ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

This article reports a first case of combined infection with severe fever with thrombocytopenia syndrome(SFTS)and scrub typhus in Dalian City.The patient was admitted to the hospital due to recurrent fever for 7 days and loss of consciousness for 1 day.Pathogen metagenomic sequencing(mNGS),SFTSV quantitative PCR,and enzyme-linked immunosorbent assay(ELISA)IgM tests were performed,showing positive results for Orientia tsutsugamushi and SFTSV nucleic acids.Based on clinical manifestations and epidemiological history,the patient was diagnosed with combined infections.

Objective:To investigate the value of MRI perfusion multiple parameters in preoperative classification of glioma and differential diagnosis of single brain metastases.Methods:A retrospective analysis was conducted on 78 patients initially diagnosed with glioma or single brain metastasis admitted to Cangzhou People's Hospital from January 2018 to July 2024,including 36 cases of glioma and 42 cases of single brain metastasis.Preoperative brain magnetic resonance imaging was performed to measure dynamic sensitive contrast magnetic resonance imaging(DSC-MRI),dynamic enhanced magnetic resonance imaging(DCE-MRI),and microvascular diameter imaging(VSI)parameters.Compare multiple parameters of magnetic resonance perfusion in patients with gliomas,solitary brain metastases,and gliomas of different pathological grades.Draw the working characteristic curve of the subjects and calculate the area under the curve(AUC)to analyze the diagnostic value of multi parameter magnetic resonance perfusion for gliomas.Spearman analysis was used to investigate the correlation between multiple parameters of magnetic resonance perfusion and pathological grading of glioma patients.Results:Cerebral blood volume(rCBV),cerebral blood flow(rCBF),volume transport constant(Ktrans),extracellular space volume ratio(Ve)and VSI values of glioma patients were significantly higher than those of single brain metastases,and the differences were statistically significant(t=25.066,26.892,22.856,70.455,27.984,P<0.05).The sensitivity of rCBV,rCBF,Ktrans,Kep,Ve,and VSI in diagnosing gliomas were 79.44%,78.54%,80.11%,63.32%,74.61%,and 77.29%,respectively.The specificity was 77.27%,76.49%,78.14%,61.38%,72.58%,and 75.13%,respectively.The AUC was 0.861,0.843,0.815,0.532,0.883,and 0.762,respectively;The sensitivity,specificity,and AUC of the combined detection of rCBV,rCBF,Ktrans,Kep,Ve,and VSI for diagnosing gliomas were 85.98%,82.24%,and 0.911,respectively.The diagnostic efficacy of the combined detection for gliomas was superior to that of individual indicators(Z=0.431,0.335,0.512,0.408,0.369,0.358,P<0.05).The rCBV,rCBF,Ktrans,Ve and VSI values of patients with grade Ⅰ,Ⅱ,Ⅲ and Ⅳ glioma increased successively,and the comparison between groups was statistically significant(F=119.972,100.884,74.180,74.180,118.485,P<0.05).The values of rCBV,rCBF,Ktrans,Ve and VSI were significantly positively correlated with the pathological grade of glioma patients(r=0.685,0.726,0.745,0.668,0.714,P<0.05).Conclusion:There are great differences in the multiple parameters of MRI perfusion between brain glioma and single brain metastases.Therefore,MRI perfusion multiple parameters have high differential diagnosis value,and are helpful for preoperative diagnosis and pathological classification of brain glioma,and have clinical guiding significance.

Objective:To study the dosimetric characteristics of the Avoidance Sectors function in the Eclipse planning system in the design of volumetric intensity-modulated arc radiotherapy(VMAT)plan for non-small cell lung cancer(NSCLC).Methods:The case data of 20 NSCLC patients who admitted to Hunan Provincial Cancer Hospital in 2024 were retrospectively selected,both free avoidance sectors volumetric(FASV)modulated arc therapy and avoidance sectors volumetric(ASV)modulated arc therapy were formulated for all patients.The dose parameters and the total number of machine unit(MU)of accelerator of the target area and organs at risk between two kinds of plans were compared.The correlation between the ratio(VPTV/Vlung)of planning target volume(PTV)to whole lung volume and the exposure dosimetry index of whole lung were further analyzed.Results:Comparative result between FASV plan and ASV plan indicated that the conformity index(CI)of the FASV plan was(0.83±0.07),which was better than that of the ASV plan(0.78±0.06),and the difference was significant(t=2.086,P<0.05).The V5 value(48.35±7.28)%of the whole lung in the ASV plan was significantly lower than that(57.68±6.63)%in the FASV plan(t=3.670,P<0.05).There were not statistically significant differences in the V20,V30 and mean dose(Dmean)of the whole lung and heart between two kinds of plans(P>0.05).There were not statistically significant differences in the maximum doses of the spinal cord and esophagus between two kinds of plans(P>0.05).The total MU value(444.8±78.9)of the ASV plan was less than that(518.27±70.9)of the FASV plan(t=2.682,P<0.05).The results of Pearson correlation analysis indicated that the correlative values between VPTV/Vlung and V20,V30,and Dmean of whole lung were respectively r=0.756,0.697,and 0.732 in FASV plan(P<0.05).Conclusion:For NSCLC patients,the ASV plan can effectively reduce V5 value of lung tissue,and decrease the total MU value of accelerator's irradiation.The avoidance sectors function is worthy of recommendation.In FASV plan,the VPTV/Vlung value appeared a positive correlation with whole lung V20,V30,and Dmean.It is very necessary to adopt individual management strategies for respiratory motion in reducing the irradiation range of target area.

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Life Style ; Pneumonia/etiology* ; Prognosis ; Risk Factors ; Smoking

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

BACKGROUND: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. METHODS: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. RESULTS: Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring ( Pnonlinear <0.0001). CONCLUSIONS Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Morbidity ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Family Characteristics ; Mortality ; East Asian People

This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
Humans ; Apoptosis/drug effects* ; Hep G2 Cells ; Glycyrrhetinic Acid/pharmacology* ; Doxorubicin/pharmacology* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/physiopathology* ; Mitochondria/metabolism* ; Endoplasmic Reticulum/metabolism* ; Cell Survival/drug effects* ; Membrane Proteins/genetics*