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BACKGROUND: Antiretroviral Therapy (ART) is pivotal in extending the lives of people living with HIV (PLWH) and minimizing transmission. Rapid ART initiation, defined as commencing ART within seven days of HIV diagnosis, is recommended for all PLWH. METHOD: A retrospective cohort study was conducted using data from the China Information System for Disease Control and Prevention. This study included PLWH diagnosed between January 2018 and December 2021 and treated by December 2022. Factors influencing rapid ART initiation were examined using univariate and multivariate Cox regression analyses. RESULTS: The study analyzed 1310 cases. The majority were male (77.4%), over 50 years old (46.7%), and contracted HIV through heterosexual transmission (70.0%). Rapid ART initiation was observed in 36.6% (n = 479) of cases, with a cumulative treatment rate of 72.9% within 30 days post-diagnosis. Heterosexual contact was associated with longer intervals from diagnosis to treatment initiation compared to homosexual contact (Adjusted Hazard Ratio (HR) = 0.813, 95% Confidence Interval (CI): 0.668-0.988). Individuals older than 50 years (Adjusted HR = 1.852, 95%CI: 1.149-2.985) were more likely to initiate ART rapidly. Conversely, treatment at the Second Public Hospital (Adjusted HR = 0.483, 95% CI: 0.330-0.708) and a CD4 cell counts above 500 (Adjusted HR = 0.553, 95% CI: 0.332-0.921) were associated with a lower likelihood of initiating treatment within seven days. CONCLUSIONS: A higher CD4 cell counts and receiving care in local public hospitals may deter rapid ART initiation. Providing CD4 counts results at diagnosis and offering testing and treatment in the same facility could enhance the rate of rapid ART initiation.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Estudos Retrospectivos , Contagem de Linfócito CD4 , China/epidemiologia , Modelos de Riscos Proporcionais , Fármacos Anti-HIV/uso terapêuticoRESUMO
OBJECTIVE: Report three cases of simultaneous triple semicircular canal occlusion (TSCO) and cochlear implantation (CI) as the treatment of intractable Meniere's disease (MD). CASE REPORTS: Patients with MD can present occasionally with intractable vertigo and profound sensorineural hearing loss (SNHL). TSCO and CI have been proposed to control vertigo and restore profound deafness in patients with MD separately. However, a few studies have reported simultaneous TSCO and CI in the same surgical procedure for the treatment of MD. In the present study, we described three patients with MD showing incapacitating vertigo and severe SNHL who underwent simultaneous TSCO and CI after examinations of auditory system, vestibular system, and imaging. Their symptoms were significantly alleviated during the follow-up period. CONCLUSION: The combined TSCO and CI remains a viable treatment option which is effective for the control of vertigo as well as the restoring of hearing in patients with MD.
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Implante Coclear , Perda Auditiva Neurossensorial , Doença de Meniere , Humanos , Doença de Meniere/complicações , Doença de Meniere/cirurgia , Vertigem/etiologia , Vertigem/cirurgia , Canais Semicirculares/cirurgia , Audição , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/cirurgiaRESUMO
Myelin undergoes various changes after nerve injury, and c-Jun has a close relationship with Schwann cells (SCs). However, it remains unclear whether c-Jun can be involved in nerve repair by regulating ferroptosis. To explore this, we first set up a facial nerve injury model and detected the changes of ferroptosis-related proteins and c-Jun by immunofluorescence and Western blot. Then, we cultured RSC 96 and pSCs, and studied the potential regulatory relationships by a combination of experimental methods such as CCK-8, ELISA, immunofluorescence, qRT-PCR, Western blot and viral transfection. Finally, we corroborated the role of c-Jun through animal experiments. Our experiments revealed that ferroptosis occurs after facial nerve injury. Erastin decreased GPX4, c-Jun proteins and GSH content, while PTGS2, NRF2, HO-1 proteins, MDA, Fe2+ and ROS contents increased. This effect was inhibited after c-Jun overexpression but was reversed after the addition of c-Jun siRNA. Besides, we proved in vivo that c-Jun could inhibit ferroptosis and promote the recovery of facial nerve function. In conclusion, our study identified the relationship between c-Jun and ferroptosis during peripheral nerve injury repair, which provides new ideas for studying peripheral nerve injury and repair.
