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BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) exerts neuroprotective effects early in cerebral ischemia/reperfusion (I/R) injury. Intermittent theta-brust stimulation (iTBS), a more time-efficient modality of rTMS, improves the efficiency without at least decreasing the efficacy of the therapy. iTBS elevates cortical excitability, and in recent years it has become increasingly common to apply iTBS to patients in the early post-IS period. However, little is known about the neuroprotective mechanisms of iTBS. Endoplasmic reticulum stress (ERS), and ferroptosis have been shown to be involved in the development of I/R injury. We aimed to investigate the potential regulatory mechanisms by which iTBS attenuates neurological injury after I/R in rats. METHODS: Rats were randomly divided into three groups: sham-operated group, MCAO/R group, and MCAO/R + iTBS group, and were stimulated with iTBS 36 h after undergoing middle cerebral artery occlusion (MCAO) or sham-operated. The expression of ERS, ferroptosis, and apoptosis-related markers was subsequently detected by western blot assays. We also investigated the mechanism by which iTBS attenuates nerve injury after ischemic reperfusion in rats by using the modified Neurological Severity Score (mNSS) and the balance beam test to measure nerve function. RESULTS: iTBS performed early in I/R injury attenuated the levels of ERS, ferroptosis, and apoptosis, and improved neurological function, including mNSS and balance beam experiments. It is suggested that this mode of stimulation reduces the cost per treatment by several times without compromising the efficacy of the treatment and could be a practical and less costly intervention.
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Ferroptosis , Daño por Reperfusión , Humanos , Ratas , Animales , Estimulación Magnética Transcraneal , Daño por Reperfusión/terapia , Reperfusión , Estrés del Retículo EndoplásmicoRESUMEN
Stroke is a cerebrovascular disease that impairs blood supply to localized brain tissue regions due to various causes. This leads to ischemic and hypoxic lesions, necrosis of the brain tissue, and a variety of functional disorders. Abnormal cortical activation and functional connectivity occur in the brain after a stroke, but the activation patterns and functional reorganization are not well understood. Rehabilitation interventions can enhance functional recovery in stroke patients. However, clinicians require objective measures to support their practice, as outcome measures for functional recovery are based on scale scores. Furthermore, the most effective rehabilitation measures for treating patients are yet to be investigated. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging method that detects changes in cerebral hemodynamics during task performance. It is widely used in neurological research and clinical practice due to its safety, portability, high motion tolerance, and low cost. This paper briefly introduces the imaging principle and the advantages and disadvantages of fNIRS to summarize the application of fNIRS in post-stroke rehabilitation.
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Espectroscopía Infrarroja Corta , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Espectroscopía Infrarroja Corta/métodos , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/diagnóstico por imagen , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Recuperación de la Función/fisiologíaRESUMEN
BACKGROUND: Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years. METHODS: The ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated. RESULTS: ACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females. CONCLUSIONS: The results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients.
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Peptidil-Dipeptidasa A , Receptor de Angiotensina Tipo 1 , Humanos , Masculino , Femenino , Anciano , Receptor de Angiotensina Tipo 1/genética , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/sangre , Polimorfismo de Nucleótido Simple , Lípidos/sangre , Lípidos/genética , Pueblo Asiatico/genética , Triglicéridos/sangre , Anciano de 80 o más Años , HDL-Colesterol/sangre , HDL-Colesterol/genética , Diabetes Mellitus/genética , Diabetes Mellitus/sangre , Mutación INDEL , LDL-Colesterol/sangre , LDL-Colesterol/genética , Estudios de Asociación Genética , China/epidemiología , Predisposición Genética a la Enfermedad , Pueblos del Este de AsiaRESUMEN
Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of â¼5k c p s, and a low time jitter of â¼171p s, operated at a near-infrared of 1550 nm and a temperature of â¼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.
