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Daozhen Chen,1,3,* Qiusha Tang,2,* Xiangdong Li,3,* Xiaojin Zhou,1 Jia Zang,1 Wen-qun Xue,1 Jing-ying Xiang,1 Cai-qin Guo11Central Laboratory, Wuxi Hospital for Matemaland Child Health Care Affiliated Medical School of Nanjing, Jiangsu Province; 2Department of Pathology and Pathophysiology, Medical College, Southeast University, Jiangsu Province; 3The People’s Hospital of Aheqi County, Xinjiang, China *These authors contributed equally to this workBackground: The objective of this study was to evaluate the synthesis and biocompatibility of Fe3O4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells.Methods: Magnetic Fe3O4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays.Results: Transmission electron microscopy revealed that the shapes of the Fe3O4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe3O4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe3O4. The vibrating sample magnetometer hysteresis loop suggested that the Fe3O4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD50) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe3O4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe3O4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe3O4 nano magnetofluid concentration.Conclusion: The Fe3O4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.Keywords: characterization, biocompatibility, Fe3O4, magnetic nanoparticles, hyperthermia

Qiu-Sha Tang1,*, Dao-Zhen Chen2,*, Wen-Qun Xue2, Jing-Ying Xiang2, Yong-Chi Gong1, Li Zhang2, Cai-Qin Guo21Department of Pathology and Pathophysiology, Medical College, Southeast University, Nanjing, Jiangsu; 2Central Laboratory, Wuxi Hospital for Maternal and Child Health Care, Affiliated Medical School of Nanjin, Wuxi, Jiangsu, China *Authors contributed equally to this workBackground: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide 188Re-labeled folic acid ligand (188Re-folate-CDDP/HSA).Methods: Human serum albumin was labeled with 188Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of 188Re-folate-CDDP/HAS magnetic nanoparticles was assessed.Results: Optimal conditions for 188Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and 188ReO4 eluent (0.1 mL). The rate of 188Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the 188Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of 188Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo.Conclusion: These results indicate that 188Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide (188Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.Keywords: cisplatin, folic acid, albumin, magnetic nanoparticles, 188Re, ovarian cancer

Competing Interests: The authors declare that they have no conflict of interest.

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

Competing Interests: The authors declare that they have no conflict of interest.

