Objective To investigate the effect and mechanism of ammonium pyrrolidine dithiocarbamate(PDTC)on neuroinflammatory injury in the penumbra of traumatic brain injury(TBI)in rats.Methods Sixty Sprague Dawley rats were divided into the PDTC group,TBI group,sham operation group and control group according to the random number table method,with 15 rats in each group.Rats in the PDTC group were intraperitoneally injected with PDTC(100 mg·kg-1)at 15 minutes before surgery;while the rats in the TBI group,sham operation group,and control group were intraperitoneally injected with the same volume of double distilled water.After the cranial window of rats in the TBI group and PDTC group was created,a 2.5 g steel rod with an inner diameter of 6.0 mm was dropped freely from a height of 75 cm through a transparent polyvinyl chloride tube with an inner diameter of 7.0 mm to impact the dura mater and induce right parietal lobe contusion and laceration to establish the TBI model;rats in the sham operation group were sealed with bone wax after the cranial window creation,without any impact applied;rats in the control group were raised under normal conditions.The modified neurological severity score(mNSS)was used to evaluate the degree of neurobehavioral damage in rats in each group at 1,4 and 7 days after modeling.At 2 days after modeling,5 rats in each group were decapitated,and brain tissues were taken for hematoxylin & eosin(HE)staining,and morphological changes of the brain tissues were observed under an optical microscope.The expressions of β-amyloid precursor protein(β-APP)and glial fibrillary acidic protein(GFAP)in the brain tissues of rats in each group were detected by immunohistochemical staining.At 24 hours after modeling,5 rats in each group were decapitated,and the right injured penumbra tissues were obtained;the expressions of nuclear transcription factor-κB(NF-κB)P65,phosphorylated NF-κB P65,inhibitor of NF-κB(IκB),phosphorylated IKB,NOD-like receptor protein 3(NLRP3)and caspase-1 protein in the right injured penumbra tissue of rats in each group were detected by Western blot,and the expressions of NF-κB P65,IκB,NLRP3 and caspase-1 mRNA in the right injured penumbra tissue of rats in each group were determined by real-time quantitative polymerase chain reaction.Results At 1,4,and 7 days after modeling,the mNSS scores of rats in the TBI group were signifi-cantly higher than those in the PDTC group,control group and sham operation group.The mNSS scores of rats in the PDTC group were significantly higher than those in the control group and sham operation group(P＜0.05);there was no statistically significant difference in mNSS scores between the sham operation group and the control group(P＞0.05).The neurons and neurogliocyte of rats in the control group and the sham operation group exhibited normal morphology,without swelling and wide-ning of intercellular space.Diffuse hemorrhagic changes were observed in the brain tissues of rats in the TBI group,with different morphologies of neuronal cell body,unclear cell membrane and cytoplasm,pyknosis of cell nuclei,often triangular shape,disappearance of normal structure and nucleoli,and diffuse white blood cells and red blood cells filling the field of vision.The lesion surrounding area of rats in the PDTC group showed ischemic changes,with mild shrinkage of neuronal volume,a uniform light red color,karyopyknosis,nuclear-cytoplasmic dissociation,disappearance of normal structure and nucleoli,and localization of neuroinflammation.There was no significant expression of β-APP and GFAP in the cerebral cortex of rats in the control group and the sham operation group,while the accumulation of β-APP and GFAP in neuronal serosae and/or axons was observed in the brain tissues of rats in the TBI group and the PDTC group.Compared with the TBI group,a decrease in the number and the expression intensity of β-APP and GFAP-positive stained neuronal cells in the cerebral cortex of rats was observed in the PDTC group.The relative expression of NF-κB P65 protein in the brain tissues of rats in the sham operation group,TBI group and PDTC group was significantly higher than that in the control group,and the relative expression of NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P＜0.05).The relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group and the sham operation group was significantly lower than that in the control group,the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group and the sham operation group,and the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly lower than that in both TBI group and sham operation group(P＜0.05).There was no significant difference in the relative expression of IκB protein in the brain tissues of rats between the sham operation group and the control group(P＞0.05);the relative expression of IκB protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group,and the relative expression of IκB protein in the brain tissues of rats in the PDTC group was significantly lower than that in the control group,sham operation group,and TBI group(P＜0.05).The relative expression of phosphorylated IκB protein in the brain tissues of rats in the TBI group was significantly lower than that in the control group and the sham operation group,and the relative expression of phosphorylated IκB protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P＜0.05).The relative expression of NLRP3 protein in the brain tissues of rats in the sham opera-tion group was significantly higher than that in the control group,the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group and the PDTC group was significantly lower than that in the sham operation group and the control group,and the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group was significantly lower than that in the PDTC group(P＜0.05).The relative expression of caspase-1 protein in the brain tissues of rats in the sham opera-tion group,PDTC group,and TBI group was significantly higher than that in the control group,and the relative expression of caspase-1 protein in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group,TBI group,and sham operation group was significantly higher than that in the control group,the relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expres-sion of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of IκB mRNA in the brain tissues of rats in the PDTC group and TBI group were signifi-cantly higher than that in the control group,and the expression of IκB mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group(P＜0.05).The relative expression of IκB mRNA in the brain tis-sues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of IκB mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of caspase-1 mRNA in the brain tissues of rats in the sham operation group,TBI group,and PDTC group was significantly lower than that in the control group,the relative expression of caspase-1 mRNA in the brain tissues of rats in the TBI group and PDTC group was significantly higher than that in the sham operation group(P＜0.05).Conclusion PDTC can effectively improve neural functional deficit score and reduce neuroinflammatory injury in TBI rats,the mechanism of which may be related to regulating mRNA and protein expression of NF-κB/NLRP3 axis-related inflammatory injury indicators and regulating downstream inflammatory factors.

