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Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis.
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Secuenciación del Exoma , Mutación , Pez Cebra , Humanos , Animales , Pez Cebra/genética , Masculino , Femenino , Fibroblastos/metabolismo , Exoma/genética , Estudio de Asociación del Genoma Completo , Adulto , Miopía/genética , Miopía/metabolismo , Miopía/patología , Esclerótica/metabolismo , Esclerótica/patología , Matriz Extracelular/metabolismo , Matriz Extracelular/genética , Predisposición Genética a la Enfermedad , Análisis de la Célula Individual , Estudios de Casos y Controles , Niño , Adulto JovenRESUMEN
BACKGROUND: To investigate the outcome and prognosis after Unicondylar knee arthroplasty (UKA) in patients with medial compartment arthritis of the knee combined with anterior cruciate ligament(ACL) dysfunction. METHODS: A total of 122 patients diagnosed with knee osteoarthritis and treated with medial mobile platform unicondylar replacement at our center from January 2019 to December 2021 were retrospectively included in the study, and were divided into two groups according to ACL function, namely the normal ACL function group (ACLF) and the poor ACL function (N-ACLF) group. The postoperative results and prognosis of the two groups were evaluated and compared. RESULTS: This study included 122 patients who underwent UKA surgery. There were no statistical differences in preoperative and postoperative posterior tibial tilt angle, knee mobility, KOOS, and prognosis between the two groups (P > 0.05). CONCLUSION: For medial compartment arthritis of the knee combined with ACL malfunction, surgery resulted in pain relief, improved quality of life and a good prognosis for such patients. It is hoped that clinicians will perform UKA in patients with ACL dysfunction after a comprehensive evaluation to improve their quality of life.
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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Masculino , Estudios Retrospectivos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/complicaciones , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Calidad de Vida , Pronóstico , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/complicacionesRESUMEN
BACKGROUND: Patients who underwent knee joint arthroplasty were at risk of venous thromboembolic events (VTEs), however, less studies were conducted to demonstrate the epidemiology and risk factors of deep venous thrombosis (DVT) following unicompartmental knee arthroplasty (UKA). Objective of this study was to explore the incidence and prognostic factors of DVT after UKA. METHODS: Patients who underwent primary UKA from December 2018 to June 2022 were recruited in this study. Demographic characteristics, operation related variables and laboratory index were extracted and analyzed. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for variables of interest. Univariate and multivariate logistic analysis were performed to identify risk factors of DVT. RESULTS: 351 UKAs with a mean age of 65.4 ± 7.1 years were reviewed. After 12.9 ± 11.2 months follow-up, 35 DVTs were confirmed which indicating an incidence of 9.9%. The results showed that occupation (agricultural laborer) (P = 0.008), disease duration > 8.5 years (P = 0.035), operation time > 169 min (P = 0.003), intraoperative blood loss > 102 ml (P < 0.001), BMI > 26.8 kg/m 2 (P = 0.001), preoperative D-dimer > 0.29 mg/L (P = 0.001), prothrombin time < 10.7 s (P = 0.033) and INR < 0.98 (P = 0.032) between DVT and Non-DVT group were significantly different. Multivariate logistic regression analysis showed intraoperative blood loss > 102 ml (OR, 3.707; P, 0.001), BMI > 26.8 kg/m 2 (OR, 4.664; P, 0.004) and D-dimer > 0.29 mg/L (OR, 2.882; P, 0.009) were independent risk factors of DVT after UKA. CONCLUSION: The incidence of DVT in the present study was 9.9%, extensive intraoperative blood loss, advanced BMI and high level of D-dimer would increase the risk of lower extremity thrombosis by 2-4 times.
