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Terapia de Reemplazo Enzimático , Enfermedad del Almacenamiento de Glucógeno Tipo II , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Humanos , Femenino , Terapia de Reemplazo Enzimático/métodos , alfa-Glucosidasas/uso terapéutico , alfa-Glucosidasas/genética , MutaciónRESUMEN
OBJECTIVE: To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. METHODS: Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. RESULTS: The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. CONCLUSION: Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.
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Astrocitos , Piruvato Quinasa , Transducción de Señal , Traumatismos de la Médula Espinal , Proteínas Señalizadoras YAP , Animales , Ratas , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Proteínas de la Membrana/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Proteínas de Unión a Hormona Tiroide , Hormonas Tiroideas/metabolismoRESUMEN
Objective: To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns. Methods: This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing. Results: Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P<0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P<0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group (Z =-4.67, P<0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P<0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P<0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ2 values of 4.13 and 3.91, respectively, P<0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups (P>0.05). Conclusions: For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.
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Dermis Acelular , Quemaduras , Desbridamiento , Trasplante de Piel , Humanos , Masculino , Quemaduras/terapia , Quemaduras/cirugía , Femenino , Estudios Retrospectivos , Lactante , Preescolar , Trasplante de Piel/métodos , Desbridamiento/métodos , Niño , Cicatrización de HeridasRESUMEN
Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9â¶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.
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Enfermedad de Crohn , Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedad de Crohn/genética , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Estudios Retrospectivos , Mucinas , Células Epiteliales/patología , Biología MolecularRESUMEN
Objective: To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network. Methods: Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia. Results: The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension (OR=3.99, 95%CI: 1.81-8.80), diabetes (OR=4.64, 95%CI: 1.64-13.15) and dyslipidemia (OR=4.26, 95%CI: 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions: The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.
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Diabetes Mellitus , Dislipidemias , Hipertensión , Humanos , Anciano , China/epidemiología , Diabetes Mellitus/epidemiología , Hipertensión/epidemiología , Hipertensión/complicaciones , Factores de Riesgo , Dislipidemias/epidemiología , Dislipidemias/complicaciones , Estilo de VidaRESUMEN
Objective: To investigate the effects of carbon black and cadmium (Cd) combined exposure on autophagy and inflammatory response mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in human bronchial epithelial (16HBE) cells. Methods: In January 2022, human bronchial epithelial (16HBE) cells were resuscitated and cultured. Carbon black nanoparticles (CBNPs) were oxidized to adsorb Cd ions to construct "CBNPs-Cd" complexes. CCK-8 assay was used to detect the effects of different concentrations and time combinations of CBNPs and Cd on the viability of 16HBE cells. The subsequent dose groups were exposed to 2 µg/ml Cd, 100 µg/ml CBNPs, 100 µg/ml CBNPs+2 µg/ml Cd for 24 h. The number of autophagosomes and autolysosomes was detected by transmission electron microscopy. Western blotting was used to detect the protein expressions of PERK, eukaryotic initiation factor 2α (eIf2α), activating transcription factor 4 (ATF4), sequestosome 1 (SQSTM1/P62), and microtubule-associated protein 1 light chain 3 (LC3). After PERK gene was silenced by siRNA technology, the changes of autophagy marker proteins P62 and LC3 were detected, and the expressions of inflammatory factors interleukin-6 (IL6) and interleukin-8 (IL8) were detected by fluorescence quantitative PCR technique. One-way ANOVA analysis was used to compare three groups or more. LSD test was used for comparison between two groups. Factorial analysis was used for multivariate component analysis. Results: There was no significant change in cell viability of 16HBE after 24 h exposure to CBNPs and Cd alone or combined (P>0.05). Compared with the control group, the expressions of P62 and LC3 in 16HBE cells were significantly increased in the CBNPs and Cd alone/combined exposure group (P<0.05), and the number of autophagosomes and autophagolysosomes in the combined exposure group was increased compared with other groups. Compared with the control group, CBNPs and Cd alone exposure group had no significant effects on p-PERK/PERK and p-eIf2α/eIf2α protein expression (P>0.05). However, the protein expressions of p-PERK/PERK and p-eIf2α/eIf2α and ATF4 were all increased in the combined exposure group (P<0.05), and the levels of IL6 and IL8 in 16HBE cells in the combined exposure group of CBNPs and Cd were significantly higher than those in the control group (P<0.05). The levels of LC3 protein, IL6 and IL8 were decreased in the CBNPs-Cd combined exposure group after knockdown of PERK gene (P<0.05). The results of factorial analysis showed that exposure to CBNPs and Cd had significant effects on the expression of P62, LC3 and IL6 (P<0.05), but the interaction between the two chemicals had no statistical significance (P>0.05) . Conclusion: CBNPs-Cd combined exposure may inhibit autophagy and increase inflammation in human bronchial epithelial cells through activation of PERK-eIf2α-ATF4 pathway.