OBJECTIVE To explore the causal relationship of circulating cytokines and sensorineural deafness by Mendelian randomization.METHODS Large-scale genome-wide association studies(GWAS)data sets based on UK Biobank were used to identify single nucleotide polymorphisms(SNP)associated with exposure and outcome.The SNP(F>10)significantly associated with exposure data(P<5e-6)and strongly associated with exposure in the F statistic was selected as the instrumental variable for a two-sample Mendelian randomization analysis.The causal effect was estimated using MR-Egger,regression and inverse variance weighting(IVW).Sensitivity analysis was performed to assess the robustness of the results.RESULTS This study confirmed that VEGF(OR=1.04,95%CI:1.01-1.07,P=0.00),SDF-1α(OR=1.10,95%CI:1.02-1.18,P=0.01)and IL-13(OR=1.04,95%CI:1.01-1.06,P=0.01),IL-10(OR=1.06,95%CI:1.02-1.11,P=0.01),IL-7(OR=1.05,95%CI:1.01-1.08,P=0.00)increased the risk of sensorineural deafness.The backward analysis did not find that sensorineural deafness significantly affected the levels of these cytokines.No significant heterogeneity or horizontal pleiotropy was observed among the instrumental variables.CONCLUSION This study reveals a positive correlation between elevated levels of VEGF,SDF-1α,IL-13,IL-10,and IL-7 with sensorineural hearing loss,providing novel targets for further development of biomarkers for the prediction,treatment,and prevention of sensorineural hearing loss.

