The blood-brain barrier in humans significantly restricts the effective delivery of drugs into the brain,resulting in poor therapeutic efficacy and difficulty in brain disease management.In recent years,innovative strategies and novel preparations have been studied and developed in order to circumvent the blood-brain barrier,achieve efficient drug entry into the brain,minimize the incidence of peripheral adverse effects,and bring significant therapeutic outcomes to patients.This review summarizes some key development strategies for treating encephalopathy,to provide some insights for the development of the next generation of drugs.

Objective To obtain the range of anatomical parameters of healthy knee joints in Chinese males and validate a statistical shape model(SSM)based on the geometric shape of a healthy knee to provide references for the design of knee SSM-based prostheses.Methods Computed tomography(CT)images of knee joints from 112 healthy males were acquired to build three-dimensional(3D)knee joint models.Each model was the target model separately,and the remaining models were used as the training set for principal component analysis(PCA).The obtained knee SSM was fitted to the target model to predict the SSM.The exact anatomical measurement points were marked on the sample and SSM prediction models,and 17 linear and 3 angular parameters were derived.The values of the anatomical parameters were statistically tested using an independent samples t-test and Mann-Whitney U-test,and the validity of the SSM in terms of geometric shape was demonstrated if the resulting P-values were all greater than 0.05.Results Qualitative and quantitative comparative analyses of anatomical parameters showed that the mean deviation of linear parameters was less than 6 mm,and that of angular parameters was less than 2.5°.The results of statistical tests showed P＞0.05 for all anatomical parameters,proving that the knee SSM prediction model was not statistically different from the true healthy model in terms of geometric shape.Conclusions This study derived a reference range of anatomical parameters for a healthy knee and demonstrated that the knee SSM model was consistent with the real healthy model in terms of shape.The results provide a reference for the design of knee SSM-based prostheses.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of pseudocarcinomatous hyperplasia of the fallopian tubes.Methods:Sixteen cases of pseudocarcinomatous hyperplasia of the fallopian tubes diagnosed at Obstetrics and Gynecology Hospital of Fudan University from January 2011 to January 2024 were collected.The pathological sections were reviewed, the clinical and pathological data were consulted, and immunohistochemical examination was conducted along with follow-up.Results:The patients were aged from 19 to 57 years, with an average age of 41 and a median age of 38. Among the 16 cases, 4 were located in the right fallopian tubes, 6 in the left fallopian tubes, while the remaining cases presented bilaterally. The general manifestations were tubal edema, crispness and purulent secretion in the lumen. Morphologically, the fallopian tube mucosa exhibited a significant infiltration of neutrophils, lymphocytes and plasma cells. The epithelial cells of the fallopian tube displayed evident proliferation, stratification and disorganized arrangement leading to formation of small glandular cavity with back-to-back, fissure-like and sieve-like structures. Immunohistochemical analysis revealed positivity for CK7 and WT1, along with wild-type p53 expression, Ki-67 index ranged from 5% to 20%. During the follow-up period ranging from 1 to 156 months, all the patients remained free of disease.Conclusions:Pseudocarcinomatous hyperplasia of the fallopian tube is a rare non-neoplastic lesion, which can lead to epithelial hyperplasia and atypical hyperplasia. The most important significance of recognizing this lesion lies in avoiding misdiagnosis of fallopian tube cancer during intraoperative and postoperative pathological examination. This ensures that clinicians can administer correct clinical interventions.

