Heart failure with preserved ejection fraction (HFpEF) exhibits an inflammatory‐metabolic phenotype in association with multiple factors. Among them, epicardial adipose tissue (EAT), a type of visceral adipose tissue surrounding the heart, has been gaining attention. EAT expansion is associated with the development of HFpEF, the increased risk for heart failure–related mortality in patients with HFpEF, independent of age, body mass index, diabetes, and sex. Thus, reducing EAT expansion has been proposed as a promising therapeutic strategy for treating HFpEF. Although specific treatment for EAT expansion is unavailable, modulating the inflammatory response and systemic energy metabolism are beneficial in improving clinical symptoms or prognosis in patients with HFpEF. To further enhance our capacity in effectively treating HFpEF, this review discusses the knowledge gaps between EAT expansion and the lack of a platform to reduce EAT expansion in HFpEF, including the choices of appropriate animal models, the conceptual mechanisms of glucose and lipid metabolism in EAT expansion toward potential strategies for selective EAT‐targeted therapeutic avenues.

While the cardioprotective role of heat shock proteins (HSPs) in cardiovascular diseases is well established, the isoform-specific functions of HSP70 members in ischemia-reperfusion (I/R) injury remain unclear. This study investigates the role of Hspa1b, a stress-inducible HSP70 isoform, in cardiac I/R injury and elucidates its underlying mechanisms. In vivo, male C57BL/6 J mice were subjected to myocardial I/R surgery. In vitro, H9C2 cardiomyocytes were transfected with siRNA targeting Hspa1b or p53 and subjected to a hypoxia/reoxygenation (H/R) model. Cellular injury was quantified via lactate dehydrogenase (LDH) release, while viability was assessed using the CCK-8 assay. Apoptotic (Bax, Bcl2, and cleaved Caspase3) and ferroptotic (GPX4, XCT/SLC7A11) markers were analyzed by Western blotting. We found that I/R injury in mouse hearts upregulated Hspa1b and p53 protein levels, accompanied by increased infarct size and elevated plasma CK-MB levels. Similarly, H/R treatment in H9C2 cells increased Hspa1b and p53, which coincided with increased apoptosis and ferroptosis. Knockdown of Hspa1b exacerbated H/R-induced cellular injury, as evidenced by further increases in LDH release and reductions in cell viability, and amplified the changes in apoptotic and ferroptotic markers. Crucially, co-silencing Hspa1b and p53 partially rescued these effects, restoring cell viability and suppressing death pathways. Hspa1b confers cardioprotection against H/R injury by suppressing p53-mediated apoptosis and ferroptosis. These findings identify Hspa1b as a key protective regulator that mitigates I/R injury through dual regulation of cell death pathways.

Ethnopharmacological relevance In traditional Chinese medicine (TCM) theory, both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease (MAFLD) are commonly associated with the syndrome of “qi stagnation and blood stasis,” which manifests as cardiac dysfunction and hepatic metabolic disturbance, respectively. Taohong Siwu decoction (THSWD), a classic TCM formula documented in Yi Zong Jin Jian for promoting blood circulation and resolving stasis, is therefore a rational candidate to address this shared pathological basis. While THSWD’s separate benefits for heart and liver have been reported, its potential to treat the interconnected pathology of HFpEF-associated MAFLD remains unexplored. Aim of the study This study aimed to investigate THSWD's therapeutic potential against HFpEF-associated MAFLD and its molecular mechanisms. Materials and Methods A two-hit HFpEF model was established in female mice. Hepatic lipid accumulation was evaluated by measuring triglyceride content, along with Oil Red O and H&E staining. THSWD constituents were identified by UPLC-Q-ToF/MS, and molecular targets were predicted through network pharmacology integrated with RNA-seq of liver tissues, then validated by qPCR and Western blotting. An in vitro steatotic HepG2 model further evaluated the effects of THSWD on lipid accumulation. Results THSWD significantly reduced hepatic lipid accumulation in HFpEF mice. UPLC-Q-ToF/MS identified 51 compounds in THSWD. Network pharmacology suggested these compounds target multiple lipid metabolism genes, particularly via the AMPK pathway. RNA-seq confirmed downregulation of key lipogenic SREBP1-regulated lipogenic genes (Acaca, Fasn, Scd1), validated by qPCR and Western blotting. In steatotic HepG2 cells, THSWD reduced lipid accumulation via AMPK/SREBP1 signaling, as this effect was abolished by either AMPK selective inhibitor or AMPKα1/α2 siRNA knockdown. Furthermore, when SREBP1 knockdown was combined with THSWD treatment, no additive effect on lipid reduction was observed compared to THSWD alone, indicating that SREBP1 mediates the lipid-lowering action of THSWD as a key downstream effector. Conclusion This study provides the first evidence that THSWD alleviates HFpEF-associated MAFLD by suppressing lipid biosynthesis through AMPK/SREBP1 signaling, highlighting its potential as a therapeutic strategy for hepatic steatosis in HFpEF.

