ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

Objective To analyze the clinical features of chronic obstructive pulmonary disease (COPD) patients with heart failure (HF) in Nanjing and explore the influencing factors. Methods A total of 773 COPD inpatients were selected from January 2021 to January 2024 in Nanjing Combined Hospital of Traditional Chinese and Western Medicine, Nanjing Qixia District Hospital, Nanjing Lishui District People's Hospital, Nanjing Pukou District Hospital of Traditional Chinese Medicine and Nanjing First Hospital., and were divided into 2 groups according to the presence or absence of combined HF. The general data and medical records of the two groups were compared, the clinical characteristics of COPD patients with HF were summarized, and the influencing factors of COPD patients with HF were analyzed by multivariate logistic regression. Results Among the 242 patients (31.31%) with COPD had HF, chronic paroxysmal dyspnea was the most common first symptom, 169 patients (69.83%) had left heart failure, 63 patients (30.17%) were diagnosed as right heart failure or global heart failure , 17 patients (7.02%) had myocardial infarction. Multivariate logistic regression analysis showed that the risk of HF was 1.678 times and 1.691times higher in COPD groups ≥ 50 years old and male COPD groups than in < 50 years old and female groups, respectively; the risk of HF was 1.491 times higher in COPD groups engaged in physical work than in physical work groups; the risk of HF was 1.447 times and 1.580 times higher in COPD groups with hypertension and coronary heart disease than in COPD groups without hypertension and coronary heart disease, respectively; the risk of HF was 1.859 times higher in COPD groups smoking>400 vial/year than in COPD groups≤400 vial/ year; the risk of HF was 1.757 times higher in COPD groups with acute exacerbation frequency≥2 times/year than in COPD groups<2 times/year; the above differences were statistically significant (P<0.05). Conclusion Attention should be paid to elderly, male and heavy physical work group of COPD patients. Active treatment of hypertension and coronary heart disease, effective tobacco control and reduction of the frequency of acute exacerbation are effective ways to reduce the risk of HF in COPD patients in Nanjing.

OBJECTIVE To promote the application of drones in emergency rescue and related fields， expand “low-altitude+ medical” rescue services， and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones （2025 Edition） （hereinafter referred to as the Consensus） was jointly initiated by the Division of Therapeutic Drug Monitoring， Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit， organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline， resulting in a preliminary draft. Delphi method was employed， and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated， the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose， principles， and applicable scenarios， basic requirements， and operational procedures for low-altitude transport and delivery of emergency medications； distribution requirements and precautions for controlled substances， fragile medications， and temperature-sensitive medications； and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.

OBJECTIVE To investigate the efficacy and safety of the interleukin-1 （IL-1） receptor antagonist anakinra in the treatment of refractory adult onset Still’s disease （AOSD）， and provide more real-world evidence and practical experience for the treatment of AOSD with this drug. METHODS A retrospective analysis was conducted on the diagnosis and treatment process of a patient with AOSD complicated with dermatomyositis who received anakinra； systematically searched for relevant literature on the treatment of AOSD with anakinra in Chinese and English databases such as CNKI， PubMed， Medline， etc.， and conduct literature review on its efficacy and safety. RESULTS The patient in this case had poor treatment with multiple traditional drugs and was considered to have AOSD combined with dermatomyositis. After being admitted to the hospital and treated with a combination therapy of anakinra and glucocorticoids for several days， the patient’s clinical symptoms and inflammatory indicators significantly improved， and no serious adverse drug reactions occurred. Pharmacists designed specialized pharmaceutical monitoring pathways and conduct regular follow-up after discharge. After discharge， the patient took medication regularly， and the condition was maintained and relieved； during this period， there was redness and swelling at the injection site which resolved on its own without any other obvious discomfort. Literature review showed that anakinra could increase the response rate and remission rate of AOSD patients， and significantly reduce the dosage of glucocorticoids； adverse events were mainly injection site reactions， with a low overall risk of infection and good safety； however， there was a significant difference in the treatment course， and there was currently no unified plan. CONCLUSIONS Anakinra is an efficient and safe biological agent for treating AOSD， which can rapidly induce and maintain disease remission. For AOSD patients， clinical consideration may be given to using IL-1 antagonists to reduce glucocorticoid dependence， while strengthening long-term medication monitoring.

Objective To explore the application value of ultrasound-guided use of bupivacaine for subarachnoid block in hip replacement surgery for elderly femoral neck fractures.Methods A total of 108 elderly patients who underwent hip replacement surgery at Ganzhou Traditional Chinese Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into conventional anesthesia group and ultrasound guided anesthesia group by means of random number table,54 cases in each group.Patients in the conventional anesthesia group received routine general anesthesia;Patients in the ultrasound guided anesthesia group received unilateral lumbar anesthesia with bupivacaine under ultrasound-guided guidance.Compare the effectiveness of two anesthesia methods during surgery.Results Compared with the conventional anesthesia group,the anesthesia effect of the ultrasound guided anesthesia group was better(P<0.05);The surgery time,amount of bleeding during surgery,postoperative recovery time,and length of hospital stay in the ultrasound guided anesthesia group were all lower than those in the conventional anesthesia group(P<0.05).The ultrasound guided anesthesia group performed better in terms of hemodynamic stability,with a smaller range of changes,and significantly lower pain scores at different postoperative time points compared to the conventional anesthesia group(P<0.05).Conclusion In elderly patients undergoing hip replacement surgery,using ultrasound-guided bupivacaine for subarachnoid block can achieve ideal anesthesia and analgesic effects compared to traditional general anesthesia,shorten drug onset time,alleviate pain in elderly patients,maintain hemodynamic stability,and have significant clinical application effects.