Objective:To investigate the association between oxygen desaturation rate and blood pressure (BP) among severe obstructive sleep apnea syndrome (OSAS) and the possible mechanism.Methods:Patients with snoring were enrolled from the Department of Sleep Medicine Center, the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University form March 2018 to January 2019 and underwent polysomnography (PSG). Noninvasive BP and Heart rate variability were full-night monitored continuously and synchronized with PSG. Based on the PSG results and exclusion criteria, a total of 86 severe OSAS patients were enrolled in this study and divided into two groups according to the ambulatory BP measurements: hypertensive group ( n=44) and normotensive group ( n=42). Oxygen desaturation rate was expressed as the change in the percentage of pulse oxyhemoglobin saturation (SpO 2) per second during desaturation events after the obstructive apnea events occurred. The PSG parameters were compared between the two group and the multiple regression analyses were used to explore the association between oxygen desaturation rate and BP and its possible mechanism. Results:The apnea-hyperpnoea index (AHI) and respiratory event-related arousals (RERAs) were significantly higher in hypertensive group than those in normotensive group [(69.8±18.2) vs. (56.5±13.9) event/h; (40.5±17.4) vs. (30.2±14.6) event/h, both P<0.01]. In addition, hypoxia exposure conditions in the hypertensive group were more severe than those in the normotensive group, especially oxygen desaturation rate [(0.45±0.14)%/s vs. (0.33±0.10)%/s, P<0.001]. After adjusting for age, sex, neck circumference, waist circumference, smoking, drinking, the regression analyses showed that only the oxygen desaturation rate was significantly associated with both awake and asleep BP in OSAS patients ( β=0.473, 0.478, both P<0.01) and the correlation analyses suggested that the oxygen desaturation rate was related to the both awake and asleep sympathetic-parasympathetic imbalance ( r=0.367, 0.337, both P<0.01). Conclusion:Oxygen desaturation rate is closely related to BP levels in patients with severe OSAS, and the underlying mechanism is associated with the increased sympathetic activity.

Objective: To analyze the treatment efficacy in the vertically impacted maxillary central incisors using cone-beam CT (CBCT) and explore the treatment timing and the influence of orthodontic traction on the root development and alveolar bone height in the mixed dentition. Methods: Twenty-two patients with vertically impacted maxillary central incisor who were admitted to the Department of Orthodontics, Stomatological Hospital affiliated to Nanjing Medical University from December 2012 to December 2017 were selected [12 males and 10 females, (9.2±0.9) years]. Based on the dental age, patients were classified as early treatment group (teeth ranging from a third to two thirds of root formation, n=12) and late treatment group (teeth with nearly or fully complete root formation, n=10). The contralateral maxillary central incisor was used as the control. Three-dimensional reconstruction of CBCT before treatment, after treatment and one year after treatment was carried out to measure root length, tooth surface area, tooth volume, labial and lingual apical alveolar bone thickness, the loss of labial alveolar bone height and intraosseous root ratio. The clinical crown length was measured in the mouth. The difference values of the measurement variables between the impacted teeth and the control teeth were calculated and analyzed(measurement values of impacted teeth were subtracted from control values). Results: The values of root length difference beween the impacted teeth and the control teeth in the early and late treatment group were (1.58±1.56) mm and (2.57±1.00) mm, respectively after the treatment and the values were significantly less than those corresponding values before treatment [(3.47±1.40) and (3.36±0.79) mm] (P<0.05). After the treatment, the values of the surface area and volume difference between the impacted teeth and the control teeth in the early treatment group [(0±34) mm² and (-10±44) mm³] were significantly less than those corresponding values before treatment [(38±31) mm² and (55±70) mm³] (P<0.05). The value differences of any measurement variables between the early and late treatment group were not significantly different after the treatment (P>0.05). The root length and intraosseous root ratio of the impacted teeth after the treatment in the early and late treatment group were significantly less than those of the control teeth after the treatment (P<0.05). The clinical crown length, the loss of labial alveolar bone height of the impacted teeth after the treatment were significantly larger than those of the control teeth after the treatment (P<0.05). Conclusions Orthodontic traction promoted the root growth and development of the vertically impacted maxillary central incisors. However, the root length and alveolar bone height still cannot reach the normal level after treatment. Treatment timing had no effect on root development and alveolar bone height of vertically impacted maxillary central incisors in mixed dentition.

