Phyllofenones F-M, Scalarane Sesterterpenes from the Marine Sponge Phyllospongia foliascens.

Eight new scalarane sesterterpenes, phyllofenones F-M (1-8), together with two known analogues, carteriofenones B and A (9-10), were isolated from the marine sponge Phyllospongia foliascens collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated. Among them, only compounds 4 and 6 displayed weak inhibitory activity against Staphylococcus aureus and Escherichia coli, with MIC values of 16 µg/mL and 8 µg/mL, respectively. Compounds 1-10 exhibited cytotoxic activity against the HeLa, HCT-116, H460, and SW1990 cancer cell lines, with IC50 values ranging from 3.4 to 19.8 µM.

Development of a 3D Eulerian/Lagrangian Aircraft Icing Simulation Solver Based on OpenFOAM.

A 3D icing simulation code is developed in the open-source CFD toolbox OpenFOAM. A hybrid Cartesian/body-fitted meshing method is used to generate high-quality meshes around complex ice shapes. Steady-state 3D Reynolds-averaged Navier-Stokes (RANS) equations are solved to provide the ensemble-averaged flow around the airfoil. Considering the multi-scale nature of droplet size distribution, and more importantly, to represent the less uniform nature of the Super-cooled Large Droplets (SLD), two droplet tracking methods are realized: the Eulerian method is used to track the small-size droplets (below 50 µm) for the sake of efficiency; the Lagrangian method with random sampling is used to track the large droplets (above 50 µm); the heat transfer of the surface overflow is solved on a virtual surface mesh; the ice accumulation is estimated via the Myers model; finally, the final ice shape is predicted by time marching. Limited by the availability of experimental data, validations are performed on 3D simulations of 2D geometries using the Eulerian and Lagrangian methods, respectively. The code proves to be feasible and accurate enough in predicting ice shapes. Finally, an icing simulation result of the M6 wing is presented to illustrate the full 3D capability.

Productive life cycle of adeno-associated virus serotype 2 in the complete absence of a conventional polyadenylation signal.

We showed that WT adeno-associated virus serotype 2 (AAV2) genome devoid of a conventional polyadenylation [poly(A)] signal underwent complete genome replication, encapsidation and progeny virion production in the presence of adenovirus. The infectivity of the progeny virion was also retained. Using recombinant AAV2 vectors devoid of a human growth hormone poly(A) signal, we also demonstrated that a subset of mRNA transcripts contained the inverted terminal repeat (ITR) sequence at the 3' end, which we designated ITR in RNA (ITRR). Furthermore, AAV replication (Rep) proteins were able to interact with the ITRR. Taken together, our studies suggest a new function of the AAV2 ITR as an RNA element to mediate transgene expression from poly(A)-deleted mRNA.

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial.

BACKGROUND: As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP. OBJECTIVE: The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm. MAIN OUTCOME MEASURES: Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools. RESULTS: Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants' pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial. CONCLUSION: The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655). Please cite this article as: He JY, Tu XY, Yin ZF, Mu H, Luo MJ, Chen XY, Cai WB, Zhao X, Peng C, Fang FF, Lü C, Li B. Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial. J Integr Med. 2024; 22(1): 39-45.

Eutypellaolides A-J, Sesquiterpene diversity expansion of the polar fungus Eutypella sp. D-1.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.

Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3ß/ß-catenin pathway.

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3ß/ß-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3ß/ß-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3ß/ß-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION: Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3ß/ß-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3ß/ß-catenin pathway. J Integr Med. 2023; 21(2): 184-193.

Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/ß-catenin pathway under hypoxia.

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/ß-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/ß-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/ß-catenin pathway. CONCLUSION: JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/ß-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/ß-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.

[A comparison study of pharmacokinetics between bufalin-loaded bovine serum albumin nanoparticles and bufalin in rats].

