average] after surgery. Incisions at the donor sites of iliac bone flap healed in stage I. Postoperative follow-up lasted between 3 months and 3 years. There was no incision hernia and other complication in the donor sites of the iliac bone flap. There was a significant difference in Harris scores between at 9, 12 and 18 months after surgery and that before the surgery, respectively( P<0.05). After 18 months, Harris score were at a better level. Conclusion:The "retrograde anatomical method" can quickly determine the nutrient vessels of an iliac bone flap with deep circumflex iliac vessels. The surgical procedure is relatively simple with safe and reliable anatomy. Donor site damage and postoperative complications are greatly minimised. This surgical technique can be considered to be applied clinically.
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Objective To propose a total time prediction method of MRI examination based on BP neural network.Methods The clinical data of MRI equipment in some tertiary grade A hospital was mined deeply.Totally 63 examination sites and 26 examination methods were combined into several examination sequences,and the examination sequence vector and total examination time were used as the input and output of BP neural network,respectively,so as to construct a BP neural network model.The BP neural network model established was compared with the ridge regression model and Lasso regression model with the mean absolute error(MAE)as the evaluation index when used for predicting MRI examinations.Results The BP neural network model behaved better than the ridge regression model and Lasso regression model with the predicted value close to the measured value and MAE being 53.14 s.Conclusion The proposed method accurately predicts the total MRI examination time and can assist hospital staff in scheduling patient examinations.[Chinese Medical Equipment Journal,2023,44(10):13-16]
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A 62-year-old female patient was admitted to the hospital with a mass in the left kidney finding during medical check-up by color doppler imaging 1 day before admission. Unenhanced and contrast enhanced CT of urinary tract showed a mass on the inferior pole of left kidney. The left kidney cancer was diagnosed preoperatively and a left radical nephrectomy was performed laparoscopically. Postoperative diagnosis was thyroid-like follicular carcinoma of the left kidney and suspected derived from thyroid tumors by metastasis. Color doppler and CT examination of thyroid confirmed a mass in the right thyroid. Thyroid fine needle aspiration confirmed follicular carcinoma of the right thyroid, and follicular carcinoma of the right thyroid was diagnosed subsequently. The patient underwent radical resection of thyroid cancer according to the intraoperative frozen-section pathological results, and postoperative pathological diagnosis confirmed follicular carcinoma of the right thyroid and papillary carcinoma of the left thyroid. I 131 radio-iodine therapy and L-thyroxine tablets were administered based on the postoperative diagnosis of thyroid collision tumor. Seven months after surgery, the follow-up CT scan revealed no recurrence or metastases for renal area. Nine months later, no thyroid carcinoma recurrence was observed and no significant abnormality was detected in I 131 image. The composition of collision tumor is complicated and origin is unknown. Thyroid collision tumor with kidney metastasis is extremely rare, and the prognosis is better than primary renal carcinoma. The diagnosis depends on pathological examination.
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Recent studies have found that the pathological changes of Tau proteinopathy, such as Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), involve transmission or circulatory disturbance of synaptic vesicles. This article reviews the relations of AD/PSP with circulatory disturbance of synaptic vesicles and explore the pathogenesis of these diseases, aiming to provide a new perspective for new therapeutic drugs.
