AIM:To establish a nomogram model to predict the effect of serum ferritin on diabetic retinopathy and evaluate the model.METHODS:A total of 21 variables, including ferritin, were screened by univariate and multivariate regression analysis to determine the risk factors of diabetic retinopathy. A nomogram prediction model was established for evaluation and calibration.RESULTS:Ferritin, duration of diabetes, hemoglobin, urine microalbumin, regularity of medication and body mass index were included in the nomogram model. The consistency index of the prediction model with serum ferritin was 0.813(95%CI: 0.748-0.879). The calibration curves of internal and external verification showed good performance, and the probability of the threshold suggested by the decision curve was in the range 10% to 90%. The model had a high net profit value.CONCLUSIONS:Serum ferritin is an important risk factor for diabetic retinopathy. A new nomogram model, which includes body mass index, duration of diabetes, ferritin, hemoglobin, urine microalbumin and regularity of medication, has a high predictive accuracy and could provide early prediction for clinicians.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

OBJECTIVE To explore the antitumor effect and mechanism of total alkaloids of Gelsemium elegans （TA） and sempervirine （SPV） in vitro. METHODS The effects of low， medium and high concentrations of TA （50， 100， 200 μg/mL） and SPV （10， 30， 50 μmol/L） on the morphology of human hepatoma cells （HepG2， Bel-7402）， human lung cancer cells （A549） and human colon cancer cells （HCT-8） were observed， and the toxicity of TA and SPV to four tumor cells was monitored. The effects of TA and SPV on the contents of caspase-3 and caspase-9 in the supernatant of HCT-8 cells， the protein expressions of phosphorylated protein kinase B （p-Akt） （Thr308， Ser473）， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， survivin， C/EBP-homologous protein （CHOP）， immunoglobulin binding protein （Bip） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） in HCT-8 cells were detected. RESULTS After the intervention of TA and SPV， the volume reduction and nuclear shrinkage were founded in four tumor cells； the cell activity decreased to varying degrees， among which TA and SPV had the best inhibitory effect on HCT-8 cells. After the intervention of TA and SPV， the contents of caspase-3 and caspase-9 in the supernatant of HCT-8 cells， the protein expressions of Bax， CHOP， Bip and LC3Ⅱ all increased to different degrees， while the protein expressions of p-Akt （Thr308， Ser473）， Bcl-2 and survivin in HCT-8 cells all decreased to different degrees. CONCLUSIONS TA and SPV have inhibitory effects on the above four tumor cells， and the inhibitory effect on HCT-8 cells is the best. The mechanism of their action on HCT-8 cells may be related to promoting apoptosis， activating endoplasmic reticulum stress and autophagy.

Global Burden of Disease ; Risk Factors ; Quality-Adjusted Life Years

【Objective】 To explore the effect of lactate and alkali deficiency on the need for red blood cell transfusion in emergency of patients with traumatic hemorrhagic shock. 【Methods】 A total of 126 patients with traumatic hemorrhagic shock in our hospital from January 2019 to December 2021 were retrospectively analyzed, and the 99 cases with effective treatment were divided into two groups according to the outcome of blood transfusion within 24 hours after admission: non-transfusion group (n=36) and transfusion group (n=63). The changes of lactic acid (Lac), alkali deficiency (BE), hemoglobin (Hb), hematocrit (Hct) at admission, hemoglobin (Hb), hematocrit (Hct) 24 hours after admission and the length of stay in ICU were compared between the two groups. The binary logistic regression was used to analyze the risk factors of whether there was a need for blood transfusion at the time of emergency admission. The correlation between individual and combined indicators of each risk factor and the need for blood transfusion were analyzed by the receiver operating curve (ROC). 【Results】 The mean level of Lac (2.90±1.82) in the non-transfusion group at admission was lower than that in the transfusion group (5.80±2.83) (P<0.05), while BE、Hb and Hct (-1.76±3.24, 120.78±20.83, 35.76±6.11) were higher than those in the transfusion group (-5.91±4.69, 101.32±29.68, 29.97±8.48) (P<0.05). The mean levels of Hb and Hct in the two groups 24 hours after admission (92.75±16.66, 78.49±15.91) and (27.62±5.24, 22.60±4.74) were lower than those at admission (P<0.05). Binary logistic statistical analysis confirmed that Lac (OR=1.74, 95% CI 1.493-2.927, P<0.01), BE (OR=0.77, 95% CI 0.676-0.883, P<0.01), Hb (OR=0.97, 95% CI 0.954-0.989, P<0.01), Hct (OR=0.90, 95% CI 0.844=0.96, P<0.01) had guiding significance for patients with traumatic hemorrhagic shock to have red blood cell transfusion demand, and the increase of blood lactic acid was an independent risk factor (P<0.05), while age and gender had no significant effect on it(P>0.05)The maximum AUG of Lac and BE(0.875, 0.766) in predicting the need for emergency red blood cell transfusion in patients with traumatic hemorrhagic shock was significantly better than that of Hb and Hct (0.692, 0.682); the optimal threshold for Lac was >3.6 mmol/L, while the optimal threshold for Hb is ≤106 g/L; the maximum AUG obtained by ROC curve analysis combined with Lac, BE, Hb and Hct was 0.910, which was higher than that of the sole virable. Comparative predictive value using the optimal thresholds of Lac and Hb as indications for transfusion showed that Lac had better predictive value than Hb. 【Conclusion】 Lac and be can be instructive for patients with traumatic hemorrhagic shock as to whether they need red blood cell transfusion in an emergency setting, and combination of Lac, BE, Hb and Hct may help to determine the transfusion needs of patients more timely and accurately and optimize the transfusion management of emergency patients.

