BACKGROUND:In the initial stage of growth plate injury inflammation,platelet-derived growth factor BB promotes the repair of growth plate injury by promoting mesenchymal progenitor cell infiltration,chondrogenesis,osteogenic response,and regulating bone remodeling. OBJECTIVE:To elucidate the action mechanism of platelet-derived growth factor BB after growth plate injury. METHODS:PubMed,VIP,WanFang,and CNKI databases were used as the literature sources.The search terms were"growth plate injury,bone bridge,platelet-derived growth factor BB,repair"in English and Chinese.Finally,66 articles were screened for this review. RESULTS AND CONCLUSION:Growth plate injury experienced early inflammation,vascular reconstruction,fibroossification,structural remodeling and other pathological processes,accompanied by the crosstalk of chondrocytes,vascular endothelial cells,stem cells,osteoblasts,osteoclasts and other cells.Platelet-derived growth factor BB,as an important factor in the early inflammatory response of injury,regulates the injury repair process by mediating a variety of cellular inflammatory responses.Targeting the inflammatory stimulation mediated by platelet-derived growth factor BB may delay the bone bridge formation process by improving the functional activities of osteoclasts,osteoblasts,and chondrocytes,so as to achieve the injury repair of growth plate.Platelet-derived growth factor BB plays an important role in angiogenesis and bone repair tissue formation at the injured site of growth plate and intrachondral bone lengthening function of uninjured growth plate.Inhibition of the coupling effect between angiogenesis initiated by platelet-derived growth factor BB and intrachondral bone formation may achieve the repair of growth plate injury.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

OBJECTIVE To solve the problem of insolubility of itraconazole, improve its dissolution in vitro, and provide a reference for further industrial scale-up of the itraconazole multiparticle system. METHODS Itraconazole multiparticle system pellets were dissolved in an organic solvent and prepared in a fluidized bed by bottom spraying. Itraconazole and hydroxypropyl methylcellulose were sprayed onto the surface of the sucrose pellet core to form a uniform solid dispersion. The preparation parameters of the fluidized bed bottom spray coating were investigated by single factor method. The mass ratio of drug to carrier and core weight gain of the itraconazole multiparticle system were optimized by central composite design and response surface methodology with accumulative dissolution rate, application efficiency and adhesion rate as response values. Samples were prepared to verify the optimized prescription, the microscopic hierarchical structure of the itraconazole multiparticle system was observed by scanning electron microscope, and the solid dispersion in the itraconazole multiparticle system pellets was characterized by differential scanning calorimetry(DSC) and X-ray diffraction(XRD). The dissolution curves of itraconazole pellets and the physical mixture in 0.1 mol·L−1 HCl dissolution medium were compared to verify the solubilization effect. RESULTS Single factor method was used to determine the bottom spray coating parameters of the fluidized bed. The pumping speed was set as 3.0−5.0 mL·min−1, the atomization pressure was set as 1.5 bar, the inlet air volume was set as 110 m3·h−1, and the material temperature was set as 35 ℃. According to the central composite design and response surface methodology, the mass ratio of drug to carrier of the optimized prescription was 1∶1.5 and the core weight of the pill was 75%, and the response values reached the expected value. The result of scanning electron microscopy showed that the diameter of the itraconazole multiparticle system pellet was about 910 µm, the diameter of the sucrose pellet core was about 570 µm, the thickness of the drug loading layer was about 110 µm, and the thickness of encapsulation layer was about 11 µm. The results of DSC and XRD showed that itraconazole formed a uniform solid dispersion in the itraconazole multiparticle system pellets, which was amorphous. In the dissolution medium of 0.1 mol·L−1 HCl, the accumulative dissolution rate of the multiparticle system after 90 min was about 10 times that of the physical mixture, which showed that the solubilization effect was remarkable. CONCLUSION The dissolution of itraconazole in vitro can be significantly improved by processing itraconazole into pellets with multiparticle system and forming solid dispersion.

Objective:To explore the relationship among suicide risk,distress tolerance,and resilience in pa-tients with depression.Methods:A total of 130 patients with depression who met the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)diagnostic criteria were included.The Chinese version of the Mini International Neuropsychiatric Interview(MINI)suicide module was used to assess suicide risk.According to the interview results,the patients with depression were divided into suicide risk group(98 cases)and non-suicide risk group(32 cases).The Hamilton Depression Rating Scale(HAMD),Distress Tolerance Scale(DTS),10-item Connor-Davidson Resilience Scale(CD-RISC-10)were used to assess severity of depressive symptoms,level of distress tolerance and resilience,respectively.Results:The DTS total scores were positively correlated with the CD-RISC-10 total scores(r=0.50,P＜0.01).The total scores of MINI suicide module were negatively correlated with the total scores of DTS and CD-RISC-10(r=-0.34,-0.34,Ps＜0.01).Distress tolerance had a direct effect on suicide risk(β=-0.26,P＜0.05),and resilience played a mediating effect on the relationship between distress tolerance and suicide risk(β=-0.13,P＜0.05),and the mediating effect accounted for 33.5％of the total effect.Conclusion:Patients with depression with lower levels of distress tolerance may have higher suicide risk,and resilience may play a partially mediating role in the relationship between distress tolerance and suicide risk.

