The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the brain's internal environment, which poses challenges to the treatment of central nervous system diseases. Drug carriers can aid in the delivery of therapeutic agents across the BBB to exert their pharmacological effects. The article reviewed the pathways for drug delivery across the BBB, the intracerebral fate and the classification of drug carriers and focuses on the functions and characteristics of liposomes, exosomes, apoptotic bodies, cell-penetrating peptides, and cell-targeting peptides. The review will provide an outlook on the future and challenge of research in the field of drug delivery across the BBB.

Objective To report 5 cases of amyloid arthropathy with joint flexion contracture as the first manifestation,and perform a literature review to improve the understanding of the disease.Methods Retrospective analysis of the clinical manifestations,laboratory and imaging results clinical data of patients with immunoglobulin light chain(AL)amyloidosis related amyloid arthropathy with joints flexion contracture as the first manifestation at the Department of Rheumatology and Immunology,the First Medical Center of People's Liberation Army General Hospital from January 2012 to February 2022.Meanwhile searching the database(CNKI,Wanfang Data,PubMed),excluding myeloma-associated amyloid arthropathy,and analyzing the literature results comprehensively.Results There were a total of 5 patients with amyloid arthropathy with joint flexion contracture as the initial manifestation in this center,including 4 males and 1 female.By February 2022(searching CNKI,Wanfang Data and PubMed),two eligible patients were selected,all males.A total of 7 patients were included with male-to-female ratio of 6:1.The median age was 30-year-old(range from 19 to 73).Spine and limb joints were involved,especially finger joints(7 cases,100%).Soft tissue was involved in 5 patients(71.4%),carpal tunnel syndrome in 4 patients(57.1%),giant tongue in 3 patients(42.9%),shoulder pad sign in 2 patients(28.6%),muscle swelling in 2 patients(28.6%).Five patients were misdiagnosed as rheumatoid arthritis(RA)and 1 patient was misdiagnosed as spondyloarthritis(SpA).The median time of delayed diagnosis was 24 months(2-204 months).The laboratory results showed that 3 patients(42.9%)were positive for immunoelectrophoresis,all of which were λ light chain.Only 1 patient was positive for HLA-B27,while the other patients were negative for autoantibodies and rheumatoid factors.Only 1 patient had elevated C reactive protein(CRP)and erythrocyte sedimentation rate(ESR).Ultrasound examination of the lesion site of 5 patients(71.4%)showed hypoechoic area around the joint,thickening of ligaments or periarticular tenosynovitis.Five patients(71.4%)underwent X-ray examination,of which 4 patients had no bone destruction,1 patient had soft tissue swelling with bone erosion and subchondral cyst.MRI was performed in 5 patients(71.4%),in which low signal on T1 weighted image,medium signal on T2 weighted image and edema signal on peripheral tendon sheath were seen in 1 patient.One patient(14.3%)underwent emission computed tomography(ECT)without abnormal uptake.Conclusion Joint flexion contracture may be the first sign of amyloid arthropathy.Vigilance for amyloid arthropathy is warranted when there is associated soft tissue involvement,negative autoantibodies,and imaging showing no joint destruction but surrounding soft tissue abnormalities.

Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.