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Traumatismos do Nervo Facial , Ferroptose , Traumatismos dos Nervos Periféricos , Animais , Nervo Facial/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Piperazinas , Células de Schwann/metabolismo , Transdução de SinaisRESUMO
The facial nerve is one of the vulnerable nerves in otolaryngology. Repair and recovery of facial nerve injury have a high priority in clinical practice. The proliferation and migration of Schwann cells are considered of great significance in the process of nerve injury repair. Danhong injection (DHI), as a common drug for cardiovascular and cerebrovascular diseases, has been fully certified in neuroprotection research, but its role in facial nerve injury is still not clear. Our study found that DHI can promote the proliferation and migration of RSC96 cells, a Schwann cell line, and this effect is related to the activation of the PI3K/AKT pathway. LY294002, an inhibitor of PI3K, inhibits the proliferation and migration of RSC96 cells. Further studies have found that DHI can also promote the expression of CXCL12 and GDNF at gene and protein levels, and CXCL12 is, while GDNF is not, PI3K/AKT pathway-dependent. Animal experiments also confirmed that DHI could promote CXCL12 and GDNF expression and promote facial nerve function recovery and myelin regeneration. In conclusion, our in vitro and in vivo experiments demonstrated that DHI could promote the proliferation and migration of Schwann cells through the PI3K/AKT pathway and increase the expression of CXCL12 and GDNF to promote facial nerve function repair.
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Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Proliferação de Células , Medicamentos de Ervas Chinesas , Nervo Facial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Regeneração Nervosa , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células de Schwann/metabolismoRESUMO
Resveratrol is a non-flavonoid polyphenol compound that exists in many plants, and is considered an antitoxin. This study explores the effects from the regulation of miR-455-5p by resveratrol on cisplatin-induced ototoxicity via the PTEN-PI3K-AKT signaling pathway. For this, House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were transfected with miR-455-5p inhibitor and treated with cisplatin and resveratrol, then cell proliferation, apoptosis, and oxidative stress were evaluated. A mouse model of hearing loss was established, and these mice were treated with cisplatin, resveratrol, or cisplatin combined with resveratrol, by intraperitoneal injection. The auditory brainstem response (ABR) threshold was measured, and hair cells were examined using immunofluorescence staining. The expression levels of miR-455-5p, PTEN, and PI3K/Akt proteins were examined. The results from our in-vitro experiments indicate that resveratrol promoted viability and reduced apoptosis and oxidative stress in cisplatin-induced HEI-OC1 cells. Resveratrol upregulated miR-455-5p, downregulated PTEN, and activated the PI3K-Akt axis. These effects of resveratrol were reversed by knock-down of miR-455-5p. The results from our in-vivo experiments indicate that resveratrol protected hearing and inhibited the hair-cell injury caused by cisplatin ototoxicity. Resveratrol also upregulated miR-455-5p, downregulated PTEN, and activated the PTEN-PI3K-Akt axis in cochlear tissues from cisplatin-treated mice. These results indicate that resveratrol upregulates miR-455-5p to target PTEN and activate the PI3K-Akt signaling pathway to counteract cisplatin ototoxicity.
