Diabetic kidney disease(DKD)is a high incidence microvascular complication caused by diabetes mellitus(DM).Persistent high glucose induces oxidative stress in the body.nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)can play an anti-inflammatory and anti-oxidative role by inhibiting the accumulation of extracellular matrix in glomerular mesangium,inhibiting epithelial-mesenchymal transition in renal tubular epithelial cells,and inhibiting iron apoptosis,so as to improve renal function damage and delay the process of DKD.This article reviews the relationship between Nrf2/HO-1 pathway and DKD and the effect of traditional Chinese medicine active ingredients on DKD through Nrf2/HO-1 signaling pathway,in order to provide a basis for the development of new drugs.

Objective:To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion.Methods:Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay.Results:The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin ( r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4 -/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size ( P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4 -/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4 -/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions:TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Objective:To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion.Methods:Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay.Results:The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin ( r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4 -/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size ( P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4 -/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4 -/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions:TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Objective:To reconstruct the dose of nasopharyngeal carcinoma and verify the results of the whole-process radiotherapy plan based on log files and cone beam CT (CBCT).Methods:A total of 15 patients with nasopharyngeal carcinoma who received volumetric modulated arc therapy (VMAT) with Halcyon accelerator in the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February to September 2022 were retrospectively selected. Log files and CBCT for all fractionated radiotherapy were recorded. The errors of monitor unit (MU), gantry angle, and multi-leaf collimator (MLC) leaf position per control point were analyzed. The adaptive CT (aCT) were generated according to CBCT and planned CT (pCT) using a commercial software Velocity TM, and the similarities among aCT, pCT and CBCT were analyzed. The original plan was modified from the log files and imported into the treatment planning system to calculate the delivered dose on the corresponding fractionated aCT to reconstruct the fractionated dose. And all the reconstructed doses were mapped back to pCT to obtain the cumulative dose. Theγpass ratios with criteria of 2 mm/2% and 2 mm/3% and the dose differences between the planned dose and the cumulative dose in the planning target volume (PTV) and organs at risk (OAR) were compared. Results:The root mean square (RMS) and the 95th percentile of the errors of MU, gantry angle and MLC leaf position errors were within an acceptable range. The aCT generated by Velocity TM had the anatomical structure of CBCT and the resolution, contrast, noise characteristics of pCT, which could be directly used for dose calculation. Compared with the planned dose, the changes of V 70 Gy of nasopharyngeal primary tumor (PTV nx), V 68 Gy of cervical glands (PTV nd) and V 60 Gy of planning target volume (PTV1) were -0.88%±1.91%, -2.99%±2.99% and -0.63%±0.93%, respectively, and V 40 Gy of parotid gland was increased to 2.65%±2.63%. Cumulative dose showed different degrees of PTV dose decrease ( P<0.05) and parotid dose was increased ( P<0.05). The γ pass ratio (2 mm/3%) between the cumulative dose and planned dose was 97.3%±2.7% and >95.0% in 86.7% of patients. Conclusions:Based on the log files and CBCT, the whole-process dose reconstruction of nasopharyngeal carcinoma patients can be carried out. According to the results of dose reconstruction, the radiotherapy effect of the target area and OAR can be quantitatively evaluated. In the case of high dose coverage and conformity of the original plan, the reconstruction results show that the cumulative dose coverage of the target area is decreased, whereas that of the parotid gland is increased.

Objective: To understand the infection status and epidemiological characteristics of hepatitis C in people aged 1-69 years in Henan Province in 2020. Methods: The estimated sample size was 5 827. From August to December 2020, multistage sampling was used to select 8 counties (districts) in Henan, and two survey sites were selected in each county (district), and a questionnaire survey was conducted in local people aged 1-69 years, blood samples were collected from them for anti-HCV, HCV RNA and genotype detections. Results: A total of 5 165 people aged 1-69 years completed the questionnaire survey. Men accounted for 44.76% (2 312/5 165), women accounted for 55.24% (2 853/5 165). In the people aged 1-69 years, the overall prevalence rates of anti-HCV and HCV RNA were 0.69% (95%CI: 0.68%-0.70%) and 0.20% (95%CI: 0.19%-0.21%) respectively. The prevalence rates of anti-HCV and HCV RNA were 0.48% (95%CI: 0.46%-0.50%), 0.09% (95%CI: 0.08%-0.10%) in men and 0.86% (95%CI: 0.85%-0.87%), 0.30% (95%CI: 0.28%-0.32%) in women. The prevalence rates of anti-HCV and HCV RNA increased with age. The prevalence rates of anti-HCV and HCV RNA were 0.87% (95%CI: 0.86%-0.88%), 0.28% (95%CI: 0.26%-0.30%) in urban residents and 0.53% (95%CI: 0.51%-0.55%), 0.14% (95%CI: 0.13%-0.15%) in rural residents. The genotyping results of 10 HCV RNA positive samples ware genotype 1b (4/10), genotype 2 (3/10), genotype 1b/3 (1/10), genotype 1b/3/6 (1/10) and genotype 2/6 (1/10). Conclusions: The prevalence of hepatitis C was low in Henan in 2020. It is necessary to strengthen hepatitis C surveillance in people aged 40 years and above. The major HCV genotypes were 1b and 2, and mixed genotype infection existed.
Female ; Humans ; Male ; Coinfection ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/epidemiology* ; Hepatitis C Antibodies/genetics* ; Prevalence ; RNA, Viral/genetics* ; Surveys and Questionnaires ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

