Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Background/Aims: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. Methods: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. Results: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). Conclusions FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

A protective device was designed that can be worn on the elderly, which consists of protective airbag, control box and protective mechanism. The combined acceleration, combined angular velocity and human posture angle are selected as the parameters to determine the fall, and the threshold algorithm and SVM algorithm are used to detect the fall. The protective mechanism is an inflatable device based on CO₂ compressed air cylinder, and the equal-width cam structure is applied to its transmission part to improve the puncture efficiency of the compressed gas cylinder. A fall experiment was designed to obtain the combined acceleration and angular velocity eigenvalues of fall actions (forward fall, backward fall and lateral fall) and daily activities (sitting-standing, walking, jogging and walking up and down stairs), showing that the specificity and sensitivity of the protection module reached 92.1% and 84.4% respectively, which verified the feasibility of the fall protection device.
Humans ; Aged ; Monitoring, Ambulatory ; Activities of Daily Living ; Wearable Electronic Devices ; Walking ; Acceleration ; Algorithms

Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

Objective:To investigate the risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer, and application value of a nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 228 patients with stage Ⅱ-Ⅲ colon cancer who underwent radical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to June 2016 were collected. There were 118 males and 110 females, aged from 25 to 87 years, with a median age of 62 years. All patients underwent open or laparoscopic-assisted radical resection of colon cancer. Observation indicators: (1) postoperative tumor recurrence; (2) risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer; (3) development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. Follow-up using outpatient examination and telephone interview was performed to detect postoperative 3-year tumor recurrence up to June 2019. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the Pearson chi-square test or Fisher exact probability. Multivariate analysis was performed using Logistic stepwise regression analysis. The independent risk factors were included into R 3.6.1 software to construct a nomogram prediction model. The receiver operating characteristic curve (ROC) was drawed, and the area under curve (AUC) was used to evaluate discrimination of the nomogram prediction model. The calibration chart with R software was used to evaluate consistency of the nomogram prediction model. Results:(1)Postoperative tumor recurrence: 53 of 228 patients had postoperative tumor recurrence including 19 cases with locoregional recurrence and 34 cases with distant metastasis. Of the 34 patients with distant metastasis, there were 14 cases with liver metastasis, 7 cases with lung metastasis, 4 cases with brain metastasis, and 9 cases with multiple metastasis or isolated metastasis in other sites. The time to recurrence was 12 months (range, 6-19 months). (2) Risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer:results of univariate analysis showed that bowel obstruction, preoperative carcinoembryonic antigen (CEA) level, ascites, vascular invasion were related factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( χ2=4.463, 13.622, 10.914, 5.911, P<0.05). Pathological N stage was also a related factor for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( P<0.05). Results of multivariate analysis showed that preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 were independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( odds ratio=3.129, 3.071, 7.634, 3.439, 15.467, 95% confidence interval as 1.328-7.373, 1.047-9.007, 1.103-52.824, 1.422-8.319, 3.498-68.397, P<0.05). (3) Development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer: based on preoperative CEA level, ascites, vascular invasion and pathological N stage of multivariate analysis, a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was developed using R 3.6.1 software. The nomogram score was 41.7 for preoperative CEA level >5 μg/L, 41.0 for ascites, 74.2 for vascular invasion, 45.1 and 100.0 for pathological N stage as stage N1 and N2, respectively. The total of different scores for risk factors corresponded to the probability of postoperative recurrence. The ROC of nomogram for recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was drawed,with the AUC of 0.805(95% confidence interval as 0.737-0.873, P<0.05). The calibration chart showed a good consistency between the probability of recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer predicted by nomogram and the actual probability of postoperative recurrence. Conclusions:Preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 are independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. The nomogram prediction model contributes to prediction of the recurrent risks after radical resection of stage Ⅱ-Ⅲ colon cancer.

