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Objective To observe the therapeutic effect and mechanism of Modified Banxia Shumi Decoction on p-chlorophenylalanine(PCPA)-induced insomnia model rats.Methods Forty-eight male SD rats were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Chinese medicine and the Diazepam group,with 8 rats in each group.For 7 consecutive days before modeling,rats in the Chinese medicine low-,medium-and high-dose groups were treated with Modified Banxia Shumi Decoction for prophylactic treatment.Except for the normal group,PCPA-induced insomnia rat model was established in all groups.After modeling on day 1,each group continued to be administered the corresponding drug for 7 days.Body mass was monitored,open-field behavioral tests were performed,serum levels of orexin A(OXA)and orexin B(OXB)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of hypothalamic orexin receptor 1(OX1R)was determined by immunohistochemistry,and hematoxylin-eosin(HE)staining was used to observe the pathologic changes in the hypothalamus of rats.Results(1)Before modeling,the growth trend of body mass of rats in each group was smooth,with no significant difference between groups;after modeling,except for the normal group,the growth rate of body mass of rats in each group slowed down or even declined;after 14 days of administration of Modified Banxia Shumi Decoction,the body mass of the Chinese medicine medium-dose group was significantly increased compared with that of the model group(P<0.01).(2)Compared with the normal group,the model group showed an increase in the total distance of activity in the open field,the distance of activity in the central region and the number of times of entering the central region(P<0.01),a significant increase in serum OXA and OXB contents(P<0.01),a significant increase in the expression of hypothalamic OX1R(P<0.01),and HE staining showed mild hyperplasia of the hypothalamic glial cells;compared with the model group,the total distance of activity in the open field,the distance of activity in the central region and the number of times entering the central region were reduced in the rats in the Chinese medicine medium-dose group and the Diazepam group(P<0.01),the levels of serum OXA and OXB were significantly reduced(P<0.01),the expression of hypothalamic OX1R was significantly reduced(P<0.01),and the HE staining showed that a large number of neurons with perineurial interspace enlarged and the local glial cell hyperplasia.Conclusion Modified Banxia Shumi Decoction can improve insomnia and reduce anxiety in rats by down-regulating the levels of OXA and OXB in serum and the expression of OX1R in the hypothalamus.
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Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.
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Objective:To investigate the relationship between thyroid-stimulating hormone(TSH) levels and 10-year mortality in women aged 40 years and older.Methods:Residents aged 40 and over in urban areas of Guiyang City who participated in the " Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)" were followed up in 2011. Finally, 5 614 people were enrolled, and the baseline general information, physical examination and TSH detection were carried out. The average follow-up was(9.77±1.55) years, and the treatment and death of thyroid-related diseases were recorded. The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women, and plotting survival time curves(Kaplan-Meier curves) to study the association between elevated TSH levels and lifespan in subjects under 65 years old. Results:The multivariate Cox proportional hazards model showed that compared with the normal group, after multivariate adjustment, the risk of death in the TSH increased group was decreased( HR=0.644, 95% CI 0.478-0.868, P<0.05); after stratifying the elevated TSH group, the risk of death was decreased in the slightly elevated TSH group( HR=0.566, 95% CI 0.405-0.791, P<0.001); the elevated TSH group was further stratified by age. In the group under 65 years old, compared to the normal group, the mildly elevated group showed a reduced risk of mortality( HR=0.429, 95% CI 0.245-0.751, P=0.003). In the group aged 65 and above, there were no statistically significant differences in mortality risk between the mildly elevated group, severely elevated group, and the normal group( P>0.05). In the group under 65 years old, the K-M curve indicated that the survival rate of the mildly elevated TSH group was significantly higher than that of the normal group( χ2=11.931, P=0.003), the difference was statistically significant. Conclusion:Mildly elevated TSH levels in women aged 40-65 years are associated with a reduced risk of all-cause death and longer lifespan.
