Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

Objective To observe the impacts of acupuncture and moxibustion on kelch like epichlorohydrin related protein 1(Keap1)and nuclear factor E2 related factor 2(Nrf2)signal pathway in kidney tissue of cisplatin(DDP)-induced kidney injury model mice,and to explain the protective mechanism of acupuncture and moxibustion on improving kidney injury caused by DDP.Methods Forty SPF male KM rats were randomly divided into 4 groups,with 10 rats in each group.One day before the start of treatment,the three groups of mice outside the blank group were intraperitoneally injected with cisplatin 10 mg·kg-1 according to their body weight,and the blank group was injected with the same dose of 0.9%NaCl solution.The model was established 24 hours later.Both acupuncture group and moxibustion group selected"Dazhui"(GV14),"Ganshu"(BL18),"Shenshu"(BL23)and"Zusanli(Housanli)"(ST36)for acupuncture and moxibustion respectively,once a day for 5 days.The other two groups were fixed every day without treatment.After fasting for 1 day,the contents of BUN,Scr,CysC and NGAL in serum and Keap1 and Nrf2 in renal tissue were detected by ELISA;Western blot and Real-time PCR were used to detect the protein expression and gene transcription of Keap1 and Nrf2 in the kidney tissue of mice in each group.Results Compared with the blank group,the content of Keap1 protein,protein expression and relative expression of mRNA in the model group increased(P<0.05),the content of Nrf2 protein,protein expression decreased(P<0.05),Nrf2 relative expression of mRNA increased(P<0.05);Compared with the model group,the content of Keap1 protein,the expression of Keap1 protein and the relative expression of Keap1 mRNA in the kidney of mice in the acupuncture and moxibustion groups decreased(P<0.05);Nrf2 protein content,protein expression and relative mRNA expression increased(P<0.05).Conclusion Acupuncture and moxibustion can improve the renal function of DDP renal injury model mice and enhance their antioxidant stress ability,so as to improve the renal injury caused by DDP chemotherapy.Its mechanism may be related to Keap1/Nrf2 signal pathway.

Head ; Humans ; Skull Base ; Solitary Fibrous Tumors/surgery* ; Virtual Reality

Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.

Objective:To explore the clinical application and effect of repairing the donor site of ipsilateral fibular hallux flap with the transverse V-Y advancement flap of the great toe.Methods:Form January 2017 to January 2020, the donor sites of the ipsilateral fibular hallux flap were repaired by the transverse V-Y advancement flap of the great toe in the Department of Hand Surgery, 521 Hospital of Weapon Industry on 20 patients, including 16 males and 4 females with an average age of 33 (18-52) years old. First, the donor site of the fibular hallux flap was sutured to reduce the size of wound. The width of the remaining wound was 0.4 to 1.6 cm, and the area of the remaining wound was 0.5 cm×0.8 cm-1.6 cm×1.8 cm. Then the remaining wound was repaired with the transverse V-Y advancement flap of the ipsilateral great toe. The distance for transfer of transverse advancement V-Y flap was 0.2-0.8 cm, and the area of the transverse V-Y advancement flap was 1.0 cm×1.4 cm-1.8 cm×2.4 cm. The end of postoperative follow-up was scheduled in July 2021. The follow-up items included: survival of the transverse V-Y advancement flap, wound infection, appearance, shape, texture and sensation of the V-Y advancement flap, pain on the V-Y advancement flap and the great toe, cold tolerance and the scar condition at the donor site of the ipsilateral fibular hallux flap and the V-Y advancement flap, the appearance, sensation and flexion and extension of the great toe at the donor site, other discomforts in the donor site of great toe, walking and other functions affected by the discomforts.Results:The postoperative follow-up lasted from 12 to 18(average of 14) months. All the V-Y advancement flaps survived without infection at the donor sites of the great toe, and donor sites healed primarily. The appearance, shape and texture of the advancement V-Y flap were close to the skin of the same area of the contralateral great toe. The TPD of the V-Y advancement flap and the ipsilateral great toe ranged from 4 to 7 mm. The average score of the Visual analog scale(VAS) was 0.3 and 0.6 respectively in the evaluation of cold tolerance of the advancement V-Y flap and the ipsilateral great toe. The average score of the Vancouver scar scale(VSS) was 0.2 and 1.2 respectively in the scar evaluation of the V-Y advancement flap and the ipsilateral great toe. There was no visual difference between the appearance of the great toe at the donor site and the contralateral toe. There was no pain and other discomfort on the V-Y advancement flap and the ipsilateral great toe. The functions of the donor foot were not affected in walking, running, jumping and tiptoeing in all cases.Conclusion:It is a simple, safe and effective method to repair the donor site of the small-area ipsilateral fibular hallux flap by the transverse V-Y advancement flap of the great toe. It only causes a small wound but the appearance and function of the ipsilateral great toe can be repaired with a transverse V-Y advancement flap of the great toe.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trial-and-error analyses to investigate suitable product's material, structure, mechanical properites etc. The whole process from
Cell Differentiation ; Cell Movement ; Cell Proliferation ; Computer Simulation ; Tissue Engineering

