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Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.
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Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic originated in Wuhan, China, in December 2019, the first case diagnosed since January 2020 in Taiwan. The study about the potential impact of the COVID-19 pandemic on event, location, food source, and pathogens of foodborne disease (FBD) is limited in Taiwan. Our aim in this study is to investigate FBD in the context of the COVID-19 pandemic. Materials and Methods: We collected publicly available annual summary data from the FBD dataset in the Taiwan Food and Drug Administration and Certifiable Disease on reported FBD in Taiwan from 2019 to 2020. We used logistic regression to evaluate changes in the occurrence or likelihood of FBD cases and Poisson regression to examine the relative risk (RR) between FBD and climate factors. Results: Similar events occurred in 2019 and 2020, but the total number of FBD cases decreased from 6935 in 2019 to 4920 in 2020. The places where FBD decreased were in schools, hospitals, outdoors, vendors, and exteriors. The top place in FBD shifted from schools to restaurants. The top food source for FBD has changed from boxed food to compound food. Bacillus cereus and Salmonella emerged as the top two observed bacterial pathogens causing FBD. The risk of FBD cases increased with a higher air temperature, with an RR of 1.055 (1.05-1.061, p < 0.001) every 1 °C. Conclusion: The incidence of FBD decreased significantly during the COVID-19 pandemic in Taiwan. This decline may be attributed to protective measures implemented to control the spread of the virus. This shift in locations could be influenced by changes in public behavior, regulations, or other external factors. The study emphasizes the importance of understanding the sources and effectiveness of severe infection prevention policies. The government can use these findings to formulate evidence-based policies aimed at reducing FBD cases and promoting public health. Consumers can reduce the risk of FBD by following safe food handling and preparation recommendations.
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COVID-19 , Doenças Transmitidas por Alimentos , Humanos , COVID-19/epidemiologia , Pandemias , Taiwan/epidemiologia , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Saúde PúblicaRESUMO
Obstract: To explore the application of electrophysiological appropriate technology in perioperative nursing of patients undergoing microdissection testicular sperm extraction. METHODS: A retrospective analysis was conducted on the medical records of 108 patients who underwent testicular incision and sperm extraction under a microscope at our center from May 2022 to June 2023. Among them, 51 patients received routine care and 57 patients received electrophysiological treatment. Evaluate the perioperative nursing effects of appropriate electrophysiological techniques through VAS pain score, Self Rating Anxiety Scale (SAS) score, Pittsburgh Sleep Quality Score, and Kolcaba Comfort Scale. RESULT: Patients who received appropriate electrophysiological interventions had lower VAS pain scores (2.36 ± 1.37 vs 4.16 ± 1.38, P<0.001) than the control group, and higher KOLCABA comfort scale scores than the control group (70.73 ± 19.46 vs 52.06 ± 17.50, P<0.001); There was no statistically significant difference in the Self Rating Anxiety Scale (SAS) score and Pittsburgh Sleep Quality Score. CONCLUSION: Electrophysiological techniques can effectively improve postoperative pain and comfort in patients undergoing testicular incision and sperm extraction under a microscope, and have clinical application value.
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Azoospermia , Ferida Cirúrgica , Humanos , Masculino , Azoospermia/cirurgia , Estudos Retrospectivos , Microdissecção , Enfermagem Perioperatória , Recuperação Espermática , Sêmen , Testículo/cirurgia , Espermatozoides , DorRESUMO
OBJECTIVE: To explore nursing cooperation in surgical collection of the testis tissue from prepubertal male patients for cryopreservation. METHODS: We retrospectively analyzed the methods and effects of perioperative nursing in surgical collection of the testis tissue from 4 prepubertal male patients for cryopreservation in our Center of Reproductive Medicine. Before, during and after operation, we took strict measures in making sterilized ice containers, intraoperative nursing cooperation, protection of the isolated testis tissues and transferring of the samples. RESULTS: Testis tissues were successfully collected from all the 4 prepubertal males, 31, 31, 20 and 34 samples from each case respectively, well protected and subjected to slow cryopreservation after standard processing in the embryo laboratory. CONCLUSION: In surgical collection of the testis tissue for cryopreservation, preparation of sterilized ice containers, intraoperative nursing cooperation and protection and transferring of the samples are essential for standard processing and cryopreservation of the testis tissue in the embryo laboratory.
