BACKGROUND:There are some problems such as bone fusion failure or peri-implant infection after implantation of pure titanium implants.Therefore,surface improvement of titanium implants has become a hot topic in research.Macrophages are an immune defense line of the body in response to external stimuli,and the relevant immune response of any biomaterials implanted in the body is related to macrophages. OBJECTIVE:The graphene oxide/hydroxyapatite composite coating on titanium alloy surface was prepared by electrochemical deposition method.The surface characteristics of the coating and the growth and polarization of macrophage RAW264.7 on the surface were analyzed. METHODS:The graphene oxide coating and graphene oxide/hydroxyapatite composite coating on titanium alloy surface was prepared by electrochemical deposition method.The physical properties of the coating were characterized.Pure titanium sheets(blank group),titanium sheets deposited with pure GO coating(control group)and titanium sheets deposited with graphene oxide/hydroxyapatite composite coating(experimental group)were co-cultured with macrophages RAW264.7,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell adhesion on the surface of titanium was observed by scanning electron microscopy,and cell polarization phenotype was detected by flow cytometry. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the pure titanium sheet showed directional scratches and a few punctate pits.After the pure graphene oxide coating was deposited,the surface of titanium sheet showed more cracks,gullies and particles of uneven size,and the wrinkle-like structure characterized by graphene oxide.After the composite coating was deposited,the surface of the titanium sheet was smooth,and the pellet size was more uniform.The water contact angle of composite coated titanium sheet was lower than that of pure titanium sheet and pure graphene oxide coated titanium sheet(P<0.05).(2)CCK-8 assay and DAPI staining showed that compared with the blank group and the control group,the cell proliferation in the experimental group was faster.Scanning electron microscopy showed that RAW264.7 cells all adhered to the surface of the three groups of titanium sheets.With the extension of culture time,cell morphology changed from round to spindle shape.After 7 days of culture,cells in the blank group extended short and few pseudopods;cells in the control group extended long and more pseudopods,and cells in the experimental group extended short and more pseudopods,and the overall cell fullness in the experimental group was the best.Flow cytometry results showed that the cells in the experimental group showed a higher proportion of M2 polarization in the anti-inflammatory direction.(3)These findings conclude that graphene oxide/hydroxyapatite composite coating has good physical,chemical,and biological properties.

Objective The critical genes associated with exhausted CD8+T cells were screened and validated by mapping the single-cell transcriptome profile of high-grade serous ovarian cancer(HGSOC).Methods The specific subtypes of T cells in the tumor microenvironment were analyzed using the single-cell sequencing data from the early stage of laboratory(SRA database:PRJNA756768)and integrating 5 HGSOC sequencing from the database,and the differentiation trajectory of T cell subsets was ex-plored through pseudotime analysis.Differential gene enrichment was used to determine immunosuppressed CD8+IL-2Low and CD8+IFN-γLow T cell subsets and differential genes,and candidate molecules closely related to exhausted CD8+T cells were screened based on patient prognosis.Flow cytometry was used to analyze the expression of PHLDA1 on CD8+T cells,CD4+T cells and Treg cells dur-ing the activation to exhaustion process of T cells in human PBMCs.ELISA was used to detect the levels of IFN-γ and IL-2 secreted by CD8+T cells in PHLDA1High and PHLDA1Low.Finally,flow cytometry was used to analyze the association between PHLDA1 and ex-hausted markers PD-1 and TIM-3.Results The results showed that T cells were grouped in three ways:(1)IL-2High and IL-2Low;(2)IFN-γHigh and IFN-γLow;and(3)exhausted and cytotoxic CD8+T cells.Subsequently,the intersection of its differentially expressed genes was taken,and the key gene PHLDA1 was ultimately screened.Flow cytometry analysis suggested that during the process of T cell activation to exhaustion,the expression of PHLDA1 continued to increase on CD8+T cells,CD4+T cells and Treg cells;The ELISA results showed that the levels of IFN-γ and IL-2 secreted by CD8+PHLDA1High T cells were significantly lower than those of CD8+PHLDA1Low T cells.Meanwhile,the CD8+PHLDA1High T cell subset could simultaneously cover the exhausted T cell types of CD8+TIM-3+and CD8+PD-1+.Conclusion Based on single-cell sequencing data,this study identified PHLDA1 as a key molecule responsi-ble for CD8+T cell exhaustion in OC,providing new insights for immunotherapy of OC.

BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION Chictr.org, ChiCTR 1800018895.
Humans ; Aged ; Sarcopenia/diagnosis* ; Deep Learning ; Aging ; Algorithms ; Biomarkers

Objective:To study the expression level of programmed death ligand 1 (PD-L1) in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and its correlation with the clinical characteristics and prognosis.Methods:The clinical data of 75 patients with cHCC-CCA undergoing surgery in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019, including 61 males and 14 females, with a median age of 55 years (36 to 77). Immunohistochemistry was conducted to determine the PD-L1 expression in tumor. The status of PD-L1 expression, clinicopathological data and prognosis of patients were analyzed.Results:In low-differentiated cHCC-CCA tissues, the proportion of PD-L1 expression (21.1%, 8/38) was higher than that in moderately to well-differentiated cHCC-CCA tissues (2.70%, 1/37, χ2=4.366, P=0.037). The median disease-free survival (DFS) and overall survival (OS)of PD-L1 positive patients were 12.3 and 15.1 months, respectively, lower than those of PD-L1 negative patients (14.4 and 23.3 months). The difference of DFS was statistically significant ( χ2=4.052, P=0.044). In multivariate analysis, major vascular invasion (DFS: HR=1.965, 95% CI: 1.119-3.450, P=0.019; OS: HR=1.781, 95% CI: 1.022-3.105, P=0.042) and lymph node metastasis (DFS: HR=2.451, 95% CI: 1.1033-5.814, P=0.042; OS: HR=2.652, 95% CI: 1.120-6.279, P=0.027) were identified as independent prognostic factors affecting DFS and OS. Conclusions:The proportion of PD-L1 positive is higher inthe low-differentiated cHCC-CCA tissue compared to that in moderately to well-differentiated cHCC-CCA. The major vascular invasion and lymph node metastasis are independent factors affecting the prognosis of patients with cHCC-CCA.

Objective:To investigate the clinicopathologic characteristics of hepatic echinococcus granulosus (HEG).Methods:Thirteen cases of HEG were collected from Linzhi People′s Hospital between January 2017 to October 2020, and their clinicopathologic features, ultrasound classi?cation, immunophenotype and histochemical data were analyzed, retrospectively and the relevant literature was reviewed.Results:Thirteen patients (5 male patients, 8 female patients) were included in this cohort, and the mean age was 40 years. The most common clinical presentation was mild abdominal distention and pain (9/13). Based on WHO-IWGE ultrasound standardized classi?cation, these cases were classified into 5 types, including type CL (1 case), type CE1 (2 cases), type CE2 (4 cases), type CE3 (3 cases) and type CE4 (3 cases). Gross examination revealed a solitary cyst localized in the liver, varying from 2.7 to 13.5 cm in diameter, and most of them(10/13)were more than 10 cm. Histopathologically, these cysts possessed a thin inner germinal layer and outer adventitial layer, and a central cavity ?lled with a clear"hydatid"?uid. The germinal layer was continuous and generated brood capsules and protoscoleces. The laminated membranes were clearly demonstrated by elastic fiber and Gomori′s stains. Inside the"mother"cyst, there were a varying number of"daughter"vesicles of variable sizes. The inflammatory reaction around the cyst consisted of eosinophils, mononuclear cells immediately next to the cyst layer and sometimes formed granuloma and giant cells resembling the Langhan′s type giant cells. The lymphoid cells were positive for CD20 and CD3. The CD68 immunohistochemistry clearly demonstrated epithelioid cells of granuloma in two cases. Moreover, immunohistochemistry revealed plasma cells were locally positive for CD38, IgG and IgG4, but not meeting the criteria for IgG4 related lesion.Conclusions:Hepatic echinococcus granulosus is a zoonotic parasitic disease prevalent in pastoral areas such as Tibet. It is important to understand its clinical features, ultrasound characteristics and histological morphology.

Objective:To explore the protective effect of vitamin D in acute liver failure through a mouse model.Methods:Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1β, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test.Results:Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1β, and NLRP-3 mRNA expression ( P < 0.05), and increased macrophages quantitation ( P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury ( P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise ( P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues ( P < 0.05). Conclusion:Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.

Objective:To develop a geriatric nursing core literacy evaluation scale and to test its validity and reliability.Methods:The scale item pool was constructed by referring to relevant literatures and expert consultation method was used to form initial scale. A preliminary investigation was conducted among 40 nurses to form the formal scale, and then 252 nurses were selected to test the validity and reliability of the formal scale.Results:The formal scale consisted of four dimensions and 37 items. The Cronbach α coefficient of the formal scale was 0.980, the content validity index was 0.912, exploratory factor analysis identified 4 principal factors (knowledge geriatric nursing core literacy, skill geriatric nursing core literacy, cognitive geriatric nursing core literacy, belief geriatric nursing core literacy) and explained 73.135% of the total variance.Conclusion:The geriatric nursing core literacy evaluation scale has good reliability and validity, which can be used to evaluate the geriatric nursing core literacy of nursing staffs.