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
Female ; Humans ; Male ; Bilirubin ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Adult ; Middle Aged ; Glucuronosyltransferase/genetics*

OBJECTIVE: To investigate the regulatory effects of miR-26a-5p on the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) by regulating cAMP response element binding protein 1 (CREB1). METHODS: The adipose tissues of four 3-4 weeks old female C57BL/6 mice were collected and the cells were isolated and cultured by digestion separation method. After morphological observation and identification by flow cytometry, the 3rd-generation cells were subjected to osteogenic differentiation induction. At 0, 3, 7, and 14 days after osteogenic differentiation induction, the calcium deposition was observed by alizarin red staining, ALP activity was detected, miR- 26a-5p and CREB1 mRNA expressions were examined by real-time fluorescence quantitative PCR, and CREB1 protein and its phosphorylation (phospho-CREB1, p-CREB1) level were measured by Western blot. After the binding sites between miR-26a-5p and CREB1 was predicted by the starBase database, HEK-293T cells were used to conduct a dual-luciferase reporter gene experiment to verify the targeting relationship (represented as luciferase activity after 48 hours of culture). Finally, miR-26a-p inhibitor (experimental group) and the corresponding negative control (control group) were transfected into ADSCs. Alizarin red staining, ALP activity, real-time fluorescent quantitative PCR (miR-26a-5p) and Western blot [CREB1, p-CREB1, Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN)] were performed at 7 and 14 days after osteogenic induction culture. RESULTS: The cultured cells were identified as ADSCs. With the prolongation of osteogenic induction culture, the number of calcified nodules and ALP activity significantly increased ( P<0.05). The relative expression of miR-26a-5p in the cells gradually decreased, while the relative expressions of CREB1 mRNA and protein, as well as the relative expression of p-CREB1 protein were increased. The differences were significant between 7, 14 days and 0 day ( P<0.05). There was no significant difference in p-CREB1/CREB1 between different time points ( P>0.05). The starBase database predicted that miR-26a-5p and CREB1 had targeted binding sequences, and the dual-luciferase reporter gene experiment revealed that overexpression of miR-26a-5p significantly suppressed CREB1 wild-type luciferase activity ( P<0.05). After 7 and 14 days of osteogenic induction, compared with the control group, the number of calcified nodules, ALP activity, and relative expressions of CREB1, p-CREB1, OCN, and RUNX2 proteins in the experimental group significantly increased ( P<0.05). There was no significant difference in p-CREB1/CREB1 between the two groups ( P>0.05). CONCLUSION Knocking down miR-26a-5p promoted the osteogenic differentiation of ADSCs by up-regulating CREB1 and its phosphorylation.
Animals ; Female ; Mice ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Mesenchymal Stem Cells ; Mice, Inbred C57BL ; MicroRNAs/metabolism* ; Osteocalcin/metabolism* ; Osteogenesis/genetics* ; RNA, Messenger/genetics*

OBJECTIVE: To evaluate outcomes of mixed unicompartmental knee arthroplasty(UKA) and total knee arthroplasty(TKA) in the treatment of medial osteoarthritis(OA) of the knee. METHODS: Retrospective analysis of 156 patients, 44 males and 112 females, aged from 50 to 75 years old with an average of(58.76±4.97) years old, who underwent knee arthroplasty from October 2017 to October 2019. The patients were divided into two groups:81 cases(81 knees) underwent TKA, including 23 males and 58 females, aged from 51 to 75 years old with an average of (58.60±5.01) years old, and 75 case (75 knees) underwent UKA with mixed phase 3 Oxford, including 21 males and 54 females, aged from 50 to 72 years old with an average of (58.92±4.95) years old. The two groups were compared regarding to the clinical outcomes, assessed using surgical information and complications, American Knee Society score(AKSS) clinical score and functional score. Radiographs were assessed using hip-knee-ankle angle(HKA), tibial component valgus/varus angle(TCVA), tibial component posterior slope angle(TCPSA), femoral component valgus/varus angle(FCVA), femoral component posterior slope angle(FCPSA), looking for bearing dislocation, prosthesis loosening, progression of OA in lateral compartment. RESULTS: Intraoperative bleeding, operative time and hospital days were significantly better in the UKA group than in the TKA group (P<0.05), and there were no postoperative complications in either group. Patients in both groups were enrolled with an average follow-up time of (38.01±8.90) months, ranged from 24 to 54 months. AKSS functional, AKSS clinical, HKA in both groups significantly improved at the final follow-up compared with those before operation. At the final follow-up, the UKA group was significantly better than the TKA group in AKSS functional and AKSS clinical, whereas HKA in the TKA group was better. At the final follow-up. TCVA and FCVA between the two groups were not significantly different, while TCPSA and FCPSA in the UKA group were significantly greater than the TKA group. No signs of progression of OA to the lateral compartment were observed. CONCLUSION Mixed phase 3 Oxford UKA in medial unicompartmental knee osteoarthritis was considerably better than TKA for less blood loss, shorter operation time, shorter hospital stay, rapid postoperative recovery, helping achieve satisfactory function, provided satisfactory outcome.
Male ; Female ; Humans ; Middle Aged ; Aged ; Arthroplasty, Replacement, Knee ; Osteoarthritis, Knee/surgery* ; Retrospective Studies ; Treatment Outcome ; Knee Joint/surgery* ; Knee Prosthesis

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome