Objective To establish normal reference values for left ventricular trabecular and papillary muscle mass(TPMM)in Chinese adults using MRI and to explore its impact factors.Methods A total of 168 healthy Chinese adults were retrospectively included,and compacted and total left ventricular myocardial mass(LVM)were measured using traditional and dedicated methods,respectively.TPMM was calculated from the difference between total and compacted LVM.Independent sample t-tests and analysis of variance were used to explore the differences in TPMM among genders and age groups,while multiple linear regression was used to explore the independent correlation between TPMM and age,gender,heart rate,systolic blood pressure(SBP),fasting blood glucose(FBG),and body mass index(BMI).Results TPMM for men was significantly larger than that for female(P<0.001).TPMM in the elderly group was significantly larger in female(P<0.05),but not in men.Multiple linear regression showed that BMI and SBP were both independently positively correlated with TPMM,and female and heart rate were independently negatively correlated with TPMM(P<0.05).Conclusion This study provides age-and gender-specific normal reference values for TPMM in Chinese adults.Gender,heart rate,BMI,and SBP are all independently associated with TPMM.

Objective To establish the animal model of comorbidity of knee osteoarthritis(KOA)and hypertension with pattern of liver and kidney deficiency and evaluate its characteristics of comorbidity and pattern.Methods Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHR)were assigned to the WKY control group(control group),hypertension combined with KOA sham-operation group(sham-operation group),hypertension combined with KOA group(model group),hypertension combined with KOA and liver-kidney deficiency pattern group(LKD group).The animal model of KOA combined with hypertension was prepared by anterior cruciate ligament transection(ACLT)in spontaneously hypertensive rats.ACLT combined with intramuscular injection of hydrocortisone was performed to prepare an animal model of KOA with liver-kidney deficiency(LKD)pattern type,combined with hypertension.Then,the related indexes of LKD syndrome were detected in turn,including the contents of thyroid stimulating hormone(TSH),testosterone(T),corticosterone(CORT),adrenocorticotropic hormone(ACTH)in serum,and enzyme activities of alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP)in serum,the mass ratio of liver,kidney,spleen,thymus to the brain,body weight,anal temperature,activity situation,and emotion.Systolic blood pressure,diastolic blood pressure,and other blood pressure-related indices were also detected.The levels of serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),plantar mechanical pain sensitivity threshold,weight difference score of both hind limbs,hind limb joint swelling,and quadruped gait parameters were also measured.Furthermore,hematoxylin-eosin,safranine-fast green,and Masson staining were performed to observe pathological changes,cartilage degeneration,and bone destruction of the knee joint,and the microstructure parameters of the tibia were detected by Micro-CT imaging.Results Compared to the model group,the contents of serum TSH,ACTH,T,CORT and the mass ratio of the kidney,spleen,and thymus to the brain in the LKD group decreased(P<0.05).Compared to the control group,the systolic blood pressure and diastolic blood pressure of the other three groups increased significantly(P<0.05).Compared to the sham-operation group,serum TNF-α and IL-1β levels increased,plantar mechanical pain threshold decreased,weight difference score of both hind limbs and joint swelling of the affected limb increased(P<0.05),and gait parameters(e.g.,gait length and standing time of the affected limbs)became abnormal in the model and LKD groups.Simultaneously,the cartilage surface defect of the rat knee joint was severe,the arrangement of the surface chondrocytes was altered,the cartilage layer became thinner,the muscle fibers increased,and the cartilage ossification was severe.Furthermore,the relative volume,thickness,and number of trabeculae of the knee joint decreased significantly(P<0.05).Conclusion The rat model established in this study is consistent with the clinical characteristics of integrated traditional Chinese and Western medicine in patients with comorbidities of hypertension and KOA with liver and kidney deficiency pattern.This rat model can characterize the typical symptoms of liver and kidney deficiency pattern.It has typical pathological changes in knee cartilage and subchondral bone tissues and can maintain a stable range of high systolic and diastolic blood pressure.It also explore the scientific connotation of simultaneous treatment of different diseases in traditional Chinese medicine,revealing the therapeutic mechanism and developing new drugs.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.

[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.