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Diabetic peripheral neuropathy (DPN) is one of the chronic complications of diabetic neuropathy, and also the main cause of chronic wounds and disability. Exosomes and exosomal-microRNAs (miRNAs) are closely related to DPN and participate in the signal transduction and protein expression of the peripheral nervous system by mediating intercellular communication. However, the specific role and mechanism of EVs and exosomal-miRNAs in the occurrence and development of DPN in high-glucose environments are not fully understood. This article reviews the promotion of EVs and exosomal-miRNAs in the occurrence and development of DPN in inhibiting axon growth, promoting inflammatory response, and inducing vascular injury in a high glucose environment.
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Humanos , MicroARNs/genética , Exosomas/metabolismo , Neuropatías Diabéticas/metabolismo , Transducción de Señal , Glucosa/metabolismo , Diabetes MellitusRESUMEN
Diabetic peripheral neuropathy (DPN) is one of the chronic complications of diabetic neuropathy, and also the main cause of chronic wounds and disability. Exosomes and exosomal-microRNAs (miRNAs) are closely related to DPN and participate in the signal transduction and protein expression of the peripheral nervous system by mediating intercellular communication. However, the specific role and mechanism of EVs and exosomal-miRNAs in the occurrence and development of DPN in high-glucose environments are not fully understood. This article reviews the promotion of EVs and exosomal-miRNAs in the occurrence and development of DPN in inhibiting axon growth, promoting inflammatory response, and inducing vascular injury in a high glucose environment.
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Humanos , MicroARNs/genética , Exosomas/metabolismo , Neuropatías Diabéticas/metabolismo , Transducción de Señal , Glucosa/metabolismo , Diabetes MellitusRESUMEN
Objective To analyze the disease burden of type 2 diabetes mellitus(T2DM)attributable to high body mass index(BMI)in China from 1990 to 2019 in the context of rapid growth in high BMI rates.Methods Data was extracted from GBD 2019,and the disease burden of T2DM attributable to high BMI in China from 1990 to 2019 was analyzed for overall and subgroups defined by age and sex separately and jointly.The joinpoint regression models were used to analyze the trends of standardized death rate and standardized disability-adjusted life year(DALY)rate.Results From 1990 to 2019,the prevalence of T2DM increased from 2928.78 per 100000 to 6328.79 per 100000 in China.The number of T2DM deaths attributed to high BMI increased from 10500 to 47500 and the standardized death rate increased from 1.25 per 100000 to 2.39 per 100000.The attributed DALY increased from 771800 person-years to 3737600 person-years,and the standardized DALY rate increased from 80.21 per 100000 to 181.54 per 100000.Years of life lost(YLL)and years lived with disability(YLD)and their standardized rates also increased.From 1990 to 2019,the annual average percentage change of the standardized death rate and the standardized DALY rate of T2DM attributable to high BMI were 2.28%and 2.81%,respectively,which were statistically significant(P<0.05)and males were both higher than females.The standardized DALY rate and the standardized death rate of males exceeded that of females in 2010 and 2014,respectively.Age-stratified results showed that the burden of T2DM,which is attributed to a high BMI,is even greater in people over 50 years old.The YLD rate attributable to high BMI increased the most among the 15~49 age group,reaching 323.99%.Conclusion From 1990 to 2019,the disease burden of T2DM that can be attributed to high BMI increased significantly in China.It is necessary to strengthen prevention and control efforts,effectively manage population BMI,and adopt key interventions for high-risk groups to reduce the disease burden of T2DM.
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This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.
