BACKGROUND:Dyslipidemia affects chondrocyte metabolism and plays an important role in the occurrence and progression of osteoarthritis,yet its underlying mechanisms remain unclear.OBJECTIVE:To identify characteristic genes related to lipid metabolism in chondrocytes of osteoarthritis through the weighted gene co-expression network analysis combined with machine learning algorithms and to conduct the preliminary experimental validation.METHODS:Based on the weighted gene co-expression network analysis and linear models for microarray data,differentially co-expressed genes were identified.Machine learning methods were used for screening characteristic genes related to lipid metabolism.Protein-protein interaction analysis was conducted to explore the interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were employed to investigate the signaling pathways involved in the differentially co-expressed genes.Subsequently,immune correlation analysis was utilized to identify the associations between the characteristic genes and immune infiltration patterns.Furthermore,in vitro molecular experiments were performed to validate the mRNA and protein levels of the characteristic genes.RESULTS AND CONCLUSION:(1)A total of 123 high-expression and 110 low-expression differentially co-expressed genes were identified after data normalization and application of principal component analysis,weighted gene co-expression network analysis,and linear models for microarray data.(2)Thirty-seven characteristic genes were screened using logistic regression,random forest,and support vector machine,among which SMPD3 and CYP4F3 were identified as two characteristic genes related to lipid metabolism.(3)Protein-protein interaction analysis revealed that SMPD3 and CYP4F3 proteins showed relatively low levels of interaction.(4)Gene Ontology analysis indicated that these genes were primarily enriched in multiple biological processes,including neutrophils and their immune responses,immune system processes,and neutrophil activation.Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that they were mainly involved in key pathways such as extracellular matrix-receptor interaction and cell adhesion.(5)Cell type Identification by estimating relative subsets of RNA transcripts immune infiltration analysis showed significant differences in eight types of immune cells in osteoarthritis.Further correlation analysis revealed that SMPD3 was significantly positively correlated with resting dendritic cells(r=0.44,P=3.6×10-3)and significantly negatively correlated with neutrophils(r=-0.48,P=1.7×10-3),whereas CYP4F3 was significantly positively correlated with monocytes and neutrophils(r=0.76,P=7.6×10-9;r=0.73,P=6.0×10-8),and significantly negatively correlated with T follicular helper cells and resting dendritic cells(r=-0.38,P=0.01;r=-0.38,P=0.01).(6)In vitro molecular experiments demonstrated that SMPD3 mRNA and protein levels were significantly increased in the osteoarthritis group,while CYP4F3 mRNA and protein levels were decreased.To conclude,the lipid metabolism-related SMPD3 and CYP4F3 of osteoarthritis can serve as potential biomarkers for the targeted therapy of osteoarthritis and for assessing cartilage repair or degeneration,which provides a new strategy for exploring the relationship between dyslipidemia and osteoarthritis and for clinical targeted treatment in Chinese population.

BACKGROUND:Dyslipidemia affects chondrocyte metabolism and plays an important role in the occurrence and progression of osteoarthritis,yet its underlying mechanisms remain unclear.OBJECTIVE:To identify characteristic genes related to lipid metabolism in chondrocytes of osteoarthritis through the weighted gene co-expression network analysis combined with machine learning algorithms and to conduct the preliminary experimental validation.METHODS:Based on the weighted gene co-expression network analysis and linear models for microarray data,differentially co-expressed genes were identified.Machine learning methods were used for screening characteristic genes related to lipid metabolism.Protein-protein interaction analysis was conducted to explore the interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were employed to investigate the signaling pathways involved in the differentially co-expressed genes.Subsequently,immune correlation analysis was utilized to identify the associations between the characteristic genes and immune infiltration patterns.Furthermore,in vitro molecular experiments were performed to validate the mRNA and protein levels of the characteristic genes.RESULTS AND CONCLUSION:(1)A total of 123 high-expression and 110 low-expression differentially co-expressed genes were identified after data normalization and application of principal component analysis,weighted gene co-expression network analysis,and linear models for microarray data.