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Cadmio , Hollín , Humanos , Cadmio/toxicidad , Hollín/toxicidad , Interleucina-8 , Interleucina-6 , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/farmacología , Autofagia , Células Epiteliales/metabolismo , Estrés del Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , InflamaciónRESUMEN
OBJECTIVES: To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural-urban communities of Southwestern China. STUDY DESIGN: Retrospective cohort study. METHOD: Data on HIV/AIDS cases reported in 2005-20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural-urban regions were compared using Kaplan-Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. RESULTS: Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28-1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29-1.55; p < 0.0001), AHD cohort (1.38, 1.24-1.54; p < 0.0001), and SIS cohort (1.49, 1.23-1.81; p < 0.0001). CONCLUSIONS: A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Estudios Retrospectivos , Infecciones por VIH/epidemiología , Infecciones por VIH/diagnóstico , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
The objective was to evaluate the efficacy of curcumin in improving mouth opening (MO), burning sensation (BS), and tongue protrusion (TP) symptoms in patients with oral submucous fibrosis (OSF). An electronic search up to November 2022 was conducted in the PubMed, Web of Science, Embase, EBSCO, ProQuest, and Cochrane Library databases to identify studies using curcumin in the treatment of OSF with comparison to control groups (drugs previously proven to be effective for OSF treatment) or placebo. Only randomized controlled trials (RCTs) were considered. RevMan 5.3 software was used for the meta-analysis. Thirteen RCTs met the eligibility criteria and were included in the analysis. The results showed no significant improvement in MO (in millimetres) for curcumin when compared to control at 1 month (P = 0.91), 2 months (P = 0.54), 3 months (P = 0.56), or 6 months (P = 0.17) of treatment. There was no significant difference in BS (assessed using a visual analogue scale) between curcumin and control after 1 month (P = 0.05), 2 months (P = 0.64), 3 months (P = 0.13), or 6 months (P = 0.56) of treatment. Compared with the control groups, treatment with curcumin for 1 month (P = 0.32), 2 months (P = 0.07), and 3 months (P = 0.14) did not significantly improve the TP (in millimetres) of patients. The administration of curcumin, whether topically applied or taken orally, did not confer statistically significant improvements in MO, BS, or TP in comparison to the control treatments, among patients with OSF. The results of this meta-analysis showed that compared to placebo, the application of curcumin for 6 months markedly alleviated BS (P < 0.001). Curcumin treatment in OSF reaches a clinically effective range, but more bioavailability-centred outcomes should be reported. Robust multicentre RCTs are warranted to elucidate the efficacy of curcumin in improving specific outcomes like MO, BS, and TP in patients with this condition. Defining the therapeutic role of this natural compound may provide an effective botanical alternative for managing OSF.
