ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

Background: Multiple perinatal factors influence hemodynamically significant patent ductus arteriosus (HS PDA) in preterm infants.Purpose: This study aimed to identify the risk factors associated with HS PDA in very low birth weight infants (VLBWIs) and determine the predictors of surgical ligation. Methods: This retrospective study included VLBWIs born at 23–32 weeks’ gestation whose HS PDA properties could be identified using echocardiography. The infants were stratified into 2 groups based on gestational age (23–27 and 28–32 weeks). Results: Among the 496 included VLBWIs, 171 had no PDA, 90 had non-HS PDA, and 235 had HS PDA. In infants born at 23–27 weeks’ gestation, risk factors for HS PDA included low birth weight, the absence of histological chorioamnionitis, and premature rupture of membranes. For VLBWIs born at 28–32 weeks’ gestation, HS PDA was associated with lower birth weight, frequent surfactant treatment, and maternal hypertension. Within the HS PDA group, infants with a lower birth weight or who received incomplete antenatal steroid administration had an increased likelihood of requiring surgical ligation, whereas those with a small-for-gestational-age status had a decreased need for surgical ligation. Conclusion Recognizing these risk factors can aid the development of targeted treatment strategies for HS PDA in VLBWIs, enabling early ligation and potentially reducing the need for surgical management.

ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

ObjectiveTo investigate the protective effect of magnolol ester derivative YW against cisplatin （Cis）-induced acute kidney injury （AKI） and to explore its effect and preliminary mechanisms on Cis-induced AKI. MethodsThe research group designed and synthesized the magnolol ester derivative YW using magnolol as the parent core. Molecular docking was employed to predict the binding interaction between YW and lysine acetyltransferase 7 （KAT7）. A Cis-induced AKI model was established in C57BL/6J mice. Mice were divided into the normal control group， model group， YW low/medium/high dose groups （17.5， 35， 70 mg/kg）， and the positive control amifostine group. Renal function was assessed by measuring serum creatinine （Scr） and blood urea nitrogen （BUN） levels. Pathological changes were evaluated via HE staining and scoring of kidney tissues. Protein expression levels of kidney injury molecule 1 （KIM-1）， lysine acetyltransferase 7 （KAT7）， and cyclin-dependent kinase inhibitor 1A （p21） in kidney tissues were detected by Western blot （WB）. HK-2 cells were treated with different concentrations of YW； cell viability was measured by CCK-8 assay. WB was used to detect the expression levels of the renal injury marker KIM-1， KAT7， and its downstream protein p21. Cellular senescence was assessed by senescence-associated β-galactosidase （SA-β-Gal） staining. ResultsYW could stably bind to KAT7. In vivo experiments showed that， compared with the model group， all YW dose groups， especially the medium and high doses， significantly reduced the elevated levels of Scr and BUN in AKI mice （P<0.001） and effectively ameliorated renal histopathological damage. YW significantly downregulated the protein expression levels of KIM-1， KAT7， and p21 in kidney tissues （P<0.05）. Concentrations of YW≤10 μmol/L had no significant effect on HK-2 cell viability. YW inhibited the Cis-induced decline in HK-2 cell viability （P<0.05）， suppressed the Cis-induced upregulation of KIM-1， KAT7， and p21 proteins （P<0.05）， and significantly decreased the percentage of SA-β-Gal-positive cells （P<0.01）. ConclusionYW suppresses the expression of KAT7 and p21 proteins and inhibits the decline in HK-2 cell viability in cisplatin-induced AKI， significantly mitigates HK-2 cell senescence， and improves renal function， providing preliminary experimental evidence for developing AKI treatment strategies based on structural optimization of natural products.