Objective:To investigate the effect of 3D-printed customized flanged cup in hip revision with severe acetabular bone defects.Methods:Since February 2017, 10 cases of 3D-printed customized flanged cups were used in hip revision with severe acetabular bone defects, including 2 cases of Paprosky type IIIA and 8 cases of Paprosky type IIIB. There were 5 males and 5 females, mean age 73.6±8.1 yrs (range, 62-87 yrs), 5 left and 5 right cases. The preoperative thin-layer CT scan was preformed to reverse reconstruct digital pelvis. Five cases of one-piece flanged cups and 5 cases of decomposed flanged cups, including 3 cases of composite one-piece cups were designed by computer. The surgery was performed strictly according to the plan.Postoperative follow-up was performed to evaluate the Harris score. Operation time,intraoperative bleeding and other complications such as vascular and nerve injury, postoperative infection, and dislocation were counted. Pelvic X-ray was used to assess the height and horizontal position of the center of rotation and the stability of the prosthesis.Results:The surgical procedure was successful, with an average operative time of 147.9±48.3 min (range, 96-212 min) and an average intraoperative bleeding of 730.4±262.6 ml (range, 500-1 300 ml). The mean time of final follow-up was 40.8±18.7 months (range, 16-70 months) after surgery. At the last follow-up, the average Harris score was 83.80±6.73, with 4 cases excellent, 5 cases good, and 1 case fair. The excellent and good rate was 90%. The last Harris score was significantly higher than that before operation 28.60±8.40 ( t=16.84, P<0.001). The height of affected hip joint rotation center decreased from 46.24±7.74 mm before operation to 15.54±2.54 mm after operation with significant difference ( t=14.61, P<0.001). It was slightly higher than the opposite side (13.81±1.48 mm), which had no significant difference ( t=1.83, P=0.100). The horizontal distance of affected hip joint rotation center increased from 33.79±5.27 mm before operation to 40.53±4.50 mm after operation with significant difference ( t=3.62, P=0.006). It had no significant difference ( t=1.28, P=0.232) compared with the opposite side (38.54±3.46 mm). All incisions were healed in one stage without infection, vascular or nerve injury. During the following-up, all prostheses were in satisfied position without loosening, dislocation or screw breaks. Conclusion:Digitally assisted 3D-printed flanged cups can be used in hip revision with severe acetabular bone defect. It can not only improve hip joint function, but also restore the acetabular rotation center and the prosthesis stability, which can achieve good early and mid-term effect.

Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation, sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases. This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.

Objective:To detect the expression of ARK5 in peripheral blood circulating tumor cells (CTCs) from pancreatic cancer patients and explore its correlation with the efficacy and prognosis for gemcitabine chemotherapy.Methods:A total of 175 peripheral blood samples of pancreatic cancer patients who were treated in the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Jiaxing University from January 2016 to June 2021 were collected. CTCs were enriched by nano-microfluidic chip technology. The expression of ARK5 in CTCs was detected by immunofluorescence. According to the expression of ARK5, the patients were divided into two groups: positive group and negative group. The differences on clinicopathological features, the efficacy of chemotherapy, median survival and progression-free survival time between the two groups were compared.Results:CTCs were enriched in 98 of 175 patients (55.6%), including 70 ARK5 positive and 28 ARK5 negative patients. There were no significant differences on clinical features between the two groups, and the two groups were comparable. In the 70 ARK5 positive patients, 64 patients (91.4%) were resistant to gemcitabine, while only 12 of the 28 ARK5 negative patients (42.8%) were resistant to gemcitabine. The incidence of gemcitabine resistance in ARK5 positive patients was significantly higher than that in ARK5 negative patients, and the difference was statistically significant ( P<0.001). The median survival time was 11.5 months in ARK5 positive group and 14 months in ARK5 negative expression group, and the progression-free survival time was 6 months in ARK5 positive expression group and 8 months in negative expression group. The survival time of ARK5 positive group was significantly shorter than that of ARK5 negative group, and the difference was statistically significant ( P<0.05). Conclusions:The pancreatic cancer patients with ARK5 positive CTCs have significantly higher incidence of gemcitabine resistance and shorter survival time than those with ARK5 negative CTCs. Detection of ARK5 expression in CTCs may be a new method to judge chemotherapy efficacy and prognosis for pancreatic cancer patients.

Hepatocellular carcinoma is one of the common causes of tumor-related death, and it has high morbidity and mortality rates in China. Recent studies have shown that platelets are closely associated with the development of hepatocellular carcinoma. Literature review shows that platelets not only participate in hemostasis, but also act on liver cells and tumor microenvironment, promote the formation of new blood vessels, and participate in the development and progression of hepatocellular carcinoma as a cell mediator through immune response and other pathways. In addition, platelets and their derivatives can be used as potential therapeutic targets for hepatocellular carcinoma. Therefore, antiplatelet therapy is expected to become a new adjuvant strategy for the treatment of hepatocellular carcinoma, which has important clinical significance.