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Cisplatino/toxicidade , MicroRNAs/genética , Ototoxicidade/tratamento farmacológico , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/farmacologia , Animais , Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ototoxicidade/etiologia , Ototoxicidade/metabolismo , Ototoxicidade/patologia , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genéticaRESUMO
OBJECTIVE: Horizontal nystagmus can be observed in the acute stage of vestibular neuritis, Although the direction of the nystagmus is gravity independent, its intensity can be influenced by gravity. In this study, we compared the slow phase velocity (SPV) of horizontal nystagmus in different head positions in patients with vestibular neuritis to analyze the static effects of gravity on horizontal nystagmus. METHODS: The study enrolled 22 vestibular neuritis patients with spontaneous horizontal nystagmus (9 men, 13 women; median age 40 years). The deficits were right-sided in 9 patients and left-sided in 13. The nystagmus was recorded in the sitting, supine, right and left ear down positions. The intensity of spontaneous nystagmus in the sitting versus while supine position, and SPV in affected ear down (AED), healthy ear down (HED), and supine positions were compared. The position-induced nystagmus was calculated to quantify the effect of head positions on nystagmus. RESULTS: The nystagmus intensity in the supine position had no statistic difference than when sitting, with a median value of 6.3°/s and 5.6°/s, respectively(P = 0.355). SPV in AED had a median value of 7.8°/s, which was greater than when supine (P = 0.008) and HED (4.8°/s) (P < 0.001). Position-induced nystagmus in left and right ear-down positions were 1.4°/s and -1.4°/s respectively, which were significantly correlated (Spearman's ρ = -0.848, P < 0.001). CONCLUSIONS: The nystagmus intensity in vestibular neuritis is gravity dependent; it's greater in AED than in supine and HED, and the effect of head position on nystagmus was nearly symmetrical in left and right ear-down positions.
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Gravitação , Nistagmo Patológico/etiologia , Postura/fisiologia , Neuronite Vestibular/complicações , Adulto , Orelha/fisiologia , Feminino , Cabeça/fisiologia , Humanos , Masculino , Decúbito Dorsal/fisiologiaRESUMO
Autophagy and apoptosis have a complex interplay in the early embryo development. The development of spiral ganglion neurons (SGNs) in addition to Corti's organ in the mammalian cochlea remains crucial in the first two-week postnatal period. To investigate the roles of apoptosis and autophagy in the development of SGNs, light microscopy was used to observe the morphological changes of SGNs. The number of SGNs was decreased from P1 to P7 and plateaued from P10 to P14. Immunohistochemistry results revealed positive expression of cleaved-caspase3, bcl-2, microtubule-associated protein light chain 3-II (LC3-II), Beclin1, and sequestosome 1 (SQSTM1/P62) in SGNs. The apoptotic bodies and autophagosomes and autolysosomes were also identified by transmission electron microscopy at P1 and P7. Real-time PCR and western blotting results revealed that the apoptotic activity peaked at P7 and the autophagy activity was gradually upregulated along with the development. Taken together, our results for the first time showed that autophagy and apoptosis in SGNs play distinct roles during specific developmental phases in a time-dependent manner.
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Apoptose , Proteínas Relacionadas à Autofagia/metabolismo , Neurônios/metabolismo , Gânglio Espiral da Cóclea/crescimento & desenvolvimento , Gânglio Espiral da Cóclea/metabolismo , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Ratos Sprague-DawleyRESUMO
The acceptable noise level (ANL) was defined by subtracting the background noise level (BNL) from the most comfortable listening level (MCL) (ANL = MCL - BNL). This study compared the ANL obtained through different methods in 20 Chinese subjects with normal hearing. ANL was tested with Mandarin speech materials using a loudspeaker or earphones, with each subject tested by himself or by the audiologist. The presentation and response modes were as follows: (1) loudspeaker with self-adjusted noise levels using audiometer controls (LS method); (2) loudspeaker with the subject signaling the audiologist to adjust speech and noise levels (LA method); (3) earphones with self-adjusted noise levels using audiometer controls (ES method); and (4) earphones with the subject signaling the audiologist to adjust speech and noise levels (EA method). ANL was calculated from three measurements with each method. There was no significant difference in the ANL obtained through different presentation modes or response modes sound. The correlations between ANL, MCL, and BNL obtained from each two methods were significant. In conclusion, the ANL in normal-hearing Mandarin listeners may not be affected by presentation modes such as a loudspeaker or earphones nor is it affected by self-adjusted or audiologist-adjusted response modes. Earphone audiometry is as reliable as sound field audiometry and provides an easy and convenient way to measure ANL.
