ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

Objective To compare the differences in the average transaction costs per-referral patients under different models of Integrated Delivery Systems(IDS).Methods Using a typical case sampling method,it selected referred patients from three IDS models:the county medical alliance in D City(Qinghai Province),the urban medical consortium in J District(Zhengzhou City,Henan Province),and the health management coalition in N County(Shandong Province).Structured questionnaires collected demographics,average transaction costs per-referral and cost perceptions.t-tests and ANOVA assessed cost differences;generalized linear regression identified influencing factors.Results Among 915 patients,the average transaction costs per-referral were 1 035.05 yuan(county alliance),195.31 yuan(urban consortium),and 700.97 yuan(health management coalition),with statistically significant differences(P＜0.05).The urban consortium exhibited lower time costs and specialized input costs.Key influencing factors included older age(county alliance),education level,employment status,and referral travel time(urban consortium),as well as urban-rural disparities(health management coalition).Patients'cost perceptions significantly differed across models(P＜0.05).Conclusion The urban medical consortium demonstrated the lowest patient the average transaction costs,highlighting its institutional advantage in minimizing financial burdens.

Objective To compare the differences in the average transaction costs per-referral patients under different models of Integrated Delivery Systems(IDS).Methods Using a typical case sampling method,it selected referred patients from three IDS models:the county medical alliance in D City(Qinghai Province),the urban medical consortium in J District(Zhengzhou City,Henan Province),and the health management coalition in N County(Shandong Province).Structured questionnaires collected demographics,average transaction costs per-referral and cost perceptions.t-tests and ANOVA assessed cost differences;generalized linear regression identified influencing factors.Results Among 915 patients,the average transaction costs per-referral were 1 035.05 yuan(county alliance),195.31 yuan(urban consortium),and 700.97 yuan(health management coalition),with statistically significant differences(P＜0.05).The urban consortium exhibited lower time costs and specialized input costs.Key influencing factors included older age(county alliance),education level,employment status,and referral travel time(urban consortium),as well as urban-rural disparities(health management coalition).Patients'cost perceptions significantly differed across models(P＜0.05).Conclusion The urban medical consortium demonstrated the lowest patient the average transaction costs,highlighting its institutional advantage in minimizing financial burdens.

Objective:To explore the differences in clinical and injured vertebra radiological parameters between patients with non-traumatic osteoporotic vertebral compression fracture (OVCF) and those with traumatic OVCF after percutaneous vertebroplasty (PVP).Methods:A retrospective study was conducted to analyze the 369 OVCF patients (with 458 vertebrae injured) who had been treated by PVP at Department of Orthopaedics, Beijing Luhe Hospital between October 2015 and March 2017. There were 292 females and 77 males with a mean age of 73 (60, 79) years. Based on the absence or presence of a trauma history, the patients were stratified into a non-traumatic group (127 patients with 160 vertebrae injured) and a traumatic group (242 patients with 298 vertebrae injured). Clinical parameters [age, gender, body mass index, symptomatic duration, and number of injured vertebrae, visual analogue scale (VAS), Oswestry disability index (ODI), duration of follow-up, and rate of new OVCFs] and injured vertebra radiological parameters (position of injured vertebra, fracture type, compression severity, fracture range, cortical defect, intravertebral cleft, spinal canal compromise, basivertebral foramen, morphology of bone cement, range of bone cement, cement leakage, cement volume, rate of vertebral height restoration, recollapse of cemented vertebrae) were recorded perioperatively. All the clinical and radiological parameters were compared between the 2 groups.Results:Compared with the traumatic group, the non-traumatic group had an older age [75 (71, 83) years versus 71 (65, 76) years], more females (85.0% versus 76.0%), a longer symptomatic duration [10.0 (7.0, 15.0) d versus 6.5 (2.0, 12.0) d], a lower preoperative VAS pain score [7 (6, 8) points versus 7 (7, 8) points], a lower VAS pain score at postoperative day 1 [2 (2, 3) points versus 2 (2, 3) points], a lower preoperative ODI [66% (63%, 72%) versus 70% (65%, 73 %)], a lower ODI at postoperative day 1 [32% (30%, 34%) versus 32% (31%, 34%)], a higher rate of new OVCFs during follow-up (34.6% versus 12.8%), a lower rate of thoracolumbar lesions (51.9% versus 70.1%), more deformed fractures (mostly amphicoelous type), a lower rate of cortical defects in the anterior wall (20.0% versus 31.5%), a higher rate of trabecular pattern of cement (83.1% versus 71.8%), a higher rate of type-B cement leakage (50.6% versus 31.9%), a lower rate of type-C cement leakage (5.6% versus 12.8%), a lower rate of recollapse of cemented vertebrae (43.8% versus 55.4%). All the comparisons above were statistically significant ( P<0.05). There were no significant differences between the 2 groups in the other clinical or radiological parameters ( P>0.05). Conclusions:There are statistically significant differences in a significant number of clinical and injured vertebra radiological parameters between patients with non-traumatic OVCF and those with traumatic OVCF after PVP. It is noteworthy that non-traumatic OVCFs are one specific subgroup of OVCFs.

