To summarize the clinical experience of Professor LIU Shangyi in treating pruritus vulvae. It is believed that women have the physiological characteristics of liver and kidney as the root， and their pubic area is easily attacked by wind-dampness pathogenic qi， so the core mechanism of pruritus vulvae is proposed as wind-dampness accumulation and deficiency of liver and kidney. The core treatment method is to dispel wind-dampness and nourish the liver and kidneys， and modify the Danggui Decoction （当归饮子） to form a self-prescribed Yinyang Formula （阴痒方） as the basic prescription to treat pruritus vulvaen.

ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription （YHP） on the learning and memory of accelerated aging model mice， as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups， including the model group， low-dose YHP group， high-dose YHP group， and donepezil group. Additionally， 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group， each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg^-1 and 12.48 g·kg^-1， while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg^-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial （MG） polarization marker inducible nitric oxide synthase （iNOS） and M2 MG polarization marker arginase-1 （Arg-1） in the hippocampus region. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of pro-inflammatory factor interleukin 1β （IL-1β） and anti-inflammatory factor transforming growth factor-β₁ （TGF-β₁）. Furthermore， Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 （Aβ_1-42） along with triggering receptor expressed on myeloid cells 2 （TREM2）/nuclear factor kappa B （NF-κB） signaling pathway-related proteins TREM2， phospho （p）-NF-κB p65， and phospho-inhibitory kappa B kinase β （IKKβ） in the hippocampus. ResultCompared with the control group， the model group exhibited a significantly prolonged escape latency （P<0.01）， a significant reduction in neuron-specific nuclear protein （NeuN） expression in the hippocampus， a significant increase in iNOS expression in MG， and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased， while the TGF-β₁ content was significantly decreased. Additionally， there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions （P<0.05， P<0.01）. However， no significant changes were observed in escape latency， times of crossing the platform， and hippocampal NeuN expression in the YHP treatment control group. Conversely， iNOS expression in MG as well as the hippocampal p-NF-κB p65， p-IKKβ， and Aβ_1-42 expressions were significantly decreased. Furthermore， TREM2 expression was significantly increased （P<0.05， P<0.01）. In comparison to the model group， the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform （P<0.05， P<0.01）. In the high-dose YHP group， the escape latency was significantly shortened （P<0.05）. In the low-dose YHP group， high-dose YHP group， the expression of NeuN in the hippocampus was significantly increased， the expression of iNOS in MG was significantly decreased， and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased， while the TGF-β₁ content was significantly increased. Furthermore， the expression of TREM2 in the hippocampus was significantly increased， and the expressions of p-NF-κB p65， p-IKKβ， and Aβ_1-42 were significantly decreased （P<0.01）. ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway， reduce the release of neuroinflammatory factors， protect hippocampal neurons， and reduce the deposition of Aβ_1-42， and finally delay the occurrence of learning and memory decline in SAMP8 mice.

Objective:To investigate the comorbidity status of hypertension, diabetes, and dyslipidemia (the"three diseases") among residents aged≥40 in Liaoning Province, and to explore the correlation between the comorbidity and cardiovascular disease mortality.Methods:This investigation was a prospective cohort study. From February 2017 to March 2019, a multi-stage stratified cluster random sampling method was used to carry out a baseline survey of 18 758 permanent residents aged≥40 years in Liaoning Province. Demographic information and history of hypertension, diabetes, and dyslipidemia were collected and followed up every year. Death was mainly identified by linkage to the Population Death Information Registration Management System. Cox proportional hazard regression model was used to analyze the association between the comorbidity of the "three diseases" and cardiovascular disease mortality risk.Results:A total of 18 758 residents aged≥40 in Liaoning Province were included, with an age of (60.3±9.9) years and 7 325 males (39.1%). The comorbidity rate of hypertension, diabetes, and dyslipidemia was 6.7% (1 256/18 758), and the standardized prevalence rate was 5.4%. The comorbidity rate increased with age (P<0.001), which was higher in women than in men, and more significant in urban areas than in rural areas (all P<0.001). The comorbidity of "three diseases" accounted for 39.3% (1 256/3 198), 18.7% (1 256/6 710), and 11.8% (1 256/10 653) in patients with diabetes, dyslipidemia, and hypertension, respectively. With a follow-up of (4.3±0.6) years, 463 people died of cardiovascular disease. The mortality rate of cardiovascular disease in the comorbidity of hypertension, diabetes, and dyslipidemia was 8.74/1 000 person-years. After adjusting potential confounders, Cox proportional hazard regression model analysis showed that compared with normal individuals, the hazard ratio of cardiovascular disease mortality in patients with the "three diseases" was 2.55 (95% CI: 1.63-3.99). Conclusion:The prevalence of comorbidity of hypertension, diabetes, and dyslipidemia among residents aged≥40 in Liaoning Province was relatively high, and the risk of cardiovascular disease mortality in patients with the "three diseases" was increased.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Objective:To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality.Methods:A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality.Results:The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio ( HR)=1.68, 95% CI: 1.44-1.94] and an increased risk of CVD mortality by 1.56 times ( HR=1.56, 95% CI: 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P>0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P<0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P<0.05). Conclusions:The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.