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Curcumina , Fibrosis de la Submucosa Bucal , Enfermedades de la Lengua , Humanos , Fibrosis de la Submucosa Bucal/tratamiento farmacológico , Curcumina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Objective: To explore the toxic effect of carbon black nanoparticles on human bronchial epithelial cells, and identify the differentially expressed circular RNA based on the full transcriptome high-throughput sequencing, so as to provide evidence for the development of biomarkers exposed to carbon black nanoparticles and their application on epigenetic toxicology. Methods: In June 2020, 16 HBE cells were treated with carbon black nanoparticles at concentrations of 20, 40 and 80 µg/ml, and 16 HBE cells without any intervention were used as the control group. The cytotoxicity of carbon black nanoparticles was detected by CCK8 and LDH experiments. Real-time quantitative fluorescent PCR (qRT-PCR) and ELISA were used to detect the changes of interleukin-6 (IL-6) and interleukin-8 (IL-6, IL-8) mRNA and protein levels of carbon black nanoparticles with concentration gradient after 72 h exposure. Western blot analysis was conducted to detect the expression levels of toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (P-NF-κB), apoptosis-related speckled protein (ASC) and Caspase-1 associated with nuclear factor-κB. According to high-throughput sequencing results, differentially expressed Circrnas were screened and identified by qRT-PCR, and those with stable differentially expressed circrnas and the strongest association with the NF-κB pathway were selected for ring performance identification. Results: After being exposed to carbon black nanoparticles for 72 h, the activity of 16HBE cells decreased significantly (P<0.05), and the release of lactate dehydrogenase increased significantly (P<0.05). Compared with control group, mRNA expression levels of IL-6 and IL-8, protein levels of IL-6 and IL-8 were increased, and protein levels of TLR4, p-NF-κB, ASC and Caspase-1 were significantly up-regulated in 16 HBE cells of different concentrations, with statistical significance (P<0.05). Compared with the control group, a total of 492 differentially expressed circular Rnas (|log2 FC|>1) were detected. Among the 5 differentially expressed (P<0.05) circular Rnas, circ_002642 was selected as the object of subsequent research on circular Rnas, affter 72 hours of exposure to 80 µg/ml CBNPs, 16HBE cells showed signlficantly higher expression of circ_002642 (P<0.05) . Conclusion: Carbon black nanoparticles can induce differentially expressed circular RNAs associated with inflammatory response in human bronchial epithelial cells.
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FN-kappa B , ARN Circular , Humanos , Interleucina-8 , Hollín/toxicidad , Receptor Toll-Like 4 , Interleucina-6 , Células Epiteliales , Caspasa 1RESUMEN
Objective: To evaluate the efficacy and safety of superpulse thulium laser lithotripsy in the intracavitary treatment of urinary calculi. Methods: From May 2021 to July 2022, patients diagnosed with urinary calculi were screened in four medical centers. Those who met the criteria were treated with superpulse thulium fiber laser under endoscope. The patients' perioperative conditions were recorded. The main effective index was stone-free rate (SFR) 4 weeks after operation, the main safety index was the failure rate of the experimental instruments during operation, and the secondary safety index was the incidence rate of perioperative complications. Results: A total of 76 eligible patients completed superpulse thulium fiber laser lithotripsy, with an average age of (52.0±11.1) years, 54 males and 22 females. There were 31 renal stones, 43 ureteral stones and 2 bladder stones. Percutaneous nephrolithotomy was performed in 17 patients. Ureteroscopy lithotripsy/flexible ureteroscopy lithotripsy was performed in 57 patients and transurethral bladder lithotripsy was in 2 patients. The lithotripsy time of all patients was (50.9±31.4) minutes. There was no failure of experimental instruments during the operation. Six patients refused follow-up examination after operation. The incidence of postoperative adverse events was 61.8% (47/76). One patient needed hospitalization due to inguinal hernia after operation, and the rest were classified as Clavien-dindo grade 1-2. The SFR was 94.3% (66/70) at 4 weeks after operation. Conclusion: It is effective and safe to use superpulse thulium fiber laser in the treatment of urinary calculi.
