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 investigate the clinical features of adherent perirenal fat (APF) in patients undergoing laparoscopic adrenal surgery through peritoneal approach, and to analyze its predictors and risk factors, so as to provide reference for clinical diagnosis and treatment.Methods:A total of 86 patients who received transabdominal approach laparoscopic adrenal surgery in the Department of Urology, the Rizhao Hospital of Traditional Chinese Medicine and the First Department of Minimally invasive Urology of Shandong Provincial Hospital from February 2021 to February 2024 were retrospectively selected as the study objects. According to whether patients developed APF during the operation, they were divided into APF group (29 cases) and non-APF group (57 cases). The Mayo Adhesive Probability (MAP) score and preoperative perirenal fat CT density were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in predicting the occurrence of APF. Univariate and multivariate logistic regression models were used to analyze the influencing factors of the occurrence of APF.Results:The MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal gland level) and CT density score of the APF group were higher than those of the non-APF group, with statistical significance (all P<0.05). Age, body mass index (BMI), perirenal fat thickness and the proportion of diabetes mellitus and hyperlipidemia in the APF group were significantly higher than those in the non-APF group, with statistical significance (all P<0.05). The area under ROC curve predicted by MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal level) and CT density score for APF in patients undergoing laparoscopic adrenal surgery were 0.921, 0.655, 0.628, 0.538, and 0.912, respectively. Logistic regression model results showed that high MAP score, high CT density score, old age, high BMI, large perirenal fat thickness, and complicated diabetes were independent risk factors for APF in patients undergoing peritoneal laparoscopic adrenal surgery (all P<0.05). Conclusions:In patients with adrenal tumor treated by peritoneal laparoscopic adrenal surgery, MAP score and CT perirenal fat density examination before operation are beneficial to predict whether APF will occur, which has certain guiding significance for the formulation of surgical plan.

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:To investigate the clinical features of adherent perirenal fat (APF) in patients undergoing laparoscopic adrenal surgery through peritoneal approach, and to analyze its predictors and risk factors, so as to provide reference for clinical diagnosis and treatment.Methods:A total of 86 patients who received transabdominal approach laparoscopic adrenal surgery in the Department of Urology, the Rizhao Hospital of Traditional Chinese Medicine and the First Department of Minimally invasive Urology of Shandong Provincial Hospital from February 2021 to February 2024 were retrospectively selected as the study objects. According to whether patients developed APF during the operation, they were divided into APF group (29 cases) and non-APF group (57 cases). The Mayo Adhesive Probability (MAP) score and preoperative perirenal fat CT density were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in predicting the occurrence of APF. Univariate and multivariate logistic regression models were used to analyze the influencing factors of the occurrence of APF.Results:The MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal gland level) and CT density score of the APF group were higher than those of the non-APF group, with statistical significance (all P<0.05). Age, body mass index (BMI), perirenal fat thickness and the proportion of diabetes mellitus and hyperlipidemia in the APF group were significantly higher than those in the non-APF group, with statistical significance (all P<0.05). The area under ROC curve predicted by MAP score, CT density of perirenal fat (renal vein level, adrenal tumor level, normal adrenal level) and CT density score for APF in patients undergoing laparoscopic adrenal surgery were 0.921, 0.655, 0.628, 0.538, and 0.912, respectively. Logistic regression model results showed that high MAP score, high CT density score, old age, high BMI, large perirenal fat thickness, and complicated diabetes were independent risk factors for APF in patients undergoing peritoneal laparoscopic adrenal surgery (all P<0.05). Conclusions:In patients with adrenal tumor treated by peritoneal laparoscopic adrenal surgery, MAP score and CT perirenal fat density examination before operation are beneficial to predict whether APF will occur, which has certain guiding significance for the formulation of surgical plan.