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Artroplastia de Reemplazo de Rodilla , Trombosis de la Vena , Humanos , Persona de Mediana Edad , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Pronóstico , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Factores de RiesgoRESUMEN
Purpose: This observational study aimed to identify mutations in monogenic syndromic high myopia (msHM) using data from reported samples (n = 9370) of the Myopia Associated Genetics and Intervention Consortium (MAGIC) project. Methods: The targeted panel containing 298 msHM-related genes was constructed and screening of clinically actionable variants was performed based on whole exome sequencing. Capillary sequencing was used to verify the identified gene mutations in the probands and perform segregation analysis with their relatives. Results: A total of 381 candidate variants in 84 genes and 85 eye diseases were found to contribute to msHM in 3.6% (335/9370) of patients with HM. Among them, the 22 genes with the most variations accounted for 62.7% of the diagnostic cases. In the genotype-phenotype association analysis, 60% (201/335) of suspected msHM cases were recalled and 25 patients (12.4%) received a definitive genetic diagnosis. Pathogenic variants were distributed in 18 msHM-related diseases, mainly involving retinal dystrophy genes (e.g. TRPM1, CACNA1F, and FZD4), connective tissue disease genes (e.g. FBN1 and COL2A1), corneal or lens development genes (HSF4, GJA8, and MIP), and other genes (TEK). The msHM gene mutation types were allocated to four categories: nonsense mutations (36%), missense mutations (36%), frameshift mutations (20%), and splice site mutations (8%). Conclusions: This study highlights the importance of thorough molecular subtyping of msHM to provide appropriate genetic counselling and multispecialty care for children and adolescents with HM.
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Miopía , Distrofias Retinianas , Canales Catiónicos TRPM , Niño , Adolescente , Humanos , Secuenciación del Exoma , Mutación , Miopía/diagnóstico , Miopía/genética , Mutación del Sistema de Lectura , Distrofias Retinianas/genética , Linaje , Receptores Frizzled/genética , Canales Catiónicos TRPM/genéticaRESUMEN
Importance: High myopia (HM) is one of the leading causes of visual impairment worldwide. Genetic factors are known to play an important role in the development of HM. Objective: To identify risk variants in a large HM cohort and to examine the implications of genetic testing of schoolchildren with HM. Design, Setting, and Participants: This cohort study retrospectively reviewed whole-exome sequencing (WES) results in 6215 schoolchildren with HM who underwent genetic testing between September 2019 and July 2020 in Wenzhou City, China. HM is defined as a spherical equivalent refraction (SER) of -6.00 diopters (D) or less. The study setting was a genetic testing laboratory and a multicenter school census. Data were analyzed from July 2021 to June 2022. Main Outcomes and Measures: The frequency and distribution of positive germline variants, the percentage of individuals with HM in both eyes, and subsequent variant yield for common high myopia (CHM; -8.00 D ≤ SER ≤ -6.00 D), ultra myopia (UM; -10.00 D ≤ SER < -8.00 D), and extreme myopia (EM; SER < -10.00 D). Results: Of the 6215 schoolchildren with HM, 3278 (52.74%) were male. Their mean (SD) age was 14.87 (2.02) years, including 355 students in primary school, 1970 in junior high school, and 3890 in senior high school. The mean (SD) SER was -7.51 (-1.36) D for the right eye and -7.46 (-1.34) D for the left eye. Among schoolchildren with HM, genetic testing yielded 271 potential pathogenic variants in 75 HM candidate genes in 964 diagnoses (15.52%). A total of 36 known variants were found in 490 HM participants (7.88%) and 235 protein-truncating variants (PTVs) in 506 participants (8.14%). Involved variant yield was significantly positively associated with SER (Cochran-Armitage test for trend Z = 2.5492; P = .01), which ranged from 7.66% in the CHM group, 8.70% in the UM group, to 11.90% in the EM group. We also found that primary school students with EM had the highest variant yield of PTVs (8 of 35 students [22.86%]), which was 1.77 and 4.78 times that of the UM and CHM, respectively. Conclusions and Relevance: In this cohort study of WES for HM, several potential pathogenic variants were identified in a substantial number of schoolchildren with HM. The high variation frequency in younger students with EM can provide clues for genetic screening and clinical examinations of HM to promote long-term follow-up assessment.