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Percepção Auditiva/fisiologia , Limiar Auditivo/fisiologia , Ruído/efeitos adversos , Transdutores/estatística & dados numéricos , Adulto , Audiometria/instrumentação , Audiometria/métodos , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: To review the classification and management of petrous bone cholesteatomas (PBCs) at our center and the outcomes of facial nerve (FN) management in these lesions. METHODS: This was a retrospective study. The setting was a quaternary referral center for skull base pathology in Italy. A total of 200 patients with 201 PBCs were included in the study. All patients diagnosed radiologically with PBCs were classified according to the Sanna classification. All patients were surgically treated and followed up with radiology. The main outcome measures - classification of PBCs, the surgical approach used, disease control, and FN outcomes - were analyzed. RESULTS: Supralabyrinthine PBCs were the most common type with 92 cases (45.8%) followed by the massive PBCs with 72 cases (35.8%). Preservation of preoperative FN function was highest in the infralabyrinthine (72.2%) and infralabyrinthine-apical (73.3%) types. The transotic approach was used in 66 cases (32.8%) in this series. The modified transcochlear approach type A was applied in 55 cases (27.3%). Active management of the nerve (rerouting, anastomosis, or grafting) was required in 53 cases (26.4%). Postoperatively, of the 116 cases with FN House-Brackmann grade I and II, 107 cases (92.2%) retained the same grade or improved. Recurrence was seen in 7 cases (3.5%). The mean duration of follow-up was 6.3 years. CONCLUSIONS: Radical disease clearance must take precedence over hearing and FN preservation in PBCs. Active FN management, including rerouting, end-to-end anastomosis, and cable nerve grafting, routinely come to play in the surgical management of PBCs, and the postoperative FN results after such interventions can be satisfactory in most cases.
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Doenças Ósseas/cirurgia , Colesteatoma/cirurgia , Doenças do Nervo Facial/prevenção & controle , Traumatismos do Nervo Facial/prevenção & controle , Osso Petroso/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Nervo Facial/cirurgia , Doenças do Nervo Facial/epidemiologia , Doenças do Nervo Facial/cirurgia , Traumatismos do Nervo Facial/epidemiologia , Traumatismos do Nervo Facial/cirurgia , Feminino , Audição , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Our previous research demonstrated that resveratrol counters DDP-induced ototoxicity by upregulating miR-455-5p, which targets PTEN. This study aimed to elucidate the underlying mechanisms involving GAS5 and DNA methyltransferase 1 (DNMT1) in resveratrol's protective action. METHODS: A luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to study the binding between GAS5 and miR-455-5p, as well as between miR-455-5p and PTEN. HEI-OC1 cells treated with DDP were transfected with vectors for GAS5, si-GAS5, DNMT1, si-DNMT1, and miR-455-5p mimics, as well as PTEN. Subsequently, they were treated with resveratrol and exposed to DDP, both separately and in combination. The distribution of CpG islands in the GAS5 promoter was identified using MethyPrimer, and methylation-specific PCR (MSP) was conducted to determine the methylation levels of GAS5. Chromatin immunoprecipitation (ChIP) was utilized to examine the interaction between DNMT1 and GAS5. The viability of HEI-OC1 cells, catalase (CAT) activity, apoptosis, and ROS levels were assessed using the CCK-8 assay, CAT assay, TUNEL staining, and flow cytometry, respectively. An in vivo mouse model was developed to measure auditory brainstem response (ABR) thresholds, while RT-qPCR and Western blot analysis were employed to evaluate molecular levels. RESULTS: Our study discovered that GAS5 acts as a sponge for miR-455-5p, thereby increasing PTEN expression in DDP-treated HEI-OC1 cells. This process was reversed upon treatment with resveratrol. Importantly, DNMT1 promoted the methylation of the GAS5 promoter, leading to the suppression of GAS5 expression. This suppression enhanced the effectiveness of resveratrol in combating DDP-induced apoptosis and ROS in HEI-OC1 cells and amplified its protective effect against DDP's ototoxicity in vivo. CONCLUSIONS: Our research emphasizes the significance of the DNMT1/GAS5/miR-455-5p/PTEN axis as a promising new route to boost resveratrol's effectiveness against DDP-induced ototoxicity.