Objective To analyze the treatment efficacy in the vertically impacted maxillary central incisors using cone?beam CT (CBCT) and explore the treatment timing and the influence of orthodontic traction on the root development and alveolar bone height in the mixed dentition. Methods Twenty?two patients with vertically impacted maxillary central incisor who were admitted to the Department of Orthodontics, Stomatological Hospital affiliated to Nanjing Medical University from December 2012 to December 2017 were selected [12 males and 10 females, (9.2±0.9) years]. Based on the dental age, patients were classified as early treatment group (teeth ranging from a third to two thirds of root formation, n=12) and late treatment group (teeth with nearly or fully complete root formation, n=10). The contralateral maxillary central incisor was used as the control. Three?dimensional reconstruction of CBCT before treatment, after treatment and one year after treatment was carried out to measure root length, tooth surface area, tooth volume, labial and lingual apical alveolar bone thickness, the loss of labial alveolar bone height and intraosseous root ratio. The clinical crown length was measured in the mouth. The difference values of the measurement variables between the impacted teeth and the control teeth were calculated and analyzed (measurement values of impacted teeth were subtracted from control values). Results The values of root length difference beween the impacted teeth and the control teeth in the early and late treatment group were (1.58±1.56) mm and (2.57±1.00) mm, respectively after the treatment and the values were significantly less than those corresponding values before treatment [(3.47 ± 1.40) and (3.36 ± 0.79) mm] (P<0.05). After the treatment, the values of the surface area and volume difference between the impacted teeth and the control teeth in the early treatment group [(0 ± 34) mm2 and (-10 ± 44) mm3] were significantly less than those corresponding values before treatment [(38±31) mm2 and (55±70) mm3] (P<0.05). The value differences of any measurement variables between the early and late treatment group were not significantly different after the treatment (P>0.05). The root length and intraosseous root ratio of the impacted teeth after the treatment in the early and late treatment group were significantly less than those of the control teeth after the treatment (P<0.05). The clinical crown length, the loss of labial alveolar bone height of the impacted teeth after the treatment were significantly larger than those of the control teeth after the treatment (P<0.05). Conclusions Orthodontic traction promoted the root growth and development of the vertically impacted maxillary central incisors. However, the root length and alveolar bone height still cannot reach the normal level after treatment. Treatment timing had no effect on root development and alveolar bone height of vertically impacted maxillary central incisors in mixed dentition.

Insect repellent DEET and sunscreen ingredient oxybenzone play an essential role in minimizing vector-borne diseases and skin cancers. The purpose of this study was to investigate the effects of emulsion type, addition of thickening agent and droplet size in three emulsion-based lotions on percutaneous permeation of DEET and oxybenzone using in vitro diffusion experiments, in order to minimize overall systemic permeation of the substances. Formulation C (water-in-oil emulsion) significantly increased overall permeation of DEET through human skin (56%) compared to Formulation A (oil-in-water emulsion). Formulation B (oil-in-water emulsion with thickening agent xanthan gum) significantly decreased the size of oil droplet containing DEET (16%), but no effect on oil droplets containing oxybenzone. Adding xanthan gum also increased overall permeation of DEET and oxybenzone (21% and 150%) when compared to Formulation A; presence of both ingredients in Formulation B further increased their permeation (36% and 23%) in comparison to its single counterparts. Overall permeation of oxybenzone through LDPE was significantly higher by 26%-628% than that through human skin; overall permeation of DEET through human skin was significantly higher by 64%-338% than that through LDPE.

Objective:To explore a new method of the cultivation of adoptive immunotherapy cells.Methods: Mononuclear cells was isoplated by density gradient centrifugation and then proliferated by using CD 40-agonist monoclonal antibody 5C11、cytokine of IFN-αand IL-7(CD40 group)in vitro.During the culturing procedure ,the cell morphology was obersved by optical microscope.The percentage of T-lymphocytes, NK-T cells, Treg cells and the cell proliferation, which were compared with CIK group CD3mAb activated,was detected on the 9th day.Results:There was no significant difference of CD 4+/CD8+T cells percentage between the two groups.But the Treg cells percentage of CIK group was far higher than that of CD 40 group,while the percentage of CD3+CD56+NK-T cells was lower than that of CD 40 group.And a group of Mo-NK-DC cells were observed in the CD 40 group.Conclusion: The new method of adoptive immunity therapy has been established in this study could increase the percentage of NK -T cells which had the ability to kill tumor cells.Simultaneously ,it is reduced the amount of Treg cells significantly.