Hypoxia-inducible factor 1 (HIF-1), as a main transcriptional regulator of metabolic adaptation to changes in the oxygen environment, participates in many physiological and pathological processes in the body, and is closely related to the pathogenesis of many diseases. This review outlines the mechanisms of HIF-1 activation, its signaling pathways, natural inhibitors, and its roles in diseases. This article can provide new insights in the diagnosis and treatment of human diseases, and recent progress on the development of HIF-1 inhibitors.
Disease ; Humans ; Hypoxia-Inducible Factor 1/physiology* ; Oxygen ; Signal Transduction

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

OBJECTIVE: To study the clinical characteristics of the patients with tiny lumbar disc herniation and severe symptoms(tLDHSS) and the therapeutic effects of percutaneous endoscopic lumbar discectomy(PELD). METHODS: From January 2014 to February 2019, 34 patients with tLDHSS were reviewed retrospectively, including 20 males and 14 females, aged from 31 to 73 (48.8±10.1) years, with a follow up duration ranged from 8 to 48 (21.8±10.3) months. The clinical manifestations, imaging and surgical data were analyzed. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores were analyzed before operation, 1 month after operation and at the latest follow-up. The preoperative and postoperativescores were compared. At the latest follow up, the Macnab system was used to evaluate the effects of the operation. RESULTS: The main symptom of 34 cases was severe radiation pain on one side of lower limbs. The duration of preoperative symptoms ranged from 0.33 to 84 months. The disc herniation was found in 7 cases of L and 27 cases of LS. According to the MSU division of lumbar disc herniation, 31 cases were located in area B. In all cases, it was confirmed that the protruding nucleus compressed the nerve root, and in 26 cases, the nerve root was obviously inflamed. The operation time ranged from 30 to 80 min, with a mean time of (43.5±9.5) min. The preoperative VAS score was 8.1±1.3 and ODI score was 31.8±6.7. And the VAS score was 1.1± 0.3, 0.7±0.4 on the first month after operation and the latest follow up, respectively. The ODI score was 5.3±2.1 and 0 to 10 (with a median score of 2) on the first month after operation and the latest follow-up respectively. The postoperative VAS and ODI scores were improved compared with preoperative scores.At the latest follow up, 28 cases got an excellent result and 6 cases good according to Macnab evaluation system. During the follow-up period, only one patient had recurrent disc herniation. CONCLUSION The main symptom of patients with tLDHSS is severe radiation pain on one side of lower limb. It manifests as sudden onset and shorter course of disease. Severe local inflammation was induced by local compression of the protruding nucleus pulposus on the nerve root out of the dura. For this kind of patients, thin layer CT scan has an important diagnostic value. In the treatment of this kind of patients, the symptoms are relieved rapidly, the curative effect is definite and the recurrence rate is low.
Adult ; Aged ; Diskectomy, Percutaneous ; Endoscopy ; Female ; Humans ; Intervertebral Disc Displacement ; Lower Extremity ; Lumbar Vertebrae ; Male ; Middle Aged ; Pain ; Retrospective Studies ; Treatment Outcome