Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

ObjectiveTo construct and evaluate various machine learning models for predicting the risk of chronic obstructive pulmonary disease （COPD） in individuals， thereby providing data support for early screening and intervention. MethodsA total of 823 subjects were selected for this study， comprising 142 individuals in the high-risk group for COPD and 681 individuals in the low-risk group. Data collected included demographic characteristics， smoking history， symptoms （such as cough and shortness of breath）， and scores from the Chronic obstructive pulmonary disease screening questionnaire. Four machine learning algorithms—Logistic regression， random forest， support vector machine， and XGBoost—were utilized to construct risk prediction models. The performance of these models was assessed using 5-fold cross-validation， with evaluation metrics including accuracy， precision， recall， F1-score， area under the receiver operating characteristic curve （AUC）， and average precision （AP）. Furthermore， a feature importance analysis was performed. ResultsThe Logistic Regression model exhibited superior performance， achieving an AUC of 0.982 and an AP of 0.939. This was closely followed by the Random Forest model， which recorded an AUC of 0.975 and an AP of 0.890. Feature importance analysis revealed that smoking history， symptoms of shortness of breath， and body weight were significant predictors. All models demonstrated robust performance in identifying low-risk populations； however， variations were observed in their efficacy in identifying high-risk populations. ConclusionMachine learning models have proven effective in identifying individuals at high risk for COPD. Among these， the Logistic regression model exhibits the best overall performance， efficiently identifying high-risk populations and serving as a valuable clinical auxiliary screening tool. Various models， each with distinct performance characteristics， are suited to different clinical screening scenarios， thereby offering targeted decision-making support for the establishment of a hierarchical and intelligent COPD screening pathway.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

OBJECTIVE: To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO). METHODS: Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement). RESULTS: All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L^-1 and (204.47±35.59) μg·L^-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L^-1 and (311.12±42.23) μg·L^-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s^-1, (0.57±0.15) m, and (0.99±0.11) m·s^-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s^-1, (0.50±0.14) m, and (0.95±0.09) m·s^-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05). CONCLUSION The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Tibia/physiopathology* ; Aged ; Biomechanical Phenomena ; Retrospective Studies ; Osteoarthritis, Knee/physiopathology*

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

In recent years,the market share of food and medicine homology substances has continued to grow,and various types of contamination issues have become the focus of attention both inside and outside the industry.The contamination not only affects the original medicinal quality,but also leads to the accumulation of toxic substances in the human body,causing acute and chronic severe hazards such as vomiting,poisoning and cancer.Therefore,the development of biosensors that can conveniently,accurately and sensitively detect various pollutants in food and medicine homology substances has become a research hotspot.Aptasensors based on metal-organic frameworks(MOFs)with advantages such as strong specificity,rapid response and simple operation,have been widely used in detection of various pollutants.This review focused on the research progress of aptasensors based on MOFs for detection of food and medicine homology contamination in the past few years,and provided a detailed comparison and analysis for detection of chemical pollutants(such as pesticide residues,heavy metal residues,mycotoxins,etc.)and microbial contamination in food and medicine homology substances.Besides,the development trend and possible challenges of MOFs aptasensors in detection of food and medicine homology substances in the future were discussed,which was anticipated to provide a reference for the development of new MOFs aptasensors.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

Objective:To evaluate the effect of digital design combined with 3D printing technology in the repair of mandibular defects with fibular myocutaneous flap.Methods:From July 2017 to August 2022, 25 patients with mandibular defects repaired by fibular musculocutaneous flap after oral tumor surgery were retrospectively analyzed. The cohort consisted of 25 patients (16 male, 9 female) aged 19-68 (42.5±5.3) years. The patients were divided into two groups according to different fibula shaping methods: Study group (11 cases): digital design combined with 3D printing technology was used for fibula shaping; Control group (14 cases): conventional fibula shaping was performed based on the surgeon's experience.Results:The fibula shaping time in the study group was (51.2±4.2) min, which was shorter than that in the control group (79.1±8.0) min ( P<0.001). The study group showed higher satisfaction scores for facial appearance compared to the control group [(8.3±0.8) vs (6.9±0.6) points, P<0.001]. The survival rates were 11/11 in the study group and 13/14 in the control group, with a significantly higher survival rate observed in the study group ( P<0.001). At 3 months postoperatively, the mouth opening measurements were (3.5±0.2) cm in the study group and (3.5±0.1) cm in the control group, showed no statistically significant difference ( P=0.334). Conclusion:The application of digital design combined with 3D printing technology in fibula musculocutaneous flap reconstruction of mandibular defects reduces fibula shaping time, improves flap survival rates, and yields higher patient satisfaction with facial aesthetics.