Objective: To investigate the effects of micronutrient supplementation for the elderly on plasma homocysteine level and cognitive function in institutional older adults. Methods: A total of 98 older adults with the score≤11 by mini nutritional assessment short-form aged 65-100 years were enrolled and assigned to either intervention group or control group (n=49 each), with either a package of micronutrient pack or placebo daily, for three months. Fasting blood samples were collected both at baseline and the end of study to detect serum vitamin B₁₂, folate and plasma homocysteine (Hcy) concentrations. Global cognitive function was assessed using the mini-mental state examination (MMSE). The paired t test was used to compare the continuous variables between the two groups after intervention. The relationship between changes in MMSE score and changes in plasma Hcy concentrations was examined by least-squares linear regression. Results: Eighty-two patients completed the study, and 17 patients withdrew from the study due to diarrhea and hospital discharge with the drop rate of 17.3%. Compared to the control group, concentrations of serum vitamin B₁₂ (128.8±34.8 vs 13.3±16.0 pmol/L, P=0.003) and folate (21.1±1.6 vs 0.6±0.5 nmol/L, P<0.01) significantly increased in the intervention group over 3-month supplementation, while plasma Hcy levels were remarkably reduced (-5.3±0.7 vs 1.7±0.3 μmol/L, P<0.01). The incidences of deficiency of folate, deficiency of serum vitamin B₁₂and high Hcy all decreased in intervention group. Although individual item scores in MMSE were not changed markedly, change of total MMSE score in intervention group were higher than that in the control group (1.2±3.0 vs -0.2±2.5, P<0.05). Conclusions The supplementation of the micronutrient pack in long-term care facilities can reduce the incidence of hyperhomocysteinemia, and improve the total MMSE score.

Objective To investigate the effect of expression of Cullin 4B (CUL4B) on the prognosis of patients after liver transplantation for hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 79 patients who underwent liver transplantation for HCC in the First Affiliated Hospital of Sun Yat-sen University between January 1,2014 and June 30,2015 were collected.The specimens of HCC tissues were collected and embedded in paraffin,and then were detected by immunohistochemistry staining.Observation indicators:(1) expression of CUL4B in HCC tissues;(2) follow-up and survival;(3) prognostic factors analysis after liver transplantation;(4) association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation.Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis and survival up to June 2018.Measurement data with normal distribution were represented as (x)±s.The comparison between groups of count data was done using the chi-square test.The survival curve drawn using the Kaplan-Meier method,and the survival analysis was done by Log-rank test.The univariate and multivariate analysis were respectively done using the COX regression model.The association analysis was done using the Pearson test.Results (1) Expression of CUL4B in HCC tissues:immunohistochemistry staining showed that CUL4B was mainly expressed in the cytoplasm,with a powerful brownish-yellow staining.The high expression and low expression of CUL4B in HCC tissues were detected in 64 and 15 patients,respectively.(2) Follow-up and survival:79 patients were followed up for 38-56 months,with an average time of 46 months.During the follow-up,37 patients had no tumor recurrence and 42 had tumor recurrence (32 with tumor extrahepatic metastasis and 10 with intrahepatic metastasis);36 had survival and 43 died;the 1-and 3-year overall survival rates were respectively 86.84％ and 63.25％,and 1-and 3-year tumorfree survival rates were respectively 62.31％ and 51.27％.(3) Prognostic factors analysis after liver transplantation:① Results of univariate analysis showed that preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Hazard Ratio (HR) =2.17,3.36,3.66,2.43,2.19,3.36,2.84,95％ confidence interval(CI):1.17-4.04,1.53-7.42,2.10-6.42,1.33-4.17,1.08-9.04,1.58-7.59,1.17-6.32,P＜ 0.05].The preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (HR =2.06,3.72,3.16,2.36,2.83,3.21,1.69,95％CI:1.34-4.85,1.72-8.63,1.79-7.31,1.46-4.86,1.19-8.63,1.19-7.92,1.06-4.87,P＜0.05).② Results of multivariate analysis showed that maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Odds ratio(OR) =3.43,3.69,2.81,95％CI:1.16-6.02,1.96-9.38,1.04-9.63,P＜0.05].The maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (OR=2.25,4.72,2.74,95％C1:1.16-4.02,1.98-9.47,1.03-7.10,P＜ 0.05).The 3-year overall survival rate in patients with high-and low-expressions of CUL4B was respectively 66.7％ and 32.8％,with a statistically significant difference (x2 =5.69,P＜0.05).The 3-year tumor-free survival rate in patients with high-and low-expressions of CUL4B was respectively 73.3％ and 18.6％,with a statistically significant difference (x2 =4.63,P＜0.05).(4) Association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation:results of Pearson test showed that expression of CUL4B was significantly associated with HCC recurrence and metastasis after liver transplantation (r =0.62,P＜0.05).The further analysis showed that expression of CUL4B was significantly associated with extrahepatic metastasis after liver transplantation (r=0.84,P ＜ 0.05).Conclusion The expression of CUL4B is associated with HCC recurrence after liver transplantation,and it can be as a predictor for HCC recurrence and distant metastasis after liver transplantation.