Pre-rheumatoid arthritis （Pre-RA） is the asymptomatic state of rheumatoid arthritis （RA）， and its progression showed complexity， dynamics and significant individual differences. The dynamic prediction model is valuable in identifying individual risks and taking timely preventive and control measures. It is believed that applying the dynamic prediction model to traditional Chinese medicine （TCM） clinical studies of Pre-RA is expected to predict the critical state of Pre-RA to RA， reveal the evolution of Pre-RA， reflect the external authenticity of the TCM clinical studies， and complement the clinical efficacy evaluation method. Accordingly， it is envisioned to construct a dynamic prediction model for Pre-RA progression based on TCM clinical trial data through the dynamic prediction model algorithm， and to apply long-term follow-up cohort data for external validation， thereby providing a basis for scientific warning and clinical decision-making on the evolution of Pre-RA.

Alginate composite hydrogel is one of the research hotspots of tumor drug delivery system materials at present. Alginate hydrogel has good biocompatibility and regeneration properties. However, the natural alginate saline gel may not achieve the expected results in the body environment due to the slow degradation and instability of the gel. Alginate has found extensive application in cancer therapy through its combination with other materials and the utilization of ionic cross-linking, covalent cross-linking, and free radical polymerization to form hydrogels. Based on the composite system of alginate brine gel, this paper summarizes the structure and properties of alginate hydrogel, with a focus on recent research into alginate composite hydrogel in common cancer treatments application, summarizes the current research focus and discuss the existing problems of alginate composite hydrogel, so as to provide reference for further expanding the research of alginate composite hydrogel in clinical cancer treatment.

Objective:To explore the driving mechanism contributing to doctors′ turnover intention in public hospitals based on the grounded theory.Methods:" Willingness or intention for doctors to quit public hospitals" was used as the theme word, and the literature was retrieved from CNKI published from January 1, 2017 to January 1, 2022. Based on the grounded theory, NVivo 11.0 software was used for a qualitative analysis of the literature. The three-level coding method of open coding, axial coding and selective coding was used to identify the main categories affecting the willingness of doctors to quit public hospitals. On this basis, the driving mechanism model was integrated. In-depth interviews with hospital managers were used to test the theoretical saturation.Results:When 31 papers were coded, four level-1 influencing factors of the formation of doctors′ turnover intention in public hospitals were summarized: career selection deviation, practice reality, perceived experience and external opportunity. Among them, perceived experience was the direct driving factor; career selection deviation was the initial driving factor, and the practice reality was the key driving factor, both of them affected the perceived experience; external opportunity was the possible driving factor.Conclusions:In order to prevent doctors from willing to leave, the following measures are expected: the hospital management should improve both its recruitment evaluation indexes and recruitment effectiveness; pay attention to doctors′ psychological capital management and cultivate positive perception; promote the reform of performance pay, emphasize fairness and value; pay attention to employee relationship management and build a supportive hospital culture.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Objective:To investigate the association of ocular dominance with the severity of chronic primary angle-closure glaucoma (PACG).Methods:Ocular dominance was assessed via the " hole in card" method.The anatomical symmetry (including anterior chamber depth, lens thickness and axial length) in both eyes was analyzed via A scan ultrasound.The severely glaucomatous eye was determined by the mean defect of visual field.The association of ocular dominance with the severity of chronic PACG was then analyzed.This study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong.Written informed consent was obtained from all subjects prior to their entering the study cohort.Results:Visual acuity (LogMAR) was 0.39±0.24 in the dominant eye group, and 0.43±0.29 in the non-dominant eye group.Anterior chamber depth was (2.53±0.26)mm in the dominant eye group, and (2.54±0.29)mm in the non-dominant eye group.Lens thickness was (4.96±0.31)mm in the dominant eye group, and (4.92±0.33)mm in the non-dominant eye group.Axial length was (22.58±0.61)mm in the dominant eye group, and (22.73±1.11)mm in the non-dominant eye group.No significant difference was found in visual acuity, anterior chamber depth, lens thickness or axial length between the dominant and non-dominant eye groups ( t=-1.643, -0.797, 1.867, -1.345; all at P>0.05). The vertical cup-disc ratio of the dominant eye group was lower than that of the non-dominant eye group (0.55 [0.40, 0.80] vs. 0.80 [0.63, 0.90]). The mean defect in the visual field of the dominant eye group was lower than that in the non-dominant eye group (-6.54 [-16.70, -3.85]dB vs.-18.77 [-28.19, -8.55]dB), and the intraocular pressure in the dominant eye group was lower than that in the non-dominant eye group (21.00 [17.00, 27.75]mmHg vs. 24.50 [19.00, 36.25]mmHg) (1 mmHg=0.133 kPa). Significant differences were found in mean defect, vertical cup-disc ratio and intraocular pressure between the two groups ( Z=-3.781, -3.528, -2.126; all at P<0.05). The ratio of the severely glaucomatous eye being the non-dominant eye was 84.09%, which was much higher than that of the severely glaucomatous eye being the dominant eye (15.91%). The non-dominant eye was related to the severity of chronic PACG ( χ2=40.909, P<0.001, Pearson contingency coefficient r=0.563). Conclusions:The non-dominant eye is associated with the severity of chronic PACG.