OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

OBJECTIVE: To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation. METHODS: A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared. RESULTS: A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (F_time = 105.975, P < 0.001), intervention effects (F_intervention = 7.378, P = 0.008), and interaction effects (F_interaction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO₂) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO₂) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05]. CONCLUSIONS Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans ; Transcutaneous Electric Nerve Stimulation ; Respiration, Artificial/adverse effects* ; Diaphragm/physiopathology* ; Phrenic Nerve ; Intensive Care Units ; Male ; Female ; Middle Aged

Objective:To investigate the prevalence of the decline of intrinsic capacity(IC)and to explore the effect of intrinsic capacity decline on falls and hospital readmission during 1 year follow-up.Methods:A total of 311 elderly patients treated in Geriatrics Department of Zhejiang Hospital were enrolled.General information and intrinsic ability data, including cognitive(simple mental state inventory), motor(Tinetti-Balance Scale and 4 m test), vitality(grip strength and mini-nutrition assessment table), perception(self-rated vision or hearing impairment), and psychosocial(Geriatric depression scale), were collected at admission.Falls and hospital readmission within 1 year after discharge were followed up.Multivariate Logistic regression analysis was used to investigate the relationship of baseline intrinsic ability at admission with falls and hospital readmission during 1-year follow-up.Results:Of 311 elderly hospitalized patients, 282(90.7%)had intrinsic capacity decline.During 1 year follow-up, 38 elderly patients(12.2%)had falls and 69 elderly patients(22.2%)were hospital readmitted.After adjusting for confounding factors such as age, gender, education level, comorbidities, multiple medications, fear of falling, and assistive tool use and so on, Logistic regression analysis showed that decreased balance ability was a risk factor for falls within 1 year in elderly patients( OR=3.515, 95% CI: 1.089-11.346, P=0.036), and slow walking speed was a risk factor for one-year hospital readmission( OR=2.426, 95% CI: 1.181-4.983, P=0.016). Conclusions:Decreased motor capacity is closely associated with falls and hospital readmission within 1 year in older patients.Great attention should be paid to the assessment and intervention of motor ability in elderly patients.

Worldwide, the incidence of cancer is greatest in China. Tumor screening is effective to achieve early diagnosis, improve prognosis, increase the quality of life, and reduce mortality among cancer patients. Positron emission tomography/computed tomography (PET/CT) imaging provides metabolic data to support initial staging, treatment planning, and response evaluation in tumor screening, as well as tumor follow-up. The progressive integration of PET/CT imaging in radiotherapy has its basic principle in the biological heterogeneity of inter- and intra-tumor malignant lesions, and the radiation dose is required to be adjusted to achieve effective local tumor control among cancer patients. In addition, PET/CT imaging provides data on the biological features of tumor lesions, such as metabolism, hypoxia, and proliferation, which is useful to identify radiation-resistant regions and optimize treatment plans. These data are effective to reduce the uncertainty and variability in the anatomic description of tumor sites. This review summarizes the application of PET/CT imaging in common tumors.

The combination of conventional single-photon emission computed tomography (SPECT) and computed tomography (CT) may display the morphological changes of lesions and distribution of imaging agents, which is effective to improve the imaging sensitivity and specificity of tumors and non-tumor diseases. SPECT/CT is feasible to analyze the anatomical structure and metabolic status through displaying multi-site lesions with single imaging, thereby improving differential diagnosis and diagnostic accuracy of diseases. In addition, the novel mixed SPECT/CT device shortens the duration of image acquisition and provides precise attenuation correction and fusion imaging, which provides a scientific basis for rational selection of treatment regimens in clinical practice. This review describes the advances in clinical application of SPECT/CT.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective:To explore the risk factors of intensive care unit-acquired weakness (ICU-AW), and to establishment and verify its risk prediction model.Methods:A modeling group of 231 patients who met the inclusion criteria and were admitted to the intensive care unit (ICU) of the First Hospital of Jiaxing from July 2019 to June 2020 was collected by convenience sampling method. According to whether they developed ICU-AW, they were divided into ICU-AW group (55 cases) and non ICU-AW group (176 cases). The clinical data were collected concerning patients' individual information, disease-related factors, treatment-related factors and laboratory indicators, and the differences of the above indexes between two groups were compared. Logistic regression was used to analyze the ICU-AW risk factors and a risk prediction model was constructed. Calculate the area under ROC curve (AUC) to test the prediction effect of the model. At the same time, 60 patients who admitted to ICU from July to October 2020 and met the standards were collected to verify the model.Results:Compared with non ICU-AW group, there were more males in ICU-AW group [61.8% (34/55) vs. 44.3% (78/176), P < 0.05], with higher levels of systemic inflammatory response syndrome (SIRS), sepsis, immobilization and the use of neuromuscular blockers [SIRS: 30.9% (17/55) vs. 3.4% (6/176), sepsis: 12.7% (7/55) vs. 2.3% (4/176), immobilization: 72.7% (40/55) vs. 39.2% (69/176), the use of neuromuscular blockers: 50.9% (28/55) vs. 14.2% (25/176), all P < 0.05], and acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, blood lactic acid level and duration of mechanical ventilation, length of hospital stay were all increased [APACHEⅡ score: 18 (15, 24) vs. 12 (8, 17), blood lactic acid (mmol/L): 2 (1, 2) vs. 1 (1, 2), duration of mechanical ventilation (days): 7 (4, 12) vs. 2 (2, 5), length of hospital stay (days): 10 (6, 16) vs. 5 (3, 9), all P < 0.05]. SIRS, APACHEⅡ score, duration of mechanical ventilation and blood lactic acid were included to construct a risk prediction model [odds ratio ( OR) values were 4.835, 1.083, 1.210, 1.790, P values were 0.018, 0.013, 0.015, 0.013]. The model equation was P = exp [-5.207+(1.576×SIRS)+(0.079×APACHEⅡ)+(0.191×duration of mechanical ventilation)+(0.582×blood lactic acid)]. Internal verification: Calibration diagram showed the calibration curve above the ideal curve, AUC = 0.888, 95% confidence interval (95% CI) was 0.839-0.938; when the cut-off value was 0.166, the sensitivity was 89.1%, the specificity was 75.6%, and the maximum index was 0.649. External verification: Calibration diagram showed that the calibration curve was above the ideal curve, and the plotted AUC = 0.853, 95% CI was 0.753-0.953. When the cut-off value of the corresponding predictive risk value was 0.367, the sensitivity was 68.8%, the specificity was 86.4%, and the maximum approximate index was 0.552. Conclusion:The risk prediction model of ICU-AW constructed in this study has good consistency and prediction efficiency, which can provide reference for medical personnel to identify high-risk groups of ICU-AW patients in the early stage and provide targeted interventions in advance.