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Sarcopenia is an age-related condition characterized by a decrease in muscle mass and a decline in muscle strength.Sarcopenia increases the risk of falls,severely affecting the quality of life of patients,and it may be associated with various age-related chronic diseases.Advanced glycation end products(AGEs)are a class of stable glycation products produced by condensation,rearrangement,cleavage,and oxidative modification between the free amino groups of proteins,lipids or nucleic acids and the free carbonyl groups of reducing sugars.Studies have revealed associations of AGEs with muscle mass,muscle strength,and sarcopenia.AGEs can lead to hardening of the extracellular matrix of skeletal muscle through glycation cross-linking.The binding of AGEs to receptors induces inflammation and oxidative stress,consequently resulting in decreases in muscle mass and muscle strength.Therefore,AGEs may play a role in the occurrence and development of sarcopenia.This review summarizes the role of AGEs in the pathogenesis of sarcopenia,offering theoretical support for probing into the mechanisms underlying sarcopenia.
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Sarcopenia , Humanos , Calidad de Vida , Fuerza Muscular , Músculo Esquelético , Productos Finales de Glicación AvanzadaRESUMEN
We propose a method for coupling a tapered optical fiber to an inverted tapered SiN waveguide by fabricating a microfiber using 3D nanoprinting lithography. The microfiber consists of three parts: a tapered cladding cap, an S-bend, and a straight part, all composed of high-refractive-index material. Light is adiabatically coupled from the tapered fiber to the printed microfiber through the cladding cap. The light is then transmitted through the S-bend and the straight part with low loss and is finally coupled to the waveguide through the evanescent field. In the simulation, our design can achieve a high coupling efficiency (TE mode) of â¼97% at a wavelength of 1542 nm with a wide bandwidth of â¼768n m at the 1-dB cutoff criterion.
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OBJECTIVE: To explore the role of adiponectin-resistin (AR) index as a better indicator of obesity-related hypertension. METHOD(S): This study continued a case control study that had finished recruiting 153 subjects divided as four characteristic groups. Fasting serum resistin levels (FSR) and Fasting serum adiponectin levels (FSA) were tested by ELISA. And, other related anthropometric clinical and metabolic data were collected. Analyzation on correlations between research index and differences between groups were done by SPSS. AR index's performance was also validated by the receiver operating characteristic (ROC) curves, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULT(S): The AR index was defined as 1+ log10(R0)-log10(A0). AUC of the AR index was 0.660 and NRI and IDI indicated AR index outperformed FSA alone. AR index statistically significantly negatively correlated with SB and DB and positively with ALB and SCR. AR index was statistically significantly different between the NH group and OH group and more specific than FSR alone as a biomarker of obesity-related hypertension. CONCLUSION(S): The AR index was more strongly associated with increased risk of obesity-related hypertension than the solely index of FSR or FSA and was useful for early diagnosis of obesity-related hypertension.
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Hipertensión , Resistencia a la Insulina , Adiponectina , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , China/epidemiología , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Obesidad/complicaciones , ResistinaRESUMEN
Objective: To explore the role of resistin in the onset and development of obesity-related hypertension.Methods: Resistin serum levels were tested by ELISA in 153 adult subjects among four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Following, correlations between research index and differences between groups were analyzed using SPSS.Results: Serum resistin levels statistically significantly negatively correlated with SB, DB and BMI, but statistically significantly positively correlated with serum creatinine (SCR) and serum albumin (ALB), even after adjustment for age and/or gender. The serum level of resistin in the normal healthy subject group (NH) was higher than in other groups.Conclusions: Resistin's role in the onset of obesity-related hypertension may be more important than what has been previously assumed. More pathway substances in the early onset of obesity-related hypertension should be tested.Abbreviations: WC, waist circumference; GGT, Gamma-glutamyltransferase; ALB, Albumin; ALT, Alanine aminotransferase; LDL, Low density lipoprotein cholesterol; TG, Triglyceride; HDLC, High density lipoprotein cholesterol; FA Fructosamine; SCR, serum creatinine; IB, Indirect bilirubin; ALP, Alkaline phosphatase; CB, Conjugated bilirubin; UREA, Urea; Ua, Uric acid; FBG, fasting blood glucose; TC, Total cholesterol; TB, Total bilirubin; TP, Total protein; TC/HDLC, TC/HDLC ratio; SB, systolic blood pressure; DB, diastolic blood pressure.
