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Bromine-based flow batteries (BFB) have always suffered from poor kinetics due to the sluggish Br3 -/Br- redox, hindering their practical applications. Developing cathode materials with high catalytic activity is critical to address this challenge. Herein, the in-depth investigation for the free energy of the bromine redox electrode is conducted initially through DFT calculations, establishing the posterior desorption during oxidation as the rate-determining step. An urchin-like titanium nitride hollow sphere (TNHS) composite is designed and synthesized as the catalyst for bromine redox. The large difference in Br- and Br3 - adsorption capability of TNHS promotes rapid desorption of generated Br3 - during the oxidation process, liberating active sites timely to enable smooth ongoing reactions. Besides, the urchin-like microporous/mesoporous structure of TNHS provides abundant active surface for bromine redox reactions, and ample cavities for the bromine accommodation. The inherently high conductivity of TNHS enables facile electron transfer through multiple channels. Consequently, zinc-bromide flow batteries with TNHS catalyst exhibit significantly enhanced kinetics, stably operating at 80 mA cm-2 with 82.78% energy efficiency. Overall, this study offers a solving strategy and catalyst design approach to the sluggish kinetics that has plagued bromine-based flow batteries.
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Homoprejudiced violence is a type of aggression against an individual or a community based on their actual or perceived sexual orientation. It may be linked to risks of acquiring HIV/STI via psychosocial variables. This study explored the association between homoprejudiced violence experiences and high-risk sexual behaviors, and potential psychosocial mediators. Using cross-sectional survey data collected in China through Blued among men who have sex with men (MSM) in January 2021, this study conducted multiple mediation analyses. Standard instruments were used to collect data on depressive symptoms in the last two weeks (PHQ-9), recreational drug usage in the last three months, and ever experiencing homoprejudiced violence (12-item survey instrument). Dependent variables were having condomless anal sex and having three or more sexual partners in the last three months. Among 1828 MSM, nearly half (847, 46%) had experienced homoprejudiced violence. Twenty-three percent (427) reached a score that suggested moderate or severe depression and 35% (644) had used recreational drugs. In the last three months, 40% (731) had condomless anal sex and 34% (626) had three or more sexual partners. The indirect mediational coefficients through depression on condomless anal sex and multiple sexual partners were 0.04 (95% CI: [0.02, 0.07]) and 0.02 (95% CI: [0.001, 0.05]), respectively. The indirect mediational coefficient of homoprejudiced violence experience on multiple sexual partners through recreational drug use was 0.05 (95% CI: [0.03, 0.08]). These findings suggest that more comprehensive interventions are needed to address the syndemic of homoprejudiced violence, mental health issues, and HIV/STI-related risks.
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Infecciones por VIH , Drogas Ilícitas , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Humanos , Masculino , Femenino , Homosexualidad Masculina/psicología , Depresión , Estudios Transversales , Conducta Sexual/psicología , Parejas Sexuales/psicología , Violencia , ChinaRESUMEN
BACKGROUND: Adolescent girls in China have a low HPV vaccination rate. Although vaccination is recommended by the Chinese health authorities, the cost is not covered by the national immunisation programme. Vaccination delay, among other reasons such as supply shortage and poor affordability, may contribute to low uptake. This sequential mixed methods study aimed to identify potential factors of delayed HPV vaccination among Chinese adolescent girls. METHODS: Quantitative data about the attitudes and perceptions of HPV vaccination were collected from 100 caregivers of 14-18-year-old girls using an online survey in Chengdu, China. The survey data informed a subsequent qualitative study using four focus group discussions. We conducted a descriptive analysis of the survey data and a thematic analysis of the qualitative data. The findings were interpreted using a health behaviour model adapted from the Health Belief Model and the Andersen's Behavioural Model for Health Services Use. RESULTS: A total of 100 caregivers - 85 were mothers and 15 were fathers - participated in the survey; 21 caregivers joined focus group discussions. When asked about their intended course of action if the 9vHPV vaccine was out-of-stock, 74% chose to delay until the 9vHPV vaccine is available while 26% would consider 2vHPV or 4vHPV vaccines or seek alternative ways to procure the vaccine. Qualitative results confirmed that caregivers preferred delaying HPV vaccination for adolescent girls. The intent to delay was influenced by systemic barriers such as supply shortage and individual-level factors such as a preference for the 9vHPV vaccine, safety concerns, inadequate health communication, and the belief that adolescents were unlikely to be sexually active. CONCLUSION: In urban areas, Chinese caregivers' intent to delay vaccination in favour of 9vHPV vaccine over receiving the more accessible options was influenced by a mix of individual and contextual factors. Focussed health communication strategies are needed to accelerate HPV vaccination among adolescents.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Adolescente , Humanos , Cuidadores , Infecciones por Papillomavirus/prevención & control , Vacilación a la Vacunación , Vacunación , China , Conocimientos, Actitudes y Práctica en Salud , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
The purpose of this study was to explore the therapeutic effect of the oral administration of pseudo-ginsenoside RT4 (RT4) on ulcerative colitis (UC), and to determine the rate of absorption and distribution of RT4 in mice with UC. Balb/c mice were induced using dextran sulfate sodium salts (DSS) to establish the UC model, and 10, 20, or 40 mg/kg of RT4 was subsequently administered via gavage. The clinical symptoms, inflammatory response, intestinal barrier, content of total short-chain fatty acids (SCFAs), and gut microbiota were investigated. Caco-2 cells were induced to establish the epithelial barrier damage model using LPS, and an intervention was performed using 4, 8, and 16 µg/mL of RT4. The inflammatory factors, transient electrical resistance (TEER), and tight-junction protein expression were determined. Finally, pharmacokinetic and tissue distribution studies following the intragastric administration of RT4 in UC mice were performed. According to the results in mice, RT4 decreased the disease activity index (DAI) score, restored the colon length, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), and boosted the levels of immunosuppressive cytokine IL-10, increased the content of SCFAs, improved the colonic histopathology, maintained the ultrastructure of colonic mucosal epithelial cells, and corrected disturbances in the intestinal microbiota. Based on the results in caco-2 cells, RT4 reduced the levels of TNF-α, IL-6, and IL-1ß; protected integrity of monolayers; and increased tight-junction protein expression. Additionally, the main pharmacokinetic parameters (Cmax, Tmax, t1/2, Vd, CL, AUC) were obtained, the absolute bioavailability was calculated as 18.90% ± 2.70%, and the main distribution tissues were the small intestine and colon. In conclusion, RT4, with the features of slow elimination and directional distribution, could alleviate UC by inhibiting inflammatory factors, repairing the intestinal mucosal barrier, boosting the dominant intestinal microflora, and modulating the expression of SCFAs.
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Colitis Ulcerosa , Microbioma Gastrointestinal , Ginsenósidos , Animales , Ratones , Humanos , Distribución Tisular , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Células CACO-2 , Interleucina-6 , Factor de Necrosis Tumoral alfa , Citocinas , Interleucina-1beta , Ratones Endogámicos BALB CRESUMEN
The cultivation of ginseng in fields is time-consuming and labor-intensive. Thus, culturing adventitious ginseng root in vitro constitutes an effective approach to accumulating ginsenosides. In this study, we employed UPLC-QTOF-MS to analyze the composition of the cultured adventitious root (cAR) of ginseng, identifying 60 chemical ingredients. We also investigated the immunomodulatory effect of cAR extract using various mouse models. The results demonstrated that the cAR extract showed significant activity in enhancing the immune response in mice. The mechanism underlying the immunomodulatory effect of cAR was analyzed through network pharmacology analysis, revealing potential 'key protein targets', namely TNF, AKT1, IL-6, VEGFA, and IL-1ß, affected by potential 'key components', namely the ginsenosides PPT, F1, Rh2, CK, and 20(S)-Rg3. The signaling pathways PI3K-Akt, AGE-RAGE, and MAPK may play a vital role in this process.