Objective: To investigate whether melatonin (MT) secretion in different parts of the gastrointestinal tract (GIT) exhibits seasonal variations and its correlation with immune regulation. Methods: Sixty Sprague-Dawley rats were divided into control and model groups, and the pineal gland was removed in the model group. Stomach, jejunum, ileum, and colon tissues were obtained during the spring equinox, summer solstice, beginning of autumn, autumn equinox, and winter solstice. The levels of MT, MT receptors (MR), arylalkylamine N-acetyltransferase (AANAT), hydroxyindole-O-methyltransferase (HIOMT), interleukin-2 (IL-2), and interleukin-10 (IL-10) in the GIT were measured using enzyme-linked immunosorbent assay. Results: Except for the stomach, the jejunum, ileum, and the colon showed seasonal tendencies in MT secretion. In the control group, MT secretion in the jejunum and ileum was the highest in the long summer, and colonic MT secretion was the highest in winter. In the model group, MT levels in the colon were highest in the summer. The seasonal rhythms of the MR, AANAT, HIOMT, IL-2, and IL-10 in the colon were roughly similar to those of MT, and changed accordingly after pinealectomy. Conclusions Gastrointestinal MT secretion is related to seasonal changes, and MT secretion in each intestinal segment is influenced by different seasons. The biological effects of MT in the gut are inextricably linked to the mediation of MR, and a hormone-receptor linkage exists between MT and MR. The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

OBJECTIVE To study the effects of transferrin-targeting peptide T7 （7pep） on intracellular transportation of polyethylene glycol-polycaprolactone （PEG-PCL） micelles in human cervical cancer HeLa cells. METHODS Using coumarin-6 （C6） as fluorescent indicator probe， both coumarin-6 （C6）-loaded PEG-PCL （PEG-PCL-C6） micelles and 7pep-modified PEG- PCL （7pep-PEG-PCL-C6） micelles were prepared by film-dispersion method. The particle size， polydispersity index and appearance morphology were compared between two types of micelles； the real-time uptake of two types of micelles by HeLa cells was compared， and the colocalization of two types of micelles with early endosomes （EE）， endocytic recycling compartments （ERC） and late endosomes （LE） after entry into the cells was observed. RESULTS The particle sizes of PEG-PCL-C6 and 7pep-PEG-PCL- C6 micelles were（75.0±2.3）and（82.0±1.5）nm； the polymer dispersity indexes were 0.17±0.20 and 0.17±0.32， respectively， with a regular spherical appearance. The colocalization results showed that entry speed and amount of 7pep-PEG-PCL-C6 micelles were significantly faster/more than those of PEG-PCL-C6 micelles. 7pep-PEG-PCL-C6 micelles entered EE faster than PEG-PCL-C6 micelles， while PEG-PCL-C6 micelles entered ERC at a faster rate than 7pep-PEG-PCL-C6 micelles， and both PEG-PCL-C6 micelles and 7pep-PEG-PCL-C6 micelles tended to accumulate gradually in LE； Pearson coefficient， signal overlap ratio， and colocalization ratio of 7pep-PEG-PCL-C6 micelles with LE were significantly lower 60 minutes after entering the cell than those 30 minutes after entering the cell （P＜0.05 or P＜0.01）. CONCLUSIONS Targeting 7pep modification can increase the entry speed and amount of PEG-PCL-C6 micelles， and also alter their intracellular transportation behavior.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective:To evaluate the value of integrated PET/MR in assessing myocardial viability in ischemic heart disease.Methods:A total of 39 patients (28 males, 11 females; age (60.1±12.0) years) diagnosed with ischemic heart disease in Xuanwu Hospital, Capital Medical University were retrospectively enrolled from September 2020 to December 2021. All patients underwent cardiac 13N-NH 3·H 2O and 18F-FDG PET/MR examinations. Late gadolinium enhancement (LGE) sequence was included in MRI scan. PET and MRI images were analyzed and myocardial viability of each myocardial segment was evaluated according to the American Heart Association (AHA) 17 segment method. The extent of left ventricular infarcted myocardium was measured based on PET and MRI images. Weighted Kappa test was used to evaluate the agreement of PET and MRI in assessing myocardial viability. The extent of infarcted myocardium measured by PET and MRI was compared by paired- t test, and Pearson correlation analysis was used to assess the correlation between them. Results:There was a moderate agreement between PET and MRI in assessing myocardial viability ( Kappa=0.532, P<0.001), with the agreement rate of 69.83%(463/663). There was no significant difference but strong correlation between the extents of infarcted myocardium measured by PET and MRI ((23.89±14.23)% vs (23.55±11.90)%; t=-0.24, P=0.809; r=0.79, P<0.001). In segments with normal perfusion and metabolism on PET, 22.52% (100/444) showed abnormal enhancement on MRI. On the other hand, 39.89% (73/183) of the segments classified as non-viable on MRI showed normal or viable on PET. Conclusion:Integrated PET/MR is able to take full advantage of the complementary nature of PET and MRI, achieving the comprehensive and accurate evaluation of myocardial viability.

Allergic rhinitis（AR） is an independent risk factor for allergic asthma. Some AR patients may have developed airway hyperresponsiveness（AHR） in the absence of asthma symptoms. In this stage, AHR is often neglected due to the absence of typical asthma symptoms. Exploring the clinically relevant risk factors for AHR in patients with AR, as well as the clinical indicators and biomarkers to predict AHR in patients with AR, is of great significance to the prevention of the occurrence of AHR and asthma. This review summarized the risk factors for the development of AHR in AR patients, and gave hints to the prevention of AHR in AR patients.
Humans ; Rhinitis, Allergic ; Respiratory Hypersensitivity ; Asthma ; Risk Factors

Objective To investigate the correlation between left ventricular dysfunction and cogni-tive impairment in patients with ischemic heart disease(IHD),and explore the potential patho-genesis of cognitive impairment in IHD patients.Methods Fifty IHD patients who underwent hybrid cardiac PET/MR in our hospital from September 2020 to December 2022 were retrospec-tively enrolled in this study.According to their Montreal cognitive assessment(MoCA)scores,they were categorized into a cognitively normal group(21 cases,MoCA score ≥26)and a cogni-tively declining group(29 cases,MoCA score＜26).All patients received 13N-NH3·H2O myocar-dial perfusion imaging and 18F-FDG cardiac PET/MR to evaluate cardiac function and obtain car-diac imaging parameters.Spearman correlation analysis was applied to analyze the correlation between cardiac PET/MR parameters and MoCA scores.General linear model analysis was applied to analyze the correlation between MoCA scores and cardiac PET/MR parameters after adjusting for co variates.Results Compared with the cognitively normal group,the patients in the cognitively declining group had significantly lower stroke volume[56.95(47.51,77.64)ml vs 82.66(73.88,92.92)ml,P=0.001],stroke volume index[34.07(28.93,43.20)ml/m2 vs 44.28(38.06,49.49)ml/m2,P=0.008],cardiac output[3.92(3.18,5.34)L/min vs 5.13(4.58,5.67)L/min,P=0.007],and cardiac index[(2.42±0.68)L/(min·m2)vs(2.78±0.39)L/(min·m2),P=0.021].Spearman correlation analysis revealed that MoCA score was positively correlated with stroke volume(r=0.497,P=0.001),stroke volume index(r=0.365,P=0.009)and cardiac output(r=0.361,P=0.010).After adjusting for sex,age,education level and vascular risk factors,MoCA score re-mained positively correlated with stroke volume(r=0.497,P=0.003).Conclusion Systemic hy-poperfusion in IHD patients may be one of the mechanisms leading to cognitive impairment.