Objective:To investigate the symptoms and symptom clusters of elderly stroke patients in the acute phase, analyze the factors influencing the symptom clusters and to provide a basis for the implementation of targeted symptom management in elderly stroke patients.Methods:Convenience sampling method was used to select 257 acute-phase elderly stroke patients who attended Fenyang Hospital in Shanxi Province from October 2022 to January 2023, and a cross-sectional survey was conducted by the General Information Questionnaire, Memory Symptom Evaluation Inventory, Modified Barthel Index Scale (MBI), and the National Institutes of Health Stroke Scale (NIHSS), and the symptom clusters were extracted by means of exploratory factor analysis, and the factors influencing symptom clusters were explored by means of binary logistic regression analysis.Results:Of the 257 patients, 138 were male and 119 were female, aged 60 to 90 (70.34 ± 6.94) years old. Factor analysis yielded four symptom clusters, which were named oral-intestinal symptom cluster, negative emotional symptom cluster, fatigue symptom cluster, and perceptual symptom cluster according to the symptom characteristics; regression analysis showed that: stroke site and NIHSS scores were the influencing factors of the oral-intestinal symptom cluster (all P<0.05); per capita monthly family income, number of episodes and MBI scores were the influencing factors of the negative emotional symptom cluster (all P<0.05); number of chronic diseases, type of stroke, and gender were the influencing factors of the fatigue emotional symptom cluster (all P<0.05); and literacy and stroke site were influencing factors of the perception symptom cluster (all P<0.05). Conclusions:Elderly stroke patients in the acute phase of the existence of more symptoms, symptoms interact with each other to form symptom clusters, health care personnel should be symptom clusters as a unit, the implementation of interventions for their influencing factors, effective symptom management, in order to improve the quality of life of patients.

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective:To analyze the clinical characteristics of different types of anomalous origin of the coronary artery.Methods:A case-series study was conducted.Based on the clinical data of children diagnosed with anomalous origin of the coronary artery at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from January 2013 to January 2023, the diseases of different types of anomalous origin of the coronary artery were summarized.Results:A total of 177 children with anomalous origin of the coronary artery were treated.Among them, 122 children developed the anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), including 54 males and 68 females, with a median age of 1.2 years; 6 children developed the anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), including 3 males and 3 females, with a median age of 4.3 years; 9 children developed the anomalous left coronary artery from the right coronary sinus (ALCA), including 6 males and 3 females, with a median age of 9.5 years; 40 children developed the anomalous right coronary artery from the left coronary sinus (ARCA), including 24 males and 16 females, with a median age of 7.7 years.Most children diagnosed with ALCAPA had onset within 1 year of age, with chronic heart failure as the main manifestation, and young children were often accompanied by severe mitral regurgitation.A total of 111 children underwent surgery, and 11 children died.Six children with ARCAPA had no obvious clinical symptoms and were treated by operation according to the principle of double coronary circulation after diagnosis.Nine children with ALCA started with syncope, chest pain or abdominal pain after exercise.Eight of the children underwent surgical treatment, including 1 who received a heart transplant.Of the 40 children with ARCA, 23 children had clinical manifestations, with chest tightness, syncope, and chest pain after exercise as chief complaints; 16 children were tested positive for treadmill exercise before surgery; and a total of 13 children received surgical treatment.Conclusions:Different types of anomalous origin of the coronary artery vary in severity.The clinical manifestations of the anomalous origin of the left coronary artery are generally serious, and most of such patients have the risk of cardiac insufficiency or sudden death.Once diagnosed, surgical treatment should be performed timely.The clinical manifestations of the anomalous origin of the right coronary artery are relatively mild, and only a few may have serious consequences, which are usually treated according to the principle of individualization or double coronary circulation.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Objective:To investigate diagnostic and prognostic value of actin-binding protein ANLN in clear cell renal cell carcinoma(ccRCC)and its relationship with tumor microenvironment.Methods:Gene expression data and clinical data for ccRCC were downloaded from The Cancer Genome Atlas(TCGA).Relationship between ANLN expression and clinicopathological features was assessed by Wilcoxon rank sum test and Logistic regression.Receiver operating characteristic(ROC)curve was used to assess diagnostic value of ANLN expression in ccRCC.Kaplan-Meier and Cox regression analysis were used to investigate effect of ANLN expression on overall survival.Gene set enrichment analysis(GSEA)was used to identify signaling pathways associated with ANLN in ccRCC.Relationship between ANLN expression and immune infiltration was analyzed by ESTIMATE algorithm,tumor immune estima-tion resource(TIMER)and CIBERSORT algorithms.Relationship between ANLN and drug sensitivity was calculated using CellMiner database.Results:ANLN expression was significantly upregulated in ccRCC tissues.ANLN expression in ccRCC was correlated with clinicopathological features.ROC analysis showed that ANLN had a high diagnostic value in ccRCC.High ANLN expression was signifi-cantly associated with poor prognosis.Multivariate Cox regression analysis showed that high ANLN expression was an independent risk factor for overall survival in ccRCC patients.GSEA showed that ANLN was associated with multiple signaling pathways.In terms of immunity,ANLN was closely associated with tumor microenvironment,immune infiltration and immune checkpoint molecules in ccRCC.ANLN expression was negatively correlated with sensitivity of most antitumor drugs.Conclusion:ANLN is a potential diagnos-tic and prognostic biomarker and immunotherapeutic target for ccRCC.