(2)Thirty-seven characteristic genes were screened using logistic regression,random forest,and support vector machine,among which SMPD3 and CYP4F3 were identified as two characteristic genes related to lipid metabolism.(3)Protein-protein interaction analysis revealed that SMPD3 and CYP4F3 proteins showed relatively low levels of interaction.(4)Gene Ontology analysis indicated that these genes were primarily enriched in multiple biological processes,including neutrophils and their immune responses,immune system processes,and neutrophil activation.Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that they were mainly involved in key pathways such as extracellular matrix-receptor interaction and cell adhesion.(5)Cell type Identification by estimating relative subsets of RNA transcripts immune infiltration analysis showed significant differences in eight types of immune cells in osteoarthritis.Further correlation analysis revealed that SMPD3 was significantly positively correlated with resting dendritic cells(r=0.44,P=3.6×10-3)and significantly negatively correlated with neutrophils(r=-0.48,P=1.7×10-3),whereas CYP4F3 was significantly positively correlated with monocytes and neutrophils(r=0.76,P=7.6×10-9;r=0.73,P=6.0×10-8),and significantly negatively correlated with T follicular helper cells and resting dendritic cells(r=-0.38,P=0.01;r=-0.38,P=0.01).(6)In vitro molecular experiments demonstrated that SMPD3 mRNA and protein levels were significantly increased in the osteoarthritis group,while CYP4F3 mRNA and protein levels were decreased.To conclude,the lipid metabolism-related SMPD3 and CYP4F3 of osteoarthritis can serve as potential biomarkers for the targeted therapy of osteoarthritis and for assessing cartilage repair or degeneration,which provides a new strategy for exploring the relationship between dyslipidemia and osteoarthritis and for clinical targeted treatment in Chinese population.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To observe the analgesic and rehabilitation effects of non μ-opioids anesthesia/analgesia(NΜOA)based on quadratus lumborum block(QLB)in emergency cesarean section under general anesthesia.Methods The retrospective study method was adopted,50 pregnant women undergoing hysterectomy under emergency general anesthesia in Langfang People's Hospital from January 2023 to December 2024 were selected as the study objects.The patients were divided into μ-opioids anesthesia/analgesia(ΜOA)group and NΜOA group according to different anesthesia/analgesia methods,25 cases in each group.ΜOA group received ΜOA;NΜOA group received NΜOA+QLB.Incisional pain and uterine contraction pain numerical rating scale(NRS)at out of the post-anesthesia care unit(T1),intravenous injection of oxytocin(T2),press the palace bottom 24 hours(T3),out of bed activity after operation(T4)and first analgesic time of incision pain,first analgesic time of uterine contraction pain,first no vomiting eating time,first exhaust time was observed and recorded.The incidence of vasoactive agents during the anesthetic period,rescue analgesia,rescue antiemetic,constipation,sleep disturbance after operation within 48 hours after operation were also recorded.Results The NRS scores at T1,T2,T3 and T4 in ΜOA group were significantly higher than those in NΜOA group(incisional pain 3.36±1.25 vs.1.12±0.97,3.68±1.18 vs.2.00±0.91,5.76±1.67 vs.4.20±1.00,4.48±1.29 vs.3.32±0.95;uterine contraction pain 3.72±1.49 vs.1.24±1.05,4.64±1.60 vs.3.04±1.27,7.56±1.71 vs.5.16±1.37,3.56±0.22 vs.2.56±0.16,all P<0.05).The first analgesic time of incision pain,first analgesic time of uterine contraction pain in ΜOA group were significantly less than that in NΜOA group(hours:3.06±2.02 vs.17.48±10.93,2.68±2.22 vs.15.80±11.39,both P<0.05),the first no vomiting eating time,first exhaust time in ΜOA group were significantly longer than those in NΜOA group(hours:8.56±0.57 vs.6.32±0.14,15.44±1.42 vs.10.16±1.14,both P<0.05),the incidence of vasoactive agents,rescue analgesia,rescue antiemetic,constipation,sleep disturbance after operation within 48 hours in ΜOA group were significantly higher than those in NΜOA group[64.0%(16/25)vs.32.0%(8/25),48.0%(12/25)vs.20.0%(5/25),44.0%(11/25)vs.16.0%(4/25),64.0%(16/25)vs.36.0%(9/25),60.0%(15/25)vs.32.0%(8/25),all P<0.05].Conclusion NΜOA based on QLB safely and effectively reduced side effects of μ-opioids and enhanced recovery compared to ΜOA on emergency cesarean section patients undergoing general anesthesia.

