RESUMEN
All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene1. This approach is fundamentally different from the biosynthesis of short-chain (C10-C25) terpenes that are formed from polyisoprenyl diphosphates2-4. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene synthase (MpMS), were characterized. Both enzymes use dimethylallyl diphosphate and isopentenyl diphosphate or hexaprenyl diphosphate as substrates, representing the first examples, to our knowledge, of non-squalene-dependent triterpene biosynthesis. The cyclization mechanisms of TvTS and MpMS and the absolute configurations of their products were investigated in isotopic labelling experiments. Structural analyses of the terpene cyclase domain of TvTS and full-length MpMS provide detailed insights into their catalytic mechanisms. An AlphaFold2-based screening platform was developed to mine a third TrTS, Colletotrichum gloeosporioides colleterpenol synthase (CgCS). Our findings identify a new enzymatic mechanism for the biosynthesis of triterpenes and enhance understanding of terpene biosynthesis in nature.
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Ascomicetos , Talaromyces , Triterpenos , Ascomicetos/enzimología , Colletotrichum/enzimología , Ciclización , Difosfatos/metabolismo , Escualeno/química , Especificidad por Sustrato , Talaromyces/enzimología , Triterpenos/química , Triterpenos/metabolismoRESUMEN
This study utilized Mendelian randomization (MR) analysis and genome-wide association study (GWAS) data to investigate the association between commonly prescribed drugs and bladder cancer (BLCA) risk. Our results revealed that HMG CoA reductase (HMGCR) inhibitors, specifically simvastatin, are significantly associated with reduced BLCA risk. We further showed that simvastatin could significantly inhibit BLCA proliferation and epithelial-mesenchymal transition in animal models, with transcriptomic data identifying several pathways associated with these processes. Higher expression of HMGCR were linked with BLCA development and progression, and certain blood lipids, such as lipoprotein particles and very low density lipoprotein (VLDL) cholesterol, might influence BLCA risk. These findings suggested that HMGCR inhibitors, particularly simvastatin, could be potential treatment options or adjuvant therapies for BLCA.
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Estudio de Asociación del Genoma Completo , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Análisis de la Aleatorización Mendeliana , Simvastatina , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Animales , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Humanos , Simvastatina/efectos adversos , Transcriptoma/genética , Hidroximetilglutaril-CoA Reductasas/genética , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Polimorfismo de Nucleótido Simple/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , RatonesRESUMEN
The emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs booster vaccination. We evaluated the long-term safety and immunogenicity of heterologous boosting with a SARS-CoV-2 messenger RNA vaccine SYS6006. A total of 1000 participants aged 18 years or more who had received two (Group A) or three (Group B) doses of SARS-CoV-2 inactivated vaccine were enrolled and vaccinated with one dose of SYS6006 which was designed based on the prototype spike protein and introduced mutation sites. Adverse events (AEs) through 30 days and serious AEs during the study were collected. Live-virus and pseudovirus neutralizing antibody (Nab), binding antibody (immunoglobulin G [IgG]) and cellular immunity were tested through 180 days. Solicited all, injection-site and systemic AEs were reported by 618 (61.8%), 498 (49.8%), and 386 (38.6%) participants, respectively. Most AEs were grade 1. The two groups had similar safety profile. No vaccination-related SAEs were reported. Robust wild-type (WT) live-virus Nab response was elicited with peak geometric mean titers (GMTs) of 3769.5 (Group A) and 5994.7 (Group B) on day 14, corresponding to 1602.5- and 290.8-fold increase versus baseline, respectively. The BA.5 live-virus Nab GMTs were 87.7 (Group A) and 93.2 (Group B) on day 14. All participants seroconverted for WT live-virus Nab. Robust pseudovirus Nab and IgG responses to wild type and BA.5 were also elicited. ELISpot assay showed robust cellular immune response, which was not obviously affected by virus variation. In conclusion, SYS6006 heterologous boosting demonstrated long-term good safety and immunogenicity in participants who had received two or three doses of SARS-CoV-2 inactivated vaccine.
