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1.
Int J Clin Exp Pathol ; 17(4): 121-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716350

RESUMEN

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(3): 272-277, 2024 Mar 15.
Artículo en Chino | MEDLINE | ID: mdl-38500418

RESUMEN

Objective: To discuss the application of anterior region suture of the popliteal hiatus (PH) under arthroscopy in the treatment of discoid lateral meniscus (DLM) injury with instability in the popliteal tendon region. Methods: The clinical data of 53 patients (56 knees) with DLM injury who met the selection criteria between March 2014 and November 2022 were retrospectively analyzed. There were 15 males and 38 females, aged 8-55 years with an average age of 36.5 years. Fourteen cases had a history of trauma, while the remaining 39 cases had no clear history of trauma. The disease duration ranged from 1 day to 6 years, with an average duration of 15.6 months. According to the Watanabe classification, there were 40 knees of complete type and 16 knees of incomplete type. The preoperative International Knee Documentation Committee (IKDC) knee joint score was 51.2±8.3, the Lysholm score was 59.6±11.2, and the visual analogue scale (VAS) score was 4.7±1.3. After the arthroscopic meniscal plasty, the instability of the popliteal tendon region meniscus was checked by probing traction. Subsequently, the Out-inside technique or a combination of Out-inside and All-inside techniques was used to suture the anterior region of the PH. The stability of the meniscus after suturing was assessed, and if necessary, further suturing using the All-inside technique at the posterior region of the PH, the posterior horn of the meniscus, and using the Out-inside technique at the anterior horn of the meniscus was performed. Postoperative complications were recorded. The effectiveness was evaluated using pre- and post-operative IKDC scores, Lysholm scores, and VAS scores. Results: After operation, knee joint pain, crepitus, and locking disappeared, with McMurray and grinding tests turning negative. All patients were followed up 12-93 months with an average of 57.5 months. There was no complication such as common peroneal nerve injury, deep vein thrombosis of the lower limbs, joint infection, or joint stiffness. At last follow-up, the IKDC knee joint score was 76.7±5.5, the Lysholm score was 94.0±4.1, and the VAS score was 1.1±0.8. The differences compared with preoperative scores were significant ( t=-22.090, P<0.001; t=-23.704, P<0.001; t=19.767, P<0.001). Conclusion: Suturing of the anterior region of the PH is crucial in the treatment of DLM injury with instability in the popliteal tendon region.


Asunto(s)
Enfermedades de los Cartílagos , Lesiones de Menisco Tibial , Masculino , Femenino , Humanos , Adulto , Meniscos Tibiales/cirugía , Estudios de Seguimiento , Estudios Retrospectivos , Lesiones de Menisco Tibial/cirugía , Articulación de la Rodilla/cirugía , Extremidad Inferior , Artroscopía/métodos , Suturas , Resultado del Tratamiento
3.
J Transl Med ; 22(1): 280, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491511

RESUMEN

BACKGROUND: Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression. METHODS: Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression. RESULTS: Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth. CONCLUSION: Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Ováricas , Humanos , Femenino , Fibroblastos Asociados al Cáncer/metabolismo , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Factor 7 de Crecimiento de Fibroblastos/farmacología , Línea Celular Tumoral , Transducción de Señal , Neoplasias Ováricas/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Transición Epitelial-Mesenquimal/genética , Movimiento Celular/genética
4.
Mol Biotechnol ; 66(1): 1-10, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37154864

RESUMEN

Osteoarthritis (OA), a chronic degenerative disease characterized mainly by damage to the articular cartilage, is increasingly relevant to the pathological processes of senescence, apoptosis, autophagy, proliferation, and differentiation of chondrocytes. Clinical strategies for osteoarthritis can only improve symptoms and even along with side effects due to age, sex, disease, and other factors. Therefore, there is an urgent need to identify new ideas and targets for current clinical treatment. The tumor suppressor gene p53, which has been identified as a potential target for tumor therapeutic intervention, is responsible for the direct induction of the pathological processes involved in OA modulation. Consequently, deciphering the characteristics of p53 in chondrocytes is essential for investigating OA pathogenesis due to p53 regulation in an array of signaling pathways. This review highlights the effects of p53 on senescence, apoptosis, and autophagy of chondrocytes and its role in the development of OA. It also elucidates the underlying mechanism of p53 regulation in OA, which may help provide a novel strategies for the clinical treatment of OA.


