This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

Objective:To analyze the distribution of different SF3B1 genotypes in patients with myelodysplastic syndromes (MDS) and its prognostic value.Methods:Totally, 377MDS patients who were initially diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to January 2022 were included in the retrospective analysis.The patients were divided into three different groups according to mutation stcote of SF3B1, including 317 patients with SF3B1 wild type (SF3B1 WT) (214 males and 103 females, 63(49, 71) years old),39 patients with SF3B1 K700E mutation(SF3B1 K700E(17 males and 22 females, 65(52, 73)years old)) and 21 patients with SF3B1 non-K700E mutation(SF3B1 non-K700E)(13 males and 8 females, 67(63, 73) years old). MDS-related 20 gene mutations were detected using targeted sequencing technology; Survival curves were constructed by the Kaplan-Meier method; Cox proportional hazards model was established to evaluate different factors at diagnosis on survival by univariate and multivariate analyses.. Results:Compared with SF3B1 non-K700E patients, SF3B1 K700E patients had a higher median absolute neutrophil count ( P=0.002) and were likely to be in the low/int-1 International Prognostic Scoring System (IPSS) categories ( P=0.023). A 20-gene targeted sequencing analysis showed that, compared with SF3B1 WT patients, SF3B1 K700E patients were associated with lower frequency of ASXL1 and U2AF1 mutations ( P=0.018 and P=0.003); while compared with SF3B1 non-K700E patients, the frequency of ASXL1 mutation was significantly lower in SF3B1 K700E cases ( P=0.029). Patients with SF3B1 K700E had better overall survival (OS) in comparison with SF3B1 WT and SF3B1 non-K700E in MDS patients ( P<0.001 and P=0.045, respectively). In comparison with SF3B1 WT patients, SF3B1 MUT patients had more favorable OS and progression-free survival (PFS) in MDS without excess blasts ( P<0.001 and P<0.001, respectively), but no significant difference was found in MDS with excess blasts ( P>0.05). Compared with SF3B1 WT patients, SF3B1 K700E patients had superior OS and PFS in the int-1 IPSS category ( P=0.010 and P=0.013, respectively). By multivariable analysis, the presence of SF3B1 K700Ewas an independent predictor of superior OS ( HR=0.461,95% CI 0.262-0.811, P=0.007). Conclusion:SF3B1 K700E and SF3B1 non-K700E patients had significantly improved OS in comparison with SF3B1 WT MDS patients. Furthermore, SF3B1 K700E patients were associated with a better OS compared with SF3B1 non-K700E MDS patients. SF3B1 mutation could not overcome the poor prognostic effect of excess blasts, which highlights the importance of the SF3B1 mutation subtype in risk assessment of MDS without excess blasts.

Objective:To investigate the correlation between heart rate variability (HRV) and cognitive impairment in patients with obstructive sleep apnea (OSA).Methods:Patients received polysomnography in Weihai Municipal Hospital from June 2019 to November 2020 were enrolled as the subjects of cross-sectional analysis. According to the Montreal Cognitive Assessment score, the patients with OSA were divided into a cognitive impairment group and a non-cognitive impairment group. Multivariate logistic regression analysis was used to determine whether HRV parameters were the independent influencing factors of cognitive impairment in patients with OSA. Multiple linear regression analysis was used to determine the independent correlation between HRV parameters and overall cognition as well as each cognitive domain in patients with OSA. Results:A total of 115 patients with OSA were included, including 80 males (69.6%), aged 58.25±9.88 years. Among them, there were 61 in the cognitive impairment group (53.0%) and 54 in the non-cognitive impairment group (47.0%). The standard deviation of the R-R interval in normal sinus beats (SDNN), the square root of the mean of the sum of the squares of the difference between adjacent NN intervals (RMSSD), the percentage of the number of pairs of adjacent R-R intervals differing by more than 50 ms (pNN50) and the power in high-frequency range (HF; 0.15-0.40 Hz) in the cognitive impairment group were significantly lower than those in non-cognitive impairment group (all P<0.05). Multivariate logistic regression analysis showed that SDNN (odds ratio [ OR] 0.551, 95% confidence interval [ CI] 0.380-0.798; P=0.002), RMSSD ( OR 0.516, 95% CI 0.342-0.779; P=0.002), pNN50 ( OR 0.900, 95% CI 0.834-0.971; P=0.006), LF ( OR 0.821, 95% CI 0.687-0.982; P=0.030) and HF ( OR 0.687, 95% CI 0.525-0.899; P=0.006) were the independent protective factors of cognitive impairment in patients with OSA. Multiple linear regression analysis showed that SDNN ( β=0.208, P=0.023), RMSSD ( β=0.228, P=0.011), pNN50 ( β=0.186, P=0.040), HF ( β=0.235, P=0.010) is independently correlated with overall cognitive function in patients with OSA. Conclusion:The decline of HRV parameters SDNN, RMSSD, pNN50 and HF is independently correlated with cognitive impairment in patients with OSA, suggesting that the decline of vagus nerve function may be involved in the mechanism of cognitive impairment in patients with OSA.