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Ginsenósidos , Panax , Animales , Ratones , Ginsenósidos/farmacología , Fosfatidilinositol 3-Quinasas , Modelos Animales de Enfermedad , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: Saussurea pulchella (SP) is a traditional medicinal plant that is widely used in folk medicine because of its diverse biological activities, particularly its anti-inflammatory effects. However, the alleviation effect of SP on ulcerative colitis (UC) has not yet been realized. PURPOSE: To investigate the chemical composition and therapeutic effect of SP extract against UC. METHODS: First, qualitative and quantitative analysis of SP 75% ethanol extract was performed by UPLC-Q/TOF-MS. Second, a dextran sodium sulfate (DSS) model of UC mice was developed to study the effects of SP on the symptoms, inflammatory factors, oxidative stress indexes and colon histopathology. Third, an integration of network pharmacology with metabolomics was performed to investigate the key metabolites, biological targets and metabolisms closely related to the effect of SP. RESULTS: From the SP ethanol extract, 149 compounds were identified qualitatively and 20 were determined quantitatively. The SP could dose-dependently decrease the DAI score, spleen coefficient and the levels of TNF-α, IL-6, iNOS, MPO and MDA; increase the colon length, GSH level and SOD activity; and protect the intestinal barrier in the UC mice. Moreover, 10 metabolite biomarkers,18 targets and 5 metabolisms were found to play crucial roles in the treatment of UC with SP. CONCLUSIONS: SP 75% ethanol extract could effectively alleviate the progression of UC and, therefore, could be classified as a novel natural treatment for UC.
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Colitis Ulcerosa , Saussurea , Factor de Necrosis Tumoral alfa , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Colon/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Estrés Oxidativo , Saussurea/química , Factor de Necrosis Tumoral alfa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Fitoquímicos/químicaRESUMEN
Spousal bereavement poses considerable challenges to adults in late life. Some populations, such as older immigrants, may experience heightened negative outcomes as a consequence of spousal bereavement, due to migratory stress and social isolation. Spousal bereavement is culturally embedded as it is related to cultural beliefs and attitudes concerning death and family relationships. However, studies on spousal bereavement or widowhood among older immigrants are extremely limited. This study aims to fill the gap by exploring, via a phenomenological approach, the lived experiences of widowed older Chinese immigrants in Calgary and responding to the question: What are the lived experiences of widowed Chinese older immigrants in coping with their spousal bereavement? With the data drawn from 12 in-depth qualitative interviews, findings were categorized into individual, family, community and societal levels. Study participants experienced long-lasting grief that was private and impacted by their culture and immigration status. Although family and ethno-cultural communities provided various types of supports during participants' widowhood, they did not directly assist them in coping with spousal loss. Most participants did not access social services for bereavement support, more often relying on cultural rituals and faith practices. Findings suggest the need for culturally appropriate bereavement supports and family/community involvement for older immigrant adults who have experienced spousal loss.
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Aflicción , Emigrantes e Inmigrantes , Viudez , Humanos , Femenino , Pueblos del Este de Asia , Pesar , Adaptación PsicológicaRESUMEN
BACKGROUND: HIV self-testing (HIVST), especially the secondary distribution of HIVST (SD-HIVST) initiated by sexual health influencers (SHIs), has been recognized as an effective strategy in promoting HIV testing, especially among men who have sex with men (MSM). This quasi-experimental study aimed to evaluate whether SHIs identified through the ensemble machine learning approach can distribute more HIVST than those who identified by the empiricalscale. METHODS: We will recruit eligible adults (≥18 years old) who were assigned male gender at birth, and willing to participate in potential SD-HIVST online. Participants will be assigned randomly to two groups (scale group or machine learning group), followed by a separate process of SHI identification based on the group assignment. After identification, all index participants (defined as identified SHIs who are verbally consented to participate in SD-HIVST or who directly order HIVST kits) will follow the same procedure for SD-HIVST acquisition and distribution. Index participants can order HIVST online and distribute them to members within their social networks (defined as alters) in-person or virtually through a personalized peer referral link. Once a unique alter uploads a photographed test result to the platform, both the alter and the corresponding index participant will receive a fixed incentive of 3 USD. The index MSM can order up to five HIVST in the first three months and ten HIVST in the following three months. Each index participant will need to complete a baseline survey at the first-time ordering and one to two follow-upbased on the times of ordering,, three months after ordering. This trial will be comparing 1) the mean number of alters motivated by each index participant in each group and 2) the mean number of newly-tested alters motivated by each index participant in each group. DISCUSSION: In promoting the efficacy of identifying SHIs for SD-HIVST, our study has the potential to enhance testing coverage, particularly among marginalized individuals and those who are reluctant to for HIV and other sexually transmitted infections. TRIAL REGISTRATION: We registered the study on the Chinese Clinical Trial Registry website on 4th November 2021, with registration number ChiCTR2000039632 .