Asunto(s)
Cartílago Articular , Osteoartritis , Humanos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Osteoartritis/genética , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Condrocitos/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/patología , Transducción de Señal , Apoptosis/genética , Autofagia
5.
Int Immunopharmacol ; 127: 111416, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38145599

RESUMEN

BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC. METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene. RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.


Asunto(s)
Condrocitos , Condromatosis Sinovial , Humanos , Condrocitos/patología , Condromatosis Sinovial/patología , Biomarcadores , Ciclo Celular/genética , Colágeno , Biología Computacional/métodos , Colágeno Tipo III
6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(11): 1342-1346, 2023 Nov 15.
Artículo en Chino | MEDLINE | ID: mdl-37987042

RESUMEN

Objective: To investigate the effectiveness of arthroscopic multi-point fixation with anchor and suture in the treatment of tibial insertion avulsion fracture of anterior cruciate ligament (ACL) involving the anterior root of lateral meniscus (LM). Methods: A retrospective analysis was conducted on the clinical data of 28 patients with tibial insertion avulsion fracture of ACL involving the anterior root of LM who were treated with arthroscopic multi-point fixation with anchor and suture between October 2017 and January 2023. There were 12 males and 16 females with the mean age of 26 years (range, 13-57 years). There were 20 cases of sports injury and 8 cases of traffic accident injury. In 2 cases of old fracture, the time from injury to operation was 45 days and 90 days, respectively; in 26 cases of fresh fracture, the time from injury to operation was 3-20 days (mean, 6.7 days). According to the Meyers-McKeever classification, there were 4 cases of type Ⅱ, 11 cases of type Ⅲ, and 13 cases of type Ⅳ. The preoperative Lysholm knee function score was 42.1±9.0, the International Knee Documentation Committee (IKDC) score was 40.0±7.3, and the Tegner score was 0.7±0.7. Results: All operations were successfully completed, and the incisions healed by first intention. All the 28 patients were followed up 5-60 months (mean, 20.4 months). During the follow-up, there was nocomplication such as infection, vascular or nerve injury, loosening or breakage of internal fixator, or stiffness of knee joint. Postoperative X-ray films showed satisfactory fracture reduction and firm fixation. All fractures healed clinically, and the healing time was 8-16 weeks (mean, 10.3 weeks). At last follow-up, Lachman test and anterior drawer test were negative. At last follow-up, Lysholm knee function score was 92.4±5.5, IKDC score was 91.6±4.4, and Tegner score was 5.2±1.1, which significantly improved when compared with preoperative scores ( t=-22.899, P<0.001; t=-29.870, P<0.001; t=-19.979, P<0.001). Conclusion: Multi-point fixation with anchor and suture in the treatment of tibial insertion avulsion fracture of ACL involving the anterior root of LM can not only fix the LM, but also effectively reduce and fix the avulsion fracture, which can obtain good effectiveness.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Fracturas por Avulsión , Fracturas de la Tibia , Masculino , Femenino , Humanos , Adulto , Ligamento Cruzado Anterior/cirugía , Meniscos Tibiales/cirugía , Fracturas por Avulsión/cirugía , Estudios Retrospectivos , Lesiones del Ligamento Cruzado Anterior/cirugía , Resultado del Tratamiento , Artroscopía , Fracturas de la Tibia/cirugía , Articulación de la Rodilla/cirugía , Suturas , Técnicas de Sutura
7.
J Cosmet Laser Ther ; 25(1-4): 7-19, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37493187

RESUMEN

BACKGROUND: Laser hair removal is an increasingly prevalent trend of cosmetic procedures. The purpose of this study was to assess the effectiveness of hair reduction among several types of laser interventions. METHODS: The selected studies searched in PubMed and EMBASE were assessed for quality of evidence, and extracted data on absolute hair count and hair reduction rate. Qualitative data were synthesized using standardized mean difference (SMD) in frequentist network meta-analysis because various measurement units were used among selected studies. Inconsistency and small study effects were examined by design-by-treatment interaction model and comparison-adjusted funnel plot. RESULTS: A total of 13 randomized controlled trials (RCTs) (n = 652) were contributed to network meta-analysis. Pooled results revealed that diode laser showed significantly lower absolute hair count within three-month (SMD = -13.21, 95% confidence interval [CI]: -22.25 to -4.17) and around six months follow-up (SMD = -11.01, 95% CI: -18.24 to -3.77) as compared with those in control group, but no significant difference among laser interventions. All side effects observed were transient without leaving any permanent scars. CONCLUSION: Eliminating unwanted hair with lasers or intense pulsed light is safe and effective; however, which type of intervention is more beneficial in the long-term process should be studied with a longer follow-up time.