OBJECTIVE: To evaluate the clinical features, laboratory and imaging results, treatment and outcomes of eosinophilic fasciitis (EF) and assess the value of ultrasound in the diagnosis of EF. METHODS: We retrospectively analyzed the clinical data of 45 patients with EF treated in our center from January 1, 2006 to February 28, 2022. The consistency between the diagnoses of EF based on ultrasound and MRI findings was assessed. RESULTS: In the 45 EF patients (male/female ratio 3.5:1), the age of onset ranged from 16 to 64 years with a mean disease course of 22.6 months. The average time from symptom onset to diagnosis was 16 months. The most common possible trigger of the disease was vigorous exercise (10/45), causing symmetrical lesions in the limbs, most commonly in the forearms (86.7%) and lower legs (80%). Clinical features of EF included subcutaneous swelling and induration (95.6%), arthralgia and arthritis (55.6%), groove sign (42.2%), hand joint contractures (42.2%), skin pigmentation (37.8%), and peau d'orange appearance (13.3%). Eosinophilia was found in 31 patients (68.9%). Hypergammaglobulinemia was seen in 23/44 (52.3%) and positive antinuclear antibodies in 9 (20%) of the patients. Twentyone of the patients were treated with high-dose methylprednisolone (≥200 mg daily for 3 to 5 consecutive days), and compared with the patients who did not receive this treatment, these patients more frequently experienced relapse before admission, had more extensive involvement, and had a higher rate of hypergammaglobulinemia without fever, but these differences were not statistically significant. Of the 31 patients (68.9%) with follow-up data (for a median of 3.2 years [range 0.2-15.9]), complete remission was achieved in 12 (38.7%) patients, and the accumulative complete remission rate was 44.1% at 5.5 years. No specific baseline characteristics or immunosuppressants were found to correlate with the treatment response. A total of 26 patients underwent both ultrasound and MRI examination, and the Kappa value of the diagnostic results between ultrasound and MRI was 0.91. CONCLUSION EF is characterized by symmetrical subcutaneous swelling and induration in the limbs, accompanied by eosinophilia and hypergammaglobulinemia. Glucocorticoid is effective for treating EF. Ultrasound examination can identify thickening of subcutaneous fascia for an early diagnosis of EF.
Humans ; Female ; Male ; Infant ; Child, Preschool ; Retrospective Studies ; Hypergammaglobulinemia ; Eosinophilia ; Ultrasonography ; Hand ; Contracture ; Treatment Outcome

Objective: To measure and analyze the shoulder circumferences of adults' permanent teeth crown preparations based on data collected through the intraoral scanning, so as to provide dental anatomy data for clinical diagnosis and analysis. Methods: Intraoral scanning data of 840 complete crown preparations were collected, and were entrusted to the World Dental Laboratory Co., Ltd. in Fuzhou between March 2021 and June 2022. Except the data of the third molar, the rest data were categorized in terms of 14 tooth positions in the upper and lower jaw (each category involved 30 samples from male group and 30 samples from female group). Image measurement software was used to measure the shoulder circumferences of permanent teeth crown preparations. And analysis was conducted to reveal the difference of shoulder circumference diameters between male and female groups. And then they were grouped according to the mean value at each tooth position, on the premise that the difference between the maximum and minimum values and the mean value of the entire group was≤±1.00 mm. Analysis were further conducted to determine the differences of shoulder circumference diameters between each dental position and the differences between male and female in the same groups. Results: Bivariate analysis of variance showed that gender had no effect on the shoulder circumference of full crown preparations (F=0.55, P=1.457), while tooth position had a significant impact on the shoulder circumference of full crown preparations (F=273.15, P<0.001). The samples were classified into 5 groups according to the mean values of shoulder circumference diameters relating to each tooth position. Statistical analysis showed that Group 1, covering maxillary lateral incisor, mandibular central incisor and mandibular lateral incisor, had shoulder circumference with diameters of (16.62±2.21) mm; Group 2, consisting of maxillary central incisor, maxillary cusp, mandibular cusp, mandibular first premolar and mandibular second premolar, had diameters of (20.78±2.48) mm; Group 3, consisting of maxillary first premolar and maxillary second premolar, had diamerters of (22.09±2.72) mm; Group 4, covering maxillary first molar, maxillary second molar and mandibular first molar, had diamerters of (30.21±2.67) mm; while group 5, with mandibular second molar alone its member, had diamerters of (31.34±3.18) mm. The difference among the 5 groups was statistically significant (P<0.05). Conclusions: Significant differences of shoulder circumference diameters could be found between different tooth positions, while at the same tooth position, the differences between male and female are not significant. The 14 tooth positions could be grouped into 5 groups according to their shoulder circumference diameters. Future research could take the grouping as reference.