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Preservação da Fertilidade , Testículo , Humanos , Masculino , Preservação da Fertilidade/métodos , Gelo , Estudos Retrospectivos , Criopreservação/métodosRESUMO
Hepatic cysts are found in heterogeneous disorders with different pathogeneses, of which simple hepatic cysts and polycystic liver diseases are two major types. The process of hepatic cytogenesis for these two diseases is caused by defects in remodelling of the ductal plate during biliary tract development, which is called ductal plate malformation. SOX9 is a transcription factor participating in the process of bile duct development, and thus, its dysregulation may play important roles in hepatic cystogenesis. SEC63 encodes an endoplasmic reticulum membrane protein that is mutated in human autosomal dominant polycystic liver disease. However, the transcriptional regulation of SEC63 is largely unknown. In the present study, a liver-specific Sox9 knockout (Sox9LKO ) mouse was generated to investigate the roles and underlying mechanism of SOX9 in hepatic cystogenesis. We found that hepatic cysts began to be observed in Sox9LKO mice at 6 months of age. The number and size of cysts increased with age in Sox9LKO mice. In addition, the characteristics of hepatic cytogenesis, including the activation of proliferation, absence of primary cilium, and disorder of polarity in biliary epithelial cells, were detected in the livers of Sox9LKO mice. RNAi silencing of SOX9 in human intrahepatic biliary epithelial cells (HIBEpic) resulted in increased proliferation and reduced formation of the primary cilium. Moreover, Sec63 was downregulated in primary biliary epithelial cells from Sox9LKO mice and SEC63 in HIBEpic transfected with siSOX9. Chromatin immunoprecipitation assays and luciferase reporter assays further demonstrated that SOX9 transcriptionally regulated the expression of SEC63 in biliary epithelial cells. Importantly, the overexpression of SEC63 in HIBEpic partially reversed the effects of SOX9 depletion on the formation of primary cilia and cell proliferation. These findings highlight the biological significance of SOX9 in hepatic cytogenesis and elucidate a novel molecular mechanism underlying hepatic cytogenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Cistos/metabolismo , Regulação da Expressão Gênica/fisiologia , Hepatopatias/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição SOX9/metabolismo , Animais , Linhagem Celular , Cistos/patologia , Regulação para Baixo , Humanos , Hepatopatias/patologia , Camundongos , Camundongos KnockoutRESUMO
According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Injeções , SíndromeRESUMO
OBJECTIVE: Autophagy participates in the progression of hepatocellular carcinoma (HCC) and the resistance of HCC cells to sorafenib. We investigated the feasibility of sensitising HCC cells to sorafenib by modulating miR-541-initiated microRNA-autophagy axis. DESIGN: Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the malignant properties and autophagy of human HCC cells. Autophagy was quantified by western blotting of LC3, transmission electron microscopy analyses and confocal microscopy scanning of mRFP-GFP-LC3 reporter construct. Luciferase reporter assays were conducted to confirm the targets of miR-541. HCC xenograft tumours were established to analyse the role of miR-541 in sorafenib-induced lethality. RESULTS: The expression of miR-541 was downregulated in human HCC tissues and was associated with malignant clinicopathologic phenotypes, recurrence and survival of patients with HCC. miR-541 inhibited the growth, metastasis and autophagy of HCC cells both in vitro and in vivo. Prediction software and luciferase reporter assays identified autophagy-related gene 2A (ATG2A) and Ras-related protein Rab-1B (RAB1B) as the direct targets of miR-541. Consistent with the effects of the miR-541 mimic, inhibition of ATG2A or RAB1B suppressed the malignant phenotypes and autophagy of HCC cells. Furthermore, siATG2A and siRAB1B partially reversed the enhancement of the malignant properties and autophagy in HCC cells mediated by the miR-541 inhibitor. More interestingly, higher miR-541 expression predicted a better response to sorafenib treatment, and the combination of miR-541 and sorafenib further suppressed the growth of HCC cells in vivo compared with the single treatment. CONCLUSIONS: Dysregulation of miR-541-ATG2A/RAB1B axis plays a critical role in patients' responses to sorafenib treatment. Manipulation of this axis might benefit survival of patients with HCC, especially in the context of the highly pursued strategies to eliminate drug resistance.
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Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/metabolismo , Sorafenibe/farmacologia , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Estudos de Viabilidade , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Recidiva Local de Neoplasia , FenótipoRESUMO
To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.