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Cisplatino , DNA (Citosina-5-)-Metiltransferase 1 , Epigênese Genética , MicroRNAs , Ototoxicidade , PTEN Fosfo-Hidrolase , RNA Longo não Codificante , Resveratrol , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ototoxicidade/prevenção & controle , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Epigênese Genética/efeitos dos fármacos , Linhagem Celular , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
Sarcopenia prevalence and its risk factors in chronic obstructive pulmonary disease (COPD) vary partly due to definition criteria. This systematic review aimed to identify the prevalence and risk factors of sarcopenia in COPD patients. This review was registered in PROSPERO (CRD42022310750). Nine electronic databases were searched from inception to September 1st, 2022, and studies related to sarcopenia and COPD were identified. Study quality was assessed using a validated scale matched to study designs, and a meta-analysis was performed to evaluate sarcopenia prevalence. COPD patients with sarcopenia were compared to those without sarcopenia for BMI, smoking, and mMRC. The current meta-analysis included 15 studies, with a total of 7,583 patients. The overall sarcopenia prevalence was 29% [95% CI: 22%-37%], and the OR of sarcopenia in COPD patients was 1.51 (95% CI: 1.19-1.92). The meta-analysis and systematic review showed that mMRC (OR = 2.02, P = 0.04) and age (OR = 1.15, P = 0.004) were significant risk factors for sarcopenia in COPD patients. In contrast, no significant relationship was observed between sarcopenia and smoking and BMI. Nursing researchers should pay more attention to the symptomatic management of COPD and encourage patients to participate in daily activities in the early stages of the disease.
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Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , PrevalênciaRESUMO
Pediatric auditory neuropathy spectrum disorder is a particular type of hearing loss caused by abnormal sound transmission from the cochlea to the brain. It is due to defective peripheral synaptic function or improper neuronal conduction. Using trio whole-exome sequencing, we have identified novel biallelic variants in the PLEC gene in three individuals with profound deafness from two unrelated families. Among them, one pediatric patient diagnosed with auditory neuropathy spectrum disorder had a good cochlear implantation outcome. The other two adult patients were diagnosed with non-syndromic hearing loss. Studies in mice and zebrafish confirmed that plectin is developmentally expressed in the inner ear. Moreover, plectin's knockdown resulted in a reduction of synaptic mitochondrial potential and loss of ribbon synapses, reinforcing the idea of a role for plectin in neuronal transmission. Altogether, the results presented here, point to a new unconventional role for plectin in the inner ear. Contrary to the well-characterized association of plectin to skin and muscle diseases, we found that specific plectin mutations can result in hearing loss with no other clinical manifestations. This is important because 1) it provides evidence of plectin's involvement in inner ear function and 2) it will help clinicians at the time of diagnosis and treatment.
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Surdez , Perda Auditiva , Camundongos , Animais , Plectina/genética , Peixe-Zebra/genética , Perda Auditiva/genéticaRESUMO
Background: Sudden sensorineural hearing loss (SSNHL) in patients with single-sided deafness (SSD) is rare. The prognosis of the sole serviceable hearing ear is very important for these patients. However, the clinical characteristics and prognosis of SSNHL in SSD patients are not well-documented. Objective: This study aimed to investigate the clinical features and treatment outcomes of SSNHL in SSD patients. Methods: Clinical data of 36 SSD patients and 116 non-SSD patients with unilateral SSNHL from January 2013 to December 2022 were retrospectively investigated. The clinical characteristics of the SSD patients were analyzed. All SSD patients were treated with intratympanic steroids plus intravenous steroids. Pure-tone average (PTA) and word recognition score (WRS) before and after treatment were recorded. The hearing recovery of SSNHL in SSD patients in comparison with non-SSD patients was explored. Auditory outcomes in SSD patients with different etiologies were also compared. Results: Initial hearing threshold showed no significant differences between the SSD group and the non-SSD group (66.41 ± 24.64 dB HL vs. 69.21 ± 31.48 dB HL, p = 0.625). The SSD group had a higher post-treatment hearing threshold (median (interquartile range, IQR) 53.13(36.56) dB HL) than the non-SSD group (median 32.50(47.5) dB HL, p < 0.01). Hearing gains (median 8.75(13.00) dB) and the rate of significant recovery (13.89%) were lower in the SSD