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

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 in-vestigations 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 inflam-mation 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 circu-lation 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:Multivariate logistic regression analysis was performed to analyze the risk factors for intensive care unit-acquired weakness (ICU-AW) in critically ill patients.Methods:A total of 220 critically ill patients who were admitted to Intensive Care Unit, The First Hospital of Jiaxing from January 2020 to January 2022 were included in this study. The incidence of ICU-AW was recorded. Univariate analysis was conducted to investigate the factors related to ICU-AW, while multiple logistic regression analysis was performed to identify independent risk factors for ICU-AW in critically ill patients.Results:Among the 220 critically ill patients, 64 developed ICU-AW, resulting in an incidence of 29.1% (64/220). There were no significant differences in sex, age, history of alcoholism, history of smoking, marital status, hypertension, diabetes, or use of glucocorticoid (methylprednisolone sodium succinate for injection) between the ICU-AW group and the non-ICU-AW group (all P > 0.05). The proportion of patients with sepsis in the ICU-AW group was higher than that in the non-ICU-AW group [46.9% (30/64) vs. 15.4% (24/156)]. The proportion of patients who were immobilized in the ICU-AW group was higher than that in the non-ICU-AW group [89.1% (37/64) vs. 64.1% (100/156)]. The use of nerve blocker (vecuronium bromide for injection) was more prevalent in the ICU-AW group than that in the non-ICU-AW group [57.8% (37/64) vs. 23.1% (36/156)]. The Acute Physiology And Chronic Health Evaluation Ⅱ score in the ICU-AW group was higher than that in the non-ICU-AW group [16 (11, 23) vs. 12 (8, 17)]. The duration of mechanical ventilation in the ICU-AW group was longer than that in the non-ICU-AW group [8 (4, 13) days vs. 4 (3, 6) days]. The length of hospital stay in the ICU-AW group was longer than that in the non-ICU-AW group [10 (7, 17) days vs. 7 (5, 11) days]. The blood lactate level in the ICU-AW group was higher than that in the non-ICU-AW group [2 (1, 2) mmol/L vs. 1 (1, 2) mmol/L]. All differences were statistically significant ( χ2 = 24.30, 13.83, 24.70, Z = 3.83, 4.59, 3.97, 2.70, all P < 0.05). The results of the univariate analysis, when included in the multivariate logistic regression analysis, showed that sepsis, immobilization, duration of mechanical ventilation, blood lactate level, and Acute Physiology And Chronic Health Evaluation Ⅱ score were independent risk factors for ICU-AW (all P < 0.05). Conclusions:The incidence of ICU-AW is high and the risk factors for ICU-AW are complex. Therefore, targeted control of high-risk factors should be actively performed to prevent and treat ICU-AW.

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.

Objective:Multivariate logistic regression analysis was performed to analyze the risk factors for intensive care unit-acquired weakness (ICU-AW) in critically ill patients.Methods:A total of 220 critically ill patients who were admitted to Intensive Care Unit, The First Hospital of Jiaxing from January 2020 to January 2022 were included in this study. The incidence of ICU-AW was recorded. Univariate analysis was conducted to investigate the factors related to ICU-AW, while multiple logistic regression analysis was performed to identify independent risk factors for ICU-AW in critically ill patients.Results:Among the 220 critically ill patients, 64 developed ICU-AW, resulting in an incidence of 29.1% (64/220). There were no significant differences in sex, age, history of alcoholism, history of smoking, marital status, hypertension, diabetes, or use of glucocorticoid (methylprednisolone sodium succinate for injection) between the ICU-AW group and the non-ICU-AW group (all P > 0.05). The proportion of patients with sepsis in the ICU-AW group was higher than that in the non-ICU-AW group [46.9% (30/64) vs. 15.4% (24/156)]. The proportion of patients who were immobilized in the ICU-AW group was higher than that in the non-ICU-AW group [89.1% (37/64) vs. 64.1% (100/156)]. The use of nerve blocker (vecuronium bromide for injection) was more prevalent in the ICU-AW group than that in the non-ICU-AW group [57.8% (37/64) vs. 23.1% (36/156)]. The Acute Physiology And Chronic Health Evaluation Ⅱ score in the ICU-AW group was higher than that in the non-ICU-AW group [16 (11, 23) vs. 12 (8, 17)]. The duration of mechanical ventilation in the ICU-AW group was longer than that in the non-ICU-AW group [8 (4, 13) days vs. 4 (3, 6) days]. The length of hospital stay in the ICU-AW group was longer than that in the non-ICU-AW group [10 (7, 17) days vs. 7 (5, 11) days]. The blood lactate level in the ICU-AW group was higher than that in the non-ICU-AW group [2 (1, 2) mmol/L vs. 1 (1, 2) mmol/L]. All differences were statistically significant ( χ2 = 24.30, 13.83, 24.70, Z = 3.83, 4.59, 3.97, 2.70, all P < 0.05). The results of the univariate analysis, when included in the multivariate logistic regression analysis, showed that sepsis, immobilization, duration of mechanical ventilation, blood lactate level, and Acute Physiology And Chronic Health Evaluation Ⅱ score were independent risk factors for ICU-AW (all P < 0.05). Conclusions:The incidence of ICU-AW is high and the risk factors for ICU-AW are complex. Therefore, targeted control of high-risk factors should be actively performed to prevent and treat ICU-AW.

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.

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.

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.

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.