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AIM: To evaluate the efficacy and safety of foveal-sparing internal limiting membrane peeling(FSIP)or complete internal limiting membrane peeling(CMIP)for the treatment of myopic traction maculopathy(MTM)during vitrectomy.METHODS: CNKI, Wanfang, VIP, PubMed, Embase, Cochrane Library, and Web of Science were searched from January 1th 2000 to July 1th 2022, and studies that compared FSIP and CMIP for MTM were collected. The change and recovery rate of best corrected visual acuity(BCVA), incidence of full-thickness macular hole(FTMH), change of central foveal thickness(CFT)and the rate of complete reattachment.RESULTS: A total of 484 eyes from 12 literatures were included, with 203 eyes in the FSIP group and 281 eyes in the CMIP group. The results of Meta-analysis showed that FSIP group were superior to the CMIP group in the mean change of BCVA(SMD=0.52, 95%CI: 0.20~0.85, P=0.002), the improvement rate of BCVA(RR=1.50, 95%CI: 1.22~1.85, P=0.0002)and the incidence of postoperative FTMH(RR=0.23, 95%CI: 0.10~0.54, P=0.0008). There was no statistical difference between the two surgical methods in terms of mean change in CFT(SMD=0.04, 95%CI: -0.19~0.26, P=0.75)and the rate of complete reattachment(RR=1.12, 95%CI: 0.94~1.32, P=0.20).CONCLUSION: FSIP have similar anatomical outcomes compared to CMIP, but FSIP resulted in better visual acuity and lower incidence of postoperative FTMH.
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OBJECTIVE To provide reference for clinically safe application of avapritinib. METHODS The adverse drug event (ADE) reports of avapritinib from January 9th,2020,to September 30th,2022 were collected from FDA Adverse Event Reporting System (FAERS) database. For data mining and analysis,reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method in the proportional imbalance method were utilized. RESULTS A total of 10 895 ADE reports with avapritinib as the main suspect drug were gathered,and 201 ADE signals involving 19 systematic organ classifications were found after eliminating invalid signals. The instruction of the drugs did not mention any of the ADE,including tinnitus,dementia,chilly limbs, the reduction of blood iron,the reduction of blood sugar,fever,the reduction of vitamin D and vitamin B12,as well as all ADE in the 2 SOCs of musculoskeletal and connective tissue illnesses,diseases of the reproductive system,and diseases of the breast. The majority of the ADE reports 670 cases with complete drug information were for the nervous system (230 cases,accounting for 34.33%) and ocular organ (277 cases,accounting for 41.34%). Compared with other systems,daily dose and treatment course showed significant effects on ADE of neurological system and ocular organ (P<0.05),and the patient’s age had a significant impact on the ADE of the nervous system (P<0.05). CONCLUSIONS A greater incidence of ADE after using avapritinib is present in patients older than 65 with a daily dose of 300 mg/d and a treatment period lasting between 31 and 90 days; patients receiving a daily dose of 300 mg/d and a treatment regimen lasting 31 to 90 days are more likely to experience ADE of the ocular organ. Attention should be given to the aberrant symptoms of the patient’s eyes and nervous system throughout clinical use of avapritinib,and prompt intervention should be given.
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OBJECTIVE@#To explore the influence of the thickness of mixed cardboard on the compressive strength of glass ionomer cement and the associated factors.@*METHODS@#Three different types of glass ionomer cements were mixed on the top of 60, 40, 20 and 1 pieces of paper (P60, P40, P20 and P1), respectively. The compressive strength of the materials was tested after solidification, and the bubble rate was calculated with the assistance of scanning electron microscope.@*RESULTS@#(1) Compressive strength: ① ChemFil Superior glass ionomer (CF): The average compressive strength of P1 group was the highest, which was significantly different from that of P40 and P60 groups (P values were 0.041 and 0.032 respectively); ② To Fuji IX GP glass ionomer (IX): The average compressive strength of P1 group was the highest, which was statistically different from that of P40 and P60 groups (P values were 0.042 and 0.038 respectively); ③ Glaslonomer FX-Ⅱ glass ionomer cement (FX): The average compressive strength of P1 group was the highest, which was statistically different from that of P20, P40 and P60 groups (P values were 0.031, 0.040 and 0.041 respectively), but there was no statistical difference among the other groups. All the three materials showed that the compressive strength of glass ions gradually increased with the decrease of the thickness of the blended paperboard, and the two materials had a highly linear negative correlation, the correlation coefficients of which were CF-0.927, IX-0.989, FX-0.892, respectively. (2) Scanning electron microscope: P1 group had the least bubbles among the three materials.@*CONCLUSION@#It indicates that the thickness of mixed cardboard has a negative correlation with the compressive strength of glass ions. The thicker the mixed cardboard is, the greater the elasticity is. Excessive elasticity will accelerate the mixing speed when the grinding glass ions. Studies have shown that the faster the speed of artificial mixing is, the more bubbles is produced.The thicker ther mixed cardboard is, the more bubblesn are generated by glass ionomer cement, and the higher the compressive strength is. Using one piece of paper board to mix glass ionomer cement has the least bubbles and can obtain higher compressive strength.