group than in the non-SSD group (median 23.75(34.69) dB, 45.69%). The etiology of SSD was classified as SSNHL, special types of infection, chronic otitis media, and unknown causes. SSNHL accounted for the maximum proportion (38.9%) of causes of SSD in the SSD group. Hearing gains were lower in the SSNHL-SSD group than in other causes of the SSD group. A binary logistic regression analysis demonstrated that SSD serves as an indicator of unfavorable hearing recovery outcomes (OR = 5.264, p < 0.01). Conclusion: The prognosis of SSNHL in SSD patients is unsatisfactory. SSNHL accounts for the maximum proportion of causes of SSD in this group of patients. For SSD patients caused by SSNHL, less hearing improvement after treatment was expected when SSNHL occurred in the contralateral ear in comparison with SSD patients with other causes.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the most burdened chronic respiratory disease in the world, resulting in a reduced quality of life and limited physical activity for patients. Pulmonary rehabilitation (PR) is an effective therapy for COPD. Effective PR relies on an accurate pulmonary rehabilitation program. An adequate pre-rehabilitation assessment helps healthcare professionals to develop an accurate pulmonary rehabilitation program. However, pre-rehabilitation assessment strategies lack specific selection criteria and an assessment of the patient's overall functioning. METHODS: This study explored the functional characteristics of COPD patients before pulmonary rehabilitation and collected COPD patients from October 2019 to March 2022. A cross-sectional survey of 237 patients was conducted using the ICF brief core set as the study tool. Latent profile analysis identified subgroups of patients with different rehabilitation needs based on body function and activity participation. RESULTS: Four subgroups of functional dysfunction were identified: 5.42%, 21.03%, 29.44%, and 34.11% in the high dysfunction group, the moderate dysfunction group, the lower-middle dysfunction but high mobility impairment group, and the low dysfunction group, respectively. Patients in the high dysfunction group were older, had a higher proportion of widowed spouses, and experienced more exacerbation. Most patients in the low-dysfunction group did not use inhaled medication and had a lower participation rate in oxygen therapy. Patients with a more severe disease classification and symptom burden mostly belonged to the high dysfunction group. CONCLUSIONS: COPD patients require an adequate assessment before implementing a pulmonary rehabilitation program to determine their rehabilitation needs. The four subgroups were heterogeneous in terms of the degree of functional impairment in body function and activity participation. Patients in the high dysfunction group can improve basic cardiorespiratory fitness; patients in the moderate dysfunction group should focus on improving cardiorespiratory endurance and muscle fitness, patients in the lower-middle-dysfunction but high mobility impairment group should focus on improving mobility and patients in the low functional disability group should focus more on preventive measures. Healthcare providers can tailor rehabilitation programs to the functional impairments of patients with different characteristics. TRIAL REGISTRATION: This study has been registered in the Chinese Clinical Trials Registry (ChiCTR2000040723).
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Aptidão Cardiorrespiratória , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Transversais , Doença Pulmonar Obstrutiva Crônica/reabilitação , Qualidade de VidaRESUMO
Cisplatin is a first-line chemotherapeutic agent in the treatment of malignant tumors with remarkable clinical effects and low cost. However, the ototoxicity and neurotoxicity of cisplatin greatly limit its clinical application. This article reviews the possible pathways and molecular mechanisms of cisplatin trafficking from peripheral blood into the inner ear, the toxic response of cisplatin to inner ear cells, as well as the cascade reactions leading to cell death. Moreover, this article highlights the latest research progress in cisplatin resistance mechanism and cisplatin ototoxicity. Two effective protective mechanisms, anti-apoptosis and mitophagy activation, and their interaction in the inner ear are discussed. Additionally, the current clinical preventive measures and novel therapeutic agents for cisplatin ototoxicity are described. Finally, this article also forecasts the prospect of possible drug targets for mitigating cisplatin-induced ototoxicity. These include the use of antioxidants, inhibitors of transporter proteins, inhibitors of cellular pathways, combination drug delivery methods, and other mechanisms that have shown promise in preclinical studies. Further research is needed to evaluate the efficacy and safety of these approaches.