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Colite Ulcerativa , Medicamentos de Ervas Chinesas , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Camundongos , Fator A de Crescimento do Endotélio VascularRESUMO
Objective: To investigate the value of micro- dissection testicular sperm extraction (micro-TESE) in the treatment of non-obstructive azoospermia (NOA) in patients with the history of secondary testicular injury. METHODS: Totally, 121 NOA patients with the history of secondary testicular injury underwent micro-TESE in our hospital from September 2014 to December 2017. We analyzed the correlation of the sperm retrieval rate with the causes of testicular injury and compared the outcomes of the ICSI cycles with the sperm retrieved from the NOA males by micro-TESE (the micro-TESE group) and those with the sperm ejaculated from severe oligospermia patients (sperm concentration <1×106/ml, the ejaculate group). Comparisons were also made between the two groups in the female age, two-pronucleus (2PN) fertilization rate, transferrable embryos on day 3 (D3), D3 high- quality embryos, D14 blood HCG positive rate, embryo implantation rate, and clinical pregnancy rate. RESULTS: Testicular sperm were successfully retrieved by micro-TESE in 86.0% of the patients (104/121), of whom 98.4% had the history of orchitis, 75.5% had been treated surgically for cryptorchidism, and 63.6% had received chemo- or radiotherapy. No statistically significant differences were observed between the micro-TESE and ejaculate groups in the 2PN fertilization rate (59.4% vs 69.3%, P > 0.05), D14 blood HCG positive rate (44.6% vs 57.9%, P > 0.05), embryo implantation rate (31.8 %% vs 32.6%, P > 0.05) and clinical pregnancy rate (41.5% vs 48.7%, P > 0.05). However, the rate D3 transferrable embryos was significantly lower in the micro-TESE than in the ejaculate group (40.5% vs 52.2%,P < 0.05), and so was that of D3 high-quality embryos (32.5% vs 42.1%, P < 0.05). CONCLUSIONS: Micro-TESE can be applied as the first choice for NOA patients with the history of secondary testicular injury, but more effective strategies are to be explored for the improvement of ICSI outcomes with the sperm retrieved by micro- TESE.
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Azoospermia/etiologia , Ejaculação , Recuperação Espermática , Testículo/lesões , Criptorquidismo/cirurgia , Implantação do Embrião , Transferência Embrionária , Feminino , Humanos , Masculino , Orquite , Gravidez , Taxa de Gravidez , Contagem de EspermatozoidesRESUMO
BACKGROUND: Locally advanced colon cancer is considered a relative contraindication for minimally invasive proctectomy (MIP), and minimally invasive versus conventional open proctectomy (COP) for locally advanced colon cancer has not been studied. METHODS: We have searched the Embase, Cochrane Library, PubMed, Medline, and Web of Science for articles on minimally invasive (robotic and laparoscopic) and COP. We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42023407029). RESULTS: There are 10132 participants including 21 articles. Compared with COP, patients who underwent MIP had less operation time (SMD 0.48; CI 0.32 to 0.65; I2â =â 0%, Pâ =â .000), estimated blood loss (MD -1.23; CI -1.90 to -0.56; I2â =â 95%, Pâ <â .0001), the median time to semi-liquid diet (SMD -0.43; CI -0.70 to -0.15; I2â =â 0%, Pâ =â .002), time to the first flatus (SMD -0.97; CI -1.30 to -0.63; I2â =â 7%, Pâ <â .0001), intraoperative blood transfusion (RR 0.33; CI 0.24 to 0.46; I2â =â 0%, Pâ <â .0001) in perioperative outcomes. Compared with COP, patients who underwent MIP had fewer overall complications (RR 0.85; CI 0.73 to 0.98; I2â =â 22.4%, Pâ =â .023), postoperative complications (RR 0.79; CI 0.69 to 0.90; I2â =â 0%, Pâ =â .001), and urinary retention (RR 0.63; CI 0.44 to 0.90; I2â =â 0%, Pâ =â .011) in perioperative outcomes. CONCLUSION: This study comprehensively and systematically evaluated the difference between the safety and effectiveness of minimally invasive and open treatment of locally advanced colon cancer through meta-analysis. Minimally invasive proctectomy is better than COP in postoperative and perioperative outcomes. However, there is no difference in oncological outcomes. This also provides an evidence-based reference for clinical practice. Of course, multi-center RCT research is also needed to draw more scientific and rigorous conclusions in the future.