OBJECTIVE: To determine the bufalin concentration in rats' plasma by establishing a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and to evaluate and compare the pharmacokinetic characteristics of bufalin-loaded bovine serum albumin nanoparticles (bufalin-BSA-NP) and bufalin. METHODS: Thirty Wistar rats were randomly divided into six groups with five rats in each group, and administered with a single dose of 0.6, 0.3 and 0.15 mg/kg of bufalin-BSA-NP or bufalin, respectively. After the administration, blood samples were collected from the orbital venous plexus at designed time points (1, 5, 8, 10, 15, 20, 30, 45, 60, 120, 180, 300 and 480 min). The concentration of bufalin in plasma at different sampling time points was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and compared. RESULTS: The established HPLC-MS/MS method had high linearity, precision and accuracy. The blood plasma area under curve, the mean retention time and the terminal half life of bufalin-BSA-NP were 1.19 to 1.81, 2.12 to 3.61 and 2.17 to 2.94 times of bufalin, respectively. CONCLUSION: Bufalin-BSA-NP has the function of sustained release thus to prolong the bufalin remaining in blood.

[Clinical application of new three-dimensional honeycomb guide in percutaneous cannulated screw fixation of femoral neck fracture].

OBJECTIVE: To design a new type of three-dimensional honeycomb guide for percutaneous cannulated screw placement in femoral neck fracture and evaluate its effectiveness. METHODS: The clinical data of 40 patients with femoral neck fracture who met the selection criteria between June 2019 and December 2020 were retrospectively analyzed. According to different intraoperative positioning methods, they were divided into control group (20 cases, free hand positioning screws) and study group (20 cases, new guide assisted positioning screws). There was no significant difference in gender, age, side, cause of injury, Garden classification, and time from injury to operation between the two groups ( P>0.05). The operation time, fluoroscopy times, guide needle puncture times, and fracture healing time of the two groups were recorded. The hip function was evaluated by Harris score at last follow-up. At immediate after operation, the following imaging indexes were used to evaluate the accuracy of screw implantation distribution: screw spacing, screw coverage area, distance from screw to cervical cortex, parallelism between screws, and screw to cervical axial deviation. RESULTS: All operations were successfully completed, and the guide needle did not penetrate the femoral neck cortex. There was no significant difference in operation time and fluoroscopy times between the two groups ( P>0.05); the guide needle puncture times in the study group was significantly less than that in the control group ( t=8.209, P=0.000). Imaging detection at immediate after operation showed that the screw spacing and screw coverage area in the study group were significantly greater than those in the control group ( P<0.05); the distance from screw to cervical cortex, parallelism between screws, and screw to cervical axial deviation were significantly smaller than those in the control group ( P<0.05). All patients were followed up 7-25 months, with an average of 19.3 months. There was no significant difference in follow-up time between the two groups ( t=-0.349, P=0.729). There were 2 cases of fracture nonunion in the control group and 1 case in the study group, and the other fractures completely healed. One case of osteonecrosis of the femoral head occurred in the control group. During the follow-up, there was no complication such as vascular and nerve injury, venous thrombosis, screw penetration, withdrawal, breakage, and refracture, etc. There was no significant difference in fracture healing time and Harris score at last follow-up between the two groups ( P>0.05). CONCLUSION: The new three-dimensional honeycomb guide has the advantages of simple structure and convenient use. It can reduce the puncture times of the guide needle and effectively improve the accuracy distribution of cannulated screw implantation.

Effect of Ultrasonic Penetration with Volatile Oil of Olibanum and Chuanxiong Rhizoma on Acute Knee Synovitis Induced by Sports Training: An Open-Label Randomized Controlled Study.