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Background: Chronic obstructive pulmonary disease (COPD) is characterised mainly by exertional dyspnoea, which may lead to activity reduction. Pulmonary rehabilitation (PR) is considered capable of mitigating these impairments. However, access to PR is limited to specialised centres, especially during the coronavirus disease 2019 pandemic. Moreover, low-cost home rehabilitation programmes have non-individualised prescriptions, which might lead to inconsistent clinical effects in patients with COPD. Therefore, it is important to develop new, low-cost protocols involving individualised prescriptions and staff supervision. Methods: This is a descriptive protocol for a randomised controlled study at the Grade III A Hospital in Tianjin. The sample size was calculated according to a described formula. Fifty-six participants will be selected and randomly allocated into two groups: (I) control (traditional PR training, medication, and nursing interventions); and (II) intervention [PR training in the hospital and at home by the Cardiopulmonary Rehabilitation System Management Platform (CSM)]. The protocol will be performed twice a week for 8 consecutive weeks in the outpatient clinic, and the training will be performed by the application of the CSM system in the final 6 months of the trial. The study will assess lung function and physical fitness and analyse the scores of the modified Medical Research Council Dyspnoea Scale, the COPD assessment test, the International Classification of Functioning, Disability, and Health, and the 6-minute walk test before and after the training protocol. Comparison of differences will be performed using repeated measures analysis of variance, a linear mixed effects analysis, or a non-parametric test, which will include only participants who completed all outcome measures and followed the intervention protocol. The study results will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. Discussion: The new, low-cost supervised rehabilitation programmes are expected to present positive results, making PR programmes more accessible and effective for patients with COPD. Trial Registration: The study was registered in the Chinese Clinical Trial Registry: ChiCTR2000040723.
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OBJECTIVE: Our aim was to determine the correlation between cognitive impairment and P300 event-related potential (ERP) in older adults with vertigo and imbalance, which further provides a reference for clinical diagnosis and patients' rehabilitation. METHODS: A total of 79 older adult patients with vertigo and imbalance in our outpatient department from January 2022 to December 2022 were selected and divided into the mild group (n = 20), moderate group (n = 39), and severe group (n = 20) according to the Dizziness Handicap Inventory (DHI). The auditory P300 component of event-related potentials (ERPs), Generalized Anxiety Disorder Questionnaire-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Mini-Mental State Examination (MMSE) were used to evaluate depression, anxiety, and cognitive function in these patients, respectively. RESULTS: The P300 latencies of the different severity groups were 292 ± 10 ms, 301 ± 8 ms, and 328 ± 5 ms, respectively, and the differences were statistically significant (p = 0.010). The P300 amplitudes of the different severity groups were 14.4 ± 2.6 µV, 3.9 ± 0.8 µV, and 5.1 ± 1.4 µV, respectively, and the differences were also statistically significant (p = 0.004). There was no statistically significant difference in the DHI evaluation or VAS visual simulation scoring between the two groups (p = 0.625, and 0.878, respectively). Compared with the short-course group, the long-course group showed prolonged P300 latency and decreased amplitude, higher scores in PHQ-9 and GAD-7, and lower scores in MMSE, and all the differences were statistically significant (p = 0.013, 0.021, 0.006, 0.004, and 0.018, respectively). CONCLUSION: Older patients with more severe symptoms of vertigo and imbalance are at higher risk of developing abnormal cognitive function. The P300 can be used as an objective neurophysiological test for the assessment of cognitive function relevant to elderly patients with vertigo and imbalance.