Asunto(s)
Remoción del Cabello , Terapia por Láser , Humanos , Remoción del Cabello/métodos , Metaanálisis en Red , Cabello , Láseres de Semiconductores/uso terapéutico , Cicatriz/etiología , Terapia por Láser/efectos adversos , Resultado del Tratamiento
8.
Nutr Res ; 117: 73-82, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37515942

RESUMEN

Studies have shown that 25-hydroxyvitamin D (25(OH)D) is predictive of survival following a diagnosis of cancer. However, evidence of the relationship between 25(OH)D and the survival of patients with pancreatic cancer has been inconsistent. We hypothesized that circulating 25(OH)D concentrations may be positively correlated with better prognosis in advanced pancreatic cancer. PubMed, EMBASE, Cochrane Library, and Web of Science database entries through April 2023, along with the reference lists of related studies, were searched. Additionally, we extracted observational studies reporting the association between 25(OH)D concentrations and the outcome of interest (overall survival [OS]) in advanced pancreatic cancer patients aged 18 years or older. Ultimately, 7 articles involving 2369 patients were included in this systematic review and meta-analysis. The results indicated that 25(OH)D concentrations were positively correlated with OS (hazard ratio = 2.37; 95% confidence interval, 2.22-2.54; P < .001). No association was found between 25(OH)D and progression-free survival. There was significant heterogeneity between studies in terms of OS (I2 = 85.5%, P < .001). Our subgroup analysis revealed that this high heterogeneity may be attributed to the studies' different regions, designs, sample sources, and detection methods of 25(OH)D. Additionally, Begg's and Egger's tests indicated the presence of publication bias. To our knowledge, this is the first meta-analysis to evaluate the association between 25(OH)D concentrations and OS among patients with pancreatic cancer. Our results suggested that circulating 25(OH)D concentrations were positively correlated with OS, indicating that 25(OH)D may be a potential prognostic marker in advanced pancreatic cancer.


Asunto(s)
Neoplasias Pancreáticas , Vitamina D , Humanos , Calcifediol , Pronóstico , Neoplasias Pancreáticas
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(7): 856-861, 2023 Jul 15.
Artículo en Chino | MEDLINE | ID: mdl-37460183

RESUMEN

Objective: To investigate the repair method of type Ⅱc injury in the lateral meniscus popliteal tendon area based on the porcine knee joint. Methods: Eighteen commercially available fresh porcine knee joints were randomly divided into 3 groups ( n=6). After preparing a type Ⅱc injury in the lateral meniscus popliteal tendon area, and the anterior (group A), posterior (group B), or anterior and posterior (group C) of the popliteal hiatus (PH) was sutured by vertical mattress. The tension meter was used to apply gradient tensions of 2, 4, 6, 8, and 10 N along the tibial plateau horizontally, respectively, to pull the midpoint of the lateral meniscus popliteal tendon area. The displacement values before modeling, after modeling, and after suture were recorded. The reduction value of lateral meniscus displacement and reduction rate after suture were calculated and compared between groups. Results: There was no significant difference between groups ( P>0.05) in the displacement values before modeling, after modeling, and after suture under different tensions. There was no significant difference between groups A and C ( P>0.05) in the reduction value of lateral meniscus displacement and reduction rate after suture under different tensions. The reduction value of lateral meniscus displacement and reduction rate after suture in group B were lower than those in groups A and C. The reduction value of lateral meniscus displacement under tension of 2 N and the reduction rates under tensions of 2, 4, and 6 N between groups A and B showed significant differences ( P<0.05). The reduction value of lateral meniscus displacement and the reduction rate under tensions of 2, 4, and 6 N between groups B and C showed significant differences ( P<0.05). Conclusion: Suturing the anterior area of PH is the key to repairing type Ⅱc injury of lateral meniscus popliteal tendon area.