Objective:To explore the effect of Gubi Decoction on serum related inflammatory factors and PI3K/Akt/mTOR signaling pathway in osteoarthritis model rats. Methods:Seventy SPF rats were randomly divided into the blank group, sham operation group, Glucosamine sulfate group, and the low, medium and high dose Gubi Decoction groups. Except the blank group and sham operation group, knee osteoarthritis animal models were prepared by the modified Hulth method in each group. On the 28th day after successful model preparation, the high, medium and low dose Gubi Decoction groups were given Gubi Decoction 24, 12 and 6 g/kg by gavage respectively; glucosamine sulfate group was given glucosamine sulfate tablet suspension 3 g/L by gavage, once a day for 28 days. The levels of TNF-α and IL-1β in serum were detected by ELISA. The gene expressions of PI3K, Akt and mTOR in cartilage tissue were detected by Real-PCR. The protein expressions of PI3K, Akt, p-PI3K, p-Akt and mTOR were detected by Western blot. Results:Compared with the model group, the knee joint diameter[(11.17 ± 1.81) mm, (11.60 ± 1.38) mm, (10.80 ± 1.17) mm vs. (12.57 ± 0.98) mm] of the rats in the glucosamine sulfate group and the medium and high dose Gubi Decoction groups significantly decreased ( P<0.05). The content of TNF-α [(111.43 ± 21.98) ng/L, (53.42 ± 13.25) ng/L vs. (157.89 ± 23.60) ng/L], IL-1β [(67.50 ± 18.44) ng/L, (48.22 ± 9.63) ng/L vs. (96.11 ± 14.85) ng/L] in the medium and high dose Gubi Decoction groups significantly decreased ( P<0.05), and the expression of PI3K (1.87 ± 0.17, 1.24 ± 0.49 vs. 2.19 ± 0.47), Akt (1.50 ± 0.51, 1.10 ± 0.32 vs. 2.68 ± 0.63), and mTOR (1.32 ± 0.54, 1.10 ± 0.33 vs. 2.94 ± 0.55) mRNA in the medium and high dose Gubi Decoction groups significantly decreased ( P<0.05). The expression of PI3K, Akt, p-PI3K, p-Akt in the low, medium and high dose Gubi Decoction groups significantly decreased ( P<0.05), and the expression of mTOR in the medium dose Gubi Decoction group significantly decreased ( P<0.05). Conclusion:Gubi Decoction can significantly reduce the level of inflammatory factors in the serum of osteoarthritis model rats, and its anti-inflammatory and analgesic effects may be related to PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the effect of bilateral repetitive transcranial magnetic stimulation (rTMS) on the pre-attentive processing of methamphetamine addicts.Methods:Forty methamphetamine addicts were screened and equally divided into the intervention group and the control group by random number table method.The intervention group was treated with bilateral simultaneous stimulation with 10 Hz on the left DLPFC and 1 Hz on the right DLPFC with 7 days of continuous intervention.The same scheme was used to intervene the control group, but with pseudo-stimulation. The changes of amplitude and latency of mismatch negative wave(MMN) before and after intervention were compared. SPSS 24.0 software was used for statistical analysis. Independent sample t-test was used for inter group comparison, and paired sample t-test was used for intra group comparison before and after intervention. Results:Before rTMS, there were no significant differences in MMN(F3, Fz, F4) amplitude (intervention group: (-0.90±0.28)μV, (-0.98±0.19)μV, (-0.96±0.19)μV; control group: (-0.92±0.21)μV, (-0.89±0.20)μV, (-0.94±0.16)μV)and latency(intervention group: (184.16±33.07)ms, (179.20±25.35)ms, (184.95±28.22)ms; control group: (184.91±26.96)ms, (180.99±25.29)ms, (181.55±23.19)ms) between the two groups (all P>0.05). After the intervention, there were significant differences in MMN(Fz, F4) amplitude(intervention group: (-1.38±0.16)μV, (-1.17±0.19)μV; control group: (-0.91±0.17) μV, (-0.99±0.16)μV) between the two