Objective To investigate the detection rate of motoric cognitive risk syndrome (MCR)and explore the possible risk factors.Methods A total of 429 elderly patients from geriatric department of Zhejiang Hospital from October 2014 to September 2018 were recruited in the crosssectional study.General information and functional assessment including fall history,self-reported visual impairment and hearing impairment,depressive symptom,cognitive function and gait speed were collected.Patients with MCR were screened out according to the MCR diagnostic criteria.Multiple logistic regression analysis was used to analyze the associated risk factors.Results Seventeen patients(4.0％)met the MCR diagnostic criteria.The proportions of obesity,polypharmacy,cerebral vascular diseases,self-reported hearing impairment,depressive symptoms and slow gait were higher in MCR patients than in non-MCR patients(P＜0.05).Compared with non-MCR patients,MCR patients had lower mini mental state examination (MMSE) scores (P ＜ 0.01).After adjusting for associated confounding factors,multiple logistic regression analysis showed obesity (OR =3.74,95 ％ CI:1.14-12.23,P ＜ 0.05) and depressive symptoms (OR =5.79,95％ CI:1.76-19.06,P ＜ 0.01) were risk factors for MCR.Conclusions MCR is not uncommon in elderly patients.Obesity and depressive symptoms are closely associated with an increased risk of MCR.

Objective To assess the predictive value for survival of BioCliM index in liver cirrhosis caused esophageal and gastric varices bleeding(EGVB)treated by endoscopic variceal ligation(EVL),endoscopic injection sclerotherapy(EIS)and endoscopic tissue adhesives(ETA).Methods From December 2006 to December 2011, the clinical data of 166 hospitalized patients with first occurrence of EGVB caused by liver cirrhosis and received endoscopic therapies were retrospectively analyzed.The scores of model for end-stage liver disease(MELD),model for end-stage liver disease-Na(MELD-Na),BioCliM index and Child-Turcotte-Pugh(CTP)were calculated. Receiver operating characteristic(ROC)curve and area under the curve(AUC)were applied to assess the accuracy of the four models in one-year and two-year prognosis evaluation,and to obtain the best critical value,and the mortality rates were compared among groups.Chi-square test,t test and rank-sum test were performed for statistical analysis.Results Among 166 patients,the levels of creatinine,bilirubin,albumin,sodium,international normalized ratio and prothrombin time were(0.10 ± 0.06)mmol/L,(0.02 ± 0.01)mmol/L,(30.13 ± 5.06)g/L, (139.13 ± 4.27)mmol/L,1.50 ± 0.32 and(17.83 ± 2.88)s,respectively.During the one-year and two-year follow-up,there were 14 patients and 23 patients dead,respectively.During the one-year and two-year follow-up, the incidences of portal thrombosis of death group were lower than those of survival group(10/14 vs 93.4%,142/152;73.9%,17/23 vs 94.4%,135/143);and the differences were statistically significant(χ2=8.029 and 10.774, both P<0.01).During the one-year and two-year follow-up,BioCliM indexes of death group were 0.12(-0.82, 1.44)and -0.81(-0.87,0.92),respectively,which were both higher than those of survival group(-0.84,-0.94 to -0.73;and -0.84,-0.94 to -0.72),and the differences were statistically significant(Z= -3.074 and -2.260,both P<0.05).During the one-year follow-up,the AUC values of MELD,MELD-Na,BioCliM index and CTP score were 0.698,0.691,0.749 and 0.723,respectively.During the two-year follow-up,the AUC values of MELD,MELD-Na,BioCliM index and CTP score were 0.587,0.582,0.647 and 0.633,respectively. But there was no statistically significant difference in AUC between BioCliM index and MELD,MELD-Na,and CTP score in one-year and two-year follow-up for prognosis evaluation(Z=0.509,0.566,0.271,0.687,0.731 and 0.162,respectively;all P>0.05).The best critical value of BioCliM index was -0.234.Followed up for one year and two years,the mortality rates of patients with BioCliM index over -0.230 were higher than that of patients with BioCliM index less than -0.234(31.0%,9/29 vs 3.6%,5/137;34.5%,10/29 vs 9.5%,13/137);and the differences were statistically significant(χ2=23.242 and 12.526,both P<0.01).Conclusions BioCliM index has a high accuracy in one-year and two-year mortality rate evaluation in liver cirrhosis patients with EGVB and received endoscopical therapies.We should pay attention to the prognosis evaluation before the endoscopical therapy.