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Miopía , Humanos , Masculino , Niño , Adolescente , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Secuenciación del Exoma , Miopía/genética , Refracción OcularRESUMEN
HTO has proven to be a cost-effective surgical procedure in the treatment of KOA, but few investigations have studied radiological changes and clinical effectiveness of OWHTO in geriatric patients. 76 patients were recruited in this retrospective study. According to the age, patients were divided into two groups (≤ 60, Group "Young"; > 60, Group "Geriatric"). Demographic data, radiological imaging and postoperative complications were analyzed. Kellgren-Lawrence grade (K-L), weight-bearing line ratio (WBLR); posterior tibial slope angle (PTS); American knee score (AKS); Western Ontario and McMaster Universities Arthritis Index (WOMAC) and visual analog scale (VAS) were introduced to estimate the clinical outcome of OWHTO. There were 18 male and 58 female patients in the present study with a mean age of 58.5 ± 9.2 years (ranges from 40 to 82 years); the average age was 51.4 ± 4.1 years and 67.3 ± 4.9 years for group Y and G respectively, 44.7% and 31.5% patients were older than 60 and 65 years. BMI for the 76 patients was 26.6 ± 3.2 kg/m2, and geriatric patients were more likely accompanied by one or more comorbidities (70.6 vs. 45.2%). There were 34 and 42 patients in group Geriatric and group Young respectively, and no significant difference of MPTA, WBLR, PTS and WOMAC, VAS, AKS and ROM between the two group (P > 0.05) were found. After more than a two-year follow-up period, postoperative WBLR, AKS, WOMAC and VAS were much more desired than preoperative, and no significant difference of these variables between the young and geriatric group (P > 0.05), however, elderly patients were more likely to suffer from a longer bone union time. OWHTO can avoid geriatric patients from undergoing secondary knee surgery in the short term, however the survival rate of OWHTO in geriatric patients should be ultimately clarified by different studies.
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Osteoartritis de la Rodilla , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Osteoartritis de la Rodilla/cirugía , Articulación de la Rodilla/cirugía , Resultado del Tratamiento , Osteotomía/efectos adversos , Osteotomía/métodos , Tibia/cirugíaRESUMEN
Background: Prostate cancer (PCa) is among the most generally diagnosed cancers in males. A long non-coding RNA (lncRNA) called AC245100.4 has been discovered and linked to PCa carcinogenesis. However, its specific and potential mechanism is uncertain in PCa. In this research, we investigated the role of AC245100.4 in cell proliferation and the underlying mechanism in PCa cells. Methods: qRT-PCR assays were utilized to detect AC245100.4 expression and confirm its downstream target. The pathways related to AC245100.4 were identified by RAP-MS. PCa cell proliferation was experimented by Cell Counting Kit-8 and Colony formation assays. Western blot was performed to detect PAR2, AKT, p-AKT, Cyclin D1 and PCNA expression. Results: AC245100.4/PAR2 overexpression promotes PCa cell proliferation and the opposite results are obtained after AC245100.4/PAR2 knockdown. Mechanistically, we found that PAR2 is confirmed as the AC245100.4 downstream target and AC245100.4 promotes PCa cell proliferation by regulating PAR2. AC245100.4 promotes PCa cell proliferation via PI3K/AKT pathway. Rescue assays validated that PAR2 knockdown reversed the impact of AC245100.4 overexpression on increasing p-AKT protein levels. Conclusion: This research revealed that AC245100.4 enhances cell proliferation in PCa cells through modulating the PAR2/PI3K/AKT axis, which may offer novel tumor markers and potential therapeutic targets for PCa.
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High myopia (HM), which is characterized by oxidative stress, is one of the leading causes of visual impairment and blindness across the world. Family and population genetic studies have uncovered nuclear-genome variants in proteins functioned in the mitochondria. However, whether mitochondrial DNA mutations are involved in HM remains unexplored. Here, we performed the first large-scale whole-mitochondrial genome study in 9613 HM cases and 9606 control subjects of Han Chinese ancestry for identifying HM-associated mitochondrial variants. The single-variant association analysis identified nine novel genetic variants associated with HM reaching the entire mitochondrial wide significance level, including rs370378529 in ND2 with an odds ratio (OR) of 5.25. Interestingly, eight out of nine variants were predominantly located in related sub-haplogroups, i.e. m.5261G > A in B4b1c, m.12280A > G in G2a4, m.7912G > A in D4a3b, m.94G > A in D4e1, m.14857 T > C in D4e3, m.14280A > G in D5a2, m.16272A > G in G2a4, m.8718A > G in M71 and F1a3, indicating that the sub-haplogroup background can increase the susceptible risk for high myopia. The polygenic risk score analysis of the target and validation cohorts indicated a high accuracy for predicting HM with mtDNA variants (AUC = 0.641). Cumulatively, our findings highlight the critical roles of mitochondrial variants in untangling the genetic etiology of HM.