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Fuerza Compresiva , Ensayo de Materiales , Cementos de Ionómero Vítreo , Dióxido de SilicioRESUMEN
Intestinal flora and its metabolites are closely related to the progression of type 2 diabetes mellitus(T2DM). Eubacterium is one of the dominant intestinal flora, and its metabolites short-chain fatty acids (SCFAs) play a leading role in regulating intestinal metabolic balance. It has been reported that SCFAs can regulate the secretion of glucagon-like peptide-1, improve the function of pancreatic β cells, participate in bile acids metabolism and regulate the production of inflammatory factors in T2DM. Based on the above research background, this article mainly reviews the relationship between Eubacterium and its metabolite SCFAs and T2DM and its regulatory mechanism.
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Humanos , Diabetes Mellitus Tipo 2 , Eubacterium/metabolismo , Ácidos Grasos Volátiles/metabolismo , Microbioma GastrointestinalRESUMEN
Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
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Femenino , Humanos , Adulto , Acetato de Medroxiprogesterona/efectos adversos , Hiperplasia Endometrial/patología , Didrogesterona/efectos adversos , Hiperplasia , Estudios ProspectivosRESUMEN
Objective To formulate a scientific and standardized follow-up checklist for postoperative patients with cervical cancer,and provide a scientific tool to support the follow-up work.Methods The first draft of the follow-up checklist was constructed through literature review and semi-structured interviews,and the final draft of the follow-up checklist was formed by conducting 2 rounds of correspondence with experts using the Delphi method from October to December 2022,screening experts'opinions and revising and improving the checklist.The convenience sampling method was adopted to select 8 nurses and 15 patients with cervical cancer after surgery from a tertiary A hospital in Liaoning Province from February to March 2023 as the research subjects.The nurses made telephone follow-up visits to the patients with the postoperative follow-up list and evaluated the follow-up list.Results The positive coefficients of the experts in the 2 rounds of correspondence were 88.89%and 100%,respectively;the authoritative coefficients were 0.88 and 0.89,respectively;the Kendal harmony coefficient of the primary,secondary and tertiary indicators were 0.177,0.245 and 0.179 in the first round and 0.170,0.118 and 0.107 in the second round,respectively(P<0.05).The final follow-up checklist for postoperative patients with cervical cancer included 4 primary indicators of physical and daily life support,information support,psychological support,and social support,12 secondary indicators,and 45 tertiary indicators.Both nurses and patients believed that the follow-up list was comprehensive with strong professional and clinical practicability.Conclusion The follow-up checklist is reasonable in structure,comprehensive in content,and reliable,specialized and practical,which can provide a scientific and standardized tool to support post-discharge follow-up of patients with cervical cancer.
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Gallbladder cancer(GBC)is a common malignancy of the biliary system with a poor diagnosis.The 5-year survival rate for patients with advanced GBC is less than 10%.Surgery is the only effective treatment for this disease.Tumor microenvironment(TME)plays an important role in GBC tumorigenesis,progression and prognosis.Tumor-associated macrophages(TAMs)are among the most abundant immune cells infiltrating the TME and are present in all stages of GBC progression.This paper has summarized the dynamic phenotypic transformation that macrophages undergo during GBC progression,discussed the impact that TAMs bring to GBC progression and the therapeutic potential of TAM-targeted strategies,and proposed the possible ways in which TAM are involved in the mechanism of GBC progression and are linked to the construction of the immunosuppressive TME.A generalization and analysis of the biological properties of TAM and their roles in GBC was carried out in the hope to provide reference for the development and innovation of GBC therapies.
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Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.
