ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum （STDP） in ameliorating angiotensinⅡ （AngⅡ）-induced cell phenotype transformation， proliferation， migration， and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%， 10%， and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin （α-SMA） and matrix metalloproteinase-2 （MMP-2）. The cell-counting kit-8 （CCK-8） assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were employed to detect the proliferation of vascular smooth muscle cells， and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 （ACE2）， angiotensin Ⅱ type 2 （AT2）， angiotensin Ⅱ type 1 （AT1）， as well as proliferation and migration proteins such as typeⅠ collagen （ColⅠ） and osteopontin （OPN）. ResultsCompared with the model group， STDP increased the expression of α-SMA， reduced the expression of MMP-2， and inhibited the proliferation and migration of vascular smooth muscle cells （P<0.05）. Furthermore， STDP up-regulated the expression levels of ACE2， AT2， and MAS1， while down-regulating the expression level of AT1， PCNA， ColⅠ， MMP-9， Rock1， Rock2， and SRF （P<0.05）. Compared with the STDP group， the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation， proliferation， and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

At present, the late diagnosis of HIV-infected patients is not optimistic, which has a significant impact on the efficacy, cost, and prognosis of HIV antiretroviral therapy and HIV transmission. Late diagnosis is an important indicator for evaluating HIV testing. This article reviews the influencing factors of late diagnosis of HIV-infected patients and provides a reference for formulating and improving HIV testing strategies and measures in China.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

BACKGROUND:Total knee arthroplasty is one of the effective methods to treat end-stage knee osteoarthritis.However,some patients still experience chronic post-surgical pain.It is significant to find out the influencing factors of chronic post-surgical pain.Demographic factors,social psychological factors and perioperative pain were the focus of previous studies,but muscle factors closely related to the occurrence and development of knee osteoarthritis were rarely reported. OBJECTIVE:To evaluate the value of preoperative quantitative ultrasound analysis of quadriceps femoris in predicting chronic post-surgical pain after total knee arthroplasty. METHODS:A total of 250 patients with knee osteoarthritis who underwent the first unilateral total knee arthroplasty under elective general anesthesia from January to August 2022 in the Affiliated Hospital of Xuzhou Medical University were selected.All patients were treated with the same anesthesia and operative methods.Before the surgery,clinical data were recorded,and the thickness and echo intensity of quadriceps femoris on the operated side were measured by ultrasound imaging,which could quantify the degree of quadriceps femoris atrophy.Multivariate logistic regression was used to analyze the independent factors affecting the occurrence of chronic post-surgical pain,and receiver operating characteristic curves were used to evaluate its predictive value. RESULTS AND CONCLUSION:(1)250 subjects were involved in the result analysis,and 91 of them had chronic post-surgical pain,with an incidence of 36.4%.(2)There were significant differences between the chronic pain and non-chronic pain groups in preoperative pain score during movement,preoperative Western Ontario and McMaster University Osteoarthritis Index,preoperative anxiety and depression scale score,preoperative muscle thickness and echo intensity of quadriceps femoris,and postoperative acute pain score(P<0.05).(3)Multivariate logistic regression analysis showed that preoperative thickness of quadriceps femoris was an independent protective factor for chronic post-surgical pain and preoperative pain score during movement was an independent risk factor for chronic post-surgical pain.(4)Receiver operating characteristic curves showed that the area under the curve of the preoperative thickness of quadriceps femoris was 0.625(95%CI:0.555-0.695),and the critical value was 2.78 cm,sensitivity was 0.802,specificity was 0.415.(5)It is concluded that the preoperative thickness of quadriceps femoris is an independent protective factor for chronic post-surgical pain,but its predictive efficacy is low,and its clinical application needs to be further verified or modified.