Bosworth fracture and dislocation is relatively rare, accounting for about 1% of ankle fractures. It is characterized by the proximal fibula fracture embedded in the posterolateral distal tibia. Due to an insufficient understanding of this fracture, it is easy to cause missed diagnosis and misdiagnosis in clinical practice. Due to the insertion of the fracture, it is challenging to perform closed reduction, and improper treatment is easy to cause complications. Surgical treatment is recommended for this type of fracture. In order to improve the understanding of orthopedic surgeons about Bosworth fracture and dislocation, this paper reports the diagnosis and treatment of 2 cases of Bosworth fracture and dislocation, and reviews the literature on Bosworth fracture's mechanism, diagnosis, classification, complications, and treatment options in recent years.
Humans ; Ankle Fractures/surgery* ; Joint Dislocations/surgery* ; Fracture Fixation, Internal ; Fibula ; Tibia

BACKGROUND: Breast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis. The study aimed to construct a novel predictive clinical model to evaluate the overall survival (OS) of patients with postoperative brain metastasis of breast cancer (BCBM) and validate its effectiveness. METHODS: From 2010 to 2020, a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University, and they were randomly assigned to the training cohort and the validation cohort. Data of another 173 BCBM patients were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database as an external validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS. The model capability was assessed using receiver operating characteristic, C-index, and calibration curves. Kaplan-Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model. The accuracy and prediction capability of the model were verified using the validation and SEER cohorts. RESULTS: LASSO Cox regression analysis revealed that lymph node metastasis, molecular subtype, tumor size, chemotherapy, radiotherapy, and lung metastasis were statistically significantly correlated with BCBM. The C-indexes of the survival nomogram in the training, validation, and SEER cohorts were 0.714, 0.710, and 0.670, respectively, which showed good prediction capability. The calibration curves demonstrated that the nomogram had great forecast precision, and a dynamic diagram was drawn to increase the maneuverability of the results. The Risk Stratification System showed that the OS of low-risk patients was considerably better than that of high-risk patients ( P < 0.001). CONCLUSION The nomogram prediction model constructed in this study has a good predictive value, which can effectively evaluate the survival rate of patients with postoperative BCBM.
Female ; Humans ; Breast Neoplasms/surgery* ; Retrospective Studies ; Prognosis ; Brain Neoplasms/surgery* ; Nomograms

【Objective】 To investigate the effects of neuropathic pain induced by selective nerve injury (SNI) on intestinal microflora diversity in C57 mice. 【Methods】 36 C57 mice were randomly divided into SNI model group (n=18), sham-operation group (n=8), and control group (n=10). At day 0,1, 3, 7, and 14 after modeling, mechanical pain threshold and thermal pain sensitivity tests were carried out. At day 14 after modeling, colon content (fresh feces) from all the mice were collected for intestinal microflora diversity analysis. 【Results】 One day after modeling, the mechanical pain threshold in SNI group decreased significantly (more than 70%) due to nerve injury, and the thermal pain threshold decreased by 40%, while sham group and control group had no significant decrease. SNI group showed foot hyperalgesia, and the difference was statistically significant compared with sham group and control group (P<0.001). Compared with control group, sham-operation group had a transient decrease in thermal pain threshold on the first day after modeling (P=0.006), but there was no difference in pain threshold between the two groups on the third day after modeling. The α-diversity analysis showed that the abundance of Observed, Chao1, ACE and Simpson in SNI group was significantly lower than that in control group (P<0.05). That is, SNI group had flora disorder due to pain stimulation. Observed, Chao1, ACE, and Simpson were less abundant in sham group than in control group (P<0.05) and the change was between SNI group and control group. 【Conclusion】 Neuropathic pain induced by SNI model resulted in the decrease of mechanical pain threshold and thermal pain threshold, which leads to the reduction of intestinal flora diversity in C57 mice.