Objective: To investigate the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on platelet function in patients with ischemic stroke. Methods: Patients with ischemic stroke treated in the Department of Neurology, Weihai Municipal Hospital from January 2017 to November 2017 were collected prospectively. The presence or absence of OSAHS was determined by polysomnography. After oral administration of aspirin enteric coated tablets for 7±1 d, the maximum aggregation ratio (MAR) induced by arachidonic acid (AA) was determined by PL-12 Platelet Function Analyzer. MAR-AA ≥50% was defined as platelet hyperresponsiveness. Multivariate logistic regression analysis was used to evaluate the risk factors for platelet hyperresponsiveness in patients with ischemic stroke, and multiple linear regression analysis was used to determine the correlation between sleep parameters reflecting the severity of sleep apnea and MAR-AA. Results: Among the 124 patients with ischemic stroke, 58 (46.77%) complicated with OSAHS, 66 (53.23%) without complicated with OSAHS; 84 (67.74%) had platelet hyperresponsiveness, and 40 (32.26%) had not platelet hyperresponsiveness. MAR-AA in the complicated OSAHS group was significantly higher than that in the non-complicated OSAHS group (48.98%±20.61% vs. 26.45%±15.15%; t=-6.858, P<0.001). Multivariate logistic regression analysis showed that OSAHS was an independent risk factor for platelet hyperresponsiveness in patients with ischemic stroke (odds ratio 9.551, 95% confidence interval 3.051-29.905; P<0.001). Multiple linear regression analysis showed that there was a significant linear relationship between apnea hypopnea index and MAR-AA (β=0.499, P<0.001). Conclusions OSAHS is an independent risk factor for platelet hyperresponsiveness in patients with ischemic stroke. Apnea hypopnea index is significantly correlated with MAR-AA.

Objective To investigate the association between serum estradiol levels and macrovascular complication of atherosclerosis in mid-aged and elderly male patients with type 2 diabetes mellitus(T2DM).Methods One hundred and twenty nine male diabetic patients aged over 45 years were recruited in this study.Serum estriol(E2), testosterone(T)and lipid levels were detected using chemiluminescent immunoassay.Carotid ultrasonography was taken to evaluate macrovascular complication of atherosclerosis.The demographic characteristics, clinical features including duration of diabetes and prevalence of carotid atherosclerosis and biochemical features were compared among patients with different serum E2levels.Correlation analysis was also performed using binary logistic analysis.Results There were 43 patients with low serum E2level(<134.1 pmol/L), 44 with intermediate E2level(134.1 -198.2 pmol/L)and 42 with high E2level(>198.2 pmol/L).Among 129 patients the carotid artery lesions were detected in 64 cases.There were significant differences in body weight[(61.0 ±10.4), (67.4 ±13.0)and(76.8 ±10.5)kg,t=3.40,P=0.00], waist circumference[(81.5 ±7.9),(86.6 ± 10.7)and(90.0 ±8.0)cm,t=3.57,P=0.00],body mass index(BMI)[(21.6 ±3.2),(23.5 ±3.8) and(26.2 ±3.0)kg/m2,t=3.72, P=0.00], systolic pressure[(140.2 ±14.8),(143.9 ±18.1)and (155.0 ±13.1)mmHg(1 mmHg=0.133 kPa),t=3.18, P=0.04]and TG[(1.46 ±0.88),(2.23 ± 1.08)and(3.35 ±0.9)mmol/L, t =2.66, P=0.04]among patients with low, intermediate and high serum E2levels.The age-adjusted incidence of carotid atherosclerotic plaque in patients with low, intermediate and high E2levels were 25.6%(11/43),56.8%(25/44)and 66.7%(28/42), respectively (χ2=15.73,P=0.00).Compared to low E2level,the risk ratio of carotid atherosclerosis in intermediate and high E2levels was 1.60(95%CI:1.04-2.46, P<0.05)and 1.80(95%CI:1.17 -2.76, P<0.05),respectively.Conclusion Serum E2level is closely associated with carotid atherosclerotic plaque in middle-aged and elderly male type 2 diabetic patients.