Objective To establish the energy expenditure(EE)prediction models of health Qigong Wuqinxi based on heart rate combined with accelerometer counts in different body parts,so to provide a reference for monitoring EE of Wuqinxi.Methods Seventy-four healthy college students aged 18-30 were selected as the research objects.They were divided into a skilled group of 39(21 males and 18 females)and a primary group of 35(17 males and 18 females)according to their level of practice,with 55 in the model group and 19 in the validation group.When performing a set of Wuqinxi,all subjects were recorded heart rate(HR),accelerometer counts[the average counts of X-axis,Y-axis,Z-axis and vector magnitude(VM)],and EE-related indicators by wearing the Polar heart rate moni-tor,ActiGraph-GT3X+accelerometers(9 parts:waist,both arms,both wrists,both thighs,and both ankles)and CORTEX Meta Max3B-R2 portable indirect calorimeter.Based on the accurate EE mea-sured by the gas metabolism meter,linear regression models of only HR,only accelerometer counts,or HR combined accelerometer counts were established,and their accuracy was analyzed and com-pared.Results The EE of Wuqinxi was significantly correlated with gender,height,weight,muscle mass,HR-related indicators,and accelerometer counts in different parts(X-axis counts of the waist,VM values of the left thigh and counts of the X-axis and Y-axis,VM values of the right thigh and the Y-axis,Z-axis count value,left ankle VM value and Y-axis count value,right ankle VM value and Y-axis,Z-axis count value)(P<0.05).Moreover,the adjusted R2 of the prediction model of only HR,only accelerometer counts,and the both were 0.582,0.508 and 0.678,respectively(P<0.05).The correlation between the predicted and measured values ranged between 0.706 and 0.817.Accord-ing to the Bland-Altman analysis,for each model,all except one error value fell outside the 95%confidence interval.That is,all models had an excellent fitting effect and high accuracy.Among them,the combined model was of the best prediction effect:EE(kcal)=-20.089+0.279×body weight(kg)+0.243×ΔHR(exercise HR-quiet HR,bpm)+0.001×Right thigh Y-axis count value+0.181×exer-cise HR(bpm)-4.202×gender(male=0,female=1).Conclusion The EE prediction model of Wuqinxi es-tablished on HR combined with accelerometer counts has the best effect and can calculate the EE more accurately.

Objective:To study the biological traits and mutations of the influenza A (H3N2) virus in order to produce a vaccine and offer references for controlling and preventing influenza epidemics.Methods:Four strains of the influenza A(H3N2) virus were chosen from the Huai′an surveillance network laboratory. Nucleic acid extraction, library building, and sequencing (CridION x5 MKI Nanopore) were used to produce the whole-genome sequences. Using homologous alignments of whole-genome sequences, phylogenetic tree construction, and amino acid variant screening, bioinformatics analysis was carried out.Results:The nucleotide identity between 8 gene segments ranged from 97.1% to 100.0%. The gene that differed the most from the reference sequences was HA (97.1%-99.9%), and the gene that differed the least was MP (98.6%-99.9%). The HA gene (3.06%) and MP gene (1.43%) were the regions with the greatest and lowest frequencies of nucleotide site change, respectively. The rates of nucleotide change varied significantly between the genes ( χ2=14.293, P=0.046). Four influenza A(H3N2) virus strains′ whole-genome phylogenies from each of the eight gene segments maintained a roughly consistent topological structure. One strain was linked to the 3C.2a1b.1b clade, which was lost at the 142NWT, 149NGT(HA1), and 436NLS(NA). Three strains were linked to the 3C.2a1b.2a.1a clade lineage. Amantadine and NA inhibitors were effective against all Huai′an strains. Conclusions:The antigenicity of one strain of Huai'an strain changed and its matching with the vaccine strain of that year was low. It is suggested that the genetic surveillance of H3N2 influenza virus should be continuously strengthened to provide scientific basis for influenza prevention and control and influenza vaccine screening.

Alzheimer's disease(AD)is the most prevalent form of cognitive impairment.Alongside common cognitive deficits, neuropsychiatric symptoms, and compromised daily activities, a growing body of research indicates that AD patients exhibit various forms of motor dysfunction, such as eye movement, upper limb movement, and gait and balance issues, even in the early stages, including the prodromal and preclinical phases of AD.This article introduced the presentation of motor dysfunction, its correlation with cognitive impairment and AD biomarkers, with the aim of aiding in the early detection, diagnosis, and treatment of AD.