Objective: To investigate the effects of knockdown of E2F transcription factor 1(E2F1) in human tongue squamous cell carcinoma cells on proliferation, migration, and invasion of tongue squamous cell carcinoma cells, and to explore its possible mechanisms. Methods: The expression ofE2F1in human tongue squamous cell carcinoma was detected by RT-PCR, and the background expression ofE2F1gene in HOEC, SCC-9, CAL-27, TSCCa and SCC-25 cells was detected by RT-PCR, and the cell lines with significantly high expression of E2F1 were screened for subsequent experiments. CCK-8, EdU, colony formation, cell scratch, Transwell, apoptosis and cell cycle experiments were used to detect the effects of knockdown ofE2F1on proliferation, migration, invasion and apoptosis of human tongue squamous cell carcinoma cells after knockdown ofE2F1gene in tongue squamous cell carcinoma candidate cells. Western blot was used to detect the expression of epithelial mesenchymal transition markers E-cadherin, N-cadherin and snail family transcription inhibitor 1(Snail) protein and WNT signaling pathway markers WNT family members 3A(WNT3A), β-catenin and cyclin D1(CCND1). Results: RT-PCR results showed that the expression ofE2F1in cancer tissues was significantly higher than that in adjacent tissues(P<0.001). At the same time, compared with HOEC cells, the expression ofE2F1in SCC-9, CAL-27, TSCCa and SCC-25 cells significantly increased(P<0.05), and the high expression in SCC-25 cells was the most obvious. SCC-25 would be used as an experimental cell line in subsequent experiments. After knocking downE2F1in SCC-25 cells, the viability of CCK-8 cells was significantly inhibited(P<0.001). The number of EdU positive cells decreased significantly(P<0.001). The number of cell clones was significantly reduced(P<0.001). The proportion of total apoptosis significantly increased(P<0.001). The proportion of cells in G1phase increased(P<0.01). The proportion of cells in G2phase decreased(P<0.01). The cell migration and invasion ability were significantly inhibited(P<0.001). Western blot showed that the expression of WNT signaling pathway proteins WNT3A, β-catenin and CCND1 decreased(P<0.001), while the expression of EMT-related proteins N-cadherin and Snail decreased(P<0.001), while the expression of E-cadherin increased(P<0.001). Conclusion Knockdown ofE2F1inhibits the proliferation, migration, invasion and EMT process of human tongue squamous cell carcinoma SCC-25 cells, and promotes apoptosis. This anti-tumor effect may be achieved by blocking the activation of WNT signaling pathway.

AIM:To observe the effect of acupuncture on adenosine A1 receptor(A1R)in the caudate puta-men(CPu)of complete Freund's adjuvant(CFA)rats,and to explore the potential mechanism of acupuncture in treat-ment of inflammatory pain.METHODS:Sixty-four 6～8-week-old male Wistar rats were randomly divided into saline group,model group(CFA group),CFA+manual acupuncture(MA)group,CFA+solvent dimethyl sulfoxide(DMSO)group,CFA+A1R agonist 2-chloro-N6-cyclopentyladenosine(CCPA)group,CFA+A1R antagonist 8-cyclopentyl-1,3-di-propylxanthine(DPCPX)group,CFA+MA+DMSO group and CFA+MA+DPCPX group.In MA groups,on the 2nd day af-ter modeling,the rats were needled at Zusanli points on both sides,30 min at a time,once per day,for 7 d.Pain threshold of plantar thermal radiation was used to observe the pain response of the rats.The content of cyclic adenosine monophos-phate(cAMP)in the CPu was detected by ELISA.The protein expression and phosphorylation levels of protein kinase A(PKA)and cAMP response element-binding protein(CREB)were detected by Western blot.The expression of A1R in the CPu was detected by immunofluorescence staining.RESULTS:Compared with saline group,CFA modeling signifi-cantly lowered the thermal pain threshold of the rats(P<0.01).Compared with CFA group,the thermal pain threshold of the rats in CFA+MA group and CFA+CCPA group was significantly increased(P<0.05 or P<0.01).Compared with CFA+ MA+DMSO group,the thermal pain threshold of the rats in CFA+MA+DPCPX group was decreased(P<0.05).Compared with CFA group,A1R protein relative expression level and positive cells in the CPu of the rats in CFA+MA group were in-creased(P<0.05 or P<0.01).Compared with saline group,cAMP content and p-CREB protein level in the CPu of the rats in CFA+MA group were decreased(P<0.05).Compared with CFA+DMSO group,cAMP content and p-CREB pro-tein level in CFA+MA+DMSO and CFA+CCPA groups were significantly decreased(P<0.01).Compared with CFA+MA+ DMSO group,the levels of cAMP,p-PKA and p-CREB in CFA+MA+DPCPX group were significantly increased(P<0.05 or P<0.01).CONCLUSION:Acupuncture on bilateral Zusanli can relieve inflammatory pain in CFA rats,and its mech-anism may be related to A1R/cAMP/p-CREB signaling pathway.

