Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

OBJECTIVE: To explore the functional rehabilitation of patients with rheumatoid arthritis (RA) after total knee arthroplasty (TKA). METHODS: A retrospective analysis was conducted on 101 patients who needed TKA due to rheumatoid arthritis (RA) involving both knees from January 2017 to December 2020, including 16 males and 85 females, aged from 41 to 65 years old with an average of (58.13±5.53) years old;body mass index (BMI) ranged from 16.88 to 33.33 kg·m^-2 with an average of (23.16±3.49) kg·m^-2;63 patients with grade 1, 29 patients with grade 2, and 9 patients with grade 3 according to classification of American Society of Anesthesiologists (ASA). According to the latest follow-up results at 12 months after operation, 82 patients returned to work and 19 patients did not return to work. Visual analogue scale(VAS) was used to evaluate the degree of pain relief before operation and 12 months after operation, and work, osteoarthritis and joint replacement questionnaire (WORQ) was used to evaluate knee joint activity status of all patients before and after operation, and the working ability index was used to evaluate working ability of all patients before operation and 12 months after operation. For the 82 patients who returned to work, the labor time stopped before operation and within 12 months after operation was compared, and the changes in labor grades, types of work and labor hours of patients before and after operation were recorded. For the 19 patients who did not return to work, the specific reasons for their non-return to work was analyzed;the postoperative satisfaction of patients was evaluated by using Likert satisfaction scale. All patients were followed up for at least 12 months. VAS was decreased from (6.49±0.59) before operation to (1.10±0.43) at 12 months after operation (P<0.05);for WORQ questionnaire survey, scores of walking, sitting posture, standing and stair climbing were increased from (1.07±0.35), (1.05±0.29), (1.06±0.34) and (1.14±0.42) before operation to (3.00±0.00), (2.87±0.33), (2.95±0.21) and (2.95±0.21) after operation, respectively, had statistically significant (P<0.05);the labor work index of all patients increased from 1.11±0.46 before operation to 2.99±0.10 at 12 months after operation, and the difference was statistically significant (P<0.05). Among the 82 patients who returned to work after operation, regarding the time of stopping labor, 81 patients stopped working within 3 months before operation, 1 patient stopped working for 4 to 6 months after operation, and the number of patients who stopped working was 81, 1, and 0 respectively. Forty patients returned to work within 3 months after operation, 4 to 6 months after operation for 29 patients, and 12 months after operation for 13 patients. 95.1% (78/82) of patients engaged in light labor before operation, and 85.4% (70/82) of patients engaged in moderate labor after operation. At 12 months after operation, the types of jobs and working hours available to all patients increased compared with those before operation. Among 19 patients who did not return to work after TKA, 7 patients had poor control of rheumatoid arthritis, 5 patients still felt pain, swelling and numbness on knee joint, 2 patients had retired, and 5 patients had other reasons. Eighty-six patients (85%) expressed great satisfaction with the postoperative working ability, 8 patients (8%) expressed satisfaction with the postoperative working ability, 6 patients (6%) expressed acceptance of postoperative working ability, and 1 patient (1%) expressed dissatisfaction with postoperative working ability. CONCLUSION TKA is an effective treatment option for patients with RA. After undergoing TKA, patients could significantly improve pain and functional activities of knee joint, and effectively enhance the quality of life and working ability. For patients whose rehabilitation labor capacity is not fully met, postoperative management and personalized rehabilitation treatment need to be strengthened to achieve the best rehabilitation effect.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/rehabilitation* ; Arthritis, Rheumatoid/physiopathology* ; Middle Aged ; Aged ; Retrospective Studies ; Adult