Asunto(s)
Articulación de la Rodilla , Meniscos Tibiales , Animales , Humanos , Rodilla , Meniscos Tibiales/cirugía , Porcinos , Tendones , Tibia
10.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2284-2297, 2023 May.
Artículo en Chino | MEDLINE | ID: mdl-37282857

RESUMEN

Heterologous biomimetic synthesis of the active ingredients of traditional Chinese medicine(TCM) is a new mode of resource acquisition and has shown great potential in the protection and development of TCM resources. According to synthetic biology and by constructing biomimetic microbial cells and imitating the synthesis of active ingredients in medicinal plants and animals, the key enzymes obtained from medicinal plants and animals are scientifically designed and systematically reconstructed and optimized to realize the heterologous synthesis of the active ingredients in microorganisms. This method ensures an efficient and green acquisition of target products, and also achieves large-scale industrial production, which is conducive to the production of scarce TCM resources. Additiona-lly, the method playes a role in agricultural industrialization, and provides a new option for promoting the green and sustainable deve-lopment of TCM resources. This review systematically summarized the important progress in the heterologous biomimetic synthesis of TCM active ingredients from three research areas: biosynthesis of terpenoids, flavonoids, phenylpropanoids, alkaloids and other active ingredients, key points and difficulties in heterologous biomimetic synthesis, and biomimetic cells with complex TCM ingredients. This study facilitated the application of new generation of biotechnology and theory to the development of TCM.


Asunto(s)
Alcaloides , Medicamentos Herbarios Chinos , Plantas Medicinales , Animales , Medicina Tradicional China , Biomimética
11.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2316-2324, 2023 May.
Artículo en Chino | MEDLINE | ID: mdl-37282860

RESUMEN

Patchoulol is an important sesquiterpenoid in the volatile oil of Pogostemon cablin, and is also considered to be the main contributing component to the pharmacological efficacy and fragrance of P. cablin oil, which has antibacterial, antitumor, antioxidant, and other biological activities. Currently, patchoulol and its essential oil blends are in high demand worldwide, but the traditional plant extraction method has many problems such as wasting land and polluting the environment. Therefore, there is an urgent need for a new method to produce patchoulol efficiently and at low cost. To broaden the production method of patchouli and achieve the heterologous production of patchoulol in Saccharomyces cerevisiae, the patchoulol synthase(PS) gene from P. cablin was codon optimized and placed under the inducible strong promoter GAL1 to transfer into the yeast platform strain YTT-T5, thereby obtaining strain PS00 with the production of(4.0±0.3) mg·L~(-1) patchoulol. To improve the conversion rate, this study used protein fusion method to fuse SmFPS gene from Salvia miltiorrhiza with PS gene, leading to increase the yield of patchoulol to(100.9±7.4) mg·L~(-1) by 25-folds. By further optimizing the copy number of the fusion gene, the yield of patchoulol was increased by 90% to(191.1±32.7) mg·L~(-1). By optimizing the fermentation process, the strain was able to achieve a patchouli yield of 2.1 g·L~(-1) in a high-density fermentation system, which was the highest yield so far. This study provides an important basis for the green production of patchoulol.


Asunto(s)
Aceites Volátiles , Pogostemon , Sesquiterpenos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Sesquiterpenos/metabolismo , Aceites Volátiles/metabolismo
12.
Nutr Cancer ; 75(6): 1413-1426, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37140894

RESUMEN

A few previous studies have investigated the prognostic value of the prognostic nutritional index (PNI) in patients treated with immune checkpoint inhibitors (ICIs); however, the results are inconsistent. Therefore, this study aimed to clarify the prognostic significance of PNI. The PubMed, Embase, and Cochrane Library databases were searched. A meta-analysis of the impact of PNI on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of adverse events (AEs) in patients treated with ICIs was performed. Twenty-three studies involving 2,386 patients were included. Low PNI was associated with significantly poor OS (hazard ratio [HR] = 2.26, 95% confidence interval [CI]: 1.81-2.82, P < .001) and short PFS (HR = 1.75, 95% CI: 1.54-1.99, P < .001). Patients with low PNI tended to have a low ORR (odds ratio [OR] = 0.47, 95% CI: 0.34-0.65, P < .001) and DCR (OR = 0.43, 95% CI: 0.34-0.56, P < .001). However, the subgroup analysis demonstrated no significant association between PNI and survival time in patients receiving a programmed death ligand-1 inhibitor. PNI was significantly associated with survival time and treatment efficacy in patients treated with ICIs.


