Humans ; Tranexamic Acid/therapeutic use* ; Arthroplasty, Replacement, Knee ; Antifibrinolytic Agents/therapeutic use* ; Blood Loss, Surgical ; Postoperative Hemorrhage

ObjectiveTo observe the effects of the South African herb Hoodia gordonii （HG） on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase （PI3K）/protein kinase B （Akt）/factor forkhead protein O1 （FoxO1） signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose： model group， metformin group （0.195 g·kg^-1）， and low dose （0.39 g·kg^-1）， medium dose （0.78 g·kg^-1）， and high dose （1.56 g·kg^-1） HG groups， with six m/m mice in each group， and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg^-1 by gavage. Body weight， water intake， and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration， serum insulin （FINS）， low-density lipoprotein cholesterol （LDL）， total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， urea， and creatinine （CREA） were measured， and liver sections were embedded and stained with hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and oil red O. Protein expression of PI3K p85， p-Akt， and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K， Akt， and FoxO1 in liver tissue was detected by real-time polymerase chain reaction （Real-time PCR）. ResultAfter six weeks of administration intervention， it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups （P<0.05）. The level of islet resistance index was significantly reduced in both the low and medium dose HG groups （P<0.05）. The expression levels of TC， TG， and LDL were reduced in all HG groups （P<0.05， P<0.01）. Pathologically， HG could alleviate hepatocyte steatosis， reduce the volume and content of lipid droplets in liver， and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low， medium， and high dose HG groups compared with the model group （P<0.01）. p-Akt protein expression was significantly increased in the medium and high dose HG groups （P<0.05， P<0.01）. p-FoxO1 protein expression was significantly increased in the low， medium， and high dose HG groups （P<0.05， P<0.01）. Compared with the model group， PI3K mRNA was increased in low dose， medium dose， and high dose HG groups （P<0.05）， and Akt mRNA was increased in high dose HG group （P<0.05）. FoxO1 mRNA was decreased in low dose， medium dose， and high dose HG groups （P<0.05）. ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice， which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.

Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.

Objective To compare the accuracy of consolidation/tumor ratio(CTR)measured at different CT thresholds for the prediction of invasiveness in small lung cancer with diameter≤2 cm using artificial intelligence-assisted measurements,and to explore the CTR thresholds and the corresponding CT thresholds for predicting lung cancer invasiveness.Methods Clinical data from 59 lung cancer patients(78 lung nodules in total)treated at Wuwei Hospital of Traditional Chinese Medicine from January 2021 to May 2023 were collected to analyze the prediction efficacy of CTR on invasiveness in small lung cancer with diameter≤2 cm measured at CT thresholds of-400,-350,-300,-250,-200,-150 HU.ROC curves were plotted to determine the optimal critical value for invasiveness prediction,followed by the corresponding CT threshold.Results The highest diagnostic efficacy for the invasiveness of lung nodules was achieved at a CT threshold of-250 HU,with an area under the curve of 0.931,sensitivity of 77.5％,specificity of 100％,and an optimal CTR threshold of 0.322.Conclusion For small lung cancers with a maximum diameter≤2 cm,CTR measured at a CT threshold of-250 HU can accurately predict lung cancer invasiveness.At CTR>0.322,the nodule is more likely to be microinvasive or invasive adenocarcinoma.

In order to obtain polyclonal antibodies against the fibrillar(Fiber)protein of fowl ade-novirus serotype 11(FAdV-11)and investigate its cross-reactivity to different serotypes of FAdV Fiber,the gene encoding the FAdV-11 Fiber protein was cloned into a prokaryotic expression vec-tor pET-32a by homologous recombination technology,then the plasmid was transformed into BL21(DE3)receptor cells,and the purified recombinant protein was used as an immunogen to im-munize rabbits to prepare polyclonal antibody after induced expression,and the cross-reactivity of the polyclonal antibody against different serotypes of FAdV Fiber proteins was identified by West-ern blot and indirect immunofluorescence(IFA).The results showed that the His-FAdV-11-Fiber recombinant protein was mainly expressed as inclusion bodies and was well expressed.Western blot and IFA showed that the prepared polyclonal antibody reacted with the Fiber proteins of FAdV-8a,FAdV-8b,and FAdV-11,but did not with the 2 Fiber of FAdV-4(Fiber 1 and Fiber 2)proteins.In conclusion,in this study,we successfully prepared rabbit polyclonal antibodies against FAdV-11 Fiber and showed that it specifically recognized the Fiber proteins of FAdV-8a,FAdV-8b and FAdV-11,which lays the foundation for further establishment of serological differential diag-nosis of FAdV-11.

BACKGROUND: Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGFb1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. METHODS: An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. RESULTS: Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and a-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-b1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of profibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. CONCLUSION Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.

[Abstract] Objective: To investigate the effect of breast cancer susceptibility gene 1 (BRCA1) on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC) H1650 cells through Wnt/β-catenin pathway. Methods: WB and qPCR were used to detect the mRNA and protein expressions of BRCA1 in NSCLC A549, H1299, H1650 cells and normal lung epithelial BEAS-2B cell. A stable BRCA1 over-expression cell line (LV-BRCA1) was constructed in H1650 cells, and blank control group (NC), negative control group (LV-BRCA1-NC), experimental group (LV-BRCA1) and inhibitor group (LV-BRCA1+XAV-939) were set up. The proliferative activity of cells in each group was detected by MTT assay, the migration ability of cells was detected by scratch test, the invasive ability of cells was detected by Transwell method, and the protein expression levels of BRCA1, cyclin D1, β-catenin, c-Myc and Cox2 were detected by WB. Results: The mRNA and protein expression levels of BRCA1 in NSCLC cells were significantly higher than those in BEAS-2B cells (all P<0.01). Up-regulation of BRCA1 expression in H1650 cells could significantly enhance cell proliferation, migration and invasion (P<0.05 or P<0.01), and increase the protein expressions of cyclin D1, β-catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). β-catenin inhibitor XAV-939 significantly down-regulated the proliferation, migration and invasion ability of H1650 cells over-expressing BRCA1, and decreased the protein expressions of cyclin D1, β-catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). Conclusion: BRCA1 can promote the proliferation, migration and invasion of NSCLC H1650 cells by activating Wnt/β-catenin pathway, and it is expected to be a potential diagnostic biomarker and treatment target for NSCLC.