Objective To investigate the feasibility of hydrogen proton magnetic resonance spectroscopy (1 H-MRS)for detection of Wallerian degeneration of the pyramidal tract after cerebral infarction.Methods Multiple metabolic indices including NAA,Cho, Cr of the bilateral cerebral peduncle were detected by using 1 H-MRS in 1 5 patients with unilateral middle cerebral artery infarction and 1 5 age-matched healthy volunteers,NAA/Cr,Cho/Cr were also calculated.Comparing the difference between cerebral infarction group and the control group ,the ROC curve was analyzed.Results The values of NAA/Cr in the ipsilateral cerebral peduncle of cerebral infarction patients were significantly lower than that of the contralateral,and there were significant differences between the two groups(P <0.05).The values of NAA/Cr in the ipsilateral cerebral peduncle of cerebral infarction patients decreased (P <0.05),as compared with that of the control group.The area under the ROC curve was 0.947,the truncation point was 1.63.The NAA/Cr val-ues of the contralateral cerebral peduncle of cerebral infarction patients had no significant differences compared with the control group (P >0.05),the Cho/Cr values of the ipsilateral and the contralateral cerebral peduncle had no significant difference compared with the control group (P >0.05).Conclusion 1 H-MRS can detect Wallerian degeneration of the pyramidal tract after cerebral infarction.

Objective To investigate the role of intestinal fatty acid binding protein(I-FABP)in evaluating intestinal dysfunction of septic rats and the effect of glutamine on I-FABP expression.Methods Rats were divided into 3 groups,control group were only fed with Peptisorb,model group were fed with Peptisorb after intraperitoneal injection with E.coli endotoxin lipopolysaccharidegiven and glutamine group were added glutamine on basis of model group.The correlation between serum I-FABP level and intestinal mucosa damage index were analyzed and the concentrations of serum I-FABP in each group were observed and compared. Results The serum level of I-FABP in rats were correlated with the Chiu’s score of intestinal mucosa,mucosa thickness and villus length(P<0.05 ).Compared with control group,the concentration of serum I-FABP in model group and glutamine group were significantly increased(P<0.05),but which in glutamine group was lower than that in model group(P<0.05).Conclusions Serum I-FABP could be an non-invasive diagnosis index for evaluating acute intestinal dysfunction in septic rats.In addition,dietary glutamine supplementation may ameliorate sepsis-induced intestinal epithelial injury in rats.

Objective The onset and progression of lung cancer correlate closely to individual genetic background .This study evaluated the correlation between the onset risk of lung cancer and short tandem repeat (STR) polymorphisms in order to find a new pathway for investigating the pathogenesis of lung cancer . Methods Using PCR and electrophoresis on 15 STR loci , we studied the gene and genotype frequencies of peripheral vein blood specimens from 120 lung cancer patients and 156 healthy individuals in Nan-jing area.According to the differences in the allele distribution of the 15 STR loci, we evaluated the susceptive and/or resistant factors relevant to lung cancer . Results There were statistically significant differences between the lung cancer patients and healthy controls at alleles 10, 15.2, and 16 of the loci CSF1PO, D19S433, and D3S1358 (P<0.05, OR>1), as well as at alleles 14 and 14.2 of the loci CSF1PO and D19S433 (P<0.05, OR<1). Conclusion It is possible that alleles 10, 15.2 and 16 of the loci CSF1PO, D19S433, and D3S1358 are susceptive factors and alleles 14 and 14.2 of the loci CSF1PO and D19S433 are resistant factors relevant to lung cancer .

BACKGROUND:Mesenchymal stem cel s can differentiate into nerve cel s by chemical induction or co-culture method, but whether mesenchymal stem cel s co-cultured with Schwann cel s differentiate into neuronal-like cel s or Schwann-like cel s is stil controversial.
OBJECTIVE:To explore the inductive role of Schwann cel s derived from rats in the differentiation of human umbilical cord mesenchymal stem cel s.
METHODS:Cocultures of human umbilical cord mesenchymal stem cel s (1×109/L) and Schwann cel s (1×109/L) from neonatal rats were performed using transwel culture dishes. After 2 weeks of cocultures, morphology of the cultured human umbilical cord mesenchymal stem cel s was observed, and the phenotypic changes of cel s were also detected with immumocytochemistry techniques.
RESULTS AND CONCLUSION:After 2 weeks of cocultures, some differentiated cel s showed neuron-like morphology, and expressed nestin, NF-200 andβ-III-tubulin, but did not express Schwann cel special marker S100 and oligodendrocytes special marker MAB1580. These findings indicate that human umbilical cord mesenchymal stem cel s can transdifferentiate into neuronal-like cel s by cocultures with rat’s Schwann cel s.