Stroke poses a significant public health challenge, especially in China, where geographical disparities in incidence rates suggest environmental, genetic, and lifestyle influences on stroke risk. Traditional diagnostic methods, while effective, have limitations that can hinder timely treatment. This study investigated the clinical significance and diagnostic utility of the biomarkers C-reactive protein (CRP), osteopontin (OPN), osteoprotegerin (OPG), and lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) in relation to atherosclerosis and stroke, aiming to enhance early diagnosis and treatment strategies. In this retrospective analysis of 156 patients with arterial stenosis leading to ischemic stroke, data on medical history, lifestyle, serum markers, and comorbidities were collected. Carotid artery stenosis was evaluated using Doppler ultrasound, and the plaque stability and stenosis degree were categorized for analysis. Biomarker levels were measured and analyzed using binary logistic regression and support vector machine optimization models to explore their correlation with stroke. Our findings indicate nuanced roles for CRP, OPN, OPG, and LOX1 in stroke risk, with CRP and OPG acting as protective factors against carotid artery occlusion, and OPN and LOX1 presenting as risk factors. This study underscores the complexity of atherosclerosis and highlights potential therapeutic targets. By elucidating the associations of these biomarkers with atherosclerosis leading to stroke, this study contributes to a better understanding of stroke etiology and opens avenues for the development of more effective diagnostic tools and treatment protocols. Further research, including longitudinal studies and clinical trials, is essential to confirm these findings and to explore their therapeutic implications.

BACKGROUND Postoperative delirium affects recovery. Dexmedetomidine shows promise in reducing it, but the ideal dose is unclear. MATERIAL AND METHODS We performed a systematic review of randomized controlled trials and meta-analyses. Studies from PubMed, Embase, Web of Science, and the Cochrane Library were retrieved. Only trials involving adults (≥18 years) were considered. The effectiveness of high (loading dose, >0.5 µg/kg) and low doses (loading dose, ≤0.5 µg/kg) of dexmedetomidine in preventing delirium was examined, along with the incidence of delirium and adverse events like hypotension and bradycardia. RESULTS High-dose dexmedetomidine was associated with a lower delirium incidence compared to low-dose. The incidence of bradycardia or hypotension did not differ significantly between the 2 groups. However, some included studies had small sample sizes, focused on intraoperative use, or had potential data bias and heterogeneity in the low-dose group. CONCLUSIONS High-dose dexmedetomidine may be more effective in reducing postoperative delirium without increasing the risk of bradycardia or hypotension. But due to study limitations, more randomized controlled trials are required to confirm these findings.