ObjectiveTo investigate the effect of total glucosides of paeony （TGP） on neurotoxicity induced by aqueous extract of Strychni Semen （SA） in mice and to explore its mechanism. MethodThirty-two male KM mice were randomly divided into normal group，SA group （19.5 mg·kg^-1），TGP group （225 mg·kg^-1），and SA+TGP group （SA 19.5 mg·kg^-1+TGP 225 mg·kg^-1）. The open field test and beam walking test were used to observe the behavioral changes in mice. Pathological changes in the Nissl bodies of the cerebral cortex were assessed through Nissl staining. The levels of malondialdehyde （MDA），glutamate （Glu） in the mouse brain tissue，and serum levels of 5-hydroxytryptamine （5-HT） were detected using enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was employed to analyze gene expression profiles in the brain tissue. Common differentially expressed genes （DEGs） underwent gene ontology （GO） and kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. The mRNA expression levels of key targets were determined using quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group，the SA group exhibited significant increases in side-to-side distance and average speed in the open field test，as well as increased walking time on the balance beam. The axons of cortical neurons were absent，and the levels of Glu and MDA in the brain tissue were significantly elevated （P<0.05，P<0.01），along with a notable increase in serum 5-HT levels （P<0.05）. In contrast to the SA group，the SA+TGP group significantly reduced the side-to-side distance，average speed，and balance beam walking time （P<0.05 or P<0.01）. The neuronal axons were clearly visible，and levels of 5-HT，Glu，and MDA were decreased （P<0.05，P<0.01）. Transcriptome analysis indicated that TGP could regulate the glutamate receptor，ionotropic，N-methyl-D-aspartate 2a （GRIN2A）/phospholipase C β₁ （PLCB1）/protein kinase C，gamma （PRKCG） signaling pathway. Compared with the normal group，SA significantly decreased the expression of GRIN2A，PLCB1，and PRKCG genes in the mouse brain （P<0.01），while the mRNA levels of GRIN2A and PRKCG significantly increased after TGP administration （P<0.05，P<0.01）. ConclusionSA induces significant neurotoxicity in the mouse brain，and TGP significantly alleviates SA-induced neurological damage，potentially through the GRIN2A/PLCB1/PRKCG signaling pathway.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups： control （pure water） and Ruyi Zhenbaowan （1.8 g·kg^-1）. The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h， the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C₁₈ column （2.1 mm × 150 mm， 1.7 μm） with a mixture of 0.1% formic acid aqueous solution （A） and acetonitrile （B） as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min，97%~80%A；15~30 min ，80%~60%A；30~40 min，60%~30%A；40~45 min，30%~5%A. The ion source was electrospray ionization， and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan， and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid， respectively. In addition， the fragmentation rules of apigenin， apigenin-7-O-glucuronide， galangin， liquiritin， piperine， glycyrrhizic acid， eugenol， gallic acid， and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo， providing theoretical support for exploring active substances and performing quality control.l.

OBJECTIVE To systematically evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists(GLP-1RA) in the renal protection of type 2 diabetes(T2DM) patients, and provide evidence for clinic. METHODS Computer retrieval of PubMed, Embase, The Cochrane Library, Clinical Trials.gov, CNKI, WanFang Data and VIP databases, and manual retrieval of the included references. Randomized controlled trials(RCTs) for T2DM using GLP-1RA alone or GLP-1RA in combination with other conventional agents(experimental group) versus conventional treatment without GLP-1RA or placebo(control group). The search period spanned from the establishment of the database to January 30, 2022. Meta-analysis of the included data was performed using RevMan 5.4 statistical software. RESULTS A total of 7 studies were included, including 7 985 cases in experimental group and 6 633 cases in control group. Meta-analysis showed that the experimental group significantly reduced the incidence of renal complex endpoint events[Z=2.17, P=0.03, RR=0.79, 95%CI(0.64, 0.98)], urinary albumin creatinine ratio[Z=11.66, P<0.00001, MD=–23.74, 95%CI(–27.73, –19.74)], incidence of new macroalbuminuria[Z=5.79, P<0.000 01, MD=0.76, 95%CI(0.69, 0.83)], hemoglobin A1c[Z=12.76, P<0.000 01, MD=–0.94, 95%CI(–1.09, –0.80)] and estimated glomerular filtration rate[P=0.0007, Z=3.39, MD=–7.37, 95%CI(–11.63, –3.10)], the differences were statistically significant. One study showed that the experimental group could significantly reduce 24-hour urinary albumin excretion rate. However, there was no significant difference in the incidence of acute renal failure between the two groups[Z=0.63, P=0.53, MD=1.13, 95%CI(0.78, 1.63)]. In terms of safety, except the incidence of hypoglycemia, the incidence of adverse reactions in the experimental group was higher than that in the control group, including diarrhea, nausea, vomiting and loss of appetite, with statistically significant differences. CONCLUSION Existing research evidence shows that the common adverse reactions of GLP-1RA are gastrointestinal reactions and can be tolerated. Compared with placebo or conventional treatment without GLP-1RA, GLP-1RA may have a protective effect on the kidney of T2DM patients, and this conclusion needs to be further verified by RCTs.