Objective:To investigate the effect of sequential suture and adhesion on craniomaxillofacial skin contusion and laceration.Methods:A total of 189 patients with craniomaxillofacial skin contusion and laceration (CMFSCL) were randomly divided into three groups: 66 cases in SSA group, 63 cases in CS group and 60 cases in TS group. Operation time, visual analogue scale (VAS), Vancouver scar scale (VSS) and adverse reactions incidence were compared and analyzed between the three groups. Effect and satisfactory scale were evaluated.Results:Operation time in SSA group (10.67±1.26) min was significantly less than that in CS (18.91±1.38) min and TS group (17.96±1.43) min ( P<0.05). VAS in SSA group 24 h post-operation (3.11±1.01) was significantly lower than that in CS and TS group ( P<0.05). VSS in SSA group 6 months post-operation (1.18±0.21) was significantly lower than that in CS (3.78±1.01) ( P<0.05) and TS group (5.98±1.06) ( P<0.01). Total effective rate of SSA group (96.5%) was significantly higher than that in CS (85.7%) ( P<0.05) and TS group (56.1%) ( P<0.01); total effective rate in CS group was significantly higher than that in TS group ( P<0.05). Infection and dehiscence rates in SSA group were lower than those in CS and TS group ( P<0.01). Satisfactory rate of SSA group (99%) was significantly higher than that of CS (89.1%) and TS group (71.3%) ( P<0.05); the satisfactory rate of CS group was significantly higher than that of TS group ( P<0.05). Conclusions:Sequential suture and adhesion technique is simple and effective for craniomaxillofacial skin contusion and laceration, which is worthy of clinical promotion.

Objective:To investigate the effects of combined exposure of fluorine, arsenic, and fluorine-arsenic on the signaling pathway related protein expression of tumor necrosis factor receptor-related factor 6 (TRAF-6)/nuclear factor κB1(NF-κB1) in a co-culture system of mouse osteoblasts MC3T3-E1 and mouse monocyte macrophage RAW264.7.Methods:MC3T3-E1 cells were co-cultured with RAW264.7 cells after induction with osteogenic inducers. The cells were cultured for 7 days in vitro, and different doses of sodium fluoride (0.0, 0.1, 0.4, 1.6 mmol/L NaF, F), sodium arsenite (0.0, 0.5, 2.5, 12.5 μmol/L NaAsO 2, As) and different doses of fluorine and arsenic were added to the culture medium and cultured for 24 h using factorial design. The expression levels of nuclear factor κB receptor activating factor (RANK), TRAF-6, NF-κB1, T cell activating factor (NFATc1), and tartrate-resistant acid phosphatase (TRAP) protein were detected by Western blotting. Results:When fluorine was used alone, compared with the control group (F 0.0As 0.0, 1.00 ± 0.00), the expressions of RANK, NF-κB1 and TRAP proteins (1.11 ± 0.04, 1.29 ± 0.05, 1.38 ± 0.04, 1.24 ± 0.04, 1.13 ± 0.03, 1.34 ± 0.05, 1.12 ± 0.03, 1.24 ± 0.04, 1.61 ± 0.06) were increased ( P < 0.05); TRAF-6 protein expressions in F 0.1 and F 1.6 groups (1.23 ± 0.04, 1.35 ± 0.03) were increased ( P < 0.05). When arsenic was used alone, compared with the control group (F 0.0As 0.0), the expressions of RANK, TRAF-6, NF-κB1 proteins were increased in As 0.5 group ( P < 0.05), the expressions of RANK and NFATc1 proteins were reduced in As 12.5 group ( P < 0.05). When fluorine was combined with arsenic, at the same dose of fluorine, RANK protein expression in F 0.1As 0.5 group and TRAF-6 protein expression in F 0.1As 12.5, F 0.4As 0.5, F 0.4As 2.5 groups, NF-κB1 protein expression in F 0.1As 0.5 F 0.4As 2.5, F 0.4As 12.5 groups, NFATc1 protein expression in F 0.1As 0.5 and F 0.4As 0.5 groups, TRAP protein expression in F 0.1As 12.5 group were higher than the corresponding fluorine groups alone (F 0.1, F 0.4, P < 0.05), but lower than the sum of fluorine and arsenic alone. At the same dose of arsenic, RANK protein expression in F 0.1As 12.5 group, TRAF-6 protein expression in F 0.1As 12.5 and F 0.4As 2.5 groups, and NF-κB1 protein expression in F 0.1As 12.5, F 0.4As 2.5, F 0.4As 12.5, and F 1.6As 2.5 groups, TRAP protein expression in F 1.6As 2.5 and F 1.6As 12.5 groups were higher than the corresponding arsenic groups alone (As 2.5, As 12.5, P < 0.05), but lower than the sum of fluorine and arsenic alone. Fluorine had a major effect on the expressions of RANK, TRAF-6, NF-κB1, NFATc1, and TRAP proteins ( F=3.41, 341.73, 66.01, 56.49, 147.40, P < 0.05); arsenic also had a main effect on all protein indicators ( F=686.71, 174.96, 107.32, 235.80, 331.37, P < 0.05); the combined effect of fluorine and arsenic had an interaction effect on each protein indicator ( F=50.39, 234.94, 116.72, 67.77, 36.56, P < 0.05). Conclusions:In the co-culture system of MC3T3-E1 and RAW264.7 cells, fluorine can activate TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins, thereby promoting osteoclast differentiation; the effects of arsenic on the expression of related proteins are not completely consistent. The interaction of fluorine and arsenic exposure on TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins is mainly antagonistic.

