AIM: To prepare a novel functionalized upconversion nanomaterial UCNPs-PEG-Tf through an improved method and observe its specific imaging phenomenon to choroidal melanoma cells(OCM-1).METHODS: NaYF4:Yb/Er(Up-conversion nanoparticles, UCNPs)was Prepared and plasma was treated to carboxylate the surface; then amino polyethylene glycol and transferrin(Tf)were respectively loaded to prepare UCNPs-PEG-Tf. Characterized them accordingly, its biocompatibility was tested accordingly, and the specific fluorescence phenomenon of OCM-1 was detected by fluorescence spectrophotometer and inverted fluorescence microscopy.RESULTS: Characterization confirmed successful synthesis of UCNPs, UCNPs-PEG, and further loading of Tf to form UCNPs-PEG-Tf. UCNPs-PEG-Tf showed excellent biocompatibility and emitted significant green fluorescence. Under the same conditions, fluorescence intensity measurement and observations from the inverted fluorescence microscope both demonstrated its significant specificity in imaging to OCM-1 cells.CONCLUSION: The synthesized novel functionalized UCNPs-PEG-Tf nanocomposite showed good biocompatibility and achieve specific imaging to OCM-1 cells.

[摘 要] 目的：探讨扁蒴藤素（PT）通过蛋白激酶B（AKT）/糖原合成酶激酶-3β（GSK-3β）信号通路对人乳腺癌细胞MCF-7多柔比星（DOX）敏感性的影响。方法：体外培养MCF-7细胞并建立DOX耐药细胞MCF-7/DOX。MCF-7细胞设NC组、L-PT组（2 μmol/L PT）、M-PT组（4 μmol/L PT）、H-PT组（8 μmol/L PT）、H-PT + SC79组（8 μmol/L PT + 10 μmol/L的AKT/GSK-3β信号通路抑制剂SC79）、H-PT + LY294002组（8 μmol/L PT + 2.5 μmol/L的AKT/GSK-3β信号通路激活剂LY294002）。MCF-7/DOX细胞设MCF-7/DOX组（未处理）、DOX组（50 nmol/L DOX）、PT + DOX组（8 μmol/L PT和50 nmol/L DOX）、PT + DOX + SC79组（8 μmol/L PT + 50 nmol/L DOX + 10 μmol/L SC79）、PT + DOX + LY294002组（8 μmol/L PT + 50 nmol/L DOX + 2.5 μmol/L LY294002）。采用MTT法、平板克隆实验、划痕愈合实验、Transwell实验及WB法分别检测细胞增殖、集落形成数、迁移、侵袭和AKT/GSK-3β信号通路蛋白表达。建立MCF-7细胞裸鼠移植瘤模型，观察PT对移植瘤生长、移植瘤组织中AKT/GSK--3β 信号通路蛋白表达的影响。结果：与NC组相比，L-PT、M-PT、H-PT组MCF-7细胞增殖率、集落形成数、划痕愈合率、侵袭细胞数及p-AKT、p-GSK-3β蛋白表达均呈PT浓度依赖性降低（均P < 0.05）；与H-PT组对比，H-PT + SC79组MCF-7细胞上述指标变化趋势与上述相反，PT + DOX + LY294002组MCF-7细胞上述指标变化趋势与上述相同（均P < 0.05）。MCF-7/DOX组与DOX组细胞增殖率、集落形成数、划痕愈合率、侵袭细胞数及p-AKT、p-GSK-3β蛋白表达无明显差异（均P > 0.05）；分别与MCF-7/DOX组、DOX组对比，PT + DOX组MCF-7/DOX细胞上述指标均降低（均P < 0.05）；对比PT + DOX组，PT + DOX + SC79组上述指标均升高，PT + DOX + LY294002组上述指标均降低（均P < 0.05）。裸鼠移植瘤实验显示，与对照组和DOX相比，PT + DOX组移植瘤质量、体积、p-AKT、p-GSK-3β蛋白表达均降低（均P < 0.05）。结论：PT抑制乳腺癌细胞增殖、迁移和侵袭，并增强其对DOX的化疗敏感性，其机制与抑制AKT/GSK-3β信号通路有关。

Objective:To compare the effect of delaying progression of myopia in children between defocus incorporated multiple segments (DIMS) spectacle lens and orthokeratology.Methods:A nonrandomized controlled clinical study was conducted.A total of 390 children (390 eyes) with myopia who were treated in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were included, with the spherical equivalent (SER) of -0.75 to -6.00 D. According to the willingness of patients and patients' guardians, the subjects were divided into DIMS group, orthokeratology group and single-vision spectacle lens group, with 130 cases (130 eyes) in each group, wearing DIMS spectacle lenses, standard or astigmatic design orthokeratology and conventional single-vision full-correction aspheric spectacle lenses, respectively.The SER of the eyes was measured using an automatic computerized refractometer in combination with subjective refraction before and one year after lens wear, and the axial length (AL) of the eyes was measured