Introduction: Endogenous Cushing syndrome is a rare manifestation of chronic cortisol excess. It may present with severe hypercortisolism complicated by life-threatening opportunistic infections. Surgical management of a cortisol-secreting tumor is the mainstay of therapy. However, when the source is not found or when surgery is not feasible, medical therapies may be employed for rapid control of hypercortisolism. CASE: A 13-year-old male presented with breathlessness for one day. He also had a cough associated with weight loss, weakness, and hallucinations for 1 month. On presentation, he was tachypneic and had moon facies, acne, fine moustache, limb wasting, and pigmented nail beds. He was also hypertensive and developed an episode of seizure during admission. Investigation results showed severe hypokalemia and lymphopenia. Radiological examination revealed pneumothorax with multiple lung cavitations and brain tuberculomas. Bronchoalveolar lavage (BAL) was positive for Aspergillus fumigatus. However, both BAL and CSF PCR and culture for TB were negative. Serum ACTH was 379 pg/mL (0–46), and morning serum cortisol was 2,948 nmol/L with loss of diurnal rhythm. His 24-hour urine cortisol was 14,252 nmol/24 hour (31.7–282). This is consistent with ACTH-dependent Cushing syndrome. He was started on anti-TB and anti-fungal treatment. Serum cortisol levels were persistently high while on high-dose intravenous dexamethasone treatment for TB meningitis. An MRI pituitary and a CT scan thorax, abdomen, and pelvis could not reveal an ACTH-secreting tumor source. Metyrapone was started and titrated upwards to control the hypercortisolism. Serum cortisol reduced to 200–300 nmol/L after 1 month, and 24-hour urinary cortisol was down to 22.4 nmol/24 hour after 4 months, requiring weaning of metyrapone doses. Conclusion Metyrapone is effective in the rapid control of severe hypercortisolism with life-threatening complications, as illustrated in this case. However, it warrants careful monitoring and titration.
Child ; Cushing Syndrome

Objective To elucidate the application scope and delineate the criteria of dobutamine stress echocardiography (DSE) in assessing surgical risk associated with valvular heart diseases in patients presenting with reduced left ventricular ejection fraction (LVEF). Methods This retrospective analysis encompassed data from patients with reduced LVEF (LVEF<40%) who underwent DSE prior to valvular heart surgery at the Valvular Surgery Center of Beijing Anzhen Hospital between May 2016 and September 2024. Patients were stratified based on the terminal dose of dobutamine into two cohorts: a limited dose group [receiving a maximum dobutamine dose of <5 µg/(kg·min) due to concomitant conditions such as suspected atrial thrombus, aortic dilation, or previous myocardial infarction] and a non-limited dose group (where dosage was adjusted to either achieve the maximum positive standard or the maximal dose tolerable by the patient). Within the non-limited dose group, patients were further classified into positive and negative response groups. The positive response post DSE was defined based on the following criteria: LVEF≥55% (the maximum positive standard), LVEF<55% but with a 5% improvement (the minimum positive standard) from resting situation, aortic maximum velocity (AVmax)≥400 cm/s, or mean pressure gradient (meanPG)≥40 mm Hg, latter two applicable only to patients with aortic stenosis. Clinical indicators were compared in the three groups. Results A total of 99 patients were enrolled, aged 35 to 87 years, with an average age of (61.7±10.1) years. The number of males was significantly higher than that of females (3:1). There were 61 (61.6%) patients undergoing aortic valve surgery, 25 (25.3%) undergoing mitral valve surgery, and 13 (13.1%) undergoing combined aortic and mitral valve surgery. Nineteen (19.2%) patients experienced adverse symptoms such as palpitations, head and face numbness, dizziness, chest tightness post DSE. Additionally, new-onset or aggravated ventricular premature ventricular contractions were in 40 (40.4%) patients. All above symptoms and signs resolved minutes after cessation of the test. No severe adverse events necessitating oxygen therapy or emergency intervention occurred. Among the 93 patients in the non-limited dose group, 86 were classified in the positive response group and 7 in the negative response group. The left ventricular end diastolic diameter, left ventricular end systolic diameter, and LVEF in the positive group all showed significant improvement compared to preoperative values, and were also significantly better than those in the negative group (P<0.05). All 7 patients with negative DSE results underwent interventional surgery, which was significantly different from the positive group (36 patients, 41.9%). In the limited dose group (n=6), 4 patients with a positive result or a positive trend on DSE underwent median sternotomy, 2 received interventional treatment due to a negative response. No significant differences in mortality were observed among the groups (P>0.05). Conclusion Dobutamine stress echocardiography significantly contributes to risk stratification in surgical interventions for patients with valvular heart disease complicated by reduced LVEF. It aids in determining optimal timing and methods for surgery. With comprehensive patient evaluation and controlled dobutamine dosing, the application of DSE can be safely expanded.

Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of Aconitum carmichaelii was selected as the research object. Its ¹H-¹³C HSQC, ¹H-¹H COSY, HMBC, and NOESY spectra were acquired by US and NUS methods, respectively. By comparing the integral values of NMR signals of three chemical groups in fuziline, it is confirmed that the NUS technique has the advantages of improving the quality of 2D NMR spectra and shortening the acquisition time in structure elucidation of small molecule compounds. In HMBC spectrum, it was further confirmed that NUS technology can improve the quality of the 2D spectra and the signal resolution. This indicates that NUS technology can improve the efficiency and reliability of the structure elucidation of small molecule compounds.

Objective To analyze the effectiveness and safety of low molecular weight heparin(LMWH)combined with urokinase thrombolysis in the treatment of elderly patients with acute ischemic stroke(AIS).Methods A total of 132 elderly AIS patients admitted in Department of Neurology of Wuhan No.1 Hospital from January 2023 to September 2024 were recruited,and randomized into control group,group A,group B and group C,with 33 cases in each group.Besides urokinase thrombolysis as basic treatment,the patients in groups A,B and C were given LMWH within 24,24-47 and 48-72 h after thrombolysis,respectively.After 1 week of treatment,the incidence rate of cerebrovascular re-occlusion was compared among the four groups.Plasma prothrombin time(PT),platelet count(PLT),fibrinogen(Fib),nerve growth factor(NGF),neuron-specific enolase(NSE),neurotrophic factor(NTF)and National Institutes of Health Stroke Scale(NIHSS)score were compared before and after treatment and among the four groups.The incidences of adverse reactions were also compared among them during treatment.Results Compared with the levels before treatment,the levels of NGF and NTF were significantly increased,while the PT,PLT,Fib and NSE levels and NIHSS score were obviously decreased in the four groups after 1 week of treatment(P＜0.05).At 1 week of treatment,group A obtained notably higher NGF and NTF levels,and remarkably lower PT,PLT,Fib and NSE levels and NIHSS score than the other three groups(P＜0.05).So were group B when compared with group C and control groups(P＜0.05),and group C when compared with control group(P＜0.05).There was no statistical significance in the comparison of total incidence rate of adverse reactions during treatment among the four groups(P＞0.05).Conclusion LMWH combined with urokinase thrombolytic therapy can effectively improve the coagulation status and neurological function for elderly AIS patients,and the earlier it is applied,the better the efficacy will be.