Background::Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid-lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated.Methods::A multicenter, double-blinded, randomized-controlled trial was conducted among individuals with low-density lipoprotein cholesterol (LDL-C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow-up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL-C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10-year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention.Discussion::This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management.Trial Registration::Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215.

Objective:To investigate the application effect of quadratus lumborum block (QLB) combined with less opioid anesthesia analgesia in laparoscopic total hysterectomy (LTH) in elderly patients with uterine prolapse.Methods:A total of 86 elderly patients with uterine prolapse who received LTH in the Langfang People’s Hospital from Jan. 2021 to Oct. 2023 were prospectively selected and divided into group A ( n=42) and group B ( n=44) according to the random number table method. Group A received transversus abdominis block (TAPB) + general anesthesia, and group B received QLB combined with less opioid anesthesia + general anesthesia. The pain duration at different time points after operation [Numeric Rating Scale (NRS) method to evaluate resting incision and visceral pain] was compared between the two groups. The dosage of opioids and the additional analgesia rate were compared between the two groups. The sleep quality of the two groups before and 72 hours after operation was compared, and the adverse reactions of anesthesia were counted. Results:Compared with 6 h after operation, NRS scores of resting incision pain and visceral pain in the two groups decreased gradually at 12, 24 and 48 h after operation, and it was lower in group B than in group A. There were statistically significant differences between groups ( P<0.05) . Dosage of sufentanil and remifentanil in group B was lower than that in group A, and the postoperative additional analgesia rate in group B (9.09%) was lower than that in group A (28.57%) ( P<0.05) . 72 hours after surgery, the sleep efficiency and total sleep time of patients in both groups were lower than those before surgery, and they were higher in group B than in group A; The awakening time and number of awakenings in both groups were higher than those before surgery, while they were lower in group B than in group A ( P<0.05) . The total incidence of adverse reactions in group B was 4.76% (2/44) , lower than 23.81% (10/42) of group A ( P<0.05) . Conclusion:QLB combined with less opioid anesthesia analgesia can effectively reduce the degree of incision and visceral pain after LTH in elderly patients with uterine prolapse, reduce the amount of opioids used during operation and the rate of additional analgesia, and reduce the incidence of adverse reactions of anesthesia.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objectives:To explore the independent and combined effects of sleep duration and physical activity(PA)on the incidence of cardiovascular disease(CVD).Methods:The study subjects were derived from three sub-cohorts of the China-PAR project.Information on sleep and PA was collected from the surveys conducted in 2007-2008,and the incidence and mortality data of CVD were obtained during the follow-up survey from 2012 to 2015.Sleep duration was categorized into≤6 h/d,>6-8 h/d,and>8 h/d,and the PA level was classified according to the tertiles of PA volume(MET-h/d).The Cox proportional hazards model stratified by cohort source was applied to estimate the associations of PA and sleep duration with CVD incidence,coronary heart disease(CHD)incidence,and stroke incidence.Results:A total of 93 933 participants were included.During an average follow-up of(5.82±0.98)years,3 862 CVD events were documented.Compared with the low PA group,the hazard ratios(HRs)and 95%confidence intervals(CIs)of the CVD incidence,CHD incidence,and stroke incidence for the high PA group were 0.73(0.65-0.82),0.62(0.49-0.77)and 0.88(0.76-1.01),respectively.A U-shaped relation between sleep duration and incidence of CVD and stroke was observed.Compared with those who slept for>6-8 h/d,the risk of CVD(HR[95%CI]:1.10[1.00-1.21],P=0.04)and stroke(HR[95%CI]:1.33[1.18-1.49],P<0.01)was higher among participants slept>8 h/d.The risk of CVD,CHD and stroke tended to be higher in the≤6 h/d sleep group.Compared with the high PA combined with>6-8 h/d,the risk of stroke was highest in the high PA combined with>8h/d sleep group(HR[95%CI]:1.74[1.37-2.22],P<0.05),while the risks of CVD(HR[95%CI]:1.69[1.39-2.04],P<0.05)and CHD(HR[95%CI]:1.99[1.41-2.81],P<0.05)were highest in the low PA combined with≤6 h/d sleep group.Conclusions:Adequate physical activity and appropriate sleep duration are associated with lower risk of morbidity from CVD,CHD and stroke.