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Cálculos Renales , Láseres de Estado Sólido , Litotripsia por Láser , Litotricia , Cálculos Ureterales , Cálculos Urinarios , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Litotripsia por Láser/efectos adversos , Tulio , Resultado del Tratamiento , Cálculos Urinarios/terapia , Cálculos Urinarios/etiología , Cálculos Renales/etiología , Cálculos Renales/cirugía , Cálculos Ureterales/terapia , Ureteroscopía/efectos adversos , Láseres de Estado Sólido/uso terapéuticoRESUMEN
BACKGROUND: The search for prognostic biomarkers indicating sensitivity to immunotherapy in lung adenocarcinoma patients has zeroed in on genes in the switch/sucrose non-fermentable (SWI/SNF) pathway. The mutational profiles of key genes are not clearly defined, however, and no comparisons have been conducted on whether mutations in the genes involved provide the same predictive value. METHODS: In this study, analysis of clinical factors, tumor mutation burden (TMB), chromosomal instability, and co-alterations was conducted for 4344 lung adenocarcinoma samples. Independent online cohorts (N = 1661 and 576) were used to supplement the analysis with survival and RNA-seq data. RESULTS: Mutational burden and chromosomal instability analysis showed that ARID family mutations (including ARID1A, ARID1B, or ARID2 mutations) and SMARC family mutations (including SMARCA4 or SMARCB1 mutations) display different profiles from wild-type (WT) samples (TMB: ARID versus WT: P < 2.2 × 10-16, SMARC versus WT: P < 2.2 × 10-16; CIN: ARID versus WT: P = 1.8 × 10-5, SMARC versus WT: P = 0.027). Both mutant groups have a higher proportion of transversions than transitions, whereas the ratio is more equal for wild-type samples. Survival analysis shows that patients with ARID mutations were more sensitive to immunotherapy treatment than wild-type and SMARC-mutated patients (P < 0.001 and P = 0.013, respectively), and multivariate Cox analysis reveals that the presence of ARID mutations is likely the main cause. CONCLUSIONS: The research presented in this study shows that mutations in the ARID gene family, including ARID1A, ARID1B, and ARID2, are primarily responsible for the sensitive response to immunotherapy treatment in patients with lung adenocarcinoma.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Humanos , Mutación , Biomarcadores de Tumor/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Inmunoterapia , Inestabilidad Cromosómica , ADN Helicasas , Proteínas Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: Methamphetamine causes considerable short- and long-term adverse health effects. Our aim was to assess the effects of methamphetamine use on pulmonary hypertension and lung diseases at the population level. METHODS: This population-based retrospective study used data from the Taiwan National Health Insurance Research Database between 2000 and 2018 that included 18,118 individuals with methamphetamine use disorder (MUD) and 90,590 matched participants of the same age and sex without substance use disorder as the non-exposed group. A conditional logistic regression model was used to estimate associations of methamphetamine use with pulmonary hypertension and lung diseases such as lung abscess, empyema, pneumonia, emphysema, pleurisy, pneumothorax, or pulmonary hemorrhage. Incidence rate ratios (IRRs) of pulmonary hypertension and hospitalization due to lung diseases were determined between the methamphetamine group and non-methamphetamine group using negative binomial regression models. RESULTS: During an 8-year observation period, 32 (0.2%) individuals with MUD and 66 (0.1%) non-methamphetamine participants suffered from pulmonary hypertension, and 2652 (14.6%) individuals with MUD and 6157 (6.8%) non-methamphetamine participants suffered from lung diseases. After adjusting for demographic characteristics and comorbidities, individuals with MUD were 1.78 times (95% confidence interval (CI) = 1.07-2.95) more likely to have pulmonary hypertension and 1.98 times (95% CI = 1.88-2.08) more likely to have a lung disease, especially emphysema, lung abscess, and pneumonia in descending order. Furthermore, compared to the non-methamphetamine group, the methamphetamine group was associated with higher risks of hospitalization caused by pulmonary hypertension and lung diseases. The respective IRRs were 2.79 and 1.67. Individuals with polysubstance use disorder were associated with higher risks of empyema, lung abscess, and pneumonia compared to individuals with MUD alone, with respective adjusted odds ratios of 2.96, 2.21, and 1.67. However, pulmonary hypertension and emphysema did not differ significantly between MUD individuals with or without polysubstance use disorder. CONCLUSIONS: Individuals with MUD were associated with higher risks of pulmonary hypertension and lung diseases. Clinicians need to ensure that a methamphetamine exposure history is obtained as part of the workup for these pulmonary diseases and provide timely management for this contributing factor.
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PURPOSE: In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications. METHODS: We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort. RESULTS: A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%, p = 1.00) and major complications (2.5% vs. 6.2%, p = 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications. CONCLUSION: Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.