To identify Salvia shandongensis and its relatives at molecular level, the psbA-trnH intergenic region of three species including Salvia shandongensis, Salvia miltiorrhiza and S. miltiorrhiza f. alba were amplified and sequenced. Sequences were assembled with CodonCode Aligner. The K2P genetic distances between Salvia shandongensis and its relatives were calculated and UPGMA tree was performed by MEGA5.0. The results indicated that the lengths of psbA-trnH regions of Salvia shandongensis were about 391 bp, while the lengths of psbA-trnH regions of Salvia miltiorrhiza and S. miltiorrhiza f. alba were about 386 bp. The psbA-trnH sequences showed considerable variations between species and thus were revealed as a promising candidate for barcoding of Salvia shandongensis and its relatives. The intra-specific genetic distances of Salvia shandongensis were 0, while the intra-specific genetic distances of Salvia miltiorrhiza and S. miltiorrhiza f. alba were 0.002 and 0.001 respectively. Additionally, the genetic distance of Salvia shandongensis and Salvia miltiorrhiza ranged from 0.034 to 0.04, and the genetic distance of Salvia shandongensis and S. miltiorrhiza f. alba ranged from 0.005 to 0.008, the intra-specific genetic distances of Salvia shandongensis were much smaller than that of Salvia miltiorrhiza and S. miltiorrhiza f. alba; clustering results showed that there were obvious differences between Salvia shandongensis, Salvia miltiorrhiza and S. miltiorrhiza f. alba, which was consistent with morphological characteristics. This study not only firstly provides the scientific basis for establishing the taxonomy position in molecular level and revealing their genetic relationships of S. shandongensis, S. miltiorrhiza and S. miltiorrhiza f. alba; but also provides DNA molecular identification scientific basis for the development of new medicinal plant resources of Salvia shandongensis. Our results suggest that the psbA-trnH intergenic spacer region can be used as a barcoding to identify Salvia shandongensis, Salvia miltiorrhiza and S. miltiorrhiza f. alba.

This research was carried out to investigate the effect of basic fibrous growth factor (bFGF) controlled release hydrogel nanoparticles on the proliferation and differentiation of mesenchymal stem cells. The dex-GMA-bFGF-NPs were prepared by an improved emulsion polymerization method; their morphology, size and encapsulated ratio were assessed by routine procedure. Dynamic dialysis method was used to determine the release characteristics of dex-GMA-bFGF-NPs in vitro. The secondary culture MSCs were divided into four groups according the different ingredients being added into the DMEM culture medium: free bFGF group (A), blank dex-GMA nanoparticles group (B), dex-GMA-bFGF nanoparticles group (C), nothing group (D). The proliferation of cultured MSCs was measured by using cell counting method, MTT method and flow cytometry. ALP kit was used to evaluate the ALP activity of the MSCs to show the differentiation of the cells by adding the dex-GMA-bFGF-NPs to the DMEM culture medium (C group) or bFGF only (A group). B group and D group were taken as the controls. The results were analyzed by statistical analysis software (SPSS11.0). All results showed that the shape of dex-GMA-bFGF-NPs was spherical. The encapsulated ratio was 88% and more than 85% of the encapsulated bFGF could be released during 14 days. The in vitro cellular study showed the control release of bFGF from nanoparticles could promote the proliferation of MSCs. After 12 days, the cell number in groups A, B and C was (21.97 +/- 0.25) x 10(4) cells/ml, (12.43 +/- 0.13) x 10(4) cells/ml, (27.45 +/- 0.78) x 10(4) cells/ml and (12.03 +/- 0.43) x 10(4) cells/ml, with the difference being statistically significant among them (P < 0.05). The flow cytometry revealed that the G2/M+S percentage in group C was the highest at 4-8 days after plate culture(P < 0.05). During the first 3 days, the proliferation and differentiation of BMSCs between group A and group B were of no significance (P > 0.05), but were much faster than those of group C and D. After 7 days, dex-GMA-bFGF-NPs could enhance BMSCs proliferation and differentiation continually, but bFGF had no enhancement any more, the difference between group A and group B became more significant (P < 0.05). So we made the conclusions the bFGF loading dex-GMA hydrogel nanoparticles can release bFGF more than 21 days and can promote the proliferation and differentiation of the BMSCs through a long period of controlled release of bFGF. Dex-GMA-bFGF-NPs may be an ideal controlled release carrier for bioactive growth factors.
Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media ; Female ; Fibroblast Growth Factor 2 ; pharmacology ; Male ; Mesenchymal Stromal Cells ; cytology ; Nanoparticles ; Rats ; Rats, Sprague-Dawley