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Pueblos del Este de Asia , Miopía , Humanos , ADN Mitocondrial/genética , Haplotipos/genética , Mitocondrias/genética , Mutación , Miopía/genéticaRESUMEN
High myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three newly identified -genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) in FKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a newly identified European ancestry-specific rare variant in FOLH1. Functional experiments revealed a mechanism whereby a single G-to-A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter of FKBP5, resulting in decreased transcription of FKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport.
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Predisposición Genética a la Enfermedad , Miopía , Proteínas de Unión a Tacrolimus , Humanos , Pueblos del Este de Asia , Exoma/genética , Miopía/genética , Factores de Transcripción/genética , Proteínas de Unión a Tacrolimus/genéticaRESUMEN
(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) is recognized as the preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance to TMZ. Our previous study found that GBM patients with EGFRvIII (+) have low sensitivity to TMZ. However, the reasons and possible mechanisms of the chemoradiotherapy resistance in GBM patients with EGFRvIII (+) are not clear. (2) Methods: In this study, tissue samples of patients with GBM, GBM cell lines, glioma stem cell lines, and NSG mice were used to explore the causes and possible mechanisms of low sensitivity to TMZ in patients with EGFRvIII (+)-GBM. (3) Results: The study found that EGFRvIII promoted the proneural-mesenchymal transition of GBM and reduced its sensitivity to TMZ, and EGFRvIII regulated of the expression of ALDH1A3. (4) Conclusions: EGFRvIII activated the NF-κB pathway and further regulated the expression of ALDH1A3 to promote the proneural-mesenchymal transition of GBM and reduce its sensitivity to TMZ, which will provide an experimental basis for the selection of clinical drugs for GBM patients with EGFRvIII (+).
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Glioblastoma , Ratones , Animales , Temozolomida/farmacología , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , FN-kappa B/genética , Línea Celular TumoralRESUMEN
The enhanced recovery after surgery (ERAS) pathway was formulated with the aim to reduce surgical stress response, alleviate pain and guarantee the best-fit experience of patients' perioperative period. However, the application of ERAS in geriatric patients who underwent unicompartmental knee arthroplasty (UKA) was relatively lacking. We hypothesize that UKA patients can benefit from the ERAS protocol. A total of 238 patients were recruited in this retrospective study from August 2018 to December 2021, and Oxford phase III UKA was applied to all patients. ERAS pathway included nutrition support, anesthesia mode, interoperative temperature, and blood pressure control, application of tranexamic acid, early initiation of oral intake and mobilization, and pain management. Demographic data, operation-relative variables, and postoperative complications were analyzed. Forgotten Joint Scores, Oxford Knee Score, Lysholm score, numerical rating scale, and knee range of motion were introduced to estimate the activity function and pain of surgical knee, and these variables were compared between the 2 groups. There were 117 patients in the ERAS group and 121 patients in the traditional group, respectively. The ERAS group had a shorter length of surgical incision and less intraoperative blood loss. Postoperative hemoglobin and albumin of patients in the ERAS group were better than those in the traditional group (P < .05), after 17.0 ± 10.8 months follow-up, the numerical rating scale, Lysholm, Oxford Knee Score, Forgotten Joint Scores, and knee range of motion of patients in the ERAS group were significantly better than the traditional group. The length of hospital stay for patients who underwent ERAS was 11.7 ± 3.8 days and the postoperative complication rate was lower for the ERAS group patients (P = .000 and 0.031). ERAS can reduce the length of hospital stay, and patients can achieve excellent postoperative knee function. The formulation and implementation of the ERAS protocol require good collaboration across multiple disciplines, as well as a deep understanding of the existing clinical evidence and the concept of the ERAS program.