using IOLMaster.A total of 327 patients in the three groups met the inclusion and exclusion criteria, including 107 in the DIMS group, 112 in the orthokeratology group, and 104 in the single-vision spectacle lens group.All the right eyes were included in this study.The changes in SER and AL before and after wearing lenses for 1 year were compared among the three groups.The relationship between AL and SER changes and baseline data in the DIMS group was evaluated by Pearson linear correlation analysis.The study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2023-KY-0174-002). The subjects and their guardians were fully aware of the purpose and methodology of the study, and voluntarily signed an informed consent form.Results:There were statistically significant overall differences in SER and AL at different time points among the three groups (SER: Fgroup=7.065, P=0.009; Ftime=183.730, P<0.001.AL: Fgroup=6.151, P=0.014; Ftime=175.290, P<0.001). One year later, the differences in SER and AL changes among the three groups were statistically significant ( F=7.065, P=0.009; F=6.151, P=0.014). The SER and AL of each group after 1 year was greater than the baseline, with the SER and AL and their changes significantly smaller in orthokeratology group and DIMS group than in single-vision spectacle lens group and greater in DIMS group than in orthokeratology group, showing statistically significant differences (all at P<0.05). Compared with single-vision spectacle lenses, wearing orthokeratology for 1 year can inhibit SER and AL progression by 58.3% and 59.0%, and wearing DIMS frame glasses for 1 year can inhibit SER and AL progression by 46.9% and 43.6%.The percentage of eyes with no change in SER was 5.77%(6/104), 24.11%(27/112) and 17.76%(19/107) in the single-vision spectacle lens group, orthokeratology group and DIMS group, respectively, and the percentage of AL was 0.00%(0/104), 8.93%(10/112) and 7.48%(8/107), respectively, showing statistically significant differences among the three groups ( χ2=9.316, 8.676; both at P<0.001). The AL change in the DIMS group was weakly negatively correlated with age ( r=-0.252, P=0.006). Conclusions:Wearing DIMS spectacle lenses is not as effective as orthokeratology in delaying myopia in children, but it is significantly better than wearing conventional single-vision spectacle lenses.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the effect of transcranial direct current stimulation(tDCS)in the left posterior sylvia temporal-parietal association area on language function in patients with post-stroke conductive aphasia.Methods The post-stroke aphasia patients admitted to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University were prospectively included from June 2021 to April 2024.A self-cross randomized controlled trial was performed in this study.The patients enrolled were assessed as conductive aphasia by Western aphasia test kit diagnostic criteria.Twelve patients with post-stroke conductive aphasia were completely randomly divided into group A(treatment sequence:stage A—washout period—stage B)and group B(treatment sequence:stage B—washout period—stage A),with 6 cases in each group.Stage A performed true tDCS therapy combined with speech and language training,and stage B performed sham tDCS therapy combined with speech and language training.During washout period,only speech