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Pueblo Asiatico , Hipertensión/sangre , Obesidad/sangre , Resistina/sangre , Adulto , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , China , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Circunferencia de la CinturaRESUMEN
About 15% couples suffer from infertility, half of which are caused by male factors. Male infertility usually manifests as teratozoospermia, oligospermia and/or asthenospermia, of which the most severe form is azoospermia. In this review, we summarize the recent progress in the study of genetic factors involved in nonobstructive azoospermia and teratozoospermia, Recently, with the rapid development of high-throughput chips and sequencing technologies, many genetic factors of spermatogenesis have been discovered and analyzed. For the nonobstructive azoospermia, genome-wide association studies (GWAS) and high-throughput sequencing revealed many risk loci of nonobstructive azoospermia. For the teratozoospermia, the application of whole-exome sequencing (WES) revealed a series of disease-causing genes, greatly enriching our knowledge of teratozoospermia including multiple morphological abnormalities of the flagella (MMAF). The discovery of lots of disease genes helped the characterization of the pathological mechanisms of male infertility. Therefore, a comprehensive and in-depth understanding of genetic factors in spermatogenesis abnormalities will play important roles in the clinical diagnosis, treatment and genetic counseling of male infertility.
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Azoospermia , Infertilidad Masculina , Azoospermia/genética , Estudio de Asociación del Genoma Completo , Humanos , Infertilidad Masculina/genética , Masculino , Mutación , Espermatogénesis/genéticaRESUMEN
A convenient and efficient indium-catalyzed approach to synthesize alkenyl iodides has been developed through direct iodoalkylation of alkynes with alcohols and aqueous HI under mild conditions. This catalytic protocol offers an attractive approach for the synthesis of a diverse range of alkenyl iodides in good to excellent yields.
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A simple palladium-catalyzed selective synthesis of structurally diverse 3,4-dihydroquinazolines from electron-rich arylamines, electron-poor arylamines and glyoxalates has been developed under mild conditions. This reaction is carried out in a tandem manner constituted by the condensation of arylamines and glyoxalates, the selective Diels-Alder cycloaddition and oxidation processes, in which 4-nitrothiophenol was used as the key ligand.
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OBJECTIVE: The present study aims to provide a comprehensive profile of the primary family caregivers of schizophrenia individuals in rural China. METHOD: A cross-sectional study was conducted with a sample of 327 primary family caregivers of schizophrenia individuals recruited through a one-stage cluster sampling in Ningxiang County of Hunan province, China. The social demographic and psychological profiles of primary caregivers were measured using standard scales and self-designed scales. RESULTS: The typical caregiver profile consists of a 58-year old married first degree relative (mostly parents or spouses) with a low socio-economic position. Most of them have been caregiving for over 10â¯years (74.3%) and have some physical illness (67.0%). The major caregiving activities were medicine management (71.6%) and hospital visit (69.4%), yet there is still 17.1% primary caregivers involved with neither of the care. Most (84%) of caregivers reported some kind of burden, with anxiety in 45.9% of caregivers and depression in 45.4%. Family caregivers also reported positive aspects of caregiving including a well-functional family (51.0%) and rewarding feelings (58.3%). CONCLUSION: The findings of the present study have brought attention to a special group of family caregivers for schizophrenia, with implications for intervention on them in the future.