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Artroplastia de Reemplazo de Rodilla , Recuperación Mejorada Después de la Cirugía , Humanos , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Articulación de la Rodilla/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Dolor/complicaciones , Tiempo de InternaciónRESUMEN
Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, concerning the cell proliferation and migration assay data shown in Figs. 6D and 7B, there were a pair of panels showing overlapping data, such that the same data had apparently been selected to show the results from different experiments. Subsequently, the authors referred back to their original data, and identified further incorrectly assembled data panels in Figs. 3B and 7B. The corrected versions of Fig. 3B (showing the correct data for the 'AC245100.4 / PC3 / 0 h' scratchwound assay data panel), Fig. 6D (showing the correct data for the 'PC3 / NCmimic' and 'DU145 / NCinhibitor' data panels) and Fig. 7D (showing the correct data for the 'PC3 / 24 h / InhibitormiR1455p + siAC245100.4' data panel) are shown on the subsequent pages. The authors regret the errors that were made during the preparation of the published figures, and confirm that these errors did not grossly affect the conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 45: 619629, 2021; DOI: 10.3892/or.2020.7894].
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Medial opening-wedge high tibial osteotomy (MOWHTO) is a well-established surgical method for treatment of isolated medial compartment osteoarthritis with varus deformity, but the surgical outcomes may be compromised by surgical site infection (SSI). This study aimed to investigate the incidence and the risk factors for SSI after MOWHTO. This retrospective study included consecutive patients who underwent MOWHTO for isolated medial compartment osteoarthritis with varus deformity in two tertiary referral hospitals from January 2019 and June 2021. Patients who developed SSI within 12 months of surgery were identified by inquiring the medical records for index hospitalisation, notes of after-discharge outpatient visits, or records of readmission for treatment of SSI. Univariate comparisons were performed to detect the differences between SSI and non-SSI groups, and multivariate logistic regression analysis was used to identify the independent risk factors. Six hundred sixteen patients with 708 procedures were included and 30 (4.2%) cases of SSI occurred, with 0.6% rate for deep SSI and 3.6% for superficial. Univariate analyses showed significant difference between groups in terms of morbidity obesity (≥32 kg/m2 ) (20.0% vs 8.9%), comorbid diabetes (26.7% vs 11.1%), active smoking (20.0% vs 6.3%), time from admission to operation (5.2 ± 4.0 vs 4.1 ± 3.0), size of osteotomy ≥12 mm (40.0% vs 20.0%), type of bone grafting and lymphocyte count (2.1 ± 0.5 vs 1.9 ± 0.6). However, in the multivariate analysis, only active smoking (OR, 3.4; 95% CI, 1.4-10.2), size of osteotomy ≥12 mm (OR, 2.8; 95% CI, 1.3-5.9) and allogeneic/artificial vs no bone grafting (OR, 2.4; 95% CI, 1.0-10.8) remained significant. SSI was not uncommon after MOWHTO, but the majority was superficial. The identified three independent factors, including smoking, size of osteotomy ≥12 mm and allogeneic/artificial bone grafting would help risk assessment and stratification, target risk factor modification and clinical surveillance, and inform patient counselling.