Objective To investigate the clinical application value of ultrasound-guided catheter drainage and vacuum-assisted Mammotome system in the treatment of lactational breast abscess. Methods The clinical data of 46 patients with lactational breast abscesses were analyzed retrospectively. All patients were divided into control group (28 patients) and treatment group (18 patients). Homemade irrigation and drainage tube was used in control group,and vacuum-assisted Mammotome system was used in treatment group. The curative effect of 2 groups was compared. Results All patients were cured. The mean healing time in treatment group was (9.5 ± 1.3) d,in control group was (12.5 ± 2.2) d, and there was significant difference (P < 0.01). The rate of breast-feeding in control group was 57.1% (16/28), in treatment group was 13/18,and there was no significant difference (χ2=1.069, P>0.05). All patients recovered well without recurrence. Conclusions Ultrasound-guided catheter drainage should be employed as first line treatment of breast abscess with diameter greater than the 3 cm. If patient′s economic conditions are good and have high requirement on the beauty outcome, vacuum-assisted Mammotome system can be applied as treatment option.

Objective To compare the value of NBI with magnify endoscopy (NBI-ME) and Lugol chromoendoscopy (LCE) in preoperative assessment of early esophageal cancer, and assess whether the former can replace the latter. Methods 59 patients, sampled in the Second Hospital of Lanzhou University, the First Hospital of Lanzhou University and the Second Hospital of Lanzhou City from January 2014 to December 2015, were examined respectively by NBI-ME and Lugol chromoendoscopy not only to distinguish the lesion boundaries but also predict the pathological types as well for statistical analysis with the combination of the final postoperative pathological results. Results Only 64.4 % (38/59) of lesion boundaries can be well-distinguished by NBI-ME, which is significantly lower than that distinguished by Lugol chromoendoscopy (91.5 %, 54/59), with its kappa value 0.208< 0.4, P < 0.01 (0.006). It indicated that poor concordance existed in these two methods. The McNemar value which reflects concordance between pathological type predicted by NBI-ME and postoperative pathology was diagnosed to be 5.397, P > 0.05 (0.369), Kappa > 0.4 (0.429), P < 0.01 (0.000), suggesting the concordance can be acceptable. However, the McNemar number diagnosed by Lugol chromoendoscopy was only 4.533, P > 0.05 (0.475), Kappa <0.4 (0.286), P < 0.01 (0.001), showing the poor concordance instead. Conclusions To some extent, pathological type predicted by NBI-ME indeed had an concordance with postoperative pathology, which was also superior to the results examined by Lugol chromoendoscopy, while there was no denying that Lugol chromoendoscopy had an obvious advantage over NBI-ME in terms of distinguishing lesion boundaries, therefore, it can not be completely replaced with NBI-ME at present.