Background: Knee synovitis is a common sports injury. We proposed the use of UTVOR, which is a combination of the use of volatile oil of Olibanum (VOO) and volatile oil of Chuanxiong Rhizoma (VOCR) and conventional ultrasound (US) therapy, to treat knee synovitis. Design, Setting, Participants, and Interventions. Participants were randomly assigned into a control group (conventional US therapy group) and a test group (UTVOR group). The control group received conventional US therapy with a coupling agent as the medium. The test group received a revised US therapy with VOO and VOCR as media. Both groups were treated once per day for three consecutive days. Main Outcome Measures. The subjects' Visual Analogue Scale (VAS) pain score, Lysholm knee score, knee swelling degree, circumference, and range of motion of the knee joint were evaluated before the first treatment and 24 h after the third treatment. The VAS pain score was considered the primary outcome, while the three other measurements were regarded as the secondary outcomes. An adverse event was reported subjectively and recorded. Results: A total of 116 participants were included in the analysis (test group: n = 64; control group: n = 52). The evaluation results showed that the VAS pain scores of the male and female participants in both groups decreased after treatment (P < 0.001), but only the difference among the male sub-group had significant between-group difference (P < 0.001). After treatment, the Lysholm scores in both groups increased significantly (all P < 0.001), the range of motion and the circumference of the injured knee decreased significantly (P < 0.001), while no between-group difference was observed in general or in the gender sub-groups (all P > 0.025). No side effect or complication was reported during the treatment. Conclusion: UTVOR had a superior analgesic effect to conventional US therapy in the male population, but its effects on alleviating joint function, swelling, and range of motion were comparable to that of conventional US therapy. Our study found that UTVOR can be an effective method to reduce pain and treat knee synovitis, and it is subjectively safe. Trial registration. This study was registered under the Chinese Clinical Trial Registry (Trial Registration Number: ChiCTR2000035671).

Opposite effect of basic combat training on mood state of recruits with different physical fitness: A study from perspective of fatigue.

Objective: Basic combat training (BCT) is a kind of necessary high-intensity training to help each military recruit convert into a qualified soldier. In China, both the physical fatigue and passive psychological state have been observed in new recruits during BCT. However, after same-intensity training, the degree of fatigue and passive mood vary among recruits. Therefore, this study aimed to explore the effect of BCT on mood state of recruits with different physical fitness levels from a perspective of fatigue. Materials and methods: Before and after BCT, the degree of fatigue and mood state of participants were evaluated via the Borg Rating of Perceived Exertion Scale and Profile of Mood States Questionnaire immediately after 20 push-ups as RPE and POMS scores [total mood disturbance (TMD), passive mood (Ttension, Tanger, Tfatigue, Tdepression, and Tconfusion) and positive mood (Tvigour and Testeem)]. The participants were divided into two groups according to the RPE score measured after BCT: (1) group 1: RPE score after BCT < 13 and (2) group 2: RPE score after BCT ≥ 13. Result: A total of 564 recruits were included (group 1: 456/564, 80.85%; group 2: 108/564, 19.15%). After BCT, in group 1, TMD (from 95.65 ± 17.89 to 87.52 ± 17.63) and passive mood Ttension (from 4.46 ± 3.18 to 3.79 ± 3.14), Tfatigue (from 4.94 ± 3.58 to 3.12 ± 3.04), Tdepression (from 2.86 ± 3.41 to 2.01 ± 2.75), Tconfusion (3.12 ± 2.72 to 2.42 ± 2.57) declined significantly (all within-group p < 0.001), but positive mood both increased significantly (Tvigour: from 13.21 ± 4.59 to 15.44 ± 5.42, Testeem: from 9.18 ± 3.36 to 11.04 ± 3.67; both within-group p < 0.001); while in group 2, only Tanger (from 4.27 ± 4.16 to 6.22 ± 5.94, within-group p = 0.001) and Testeem (from 8.36 ± 3.15 to 9.07 ± 3.67, within-group p = 0.031) increased significantly. Conclusion: BCT could alleviate passive mood and add to positive mood for recruits with better physical fitness, while had no ameliorative effects on or even deteriorate most of the passive mood for recruits with worse physical fitness.

Comprehensive evaluation of military training-induced fatigue among soldiers in China: A Delphi consensus study.