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

China/epidemiology* ; Morbidity

ObjectiveTo explore the effect of health locus of control on the early rehabilitation after anterior cruciate ligament（ACL） reconstruction. MethodsFrom July 2019 to October 2019， a prospective cohort study of 155 ACL patients receiving reconstruction （male=124 and female=31） in our hospital was conducted. The general data questionnaire， MHLC-C， Tegner activity score， IKDC Score， Lysholm Score and Y-Balance Test were used for further analysis. The correlation between HLC and early rehabilitation after ACL reconstruction was explored by Wilcoxon signed-rank tests， correlation analysis and Logistics regression analysis. ResultsPositive correlations were found between the internality health locus of control （IHLC） and the IKDC score （r_3m=0.77， r_6m=0.70， P<0.001）， as well as the Lysholm scores （r_3m=0.68， r_6m=0.64， P<0.001） and the Tegner activity score （r_3m=0.24， r_6m=0.46， P<0.05） in 3 and 6 months after surgery， and higher IHLC score indicated a better y-balance test outcome［OR 95%CI=0.86（0.76， 0.97）， P=0.016］. Chance health locus of control （CHLC） was negatively correlated with the IKDC score （r_3m=-0.71， r_6m=-0.67， P<0.001）， the Lysholm score （r_3m=-0.49， r_6m=-0.43， P<0.001） and the Tegner activity score （r_3m=-0.22， r_6m=-0.35， P<0.05） in 3 and 6 months after surgery， and higher CHLC score indicated worse outcome of y-balance test ［OR 95%CI=1.26（1.12， 1.41）， P<0.001］. There was a negative correlation between the Powerful others health locus of control （PHLC） and the IKDC score （r_3m=-0.51， r_6m=-0.50， P<0.001）， the Lysholm scores （r_3m=-0.36， r_6m=-0.40， P<0.001）， but there was no correlation with the Tegner activity score in 3 and 6 months after surgery（P>0.05）. The risk of poor y-balance test increased by higher score of PHLC ［OR 95%CI=1.74（1.29， 2.34）， P<0.001］. ConclusionA significant correlation was found between the health locus of control and the early rehabilitation effect after ACL reconstruction. Higher internality health locus of control scores indicated a better rehabilitation outcome， while higher scores of external loci of control indicated higher risk of worse rehabilitation outcome.

Objective: To establish a method for the induction of peripheral blood mononuclear cells to hepatocyte-like cells, and preliminarily investigate cell response to injury under the effect of acetaminophen (APAP). Methods: The surface marker CD45 of peripheral blood mononuclear cells wase detected cells by using flow cytometry and immunofluorescence methods. The cellular morphology of induced hepatocyte-like cells was observed under an inverted microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the expression level of hepatocyte-specific genes, such as cytochrome (CY) P1A2, CYP3A4, CYP2C9, albumin (ALB), alpha-fetoprotein (AFP), and hepatocyte nuclear factor (HNF)4α mRNA. Immunofluorescence method was used to detect intracellular hepatocyte markers AFP, HNF4α, and ALB expression at the protein level. Biochemical analyzer was used to detect hepatocyte-specific secretory functions of AFP, ALB, and urea. Luciferase chemiluminescence method was used to detect the activity of key drug metabolizing enzyme CYP3A4. Colorimetric assay was used to detect the effect of the drug acetaminophen on hepatocyte-like cells, and alanine aminotransferase (ALT) was used as an indicator of liver cell injury. The statistical differences between the data were compared with t-test and rank-sum test. Results: The positive expression rate of CD45 cell surface markers isolated from peripheral blood mononuclear cells was about 98%, and hepatocyte-like cell morphology changes appeared on 15th day of induction. Compared with isolated mononuclear cells, CYP1A2, CYP3A4, CYP2C9, ALB, AFP and HNF4α mRNA was markedly elevated. The expression level of AFP, ALB and HNF4α protein were equally increased, and the secretory function of AFP, ALB and urea were enhanced. Compared with primary hepatocytes, CYP1A2, CYP2C9, AFP, HNF4α mRNA, and CYP3A4 mRNA did not decrease. The expression levels of AFP, ALB, and HNF4α proteins in the cells did not decrease, and the secretory function of AFP, ALB, and urea did not decrease. In addition, the CYP3A4 enzyme activity produced by hepatocyte-like cells was similar to that of primary hepatocytes. Compared with hepatocyte-like cells incubated without APAP, hepatocyte-like cells incubated with APAP had higher ALT level. Under the effect of APAP, the ALT level of hepatocyte-like cells was higher than isolated mononuclear cells. Conclusion: Peripheral blood mononuclear cells can be induced into hepatocyte-like cells with partial characteristics of hepatocytes, including the activity of CYP3A4, a key enzyme of hepatocyte drug metabolism. Additionally, preliminarily ALT secretory features reflect the hepatocytes injury under the effect of acetaminophen.
Acetaminophen/pharmacology* ; Cell Differentiation ; Cells, Cultured ; Hepatocytes ; Leukocytes, Mononuclear ; RNA, Messenger