Objective To analyze the causes of blood deficiency in the process of voluntary blood donation and to adopt targeted control measures,so as to effectively reduce blood scrapping and to better ensure theclinical blood use of the hospital.Methods The data of blood collection from January 2014 to December 2016 and the various reasons of insufficient blood collection were summarized;and according to these data as the object of study,the targeted measures were taken to observe the effect.Results According to the the reasons for the lack of blood collection,the targeted measures,such as organizing staff training,strengthening communication with blood donors and so on,were taken.After the implementation of these measures,the phenomenon of insufficient blood collection from 2014 to 2016 showed declining trend,withthe proportion decreased from 0.29％ to 0.20％.Conclusion To strengthen the staff staining in order to improve them vein collection technology,to publicize further,to communicate with blood donors effectively and improve the blood donation services,to ease the feelings of blood donors and to create a warm,harmonious and orderly blood donation atmosphere;all of these should be helpful for reducing the occurrence of insufficient blood collection.

Objective To investigate the safety and clinical efficacy of recombinant human endostatin injection (endostar) continuous pumping combine with chemotherapy injection in the treatment of advanced malignancies . Methods 156 patients with advanced cancer were divided into the chemotherapy group (78 cases) and the chemotherapy combined with endostar group (78 cases). The two groups were similar in the tumor types, the neoplasm staging, the KPS and the chemotherapy agents. After two cycles chemotherapy, the efficacy was evaluated according to RECIST criteria and the quality of life (QOL) was assessed by KPS scores. Results The objective response rate (RR) of the chemotherapy combined with endostar group was 39.74%(31/78). The RR of the chemotherapy group was 17.95%(14/78). There was statistics significance in the RRs of the two groups (P<0.05). The QOL of 42 cases (53.8%) were improved, 26 cases (33.3%) were in stable and 10 cases (12.8%) were decreased in the chemotherapy combined with endostar group. The QOL were improved in 30 cases (38.5 %), stabled in 17 cases (21.8 %) and decreased in 31 cases (39.7 %) in the chemotherapy group. There were significant difference between the two groups (P< 0.05). The main adverse reactions were myelosuppression and digestive tract reaction in both groups (P>0.05), and all patients can tolerate. Conclusion The QOL of patients with advanced malignant tumors are improved by endostar combined with chemotherapy which is safe and effective. It is worthy further clinical observation.

Objective To investigate the association between polymorphisms in the tumor necrosis factor α-induced protein 3 (TNFAIP3)-interacting protein 1 (TNIP1) gene and psoriasis vulgaris in a Han population from north China.Methods Totally,465 patients with psoriasis vulgaris (PsV) and 476 healthy human controls were enrolled into the study.Five milliliters of venous blood samples were collected from these subjects after informed consent.Three single nucleotide polymorphisms (SNPs) in the TNIP1 gene,including rs17728338,rs3762999 and rs999556,were selected for genotyping with ligase detection reaction (LDR).With the PLINK 1.07 package,statistical analysis was carried out by using the chi-square test for comparisons of allele frequencies and genotype frequencies between the patient group and control group.The allelic odds ratio (OR) and its 95％ confidence interval (CI) were calculated.In addition,linkage disequilibrium analysis was performed for the three SNPs by calculating the r2 and D' values.Results There was a difference in the allele frequencies of the three SNPs between the patients with psoriasis vulgaris and controls,but the difference was statistically significant in only the allele frequencies of rs17728338,but not in those of the other two SNPs after Bonferroni correction.Under the dominant inheritance model,the genotype frequencies of the 3 SNPs all significantly differed between the patients and controls after Bonferroni correction (all P ＜ 0.016 7).Stratification analysis showed that there was a significant difference in the allele and genotype frequencies of the three SNPs between the patients with a family history and healthy controls (all P ＜ 0.016 7),and the frequency of A allele of rs17728338 was significantly lower in the controls than in the patients with psoriasis vulgaris,patients with early-onset psoriasis vulgaris (n =355),patients with late-onset psoriasis vulgaris (n =107),patients with a family history (n =68),and patients without a family history (n =394) (all P ＜ 0.0167).Strong linkage disequilibrium existed between rs3762999 and rs999556 (r2 =0.910,D' =0.982),and moderate linkage disequilibrium existed between rs17728338 and rs3762999 (r2 =0.371,D' =0.989) as well as rs999556 (r2 =0.353,D' =1).Conclusion The SNPs rs17728338,rs3762999 and rs999556 in the TNIP1 gene were associated with psoriasis vulgaris in the Chinese Han population.