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Infecciones por VIH , Salud Sexual , Minorías Sexuales y de Género , Adolescente , Adulto , China , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Humanos , Recién Nacido , Aprendizaje Automático , Masculino , AutoevaluaciónRESUMEN
With the widespread application of machine learning methods, the continuous improvement of forecast accuracy has become an important task, which is especially crucial for landslide displacement predictions. This study aimed to propose a novel prediction model to improve accuracy in landslide prediction, based on the combination of multiple new algorithms. The proposed new method includes three parts: data preparation, multi-swarm intelligence (MSI) optimization, and displacement prediction. In the data preparation, the complete ensemble empirical mode decomposition (CEEMD) is adopted to separate the trend and periodic displacements from the observed cumulative landslide displacement. The frequency component and residual component of reconstructed inducing factors that related to landslide movements are also extracted by the CEEMD and t-test, and then picked out with edit distance on real sequence (EDR) as input variables for the support vector regression (SVR) model. MSI optimization algorithms are used to optimize the SVR model in the MSI optimization; thus, six predictions models can be obtained that can be used in the displacement prediction part. Finally, the trend and periodic displacements are predicted by six optimized SVR models, respectively. The trend displacement and periodic displacement with the highest prediction accuracy are added and regarded as the final prediction result. The case study of the Shiliushubao landslide shows that the prediction results match the observed data well with an improvement in the aspect of average relative error, which indicates that the proposed model can predict landslide displacements with high precision, even when the displacements are characterized by stepped curves that under the influence of multiple time-varying factors.
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OBJECTIVES: To understand the prevalence and risk factors for chronic kidney disease (CKD) among freshmen from a university in Hunan Province in 2018. METHODS: A cross-sectional survey was conducted on 1 685 freshmen from a university in Hunan Province in 2018. Height, weight, body mass index (BMI), blood pressure, creatinine, uric acid, fasting blood glucose, triglyceride, total cholesterol, blood urea nitrogen, and other laboratory indicators were measured. The risk factors of hematuria, proteinuria, and CKD were analyzed by logistic regression. RESULTS: Among the 1 685 students, the detection rates of proteinuria, hematuria, and renal dysfunction were 2.14%, 6.65%, and 0.95%, respectively. The prevalence of CKD was 10.86%, mainly at stage 1 and 2. The awareness rate in the patients was 6.56%. The detection rate of proteinuria was not significantly correlated with gender, and the detection rate of hematuria and renal dysfunction was higher in women than in men, and the prevalence of CKD was higher in women than in men. Independent risk factors associated with CKD were hypertension and diabetes. CONCLUSIONS: In 2018, the prevalence of CKD among freshmen in this university is roughly the same as the national level. CKD patients and people with hypertension and diabetes should be checked regularly, and early intervention should be performed to delay the occurrence and development of the disease.