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Articulación de la Rodilla , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Incidencia , Tibia/cirugía , Factores de Riesgo , Osteotomía/efectos adversos , Osteotomía/métodosRESUMEN
Unicompartmental knee arthroplasty (UKA) has been proven as an ideal alternative surgical procedure to treat symptomatic isolated knee osteoarthritis, and recently this technique has gained its popularity. However, postoperative complications would inevitably compromise the effectiveness and patients' satisfaction. The objective of this study is to demonstrate the incidence and risk factors of delayed wound healing (DWH) after UKA. This retrospective cohort study was conducted from February 2021 to May 2022 and a total of 211 patients were enrolled. Demographic characteristics, operation-related variables, and laboratory indexes were extracted. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for continuous variables. Univariate and multivariate logistic regression analysis was performed to demonstrate the risk factors of DWH. There were 155 female and 56 male patients with an average age of 64. 6 ± 6.9 years included in this study. After 6.6 ± 4.9 months' follow-up, 12 cases of DWH were observed which indicated an incidence of DWH of 5.7%, mean wound healing duration for 12 patients was 43.1 ± 19.3 days. In the univariate analysis, age > 62.5 years, postoperative hospital stay < 5.5 days, surgical incision < 10.5 cm, barbed suture, body mass index (BMI) > 32.0 kg/m2 , operation duration > 102.5 minutes, intraoperative blood loss > 102.5 mL, preoperative white blood cell count > 5.95*109 /L, preoperative seroglobulin (GLB) > 29.6 g/L, postoperative total protein < 63.4 g/L, postoperative serum albumin < 36.4 g/L, and postoperative GLB > 26.8 g/L were significantly different between patients with and without DWH (P < .05). In final multivariate logistic analysis, results showed that intraoperative blood loss > 102.5 mL (odds ratio [OR], 3.09; P = .001), postoperative hospital stay < 5.5 days (OR, 1.74; P = .014), surgical incision < 10.5 cm (OR, 1.67; P = .000), and BMI > 32.0 kg/m2 (OR, 4.47; P = .022) were independent risk factors for DWH. DWH prolongs hospital stay in UKA patients and increases healthcare expenditure; also affected the implementation schedule of postoperative functional exercise plans. Surgeons should identify patients at risk, meanwhile, make timely and correct clinical interventions to decrease the incidence of this complication.
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Artroplastia de Reemplazo de Rodilla , Herida Quirúrgica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Herida Quirúrgica/etiología , Incidencia , Resultado del Tratamiento , Factores de Riesgo , Cicatrización de HeridasRESUMEN
Objective: To explore the effect of mosaic allograft osteochondral transplantation combined with corrective osteotomy in treating osteochondral lesions of the talus (OLT) on ankle and knee joint function and lower limb alignment. Methods: One hundred and thirty-three OLT patients treated in our hospital between July 2015 and October 2019 were enrolled. Regarding the various surgical approaches, they were categorized into two groups, namely, A and B including 69 and 64 cases, respectively. The patients in group A were processed with mosaic allograft osteochondral transplantation combined with corrective osteotomy, and the patients in group B were processed with microfracture surgery. The Baird ankle function score and visual analog scale (VAS) were employed for evaluating the surgical efficacy and the degree of pain prior to and following surgery. The pre- and postoperative surgery-related indicators, Ankle Hindfoot Scale (AOOFAS), HSS score, lower limb alignment, and range of motion of the ankle were compared between the two groups, and changes in growth factor levels prior to and following processing were observed. Results: Overall scores were better in group A than in group B (P < 0.05). The operation length was longer in group A, the amount of intraoperative blood loss was greater, and the length of hospitalization was less than in group B. The VAS score 48 hours after surgery was also lower (P < 0.05). Postoperative AOFAS scores in group A were better, and lower limb alignment was also less than in group B (P < 0.05). The postoperative HSS score did not differ significantly between the two groups (P > 0.05). The range of plantar flexion and dorsiflexion of the ankle joint was better in group A, and the levels of endothelial growth factor (VEGF), platelet-derived growth factor (PDG), and transforming growth factor ß1 (TGF-ß1) were lower than those in group B (P < 0.05). The occurrence of postoperative problems did not differ between the groups (P > 0.05). Conclusion: Mosaic allograft osteochondral transplantation combined with corrective osteotomy has a high effective rate in the treatment of OLT, which can promote the healing of articular cartilage and the recovery of ankle joint functions, improve the range of motions of the ankle, and improve the lower limb alignment.