Acute coronary syndromes, such as myocardial infarction (MI), lack effective therapies beyond heart transplantation, which is often hindered by donor scarcity and postoperative complications. Human induced pluripotent stem cells (hiPSCs) offer the possibility of myocardial regeneration by differentiating into cardiomyocytes. However, hiPSC-derived cardiomyocytes (hiPSC-cardiomyocytes) exhibit fetal-like calcium flux and energy metabolism, which inhibits their engraftment. Several strategies have been explored to improve the therapeutic efficacy of hiPSC-cardiomyocytes, such as selectively enhancing energy substrate utilization and improving the transplantation environment. In this review, we have discussed the impact of altered mitochondrial biogenesis and metabolic switching on the maturation of hiPSC-cardiomyocytes. Additionally, we have discussed the limitations inherent in current methodologies for assessing metabolism in hiPSC-cardiomyocytes, and the challenges in achieving sufficient metabolic flexibility akin to that in the healthy adult heart.

Neural tube defects (NTDs) constitute the second most common congenital malformation of the central nervous system. The pathogenesis of NTDs is not entirely clear. In recent years, microRNAs have become a hot spot in genetic and developmental biology research. The present study aimed to explore the potential role of microRNA (miRNA)-26a in NTDs and the underlying pathogenesis thereof. First, we found significantly increased miRNA-26a expression in fetuses with NTDs (p<0.0001), which significantly downregulated EphA2 and ERK1 mRNA and protein expression levels in fetuses with NTDs compared to normal controls (p<0.01). In addition, dual-luciferase reporter assay showed that miR-26a negatively regulated EphA2 by directly binding with the 3'-untranslated region of EphA2. Second, upregulation of miRNA-26a expression increased caspase 3 and 9 protein expression levels (p<0.01); and decreased EphA2 mRNA and protein expression levels (p<0.01), as well as ERK1 and SRF protein expression levels (p<0.01) in mouse neural stem cells (NE-4C) and human astroblastoma cells (U87MG). Furthermore, the upregulation of miRNA-26a inhibited cell proliferation and enhanced apoptosis of NE-4C and U87MG cells (p<0.05). Similar results were observed with the MAPK inhibitor PD98059 (p<0.01). These results suggest that miR-26a downregulates EphA2 to regulate SRF through the MAPK pathway, which affects nervous system development miR-26a targets EphA2, modulates phosphorylation of MAPK/ERK(MEK) pathway, regulates SRF, and participates in regulating nervous cell proliferation and apoptosis. Dysregulation of the aforementioned mechanism may be involved in the pathogenesis of NTDs.

Objective:To explore the risk factors of donor for a recovery of graft function during perioperative period of living relative donor kidney transplantation.Methods:Retrospective reviews were performed for the relevant clinical data of 327 donors and recipients of living related kidney transplantation from January 2010 to December 2018. The donor risk factors were compared.Results:No significant differences existed in operative duration, intraoperative blood loss, warm ischemic time, postoperative lymph leakage percentage or perioperative graft function between different donor nephrectomic groups ( P>0.05). However, operative duration of left donor nephrectomy was shorter than that of right donor nephrectomy and the difference was statistically significant ( P=0.008). Vascular anatomic abnormality had no effect on perioperative graft function ( P>0.05). And donor age, donor glomerular filtration rate (GFR) and difference between donor body mass index (BMI) and recipient BMI had correlations with perioperative graft function ( P=0.006, 0.002, <0.001). After multivariate analysis, donor GFR and difference between donor BMI and recipient BMI were correlated with perioperative graft function ( P=0.007, <0.001). Conclusions:Donor GFR and difference between donor BMI and recipient BMI are independent risk factors for perioperative graft function.

Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the somatosensory nervous system. The burden of diabetic neuropathy is related not only to the complexity of diabetes but also to the poor outcomes and difficult treatment options. There is no specific treatment for diabetic neuropathy other than glycemic control and diligent foot care. Although various metabolic pathways are impaired in diabetic neuropathy, enhanced cellular oxidative stress is proposed as a common initiator. A mechanism-based treatment of diabetic neuropathy is challenging; a better understanding of the pathophysiology of diabetic neuropathy will help to develop strategies for the new and correct diagnostic procedures and personalized interventions. Thus, we review the current knowledge of the pathophysiology in diabetic neuropathy. We focus on discussing how the defects in metabolic and vascular pathways converge to enhance oxidative stress and how they produce the onset and progression of nerve injury present in diabetic neuropathy. We discuss if the mechanisms underlying neuropathy are similarly operated in type I and type II diabetes and the progression of antioxidants in treating diabetic neuropathy.