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Insuficiencia Renal Crónica , Universidades , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a group of rare tumors with the presence of both cancerous and sarcoma components in tumor. In this study, we explore their cancer genomic background and the relationship with clinical prognosis. MATERIALS AND METHODS: A cohort of 32 PSC patients were retrospectively collected from the First People's Hospital of Changzhou between 2005 and 2016. Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed on 32 PSC tumors. RESULTS: EGFR (28%), KRAS (22%), and MET (16%) are the most commonly mutated oncogenes, while the top mutated tumor suppressor genes are TP53 (69%) and RB1 (25%). The majority of EGFR mutations are rare mutations, some of which have not been reported before. Moreover, 4 out of 6 MET alterations are exon 14 skipping, far more frequent than in NSCLC. Interestingly, ARID1A was found to be co-mutated with TP53 at all times. The tumor mutation burden (TMB) is ranging from 3.3 to 52.2 per megabase (MB) with a median of 11.7 per MB and 13 patients have more than 20 mutations per MB. Patients mutated in BRCA2, KMT2B, SMARCA4 or TSC2 have significantly higher TMB compared to patients with wide-type genes. CONCLUSION: Our study characterizes the genetic background of Chinese PSC patients and demonstrates the importance of involving EGFR rare mutations and MET exon 14 skipping targeted therapies into clinical trials for treating PSC patients. High TMB are seen in about 40.6% Chinese patients with PSC, which could benefit from immune checkpoint inhibitors.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Mutación , Adulto , Anciano , Pueblo Asiatico/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , ADN Helicasas/genética , Proteínas de Unión al ADN , Receptores ErbB/genética , Exones , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Pronóstico , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Factores de Transcripción/genética , Carga TumoralRESUMEN
PURPOSE: Our aim was to study the role of AK000953 silencing for the killing effect of danazol on uterine fibroids. METHODS: Quantitative PCR was applied to identify differential expression of AK000953 in uterine fibroid tissue and normal uterine tissue. Then we isolated and cultured uterine fibroid cells, designed the siRNA of AK000953 to silence its expression in uterine fibroid cells, and detected the treatment effect of danazol and AK000953 siRNA on cell proliferation, cell apoptosis, and cell invasion. Finally, guinea pig model of uterine fibroids was constructed to verify the effect of AK000953 silencing on uterine fibroid treatment with danazol in vivo. RESULTS: Quantitative PCR showed that the AK000953 gene was highly expressed in uterine fibroid tissue compared with normal uterine tissue (2.1 ± 0.15 vs. 0.8 ± 0.05, p < 0.01). After AK000953 silencing in uterine fibroid cells, we discovered that the inhibition rate in danazol-siRNA group was 56 ± 5 %, the cell apoptosis rate of danazol-siRNA group was 43 ± 2.3 %, and the invasion rate of uterine fibroid cells was 12 ± 1 %, which all showed significant differences with the control group or danazol group. Guinea pig model confirmed that the treatment of danazol and AK000953 siRNA effectively inhibited the development of fibroids in vivo. CONCLUSION: AK000953 silencing could effectively enhance the killing effect of danazol on uterine fibroid cells.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Danazol/uso terapéutico , Antagonistas de Estrógenos/uso terapéutico , Leiomioma/tratamiento farmacológico , ARN Interferente Pequeño/genética , Neoplasias Uterinas/tratamiento farmacológico , Animales , Femenino , Cobayas , Humanos , Leiomioma/metabolismo , Reacción en Cadena de la Polimerasa , Células Tumorales Cultivadas , Neoplasias Uterinas/metabolismoRESUMEN
OBJECTIVE: To construct, express and purify human fusion proteins composed of a single-chain antibody fragment scFv that recognizes the prostate specific membrane antigen (PSMA) protein, Fdt, HA2 and tp, and to analyze the binding activity of the expressed fusion proteins. METHODS: The fusion protein genes scFv, scFv-tp, and scFv-Fdt-HA2-tp were amplified by PCR, and the genes obtained were then cloned into the expression vector pET28 and expressed in E. coli BL21. The expressed products were identified by SDS-PAGE and Western blot and purified with Ni(2+)-NTA chelating agarose. The antigen-binding activity of the fusion proteins was determined by ELISA. RESULTS: The human anti-PSMA fusion gene was successfully constructed and expressed in M15 as the inclusion body after induced with IPTG. All the target proteins expressed could bind the PSMA antigen. CONCLUSION: Fusion proteins can specifically bind the PSMA antigen. This finding contributes to the study of the targeted delivery of siRNA.