and language training was performed,and each stage was trained for 5 days.The tDCS anode is the stimulation electrode and is placed at the stimulation target.The cathode is the reference electrode and is placed on the right shoulder.The intensity of tDCS was 1.4 mA,the true stimulation was 20 min/time,and the sham stimulation stopped automatically after only 30 s/time,both twice/d,and a total of 10 times treatment were performed.Speech and language training was performed 30 min/time,2 times/d,a total of 10 times treatment.The function of rehearsal and picture naming(training item and non-training item)were examined before and after treatment of stage A and B immediately,and the difference of function scores of rehearsal and picture naming(training item and non-training item)before and after treatment of stage A and B were compared.Results(1)There were no significant differences in gender,age,course of disease and educational level between group A and group B(all P＞0.05).(2)Before and after washout period,there were no statistical significance in functional scores of rehearsal and picture naming(training items and non-training items)in both group A and group B(all P＞0.05).(3)There were no significant differences in functional scores of rehearsal and picture naming(training items and non-training items)between group A and group B before and after washout treatment(all P＞0.05).(4)Compared with the difference before and after treatment of stage B,the function scores difference before and after treatment of stage A in rehearsal function,picture naming(training item)and picture naming(non-training item)were higher([6.9±1.4]scores vs.[2.2±1.0]scores,t=9.604;[6.2±1.2]scores vs.[1.8±1.1]scores,t=9.277;[6.5±1.0]scores vs.[1.5±1.0]scores,t=12.247;all P＜0.01).Conclusions Preliminary analysis suggested that tDCS intervention in the brain tissue of the temporoparietal association area of the left posterior lateral cleft may help improve the rehearsal and picture naming(training and non-training items)ability in conductive aphasia patients after stroke.The sample size of this study is small,and the results need to be further explored.

The gold-standard for bone substitution of large bone defects continues to be autogenous bone graft. Artificial bone substitutes are difficult to replace the autogenous bone grafting due to excessive immune response, fast biodegradation characteristics and inappropriate biocompatibility. Given these drawbacks, osteoimmunology and its advanced functional biomaterials have gained growing attention in recent years. Immune system plays an essential role during bone healing via regulating the shift from inflammatory to anti-inflammation phenotype, and inflammatory cytokines response. The inflammatory reaction mainly include infiltration of immune cells (such as macrophages, neutrophils, T cells, B cells, etc) and release of inflammatory factors (such as IL-1β, IL-6, TNF-α, etc.) at the bone defects, which subsequently affect the step-wised process of bone healing rejuvenation. Hence, advanced bone biomaterials with immunomodulatory properties is of great significance for the treatment of patients with recalcitrant bone defects, especially for delayed healing or non-union. The reciprocal mechanism of immuno-modulated bone healing, however, is not fully understood and more research is required in the future.
