Objective To establish a human monocytic THP-1 macrophage-derived foam cell model and analyze the role of the α subunit of coatomer protein Ⅰ(α-COP)in apolipoprotein A-1(apoA-1)-mediated cholesterol efflux from foam cells.Methods THP-1 cells were induced to adhere using PMA(PMA group),followed by treatment with acetylated low-density lipoprotein(Ac-LDL)to generate macrophage-derived foam cells(Ac-LDL group).Subsequent incubation with apoA-1 formed the apoA-1 group.Cholesterol efflux rates mediated by apoA-1 and intracellular lipid accumulation were quantified through liquid scintillation counting and oil red O staining.The expression patterns of α-COP were systematically analyzed using quantitative real-time PCR(qPCR),Western blotting,and laser scanning confocal microscopy.THP-1 macrophage-derived foam cells mediated by apoA-1 were transduced with scrambled shRNA(Scr group)or α-COP-specific shRNA lentivirus(α-COP shRNA group)to assess the effects of α-COP knockdown on cholesterol efflux efficiency and total cellular cholesterol content.Subcellular localization of adipopoilin(ADFP)and cholesterol probe Fil-ipin Ⅲ staining patterns were visualized via laser scanning confocal microscopy.Bioinformatics analysis of α-COP expression profiles in carotid atherosclerotic plaques was performed using datasets from the GEO data-base.Results Compared with the Ac-LDL group,the cholesterol efflux rate in the apoA-1 group was signifi-cantly increased[(9.77±0.79)%vs.(2.74±0.37)%,P＜0.001].Oil red O staining demonstrated reduced lipid accumulation in foam cells of the apoA-1 group compared with the Ac-LDL group.The relative mRNA expression level of α-COP in the apoA-1 group was significantly higher than that in the Ac-LDL group(P＜0.001),with corresponding elevation in protein expression(P＜0.001).Fluorescence intensity analysis re-vealed increased mean fluorescence intensity of α-COP in the apoA-1 group compared with the Ac-LDL group.Following α-COP knockdown by shRNA,the apoA-1-mediated cholesterol efflux rate was significantly de-creased(P＜0.05)and total intracellular cholesterol levels were increased(P＜0.001)in the α-COP shRNA group compared with the Scr group.The α-COP shRNA group exhibited enhanced red fluorescence intensity of ADFP(P＜0.05)and increased blue fluorescence intensity of Filipin Ⅲ(P＜0.01)compared with the Scr group.Database analysis indicated that α-COP mRNA expression was lower in carotid atherosclerotic plaques than in normal arterial tissues,with reduced expression in advanced-stage plaques compared with early-stage plaques(P＜0.05).Conclusion α-COP participates in apoA-1-mediated cholesterol efflux from foam cells,and interference with α-COP expression results in reduced cholesterol efflux and increased intracellular lipid accumulation.

Objective To investigate the effect of asperuloside(ASP)on the malignant progression and chemotherapy resistance of hepatocellular carcinoma(HCC)cells by regulating the supersonic hedgehog(SHH)/glioma-associated oncogene homolog 1(GLI1)signaling pathway.Methods The expression of SHH and GLI1 protein in human hepatocellular carcinoma cell line(SMMC-7721)/adriamycin(ADM)and SMMC-7721 cell line were detected by Western blot(WB).The HCC drug-resistant cell line SMMC-7721/ADM were divided into Control group,ADM group,L-ASP group(1 mmol/L ASP),M-ASP group(2 mmol/L ASP),H-ASP group(3 mmol/L ASP),ASP+PM group(1 μmol/L SHH/GLI1 signaling pathway activator PM).Ex-cept for Control group,5 μg/mL ADM was added to each group.The effect of ASP on the proliferation of SMMC-7721/ADM cells was detected by cell counting kit-8(CCK8)assay and plate cloning assay.The effect of ASP on the invasion and migration of SMMC-7721/ADM cells were detected by Transwell assay.The effect of ASP on the apoptosis of SMMC-7721/ADM cells was detected by flow cytometry.The expression of SHH,GLI1,proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-9(MMP-9)and B cell lymphoma-2 associated X protein(Bax)in SMMC-7721/ADM cells were detected by WB.Animal experiments verified the effect of ASP on the growth of HCC xenografts and the expression of SHH/GLI1 signaling pathway proteins.Results The expression of SHH and GLI1 in SMMC-7721/ADM cells were higher than those in SMMC-7721 cells(P＜0.05).L-ASP group,M-ASP group and H-ASP group decreased the proliferation,migration and in-vasion of SMMC-7721/ADM cells in a dose-dependent manner,decreased the expression of SHH,GLI1,PCNA and MMP-9,and promoted cell apoptosis and Bax expression(P＜0.05).SHH/GLI1 signaling pathway acti-vator PM could reverse the inhibitory effect of H-ASP treatment on malignant progression and chemotherapy resistance of SMMC-7721/ADM cells(P＜0.05).ASP could inhibit the growth of HCC transplanted tumor and the expression of SHH and GLI1(P＜0.05).Conclusion ASP can inhibit the malignant progression of HCC cells and enhance the sensitivity of chemotherapy,which may be achieved by inhibiting the SHH/GLI1 signaling pathway.