Alzheimer′s disease (AD) is the most common type of cognitive impairment, characterized by complex pathology and pathogenesis. Regrettably, the effective therapeutic approaches remain unfulfilled, underscoring the pressing need to explore innovative preventive and therapeutic avenues. Research has illuminated the potential of intervening in risk factors and modifying lifestyle choices to diminish the incidence and decelerate the progression of AD. Notably, dietary patterns, such as Mediterranean diet, ketogenic diet, and calorie restriction have emerged as promising candidates for bolstering cognitive function in AD patients. These dietary approaches achieve this by multiple mechanisms, including mitigating the accumulation of neuropathological proteins, curbing neuroinflammation and oxidative stress, fortifying autophagy, and enhancing synaptic plasticity, etc. These findings strongly suggest that dietary intervention harbors the potential to serve as a novel and viable therapeutic strategy for AD. This review summarized the effects of different dietary patterns on the occurrence, progression, pathology and mechanism of AD.

Objective To investigate the effect of lipin1(LPIN1)on the progression of Parkinson's disease(PD)in rats and the possible molecular mechanism of its regulation.Methods The PD rat model was established by injection of 6-Hydroxydopamine hydrobromide(6-OHDA)into the medial forebrain tract of rats,and the LPIN1-overexpressing adenovirus was stably transfected to evaluate the behavioral changes of rats.The content of Fe2+and Glutathione(GSH)and the protein level of tyrosine hydroxylase(TH)in rat brain were detected,and HE staining was used to observe the pathological changes in rat brains.The PD cell model was constructed in vitro,and TH,α-synuclein(α-syn),LPIN1 protein levels and cell viability were detected.LPIN1 small interfering siRNA sequence and overexpression vector and peroxisome proliferator-activated receptor(PPARA)small interfering(siRNA)and overexpression vector were transfected,or ferroptosis inducer erastin was used to treat cell for 24 h,then cells were treated with 6-OHDA for 48h.The levels of Fe2+,reactive oxygen species(ROS),malondialdehyde(MDA),GSH and inflammatory factors in cells were detected to evaluate ferroptosis.Cell viability was detected with CCK-8,and the expressions of ferroptosis related proteins were detected with Western blot.The interacting protein PPARA of LPIN1 was predicted by STRING database and verified by Co-IP analysis.The binding site of PPARA to the promoter of solute carrier family 47 member 1(SLC47A1)was predicted by JASPAR bioinformatics and verified by Ch-IP analysis.Results The fur of the rats in the model group was frightened,and PD symptoms such as continuous tremor,slow movement and weakened activity were shown.The motor behavior and PD symptoms of LPIN1 group were improved/alleviated compared with the model group.Compared with the sham operation group,the total distance of the model group was shortened,the average speed was reduced,and the step length was reduced,while the total resting time was prolonged,the step width was widened,and the gait variation rate was increased,and the differences were significant(t=4.470～26.556,all P＜0.05).Compared with sham operation group,Fe2+content in brain tissue of model group was increased,while GSH content and TH protein expression were decreased,with significance differences(t=8.305,13.305,7.709,all P＜0.05).Compared with the model group,the behavioral evaluation,the level of indexes and the pathological changes of brain tissue in LPIN1 group were improved/alleviated.In addition,6-OHDA decreased PC-12 cell viability,reduced the levels of TH and LPIN1 protein,and increased the level of α-syn protein in a dose-dependent manner,and the differences were significant(F=31.023,7.350,9.124,15.841,all P＜0.05).Silencing LPIN1 intensified the inhibitory effect of 6-OHDA on the viability of PC-12 cells(t=2.209,P＜0.05),and overexpression of LPIN1 could counteract the effect of 6-OHDA.Overexpression of Lpin1 decreased the secretion of IL-1β and IL-6,increased the protein levels of SLC47A1 and GPX4,decreased the levels of Fe2+,MDA and ROS,and increased GSH content(t=3.013～11.639,all P＜0.05).Erastin reversed the inhibitory effect of Lpin1 overexpression on ferroptosis,and reduced the viability of PC-12 cells(t=3.087～7.581,all P＜0.05).LPIN1 interacted with PPARA protein and promoted PPARA expression,while PPARA bound to SLC47A1 promoter and promoted SLC47A1 transcriptional activation.Overexpression of PPARA counteracted the effect of Lpin1 silencing on PC-12 cells.Conclusion Overexpression of LPIN1 may reduce neuronal cell apoptosis by inhibiting ferroptosis mediated by PPARA/SLC47A1 axis,thus alleviating the progression of PD model rats.