groups (both P<0.01), but there were no significant differences in MMN (F3) amplitude(intervention group: (-1.01±0.59)μV; control group: (-0.80±0.50)μV), and in MMN (F3, Fz, F4) latency(intervention group: (177.38±26.45)ms, (172.17±23.87)ms, (179.84±23.60)ms; control group: (182.08±24.95)ms, (177.94±21.30)ms, (179.18±21.62)ms)between the two groups (all P>0.05). There were statistically significant differences in MMN( Fz, F4) amplitude (before-intervention: (-0.98±0.19)μV, (-0.96±0.19)μV; after-intervention: (-1.38±0.16)μV, (-1.17±0.19)μV)before and after intervention in the intervention group (both P<0.05), but there was no significant difference in MMN(F3) amplitude(before-intervention: (-0.90±0.28)μV; after-intervention: (-1.01±0.59)μV)before and after intervention in the intervention group ( P>0.05), and there were statistically significant differences in MMN(F3, Fz, F4) latency (before-intervention: (184.16±33.07)ms, (179.20±25.35)ms, (184.95±28.22)ms; after-intervention: (177.38±26.45)ms, (172.17±23.87)ms, (179.84±23.60)ms)before and after intervention in the intervention group(all P<0.05). After pseudo-stimulation, there were no statistically significant differences in MMN( F3, Fz, F4) amplitude(before-intervention: (-0.92±0.21)μV, (-0.89±0.20)μV, (-0.94±0.16)μV; after-intervention: (-0.80±0.50)μV, (-0.91±0.17)μV, (-0.99±0.16)μV)and latency (before-intervention: (184.91±26.96)ms, (180.99±25.29)ms, (181.55±23.19)ms; after-intervention: (182.08±24.95)ms, (177.94±21.30)ms, (179.18±21.62)ms) before and after intervention in the control group (all P>0.05). Conclusion:After repeated transcranial magnetic stimulation, the pre-attentive processing of the intervention group is improved, which shows that bilateral simultaneous stimulation of the rTMS program is effective.

OBJECTIVE：To investigate the effects of rabepr azole on the pharmacokinetic characteristics of clopidogrel and its active metabolite in healthy volunteers with different CYP2C19 genotypes. METHODS ：Healthy volunteers were selected as subjects，and then randomly divided into extensive metabolizer （EM）group，intermediate metabolizer （IM）group，and poor metabolizer（PM）group with 8 subjects in each group ，according to their CYP2C19 genotypes by random number table. In single-dose，randomized，open，two-cycle-crossover design ，each group was given Clopidogrel bisulfate tablets 300 mg or Clopidogrel bisulfate tablets 300 mg+Rabeprazole sodium enteric-coated tablets 20 mg. UPLC-MS/MS method was adopted to detect the concentration of clopidogrel and its active metabolite derivative （MP-H4）. The pharmacokinetic parameters were calculated and compared by DAS 2.0 software. RESULTS ：There was no statistical significance in clinical data as age ，height， body weight ，liver enzymes and serum creatinine among 3 kinds of metabolism subjects （P＞0.05）. Compared with subjects receiving clopidogrel alone ，cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in EM group were increased by 36％ and 27％，while those of MP-H 4 were decreased by 34％ and 28％（P＜0.01）；cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in IM group were increased by 19％ and 18％，while those of MP-H 4 were decreased by 19％ and 16％ （P＜0.05 or P＜0.01）；there was no statistical significance in cmax and AUC 0－t of clopidogrel and MP-H 4 in PM group after receiving rabeprazole additionally as well as tmax of clopidogrel and MP-H 4 in all metablism subjects ，compared with clopidogrel alone（P＞0.05）. CONCLUSIONS ：Among CYP2C19 EM and IM subjects ，combined use of rabeprazole can significantly increase the exposure of clopidogrel and decrease the exposure of its active metabolite MP-H 4，but has no significant impact on clopidogrel and its active metabolite in CYP2C19 PM subjects.