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Neoplasias do Colo , Protectomia , Humanos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Protectomia/métodos , Protectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Duração da Cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
BACKGROUND: Laparoscopic total mesorectal excision (LaTME) and transanal total mesorectal excision (TaTME) are popular mid and low rectal cancer trends. However, there is currently no systematic comparison between LaTME and TaTME of mid and low rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of LaTME and TaTME in mid and low rectal cancer. METHODS: Articles included searching through the Embase, Cochrane Library, PubMed, Medline, and Web of science for articles on LaTME and TaTME. We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022380067). RESULTS: There are 8761 participants included in 33 articles. Compared with TaTME, patients who underwent LaTME had no statistical difference in operation time (OP), estimated blood loss (EBL), postoperative hospital stay, over complications, intraoperative complications, postoperative complications, anastomotic stenosis, wound infection, circumferential resection margin, distal resection margin, major low anterior resection syndrom, lymph node yield, loop ileostomy, and diverting ileostomy. There are similarities between LaTME and TaTME for 2-year DFS rate, 2-year OS rate, distant metastasis rat, and local recurrence rate. However, patients who underwent LaTME had less anastomotic leak rates (RR 0.82; 95% CI: 0.70-0.97; I2â =â 10.6%, Pâ =â .019) but TaTME had less end colostomy (RR 1.96; 95% CI: 1.19-3.23; I2â =â 0%, Pâ =â .008). CONCLUSION: This study comprehensively and systematically evaluated the differences in safety and effectiveness between LaTME and TaTME in the treatment of mid and low rectal cancer through meta-analysis. Patients who underwent LaTME had less anastomotic leak rate but TaTME had less end colostomy. There is no difference in other aspects. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.
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Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Animais , Ratos , Reto/cirurgia , Reto/patologia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Margens de Excisão , Cirurgia Endoscópica Transanal/efeitos adversos , Cirurgia Endoscópica Transanal/métodos , Neoplasias Retais/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
The allocation dynamics of soil carbon pools during soil development and land use are the key to revealing the carbon cycle process. To clarify the distribution of the soil carbon pool and its change trend, a soil reclamation chronosequence (0 a, 60 a, 160 a, 280 a, 1 000 a, and 1 500 a reclamation) was established in a typical alluvial plain in the Lower Yangtze River, and the content and density of soil organic carbon (SOC), soil inorganic carbon (SIC), particulate organic carbon (POC), and mineral-associated organic carbon (MAOC), along with carbon sequestration potential (CSP) indicators of topsoil under different land use types were measured and analyzed. The results showed that after approximately 1 500 a reclamation, the SOC content developed from the Yangtze River alluvial deposits generally increased by 4.9% after the initial decline, whereas the SIC content decreased to 0.2% from 25.8% of the total carbon content due to its rapid leaching. The MAOC content was normally higher than that of POC, and MAOC was contributing 48.0%-79.7% of the SOC accumulation. In this region, the soil organic carbon density (SOCD) accounted for 57.4%-100% of the total carbon density, the soil carbon sequestration levels (CSL) ranged from 18.6% to 56.1%, and CSP under paddy-dryland rotation increased by 20.8% compared to that under dryland. The C/N ratio and total nitrogen content are key factors in explaining soil carbon accumulation processes, and the reclamation year plays an important role in evaluating soil carbon sequestration levels. After long-term utilization, the cultivated soil in the Yangtze River floodplain must be carefully managed through balanced fertilization to maintain soil productivity, promote the accumulation of SOC, and avoid the decline in soil carbon sequestration capacity.
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AIM: To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment (RRD) using a novel foldable capsular buckle (FCB). METHODS: This was a series of case observation studies. Eighteen patients (18 eyes) who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included. The procedure was similar to conventional scleral buckling, while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad, external indentation instead of the silicone buckle. The retinal reattachment rate, best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive dioptre and astigmatism degree, and complications were evaluated and recorded. RESULTS: There were 7 males and 11 females aged 19-58y. The average time course of RRD was 12d, ranging from 7-20d. The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes, with macula-off detachments in 12 eyes. The patients were followed-up for at least 6mo. The final retinal reattachment rate was 100%. The BCVA was significantly improved compared with the baseline (P<0.05). There was no significant change in refractive dioptre or astigmatism degree at each follow-up (all P>0.05). Three patients had transiently high IOPs within one week after surgery. Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed. CONCLUSION: The success rate of FCB scleral buckling for RRD is satisfactory. This procedure can be expected to be applied in new, uncomplicated cases of RRD.
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Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of "find me" or "eat me" signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases.
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The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.