To observe the impacts of continuous lumbar plexus block (CLPB) on postoperative cognitive dysfunction (POCD) in elderly patients undergoing hip arthroplasty.
 Methods: Sixty elderly patients scheduled for hip arthroplasty with general anesthesia, were randomly allocated into a CLPB group and a PCIA group (n=30 each). In the CLPB group, lumbar plexus block was performed before trachea intubation, and CLPB was used for postoperative analgesia. In the PCIA group, intravenous analgesia was controlled in patients after operation. Visual Analogue Scale (VAS) at 12, 24, and 48 h after operation was recorded. Mini-Mental State Examination (MMSE) scale was used to evaluate the cognitive dysfunction at the 1st day before operation (D0) and at the 1st (D1), 3rd (D3), and 7th (D7) days after operation and the occurrence of POCD was recorded. S-100β concentrations were detected by ELISA at D1, D3, and D7. Postoperative adverse events were recorded.
 Results: VAS scores at 12, 24, and 48 h after operation in the CLPB group were significantly lower than those in the PCIA group (P<0.05). Compared with the PCIA group, the MMSE scores were significantly higher (P<0.05), and the incidence of POCD at D1 and D3 was obviously reduced in the CLPB group (P<0.05). S-100β concentration at D1 and D3 in the CLPB group was significantly lower than that in the PCIA group (P<0.05).
 Conclusion: Application of CLPB in elderly patients undergoing hip arthroplasty could obviously relieve their postoperative pain, inhibit the production of S-100β, and reduce the incidence of early postoperative cognitive dysfunction.
Aged ; Analgesics ; administration & dosage ; Arthroplasty, Replacement, Hip ; adverse effects ; Cognitive Dysfunction ; prevention & control ; Humans ; Incidence ; Lumbosacral Plexus ; Nerve Block ; methods ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Postoperative Complications ; prevention & control

Objective To research the efficacy of alprostadil injection combined the octreotide for acute severe pancreatitis and influence on the serum levels of tumor necrosis factor-α(TNF-α),interleukin-6,interleukin-18,occludin.Method 68 cases of patients with acute severe pancreatitis from September 2013 to February 2017 in our hospital,according to the treatment method group,34 cases in each group,control group treatmented by octreotide,the research group based on the control group treatmented by alprostadil injection,both groups was treated for five days.Clinical curative effect,alleviate clinical symptoms time,TNF-α,IL-6,IL-18,occludin,and adverse reactions occur was compared between two groups.Results The total effective rate of research group was higher than the control group(97.07％vs.79.41％,P<0.05).Bowel sounds,stomach ache,body temperature and serum amylase remission time of research group was shorter than control group(P<0.05).TNF-α,IL-6,IL-18 of research group was lower than the control group(P<0.05),the occludin of research group was higher than the control group(P<0.05).The adverse reactions was no differences between the two groups.Conclusion The exact effect of alprostadil injection combined the octreotide for acute severe pancreatitis,improve serum levels of TNF-α,IL-6,IL-18,occludin.

Objectives To observe the effect of low intensity pulsed ultrasound (LIPUS) on osteocyte injuries induced by the tricalcium phosphate(TCP) wear particles in the calvaria of mice.Methods Thirty ICR male mice of 6 to 8 weeks were randomly divided into a normal control group(n=10),a model group (n=10) and a LIPUS-treated group(n=10).A murine calvarial model of osteolysis was established in the model and LIPUS-treated groups through injecting TCP particles onto the surface of bilateral parietal bones at week 1,3,5,7 and 11.Mice in the normal group received negative ultrasound probe pressing,while those in the LIPUS-treated received LIPUS radiation.Three months later,the calvarias were obtained.The micro-CT,HE staining,flow cytometry and Western blotting were performed to estimate the calvarial osteolysis,osteocyte death,apoptosis and proteins expression of the dentin matrix protein 1 (DMP-1),sclerosis protein (SOST),glucose-regulated protein78 (GRP78),inositol-requiring enzyme(IRE 1 α),spliced X-box binding protein 1 (XBP1 s),c-Jun N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase(p-JNK) respectively.Results Compared with the normal control group,in the model group the viability of prosthetic osteocytes decreased significantly,and cell apoptosis was more obvious(P＜0.05);the osteocytic marker protein DMP-1 down-regulated significantly,but another marker protein SOST up-regulated significantly,which caused the decline in DMP-1/SOST(P＜0.05).Moreover,the expression levels of GRP78,IRE1,XBPls and p-JNK of the model group increased significantly(P＜0.05) in the calvaria osteocytes compared to the control group.However,in the LIPUS treatment group,osteocyte injuries and endoplasmic reticulum(ER) stress both decreased significantly,shown by a significant increase in the number and activity of osteocytes,DMP-1/SOST,and significant inhibition of the IRE1α-XBP1-JNK activation(P＜0.05).Conclusion LIPUS prevents osteocyte injuries induced by TCP wear particles in the calvaria of mice,which may be due to the inhibition of IRE1α-XBP1-JNK pathway activation through ER stress reaction.

