Objective To identify the features of 1H-magnetic resonance spectroscopy(1H-MRS) in patients with chronic obstructive pulmonary disease(COPD) of the hippocampus.Methods 32 patients with COPD randomly selected and 30 normal controls were selected.1H-MRS of the hippocampus was performed given to on all the subjects on hippocampus.The ratios of NAA/Cr and Cho/Cr were determined.Results In the bilateral hippocampus, the NAA/Cr ratio in patients with COPD demonstrated lower than that in normal controls(t=4.963,P=0.007 and t=4.856,P=0.023).The Cho/Cr ratio in patients with COPD showed higher than that in normal controls, the differences was were statistically significant(t=3.469,P=0.013 and t=3.019,P=0.047) Conclusion Abnormal metabolism of neurons on the hippocampus in patients with COPD is showed.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with local ablation in the treatment of unresectable primary liver cancer （PLC）， and to provide evidence-based reference for rational clinical treatment. METHODS Retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library， ClinicalTrials， Web of Science， Ovid and SinoMed， randomized controlled trial （RCT） about TACE combined with local ablation （trial group） versus TACE （control group） were collected. After screening the literature and extracting the data， the bias risk assessment tool recommended by the Cochrane System Evaluator Manual 5.1.0 was used to evaluate the quality of the included literature； Stata14.0 software was used for meta-analysis. RESULTS A total of 39 RCTs were included， including 2 294 patients， involving 6 interventions， i.e. TACE， TACE + radiofrequency ablation （RFA）， TACE + microwave ablation （MWA）， TACE + absolute ethanol injection （PEI）， TACE + cryoablation （CRA）， TACE + high-intensity ultrasound focused ablation （HIFU）， and 4 chemotherapeutic drugs， i.e. platinum， anthracycline， pyrimidine analogues， and polypeptides. The results of meta-analysis showed that in terms of objective remission rate， TACE+RFA， TACE+HIFU and TACE+MWA were higher； in terms of 1-year survival rate， TACE+PEI， TACE+HIFU and TACE+MWA were higher； in terms of 2-year survival rate， TACE+HIFU， TACE+MWA and TACE+PEI were higher； in terms of 3-year survival rate， TACE+HIFU， TACE+PEI and TACE+RFA were higher； in terms of security， TACE+MWA， TACE+RFA and TACE were 643295494@qq.com higher； there was no significant difference in the efficacy of 4 chemotherapeutic drugs in TACE+MWA （P＞0.05）. CONCLUSIONS For patients with unresectable PLC， TACE+ MWA has good efficacy and safety， which is the best combination； the 4 chemotherapeutic drugs in TACE+MWA are all effective， and suitable chemotherapeutic drugs can be selected individually.

Cardiovascular diseases are a class of circulatory system diseases involving the heart and vessels， including arrhythmia， hypertension， coronary heart disease， myocardial infarction， heart failure and so on. Due to the complicated pathogenesis， diverse disease types， and difficult treatment， cardiovascular diseases pose serious threatens to the human health. Therefore， it is urgent to develop effective therapies. Ferroptosis， a new type of cell death different from autophagy and apoptosis， is iron-dependent and accompanied by lipid peroxide accumulation. The mechanism of ferroptosis is complex. Recent studies have shown that iron homeostasis plays a role in the occurrence of ferroptosis， which may be induced by iron intake， utilization， and output and iron-related protein synthesis. In addition， iron homeostasis and ferroptosis have been confirmed to be involved in the pathological process of cardiovascular diseases， so regulating iron homeostasis and ferroptosis in cardiomyocytes may be a focus of the future research on cardiovascular diseases. Traditional Chinese medicine （TCM） provides a unique treatment method， and the unique syndrome differentiation system and treatment methods have been widely used in the clinical diagnosis， prevention， and treatment of cardiovascular diseases. Studies have demonstrated that TCM compound prescriptions and the active components in Chinese medicinal materials can regulate iron homeostasis and ferroptosis to protect cardiomyocytes. This paper introduces the mechanism of iron homeostasis in regulating ferroptosis and summarizes the effects of iron homeostasis-mediated ferroptosis on cardiovascular diseases. Furthermore， the research progress of TCM in regulating iron homeostasis-mediated ferroptosis in cardiovascular diseases is reviewed to provide new ideas for TCM prevention and treatment of cardiovascular diseases.