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Ileostomía , Neoplasias del Recto , Humanos , Ileostomía/efectos adversos , Estudios Retrospectivos , Bevacizumab/uso terapéutico , Puntaje de Propensión , Calidad de Vida , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Neoplasias del Recto/complicaciones , Resultado del TratamientoRESUMEN
We visualized negative refraction of phonon polaritons, which occurs at the interface between two natural crystals. The polaritons-hybrids of infrared photons and lattice vibrations-form collimated rays that display negative refraction when passing through a planar interface between the two hyperbolic van der Waals materials: molybdenum oxide (MoO3) and isotopically pure hexagonal boron nitride (h11BN). At a special frequency ω0, these rays can circulate along closed diamond-shaped trajectories. We have shown that polariton eigenmodes display regions of both positive and negative dispersion interrupted by multiple gaps that result from polaritonic-level repulsion and strong coupling.
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Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regenerationï¼Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade â ¢ to grade â ¡, one case improved from grade â ¡ to grade â ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade â ,â ¡,and â ¢ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade â , 2.66 ms in grade â ¡, and 3.72 ms in grade â ¢).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.
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Procedimientos Ortopédicos , Osteoartritis de la Rodilla , Plasma Rico en Plaquetas , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/terapia , Estudios Retrospectivos , Imagen por Resonancia MagnéticaRESUMEN
Corona Virus Disease 2019 (COVID-19) has caused several pandemic peaks worldwide due to its high variability and infectiousness, and COVID-19 has become a long-standing global public health problem. There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) frequently causes multi-organ injuries and more severe neurological manifestations. Therefore, increased awareness of possible neurological complications is beneficial in preventing and mitigating the impact of long-term sequelae and improving the prognostic outcome of critically ill patients with COVID-19. Here, we review the main pathways of SARS-CoV-2 neuroinvasion and the potential mechanisms causing neurological damage. We also discuss in detail neurological complications, aiming to provide cutting-edge basis for subsequent related basic research and clinical studies of diagnosis and treatment.
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COVID-19 , Enfermedades del Sistema Nervioso , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/terapiaRESUMEN
OBJECTIVE: To investigate the effect of allogeneic nanofat combined with platelet-rich plasma (PRP) for treatment of pressure injury wounds in rats. METHODS: Forty SD rat models with pressure injury wounds were randomly divided into 4 groups (n=10) for treatment with nanofat, PRP (platelet count about 6.2 times that of normal whole blood), nanofat combined with PRP, or PBS only (control group).Wound healing was observed on days 1, 3, 5, 7, 10 and 14 and wound healing rate was calculated. On days 5, 10 and 14, tissue samples were taken from the wounds for HE staining, Masson staining, immunohistochemistry, and Western blotting to observe inflammatory cell infiltration, collagen formation, deposition and arrangement, angiogenesis, inflammatory factor expression and VEGF expression in the wounds. RESULTS: The combined treatment with nanofat and PRP achieved the highest wound healing rates at all the time points of observation (P < 0.05), enhanced inflammatory cell infiltration on day 5, and accelerated dermal and epidermal growth compared with the other treatments (P < 0.05). The combined treatment also more effectively promoted collagen expression and its regular arrangement (P < 0.05) and enhanced angiogenesis in the wounds than nanofat and PRP alone, without significant difference between the latter two treatments (P > 0.05). Immunohistochemistry and Western blotting showed that the expressions of MCP-1 and VEGF in the wounds were the highest in the combined treatment group (P < 0.05) and were higher in nanofat and PRP treatment groups than in the control group (P < 0.05). CONCLUSION: Nanofat combined with PRP can significantly promote healing of pressure injury wounds in rats, and their synergistic effect sheds light on a new strategy for treatment of pressure injury wounds.
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Plasma Rico en Plaquetas , Úlcera por Presión , Animales , Ratas , Ratas Sprague-Dawley , Úlcera por Presión/terapia , Factor A de Crecimiento Endotelial Vascular , ColágenoRESUMEN
Rhegmatogenous retinal detachment (RRD) is a retinal vitreous disease, with increasing incidence in recent years. Pars plana vitrectomy is one of the most common treatments for RRD. To prevent re-detachment after the primary surgery and guarantee the visual outcome of the patients, we highlight the techniques for RRD during the PPV, including the surgical skills to manipulate the breaks, peripheral retina and vitreous base, meanwhile, empathized on the posterior vitreous detachment and posterior vitreous cortex. The aim is to increase the rate of anatomical re-attachment and to improve visual function.