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Antígenos de Superficie/inmunología , Glutamato Carboxipeptidasa II/inmunología , Anticuerpos de Cadena Única/genética , Clonación Molecular , Electroforesis en Gel de Poliacrilamida , Escherichia coli/genética , Escherichia coli/inmunología , Humanos , Masculino , Reacción en Cadena de la Polimerasa , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Anticuerpos de Cadena Única/inmunologíaRESUMEN
BACKGROUND: At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer. METHODS: 171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups. RESULTS: All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p < 0.001). No significant difference was observed between the two groups in the hospitalization costs (P = 0.664), number or stations of total lymph node dissected (p > 0.05) and postoperative respiratory complications (P > 0.05). CONCLUSIONS: The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.
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Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/instrumentación , Masculino , Femenino , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Cirugía Torácica Asistida por Video/métodos , Cirugía Torácica Asistida por Video/instrumentación , Neumonectomía/métodos , Neumonectomía/instrumentación , Tempo Operativo , Resultado del TratamientoRESUMEN
BACKGROUND: The lack of effective treatments for methicillin-resistant Staphylococcus aureus (MRSA) infection, which often leads to severe acute lung injury (ALI), poses a grave threat to human life. Sophoricoside (SOP), an isoflavone glycoside abundant in the fruit of traditional Chinese herbal Sophora japonica l., showed anti-inflammatory effects against atopic dermatitis, allergic inflammation, and lipopolysaccharide-induced ALI. However, its effect and underlying mechanism on MRSA-induced ALI remain unclear. PURPOSE: The aim of this study is to assess the protective effect of SOP in MRSA-induced ALI and elucidate its underlying molecular mechanisms. METHODS: In vivo experiments were conducted using wild-type mice to establish MRSA-induced ALI mouse model, and the effects of SOP on ALI were evaluated by hematoxylin-eosin staining, flow cytometry, quantitative real-time polymerase chain reaction, and several biochemical indicators. Adoptive transfer experiments and BTB and CNC homology 1 knockout (Bach1-/-) mice were also utilized in this study. In vitro studies employed murine macrophages RAW264.7 cells, primary bone marrow-derived macrophages (BMDMs), and primary lung macrophages to explore the underlying molecular mechanisms. RESULTS: The administration of SOP ameliorated MRSA-induced ALI by improving pulmonary histological damages, reducing neutrophil infiltration, suppressing oxidative stress levels, and decreasing the expression of inflammatory cytokines. In isolation experiments with ALI mouse lung macrophages and macrophage adoptive transfer experiments, SOP prevented macrophage activation, thereby reducing the production of proinflammatory cytokines. In vitro experiments demonstrated that SOP decreased the expression of inflammatory mediators in lipoteichoic acid (LTA)-stimulated RAW264.7 cells, BMDMs, and primary lung macrophages. Additionally, SOP inhibited protein kinase B (Akt) phosphorylation and treatment with MK2206-a specific inhibitor of Akt-eliminated SOP's ability to suppress LTA-stimulated macrophage inflammation. Furthermore, stimulation with LTA or MRSA up-regulated Bach1 expression; however, deletion of Bach1 abolished the inhibitory effect of SOP on p-Akt activation as well as inflammation and ALI development. CONCLUSION: This study provides the first evidence that SOP effectively mitigates MRSA-induced ALI via suppressing macrophage activation through the inhibition of Bach1/Akt pathway. These findings highlight the potential of SOP as a novel therapeutic agent for treating MRSA-induced ALI.