Objective To explore the immune-microenvironment of the retinas at different stages of retinal degeneration in Royal College of Surgeon (RCS) rats. Methods RCS-rdy--P+(RCS) rats at early stage (P20), middle stage (P40) and late stage (P60) were involved,12 rats at each post-natal day,RCS-rdy+-P+rats severed as control. Relative concentrations of rat cytokines in rat retina homogenate were detected by using Bio-Plex Suspension Array System. Relative expressions of interleukin-2 (IL-2),C-C motif ligand 2 (CCL2),chemokine (C-X-C motif) ligand 9 (CXCL9),CXCL10,CXCL11 and interferon-γ(IFN-γ) mRNA in rat retina were analyzed by real-time PCR. Expressions of IFN-γ and immune cells surface marker CD4,CD8 and CD161 in the retinas were detected by immunohistochemical staining. Percentage of IFN-γ positive T lymphocytes and natural killer(NK) cells in rat retina were analyzed by flow cytometry. The concentrations of IFN-γ in rat retina homogenate were evaluated by enzyme-linked immunosorbent assay ( ELISA ). The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results Lymphocytes related cytokines and chemokines mRNA expression levels in the RCS rat retinas showed increase trends with the extension of time. The expression levels of IL-2,CCL2,CXCL9,CXCL10,CXCL11 and IFN-γ mRNA in P60 RCS rat retinas were significantly increased than those in the P20 RCS rat retinas and the control rat retinas (all at P<0.05).The positive rates of CD4,CD8 and CD161 cells in the retinas of P60 RCS rats was (9.09±0.89)%, (18.77±0.38)% and (9.41±0.38)% ,respectively. The proportion of IFN-γ positive cells in the retinas of P60 RCS rats was (8.29±0.27)%,which was significantly higher than that of the control rats ([0.28±0.02]%),with a significant difference between them (t=29.03,P=0.00). CD4+,CD8+and CD161+lymphocytes were mainly distributed in the retinas of P60 RCS rats, and the expressions of IFN-γ were co-located with lymphocyte surface markers. There were significant differences in the concentrations of IFN-γ in the retinas of RCS rats and control rats at different day ages (Fgroup=16.49,P<0.01; Ftime=21.05,P<0.01),the concentration of IFN-γ in retinas of P60 RCS rats was significantly higher than that of P20 RCS rats, P40 RCS rats and control rats, and the differences were statistically significant ( all at P<0.05). Conclusions Along with the process of retinal degeneration,immune privilege balance in the retinas is disrupted, the expressions of lymphocytes related chemokines and cytokines are elevated. Lymphocytes infiltration and activation are appeared in the retina highly activated at the late stage of RP, leading to the significant up-regulation of inflammatory cytokine IFN-γ in microenvironment, which indicates that lymphocytes mediated immune response may take part in retinal degeneration.

Heart failure （HF） is a group of syndromes caused by cardiac dysfunction with impaired ventricular pumping， seriously affecting patients' health and quality of life. The pathogenesis of HF is complex， including myocardial contractility decline， myocardial fibrosis， and ventricular remodeling， and it is related to neuroendocrine regulation， inflammation， and cardiomyocyte autophagy. Autophagy is a key regulatory mechanism by which cells degrade themselves to maintain body homeostasis. In the process of HF， moderate autophagy can remove aging and damaged cardiomyocytes and maintain the balance of myocardial energy metabolism， while abnormal autophagy may lead to functional decline and pathological changes of cardiomyocytes. The adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway is one of the classical pathways regulating autophagy. This pathway can mediate the autophagy of cardiomyocytes and play a role in protecting the cardiac function and delaying HF progression. Traditional Chinese medicine （TCM） with a long history has a unique theoretical system and shows satisfactory therapeutic effects and wide application prospects amid the integration with modern medicine. The clinical practice of TCM has accumulated rich experience in the treatment of cardiovascular diseases. A large number of studies have shown that the active components and compound prescriptions of TCM and Chinese patent medicines can mediate autophagy by regulating the AMPK/mTOR signaling pathway to treat HF. This article explains the role of AMPK/mTOR signaling pathway-mediated autophagy in the treatment of HF， introduces the understanding of autophagy， AMPK/mTOR signaling pathway， and HF based on TCM theories， and reviews the research progress in the regulation of autophagy by TCM in the treatment of HF via the AMPK/mTOR pathway. This review is expected to tap the potential of TCM in the treatment of cardiovascular diseases， provide theoretical support for subsequent experimental studies， and demonstrate the advantages of TCM in clinical practice to achieve more accurate treatment.