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Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , China , COVID-19/prevención & control , Inmunoglobulina G , Vacunas de ARNm , Vacunas de Productos InactivadosRESUMEN
BACKGROUND: Many studies have investigated the transfer of skills between laparoscopic and robot-assisted surgery (RAS). These studies have considered time, error, and clinical outcomes in the assessment of skill transfer. However, little is known about the specific operations of the surgeon. Clutch control use is an important skill in RAS. Therefore, the present study aimed to propose a novel objective algorithm based on computer vision that can automatically evaluate a surgeon's clutch use. Additionally, the study aimed to evaluate the correlation between clutch metrics and surgical skill on different surgical robot platforms. METHODS: The robotic surgery training center of Wuhan University trained 30 laparoscopic surgeons as the study group between 2023 and 2024. Laparoscopic surgeons were trained by combining robotic simulator exercises and RAS animal experiments. During the training, video and hand movement data were collected. Hand movements identified by a skin-color model were combined with labeling information to classify clutch use. The metrics were validated on different robotic platforms (dv-Trainer, EDGE MP1000, Toumai™ MT1000, and DaVinci Xi system) and among surgeons with different surgical skill levels. RESULTS: On the robotic simulator, clutch accuracy in the expert group was significantly higher than in the study group for all tasks. No significant differences were observed in the number of clutches between the expert and study groups. In the RAS experiment, the number of clutches decreased significantly for both study and expert groups. The accuracy was maintained at a high level in the expert group but decreased rapidly in the study group. CONCLUSIONS: We proposed a new objective assessment of surgical skills, clutch use metrics, in cross-platform RAS. Additionally, we verified that the metrics significantly correlated with the surgical skill levels of the surgeons.
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Competencia Clínica , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Procedimientos Quirúrgicos Robotizados/educación , Humanos , Laparoscopía/educación , Laparoscopía/métodos , Animales , Entrenamiento Simulado/métodos , Algoritmos , Cirujanos/educaciónRESUMEN
OBJECTIVES: To compare the efficacy and safety of thulium fiber laser (TFL) to holmium: YAG (Ho: YAG) laser in ureteroscopic lithotripsy for urolithiasis. METHODS: PubMed, Web of Science, Embase, CENTRAL, SinoMed, CNKI database, VIP and Wanfang Database were systematically searched for all relevant clinical trials until September 2023. References were explored to identify the relevant articles. Meta-analysis was carried out for the retrieved studies using RevMan5.4.1 software, and the risk ratio, mean difference and 95% confidence interval were expressed. Statistical significance was set at p < 0.05. The main outcomes of this meta-analysis were stone-free rate (SFR), perioperative outcomes and intraoperative or postoperative complications. RESULTS: Thirteen studies, including 1394 patients, were included. According to the results of pooled analysis, TFL was associated with significantly higher stone-free rate (SFR) [0.52, 95% CI (0.32, 0.85), P = 0.009], shorter operation time [-5.47, 95% CI (-8.86, -2.08), P = 0.002], and less stone migration [0.17, 95% CI (0.06, 0.50), P = 0.001]. However, there was no significant difference in terms of the laser time, duration of hospital stay, drop of hemoglobin level, total energy, postoperative ureteral stenting, the incidence of intraoperative complications or postoperative complications between TFL and Ho: YAGs. CONCLUSION: The findings of this study demonstrated several advantages of TFL in terms of higher SFR, shorter operative time and less stone migration. TRIAL REGISTRATION: The protocol of this systematic review was listed in PROSPERO ( www.crd.york.ac.uk/PROSPERO ) (Protocol number: CRD42022362550).
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Láseres de Estado Sólido , Litotripsia por Láser , Tulio , Ureteroscopía , Humanos , Ureteroscopía/métodos , Láseres de Estado Sólido/uso terapéutico , Litotripsia por Láser/métodos , Resultado del Tratamiento , Urolitiasis/cirugía , Urolitiasis/terapiaRESUMEN
OBJECTIVE: In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. METHODS: One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. RESULTS: After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P < 0.05. Test scores also showed improvement, with students scoring (93.02 ± 11.65) after education compared to (67.83 ± 8.08) before, a statistically significant difference. CONCLUSIONS: This research helps to provide information for the good practices of laboratory animal ethics education. After receiving laboratory animal ethics education, students are better able to treat laboratory animals in a correct animal ethical manner. Laboratory animal ethics education helps improve students' knowledge of laboratory animal ethics. Students' perception towards how the laboratory animal ethics course should be delivered may vary. Still, new courses or better organized courses on laboratory animal ethics education are required in order to provide students an in-depth understanding.