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Cuidadores/psicología , Familia/psicología , Población Rural , Esquizofrenia/terapia , Psicología del Esquizofrénico , Adulto , Anciano , Ansiedad/epidemiología , Ansiedad/psicología , Ansiedad/terapia , Cuidadores/economía , China/epidemiología , Costo de Enfermedad , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Depresión/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Padres/psicología , Esquizofrenia/epidemiología , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The obesity-hypertension pathogenesis is complex. From the phenotype to molecular mechanism, there is a long way to clarify the mechanism. To explore the association between obesity and hypertension, we correlate the phenotypes such as the waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), and diastolic blood pressure (DB) with the clinical laboratory data between four specific Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group), and the results may show something. OBJECTIVE: To explore the mechanisms from obesity to hypertension by analyzing the correlations and differences between WC, BMI, SB, DB, and other clinical laboratory data indices in four specific Chinese adult physical examination groups. METHODS: This cross-sectional study was conducted from September 2012 to July 2014, and 153 adult subjects, 34 women and 119 men, from 21 to 69 years, were taken from four characteristic Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group). The study was approved by the ethics committee of Hangzhou Center for Disease Control and Prevention. WC, BMI, SB, DB, and other clinical laboratory data were collected and analyzed by SPSS. RESULTS: Serum levels of albumin (ALB)ï¼alanine aminotransferase (ALT), low density lipoprotein cholesterol (LDLC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), alkaline phosphatase (ALP), uric acid (Ua), and TC/HDLC (odds ratio) were statistically significantly different between the four groups. WC statistically significantly positively correlated with BMI, ALT, Ua, and serum levels of glucose (GLU), and TC/HDLC, and negatively with ALB, HDLC, and serum levels of conjugated bilirubin (CB). BMI was statistically significantly positively related to ALT, Ua, LDLC, WC, and TC/HDLC, and negatively to ALB, HDLC, and CB. DB statistically significantly positively correlated with ALP, BMI, and WC. SB was statistically significantly positively related to LDLC, GLU, serum levels of fructosamine (FA), serum levels of the total protein (TC), BMI, and WC. CONCLUSION: The negative body effects of obesity are comprehensive. Obesity may lead to hypertension through multiple ways by different percents. GGT, serum levels of gamma glutamyltransferase; ALB, serum levels of albumin; ALT, serum levels of alanine aminotransferase; LDLC, serum levels of low density lipoprotein cholesterol; TG, serum levels of triglyceride; HDLC, serum levels of high density lipoprotein cholesterol; FA, serum levels of fructosamine; S.C.R, serum levels of creatinine; IB, serum levels of indirect bilirubin; ALP, serum levels of alkaline phosphatase; CB, serum levels of conjugated bilirubin; UREA, Urea; Ua, serum levels of uric acid; GLU, serum levels of glucose; TC, serum levels of the total cholesterol; TB, serum levels of the total bilirubin; TP, serum levels of the total protein; TC/HDLC, TC/HDLC ratio.
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Presión Sanguínea , Índice de Masa Corporal , Hipertensión/fisiopatología , Obesidad/fisiopatología , Circunferencia de la Cintura , Adulto , Anciano , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Bilirrubina/sangre , Glucemia/metabolismo , China , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Diástole , Femenino , Fructosamina/sangre , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Fenotipo , Factores de Riesgo , Albúmina Sérica/metabolismo , Sístole , Triglicéridos/sangre , Ácido Úrico/sangre , Adulto Joven , gamma-Glutamiltransferasa/sangreRESUMEN
We report a stimulated Raman scattering threshold reduction by a factor of â¼4 using a simple uncoated SrWO4 crystal with plane/parallel faces pumped by 1.5 mJ, 11 ns single-frequency pulses at 532 nm. The weak etalon effect is sufficient to shape both the spatial and spectral characteristics of the output Raman beam. The Raman signal tends to be single-frequency close to threshold, which might be an interesting way to further seed Raman amplifiers for high-energy Fourier-limited pulses at particular visible or near-infrared wavelengths.
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Stroke represents a significant threat to global human health, characterized by high rates of morbidity, disability, and mortality. Predominantly, strokes are ischemic in nature. Ischemic stroke (IS) is influenced by various cell death pathways, notably autophagy and ferroptosis. Recent studies have increasingly highlighted the interplay between autophagy and ferroptosis, a process likely driven by the accumulation of reactive oxygen species (ROS). Post-IS, either the inhibition of autophagy or its excessive activation can escalate ROS levels. Concurrently, the interaction between ROS and lipids during ferroptosis further augments ROS accumulation. Elevated ROS levels can provoke endoplasmic reticulum stress-induced autophagy and, in conjunction with free iron (Fe2+), can trigger ferroptosis. Moreover, ROS contribute to protein and lipid oxidation, endothelial dysfunction, and an inflammatory response, all of which mediate secondary brain injury following IS. This review succinctly explores the mechanisms of ROS-mediated crosstalk between autophagy and ferroptosis and the detrimental impact of increased ROS on IS. It also offers novel perspectives for IS treatment strategies.