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Cartílago Articular , Astrágalo , Aloinjertos , Tobillo/cirugía , Articulación del Tobillo/cirugía , Cartílago Articular/trasplante , Humanos , Articulación de la Rodilla/cirugía , Extremidad Inferior , Osteotomía , Estudios Retrospectivos , Astrágalo/cirugía , Resultado del TratamientoRESUMEN
Prostate cancer (PCa) is the second most common cause of cancer-related mortality in men. Prostate cancer metastasis usually observed at the last stage is the major cause of prostate cancer-related death. Long non-coding RNAs were reported to be involved in tumorigenesis and progression of prostate cancer. This study aimed to investigate the effects and related mechanisms of AC245100.4 in prostate cancer. Knockdown and overexpression of AC245100.4 was used to detect the effect of AC245100.4 on cell migration. qRT-PCR was used to confirm the downstream target of AC245100.4. RAP-MS was used to find pathways related to AC245100.4. Western blot was performed to detect the expression of p-p38 and p38. We found that AC245100.4 promoted the migration of prostate cancer cells via regulating PAR2. The AC245100.4 or PAR2 knockdown resulted in a decrease in Vimentin but an increase in E-cadherin protein levels, while the AC245100.4 or PAR2 overexpression got the opposite results. Moreover, we discovered that AC245100.4 activated the p38-MAPK via regulating PAR2. In brief, these results have suggested that AC245100.4 and PAR2 served as oncogenic factors in cellular migration in PCa cells.
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Neoplasias de la Próstata , ARN Largo no Codificante , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Neoplasias de la Próstata/patología , ARN Largo no Codificante/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/farmacologíaRESUMEN
The Apaf-1 interacting protein (APIP), a ubiquitously expressed antiapoptotic molecule, is aberrantly expressed and of great significance in various cancers. However, little is known regarding the potential value and underlying mechanisms of APIP in prostate cancer. Here, we demonstrated that APIP expression is significantly upregulated in prostate cancer cell lines. APIP overexpression promoted tumor cell proliferation and migration and induced extracellular regulated protein kinases 1/2 (ERK1/2) activation. Pharmacological inhibition of ERK1/2 signaling reversed APIP-induced increase in cell proliferation and migration induced by APIP overexpression. Expression of APIP was hampered by miR-146a-3p. A dual luciferase reporter gene assay identified the regulatory relationship between APIP and miR-146a-3p in prostate cancer, suggesting that APIP is a direct target of miR-146a-3p. miR-146a-3p reduced cell proliferation and migration in prostate cancer. Furthermore, miR-146a-3p inhibited ERK1/2 activation. Application of an ERK1/2 inhibitor reversed the increase in cell proliferation and migration induced by miR-146a-3p inhibition. In summary, this study focused on the role of APIP in regulating cell growth and migration and proposes a theoretical basis for APIP as a promising biomarker in prostate cancer development.
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Factor Apoptótico 1 Activador de Proteasas/metabolismo , MicroARNs , Neoplasias de la Próstata , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Quinasas/metabolismoRESUMEN
Aim: To explore the role and mechanism of long noncoding RNA AC245100.4 and NR4A3 in prostate cancer (PCa). Methods: RNA-sequencing analysis was used to detect the downstream genes of AC245100.4. A series of gain- and loss-of-function approaches were used to investigate the roles of AC245100.4 and NR4A3. RNA immunoprecipitation was performed to examine the interaction between AC245100.4 and STAT3. Results: AC245100.4 was significantly upregulated in PCa cells and tissues. Knockdown of AC21500.4 significantly inhibited the tumorigenesis of PCa cells. Mechanistically, AC245100.4 deregulated the transcription of NR4A3 via increasing p-STAT3, which acted as a transcriptional repressor of NR4A3. Conclusion: Knockdown of long noncoding RNA AC245100.4 inhibits the tumorigenesis of PCa cells via the STAT3/NR4A3 axis.
Lay abstract Long noncoding RNA has recently gained attention for the vital role it plays in the mechanism of prostate cancer (PCa). In this study, the authors found that long noncoding RNA AC245100.4 inhibited the tumor formation of PCa cells via the STAT3/NR4A3 axis. A deeper understanding of the specific mechanism of AC245100.4 in PCa tumor formation will provide insights into diagnostic and prognostic strategies for PCa.