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Proteínas Adaptadoras de Transdução de Sinal , Núcleo Celular , Fatores de Transcrição SOX9 , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Proteínas de Sinalização YAP/genética , Proteínas de Sinalização YAP/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/genética , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Transporte Ativo do Núcleo Celular/genética , Camundongos , Linhagem Celular Tumoral , Animais , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Background: Minimally invasive total mesorectal excision (MiTME) and transanal total mesorectal excision (TaTME) are popular trends in mid and low rectal cancer. However, there is currently no systematic comparison between MiTME and TaTME of mid and low-rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of MiTME and TaTME in mid and low rectal cancer. Methods: We have searched the Embase, Cochrane Library, PubMed, Medline, and Web of Science for articles on MiTME (robotic or laparoscopic total mesorectal excision) and TaTME (transanal total mesorectal excision). We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022374141). Results: There are 11010 patients including 39 articles. Compared with TaTME, patients who underwent MiTME had no statistical difference in operation time (SMD -0.14; CI -0.31 to 0.33; I2=84.7%, P=0.116), estimated blood loss (SMD 0.05; CI -0.05 to 0.14; I2=48%, P=0.338), postoperative hospital stay (RR 0.08; CI -0.07 to 0.22; I2=0%, P=0.308), over complications (RR 0.98; CI 0.88 to 1.08; I2=25.4%, P=0.644), intraoperative complications (RR 0.94; CI 0.69 to 1.29; I2=31.1%, P=0.712), postoperative complications (RR 0.98; CI 0.87 to 1.11; I2=16.1%, P=0.789), anastomotic stenosis (RR 0.85; CI 0.73 to 0.98; I2=7.4%, P=0.564), wound infection (RR 1.08; CI 0.65 to 1.81; I2=1.9%, P=0.755), circumferential resection margin (RR 1.10; CI 0.91 to 1.34; I2=0%, P=0.322), distal resection margin (RR 1.49; CI 0.73 to 3.05; I2=0%, P=0.272), major low anterior resection syndrome (RR 0.93; CI 0.79 to 1.10; I2=0%, P=0.386), lymph node yield (SMD 0.06; CI -0.04 to 0.17; I2=39.6%, P=0.249), 2-year DFS rate (RR 0.99; CI 0.88 to 1.11; I2=0%, P = 0.816), 2-year OS rate (RR 1.00; CI 0.90 to 1.11; I2=0%, P = 0.969), distant metastasis rate (RR 0.47; CI 0.17 to 1.29; I2=0%, P = 0.143), and local recurrence rate (RR 1.49; CI 0.75 to 2.97; I2=0%, P = 0.250). However, patients who underwent MiTME had fewer anastomotic leak rates (SMD -0.38; CI -0.59 to -0.17; I2=19.0%, P<0.0001). Conclusion: This study comprehensively and systematically evaluated the safety and efficacy of MiTME and TaTME in the treatment of mid to low-rectal cancer through meta-analysis. There is no difference between the two except for patients with MiTME who have a lower anastomotic leakage rate, which provides some evidence-based reference for clinical practice. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022374141.
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The present study was conducted to evaluate the effects of dietary Macleaya cordata extract (MCE) supplementation on growth performance and intestinal health of American eels (Anguilla rostrata) farmed in intensive system. A total of six cement tanks of fish were randomly divided into a control group fed a commercial diet and an MCE group fed the commercial diet with 100 mg/kg MCE, respectively. There were three replicates in each group. The results suggested that 100 mg/kg MCE could improve the growth performance and intestinal health of the American eels by strengthening the barrier function and antioxidative ability in the intestine and beneficially modulating intestinal microbiota with the higher relative abundance and more species of the potential probiotics and the lower relative abundance of potentially pathogenic bacteria.