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Triplostegia glandulifera Wall (T. glandulifera) is an ethnomedicine commonly used by ethnic minorities in Yunnan, China, to treat kidney disease. However, there are few reports on the renoprotective effects of this substance, and the active ingredients remain unclear. In this study, we extracted the polysaccharide fractions TGB and TGC using the water extraction-alcohol precipitation method and determined their molecular weight (Mw) and monosaccharide composition. The study investigated the protective effects of TGB and TGC fractions against diabetic nephropathy (DN) using an in vitro high glucose-induced HRMCs model and an in vivo STZ-induced diabetic mouse model. HPLC analysis revealed that TGB contained D-galacturonic acid, D-glucose, D-galactose, and D-arabinose, and had a lower Mw than TGC. In vitro, TGB showed concentration-dependent antioxidant activity and effectively reduced abnormal proliferation and while attenuating oxidative stress in HRMCs. In mice with diabetes, TGB corrected the dysregulation of glucose-lipid metabolism and alleviated oxidative stress in the kidneys. Additionally, it improved renal function and reduced renal tissue damage. The study suggests that the low Mw polysaccharides (TGB) have better activity against DN through the antioxidative stress mechanism.
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INTRODUCTION: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. OBJECTIVE: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. METHODS AND RESULTS: Collecting duct NCOR1 knockout (KO) mice manifested increased BP and aggravated vascular and renal injury in an angiotensin II (Ang II)-induced hypertensive model. KO mice also showed significantly higher BP than littermate control (LC) mice in deoxycorticosterone acetate (DOCA)-salt model. Further study showed that collecting duct NCOR1 deficiency aggravated volume and sodium retention after saline challenge. Among the sodium transporter in the collecting duct, the expression of the three epithelial sodium channel (ENaC) subunits was markedly increased in the renal medulla of KO mice. Consistently, BP in Ang II-infused KO mice decreased significantly to the similar level as those in LC mice after amiloride treatment. ChIP analysis revealed that NCOR1 deficiency increased the enrichment of mineralocorticoid receptor (MR) on the promoters of the three ENaC genes in primary inner medulla collecting duct (IMCD) cells. Co-IP results showed interaction between NCOR1 and MR, and luciferase reporter results demonstrated that NCOR1 inhibited the transcriptional activity of MR. Knockdown of MR eliminated the increased ENaC expression in primary IMCD cells isolated from KO mice. Finally, BP was significantly decreased in Ang II-infused KO mice after treatment of MR antagonist spironolactone and the difference between LC and KO mice was abolished. CONCLUSIONS: NCOR1 interacts with MR to control ENaC activity in the collecting duct and to regulate sodium reabsorption and ultimately BP. Targeting NCOR1 might be a promising tactic to interrupt the volume and sodium retention of the collecting duct in hypertension.
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OBJECTIVE: To develop a dynamic model of Hepatitis A transmission in order to predict the long-term effectiveness of Hepatitis A vaccination on 18 months old infants and 2 to 18 years old children. METHODS: A dynamic model of HA (S-E-I-R-V) was developed using the software Berkeley-Madonna. The parameters required for the model derived from literature. A sensitivity analysis was performed to assess the stability of the model through changing parameters. RESULTS: During the period of 2010 to 2030, the cumulative cases of Hepatitis A would reach 7.8 million with an incidence of 38.8 per 100,000 without vaccination. With 38% to 57% coverage of vaccination in children of 1.5-18 years old, the cumulative cases would decrease to 4.36-4.75 million with an incidence of 17.5-19.4 per 100,000. The vaccination was predicted to reduce 3.06-3.45 million Hepatitis A cases with an incidence reduction of 19.4-21.3 per 100,000. This suggests that Hepatitis A vaccination would achieve a 54% decrease in incidence of Hepatitis A. The sensitivity analysis showed that the coverage of vaccination had a significant impact on the incidence of Hepatitis A. By 2030, the incidence of Hepatitis A would decrease from 19.4 per 100,000 to 16.0 per 100,000 when the vaccination coverage increases from 38% to 90%. CONCLUSION: Hepatitis A vaccination can effectively prevent and control the incidence of Hepatitis A.