Objectives:This study aims to investigate the association between Chinese visceral adiposity index(CVAI)and the risk of cardiovascular disease(CVD),and explore the sex differences.Methods:Participants were screened from the three sub-cohorts of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR)project,baseline information on body measure and biochemistry examinations were collected from 1998,2000-2001,and 2007-2008,separately.Participants were followed up to 2015.Cohort-stratified Cox proportional risk models were used to analyze the relationship between CVAI,both in continuous(per standard deviation increase)and categorical(quartiles,with Q1 as reference)scales,and CVD risk in the total population,men and women.The multiplicative interaction between sex and CVAI on CVD risk were calculated.Restricted cubic spline regression was employed to investigate the dose-response relationship.Results:A total of 98 464 participants without CVD at baseline were included.During the 723 508 person-years of follow-up,3 605 CVD events were recorded.After multivariate adjustment,the HRs(95％CIs)of CVD were 1.25(1.20-1.29),1.09(1.04-1.15),and 1.54(1.46-1.64)for per standard deviation increment in CVAI in the general population,men and women,respectively.Besides,compared with Q1 group,the HRs(95％CIs)in Q4 group were 1.87(1.67-2.10),1.33(1.14-1.54)and 3.84(3.09-4.78),correspondingly,and the effect of CVAI on the risk of CVD was significantly higher in women than in men(Pinteraction<0.05).Additionally,there was a positive dose-response relationship between CVAI and the risk of CVD.Conclusions:Elevated CVAI is an independent risk factor for CVD,especially in women.

Objective To observe the analgesic and rehabilitation effects of non μ-opioids anesthesia/analgesia(NΜOA)based on quadratus lumborum block(QLB)in emergency cesarean section under general anesthesia.Methods The retrospective study method was adopted,50 pregnant women undergoing hysterectomy under emergency general anesthesia in Langfang People's Hospital from January 2023 to December 2024 were selected as the study objects.The patients were divided into μ-opioids anesthesia/analgesia(ΜOA)group and NΜOA group according to different anesthesia/analgesia methods,25 cases in each group.ΜOA group received ΜOA;NΜOA group received NΜOA+QLB.Incisional pain and uterine contraction pain numerical rating scale(NRS)at out of the post-anesthesia care unit(T1),intravenous injection of oxytocin(T2),press the palace bottom 24 hours(T3),out of bed activity after operation(T4)and first analgesic time of incision pain,first analgesic time of uterine contraction pain,first no vomiting eating time,first exhaust time was observed and recorded.The incidence of vasoactive agents during the anesthetic period,rescue analgesia,rescue antiemetic,constipation,sleep disturbance after operation within 48 hours after operation were also recorded.Results The NRS scores at T1,T2,T3 and T4 in ΜOA group were significantly higher than those in NΜOA group(incisional pain 3.36±1.25 vs.1.12±0.97,3.68±1.18 vs.2.00±0.91,5.76±1.67 vs.4.20±1.00,4.48±1.29 vs.3.32±0.95;uterine contraction pain 3.72±1.49 vs.1.24±1.05,4.64±1.60 vs.3.04±1.27,7.56±1.71 vs.5.16±1.37,3.56±0.22 vs.2.56±0.16,all P<0.05).The first analgesic time of incision pain,first analgesic time of uterine contraction pain in ΜOA group were significantly less than that in NΜOA group(hours:3.06±2.02 vs.17.48±10.93,2.68±2.22 vs.15.80±11.39,both P<0.05),the first no vomiting eating time,first exhaust time in ΜOA group were significantly longer than those in NΜOA group(hours:8.56±0.57 vs.6.32±0.14,15.44±1.42 vs.10.16±1.14,both P<0.05),the incidence of vasoactive agents,rescue analgesia,rescue antiemetic,constipation,sleep disturbance after operation within 48 hours in ΜOA group were significantly higher than those in NΜOA group[64.0%(16/25)vs.32.0%(8/25),48.0%(12/25)vs.20.0%(5/25),44.0%(11/25)vs.16.0%(4/25),64.0%(16/25)vs.36.0%(9/25),60.0%(15/25)vs.32.0%(8/25),all P<0.05].Conclusion NΜOA based on QLB safely and effectively reduced side effects of μ-opioids and enhanced recovery compared to ΜOA on emergency cesarean section patients undergoing general anesthesia.