"Upper deficiency leading to vertigo" is one of the representative discussions on deficiency vertigo in Huang Di Nei Jing, which has laid the foundation for the rich development of the theory of "deficiency causing vertigo" in later generations. The brain lymphatic system can remove metabolic wastes and provide nutrients for the brain, which is involved in the development of many brain diseases. This study believes that the broad definition of "upper deficiency leading to vertigo", that is to say, vertigo is triggered by abnormalities in the local physiological functions of the brain orifices, can be used as a platform for the pathogenesis of vertigo. Based on the findings of modern medicine on the lymphoid system, the authors discussed the possible interactions between the lymphoid system, phlegm, blood stasis, deficiency, and other pathological factors of vertigo. β-amyloid, neurotransmitters, inflammatory mediators and other "toxic pathogenic factors" may also be an important cause of vertigo. This article attempted to explain the pathogenesis of "upper deficiency leading to vertigo" with the help of lymphoid system, in order to provide new thinking direction for the development of TCM clinical diagnosis and treatment of vertigo.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

ObjectiveTo explore the effectiveness and safety of Yiqi Huoxue Formula （益气活血方， YHF） in the adjuvant treatment of chronic pulmonary heart disease （CPHD） and heart failure （HF）with qi deficiency and blood stasis pattern. MethodsOne hundred and twenty patients with CPHD and HF with qi deficiency and blood stasis pattern were allocated randomly into treatment group and control group， with 60 case in each group. The control group was given conventional basic western medicine， while the treatment group was given oral administration of YHF granules in addition， one dose per day. The treatment course for both groups was 8 weeks. The TCM symptom scores， Minnesota Life Quality Scale （MLHF-Q） scores， echocardiographic indicators including right ventricular end-diastolic diameter （RVEDD）， left ventricular end-diastolic diameter （LVEDD）， left atrial end-diastolic diameter （LAEDD） and pulmonary artery mean pressure （PAMP）， six-minute walking distance （6MWD）， and plasma N-terminal pro-B-type natriuretic peptide （NT-ProBNP） level were compared between the groups. The effectiveness regarding cardiac function and TCM syndromes were compared between the two groups after treatment， and the occurrence of adverse events was observed. ResultsWith two drop-outs both in the treatment group and control group， and 58 cases in each group were included in the outcome analysis. The total effective rate regarding cardiac function and TCM syndromes in the treatment group were 91.38% （53/58） and 96.55% （56/58）， respectively， significantly higher than the corresponding 70.69% （41/58） and 48.27% （28/58） in the control group （P＜0.05）. After treatment， the TCM symptom scores and RVEDD level were significantly reduced in the treatment group， and MLHF-Q score， plasma NT-ProBNP level and PAMP level decreased significantly， while 6MWD increased in both groups （P＜0.01）. Compared to those in the control group， the TCM symptom scores， MLHF-Q score， plasma NT-ProBNP level and PAMP level significantly decreased， while 6MWD increased in the treatment group （P＜0.01）. There were no obvious abnormalities in the blood， urine， stool routine and liver and kidney function indicators in both groups. One adverse reaction each occurred in both groups， and there was no statistically significant difference in the incidence rates（P＞0.05）. ConclusionYHF combined with conventional western medicine can significantly improve the clinical efficacy， improve the clinical symptoms and cardiac function， increase the quality of life and exercise tolerance， and is relatively safe.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Objective:To investigate the causal relationship between childhood narcolepsy and allergic rhinitis using two-sample Mendelian randomization; To provide references for clinical prevention and treatment.Methods:Genetic variants closely related to narcolepsy were extracted from GWAS summary data as instrumental variables, with allergic rhinitis (AR) as the outcome variable. The narcolepsy data included 335 410 samples and 10 894 596 single nucleotide polymorphisms (SNPs). The AR data included 5 527 cases and 212 387 controls, with a total of 16 380 461 SNPs. Two-sample Mendelian randomization analyses were conducted using inverse variance weighted, weighted median, and MR-Egger regression methods mainly to evaluate the causal relationship between narcolepsy and AR with OR. Heterogeneity testing, pleiotropy assessment, and sensitivity analysis were used to evaluate the stability and reliability of the results.Results:A total of 42 SNPs were included as instrumental variables. It was found that the estimated effect of narcolepsy on AR was greater than 1 and with statistical significance [ OR(95% CI)=1.79(1.02,3.13), P=0.04]. Conclusions:There may be a positive causal relationship between narcolepsy and AR. "Phlegm-dampness impairing the spleen" is a common pathogenic mechanism between the two diseases.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.