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Lesión Pulmonar Aguda , Staphylococcus aureus Resistente a Meticilina , Proteínas Proto-Oncogénicas c-akt , Animales , Masculino , Ratones , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/microbiología , Antiinflamatorios/farmacología , Benzopiranos , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
BACKGROUND: (-)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet PURPOSE: This study aimed to assess the protective effect of SYR in UC and its underlying mechanism STUDY DESIGN AND METHODS: We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay RESULTS: In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg-1) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway. CONCLUSION: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.
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Colitis Ulcerosa , Colitis , Furanos , Lignanos , Humanos , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Células CACO-2 , Fosfatidilinositol 3-Quinasas/metabolismo , Colon/patología , Lignanos/farmacología , Lignanos/uso terapéutico , Mucosa Intestinal/metabolismo , Modelos Animales de Enfermedad , Sulfato de Dextran/efectos adversos , Ratones Endogámicos C57BL , Colitis/inducido químicamenteRESUMEN
Objective: Sexual health plays a vital role in healthy aging. However, little is known about the sexual attitudes of and the utilization of sexual and reproductive health services by older women in China. This article is based on a qualitative study of older Chinese women in suburban areas to examine their attitudes toward sexuality and their utilization of sexual and reproductive health services. Methods: Face-to-face semi-structured interviews were conducted with older women (ages 50 to 74) from suburbs of southern China. Participants were purposively sampled on a convenience basis and recruited when they were visiting community health facilities between June and December 2021. Inclusion criteria were older women aged 50 years and older who had sexual experience. A topic guide was used that focused on sexual activity, sexual attitudes, the utilization of sexual and reproductive health services, and the factors that influence these. Interviews were audio recorded and transcribed verbatim. We coded the data inductively and conducted a thematic analysis. Results: Twenty-six Chinese women participated in the study. These older women had varying attitudes regarding sexual activity and its significance for older adults. The gender norms they held concerning sexual desire deemed that men had higher sexual desire than women. Most asymptomatic women did not actively seek sexual and reproductive health services. In most cases, women only sought professional services when they started to have sexual and reproductive health problems. Factors influencing the uptake of sexual and reproductive health services by older women were cost (affordability), availability, distance (accessibility), and conservative cultural norms towards sexuality. Conclusion: The attitudes of older women towards sexual activity are diverse. While some view sexual activity as common and essential for maintaining a sense of well-being in older age, others may hold different perspectives, considering it less significant. The utilization of sexual and reproductive health services by older Chinese women, except for when they were having a specific health issue, was low. Sexual health messages and services tailored for older women are needed.
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Servicios de Salud Reproductiva , Conducta Sexual , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Salud Reproductiva , Conocimientos, Actitudes y Práctica en Salud , ChinaRESUMEN
BACKGROUND: Yinhua Miyanling tablets (YMT), comprising 10 Chinese medicinal compounds, is a proprietary Chinese medicine used in the clinical treatment of urinary tract infections. Medicinal compounds, extracts, or certain monomeric components in YMT all show good effect on ulcerative colitis (UC). However, no evidence supporting YMT as a whole prescription for UC treatment is available. PURPOSE: To evaluate the anti-UC activity of YMT and elucidate the underlying mechanisms. The objective of the study was to provide evidence for the add-on development of YMT to treat UC. METHODS: First, YMT's protective effect on the intestinal barrier was evaluated using a lipopolysaccharide (LPS)-induced Caco-2 intestinal injury model. Second, the UC mouse model was established using dextran sodium sulfate (DSS) to determine YMT's influence on symptoms, inflammatory factors, intestinal barrier, and histopathological changes in the colon. Third, an integrated method combining metabolomics and network pharmacology was employed to screen core targets and key metabolic pathways with crucial roles in YMT's therapeutic effect on UC. Molecular docking was employed to identify the key targets with high affinity. Finally, western blotting was performed to validate the mechanism of YMT action against UC. RESULTS: YMT enhanced the transepithelial electrical resistance value and improved the expression of proteins of the tight junctions dose-dependently in LPS-induced Caco-2 cells. UC mice treated with YMT exhibited alleviated pathological lesions of the colon tissue in the in vivo pharmacodynamic experiments. The colonic lengths tended to be normal, and the levels of inflammatory factors (TNF-α, IL-6, and iNOS) along with those of the core enzymes (MPO, MDA, and SOD) improved. YMT effectively ameliorated DSS-induced colonic mucosal injury; pathological changes along with ultrastructure damage were significantly alleviated (evidenced by a relatively intact colon tissue, recovery of epithelial damage, repaired gland, reduced infiltration of inflammatory cells and epithelial cells arranged closely with dense microvilli). Seven key targets (IL-6, TNF-α, MPO, COX-2, HK2, TPH, and CYP1A2) and four key metabolic pathways (arachidonic acid metabolism, linoleate metabolism, glycolysis, and gluconeogenesis and tyrosine biosynthesis) were identified to play vital roles in the treatment on UC using YMT. CONCLUSIONS: YMT exerts beneficial therapeutic effects on UC by regulating multiple endogenous metabolites, targets, and metabolic pathways, suggestive of its potential novel application in UC treatment.