Objective: Military training-induced fatigue (MIF) often results into non-combat attrition. However, standard evaluation of MIF is unavailable. This study aimed to provide credible suggestions about MIF-evaluation. Methods: A 3-round Delphi study was performed. The authority of the experts was assessed by the authority coefficient (Aa). In round 1, categories of indicators were collected via anonymous survey of experts, then potential indicators were selected via literature search. In round 2, experts should evaluate the clinical implication, practical value, and importance of each potential indicators, or recommend new indicators based on feedback of round 1. Indicators with recommendation proportions ≥ 70% and new recommended indicators would be included in round 3 to be rated on a 5-point Likert scale. "Consensus in" was achieved when coefficient of concordance (Kendall's W) of a round was between 0.2 and 0.5 and the coefficient of variation (CV) of each aspect for an indicator was < 0.5. If round 3 could not achieve "consensus in," more rounds would be conducted iteratively based on round 3. Indicators included in the recommendation set were ultimately classified into grade I (highly recommended) or grade II (recommended) according to the mean score and CV of the aspects. Results: Twenty-three experts participated with credible authority coefficient (mean Aa = 0.733). "Consensus in" was achieved in round 3 (Kendall's W = 0.435, p < 0.001; all CV < 0.5). Round 1 recommended 10 categories with 73 indicators identified from 2,971 articles. After 3-round consultation, consensus was reached on 28 indicators focusing on the cardiovascular system (n = 4), oxygen transport system (n = 5), energy metabolism/metabolite level (n = 6), muscle/tissue damage level (n = 3), neurological function (n = 2), neuropsychological/psychological function (n = 3), endocrine function (n = 3), and exercise capacity (n = 2). Among these, 11 indicators were recommended as grade I: basic heart rate, heart-rate recovery time, heart rate variability, hemoglobin, blood lactic acid, urine protein, creatine kinase, reaction time, Borg Rating of Perceived Exertion Scale, testosterone/cortisol, and vertical jump height. Conclusion: This study developed a reliable foundation for the comprehensive evaluation of MIF among soldiers.

Corrigendum to "The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways".

[This corrects the article DOI: 10.1155/2018/5629304.].

Novel piston technique versus Ilizarov technique for the repair of bone defect after lower limb infection.

BACKGROUND: We aimed to compare the effectiveness and complications of a novel piston technique versus the Ilizarov technique for the repair of bone defects after lower limb infection. PATIENTS AND METHODS: We retrospectively reviewed 41 patients who had been treated at our department for lower extremity bone defects following osteomyelitis. There were 38 men and three women with a mean age of 43.41 (range, 12-69 years). The infected bone defects involved 36 tibias and five femurs. The piston technique (PT, group A) was used in 12 patients and the Ilizarov technique (IT, group B) in 29 patients. The mean follow-up period was 28.50 months (PT) and 29.90 months (IT). The modified Application of Methods of Illizarov (ASAMI) criteria was used to evaluate bone healing and functional recovery. RESULTS: Complete eradication of the infection and union of docking sites were accomplished in both groups. The mean external fixator index (EFI) was 42.32 days/cm in group A versus 58.85 days/cm in group B (p < 0.001). The bone outcomes were similar between groups A and B (p = 0.558) (excellent [9 vs. 19], good [3 vs.10]); group A showed better functional outcomes than group B (p < 0.05) (excellent [7 vs. 6], good [4 vs. 12], fair [0 vs. 10] and poor [1 vs. 1]). Pain was the most common complaint during follow-up, and group A had fewer cases of pin tract infection (1 vs. 6), adjacent joint stiffness (3 vs. 8), and delayed healing of the joint (0 vs. 3). CONCLUSIONS: Satisfactory bone healing can be achieved by using both PT and IT, although PT demonstrated better functional results, lower EFI, and allowed early removal of the external fixation. We found that this novel piston technique can improve the comfort of patients, reduce the incidence of complications, and provide rapid and convenient rehabilitation.

Sec62 promotes pro-angiogenesis of hepatocellular carcinoma cells under hypoxia.