Objective:To explore the feasibility and safety of minimally invasive surfactant administration (MISA) in preterm neonates with respiratory distress syndrome (NRDS).Methods:In this multicenter prospective randomized controlled trial, 92 preterm infants with gestation age ≤30 weeks and diagnosed with NRDS were enrolled in 8 level Ⅲ neonatal intensive care units (NICU) in Beijing-Tianjin-Hebei Region from 1 st July 2017 to 31 st December 2018. They were randomly assigned to minimally invasive surfactant administration (MISA) group or endotracheal intubation surfactant administration (EISA) group according to random number generated by computer. Infants in both groups received calf pulmonary surfactant preparation at a dose of 70-100 mg/kg. The data of demography, perinatal situation, medication administration, complications, clinical outcomes in the two groups were compared with Chi-square test, Student′s t-test, Mann-Whitney U test or Fisher′s exact test. Results:Among the 92 preterm infants, 53 were males, 39 were females; 47 were in the MISA group (25 males), and 45 were in the EISA group (28 males). The gestational age and birth weight were (29.5±1.2) weeks and (1 271±242) g in all patients, (29.5±1.4) weeks and (1 285±256) g in the MISA group, and (29.6±0.9) weeks and (1 255±227) g in the EISA group. The duration of surfactant infusion and the length of whole procedure in the MISA group were significantly longer than that in the EISA group (60 (18, 270) s vs. 50 (30, 60) s, Z=3.009, P=0.003; 90 (60, 300) s vs. 60 (44, 270) s, Z=3.365, P=0.001). For the outcomes, the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and bronchopulmonary dysplasia (BPD) were lower in the MISA group than in the EISA group (36% (17/47) vs. 67% (30/45), χ 2=8.556, P=0.003; 26% (12/47) vs. 47% (21/45), χ 2=4.464, P=0.035). Conclusions:Minimally invasive surfactant administration is applicable in preterm infants ≤30 weeks gestational age with NRDS. Although the length of whole procedure is longer than route endotracheal administration, the benefit of decreasing the incidences of hsPDA and BPD outweighs this demerit.

OBJECTIVE： To evaluate the effectiveness of trolamine for preventing and treating radiation dermatitis （RD） and evidence quality， and to provide reference for clinical use. METHODS： Retrieved from PubMed， Cochrane library， Embase， CNKI， Wanfang and VIP database， randomized controlled trials （RCTs） about trolamine （trial group） versus usual care （control group） for preventing and treating RD were collected. After data extraction， Cochrane bias risk assessment tool 5.0.2 was used to assess the bias risk， and Rev Man 5.3 statistical software was used to perform the Meta-analysis. GRADE evidence quality grading system was used to evaluate the evidence quality of outcome indexes. RESULTS： Seven RCTs were included， involving 782 patients. Results of Meta-analysis showed that there was no statistical significance in total incidence of RD [OR＝0.50， 95％CI （0.23， 1.11）， P＝0.09]， and the incidence of grade Ⅰ RD [OR＝1.32， 95％CI（0.96，1.81）， P＝0.09]， grade Ⅱ RD [OR＝1.07， 95％CI（0.80，1.42）， P＝0.66]， grade Ⅲ RD [OR＝0.69， 95％CI（0.45，1.04）， P＝0.07] or grade Ⅳ RD [OR＝0.43， 95％CI（0.17，1.05）， P＝0.07] between 2 groups. Results of Grade evidence quality evaluation showed that total incidence of RD， and the incidence of grade Ⅱ RD and grade Ⅳ RD were recommended by moderate-level evidence in 2 groups， while the incidence of grade Ⅰ and grade Ⅲ RD were recommended by low-level evidence. CONCLUSIONS： Trolamine is not effective in preventing and treating RD， and can not reduce the incidence of RD.

Objective To compare the effects of the equivalent analgesic doses of sufentanil, fentanyl and dizosin on index of consciousness (IoC) and their adverse reactions. Methods Eighty patients undergoing painless gastroenteroscopy, aged 18～60 years, ASA grade Ⅰ to Ⅱ, were selected. The patients were randomly divided into control group (group C) , sufentanil group (group S) , fentanyl group (group F) , and dizosin group (group D) , with 20 cases in each group. Sufentanil 0.1～0.2 μg/kg, fentanyl 1～2μg/kg and dizocine 0.1～0.2 mg/kg were intravenously injected in group S, F and D respectively. Group C was given saline of equal volume, and then propofol 2～2.5 mg/kg was intravenously injected until consciousness disappeared.Intravenous infusion of propofol50～100 g/ (kg · min) maintained anesthesia. Heart rate, blood pressure, IoC and perioperative adverse events were recorded. Results There was no significant difference in operative time and recovery time among the 4 groups (P> 0.05). Compared with those in group C, the values of IoC at T2, TS, T4 and T5 in group S and F increased significantly (P < 0.05) , and the correlation coefficient between OAA/S and IoC was 0.872 (P < 0.05). Compared with that in group C, the incidence of nausea and vomiting was higher in group D, and the incidence of injection pain was significantly lower in group S, F and D (P < 0.05). Conclusion Compared with propofol alone, opioids used in painless gastrointestinal endoscopy anesthesia lead to loss of consciousness and increase of IoC value at recovery time, but have no significant effect on recovery time.