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Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Animales , Educación de Pregrado en Medicina , Masculino , Femenino , Curriculum , Animales de Laboratorio , Encuestas y Cuestionarios , Ciencia de los Animales de Laboratorio/educación , Ciencia de los Animales de Laboratorio/ética , Bienestar del Animal/ética , Experimentación Animal/ética , China , Evaluación Educacional , Adulto Joven , ConcienciaciónRESUMEN
BACKGROUND: The pathogenesis of benign prostatic hyperplasia (BPH) has not been fully elucidated. Ras homology family member A (RhoA) plays an important role in regulating cell cytoskeleton, growth and fibrosis. The role of RhoA in BPH remains unclear. METHODS: This study aimed to clarify the expression, functional activity and mechanism of RhoA in BPH. Human prostate tissues, human prostate cell lines, BPH rat model were used. Cell models of RhoA knockdown and overexpression were generated. Immunofluorescence staining, quantitative real time PCR (qRT-PCR), Western blotting, cell counting kit-8 (CCK-8), flow cytometry, phalloidine staining, organ bath study, gel contraction assay, protein stability analysis, isolation and extraction of nuclear protein and cytoplasmic protein were performed. RESULTS: In this study we found that RhoA was localized in prostate stroma and epithelial compartments and was up-regulated in both BPH patients and BPH rats. Functionally, RhoA knockdown induced cell apoptosis and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transformation (EMT) and contraction. Consistently, overexpression of RhoA reversed all aforementioned processes. More importantly, we found that ß-catenin and the downstream of Wnt/ß-catenin signaling, including C-MYC, Survivin and Snail were up-regulated in BPH rats. Downregulation of RhoA significantly reduced the expression of these proteins. Rho kinase inhibitor Y-27632 also down-regulated ß-catenin protein in a concentration-dependent manner. However, overexpression of ß-catenin did not affect RhoA-ROCK levels, suggesting that ß-catenin was the downstream of RhoA-ROCK regulation. Further data suggested that RhoA increased nuclear translocation of ß-catenin and up-regulated ß-catenin expression by inhibiting its proteasomal degradation, thereby activating Wnt/ß-catenin signaling. Overexpression of ß-catenin partially reversed the changes in cell growth, fibrosis and EMT except cell contraction caused by RhoA downregulation. Finally, Y-27632 partially reversed prostatic hyperplasia in vivo, further suggesting the potential of RhoA-ROCK signaling in BPH treatment. CONCLUSION: Our novel data demonstrated that RhoA regulated both static and dynamic factors of BPH, RhoA-ROCK-ß-catenin signaling axis played an important role in the development of BPH and might provide more possibilities for the formulation of subsequent clinical treatment strategies.
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Hiperplasia Prostática , Animales , Humanos , Masculino , Ratas , beta Catenina/metabolismo , Proliferación Celular , Fibrosis , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Vía de Señalización WntRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH. METHODS: Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson's trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments. RESULTS: Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations. CONCLUSIONS: Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.
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Ferroptosis , Hiperplasia Prostática , Anciano , Animales , Humanos , Masculino , Ratas , Proteínas Quinasas Activadas por AMP , Apoptosis , Glutatión Peroxidasa , Hiperplasia , Sistema de Señalización de MAP Quinasas , Mitocondrias , Próstata , Serina-Treonina Quinasas TORRESUMEN
Bladder cancer (BC) is a complex disease affecting the urinary system and is regulated by several carcinogenic factors. Viral infection is one such factor that has attracted extensive attention in BC. Human papillomavirus (HPV) is the most common sexually transmitted infection, and although multiple researchers have explored the role of HPV in BC, a consensus has not yet been reached. In addition, HPV-associated viruses (e.g., human immunodeficiency virus, herpes simplex virus, BK virus, and JC virus) appear to be responsible for the occurrence and progression of BC. This study systematically reviews the relationship between HPV-associated viruses and BC to elucidate the role of these viruses in the onset and progression of BC. In addition, the study aims to provide a greater insight into the biology of HPV-associated viruses, and assess potential strategies for treating virus-induced BC. The study additionally focuses on the rapid development of oncolytic viruses that provide a potentially novel option for the treatment of BC.