Objective To compare the effects of single subcutaneous injection of long-acting ropivacaine injection with ropivacaine hydrochloride on local skin wound healing.Methods Bama miniature pig 12, male and femaleeach half.After routine disinfection, each pig cut 5wounds on the back, about 2cm×2cm in size, numbered 1-5.Randomly divided into 0.3％long-acting ropivacaine injection (R1), 0.5％long-acting ropivacaine injection (R2), 0.3％ropiva-caine injection(R3), 0.5％ropivacaine injection Liquid(R4), without any treatment(R5).Take the wound and its sur-rounding skin and subcutaneous tissue into 10％neutral buffered formalin solution for fixed, routine paraffin embed-ding, slicing and HE staining.Microscopy Histopathology examination.Results There was no significant difference be-tween the two groups at R1and R3, R2and R4in the incision area on the 7th and 14th days(P＞0.05), and the differ-ence between the two groups was statistically significant(P＜0.05).The results of pathological examination showed that wound granulation tissue proliferation was more obvious, the number of blood vessels increased, epidermal cells appeared earlier and wound healing time was shortened.Similarly, on the 7th and 14th days, histopathological score(P＞0.05 ).There was difference in histopathological score between group R5and group R5 (P＜0.05).Conclusion Long-term ropivacaine injection can promote the healing of wounds in single subcutaneous injection of wound infiltration anesthesia.And ropivacaine hydrochlo-ride injection contrast, the two on the local skin wound healing no significant difference.

Objective: To investigate the effects of vitamin B12 adjuvant therapy on neural recovery after replantation of severed fingers. Methods: We retrospectively analyzed 227 patients admitted to our hospital for replantation of severed fingers. We performed the following tests on all patients 8 weeks after treatment: Return of finger pulp pressure sensation (25 g), touch sensation (4 g), pain sensation (4 g), and discrimination sensation (>5 mm). Results: A week after treatment, 7.6%, 15.1%, 32.8% and 44.5% of patients from the test group showed excellent, good, fair, and poor recovery, respectively. In contrast, 0.9%, 6.5%, 16.7% and 75.0% of patients from the control group showed excellent, good, fair, and poor recovery, respectively, (P<0.05). Three weeks after treatment, 18.5% of patients in the test vs. 8.3% of patients in the control group showed excellent recovery (P<0.05). Five weeks after treatment, 71.4% of patients in the test vs. 44.4% of patients in the control group showed excellent or good recovery (P<0.05). Eight weeks after treatment, neurological testing showed that in comparison of the test and the control group, return of pressure sensation was observed in 80.7% vs. 48.1% of patients, respectively; return of touch sensation was observed in 70.6% vs. 39.8% of patients, respectively; and return of pain sensation in 60.5% vs. 39.8% of patients, respectively. Conclusions: Vitamin B12 adjuvant therapy effectively improved the recovery of neurological function in fingers after replantation of severed fingers and should be promoted in clinical practice.

