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 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.

ObjectiveTo observe the effect of donor liver pretreated by breviscapine on liver transplantation ischemia/reperfusion injury in rats. Methods SD rats served as liver donors and recipients (n =48 each).The recipients were divided into four groups by random number table.The donors in groups A and C were not pretreated with breviscapine,but those in groups B and D were pretreated with 20 mg/L Breviscapine.The cold ischemia time in donor livers of groups A and B was 30-40 min,and that in groups C and D was 12 h. Clotting function, liver function, serum thrombomodulin,caspase3,and relative activity of NF-kB after liver transplantation were assessed,and the pathological changes and TUNEL apoptosis staining were observed.ResultsThe mortality in groups C and D was 40.0％ (8/20) and 29.4％ (5/17),respectively (P＞0.05).There were no significant changes in coagulation function in all groups after operation. The liver function was improved,pathological lesions were alleviated,and apoptosis rate,serum TM,caspase3 expression and activity of NF-kB in the liver tissues of group D were significantly decreased as compared with group C at 3rd day after operation (P＜0.01),but all these parameters in group B had no significant change compared to group A.ConclusionPretreatment of donor livers with breviscapine can reduce the ischemia/reperfusion injury and apoptosis after liver transplantation in rats probably by inhibiting the apoptosis-related pathway and alleviating the damage to the endothelial cells of the liver microcirculation.

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.

Objective To investigate the surgical operation technique,clinical curative effect and the choice of the indication in the treatment of cervical spondylosis by radiofrequency nucleoplasty.Methods From January to July in 2006,the ArthroCare system 2000 radio frequency instrument that the American ArthroCare company produce were odopted,to treat 20 patients with cervical spondylosis by radiofrequency nucleoplasty under the leading of the C form grill X-ray fluoroscopic machine.Among them,there were 9 males and 11 females with age from 38 to 62 years,equally 45.12 years old,the average course of illness was 2 years. 15 cases with lumbar disc herniation,4 cases with nerve-root cervical sDandylosis and 1 case with spinal cervical spondylosis.Single segment affection in 4 cases,double or multistage segment affection in 16 cases.Among those multistage segment eases,all choose 2 segments for research according to fixed physical sign the body advertise for and the MRI image.After the operation all cases underwent follow-up.with follow-up time for 1-6 months.Results The results shown an effect among those 20 sufferers of excellence in 16 cases,valid in 4 cases,efficient power reach to 100%in short term.Ahhough this case was limited.the early case choice compares strictly,the subjective satisfaction of sufferer was higher.Conclusion Application of radiofrequency nucleoplasty in the treatment of cervical sDondylosis has advantages of small wound,safety and high efficacy in short term.However, its indication still need further research.

Objective To evaluated the clinical outcomes of intravesical instillation resiniferatoxin(RTX) for the treatment of patients with idiopathic overactive bladder(IOAB).Methods 26 cases with IOAB were randomly divided into test(A,14 cases) and control(B,12 cases) groups.The patients in group A were treated by intravesical instillation with 40ml of 0.5% idocain retained within the bladder for 3 minutes at first and with 100ml of 100nmol/L RTX retained within the bladder for 30 minutes late.The patients in group B were treated by the same method,however,the furacilin solution(placebo) at a dilution 1∶5000 was used instead of 100nmol/L RTX.The efficacy(daily voiding frequency,urgent uresis,FDV,MCBC,Qmax) of the 2 groups were evaluated before,1 month and 3 months after treatment.Results The pre-treatment comparion with prost-treatmen at 1 month and 3 months of A group was significant(P0.05).14 patients(54%) had slightly stimulating symptom in the urethra or bladder,and were otherwise generally well tolerated.Conclusion Single administration of RTX is safe and effective in patients with IOAB.