Histone deacetylase 3 (HDAC3) is an epigenetic modification enzyme that plays a crucial role in the development and progression of diabetes and its complications. Studies have reported that increased HDAC3 activity is associated with pancreatic β-cell dysfunction in type 1 diabetes, while in type 2 diabetes, HDAC3 affects insulin resistance and signaling by regulating the metabolism of the liver, adipose tissue, and muscle. Additionally, HDAC3 plays a key role in diabetic complications such as cardiomyopathy, retinopathy, and nephropathy. Selective inhibition of HDAC3 has the potential to improve insulin sensitivity, reduce chronic inflammation, and enhance pancreatic cell function, offering a promising new therapeutic strategy for diabetes and its complications.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective To explore the effect of CircCSNK1G1 on the proliferation,apoptosis and migration of gastric cancer(GC)cells by regulating the miR-381-3p/S kinase-related protein 2(Skp2)axis.Methods HGC-27 cells were divided into non transfected group,si-NC group,si-CircCSNK1G1 group,si-CircCSNK1 G1+anti-miR-NC group,and si-CircCSNK1G1+anti-miR-381-3p group.The expressions of CircCSNK1G1,miR-381-3p and Skp2 mRNA in GC tumor tissues and GC cell lines were detected by qRT-PCR respectively;cell proliferation was detected by MTT assay;the number of cell clones was detected by clonogenic assay;apoptosis was detected by flow cytometry;cell migration and invasion ability were determined by transwell;the expression of E-cadherin and Vimentin was detected by Western Blot;and the targeting relationship among CircCSNK1G1,miR-381-3p and Skp2 was verified by double luciferase experiment.Results Compared with GES-1 in normal tissues adjacent to cancer and normal human gastric mucosal epithelial cells,the expression of CircCSNK1 G1 and Skp2 mRNA in GC tumor tissues and GC cell lines is high,and the expression of miR-381-3p is low(P＜0.05),and the expression level of miR-381-3p in HGC-27 cells is the lowest,and the expression level of CircCSNK1G1 and Skp2 mRNA is the highest,therefore,HGC-27 cells were selected and CircCSNK1G1 was knocked down for the experiment.Compared with untransfected group and si-CircCSNK1G1-NC group,transfection of si-CircCSNK1G1 could reduce the expression of CircCSNK1G1,Skp2 mRNA,cell proliferation activity,cell migration number,and the expression of Vimentin protein in HGC-27 cells(P＜0.05),the expression of miR-381-3p,apoptosis rate,and the expression of E-cadherin protein were increased(P＜0.05).The double luciferase experiment verified that CircCSNK1G1 and Skp2 had a targeting relationship with miR-381-3p,moreover,CircCSNK1G1 could be used as sponge RNA of miR-381-3p to further regulate the expression and activity of Skp2.Conclusion Knockdown of CircCSNK1G1 can target up-regulate the expression of miR-381-3p,and inhibit the expression of Skp2,thus promoting the apoptosis of GC cells,and inhibiting their proliferation and migration.

Objective To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome(NRDS)using invasive respiratory support.Methods A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital,involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS.The infants were randomly divided into a supine group(37 infants)and a prone group(40 infants).Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position,continuing in this cycle until weaning from the ventilator.The effectiveness and safety of the two approaches were compared.Results At 6 hours after enrollment,the prone group showed lower arterial blood carbon dioxide levels,inspired oxygen concentration,oxygenation index,rates of tracheal intubation bacterial colonization,and Neonatal Pain,Agitation and Sedation Scale scores compared to the supine group(P<0.05).There were no significant differences between the groups in terms of pH,arterial oxygen pressure,positive end-expiratory pressure,duration of mechanical ventilation,accidental extubation,ventilator-associated pneumonia,air leak syndrome,skin pressure sores,feeding intolerance,and grades II-IV intraventricular hemorrhage(P>0.05).Conclusions Compared to supine positioning,prone ventilation effectively improves oxygenation,increases comfort,and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS,without significantly increasing adverse reactions.