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Transformación Celular Neoplásica/genética , Proteínas de Unión al ADN/genética , Neoplasias de la Próstata/etiología , ARN Largo no Codificante/genética , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/genética , Factor de Transcripción STAT3/genética , Animales , Apoptosis , Biomarcadores de Tumor , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Masculino , Ratones , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de SeñalRESUMEN
The induction of ferroptosis is considered a new strategy for cancer treatment. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a post-transcriptional regulatory factor, whose low expression has been reported to link to the enhanced metastasis and angiogenesis of gastric cancer (GC). In this study, to explore the role of CPEB1 in ferroptosis, GC cells with overexpressed or silenced CPEB1 expression were treated with erastin, a classic ferroptosis inducer. The results showed that erastin dose-dependently decreased the viability of four GC cell lines (AGS, SNU-1, Hs-746 T, and HGC-27), suggesting that ferroptosis could be triggered in these GC cells. Interestingly, HGC-27 cells overexpressing CPEB1 were more sensitive to erastin, generated more lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and their glutathione peroxidase 4 (Gpx4) expression and GSH content were reduced. Contrarily, CPEB1-silenced AGS cells were more resistant to erastin. Mechanically, we demonstrated that CPEB1 overexpression reduced the expression of twist1, an inhibitor of activating transcription factor 4 (ATF4), thereby activating the ATF4/ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 (CHAC1) pathway (CHAC1, a molecule known to induce GSH degradation). Furthermore, re-expression of twist1 in GC cells impaired the effects of CPEB1 overexpression in presence of erastin. Additionally, similar to the in vitro results, the growth-inhibiting effects of erastin on GC xenografted tumors were also augmented by CPEB1 overexpression in vivo. Collectively, we demonstrate that CPEB1 facilitates erastin-induced ferroptosis by inhibiting twist1.
Asunto(s)
Ferroptosis/efectos de los fármacos , Proteínas Nucleares/genética , Piperazinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Factores de Transcripción/metabolismo , Proteína 1 Relacionada con Twist/genética , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones Desnudos , Proteínas Nucleares/metabolismo , Piperazinas/administración & dosificación , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Factores de Transcripción/genética , Proteína 1 Relacionada con Twist/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Factores de Escisión y Poliadenilación de ARNm/genéticaRESUMEN
BACKGROUND: Prostate cancer (PCa) refers to malignant tumors derived from prostate epithelial cells, whose morbidity and mortality rates have been increasing every year. Although new drugs for treating prostate cancer continue to emerge, the unclear mechanism underlying drug targets limits this therapy, thereby constraining identification of effective therapeutic targets. Although GDP dissociation inhibitor 2(GDI2) is highly expressed and closely associated with occurrence and development of many tumors, its role in prostate cancer remains unclear. In this study, we investigated the role of GDI2 and elucidated its underlying mechanism of action in prostate cancer. Moreover, we screened chemotherapeutic drugs that affect GDI2 expression with a view of identifying novel targets for diagnosis and treatment of prostate cancer. METHODS: We performed sequence analyses and functional assays to precisely elucidate the GDI2 role in prostate cancer. Moreover, we induced tumorigenesis in nude mice to verify the role of GDI2 in vivo. Finally, we used the CCK8 assay to ascertain the most suitable IC50 across the three drugs and performed quantitative real time polymerase chain reaction (qRT-PCR) and Western Blot to analyze the effects of drugs on expression of GDI2, p75NTR, and p-NFκB. RESULTS: GDI2 was up-regulated in prostate cancer cells and tissues. Knocking down GDI2 suppressed cell proliferation but promoted cell apoptosis. Interestingly, knocking down GDI2 activated the p75NTR signaling pathway, indicating, for the first time, that p75NTR is negatively correlated with GDI2 expression. CONCLUSION: Taken together, these results indicate that GDI2 is a therapeutic target of paclitaxel. Knocking down of GDI2 inhibits cell proliferation and promotes cell apoptosis via the p75NTR signaling pathway in prostate cancer. Notably, paclitaxel inhibits GDI2 expression, implying that GDI2 may be a promising therapeutic target in prostate cancer.