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Vacunas contra la Hepatitis A/uso terapéutico , Hepatitis A/prevención & control , Modelos Biológicos , Vacunación , Adolescente , Niño , Preescolar , Femenino , Predicción , Hepatitis A/transmisión , Humanos , Lactante , MasculinoRESUMEN
Background: Proton pump inhibitors (PPIs) are widely used and have been linked to kidney diseases. However, the role of PPI use in the development of chronic kidney disease (CKD) remains unclear. We undertook this study to examine the association between PPI use and the subsequent risk of CKD. Methods: This is a prospective analysis of 462,421 participants free of cancer diagnosis or chronic kidney disease from the United Kingdom Biobank. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by a trained staff. Incident CKD was identified based on the medical history. Overlap propensity score weighting with the Cox model was used to calculate the effect of PPI use on CKD risk. The number needed to harm (NNH) was calculated at 5 and 10 years of follow-up. Results: We documented 7,031 cases of CKD over a median follow-up of 8.1 years. Overlap propensity score weighting analysis showed that regular PPI users had a 37% higher risk of CKD incident than non-users (HR 1.37, 95% CI 1.28-1.47). The association persisted across subgroup analyses, different types of PPIs, and several sensitivity analyses. Quantitative bias analysis indicated that the result was robust to unmeasured confounding (E-value 2.08, lower 95% CI 1.88). The NNH was 147.9 and 78.6 for 5 and 10 years of follow-up, respectively. A head-to-head comparison showed that PPI users had a 19% higher risk of CKD than H2RA users (HR 1.19, 95% CI 1.02-1.39). Conclusion: The regular use of PPI is associated with a higher risk of CKD. Healthcare providers should carefully weigh up the potential benefits against the risk in prescribing PPIs, particularly for patients requiring long-term treatment.
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PURPOSE: To investigate serum levels of free fatty acids (FFAs) and their associations with routine serum lipids in diet-induced obese mice, which have been scantily reported before. METHODS: Male C57BL/6 J mice were fed high-fat diets for 12 weeks to induce obesity. Levels of serum FFAs were measured by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Obese mice had higher serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), but lower triglycerides (TG) than control mice. A total of 30 FFAs were found, and 3 saturated fatty acids (SFAs), all 8 monounsaturated fatty acids (MUFAs) and 7 polyunsaturated fatty acids (PUFAs) decreased in obese mice, but one SFA (C4:0) increased. Differences in the relative levels of individual FFAs to total FFAs, SFAs, MUFAs or PUFAs between obese and control mice were different from each other and from those evaluated by concrete levels except C4:0, C16:1, C19:1 and C18:4. Only the concrete levels of C4:0, C22:3 and C18:4 were associated with routine serum lipids, including C22:3 negatively with TG in control mice, and C4:0 and C18:4 positively with LDL-C in obese mice, although the relative levels of C4:0 to total MUFAs negatively with TC, and C23:3 to total SFAs or MUFAs negatively with TG in control mice. Different relative levels of the remaining FFAs were differently associated with different routine serum lipids in obese and/or control mice. CONCLUSION: Obesity may influence serum FFAs profiles. The relationship of individual FFAs and their relative levels to other FFAs with routine serum lipids in obese and control mice suggests that individual FFAs may interact with others and obesity on levels of routine serum lipids. Once confirmed, the interactions may be novel perspectives when fatty acids are used to improve hyperlipidemia in the subjects with obesity.