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Virus BK , Infecciones por Papillomavirus , Neoplasias de la Vejiga Urinaria , Humanos , Virus del Papiloma Humano , Virus Satélites , Infecciones por Papillomavirus/complicacionesRESUMEN
BACKGROUND: Currently, only a limited number of remote assistance modalities are utilized in the basic phase of robotic surgery training to facilitate the rapid acquisition of robotic surgery skills by surgeons. This study aimed to investigate the benefits of real-time remote surgical robotic skill training based on a multi-channel video recording and playback system. METHODS: We randomly divided 40 medical students without prior expertise in the use of surgical robots into two groups to assess the performance of trainees on a robotic simulator (Mimic dV-Trainer). The remote group received remote training, while the control group received live one-on-one guidance. We compared the learning curves of the two groups based on simulator scores. Furthermore, the NASA task load index (NASA-TLX) scale was used to measure the fatigue load of the trainers. RESULTS: We observed no significant differences in the demographics or initial baseline skill levels between the two groups. Participants in the remote group achieved higher total scores in the Match Board 2 and Thread the Rings 1 exercises compared to the control group. In addition, trainers in the remote group reported lower subjective fatigue load than in the control group. CONCLUSIONS: The remote approach to surgical robotics skills training based on the Remote Teaching System for Robotic Surgery (ReTeRoS) is both feasible and has the potential for large-scale training.
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Procedimientos Quirúrgicos Robotizados , Robótica , Entrenamiento Simulado , Cirujanos , Humanos , Procedimientos Quirúrgicos Robotizados/educación , Simulación por Computador , Programas Informáticos , Cirujanos/educación , Entrenamiento Simulado/métodos , Competencia ClínicaRESUMEN
RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.
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Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Infecciones por Coronavirus/epidemiología , Mortalidad Hospitalaria , Hipertensión/epidemiología , Neumonía Viral/epidemiología , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , COVID-19 , Infecciones por Coronavirus/complicaciones , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Pacientes Internos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicacionesRESUMEN
PURPOSE: To compare a novel vacuum suction ureteroscopic laser lithotripsy (VS-URS) with traditional ureteroscopic laser lithotripsy (T-URS) for impacted upper ureteral stones and to better define the potential benefits of VS-URS. METHODS: Between May 2019 and March 2021, 158 patients with impacted upper ureteral stones underwent ureteroscopic holmium-YAG laser lithotripsy. Of these, 76 underwent VS-URS and 82 underwent T-URS. In VS-URS procedures, the vacuum suction device is composed of a 5F ureteral catheter and a tee joint. The ureteral catheter is linked to the vacuum aspirator by the sidearm of the tee joint, and a 200 µm fiber is inserted through the tee joint and the ureteral catheter into the stone site for lithotripsy. RESULTS: When compared to the T-URS group, the VS-URS group had a shorter mean operation time (38.18 ± 6.37 min vs. 46.65 ± 5.66 min; P = 0.000), lower fever rate (3.9% vs. 14.6%; P < 0.022), less stone retropulsion (5.3% vs. 18.3%; P = 0.012), lower extra management rate (6.58% vs. 21.95%; P = 0.006), and a higher stone-free rate of the first postoperative day (88.2% vs. 72.0%; P = 0.011). There were no significant differences in stone-free rates 1 month after surgery between groups (94.7% vs. 92.7%; P = 0.748). CONCLUSIONS: VS-URS is an effective modality for impacted upper ureteral stones, and has a shorter operating time, lower fever rate, less stone retropulsion, and a higher primary stone-free rate compared with T-URS.
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Litotripsia por Láser , Litotricia , Cálculos Ureterales , Humanos , Litotricia/métodos , Litotripsia por Láser/métodos , Succión , Resultado del Tratamiento , Cálculos Ureterales/cirugía , Ureteroscopía/métodos , VacioRESUMEN
With rich carboxyl groups in the side chain, biodegradable polymalic acid (PMLA) is an ideal delivery platform for multifunctional purposes, including imaging diagnosis and targeting therapy. This polymeric material can be obtained via chemical synthesis, or biological production where L-malic acids are polymerized in the presence of PMLA synthetase inside a variety of microorganisms. Fermentative methods have been employed to produce PMLAs from biological sources, and analytical assessments have been established to characterize this natural biopolymer. Further functionalized, PMLA serves as a versatile carrier of pharmaceutically active molecules at nano scale. In this review, we first delineate biosynthesis of PMLA in different microorganisms and compare with its chemical synthesis. We then introduce the biodegradation mechanism PMLA, its upscaled bioproduction together with characterization. After discussing advantages and disadvantages of PMLA as a suitable delivery carrier, and strategies used to functionalize PMLA for disease diagnosis and therapy, we finally summarize the current challenges in the biomedical applications of PMLA and envisage the future role of PMLA in clinical nanomedicine.
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Nanomedicina , Polímeros , Biopolímeros/metabolismo , Fermentación , Malatos , Polímeros/químicaRESUMEN
OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.