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Age-related hearing loss (ARHL) is the most prevalent sensory disorder in the elderly. Currently, no treatment can effectively prevent or reverse ARHL. Aging auditory organs are often accompanied by exacerbated oxidative stress and metabolic deterioration. Here, we report the effect of deuterated oxygen (D2O), also known as "heavy water", mouse models of ARHL. Supplementing the normal mouse diet with 10% D2O from 4 to 9 weeks of age lowered hearing thresholds at selected frequencies in treated mice compared to untreated control group. Oxidative stress levels were significantly reduced and in the cochlear duct of treated vs. untreated mice. Through metabolic flux analysis, we found that D2O mainly slowed down catabolic reactions, and may delay metabolic deterioration related to aging to a certain extent. Experiments confirmed that the Nrf2/HO-1/glutathione axis was down-regulated in treated mice. Thus, D2O supplementation can hinder ARHL progression in mouse models by slowing the pace of metabolism and reducing endogenous oxidative stress production in the cochlea. These findings open new avenues for protecting the cochlea from oxidative stress and regulating metabolism to prevent ARHL.
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BACKGROUND: Meniere's disease (MD) is an inner ear disorder, characterized by recurrent attacks of vertigo, low-frequency sensorineural hearing loss, tinnitus, and aural fullness. Endolymphatic sac surgery is an effective treatment to control vertigo attacks but without causing a hearing loss for intractable MD. However, the methods and effects of endolymphatic sac surgery have been controversial for many years, and the relationship between the vertigo control rates of different endolymphatic sac surgery methods is not well-documented. OBJECTIVES: This study compared the vertigo control rate, hearing outcome, and quality of life (QOL) among different endolymphatic sac surgery, such as local endolymphatic sac decompression (LESD), endolymphatic sac mastoid shunt (ESMS), and wide endolymphatic sac decompression (WESD). MATERIALS AND METHODS: We retrospectively analyzed the patients who underwent endolymphatic sac surgery from January 2008 to June 2019. The control rate of vertigo and QOL scores were compared after 2 years of follow-up. The QOL was scored with validation of the MD patient-oriented symptom-severity index (MDPOSI). The pure tone thresholds of all patients at pre- and postoperation were also compared. RESULTS: In total, 83 MD patients with complete follow-up data were included in the study, i.e., 20 patients with LESD, 28 patients with ESMS, and 35 patients with WESD. Results showed a better vertigo control with WESD than the other groups (70% with LESD, 71.4% with ESMS, and 88.6% with WESD). The QOL was improved after surgery in all groups in which the difference was statistically significant (QOL, preoperative vs. postoperative, 38.2 vs. 10.1 with LESD, 37.8 vs. 9.6 with ESMS, and 37.6 vs. 8.3 with WESD), respectively. After endolymphatic sac surgery, the hearing was well-preserved in the three groups [pure tone averages (PTAs), dB, preoperative vs. postoperative, 41.0 ± 19.3 vs. 40.8 ± 17.9 with LESD, 39.7 ± 16.4 vs. 40.8 ± 18.2 with ESMS, and 38.5 ± 18.7 vs. 36.6 ± 19.5 with WESD]. CONCLUSION: Wide endolymphatic sac decompression has a higher vertigo control rate, better improvement of QOL, and relatively higher hearing stability or improvement rate after surgery in patients with MD compared with LESD and ESMS.
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Cisplatin is a platinum-containing drug with ototoxicity commonly used clinically and has significant efficacy against a variety of solid tumors. One of the most important mechanisms of ototoxicity is that cisplatin induces apoptosis of hair cells. According to relevant literature, X-linked inhibitor of apoptosis protein (XIAP, anti-apoptotic protein) could inhibit the apoptotic pathway. We hypothesized that this protein might protect cochlear hair cells from cisplatin-induced injury. To figure it out, we treated cochlea of normal mice with various concentrations of cisplatin to observe the response and morphology of hair cells and determine a reasonable concentration. Next, Western Blot and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) experiments were conducted to make an investigation about the expression of XIAP protein and mRNA. In addition, we constructed and identified XIAP overexpressing mice. Finally, we treated cochlear tissues of normal and overexpressing mice with cisplatin to investigate the cyto-protection of XIAP on hair cells, respectively. It was found that 50 µmol/L cisplatin resulted in significant loss and disorganization of hair cells, while simultaneously downregulating the protein and mRNA of XIAP. In XIAP overexpressing mice, the loss and disorganization of hair cells were significantly lessened. These results showed that XIAP can lessen cisplatin-induced hair cell loss and play a role in otoprotection.