OBJECTIVE: To conduct anatomical study on the iliac crest chimeric tissue flap and summarize its effectiveness of clinical application in repairing limb wounds. METHODS: Latex perfusion and anatomical study were performed on 6 fresh adult cadaver specimens with 12 sides, to observe the initial location, distribution, quantity, and direction of the common circumflexa iliac artery, the deep circumflexa iliac artery, and the superficial circumflexa iliac artery, and to measure their initial external diameter. Between December 2020 and September 2022, the iliac crest chimeric tissue flap repair was performed on 5 patients with soft tissue of limbs and bone defects. There were 3 males and 2 females, with an average age of 46 years (range, 23-60 years). Among them, there were 3 cases of radii and skin soft tissue defects and 2 cases of tibia and skin soft tissue defects. The length of bone defects was 4-8 cm and the area of skin soft tissue defects ranged from 9 cm×5 cm to 15 cm×6 cm. The length of the iliac flap was 4-8 cm and the area of skin flap ranged from 12.0 cm×5.5 cm to 16.0 cm×8.0 cm. The donor sites were directly sutured. RESULTS: Anatomical studies showed that there were 10 common circumflex iliac arteries in 5 specimens, which originated from the lateral or posterolateral side of the transition between the external iliac artery and the femoral artery, with a length of 1.2-1.6 cm and an initial external diameter of 0.8-1.4 mm. In 1 specimen without common circumflexa iliac artery, the superficial and deep circumflex iliac arteries originated from the external iliac artery and the femoral artery, respectively, while the rest originated from the common circumflex iliac artery. The length of superficial circumflex iliac artery was 4.6-6.7 cm, and the initial external diameter was 0.4-0.8 mm. There were 3-6 perforator vessels along the way. The length of deep circumflex iliac artery was 7.8-9.2 cm, and the initial external diameter was 0.5-0.7 mm. There were 3-5 muscular branches, 4-6 periosteal branches, and 2-3 musculocutaneous branches along the way. Based on the anatomical observation results, all iliac crest chimeric tissue flaps were successfully resected and survived after operation. The wounds at recipient and donor sites healed by first intention. All patients were followed up 8-24 months, with an average of 12 months. The tissue flap has good appearance and soft texture. X-ray film reexamination showed that all the osteotomy healed, and no obvious bone resorption was observed during follow-up. CONCLUSION The common circumflex iliac artery, deep circumflex iliac artery, and superficial circumflex iliac artery were anatomically constant, and it was safe and reliable to use iliac crest chimeric tissue flap in repairing the soft tissue and bone defects of limbs.
Adult ; Male ; Female ; Humans ; Middle Aged ; Plastic Surgery Procedures ; Ilium/surgery* ; Perforator Flap/blood supply* ; Skin Transplantation/methods* ; Lower Extremity/surgery* ; Soft Tissue Injuries/surgery* ; Treatment Outcome

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method

【Objective】 To investigate the effect of isoliquiritigenin on inflammatory response of vascular endothelial cells and whether the regulatory effect of isoliquiritigenin on inflammation is mediated by histone deacetylase 3 (HDAC3). 【Methods】 Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with LPS, different concentrations of isoliquiritigenin and HDAC3 specific inhibitor, respectively. Real-time PCR and Western blotting were used to detect the mRNA and protein expressions of inflammatory cytokines and HDAC3. Male C57BL/6J mice were randomly divided into vehicle group and isoliquiritigenin treatment group. The vascular inflammation model of C57BL/6J mice was established by ligation of the left carotid arteries. The mRNA expressions of inflammatory cytokines and HDAC3 in the carotid arteries of mice were detected by Real-time PCR. A molecular docking study was performed to investigate the interaction between isoliquiritigenin and HDAC3. 【Results】 Compared with the vehicle group, isoliquiritigenin reduced the mRNA expressions of inflammatory cytokines NLRP3, IL-1β, IL-18, MCP-1 and ICAM-1 and decreased the expression of HDAC3 mRNA and protein in HUVECs stimulated with LPS. In addition, isoliquiritigenin also decreased the mRNA expressions of NLRP3, IL-1β and HDAC3 in carotid arteries of ligated C57BL/6J mice. The docking of isoliquiritigenin in the active site of HDAC3 showed that isoliquiritigenin might act through HDAC3. Furthermore, HDAC3 specific inhibitor RGFP966 further promoted the inhibitory effect of isoliquiritigenin on the expression of inflammatory cytokines in vascular endothelial cells. 【Conclusion】 These results suggest that isoliquiritigenin suppresses the inflammatory response of vascular endothelial cells via HDAC3.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.