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Humanos , Calidad del Agua , Agua Potable , Fluorocarburos/análisis , Caprilatos/análisis , China , Contaminantes Químicos del Agua/análisisRESUMEN
Objective To observe the value of zero echo time(ZTE)3.0T MRI for detecting lung cancer nodules.Methods Totally 126 lung cancer patients(176 lung nodules)were prospectively enrolled and underwent 3.0T MR axial lung scanning,including T1-volumetric interpolated breath-hold examination(VIBE),T2-BLADE,T2-half-Fourier acquisition single-shot turbo spin-echo(HASTE)and ZTE sequences.The consistency between ZTE MRI and previous CT for displaying characteristics of pulmonary nodules was analyzed,and the sensitivity of different MR sequences for detecting pulmonary nodules were observed.Results Among 176 pulmonary nodules showed on CT,ZTE MRI detected 140 and missed 36 ones.The consistency between ZTE MRI and CT for displaying the maximum diameter and actual maximum diameter of pulmonary nodules were both good(ICC=0.954,0.943,both P<0.001),and the difference between ZTE MRI and CT was small.The consistency between ZTE MRI and CT for displaying tracheal vascular bundles,pleural indentation and internal bronchial inflation signs were all good(Kappa=0.894,0.912,0.917),while for displaying the type and shape of nodules were both moderate(Kappa=0.661,0.501).The sensitivity of ZTE MRI for detecting pulmonary nodules was higher than that of other individual MR sequences(all P<0.05),of combination of ZTE and T2 BLADE was higher than that of other sequence combinations(all P<0.05).Conclusion ZTE 3.0T MRI could be used to detect lung cancer nodules,which was superior to conventional MRI.Combination of ZTE 3.0T MRI with T2-BLADE could improve the sensitivity for detecting pulmonary nodules.
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Objective @# Based on metabolomics and transcriptomics analysis , to explore the molecular mechanism of spleen inflammation induced by high altitude hypoxia in mice through NOD⁃like receptor signaling pathway . @*Methods @#C57BL/6 mice were raised at an altitude of 400 m and 4 200 m respectively , with five mice in each group , and spleen tissues were collected after 30 days . Differential metabolites and differentially expressed genes in key pathways were screened by metabolomics and transcriptome analysis and correlation KEGG enrichment analysis , and the related network interaction diagram of differential metabolites and differentially expressed genes in key pathways was constructed and verified by RT⁃qPCR . @*Results @#Metabolomics analysis showed that 133 differential metabolites were screened from in the plain spleen control group (PSC group) and the plateau spleen test group (HST group) , 95 of which were up⁃regulated while 38 of which were down⁃regulated . KEGG enrichment analysis showed that they were mainly involved in NOD⁃like receptor signaling pathway , HIF⁃1 signaling pathway , cholesterol metabolism and other metabolic pathways . The results of transcriptome analysis showed that a total of 4213 differentially expressed genes were identified in PSC group and HST group , including 1947 up⁃regulated genes and 2266 down⁃regulated genes . KEGG was enriched in 173 signaling pathways , including NOD⁃like receptor signaling pathway , MAPK signaling pathway , NF⁃κB signaling pathway and other pathways . Comprehensive analysis showed that the differential metabolites and differentially expressed genes were obviously enriched in NOD⁃like receptor signaling pathway . Therefore , the correlation network interaction map was constructed for the differential metabolites ATP and differentially expressed genes in NOD⁃like receptor signaling pathway . RT⁃qPCR results showed that compared with PSC group , the expression levels of DEGs related to NOD1 and NOD2 (CHUK , TAB3 , MAPK8) in the signaling pathway of NOD⁃like receptor and NLRP1 ⁃CASP1 pathway (NLRP1b , CASP1) in HST group were significantly enhanced . The mRNA expression levels of downstream inflammatory factors IL⁃6 , IL⁃1 β , IL⁃18 , INF⁃γ and TNF⁃α were up⁃regulated and differentially expressed . @*Conclusion @# Based on the combined analysis of metabolomics and transcriptomics , it was found that hypoxia stimulation at high altitude may affect the NOD⁃like receptor signaling pathway in vivo , and the differential metabolite ATP is positively correlated with the differential key genes in the pathway . ATP mediates the release of downstream inflammatory factors by activating NOD1 , NOD2 pathways and NLRP1 inflammable⁃CASP1 pathways . Inflammatory response occurred in spleen tissue of mice.