Osteogenesis ; Cytokines ; Biocompatible Materials ; Macrophages ; T-Lymphocytes ; Bone Regeneration

Objective:To observe the effects of 0.01% atropine eye drops on ocular biometrics in myopic adolescents.Methods:A prospective cohort study was conducted.Two hundred and nineteen myopic adolescents who visited the First Affiliated Hospital of Zhengzhou University from June 2016 to June 2017 and completed the 1-year follow-up on time were enrolled.The 219 adolescents were divided into a 0.01% atropine+ single-vision spectacles (SV) group (119 cases) wearing single-vision spectacles with one drop of atropine eye drop applied to both eyes once nightly, and a simple SV group (100 cases) wearing SV only.Axial length (AL), corneal power and anterior chamber depth were measured with the IOLMaster.Lens power was calculated using the Bennett-Rabbetts formula.Intraocular pressure was measured by non-contact tonometry.Spherical equivalent (SE) was examined by cycloplegic autorefraction.Total astigmatism and corneal astigmatism were calculated by vector decomposition.The right eye data were analyzed to compare the ocular biometrics changes between the two groups, and multiple linear regression analysis was used to evaluate the influencing factors.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of First Affiliated Hospital of Zhengzhou University (No.2016-35). Written informed consent was obtained from guardians before any medical examination.Results:The SE change and AL elongation 12 months after treatment in 0.01% atropine+ SV group were (-0.47±0.45) D and (0.37±0.22) mm, respectively, which were significantly lower than (-0.70±0.60)D and (0.46±0.35)mm in simple SV group ( t=5.523, 9.651; both at P<0.001). There were significant differences in SE and AL between before and after treatment in both groups (SE: Fgroup=1.556, P=0.015; Ftime=12.538, P=0.002; AL: Fgroup=3.425, P=0.021; Ftime=18.235, P=0.008). The SE and AL at 4, 8 and 12 months after treatment were all increased in comparison with before treatment in both groups, showing statistically significant differences (all at P<0.001). The SE and AL at 8 and 12 months after treatment in 0.01% atropine+ SV group were smaller than in simple SV group, and the differences were statistically significant (all at P<0.001). At 8 and 12 months after treatment, total astigmatism and the anterior chamber depth were increased and the lens power was decreased in comparison with before treatment in both groups, and the differences were statistically significant (all at P<0.05). There was no significant difference in corneal astigmatism, corneal power and intraocular pressure at different time points before and after treatment between the two groups (all at P>0.05). In the multiple linear regression analysis, an equation of Δmyopic SE=-0.012-2.685×ΔAL-1.002×Δcorneal astigmatism-0.656×Δlens power+ 0.477×Δtotal astigmatism+ 0.363×Δanterior chamber depth-0.060×age+ 0.011×sex was used, showing the change of SE was mainly caused by the change of AL ( β=-2.685), then corneal power, lens power, total astigmatism and anterior chamber depth. Conclusions:In adolescents, 0.01% atropine eye drops can effectively retard myopia progression and axial elongation, showing no effect on astigmatism, corneal power, lens power, anterior chamber depth and intraocular pressure.The controlling effect of 0.01% atropine eye drops in the development of myopia is mainly achieved by reducing axial elongation.

Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Objective:To compare the clinical efficacy and safety of 0.01% and 0.02% atropine eye drops on myopia development in adolescents.Methods:A randomized controlled double-blind study was carried out.Two hundred and eighty myopic adolescents (280 eyes) with spherical equivalent (SE) from -1.25 to -6.0 D were enrolled in The First Affiliated Hospital of Zhengzhou University from June 2016 to June 2017.All the subjects wore full-correction single vision spectacle lenses before topical administration of atropine eye drops.The subjects were randomly divided into 0.01% atropine group (142 eyes) and 0.02% atropine group (138 eyes) according to the random number table method.Atropine 0.01% or 0.02% eye drops was topically used in the test eye once per night according to grouping, and the related parameters of the right eyes were collected for data analysis.The subjects were followed up at the 1st, 4th, 8th and 12th month following administration.The SE was measured with an autorefractor to evaluate the refractive change.The anterior chamber depth, corneal curvature and axial length (AL) were measured with an IOLMaster.The adverse responses of atropine eye drops were investigated via a questionnaire.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2016-35). Written informed consent was obtained from subjects and their guardian prior to entering the cohort.Results:The follow-up rate of 0.01% atropine group was 83.8%, and the follow-up rate of 0.02% atropine group was 84.8% at the end of following-up.SE and AL increased by (-0.47±0.32)D and (0.37±0.20)mm in 0.01% atropine group, and (-0.38±0.35)D and (0.30±0.17)mm in 0.02% atropine groups during the following-up, respectively, showing statistically significant differences between two groups ( P=0.040, 0.004). After adjusting age, body mass index and baseline SE, the analysis by generalized additive mixed model showed that the increase rate of SE was -0.039 D/month and -0.032 D/month in 0.01% and 0.02% atropine group, respectively ( Pinteraction=0.041). After adjusting age, body mass index and baseline AL, the analysis of mixed effect model showed that the increase rate of AL was 0.031 mm/month and 0.025 mm/month in 0.01% and 0.02% atropine group, respectively ( Pinteraction=0.032). In 0.01% and 0.02% atropine groups, 32 cases (26.9%) and 33 cases (28.2%) occurred photophobia from 1st to 4th week during administration, and 7 cases (5.9%) and 7 cases (6.0%) appeared near-vision blur from 2nd to 4th week.Allergic response occurred in 0.01% atropine group at 1 month of treatment, and the symptom disappeared after interruption of the medication for two days. Conclusions:The incidence of adverse resoponses of 0.01% and 0.02% atropine eye drops is similar.Atropine 0.02% eye drops is more effective in controlling myopia progression.