Assuntos
Anguilla , Probióticos , Animais , Dieta , Intestinos , Extratos Vegetais/farmacologiaRESUMO
OBJECTIVES: Previous studies have demonstrated the pivotal role of transforming growth factor (TGF)-ß signaling in activating hepatic stellate cells during liver fibrosis. In this study we aimed to demonstrate the effects and underlying mechanism of TGF-ß signaling in hepatocytes on hepatic fibrogenesis. METHODS: Hepatocyte-specific Tgfbr2-knockout (Tgfbr2HKO ) mice were generated by AAV8-TBG-Cre injection via the tail vein of Tgfbr2f/f mice. CCl4 was injected intraperitoneally twice a week for 4 weeks to establish the fibrotic mouse model. The expression of the fibrogenesis markers was evaluated by immunohistochemistry, western blot, and real-time polymerase chain reaction (PCR). RNA-seq analysis was used to detect the transcriptional profiles of primary hepatocytes isolated from Tgfbr2HKO mice and control mice. RESULTS: The expression of TßR2 (Tgfbr2) was markedly upregulated in hepatocytes of the fibrotic liver. Tgfbr2 depletion in hepatocytes decreased the expressions of profibrogenic markers (Col1a1 and Acta2) in the CCl4 -treated fibrotic liver. RNA-seq analysis revealed that Tgfbr2 deletion in hepatocytes significantly reduced the inflammatory response and suppressed epithelial-mesenchymal transition of hepatocytes accompanied by upregulation of the metabolic pathways during liver fibrosis. Moreover, the expressions of hepatocyte nuclear factors (HNFs), including Hnf4α, Foxa1, Foxa2, and Foxa3, which are important for maintaining liver metabolism and homeostasis, were decreased in fibrotic livers and significantly increased after Tgfbr2 blockade. CONCLUSION: Blocking the TGF-ß signaling pathway in hepatocytes reduces hepatic fibrosis and improves hepatic function in fibrotic livers.
Assuntos
Hepatócitos , Cirrose Hepática , Receptor do Fator de Crescimento Transformador beta Tipo II , Animais , Camundongos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/patologia , Cirrose Hepática/patologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: The MBOAT7 rs641738 single-nucleotide polymorphism (SNP) has been proven to influence various liver diseases, but its association with hepatocellular carcinoma (HCC) susceptibility has been debated. To address this discrepancy, we conducted the current systematic review and meta-analysis. AIM: To perform a systematic review and meta-analysis on association of MBOAT7 SNP and HCC susceptibility. METHODS: We performed a systematic review in PubMed, Web of Science, Scopus, and EMBASE; applied specific inclusion and exclusion criteria; and extracted the data. Meta-analysis was conducted with the meta package in R. Sensitivity and subgroup analyses were also performed. This meta-analysis was registered in PROSPERO (CRD42023458046). RESULTS: Eight studies were included in the systematic review, and 12 cohorts from 6 studies were included in the meta-analysis. Our meta-analysis revealed an association between the MBOAT7 SNP and HCC susceptibility in both the dominant [odds ratio (OR): 1.14, 95% confidence interval (95%CI): 1.02-1.26, P = 0.020] and recessive (OR: 1.21, 95%CI: 1.05-1.39, P = 0.008) models. Subgroup analysis revealed that stratification of the included patients by geographical origin showed a significant association in Asia (OR: 1.20, 95%CI: 1.03-1.39). CONCLUSION: This meta-analysis underscores the contribution of the MBOAT7 rs641738 SNP to hepatocarcinogenesis, especially in Asian populations, which warrants further investigation.
RESUMO
Objective: To systematically review and analyze the effects of exercise interventions on health behavior among middle-aged and older adults. Methods: A Meta-analysis was performed using NoteExpress software to screen randomized controlled trials (RCTs) published between January 1, 2000, and March 31, 2023, which were identified through databases including CNKI, Web of Science, Pubmed, and 6 more sources, based on predefined literature inclusion criteria. Following the quality assessment, we conducted both the overall and subgroup Meta-analyses of the exercise intervention moderator variables using Review Manager 5.4.1 software, encompassing data among the 18 RCTs. The effect size was measured as the standardized mean difference within its corresponding 95% confidence interval. Heterogeneity was assessed using the I2 metrics. Results: (1) The overall results indicate a significant impact of exercise intervention on health behaviors, characterized by a large effect size [SMD = 1.02 > 0.8, 95% CI (0.73, 1.32), P < 0.001]. (2) The highest degree of heterogeneity in the relationship between exercise interventions and health behaviors was associated with the duration of one exercise session (I2= 71.2%), which was the most influential moderator variable. (3) The aerobic and resistance intervention in group exercise lasting 30-60 min per time a day, 6-7 times per week over a period of 8-12 weeks demonstrated the most substantial effect size. Conclusion: (1) The exercise intervention significantly promotes the health behavior in middle-aged and older adults, emphasizing the importance of carefully considering the duration of individual exercise sessions when designing and implementing exercise intervention. (2) Considering the accessibility for middle-aged and older adults, the optimal exercise intervention should include the means of group practice, the types of aerobic and resistance exercise, with a duration of 30-60 min per time a day, beginning with a lower weekly frequency and gradually increase to 6-7 times per week, and lasting for 8 to 12 weeks. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024506750.