Diabetic retinopathy (DR) is a retinal disease in patients with diabetes caused by metabolic disorders of glucose, and often leads to irreversible blindness if not treated properly. Dysfunction of retinal endothelial cells (RECs) contributes to the pathogenesis of DR. In the present study we investigated the apoptotic effect of high glucose concentration. High glucose was used to induce cell injury. LDH assay kit was used to detect the leakage of LDH. Western blot was used to detect the expression of bax, cleaved-caspase-3, bcl-2 and p53 proteins. The transmission electron microscope was used to observe apoptotic morphological changes. In the present study, we found that the LDH leakage ratio was significant increased after exposing to 30 mmol/L glucose for 12 h, and both showed a concentration-department manner and time dependent fashion. Next, obvious apoptotic morphological changes were observed after treating the cells with glucose at 30 mmol/L. Further research indicated that the protein levels of p53, pro-apoptotic cleaved-caspase-3, and bax were significantly upregulated, and the level of bcl-2 was decreased after treating with glucose at 30 mmol/L. The protein levels of bax and cl-caspase-3 were significantly decreased and the expression of bcl-2 was increased after pretreated with p53 specific inhibitor pifithrin-α. In conclusion, high glucose concentration induces apoptosis in retinal endothelial cells by activating p53 signaling pathway.

Nitric oxide synthases (NOSs) are a family of enzymes that are responsible for the synthesis of nitric oxide (NO) from the amino acid L-arginine in the body. Among the three key NOSs, the expression of inducible NOS (iNOS) can only be induced by inflammatory stimuli and contribute to the large amount of NO production. iNOS-derived NO plays an important role in various physiological and pathophysiological conditions, including the ischemic heart disease. Nowadays, the development of specific iNOS inhibitors and the availability of iNOS knockout mice have provided substantial evidence to support the role of iNOS/NO signaling in the myocardium. Nevertheless, the role of iNOS/NO signaling in the myocardial ischemic reperfusion injury is very complex and highly perplexing; both detrimental and beneficial effects of iNOS have been described. Thus, this review will aim at providing basic insights into the current progress of the role of iNOS in myocardial ischemia reperfusion injury. A better understanding of the dual role of iNOS in details may help facilitate the development of more effective therapies for the management of ischemic heart diseases.

Accumulating evidence has indicated that aberrant expression of long non-coding RNAs (lncRNAs) is an important oncogenic factor. The aim of the present study was to investigate the role of LINC01296, an lncRNA that exerts a tumor-promoting function in many cancers, in the regulation of proliferation, metastasis and the cell cycle of osteosarcoma. The expression of LINC01296 in osteosarcoma tissues and adjacent healthy tissues of 30 patients was analyzed by quantitative real-time PCR (qRT-PCR). The relationship between LINC01296 expression and the survival of patients with osteosarcoma was also explored. The expression levels of LINC01296 in osteosarcoma cells and normal cells were compared. LINC01296 knockdown and overexpression were performed in MG63 and HOS8603 osteosarcoma cells by transfecting LINC01296 shRNA and an expression plasmid respectively, followed by investigation of the changes on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was used to analyze the changes of cell cycle regulators. Cyclin D1 knockdown and overexpression were carried out to verify the interaction between LINC01296 and cyclin D1. LINC01296 overexpression was demonstrated as a biomarker of osteosarcoma, which was closely correlated with the poor survival of patients with osteosarcoma. A high expression of LINC01296 was observed in osteosarcoma cells, which was closely associated with enhanced proliferation, invasion, and migration of osteosarcoma cells. Cyclin D1 expression was positively correlated with the expression of LINC01296 in osteosarcoma cells. Cyclin D1 knockdown or overexpression played a deterministic role in mediating the effect of LINC01296 on osteosarcoma cells. LINC01296 is an oncogenic lncRNA in osteosarcoma. The proliferation, invasion and migration of osteosarcoma cells could be effectively retarded by inhibition of LINC01296. The cancer-promoting effect of LINC01296 on osteosarcoma was determined by cyclin D1.