Objective: To investigate the impacts of paraquat on microRNA profiles in apoptosis of human neural progenitor cells (hNPCs) and to explore miRNA targets and biological functions. Methods: We used hNPCs as a popular in vitro cell model system for characterizing the neurotoxicity. Cell apoptosis was detected by Annexin V-APC/7-AAD after 24 h treatment with different concentrations of PQ (0, 5, 10, 20, 40, 80 μmol/L). Microarray profiling expression of PQ treated cell line and their corresponding control was determined and differentially expression miRNAs were confirmed by quantitatively real-time PCR. The target genes regulated by aberrantly expressed miRNAs were predicted by on line-available software (Target Scan, Miranda, Mirbase). The GO and KEGG pathway database were used to analyze the functions of target genes. Meanwhile, the apoptosis-related protein expressions were evaluated by western blot. Results: cell apoptosis increased with increasing PQ concentrations (from 10 to 80μmol/L) in a dose-dependent manner (P<0.05). miRNA microarray showed that 40 miRNAs were significantly up-regulated while 26 miRNAs were down-regulated after 20 μmol/L PQ treatment (P< 0.05). We selected 6 differentially expressed miRNAs to validate with qRT-PCR. The results were consistent with microarray data for all miRNAs tested. Bioinformatics analysis demonstrated target genes were enriched in regulation of neuron apoptosis and differentiation, MARK signaling pathway as well as P53 signaling pathway. The protein expressions of bax and caspase3 significantly increased while bcl-2 significantly decreased treated with PQ compared with control group (P<0.05). Conclusion There is a specific miRNA expression profile in paraquat-induced apoptosis of hNPCs. Differentially expression miRNAs regulated apoptosis of hNPCs through multiple molecular signaling pathways and especially for mitochondrial apoptosis pathway.

Objective To investigate the effects of Paraquat on human embryonic lung fibroblasts (MRC5) and explore the role of transforming growth factor-β1/connective tissue growth factor signaling pathway in paraquat-induced pulmonary fibrosis.Methods MRC5 cells were cultured with different concentration of PQ (0,12.5,25,50,100,200,400 μ mol/L) for 24 h.The viability of cells was measured by MTT.The protein level of TGF-β1 were analyzed by ELISA after PQ treatment (0,25,50,I00 μmol/L).To examine whether TGF-β1/CTGF signaling pathway was involved in paraquat-induced cytotoxicity,cells was divided into 6 groups:(1) control;(2) 25 μ mol/L PQ group;(3) 50 μ mol/L PQ group;(4) 100 μmol/L PQ group;(5) TGF-β1 positive control group (50 μmol/L rhTGF-β1);(6)stimulate group (100 μmol/L PQ+50 μ mol/L TGF-β1).The protein levels of p-Smad2,p-Smad3 and CTGF were assayed by western blot.The mRNA level of CTGF was assayed by real time RT-PCR.Results MTT showed that cell viability decreased with increasing PQ concentration (P＜0.05).The protein expression of TGF-β1 treated with PQ (25,50,100 μmol/L) significantly increased compared with control in a dose-independent manner(P＜0.05).Exposure to PQ (25,50,100 μmol/L) induced increase of protein levels of p-Smad2 and p-Smad3.Noteworthy,the expression of p-Smad2 and p-Smad3 were dramatically increased following PQ plus TGF-β1 stimulation (P＜0.05).Exposure to PQ (50,100 μmol/L) induced increase of CTGF protein expression and similar greatly increase following PQ plus TGF-β1 stimulation (P＜0.05).Real time RT-PCR showed CTGF mRNA in all groups also significantly up-regulated compared with control (P＜0.05).Conclusion TGF-β1 regulates the expression of target gene CTGF to exhibit its profibrogenic effects by activating TGF-β1/Smad signaling pathway in PQ-induced pulmonary fibrosis.