Objective:To observe the safety and efficacy of 0.01% atropine eye drops in the prevention of myopia onset in schoolchildren.Methods:A randomized double-blind controlled study was conducted.Sixty Chinese Han children (60 eyes) with binocular spherical equivalent (SE) between + 0.50 D and -0.75 D (pre-myopia) by cycloplegic autorefraction treated in The First Affiliated Hospital of Zhengzhou University were enrolled from July to October 2020.Aged 6-12 years old, the children were divided into 0.01% atropine group and control group according to a random number table, with 30 cases (30 eyes) in each group.The children were given one drop of 0.01% atropine or placebo eye drops in both eyes once a night.The SE, axial length (AL), accommodative amplitude and pupil diameter were compared before and after 3-month, 6-month of treatment between the two groups.Discomforts were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2020-KY-286). Written informed consent was obtained from guardian of each subject.Results:After treatment, 26 and 25 subjects completed the 6-month follow-up in 0.01% atropine group and control group, respectively, among which 3 subjects in 0.01% atropine group accounting for 11.5% and 9 in control group accounting for 36.0% developed myopia, showing a statistically significant difference ( χ2=4.238, P=0.040). There were significant differences in the overall comparison of SE and AL at different time points between before and after treatment ( Ftime=10.981, 81.854; both at P<0.001). At 3 and 6 months after treatment, there were significant increases in the SE and AL of control group and AL of 0.01% atropine group compared with respective baseline values (all at P<0.05). There was no significant difference in SE at 3 and 6 months after treatment compared with baseline SE in 0.01% atropine group (both at P>0.05). At 6 months after treatment, the change in SE in 0.01% atropine group was (-0.15±0.26)D, which was significantly less than (-0.34±0.35)D in control group, and the change in AL in 0.01% atropine group was (0.17±0.11)mm, Which was significantly shorter than (0.28±0.14)mm in control group, with significant differences between them ( t=2.207, P=0.032; t=3.127, P=0.003). There were significant differences in pupil diameter at different time points between before and after treatment ( Ftime=2.263, P=0.032). At 3 and 6 months after treatment, the pupil diameter was increased in comparison with baseline in 0.01% atropine group (both at P<0.05). There were significant differences in accommodative amplitude at different time points between before and after treatment in the two groups ( Fgroup=0.882, P=0.042; Ftime=0.337, P=0.033). The accommodative amplitude at 3 and 6 months after treatment were decreased in comparison with baseline in 0.01% atropine group and control group at corresponding time points (all at P<0.05). Within a month after treatment, photophobia in bright sunlight occurred in 5 cases in 0.01% atropine group, accounting for 16.7%(5/30), and 2 cases in control group, accounting for 6.7%(2/30), showing no significant difference ( χ2=0.647, P=0.421). No near-vision blur and other uncomfortable symptoms was found in the two groups. Conclusions:After 6-month application of 0.01% atropine eye drops, the prevalence of myopia in pre-myopia schoolchildren decreases and the changing rate of SE and AL slows down.The accommodative amplitude is slightly reduced and pupil diameter is slightly increased, with no obvious effects on study and life.