Objective To investigate the levels of estrogen,progesterone,follicle-stimulating hormone (FSH),and luteinizing hormone (LH) in serum and the expression of ER,PR,FSH receptor (FSHR),and LH receptor (LHR) in thyroid tissues of patients with different types of thyroid nodules.Methods Serum levels of estrogen,progesterone,FSH,and LH were measured by chemiluminescence and expression of ER,PR,FSHR,and LHR in thyroid tissue was detected by immunohistochemistry in female patients with thyroid adenoma (n＝97),nodular goiter (n＝103),thyroid papillary cancer (n＝208),poorly differentiated thyroid carcinoma (n＝17),or undifferentiated thyroid carcinoma (n＝10) and in normal controls (n＝60) from Dec.2009 to Dec.2014 in Department of Thyroid Surgery of the First Hospital of Jilin University.Results The positive rates of serum estrogen level and ER expression were significantly greater in patients with various types of thyroid nodules than in normal controls.The positive rates of ER expression were significantly lower in various types of thyroid nodules than in normal thyroid tissues,especially in poorly differentiated carcinoma and undifferentiated carcinoma.The negative rates of serum progesterone level and positive rates of PR expression in thyroid tissue were significantly greater in patients with thyroid adenoma,nodular goiter,or thyroid papillary cancer than in normal controls.The positive rates of serum FSH and LH levels and FSHR and LHR expression were significantly greater in the thyroid adenoma group than in other groups.Conclusions The occurance of thyroid nodules might be related to sex hormone.The combined detection of serum levels of sex hormones and expression of their receptors allows for a differential diagnosis and evaluation of the degree of differentiation among various types of thyroid nodules.

OBJECTIVE:To evaluate the effects of mistletoe alkali on human Osteosarcoma cells (U2OS) in vitro. SUMMARY OF BACKGROUND DATA:Osteosarcoma is the most common primary malignant tumor of bone tumor, although there are a lot of therapies such as surgery, radiotherapy and chemotherapy, its prognosis is still very poor. There is increasing interest in the protective biological function of natural antioxidants contained in Chinese medicinal herbs, which are candidates for the prevention of tumors. Mistletoe alkali is one of the compounds extracted from Viscum coloratum (Komar.) Nakai, one kind of mistletoe, whose extracts contribute to the improvement of the prognosis of patients with malignancies. METHODS:The effect of mistletoe alkali on the growth of U2OS cells was compared with 5-FU, using a Cell Counting Kit-8 (CCK-8). The influence of mistletoe alkali on U2OS's proliferation and apoptosis were tested by TUNEL staining and immunocytochemical (ICC) staining of caspase 3 and proliferating cell nuclear antigen (PCNA). Additionally, the invasion ability of U2OS cells was detected using a Boyden chamber trans-well migration assay. RESULTS:CCK-8 assays gave an IC50 of 7μg/ml for mistletoe alkali. Compared to 5-FU, mistletoe alkali inhibited U2OS proliferation and induced apoptosis more effectively. The invasion ability of U2OS was also weaker in mistletoe alkali than in 5-FU. CONCLUSIONS:Mistletoe alkali significantly inhibited growth and invasion abilities of U2OS cells and induced their apoptosis in vitro. Mistletoe alkali may be a more effective drug for Human Osteosarcoma than the standard chemotherapeutic drug 5-FU.

革兰阴性菌感染常可引起脓毒病综合征伴休克,感染灶中的微生物及其毒素等侵入血循环,影响机体各器官系统灌注。感染性休克患者,尤其是老年人,循环及体温调节能力明显下降,术前低代谢状态导致能量分解产热降低,极易发生组织细胞缺血缺氧、代谢紊乱、功能障碍,甚至多器官功能衰竭[1]。除积极控制感染外,应针对休克的病理生理给予补充血容量、纠正酸中毒,这些对于维护重要脏器的功能至关重要。晶体液是围术期液体治疗常见的类

手术创伤所致的疼痛和炎性反应可使机体产生不良反应,多途径平衡镇痛和规范化超前镇痛得到越来越多的重视。羟考酮是阿片类受体激动剂,其镇痛作用注射给药和吗啡等效或较强,副作用少于吗啡,对内脏痛效果明显[1],国内外已广泛用于术后镇痛和癌性镇痛治疗。盐酸羟考酮注射液用于超前镇痛的报道较少。本研究观察盐酸羟考酮注射液超前镇痛对经腹全子宫切除术后的患者静脉自控镇痛