Objective To establish an animal model of dampness-syndrome in mice (single model) and evaluate its characteristics of dampness-syndrome. The above-mentioned mice with dampness syndrome were used to construct mice model of ischemic stroke (double model) and observe the effect of dampness-pathogenic on the outcome of stroke. Methods Healthy C57BL/6J male mice were randomly divided into dampness-syndrome (including sham-surgery group and ischemic stroke group,with 10 mice in each group) and non dampness-syndrome groups (including sham-surgery group and ischemic stroke group,with 10 mice in each group). The dampness-syndrome group was fed with high-fat diet and the non dampness-syndrome group was fed with normal diet for 12 weeks. After the mice model of dampness-syndrome was successfully established,transient middle cerebral artery occlusion/reperfusion (tMCAO/R) surgery was used to replicate an ischemic stroke mice model. Evaluation indicators for dampness-syndrome mice model:the general status including body weight,morphology,posture,activity status,and physical characteristics,the histopathological observation of the aorta (oil red O staining,Masson-trichrome staining) and liver (HE staining,oil red O staining),electron microscopic observation of the tongue tissue (scanning electron microscopy,electron microscopy),blood lipid levels[total cholesterol(TC),triglycerides(TG)]and liver coefficient. Evaluation indicators for ischemic stroke mice model:neurological function score and the cerebral infarction volume ratio. Results Compared with the non dampness-syndrome group,the mice in the dampness-syndrome group showed an increased in body weight,poor hair color,sparse hair,fatigue and laziness,mental atrophy,anorexia and lethargy. It was observed that the aortic lumen was narrowed,the intima was significantly thickened,lipid plaque deposition was increased,and foam cells were visible. A large amount of red lipid droplets appeared in liver cells. There were obvious lipid infiltration and diffuse steatosis. Increased keratosis of the mucosal layer of tongue tissue,the thicker stratum corneum,lipofuscin,and bacteria on the tongue surface were found. Serum TG and TC levels significantly increased(P<0.01),and the liver coefficient significantly decreased (P<0.001). Compared with non dampness-syndrome group (sham-surgery group),neurological function score and the cerebral infarction volume ratio in dampness-syndrome ischemic stroke group obviously increased (P<0.001). Conclusion High-fat feeding for 12 weeks combined with tMCAO/R modeling can successfully establish a mice model with dampness-syndrome ischemic stroke,and the neurological function score and cerebral infarction volume in the dampness-syndrome ischemic stroke group was more severe than that in the non dampness-syndrome ischemic stroke group.

ObjectiveIt was reported that the transthyretin (TTR) has a neuroprotective effect on Alzheimer’s disease (AD), which is manifested by the ability of TTR to inhibit the pathological aggregation of amyloid beta protein (Aβ). In this work, we investigated the mechanism of the interactions between TTR and Aβ at the molecular level to reveal the neuroprotective effect of TTR on AD. MethodsProtein-protein docking was used to explore the models of interaction between different structural forms of TTR and Aβ, and molecular dynamics simulation was further applied to investigate the dynamic process of the interaction between the two. ResultsBoth TTR tetramer and monomer can interact with Aβ monomer, and the thyroxine-binding channel of TTR tetramer is the main binding site of Aβ monomer. In addition, the EF helix and EF loop of TTR tetramer were also able to bind Aβ monomer. When the TTR tetramer dissociates, the hydrophobic site of the internal TTR monomer is exposed, which has a strong affinity for Aβ monomer. For the interaction between Aβ aggregates and TTR, a higher degree of aggregation can be formed between TTR monomer and Aβ aggregates due to the β-sheet-rich property of TTR monomer and Aβ aggregates, which may therefore reduce the cytotoxicity of Aβ aggregates. ConclusionBoth TTR tetramer and monomer can inhibit Aβ aggregation by “sequestering” Aβ monomer, while TTR monomer can reduce the cytotoxicity of Aβ aggregates by forming large co-aggregation with Aβ aggregates. This work can provide an important theoretical basis for the design and discovery of anti-AD drugs based on the neuroprotective effects of TTR.