Asunto(s)
Neoplasias , Evaluación Nutricional , Humanos , Pronóstico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Resultado del Tratamiento
13.
Brief Bioinform ; 24(3)2023 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-37122066

RESUMEN

Peptide-major histocompatibility complex I (MHC I) binding affinity prediction is crucial for vaccine development, but existing methods face limitations such as small datasets, model overfitting due to excessive parameters and suboptimal performance. Here, we present STMHCPan (STAR-MHCPan), an open-source package based on the Star-Transformer model, for MHC I binding peptide prediction. Our approach introduces an attention mechanism to improve the deep learning network architecture and performance in antigen prediction. Compared with classical deep learning algorithms, STMHCPan exhibits improved performance with fewer parameters in receptor affinity training. Furthermore, STMHCPan outperforms existing ligand benchmark datasets identified by mass spectrometry. It can also handle peptides of arbitrary length and is highly scalable for predicting T-cell responses. Our software is freely available for use, training and extension through Github (https://github.com/Luckysoutheast/STMHCPan.git).


Asunto(s)
Algoritmos , Péptidos , Alelos , Péptidos/química , Unión Proteica , Programas Informáticos
14.
Cytotherapy ; 25(6): 615-624, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36828738

RESUMEN

BACKGROUND AIMS: Most current chimeric antigen receptor (CAR) T cells are generated by viral transduction, which induces persistent expression of CARs and may cause serious undesirable effects. Messenger RNA (mRNA)-based approaches in manufacturing CAR T cells are being developed to overcome these challenges. However, the most common method of delivering mRNA to T cells is electroporation, which can be toxic to cells. METHODS: The authors designed and engineered an exosome delivery platform using the bacteriophage MS2 system in combination with the highly expressed protein lysosome-associated membrane protein 2 isoform B on exosomes. RESULTS: The authors' delivery platform achieved specific loading and delivery of mRNA into target cells and achieved expression of specific proteins, and anti-CD3/CD28 single-chain variable fragments (scFvs) expressed outside the exosomal membrane effectively activated primary T cells in a similar way to commercial magnetic beads. CONCLUSIONS: The delivery of CAR mRNA and anti-CD3/CD28 scFvs via designed exosomes can be used for ex vivo production of CAR T cells with cancer cell killing capacity. The authors' results indicate the potential applications of the engineered exosome delivery platform for direct conversion of primary T cells to CAR T cells while providing a novel strategy for producing CAR T cells in vivo.


Asunto(s)
Exosomas , Receptores Quiméricos de Antígenos , Anticuerpos de Cadena Única , Humanos , Linfocitos T , Receptores Quiméricos de Antígenos/metabolismo , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/metabolismo , Antígenos CD28 , Exosomas/genética , Exosomas/metabolismo , Inmunoterapia Adoptiva/métodos , Línea Celular Tumoral , Ingeniería Celular/métodos , Receptores de Antígenos de Linfocitos T
15.
Arthroscopy ; 39(5): 1244-1250, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36526511

RESUMEN

PURPOSE: To verify the reliability of patellar tendon-trochlear groove angle (PTTG-A) measured by computed tomography (CT) and the clinical significance in evaluation of patellar instability. METHODS: A retrospective study of hospitalized patients with knee pain or injury and had knee CT from January 2017 to June 2021 was performed. PTTG-A and tibial tuberosity-trochlear groove (TT-TG) distance were measured on CT. Spearman correlation analysis was analyzed between the 2 measurements. The intraclass correlation coefficient was determined for inter- and intraobserver reproducibility. The capacity of PTTG-A and TT-TG to predict patellar instability was evaluated by the receiver operating characteristic curve. Data from the control group were used to determine the pathologic thresholds and logistic regression analysis. RESULTS: Included were 113 patients. There were 60 patients with the history of at least 2 episodes of patellar dislocation (study group) and 53 patients without a history of patellar dislocation (control group). The respective PTTG-A and TT-TG distances in the study group (35.2 ± 8.4° and 19.6 ± 4.6 mm) were significantly greater than those of the controls (20.8 ± 5.8° and 13.3 ± 4.5 mm) (P < .001). The correlation between the 2 measurements was strong (r = 0.730, P < .001). The inter- and intraobserver reliability of the PTTG-A were better than TT-TG distance in both groups. The AUC of PTTG-A was greater than that of the TT-TG distance (0.895 vs 0.769, respectively). With the cutoff value of PTTG-A and TT-TG being 26.3° and 16.3 mm, the value of the pathologic threshold of PTTG-A was 30.0°, with a dominance ratio of 16.88 (95% confidence interval 2.88-98.89, P = .002). CONCLUSIONS: The PTTG-A measured on a single CT slice of the distal femoral trochlear groove is a more reliable measurement than TT-TG distance for the prediction of patellar instability. LEVEL OF EVIDENCE: III; A retrospective cohort study.