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Objective To analyze Pseudomonas aeruginosa (PA) infection and drug resistance in the elderly with respiratory tract infection, so as to provide a basis for the control of nosocomial infection and rational use of antibiotics. Methods The samples from elderly inpatients with respiratory tract infection were collected between March 2020 and March 2022. PA infection/colonization were investigated, and the drug resistance of pathogens was determined according to CLSI criteria (2019 version). Results There were 123 strains of PA isolated from the sputum and bronchoscopy lavage fluid of elderly patients with respiratory tract infection. The main departments with positive PA detection were respiratory department, ICU ward and neurology department. The difference of PA detection in different years was not statistically significant (P>0.05). The proportion of nosocomial infection in 2021 was lower than that in 2020 (44.44% vs 63.33%, c2=4.410, P=0.036). The resistance rate of 123 isolated PA strains to piperacillin was >90.00%, and they were resistant to ceftazidime, cefotaxime, cefepime, aztreonam and gentamicin to varying degrees. There was no significant difference in resistance rate of PA to antibiotics in different years (P>0.05). In the 123 strains of pathogens, there were 17 strains (13.82%) of carbapenem-resistant PA, and their resistance to common antibiotics was significantly higher than that of carbapenem-sensitive PA (P<0.05). Conclusion The main pathogen of nosocomial infection is PA, and the proportion of nosocomial infection shows a downward trend. The detection rate of carbapenem-resistant PA is high. In clinical treatment, targeted antibiotics can be applied.
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Objective To explore the effect of shionone(SHI)on motor function in the mouse model of spinal cord injury(SCI)and probe into the underlying molecular mechanism.Methods C57BL/6 mice were treated to induce the SCI model and then assigned into a model group(SCI group),a SCI+SHI group,and a sham surgery(control)group.The Basso mouse scale(BMS)score was determined to evaluate the recovery of motor function in SCI mice.Hematoxylin-eosin(HE)staining,Nissl staining,and immunofluorescence staining were employed to examine the fibrosis,morphological changes of neurons,and neuron apoptosis in the spinal cord tissue of SCI mice,respectively.The mouse hippocampal neuronal cell line HT22 was cultured in vitro and then classified into tumor necrosis factor α(TNF-α)induction and SHI groups.Western blotting was employed to determine the expression of apoptosis-associated proteins.Network pharmacology,gene ontology annotation,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were employed to predict the possible molecular targets and signaling pathways of SHI in promoting functional recovery from SCI.Furthermore,the prediction results were verified by in vitro and in vivo experiments.Results Compared with the SCI group,the SCI+SHI group showed increased BMS score on days 21,28,35,and 42(P=0.003,P=0.004,P=0.023,and P=0.007,respectively),reduced area of spinal cord fibrosis(P=0.021),increased neurons survived(P=0.001),and down-regulated expression of cleaved cysteine aspastic acid-specific protease 3(cleaved Caspase-3)(P=0.017).Compared with the TNF-α group,the SHI group presented down-regulated expression levels of cleaved Caspase-3 and Bax(P=0.010,P=0.001)and up-regulated expression level of Bcl-2(P=0.001).The results of bioinformatics analysis showed that SHI might improve the motor function of SCI mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.The results of in vivo and in vitro experiments showed that SHI inhibited the phosphorylation of PI3K and Akt in SCI mice or HT22 cells exposed to TNF-α(all P<0.05).The number of apoptotic HT22 cells after treatment with insulin-like growth factor 1 was higher than that in the SHI group(P=0.003).Conclusion SHI may inhibit neuron apoptosis via the PI3K/Akt signaling pathway,thereby promoting the recovery of motor function in SCI mice.
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Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Caspase 3/metabolism , Phosphatidylinositol 3-Kinases , Tumor Necrosis Factor-alpha/metabolism , Mice, Inbred C57BL , Spinal Cord Injuries , Apoptosis , Neurons/pathology , FibrosisABSTRACT
METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
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Animals , Mice , Methylation , Chromatin , Histones/metabolism , RNA, Messenger/genetics , Methyltransferases/metabolism , RNA/metabolismABSTRACT
OBJECTIVE@#To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine.@*METHODS@#Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting.@*RESULTS@#Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway.@*CONCLUSIONS@#Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.
Subject(s)
Male , Animals , Swine , Phospholipid Hydroperoxide Glutathione Peroxidase , Ferroptosis , Brain Injuries , Glutathione , Cardiopulmonary Resuscitation , Ligases , IronABSTRACT
OBJECTIVE@#This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD).@*METHODS@#The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted.@*RESULTS@#Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression.@*CONCLUSION@#Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.