Objective To investigate the correlation between serum microRNA(miR)-24-3p,microtubule affinity-regulating kinase 4(MARK4)level expression and cardiac function in serum of patients with coronary atherosclerotic heart disease(CHD).Methods From August 2021 to April 2023,138 CHD patients who visited Sichuan Provincial People's Hospital were collected as the study subjects(CHD group).According to the New York Heart Association(NYHA)grading,patients in the CHD group were separated into grade Ⅱ(n=39),grade Ⅲ(n=68),and grade Ⅳ(n=31).Additionally,123 individuals who underwent physical examinations were selected as the health group during the same period.Real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect the expression levels of miR-24-3p and MARK4.Cardiac function indicators in the CHD and health groups were detected.Pearson method was applied to analyze the correlation among serum miR-24-3p,MARK4,and cardiac function indicators.Results Compared with the healthy group,the levels of MARK4(1.19±0.21 vs 1.00±0.20),left ventricular end-systolic dimension(LVESd),left ventricular enddiastolic dimension(LVEDd),interventricular septal thickness(IVS),left ventricular end-diastolic volume(LVEDv),left ventricular end-systolic volume(LVESv),and left ventricular mass(LV mass)in the CHD group were increased(t=7.462,18.242,23.888,9.941,2.812,12.520,11.029),while the levels of miR-24-3p(0.62±0.11 vs 1.00±0.18),left ventricular ejection fraction(LVEF),and cardiac output(CO)were reduced(t=20.821,10.212,18.188),and the differences were statistically significant(all P＜0.05).As cardiac function grading increased,MARK4 expression levels(1.09±0.19,1.18±0.17,1.32±0.22),LVESd,LVEDd,IVS,LVEDv,LVESv and LV mass were increased(F=13.025,10.606,11.920,57.956,29.680,21.253,12.954),and miR-24-3p expression levels(0.84±0.15,0.61±0.11,0.37±0.08),LVEF and CO were decreased(F=139.227,9.720,13.411),and the differences were statistically significant(all P＜0.05).Pearson correlation analysis showed a negative correlation between miR-24-3p and MARK4 expression in the serum of patients with CHD(r=-0.540,P＜0.05).The relative expression of miR-24-3p in the serum of patients with CHD was negatively correlated with LVESd,LVEDd,IVS,LVEDv,LVESv and LV mass(r=-0.656,-0.636,-0.617,-0.576,-0.492,-0.687,all P＜0.05),but positively correlated with LVEF and CO(r=0.570,0.683,all P＜0.05).The relative expression level of MARK4 was positively correlated with LVESd,LVEDd,IVS,LVEDv,LVESv,and LV mass(r=0.503,0.542,0.508,0.624,0.516,0.560,all P＜0.05),but negatively correlated with LVEF and CO(r=-0.594,-0.525,all P＜0.05).Conclusion The expression of miR-24-3p in the serum of CHD patients was decreased,while the expression of MARK4 was increased.There was an obvious correlation between the two and cardiac function indicators.

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P＞0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P＜0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P＜0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.

In order to investigate the mechanism of 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)on liver bile acid(BAs)and lipid metabolism of dairy cows with fatty liver,A liver lip-id accumulation model was established by isolating primary calf hepatocytes and treating them with high concentration of non-esterified fatty acids(NEFA)in vitro.Then,HMGCR overex-pressed adenovirus(Ad-HMGCR)and overexpressed adenovirus control(Ad-GFP)were added.Hepatocyte triglyceride(TAG)was detected by the kit,lipid droplet changes were detected by lip-id droplet fluorescence,and BAs synthesis,fatty acid synthesis and oxidation factor changes were detected by real-time fluorescence quantitative PCR.The results showed that TAG content and lip-id droplet fluorescence were significantly reduced in Ad-HMGCR+NEFA group compared with Ad-GFP+NEFA group.Real-time fluorescence quantitative PCR results showed that CYP7A1,CYP8B1,CYP7B1 and CYP27A1 of hepatocyte BAs synthesis factors in Ad-HMGCR+NEFA group,BAs transporters ABCC2 and ABCB11 and fatty acid synthesis factors ACC1,FAS and SREBP1C were significantly lower than those in Ad-GFP+NEFA group.The levels of BAs syn-thesis factor FXR and lipid oxidation factor CPT1A in Ad-HMGCR+NEFA group were higher than those in Ad-GFP+NEFA group.The results showed that overexpression of HMGCR could significantly reduce BAs and lipid accumulation in the liver of dairy cows with fatty liver.