Objective To compare image quality of 5.0T and 3.0T non-contrast MRI for displaying insulinoma.Methods Twelve patients with insulinoma were prospectively enrolled,and non-contrast abdominal T1WI,T2WI as well as diffusion-weighted imaging(DWI)were acquired using 5.0T and 3.0T MR scanners,respectively.The subjective scores of image quality of each sequence of 5.0T and 3.0T MRI,also of tumor-pancreas parenchyma contrast scores were compared.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of insulinomas were observed,and the displayed rate of insulinoma by each sequence and overall MRI were compared.Results The subjective scores of 5.0T T1WI and DWI were higher than those of 3.0T T1WI and DWI(both P＜0.05),but not significantly different between 5.0T and 3.0T T2WI(P=0.166).Furthermore,the tumor-pancreas parenchyma contrast score of 5.0T T1WI was higher than that of 3.0T T1WI(P=0.023),but not significantly different between 5.0T and 3.0T T2WI,nor between 5.0T and 3.0T DWI(both P＞0.05).SNR of insulinomas on 5.0T T2WI were higher than on 3.0T T2WI(P=0.015),however,no significant difference of SNR was found between 5.0T and 3.0T T1WI,nor between 5.0T and 3.0T DWI(both P＞0.05).CNR of insulinomas on all 5.0T MRI were not significantly different with those on 3.0T MRI(all P＞0.05).The displayed rate of insulinoma on 5.0T T1WI,T2WI and DWI was 100％(12/12),66.67％(8/12)and 83.33％(10/12),respectively,on 3.0TT1WI,T2WI and DWI was 75.00％(9/12),58.33％(7/12),66.67％(8/12),respectively.The overall displayed rate of insulinoma on 5.0T and 3.0T MRI was 100％(12/12)and 83.33％(10/12),respectively.Conclusion Compared with 3.0T MRI,5.0T MRI was superior for displaying insulinoma,hence being helpful for diagnosis.

OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

OBJECTIVE To investigate the effect of pachymic acid （PA） on renal function and fibrosis in chronic renal failure （CRF） rats and its potential mechanism based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. METHODS Using male SD rats as subjects， the CRF model was established by 5/6 nephrectomy； the successfully modeled rats were divided into model group， PA low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg PA）， high-dose PA+ROCK pathway activator lysophosphatidic acid （LPA） group （20 mg/kg PA+1 mg/kg LPA）， with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein， once a day， for 12 consecutive weeks. During the experiment， the general condition of rats was observed in each group. After the last administration， the serum renal function indexes （blood urea nitrogen， serum creatinine， uric acid） of rats in each group were detected， the renal histopathological changes were observed； the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] and inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6）， the positive expression rates of connective tissue growth factor （CTGF） and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins （RhoA， ROCK1） and fibrosis- related proteins （transforming growth factor-β1， bare corneum homologs 2， α-smooth muscle actin） were determined. RESULTS Compared with the sham operation group， the rats in model group had reduced diet， smaller body size， listless spirit and sluggish response， reduced and atrophied glomeruli， dilated renal tubules with chaotic structure， and a large number of inflammatory cells infiltrated interstitium； the serum levels of renal function indexes， renal tubule injury score， renal fibrosis area proportion， the levels of MDA and inflammatory factors， the positive expression rates of CTGF and collagen Ⅰ， and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased， while SOD level was significantly decreased （P＜0.05）. Compared with the model group， the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees，and the above quantitative indexes were significantly improved in a dose-dependent manner （P＜0.05）. LPA could significantly reverse the improvement effect of PA on the above indicators （P＜0.05）. CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats， which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.

italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of Salvia miltiorrhiza, have been a hot topic of research. The paper summarized the research findings on the regulation of tanshinone biosynthesis by transcription factors such as AP2/ERF, bHLH, MYB, bZIP, and WRKY in recent years. The review identifies the existing issues in the transcriptional regulation studies of Salvia miltiorrhiza and discusses the research direction of transcription factors in the regulation of tanshinone biosynthesis, providing a theoretical basis for the further discovery and utilization of functional genes involved in the regulation of tanshinone bioactive constituents.