This study aimed to investigate the underlying molecular pathogenic mechanism of Sec62 in hepatocellular carcinoma (HCC). Microarray analysis was conducted to profile the global gene expression in the HCC cell line Huh7 cells transfected with Sec62high vs. NC and Sec62low vs. NC. Ingenuity pathway analysis and gene set enrichment analysis were used to perform Sec62-related signaling pathway analysis from screened differentially expressed genes (DEGs). A protein-protein interaction network was constructed. Experimental validation of the expression of key DEGs was conducted. Hypoxia-induced tube formation was undertaken to investigate the role of Sec62 in angiogenesis. A total of 74 intersected DEGs were identified from Huh7 cells with Sec62high vs. NC and Sec62low vs. NC. Among them, 65 DEGs were correlated with the expression of Sec62. The P53 signaling pathway was found to be enriched in Huh7 cells with Sec62high vs. NC, while the acute phase response signaling pathway was enriched in Huh7 cells with Sec62low vs. NC. DEGs, such as serine protease inhibitor E (SERPINE) and tumor necrosis factor receptor superfamily, member 11B (TNFRSF11B), were not only identified as the lead genes of these enriched pathways, but were also found to be closely related to Sec62. Moreover, knockdown of Sec62 decreased the expression of SERPINE1 (plasminogen activator inhibitor type 1 (PAI-1)) and TNFRSF11B, whereas overexpression of Sec62 had the opposite effects. In addition, knockdown of Sec62 inhibited hypoxia-induced tube formation via PAI-1. Sec62 promoted pro-angiogenesis of HCC under hypoxia by regulating PAI-1, and it may be a crucial angiogenic switch in HCC.

Feprazone Ameliorates TNF-α-Induced Loss of Aggrecan via Inhibition of the SOX-4/ADAMTS-5 Signaling Pathway.

Background: Arthritis is a cartilage degenerative disease that is mainly induced by the degradation of the cartilage extracellular matrix (ECM), which is found to be regulated by the expression level of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMT-5), an enzyme degrading Aggrecans in the ECM. Feprazone is a classic nonsteroidal anti-inflammatory drug with promising efficacy in arthritis. The present study aims to investigate the protective effect of Feprazone on the degraded Aggrecan in the human chondrocytes induced with tumor necrosis factor-α (TNF-α) and to clarify the underlying mechanism. Methods: To investigate the effect of Feprazone, the CHON-001 chondrocytes were stimulated with TNF-α (10 ng/mL) in the presence or absence of Feprazone (3, 6 µM) for 24 h. Mitochondrial membrane potential was evaluated using the Rhodamine 123 assay. The gene expressions of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and ADAMTS-5 in the treated chondrocytes were detected using real-time quantitative polymerase chain reaction (qRT-PCR), and the protein levels of these targets were determined using enzyme-linked immunosorbent assay (ELISA). SOX-4 was knocked down by transfecting the siRNA into the chondrocytes. Western blot analysis was utilized to evaluate the expression levels of SOX-4, Aggrecan, and protein kinase C (PKCα). Results: First, the reduced mitochondrial membrane potential (ΔΨm) and secretion of proinflammatory factors (IL-1ß, IL-8, and MCP-1) induced by TNF-α were significantly reversed by treatment with Feprazone. Second, the expression of Aggrecan was significantly decreased by stimulation with TNF-α via upregulation of ADAMTS-5 but was dramatically reversed by the introduction of Feprazone. Third, we found that TNF-α elevated the expression of ADAMTS-5 by upregulating SOX-4, which was observed to be related to the activation of PKCα. Lastly, the elevated expression of SOX-4 induced by TNF-α was significantly reversed by Feprazone. Conclusions: Feprazone might ameliorate TNF-α-induced loss of Aggrecan via the inhibition of the SOX-4/ADAMTS-5 signaling pathway.

Cytotoxic meroterpenoids from the marine sponge Dactylospongia elegans.