Objective:To investigate the effects of remote ischemic preconditioning (RIPC) on myocardial injury after non-cardiac surgery (MINS) in elderly patients with hip fracture.Methods:A prospective randomized controlled trial was conducted on 78 elderly patients with hip fracture admitted to the Seventh Medical Center of the PLA General Hospital between October 2023 and September 2024. The patients were divided into RIPC group and non-RIPC group using a random number table. They were treated with closed reduction internal fixation, open reduction internal fixation, or hip arthroplasty for hip fracture under regional anesthesia. The RIPC group received RIPC intervention on the day before surgery and after entering the operating room on the day of surgery (3 cycles of 5-minute upper limb exsanguination followed by 5-minute reperfusion using an inflatable tourniquet cuff). The non-RIPC group received the same perioperative management as the RIPC group except RIPC. Plasma high-sensitivity cardiac troponin I (hs-cTnI) concentrations were measured at admission, immediately after surgery, on the morning of the first postoperative day, and on the morning of the third postoperative day and MINS incidence was calculated based on the hs-cTnI concentrations. The incidence of MINS within 3 days postoperatively and the intraoperative complications were compared in the overall cohort and in age-stratified groups (<80 years, ≥80 years). The local adverse reactions at the RIPC application sites were observed within 3 days after surgery.Results:Among the 78 elderly patients with hip fracture, including 21 males and 57 females, aged 60-99 years [79.5(70.0, 87.0)years], 40 were assigned to the RIPC group and 38 to the non-RIPC group. No significant difference was found in the general data of the two groups. There was no significant difference in the overall MINS incidence between the two groups ( P>0.05). In the patients aged <80 years, no MINS incidence was found (0/21) in the RIPC group, compared with 22% (4/18) in the non-RIPC group ( P<0.05), while in the patients aged ≥80 years, no significant difference in MINS incidence was observed between the two groups ( P>0.05). There were no significant differences in intraoperative complication rates in the overall cohort, patients aged <80 years, or patients aged ≥80 years ( P>0.05). None of the patients had local adverse reactions at the RIPC application sites. Conclusion:For elderly patients with hip fracture who received regional anesthesia, RIPC can significantly reduce the incidence of MINS in patients aged <80 years, but exerts no significant effect on MINS incidence in the overall cohort or in patients aged ≥80 years.

Objective:To explore the value of 18F-FDG PET brain glucose metabolism imaging in the subtype differential diagnosis and prognosis evaluation of autoimmune encephalitis (AE). Methods:A retrospective analysis was conducted on PET/CT brain glucose metabolism imaging data from 58 patients with AE (from August 2020 to June 2023, Xuanwu Hospital, Capital Medical University; 31 males, 27 females; age (47.4±16.9) years). Patients were divided into 4 groups: anti-leucine-rich glioma-inactivated protein 1(LGI1) antibody-related encephalitis group, anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis group, anti-γ-amino butyric acid type B receptor (GABA BR) antibody-related encephalitis group, and other types of AE group. In addition, 20 cases were included in control group (6 males and 14 females, age (58.8±7.5) years). Visual assessment was performed to evaluate changes in brain glucose metabolism among patients with different subtypes of AE, and abnormal glucose metabolism brain regions were compared by independent-sample t test between different groups. Spearman rank correlation analysis was conducted between SUV ratio (SUVR) of abnormal brain regions and modified Rankin Scale (mRS) scores at six months later. Results:Among 58 patients, 21 were diagnosed with anti-LGI1 antibody-related encephalitis, 18 were diagnosed with anti-NMDAR encephalitis, 7 were diagnosed with anti-GABA BR antibody-related encephalitis, and 12 were diagnosed with other subtypes of AE. Compared with anti-NMDAR encephalitis group: patients with anti-LGI1 antibody-related encephalitis showed increased glucose metabolism in the right occipital lobe and bilateral hippocampi, and decreased glucose metabolism in the right frontal lobe, right precentral gyrus, and bilateral superior marginal gyrus ( t values: from -5.13 to 4.89, all P<0.001); patients with anti-GABA BR antibody-related encephalitis exhibited increased glucose metabolism in the bilateral hippocampi and right fusiform gyrus, and decreased glucose metabolism in the left middle frontal gyrus ( t values: from -3.82 to 3.91, all P<0.001). Anti-NMDAR encephalitis was characterized by decreased metabolism in the bilateral parietal lobes, occipital lobes, local frontal-temporal lobes, and bilateral thalami, as well as increased metabolism in the limbic lobe and local frontal-temporal-parietal lobes ( t values: from -8.30 to 7.30, all P<0.001), and the SUVR of the right occipital lobe was negatively correlated with mRS score at six months later ( rs=-0.64, P=0.014). Other subtypes of AE showed decreased glucose metabolism in different cerebral lobes. Conclusion:18F-FDG PET/CT can evaluate brain glucose metabolism in different subtypes of AE diseases and prognosis.