OBJECTIVE To investigate the effects of Ephedra-Cinnamomum couplet medicinals on respiratory function and airway inflammation in rats with asthma of cold-fluid retention in lung syndrome and its mechanism. METHODS Sixty Wistar rats were randomly divided into blank group， model group， dexamethasone group [1 mg/（kg·d）]， and Ephedra-Cinnamomum low-， medium-， high-dose groups [0.234， 0.936， 1.872 g/（kg·d）]， with 10 rats in each group. The model and treatment groups were sensitized by intraperitoneal injection of antigen solution （ovalbumin 100 mg + aluminum hydroxide 100 mg） and challenged with 1% ovalbumin nebulization， along with exposure to a cold environment and ingestion of cold water， to establish the asthma model with cold-fluid retention in lung syndrome. From day 2， rats received corresponding drugs or normal saline intragastrically， once a day， for 21 consecutive days. The general behavioral changes in each group of rats were observed during the experimental process. The lung function parameters [peak expiratory flow （PEF）， airway resistance （Raw）， functional residual capacity （FRC）， expiratory flow at 50% of forced vital capacity （EF50%）] Δ 基金项目 国家自然科学基金青年科学基金项目（No.82004233）； were measured before modeling and after the last medication as well as serum contents of interleukin-6 （IL-6）， IL-13， tumor necrosis factor- α （TNF- α） and interferon-gamma （IFN- γ） after the last medication were determined； the histopathological morphological changes in the lung tissues of rats were also observed； mRNA expressions of IL-6， IL-3， TNF-α， IFN-γ， thymic stromal lymphopoietin （TSLP）， and Toll-like receptor 4 （TLR4）， as well as protein expressions of TSLP and TLR4 were determined in lung tissue. RESULTS Compared with model group， the lung tissue damage of rats was relieved significantly； Raw， FRC， the contents and mRNA expression levels of IL-6， IL-13 and TNF-α， as well as the mRNA and protein expressions of TSLP and TLR4 were significantly decreased （P＜0.05）， while the contents and mRNA expressions of PEF， EF50 % and IFN-γ were significantly increased in the dexamethasone group and Ephedra-Cinnamomum medium- and high-dose groups （P＜0.05）. Moreover， only a few rats in the two groups exhibited typical symptoms of asthma. CONCLUSIONS Ephedra-Cinnamomum couplet medicinals improve respiratory function and ameliorate airway inflammation in asthma rats with cold-fluid retention in lung syndrome， the mechanism of which may be associated with inhibiting TSLP/TLR4 signaling pathway and modulating Th1/Th2 imbalance.

OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase （AMPK）/silencing information regulatory factor 1 （SIRT1）/ peroxisome proliferator activated-receptor-γ coactivator-1α （PGC-1α） signaling pathway. METHODS Rats with hip fracture surgery were assigned into model group， esketamine group （10 mg/kg）， inhibitor group （250 μg/mL AMPK inhibitor Compound C）， and esketamine+inhibitor group （10 mg/kg esketamine + 250 μg/mL Compound C）， and rats undergoing sham surgery were used as the control group， with 12 rats in each group. New object recognition and Barnes maze experiments were used to E-mail：448231@163.com evaluate cognitive function in rats. The levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β），superoxide dismutase （SOD）， malondialdehyde （MDA）， gamma-aminobutyric acid （GABA）， dopamine （DA） and glutamate （Glu）， and the apoptosis of hippocampal neurons were detected. The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed. The mRNA expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax），the mRNA and protein expression of AMPK， SIRT1 and PGC-1α， as well as the expression of phosphorylated （p）-AMPK in hippocampal tissue， were detected. RESULTS Compared with the control group， the hippocampal neurons in the model group of rats were disordered， with more neurons necrotic and swollen mitochondria；the new object recognition index， the SOD， GABA， DA levels， Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly reduced， while the latency and number of errors for locating unknown holes， the TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly increased/prolonged （P＜0.05）. Compared with the model group， the esketamine group showed reduced pathological damage to the hippocampal tissue of rats， and the new object recognition index， the SOD， GABA and DA levels， the Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly increased，while the latency and error frequency for locating unknown holes， TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly decreased （P＜0.05）；the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group （P＜0.05）.AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats （P＜0.05）. CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway， inhibiting neuronal cell apoptosis， improving mitochondrial structure， and promoting postoperative cognitive function recovery.