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Nefrolitotomía Percutánea , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND: C-X-C motif chemokine ligand 13 (CXCL13), a member of the CXC subtype in chemokine superfamily, affects numerous biological processes of various types of cells and the progress of a great number of clinical diseases. The purpose of the current study was to reveal the internal mechanism between CXCL13 and benign prostatic hyperplasia (BPH). METHODS: Human serum, prostate tissues and human prostate cell lines (BPH-1, WPMY-1) were utilized. The effect of recombinant human CXCL13 (rHuCXCL13) protein and the influences of the knockdown/overexpression of CXCL13 on two cell lines were studied. Rescue experiments by anti-CXCR5 were also conducted. In vivo, rHuCXCL13 was injected into the ventral prostate of rats. Additionally, a tissue microarray of hyperplastic prostate tissues was constructed to analyze the correlations between CXCL13 and clinical parameters. RESULTS: CXCL13 was highly expressed in the prostate tissues and upregulated in the BPH group. It was observed that CXCL13 modulated cell proliferation, apoptosis, and the epithelial-mesenchymal transition (EMT) through CXCR5 via AKT and the ERK1/2 pathway in BPH-1, while it contributed to inflammation and fibrosis through CXCR5 via the STAT3 pathway in WPMY-1. In vivo, rHuCXCL13 induced the development of rat BPH. Additionally, CXCL13 was positively correlated with the prostate volume and total prostate specific antigen. CONCLUSIONS: Our novel data demonstrated that CXCL13 modulated cell proliferation, cell cycle, the EMT of epithelial cells, and induced the fibrosis of prostatic stromal cells via a variety of inflammatory factors, suggesting that CXCL13 might be rediscovered as a potential therapeutic target for the treatment of BPH.
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Próstata , Hiperplasia Prostática , Masculino , Humanos , Ratas , Animales , Próstata/metabolismo , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Ligandos , Línea Celular , Proliferación Celular , Quimiocina CXCL13/genética , Quimiocina CXCL13/metabolismoRESUMEN
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The immunophenotype of bladder cancer plays a pivotal role in the prognosis of cancer, but the effect of different epigenetic factors on different immunophenotypes in bladder tumours remains unclear. This study used multi-omics data analysis to provide molecular basis support for different immune phenotypes. Unsupervised cluster analysis revealed distinct subclusters with higher (subcluster B2) or lower cytotoxic immune phenotypes (subcluster A1) related to PD-L1 and IFNG expression. Mutational landscape analyses showed that the mutation level of TP53 in subcluster B1 was highest than other subclusters, and subcluster B1 had a lower frequency of concurrent mutation than subcluster A2. A total of 2364 differentially expressed genes were identified between subclusters A2 and B1, and the main functions of the up-regulated genes in subcluster B1 were enriched in the activation of T cells and other related pathways. We found that STAT1 was a key gene in a gene regulatory network related to immune phenotypes in bladder cancer. Finally, we constructed a prognostic prediction model by LASSO Cox regression which could distinguish high-risk and low-risk cases significantly. In conclusion, the present study addressed a field synopsis between genetic and epigenetic events in immune phenotypes of bladder cancer.
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Redes Reguladoras de Genes , Factor de Transcripción STAT1/genética , Linfocitos T/inmunología , Neoplasias de la Vejiga Urinaria/genética , Biología Computacional , Humanos , Mutación , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/inmunologíaRESUMEN
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. METHODS: Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. RESULTS: Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. CONCLUSIONS: In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.
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COVID-19 , Ácidos Nucleicos , Estudios de Cohortes , Humanos , ARN Viral , SARS-CoV-2RESUMEN
To explore any relationship between the ABO blood group and the coronavirus disease 2019 (COVID-19) susceptibility, we compared ABO blood group distributions in 2173 COVID-19 patients with local control populations, and found that blood group A was associated with an increased risk of infection, whereas group O was associated with a decreased risk.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , COVID-19 , Susceptibilidad a Enfermedades , Humanos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin-like growth factor 1 (IGF-1). METHODS: Human prostate tissues, prostate, and monocyte cell lines (WPMY-1, BPH-1, and THP-1) were used. THP-1 was polarized into several subtypes with cytokines. The expression and localization of IGF-1 and M2 macrophages were determined via immunofluorescent staining, quantitative real-time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF-1 in WPMY-1 and BPH-1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and fibrosis processes were examined. RESULTS: The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF-1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF-1 than other subtypes. Knockdown of IGF-1 in WPMY-1 and BPH-1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH-1 cells as well as the fibrotic process in WPMY-1 cells, which was reversible when cocultured with M2a macrophages. CONCLUSION: These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.