Objective:To investigate the surgical method and clinical effect of the free peroneal artery perforator flap designed by vascular localization with three-dimensional CT angiography（3D-CTA）in repairing soft tissue defects of the dorsal forefoot.Methods:A retrospective case series study was conducted to analyze the clinical data of 17 patients with soft tissue defects of the dorsal forefoot admitted to Hospital of the 80th Group Army of PLA from February 2015 to January 2019，including 11 males and 6 females，aged from 16 to 65 years［（39.2±9.7）years］. The area of soft tissue defects ranged from 3.0 cm×2.0 cm to 10.0 cm×7.0 cm，and the size of skin flap was from 3.5 cm×2.5 cm to 10.5 cm×7.5 cm. Preoperative 3D-CTA was performed to select the appropriate perforator vessels，and a personalized skin flap was designed according to the examination results and wound conditions. Of all，10 patients were repaired with the peroneal perforator flap at the first stage，and 7 patients grafted with peroneal perforator flap with wound expansion in the second stage. The perforator diameter，vertical distance from the starting point of the perforator to the tip of the lateral malleolus and horizontal distance from the starting point of the perforator to the outer edge of the lower leg were compared between preoperative 3D-CTA and actual intraoperative measurements. The survival of the flap and occurrence of the vascular crisis were observed after operation. The foot function was assessed with the American Orthopedic Foot and Ankle Society（AOFAS）ankle hindfoot score preoperatively and at postoperative 6 months. Six months after operation，effect of flap repair was evaluated by using flap satisfaction score and flap sensory function measured by the criteria established by British Medical Rresearch Council（BMRC）. Incision healing and motor function of the donor area were detected.Results:All patients were followed up for 6-12 months［（9.6±2.3）months］. There was no statistically significant differences in perforator diameter，vertical distance from the starting point of the perforator to the tip of the lateral malleolus and horizontal distance from the starting point of the perforator to the outer edge of the lower leg between preoperative 3D-CTA and actual intraoperative measurements（ P>0.05）. All flaps survived without vascular crisis. Six months after operation，a higher AOFAS ankle hindfoot score［（84.0±7.9）points］was found when compared to that preoperatively［（51.3±8.2）points］（P<0.05），with excellent results in 12 patients and good results in 5 patients. At 6 months after the operation，the thickness of the flap was flush with the surrounding skin，which did not affect the wearing of shoes；the thickness of the flap was level with the surrounding skin but did not affect the wearing of shoes. The repair effect was satisfactory with the flap satisfaction score of（8.7±2.3）points.Based on the criteria established by BMRC，the sensory function of the flap continued to improve，including 10 patients reaching the level of S 3-S 4 with the two-point discrimination of（10.2±2.0）mm and 7 patients reaching the level of S 2. All incisions at the donor area were healed well without obvious scar contracture or motion limitation. Conclusions:For soft tissue defects of the dorsal forefoot，3D-CTA assisted vascular localization is able to have individualized and precise design of peroneal artery perforator flap preoperatively to assist rapid and accurate skin flap cutting and accelerate defect healing and functional recovery in the dorsal foot. Moreover，the free peroneal artery perforator flap has advantages of high patients' satisfaction，with minor trauma on donar site or without damaging the main artery.

The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.

Objective:To explore the method and clinical effect of the free medial plantar flap with the nerve in the reconstruction of skin and soft tissue defect of heel in children.Methods:A series of retrospective analyses was conducted on the cases with heel skin and soft tissue defects admitted to the 89th Hospital of the PLA from July 2014 to February 2019. The medial plantar skin flap with cutaneous branches of the medial plantar nerve was harvested from the healthy side and transferred to the opposite side to repair the soft tissue defect of the heel of children. Then, the free skin graft was taken from the groin area to cover the donor site, and the wound was sutured directly. The appearance, texture, and color of the flap were observed, and the sensory recovery of the flap was evaluated two years after the operation. The functional condition was elevated by the American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot function scoring system.Results:A total of 6 children with heel skin and soft tissue defects were enrolled, including 4 males and 2 females, aged from 3 to 13 years.There were 4 cases on the right, and 2 cases on the left side, the size of skin and soft tissue defect was 2 cm×3 cm-6 cm×7 cm. All 6 flaps survived, the skin graft area healed in one stage, and the size of the flap was 3 cm×4 cm-7 cm×8 cm. The patients were followed up for 2-3 years. The appearance of the flap was not bloated, the color and texture of the flap were similar to the surrounding tissue, and the pedicle was flat. The two-point discrimination of the flap was 5-10 mm, with an average of 7 mm. There were only pigmentation and no obvious scar in the donor site of the uninjured foot. The ankle joint function was evaluated according to the American Association of foot and ankle surgery : 4 cases were excellent and 2 cases were good.Conclusions:The free medial plantar flap with the nerve is similar to the heel tissue, with reliable blood supply, no damage to the main blood vessels, and good sensory recovery after transplantation. It is an ideal flap for repairing heel soft-tissue defects in children.