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Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.
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Objective:To compare the efficacy and safety of omacycline with meropenem plus linezolid in the treatment of patients with pulmonary infection.Methods:The clinical data of 58 patients with pulmonary infection admitted to the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou Red Cross Hospital and Jiande First People’s Hospital from December 2021 to May 2022 were retrospectively analyzed. The patients were divided into the omacycline group ( n=29) and the meropenem combined with linezolid group (combined group, n=29). The omacycline group was given intravenous omacycline 200 mg or 100 mg, q. d, and the combined group was given intravenous meropenem (1 000 mg, t.i.d) and linezolid (600 mg, b. i.d). The clinical efficacy and drug-related adverse events of two groups were observed. SPSS 22.0 statistical software was used for data analysis. Results:In the omacycline group, 8 cases (27.6%, 8/29) were cured, 19 cases (65.5%, 19/29) were improved, and 2 cases (6.9%, 2/29) were worsened. In the combined group, 1 case (3.4%, 1/29) was cured, 26 cases (89.7%, 26/29) were improved, and 2 cases (6.9%, 2/29) died. There was a statistically significant difference between the two groups ( χ2=6.533, P=0.038). The respiratory failure occurred in 3 cases (10.3%, 3/29) of the omacycline group and 5 cases (17.2%, 5/29) of the combined group ( χ2=0.580, P=0.446). In those patients who were cured or improved, the median time from treatment initiation to disease remission was 3.0 (2.0, 5.5) d in the omacycline group and 5.0 (4.0, 6.0) d in the combined group ( Z=-2.122, P=0.034). There was no significant difference in the incidence of adverse reactions between the two groups [6.9% (2/29) vs. 13.8% (4/29), χ2=0.744, P=0.389]. Conclusion:Omacycline exhibits a good efficacy and safety in the treatment of patients with pulmonary infection, which may be prioritized for the treatment of pulmonary infections.
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Objective:To investigate the effect of the interaction between metabolic syndrome and smoking on the risk of subsequent cardiovascular events.Methods:Urban residents aged 40 and above in the Yunyan District of Guiyang City were selected from " Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) Study". The baseline survey started in 2011 and general information including gender, age, medical history, lifestyle habits, and smoking status were collected. Additionally, biochemical indicators related to metabolic syndrome(MS) were measured. The study participants were then followed up, and the first cardiovascular events occurring after the initial survey were recorded. The average follow-up period was 10.07±1.49 years. The interaction between metabolic syndrome and smoking on subsequent cardiovascular events was analyzed using Cox proportional hazards models.Results:The study included a total of 7 275 individuals, among whom 639 experienced cardiovascular events. After adjusting for multiple variables, compared to non-smokers without metabolic syndrome(MS), smokers with MS showed a higher risk of cardiovascular events, with a hazard ratio( HR) of 6.54(95% CI 4.88, 8.78). This risk was higher than that of individuals with MS who never smoked [ HR 1.39(95% CI 1.11, 1.75)] and non-MS smokers [ HR 2.48(95% CI 1.77, 3.49)]. There was an additive interaction between MS and smoking on the occurrence of cardiovascular events, with a relative excess risk due to interaction(RERI) of 3.30(95% CI 1.89, 4.70), an attributable proportion(AP) of 0.55(95% CI 0.43, 0.59), and a synergy index(S) of 3.07(95% CI 1.94, 4.84). Furthermore, when stratifying the duration of smoking cessation, long-term quitters(≥8 years) showed a lower risk of cardiovascular events compared to current smokers, regardless of whether they had MS. The hazard ratios were 0.45(95% CI 0.26, 0.78) for individuals with MS and 0.42(95% CI 0.19, 0.95) for individuals without MS. Conclusions:There is an additive interaction between smoking and MS on the risk of cardiovascular events. The coexistence of both factors significantly increases the risk of cardiovascular events.