Asunto(s)
Inestabilidad de la Articulación , Luxación de la Rótula , Ligamento Rotuliano , Articulación Patelofemoral , Humanos , Luxación de la Rótula/patología , Estudios Retrospectivos , Reproducibilidad de los Resultados , Articulación Patelofemoral/patología , Inestabilidad de la Articulación/patología , Imagen por Resonancia Magnética , Tibia/patología , Tomografía Computarizada por Rayos X
17.
BMC Musculoskelet Disord ; 23(1): 1102, 2022 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-36528565

RESUMEN

BACKGROUND: There has been no ideal treatment for freezing-phase frozen shoulder to rapidly relieve pain and improve joint mobility. No any other team directly compared the effectiveness of combination of arthroscopic release and corticosteroid hydrodilatation with corticosteroid hydrodilatation only in treatment of freezing-phase frozen shoulder. METHODS: Seventy-two patients with freezing-phase frozen shoulder were randomly assigned to combined arthroscopic release with corticosteroid hydrodilatation (group A) or corticosteroid hydrodilatation only (group B). Clinical states were examined at baseline and periodically (Weeks 1, 4, 12, 24 and 1 year) after intervention by passive ROM; visual analog scale (VAS); UCLA and Disabilities of the Arm, Shoulder, and Hand (DASH) score. RESULTS: The passive ROM, VAS, UCLA and DASH scores always improved along the time points (all p < 0.01). The passive abduction (pAB), passive forward flexion (pFL), passive external rotation (pER), passive internal rotation (pIR) were better in group A than in group B at Week 1, 4, 12, 24 (all p < 0.01). At 1 year post-operation, the pFL and pIR were better in group A than in group B (all p < 0.01). VAS scores of group A were similar with those of group B (all p > 0.01), the differences between group A and group B were all lower than minimal clinically important difference (MCID). At Week 12, the UCLA sores and DASH scores were 26.8 ± 3.8, 14.2 ± 2.0 in group A versus 22.3 ± 3.4, 22.5 ± 3.1 in group B (all p < 0.01). At Week 24 post-operation, there were 32.7 ± 2.0, 9.8 ± 1.5 in group A versus 26.3 ± 3.6, 17.5 ± 3.5 in group B (all p < 0.01). At 1 year post-operation, there were 34.5 ± 0.8, 1.7 ± 1.5 in group A versus 32.1 ± 2.3, 8.8 ± 2.8 in group B (all p < 0.01), the differences of UCLA scores between group A and group B at Week 24 was higher than the MCID. There were no complications such as infection, nerve or vascular injury. CONCLUSIONS: Combined arthroscopic release with corticosteroid hydrodilatation would yield better results in passive ROM and function than corticosteroid hydrodilatation only. TRIAL REGISTRATION: ChiCTR1900024235, July 2, 2019 (Retrospectively registered).


Asunto(s)
Bursitis , Articulación del Hombro , Humanos , Articulación del Hombro/cirugía , Congelación , Bursitis/tratamiento farmacológico , Bursitis/cirugía , Rango del Movimiento Articular/fisiología , Corticoesteroides/uso terapéutico , Dolor , Resultado del Tratamiento
18.
Nutr Res ; 107: 165-178, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36283229

RESUMEN

Several clinical trials have reported that patients with cancer cachexia can benefit from n-3 polyunsaturated fatty acids (n-3 PUFAs) supplements; however, the results have been conflicting. This systematic review and meta-analysis aimed to evaluate the effect of n-3 PUFAs on cancer cachexia. A search of the PubMed, Embase, and Cochrane Library databases was performed to identify the included randomized controlled trials. Trials including patients with cancer cachexia who were administered a course of n-3 PUFAs were included. A meta-analysis on body weight, lean body weight, proinflammatory factors, quality of life, and median duration of survival was conducted. A total of 12 randomized controlled trials with 1184 patients were included. No effect on body weight (standard mean difference [SMD], 0.10; 95% CI, -0.06 to 0.26; P = .236), lean body weight (SMD, -0.17; 95% CI, -0.36 to 0.03, P = .095), or proinflammatory factors (interleukin-6: SMD, 0.31; 95% CI, -0.14 to 0.75; P = .18; tumor necrosis factor-α: SMD, -0.85; 95% CI, -2.39 to 0.69; P = .28) was observed. The use of n-3 PUFAs was associated with a significant improvement in quality of life (SMD, 0.70; 95% CI, 0.01-1.40; P = .048) and median duration of survival (median survival ratio, 1.10; 95% CI, 1.02-1.19; P = .014). For patients with cancer cachexia, our meta-analysis indicated that n-3 PUFAs improved quality of life and survival, but not body weight.