Objective To investigate the effects of Paraquat on human embryonic lung fibroblasts (MRC5) and explore the role of transforming growth factor-β1/connective tissue growth factor signaling pathway in paraquat-induced pulmonary fibrosis.Methods MRC5 cells were cultured with different concentration of PQ (0,12.5,25,50,100,200,400 μ mol/L) for 24 h.The viability of cells was measured by MTT.The protein level of TGF-β1 were analyzed by ELISA after PQ treatment (0,25,50,I00 μmol/L).To examine whether TGF-β1/CTGF signaling pathway was involved in paraquat-induced cytotoxicity,cells was divided into 6 groups:(1) control;(2) 25 μ mol/L PQ group;(3) 50 μ mol/L PQ group;(4) 100 μmol/L PQ group;(5) TGF-β1 positive control group (50 μmol/L rhTGF-β1);(6)stimulate group (100 μmol/L PQ+50 μ mol/L TGF-β1).The protein levels of p-Smad2,p-Smad3 and CTGF were assayed by western blot.The mRNA level of CTGF was assayed by real time RT-PCR.Results MTT showed that cell viability decreased with increasing PQ concentration (P＜0.05).The protein expression of TGF-β1 treated with PQ (25,50,100 μmol/L) significantly increased compared with control in a dose-independent manner(P＜0.05).Exposure to PQ (25,50,100 μmol/L) induced increase of protein levels of p-Smad2 and p-Smad3.Noteworthy,the expression of p-Smad2 and p-Smad3 were dramatically increased following PQ plus TGF-β1 stimulation (P＜0.05).Exposure to PQ (50,100 μmol/L) induced increase of CTGF protein expression and similar greatly increase following PQ plus TGF-β1 stimulation (P＜0.05).Real time RT-PCR showed CTGF mRNA in all groups also significantly up-regulated compared with control (P＜0.05).Conclusion TGF-β1 regulates the expression of target gene CTGF to exhibit its profibrogenic effects by activating TGF-β1/Smad signaling pathway in PQ-induced pulmonary fibrosis.

Objective To discuss the effective treatments for fracture of the medial humeral epicondyle in children.Methods Twenty-five children with fracture of the medial humeral epicondyle treated from January 2008 to June 2011 were studied,including 18 males and 7 females at age of 7-14 years (mean,11.4 years).There were 7 cases accompanied with elbow joint dislocation and 2 lateral humeral epicondyle fracture.Patients were assigned to medial elbow approach to open reduction and internal fixation with absorbable rods (Group A,n =13) and open reduction and percutaneous K-wire fixation (Group B,n =12) according to the random number table.A plaster support was applied after surgery.Functional training was initiated 2-3 weeks after operation for Group A and 4-6 weeks after adequate callus formation for Group B.Moreover,follow-up was performed at regular intervals.Results All patients were followed up for 6-41 months (mean,22 months).Mean healing time was 3.8 weeks (range,3-5 weeks) in Group A and 5.6 weeks (range,4-8 weeks) in Group B.At postoperative 6 months,Bede elbow performance score was (93.7 ± 3.3) points in Group A with 10 excellent and 3 good results and (85.3 ±6.3) points in Group B with 3 excellent,7 good,and2 fair results (t=-4.24,P＜0.05).Conclusion Open reduction and internal fixation with absorbable rods gains advantages of rigid immobilization,functional recovery and minor complication and hence is effective for treatment of medial humeral epicondyle fracture in children.

OBJECTIVE To study the audiological and etiological characteristics of infants failed to pass hearing screening. METHODS 126 infants received audiological diagnostic tests,including auditory brainstem response(ABR),40 Hz auditory event related potential(40 Hz AERP),distortion product otoacoustic emissions(DPOAE),tympanometry and acoustic reflex. The degrees and types of the hearing loss,and etiological characteristics were analyzed. RESULTS Among 126 infants (252 ears),61 were diagnosed with sensorineural hearing loss(48.41%),48 were conductive hearing loss(38.09%),and 17 were found to have normal ABR thresholds(13.49%). The hearing loss was associated with various factors,including history of infection during pregnancy(21 cases),threatened abortion(9 cases),pregnancy with age at or over 35(6 cases),extension of pregnancy(7 cases),history of systematic diseases(10 cases),history of neonatal jaundice(13 cases),history of asphyxia and hypoxia(18 cases),premature and low birth weight neonates(8 cases),neonatal diseases (8 cases),family history of deafness(5 cases),craniofacial deformity(3 cases),central nervous system disorder(6 cases),and 9 cases were second child. CONCLUSION The infants who failed to pass hearing screening have various etiology characteristics in hearing loss. The infants associated with risk factors were mostly found to have sensorineural hearing loss.