BACKGROUND: Gout is a chronic disease primarily caused by elevated urate levels, severely affecting joint health. Its global distribution varies, and updated data for China are lacking. This study aimed to analyze the current burden and trends of gout globally and in China, examining the burden by gender, age, and risk factors while providing future predictions. METHODS: This descriptive epidemiological secondary analysis utilized data from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2021 study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life years (DALYs) rates (ASDR) were used to assess the gout burden. Trends from 1990 to 2021 were analyzed across global regions, genders, and sociodemographic index (SDI) levels. The burden in China was further examined by gender, age, and associated risk factors. The Bayesian age-period-cohort (BAPC) model was used to predict future trends. Gout burden in China and the United States was compared. RESULTS: In 2021, gout affected 57 million people globally, with 9.4 million new cases and 1.75 million DALYs. From 1990 to 2021, the ASIR, ASPR, and ASDR increased by 17.2%, 21.9%, and 21.3%, respectively. Males experienced a significantly higher burden, with greater ASIR, ASPR, and ASDR increasing with higher SDI levels. In China, male ASIR, ASPR, and ASDR were over 2.8 times those of females, and the burden increased with age. In 2021, 31.4% of gout-related DALYs in China were attributed to high body mass index and 7.6% to kidney dysfunction. Between 1990 and 2021, the high body mass index-related burden of gout rose annually for both genders, while the kidney dysfunction-related gout burden remained stable. By 2050, the burden of gout in China is expected to continue increasing, with a slower rise in females and a decline in males after an initial increase. However, the overall burden will remain substantial. In comparison, the gout burden will be higher in the United States than in China. CONCLUSIONS Gout is becoming a significant health burden globally and in China, particularly among Chinese males and older individuals. With the aging population and lifestyle changes exacerbating the issue, effective strategies and measures are essential to prevent or reduce gout-related health issues.
Humans ; Gout/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Prevalence ; China/epidemiology* ; Adult ; Risk Factors ; Aged ; Global Burden of Disease ; Disability-Adjusted Life Years ; Young Adult ; Adolescent ; Quality-Adjusted Life Years

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

OBJECTIVE: To explore the correlation between mechanical power normalized to dynamic lung compliance (Cdyn-MP) and weaning outcomes and prognosis in mechanically ventilated patients. METHODS: A prospective, observational cohort study was conducted. Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and used a T-tube ventilation strategy for extubation in the intensive care unit (ICU) of Lianyungang First People's Hospital and Lianyungang Second People's Hospital between January 2022 and December 2023 were enrolled. The collected data encompassed patients' baseline characteristics, primary causes of ICU admission, vital signs and laboratory indicators during the initial spontaneous breathing trial (SBT), respiratory mechanics parameters within the 4-hour period prior to the SBT, weaning outcomes and prognostic indicators. Mechanical power (MP) and Cdyn-MP were calculated using a simplified MP equation. Univariate and multivariate Logistic regression analyses were utilized to determine the independent risk factors associated with weaning failure in patients undergoing mechanical ventilation. Restricted cubic spline (RCS) analysis and Spearman rank-sum test were employed to investigate the correlation between Cdyn-MP and weaning outcomes as well as prognosis. Receiver operator characteristic curve (ROC curve) was constructed, and the area under the ROC curve (AUC) was computed to evaluate the predictive accuracy of Cdyn-MP for weaning outcomes in mechanically ventilated patients. RESULTS: A total of 366 patients undergoing IMV were enrolled in this study, with 243 cases classified as successful weaning and 123 cases classified as failed weaning. Among them, 23 patients underwent re-intubation within 48 hours after the successful withdrawal of the first SBT, non-invasive ventilation, or died. Compared with the successful weaning group, the patients in the failed weaning group had significantly increased levels of sequential organ failure assessment (SOFA) score, body temperature and respiratory rate (RR) during SBT, and respiratory mechanical parameters within the 4-hour period prior to the SBT [ventilation frequency, positive end-expiratory pressure (PEEP), platform pressure (Pplat), peak inspiratory pressure (Ppeak), dynamic driving pressure (ΔPaw), fraction of inspired oxygen (FiO₂), MP, and Cdyn-MP], dynamic lung compliance (Cdyn) was significantly reduced, and duration of IMV, ICU length of stay, and total length of hospital stay were significantly prolonged. However, there were no statistically significant differences in age, gender, body mass index (BMI), smoking history, main causes of ICU admission, other vital signs [heart rate (HR), mean arterial pressure (MAP), saturation of peripheral oxygen (SpO₂)] and laboratory indicators [white blood cell count (WBC), albumin (Alb), serum creatinine (SCr)] during SBT of patients between the two groups. Univariate Logistic regression analysis was conducted, and variables with P < 0.05 and no multicollinearity with Cdyn-MP were selected for inclusion in the multivariate Logistic regression model. The results demonstrated that SOFA score [odds ratio (OR) = 1.081, 95% confidence interval (95%CI) was 1.008-1.160, P = 0.030], and PEEP (OR = 1.191, 95%CI was 1.075-1.329, P = 0.001), FiO₂ (OR = 1.035, 95%CI was 1.006-1.068, P = 0.021) and Cdyn-MP (OR = 1.190, 95%CI was 1.086-1.309, P < 0.001) within the 4-hour period prior to the SBT were independent risk factors for weaning failure in patients undergoing IMV. The RCS analysis after adjusting for confounding factors showed that as Cdyn-MP within the 4-hour period prior to the SBT increased, the risk of weaning failure in patients undergoing IMV significantly increased (P < 0.001). The Spearman rank correlation test showed that Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with respiratory mechanical parameters including ΔPaw and MP (r values were 0.773 and 0.865, both P < 0.01), and negatively correlated with Cdyn (r = -0.587, P < 0.01). Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with prognostic indicators such as duration of IMV, length of ICU stay, and total length of hospital stay (r values were 0.295, 0.196, and 0.120, all P < 0.05). ROC curve analysis demonstrated that, within the 4-hour period preceding the SBT, Cdyn-MP, MP, Cdyn, and ΔPaw possessed predictive value for weaning failure in patients undergoing IMV. Notably, Cdyn-MP exhibited superior predictive capability, evidenced by an AUC of 0.761, with a 95%CI ranging from 0.712 to 0.810 (P < 0.001). At the optimal cut-off value of 408.5 J/min×cmH₂O/mL×10^-3, the sensitivity was 68.29%, and the specificity was 71.19%. CONCLUSION Cdyn-MP is related to weaning outcomes and prognosis in mechanically ventilated patients, and has good predictive ability in assessing the risk of weaning failure.
Humans ; Prospective Studies ; Ventilator Weaning ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Lung Compliance ; Female ; Male ; Middle Aged ; Aged

OBJECTIVE: To investigate the correlation between nucleated red blood cell (NRBC) level on the first day of intensive care unit (ICU) admission and 28-day mortality in adult septic patients, and to evaluate the value of NRBC as an independent predictor of death. METHODS: Single-cell transcriptomic analysis was performed using the GSE167363 dataset from the Gene Expression Omnibus (including 2 healthy controls, 3 surviving septic patients, and 2 non-surviving septic patients). A retrospective clinical analysis was conducted using the America Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, including adult patients (≥ 18 years) with first-time admission who met the Sepsis-3.0 criteria, excluding those without NRBC testing on the first ICU day. The demographic information, vital signs, laboratory test indicators, disease severity score and survival data on the first day of admission were collected. The restricted cubic spline (RCS) curve was used to determine the optimal cut-off value of NRBC for predicting 28-day mortality in patients. Patients were divided into low-risk and high-risk groups based on this cut-off value for intergroup comparison, with Kaplan-Meier survival curve analysis conducted. Independent risk factors for 28-day mortality were analyzed using Logistic regression and Cox regression analysis, followed by the construction of regression models. RESULTS: NRBC were detected in the peripheral blood of septic patients by single-cell transcriptomic. A total of 1 291 sepsis patients were included in the clinical analysis, with 576 deaths within 28 days, corresponding to a 28-day mortality of 44.6%. RCS curve analysis showed a nonlinear relationship between the first-day NRBC level and the 28-day mortality. When NRBC ≥ 1%, the 28-day mortality of patients increased significantly. Compared to the low-risk group (NRBC < 1%), the high-risk group (NRBC ≥ 1%) had significantly higher respiratory rate, heart rate, sequential organ failure assessment (SOFA), and simplified acute physiology score II (SAPSII), and significantly lower hematocrit and platelet count. The high-risk group also had a significantly higher 28-day mortality [49.8% (410/824) vs. 35.5% (166/467), P < 0.05], and shorter median survival time (days: 29.8 vs. 208.6, P < 0.05). Kaplan-Meier survival curve showed that compared with the low-risk group, the survival time of high-risk group was significantly shortened (Log-rank test: χ ² = 25.1, P < 0.001). After adjusting for potential confounding factors including body mass, temperature, heart rate, respiratory rate, mean arterial pressure, serum creatinine, pulse oximetry saturation, hemoglobin, hematocrit, Na⁺, K⁺, platelet count, and SOFA score, multivariate regression analysis confirmed that NRBC ≥ 1% was an independent risk factor for 28-day mortality [Logistic regression: odds ratio (OR) = 1.464, 95% confidence interval (95%CI) was 1.126-1.902, P = 0.004; Cox regression: hazard ratio (HR) = 1.268, 95%CI was 1.050-1.531, P = 0.013]. CONCLUSIONS NRBC ≥ 1% on the first day of ICU admission is an independent risk factor for 28-day mortality in septic patients and can serve as a practical indicator for early prognostic assessment.
Humans ; Sepsis/blood* ; Intensive Care Units ; Risk Factors ; Retrospective Studies ; Prognosis ; Male ; Female ; Hospital Mortality ; Middle Aged ; Aged

Objective To investigate the effects of microRNA-34a(miR-34a-5p)on the progression of chronic lymphocytic leukemia(CLL)through the Wnt/β-catenin signaling pathway.Methods Human chronic B-cell leukemia MEC-1 cells were selected for experimentation.MEC cells were divided into two groups,group one:the p53 agonist group and the control group;group two:the control group,the miR-34a-5p mimic group and its corresponding negative control,the miR-34a-5p inhibitor group and its corresponding negative control,as well as the miR-34a-5p inhibitor+Wnt inhibitor XAV-939 group.The expression levels of miR-34a-5p in each group were measured using real-time fluorescence quantitative PCR(qPCR).Cell proliferation was assessed by CCK-8 assay,while cell migration ability was evaluated using Transwell migration assay.Dual-luciferase reporter assay was employed to validate the targeting relationships between p53 and miR-34a-5p,as well as between miR-34a-5p and Wnt1.Western blot analysis was used to detect the protein expressions of β-catenin and Cyclin D1,which were key components of the Wnt/β-catenin signaling pathway.Results In MEC-1 cells:① compared with the control group,there was a increased miR-34a-5p expression and inhibited cell proliferation in the p53 agonist group(P＜0.05).Dual-luciferase reporter assay confirmed a negative regulatory correlation between miR-34a-5p and p53.② the miR-34a-5p mimic group showed significantly upregulated miR-34a-5p expression compared to the control group,leading to suppressed cell proliferation,reduced migration capability and decreased protein expressions of β-catenin and Cyclin D1(P＜0.05).Conversely,the miR-34a-5p inhibitor group demonstrated significantly downregulated miR-34a-5p expression,resulting in enhanced cell proliferation,increased migratory capacity and upregulated protein levels of β-catenin and Cyclin D1 compared to those of the control group(P＜0.05).③ A targeting relationship was observed between miR-34a-5p and Wnt1.④ Compared with the miR-34a-5p inhibitor group,the XAV-939 group exhibited significantly upregulated miR-34a-5p expression,markedly decreased numbers of migrated cells and substantially reduced protein expression levels of β-catenin and Cyclin D1(P＜0.05).Conclusion miR-34a plays the role of a tumor suppressor gene in CLL.Overexpression of miR-34a can inhibit the Wnt/β-catenin signaling pathway,reduce the proliferation activity and migration ability of cells,and promote cell apoptosis.

Objective To investigate the effects of high-altitude hypoxic environment on the pharmacokinetic characteristics and brain tissue distribution of phenytoin sodium in epileptic rats.Methods A total of 70 male SPF-grade Wistar rats aged 2 months and weighing(200±20)g were used in the study.An epilepsy model was induced in the rats using the lithium chloride-pilocarpine method.The successfully modeled rats were randomly assigned to a normoxic treatment group and a high-altitude hypoxic treatment group.Phenytoin sodium was administered via intragastric gavage at a dose of 50 mg/kg in both groups.Blood samples were collected from the orbital venous plexus before treatment and 0.5,1,2,3,4,6,8,10,and 24 h post treatment.The animals were euthanized after the final blood collection,and samples of the liver and the whole brain tissue were collected.In the brain tissue distribution experiment,brain tissue samples were collected at 0.5,1,2,and 4 h after drug administration.The concentration of phenytoin sodium in rat plasma and brain tissue was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters were calculated using WinNolin 8.1 software.The expression levels of CYP2C9 in liver tissue and those of P-gp in brain tissue of epileptic rats were determined by Western blot.Results Compared with those in the normoxia group,the peak concentration,peak time,and half-life of phenytoin sodium in the high-altitude hypoxia group were significantly decreased by 46.0%,42.3%,and 55.5%,respectively(all P<0.05);the clearance rate was significantly increased by 162.0%(P<0.05);and the area under the curve of plasma concentration-time curve was decreased by 45.6%(P<0.01).At 0.5,1,and 2 hours after administration,compared with that in the normoxia treatment group,the concentration of phenytoin sodium in the brain tissue of the high-altitude hypoxia treatment group was significantly decreased by 78.1%,63.5%,and 32.5%,respectively(all P<0.05).Western blot results showed that the expression levels of CYP2C9 in the liver tissue and P-gp in the brain tissue of rats in the high-altitude hypoxia group were approximately 1.78 and 1.65 times higher than those in the normoxia group,respectively(both P<0.05).Conclusion The hypoxic environment at high altitudes can promote the metabolism of phenytoin sodium,reduce its absorption efficiency,and change the characteristics its distribution in the brain,which may be related to the up-regulation of the expression of CYP2C9 in the liver and that of P-gp in the brain.

Intraocular ointment is conventionally placed on the eye to prevent infection after cataract surgery. The purpose of this study is to report a case and conduct a systematic review of a rare occurrence of the entry of intraocular ointment after cataract surgery. PubMed, Scopus, Embase, CNKI, WANFANG data, China Science and Technology Journal Database and Chinese Medical Journal Full-text Database were systematically searched from their commencement to 30th October 2023, and 19 literatures were screened out and 31 cases of intraocular ointment after surgery were collected. Among the 31 patients, the age of presentation ranged from 55 to 87 years with a median of 73, males accounted for 45.2% and females accounted for 32.3%. The length of the incision was generally 3.2 mm. Most of the patients detected ointment within 3 days post-operation and presented without complications(45.2%). The most common ocular manifestations were corneal edema, glaucoma and uveitis. Early postoperative follow-up is very important. Presence of anterior chamber ointment is a rare complication after cataract surgery, but it can lead to severe vision loss if not detected and treated on time. When patients complain of foreign body sensation in the in the eye after cataract surgery, ophthalmologists need to take a kin interest and examine the eye for early detection of ointment for appropriate intervention and prevent further complications.