Asunto(s)
Colitis Ulcerosa , Sulfato de Dextran , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Metabolómica , Farmacología en Red , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Humanos , Células CACO-2 , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratones , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Comprimidos , Lipopolisacáridos , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BLRESUMEN
Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection. Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported. Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings. Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136.
RESUMEN
BACKGROUND: Sexual health influencers (SHIs) are individuals actively sharing sexual health information with their peers, and they play an important role in promoting HIV care services, including the secondary distribution of HIV self-testing (SD-HIVST). Previous studies used a 6-item empirical leadership scale to identify SHIs. However, this approach may be biased as it does not consider individuals' social networks. OBJECTIVE: This study used a quasi-experimental study design to evaluate how well a newly developed machine learning (ML) model identifies SHIs in promoting SD-HIVST compared to SHIs identified by a scale whose validity had been tested before. METHODS: We recruited participants from BlueD, the largest social networking app for gay men in China. Based on their responses to the baseline survey, the ML model and scale were used to identify SHIs, respectively. This study consisted of 2 rounds, differing in the upper limit of the number of HIVST kits and peer-referral links that SHIs could order and distribute (first round ≤5 and second round ≤10). Consented SHIs could order multiple HIV self-testing (HIVST) kits and generate personalized peer-referral links through a web-based platform managed by a partnered gay-friendly community-based organization. SHIs were encouraged to share additional kits and peer-referral links with their social contacts (defined as "alters"). SHIs would receive US $3 incentives when their corresponding alters uploaded valid photographic testing results to the same platform. Our primary outcomes included (1) the number of alters who conducted HIVST in each group and (2) the number of newly tested alters who conducted HIVST in each. We used negative binomial regression to examine group differences during the first round (February-June 2021), the second round (June-November 2021), and the combined first and second rounds, respectively. RESULTS: In January 2021, a total of 1828 men who have sex with men (MSM) completed the survey. Overall, 393 SHIs (scale=195 and ML model=198) agreed to participate in SD-HIVST. Among them, 229 SHIs (scale=116 and ML model=113) ordered HIVST on the web. Compared with the scale group, SHIs in the ML model group motivated more alters to conduct HIVST (mean difference [MD] 0.88, 95% CI 0.02-2.22; adjusted incidence risk ratio [aIRR] 1.77, 95% CI 1.07-2.95) when we combined the first and second rounds. Although the mean number of newly tested alters was slightly higher in the ML model group than in the scale group, the group difference was insignificant (MD 0.35, 95% CI -0.17 to -0.99; aIRR 1.49, 95% CI 0.74-3.02). CONCLUSIONS: Among Chinese MSM, SHIs identified by the ML model can motivate more individuals to conduct HIVST than those identified by the scale. Future research can focus on how to adapt the ML model to encourage newly tested individuals to conduct HIVST. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2000039632; https://www.chictr.org.cn/showprojEN.html?proj=63068. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-021-11817-2.