Three new sesquiterpene quinones/hydroquinones, 20-demethoxy-20-isopentylaminodactyloquinone D (1), 20-demethoxy-20-isobutylaminodactyloquinone D (2), and 19-methoxy-dictyoceratin-A (3), and five known related compounds (4-8) were isolated from the marine sponge Dactylospongia elegans. Their structures were elucidated by spectroscopic analysis, ECD calculation, single-crystal X-ray diffraction, and comparison with the literature. Compounds 3 and 5-8 exhibited activities against the human cancer cell lines DU145, SW1990, Huh7, and PANC-1 with IC50 values ranging from 2.33 to 37.85 µM.

Unicondylar knee arthroplasty versus total knee arthroplasty in adults with isolated medial osteoarthritis: A matched study protocol.

BACKGROUND: The choice between unicondylar knee arthroplasty (UKA) and total knee arthroplasty (TKA) is likely to have long-term implications for patient-reported health outcomes. However, high-quality studies that compare the outcomes of TKA and UKA and their effects are still lacking in the literature. Thus, the aim of the present study was to compare the UKA and TKA techniques with regard to functional outcomes and perioperative complications in patients who had isolated medial osteoarthritis. METHODS: This was a retrospective, single-center, matched-controlled study performed with approval of our hospital (Kunshan hospital of Traditional Chinese Medicine affiliated to Nanjing University of Traditional Chinese Medicine), with the ethics number KZY2020-37. To reduce the effect of selection bias and potential confounding in this observational study, a 1:1 matching algorithm was applied. The groups were split by sex, age to within 6 years, and body mass index within 5 kg/m. Thus, we retrospectively reviewed the records of 240 consecutively enrolled patients who underwent UKA and 240 patients who underwent TKA from January 2013 to June 2015 from the database of our institution. Written informed consent was obtained from all subjects participating in the trial. Clinical outcomes included range of motion, Short Form 12 score, new Knee Society Score, Western Ontario and McMaster Universities Arthritis Index, and the complications. The outcome measures were evaluated by a physiotherapist and were assessed preoperatively and postoperatively at 6 months and 2 years. The mean follow-up time was 3 years. CONCLUSION: We hypothesized that there was no significant difference between the 2 groups in terms of postoperative outcomes. TRIAL REGISTRATION: Our study was registered in Research Registry (researchregistry5828).

Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-ß1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro. METHODS: TGF-ß1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot. RESULTS: BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-ß1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-ß1 stimulated A549 cells. CONCLUSION: These results indicate that BYHWT suppressed TGF-ß1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

[Analysis of hemostatic effect of intra-articular injection of tranexamic acid after minimally invasive unicompartmental knee arthroplasty].

OBJECTIVE: To investigate the effect of intra-articular injection of tranexamic acid on blood loss and blood transfusion rate after minimally invasive unicompartmental knee arthroplasty. METHODS: From January 2015 to September 2017, 90 patients underwent minimally invasive unicompartmental knee arthroplasty were divided into tranexamic acid group and control group, 45 cases in each group. In the tranexamic acid group, there were 22 males and 23 females, aged 62 to 69 (66.1±2.4) years;in the control group, 20 males and 25 females, aged 63 to 71(68.5±5.2) years. The amount of bleeding in the drainage ball at 48 hours after operation was recorded, and the blood transfusion rate and hematocrit level duringthe perioperative period were recorded. The factors influencing perioperative blood loss included gender, age and body mass index (BMI). RESULTS: All patients were followed up for 12.5 to 28.3 (22.8±7.9) months. During the follow-up, the wounds of the two groups healed well, and no deep vein thrombosis and pulmonary embolism occurred. There was no significant difference in postoperative blood loss between the tranexamic acid group and the control group. The postoperative bleeding volume in the tranexamic acid group was (110.0±52.1) ml, and that in the control group was (123.0±64.5) ml (P=0.39). There was no blood transfusion in the two groups. CONCLUSION: Intra articular injection of tranexamic acid can not significantly reduce the postoperative blood loss in patients with minimally invasive unicompartment.