Objective To explore the clinical effect of phalangeal fractures with self-made mini external fixator. Methods From June, 2014 to June, 2017, 16 cases of phalangeal fracture were treated with self-made mini external fixator. In the followed-up periods, the regulating rechecks of X-ray and measurement of interpha-langeal joint activity were determined. The total active movement (TAM), numerical pain ranting scale (NPRS) and morning stiffness was used to estimate the fracture healing and the hand function recovery. Results Pain and ab-normal movement around fracture was found 6 weeks after the operation in 1 case, which had been healed by re-moving the external fixation, open reduction and internal fixation with kirschner wire. The other 15 cases were fol-lowed-up of 48-72 (average, 58) weeks. The fracture has healed. And there was no osteomyelitis, no breakage and loosening of steel needles. The clinical healing time of the fracture was 14 to 16 weeks, with an average of 15.5 weeks. According to the TAM, NPRS and morning stiffness, there was excellent in 11 cases, and good in 4 cases. Conclusion The self-made mini external fixator can maintain the stability after fracture reduction, provide the tension required for the healing of collateral ligament and joint capsule, and meet the need of early functional exer-cise. It is an ideal treatment option for phalangeal fractures.

Objective: To evaluate the value of clinical application of Heart of the City type TJH-03A remote electrocardiogram recorder (remote ECG). Methods: A total of 1 014 community residents from Wuhan received ECG examination by Heart of the City type TJH-03A remote ECG recorder. Clinical and ECG data of all subjects were collected and analyzed. Results: There were 359 (35.40%) cases with normal ECG and 655 (64.60%) cases with abnormal ECG, after remote ECG examination . There were 581 cases had a variety of arrhythmia in 655 cases with abnormal ECG, so there were 828 cases times with abnormal ECG, in which there were （1）320 cases times (38.65%) with repolarization abnormality,（2）98 cases times(11.84%) with sinus bradycardia, （3）98 cases times (11.84%)with myocardial ischemia,（4）78 cases times (9.42%)with conduction block,（5）56 cases times(6.76%) with ventricular hypertrophy and high voltage,（6）43 cases times(5.19%) with atrial premature beats（7）37 cases times (4.47%)with atrial fibrillation,（8）35 cases times (4.23%)with sinus tachycardia,（9）24 cases times (2.90%)with ventricular premature beats, （10）19 cases times (2.29%)with suspected myocardial infarction according to ECG abnormality rate order. In addition, there were 5 cases times with QT interval prolongation, and abnormal ECG with abnormality rate ≤3 cases times: atrial tachycardia, atrial flutter, supraventricular tachycardia, ventricular tachycardia, Brugada wave, dextrocardia. Conclusion: Heart of the City type TJH-03A remote electrocardiogram recorder is convenient to use, it can perform remote electrocardiogram record, and find a variety of arrhythmias. It’s important for ECG diagnosis, especially for diagnosis of arrhythmias.

Objective: To investigate influence of Wenxin particle on cardiac electrophysiology in rats complicated with depression after myocardial infarction (MI). Methods: A total of 50 SD rats were randomly and equally divided into normal group, MI group, depression group, MI complicated with depression group (model group) and Wenxin particle group (Wenxin particle were given to model rats by gavage, 2 g/d, 28d). Model（MI complicated with depression）rats were made by acute ligation of left coronary artery and supply chronic unpredictable mild stress in order. The influences of Wenxin particle on cardiac electrophysiological indexes, such as monophasic action potential (MAP90), left ventricular effective refractory period (ERP) and ventricular fibrillation threshold (VFT) were evaluated in Wenxin particle group. Results: (1) Compared with normal group, there were significant decrease in behavior scores (P<0.05) in model group, after four-week treatment with Wenxin particle, their behavior scores significantly increased (P<0.01); (2) Compared with normal group, there were significant increase in MAPD90 and ERP, and significant decrease in VFT in model group (P<0.05); compared with model group, there were significant decrease in MAPD90 [(89.33±7.12) ms vs. (72.29±8.37) ms] and ERP [(84.00±6.57) ms vs. (68.00±7.43) ms], and significant increase in VFT [(7±3.11)V vs. (29±5.60)V] in Wenxin particle group, P<0.05. Conclusion: Wenxin particle can improve cardiac electrical remodeling in rats complicated with depression after myocardial infarction, including decrease monophasic action potential duration and effective refractory period, and raise ventricular fibrillation threshold.