Asunto(s)
Ácidos Grasos Omega-3 , Neoplasias , Humanos , Caquexia/tratamiento farmacológico , Caquexia/etiología , Calidad de Vida , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Suplementos Dietéticos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Front Immunol ; 13: 951582, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35874760

RESUMEN

Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Ováricas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Epitelial de Ovario/patología , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Pronóstico , Microambiente Tumoral/genética
20.
Zhongguo Gu Shang ; 35(6): 532-7, 2022 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-35730222

RESUMEN

OBJECTIVE: To compare computed tomography (CT) measurement results of external deviation angle of patellar tendon and tibia tubercle-trochlea groove (TT-TG), as well as the diagnostic ability and pathology in recurrent patellar dislocation threshold. METHODS: From January 2015 to March 2020, 46 patients with recurrent patella dislocation and 112 patients with non-patella dislocation were retrospectively analyzed. Forty-six patients with recurrent patella dislocation were divived into 2 groups according to TT-TG value, 11 patients with patellar dislocation with TT-TG≥20 mm(group A), including 7 males and 4 females, aged from 16 to 27 years old with an average of(21.00±3.98) years old; 35 patients with patellar dislocation with TT-TG<20 mm(group B), including 14 males and 21 females, aged from 16 to 37 years old with an average of(22.83±6.09) years old. While 112 patients with non-patella dislocation(group C) included 63 males and 49 females, aged 16 to 36 years old with an average of(22.87±5.69) years old. The measurement data of external deviation angle of patellar tendon and TT-TG value among three groups were compared. Spearman analysis was used to analyze correlation among them. Intraclass correlation coefficient (ICC) was used to determine repeatability within group. Receiver operating characteristic (ROC) area under the curve was used to evaluate diagnostic ability of parameters, and calculate osteotomy parameters of external deviation angle of patellar tendon, as well as external deviation angle of patellar tendon and TT-TG value in the diagnosis of recurrent patella diagnostic parameters of dislocation. RESULTS: External deviation angle of patellar tendon in group A, B and C was (22.04±3.09)°, (17.20±4.43)°and (10.22±3.45)° respectively;while TT-TG value was(21.15±0.71) mm, (15.97±2.69) mm and (11.12±3.77) mm, there were significance among three groups (P<0.01), and had difference between group A and B(P<0.01). There was strong positive correlation between external deviation angle of patellar tendon and TT-TG value (r=0.735, P<0.000 1). The intra-group ICC value(0.980, 0.982) of external deviation angle of patellar tendon in group A and B have better repeatability than TT-TG value (0.594, 0.775). The external deviation angle of patellar tendon in group C(0.956) and repeatability of TT-TG value(0.906) was very good. In the diagnosis of recurrent patellar dislocation, the area under ROC curve of external deviation angle of patellar tendon (0.916) was greater than TT-TG value(0.886), and diagnostic parameters were 13.84°and 14.69 mm, respectively;in tibial osteotomy, the area under ROC curve of external deviation angle of patellar tendon was 0.821, and osteotomy parameter was 20.15°. CONCLUSION: CT imaging could reliably measure external deviation angle of patellar tendon.There is a strong positive correlation between external deviation angle of patellar tendon and value of TT-TG, which could be used to determine pathological state of recurrent patellar dislocation, and external deviation angle of patellar tendon is superior to the TT-TG value in the diagnosis of recurrent patellar dislocation. The external deviation angle of patellar tendon could also be used to guide the formulation of the tibial osteotomy plan for recurrent patellar dislocation.


Asunto(s)
Inestabilidad de la Articulación , Luxación de la Rótula , Ligamento Rotuliano , Articulación Patelofemoral , Adolescente , Adulto , Femenino , Humanos , Masculino , Rótula/cirugía , Luxación de la Rótula/diagnóstico por imagen , Ligamento Rotuliano/diagnóstico por imagen , Estudios Retrospectivos , Tibia/cirugía , Adulto Joven
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