Objective: The primary purpose of the study was to explore the clinical efficacy of the novel snare assisted endoscopic resection of extraluminal growing gastric gastrointestinal stromal tumors (gastric GISTs) using external traction, and the secondary purpose was to compare the novel snare assisted endoscopic resection of extraluminal GISTs with the standard laparoscopic procedure., Methods: We retrospectively analyzed the patients who underwent novel external traction assisted endoscopic resection or laparoscopic resection for their extraluminal gastric GIST ≤5 cm in diameter., Results: A total of 111 patients (27 in the endoscopic group and 84 in the laparoscopic group) were included in this study. There was no significant difference in tumor diameter and complication rate between the two groups. The overall procedure time was slightly higher in the endoscopic group compared to the laparoscopic group (P = 0.034). However, postoperative hospitalization time (P < 0.001) and postoperative fasting time (P = 0.005) were shorter in the endoscopic group compared to the laparoscopic group., Conclusion: Snare external traction-assisted endoscopic resection of extraluminal growing gastric GISTs is safe and effective, and it provides a new adjunctive method for endoscopic resection of GIST., Competing Interests: Conflict of interest 1) The scientific guarantors of this publication are Xin-guang Cao. 2) The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. 3) The authors of this manuscript declare that they have no conflict of interests. 4) The protocol was approved by The First Affiliated Hospital of Zhengzhou University (No.2022-KY-1236-001) and informed consent was waived., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the safety and prognosis of enbloc or piecemeal removal after enbloc resection of a gastric GIST by comparing the clinical data of endoscopic en block resection and piecemeal removal (EP) and en block resection and complete removal (EC) of gastric GISTs., Methods: A total of 111 (43 endoscopic piecemeal, and 68 complete removal) patients with gastric GIST's ≥ 2 cm in diameter who underwent endoscopic therapy from January 2016 to June 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. In all cases, it was ensured that the tumor was intact during the resection, however, it was divided into EP group and EC group based on whether the tumor was completely removed or was cut into pieces which were then removed. The patients' recurrence-free survival rate and recurrence-free survival (RFS) were recorded., Results: There was no statistically significant difference in RFS rates between the two groups (P = 0.197). The EP group had relatively high patient age, tumor diameter, risk classification, and operation time. However, there was no statistically significant difference in the number of nuclear fission images, postoperative hospitalization time, postoperative fasting time, complication rate and complication grading between the two groups (P > 0.05)., Conclusion: Endoscopic piecemeal removal after en block resection of gastric GIST is safe and effective and achieves similar clinical outcomes as complete removal after en block resection., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Electrospun fibres have been widely used as skin dressings due to their unique structur. However, due to the lack of intrinsic antimicrobial activity, it is easy for the wound to become infected. Bacterial infection, which leads to chronic inflammation, severely hinders the normal process of skin regeneration. In this study, a polyvinyl alcohol/chitosan (PVA/CS) composite films with chemical sterilization and near-infrared (NIR) photothermal antibacterial activity was fabricated by electrospinning. Graphene oxide (GO), a photosensitiser, was incorporated into the films, and lanthanum chloride (Lacl 3 ) as a chemical antibacterial agent was also doped in the electrospun films. The structure, morphology, mechanical properties, wettability, and antimicrobial and photothermal antibacterial activity of the PVA/CS-based fibre films were investigated. The results showed that the addition of Lacl 3 to the PVA/CS/GO nanofibres (PVA/CS/GO-La) improved the hydrophilicity, tensile strength and resistance to elastic deformation of the nanofibres. The PVA/CS/GO-La12.5 mM sample exhibited the best antibacterial performance, showing high inhibition against Staphylococcus aureus (82% antibacterial efficacy) and Escherichia coli (99.7% antibacterial efficacy). Furthermore, the antibacterial efficacy of the films surface was further enhanced after exposure to NIR light (808 nm, 0.01 W) for 20 min. In addition, the nanofibre films showed no cytotoxicity against human skin fibroblasts (HSFs), indicating its potential application in the field of broad-spectrum antibacterial materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate whether abdominal compression significantly increased the total enteroscopy rate in single-balloon enteroscopy (SBE)., Methods: Consecutive patients who underwent SBE at 2 hospitals were prospectively included between June 1, 2020, and September 30, 2021. They were randomly divided into an abdominal compression group and a non-abdominal compression group with use of sealed envelopes generated by a computer. Total enteroscopy rates were compared between the groups., Results: The study included 200 patients. The total enteroscopy rates were 73% and 16% in the abdominal compression and non-abdominal compression groups, respectively (relative risk, 13.55; 95% CI, 6.79 to 27.00; P<.001). The total enteroscopy rate was higher in the 70 patients who were identified to have undergone no previous abdominal surgery or small intestinal stenosis than in the 32 patients who had undergone such procedures in the abdominal compression group (84% vs 47%; relative risk, 6.08; 95% CI, 2.36 to 15.67; P<.001). Relevant positive findings were not significantly different between the groups (58% vs 45%; P=.07). Binary logistic regression analysis found abdominal compression to be associated with a better total enteroscopy rate (odds ratio, 16.68; 95% CI, 7.92 to 35.15; P<.001), and the presence of previous abdominal surgery or small intestinal stenosis was associated with difficulty in completing the total enteroscopy procedure (odds ratio, 0.26; 95% CI, 0.12 to 0.58; P<.01)., Conclusion: Abdominal compression significantly increased the total enteroscopy rate in SBE. Complete total enteroscopy may be challenging in patients with a history of abdominal surgery or small intestinal stenosis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Primiparas are usually at high risk of experiencing perinatal depression, which may cause prolonged labor, increased blood loss, and intensified pain, affecting maternal and fetal outcomes. Therefore, interventions are necessary to improve maternal and fetal outcomes and alleviate primiparas' negative emotions (NEs)., Aim: To discusses the impact of nursing responsibility in midwifery and postural and psychological interventions on maternal and fetal outcomes as well as primiparas' NEs., Methods: As participants, 115 primiparas admitted to Quanzhou Maternity and Child Healthcare Hospital between May 2020 and May 2022 were selected. Among them, 56 primiparas (control group, Con) were subjected to conventional midwifery and routine nursing. The remaining 59 (research group, Res) were subjected to the nursing model of midwifery and postural and psychological interventions. Both groups were comparatively analyzed from the perspectives of delivery mode (cesarean, natural, or forceps-assisted), maternal and fetal outcomes (uterine inertia, postpartum hemorrhage, placental abruption, neonatal pulmonary injury, and neonatal asphyxia), NEs (Hamilton Anxiety/Depression-rating Scale, HAMA/HAMD), labor duration, and nursing satisfaction., Results: The Res exhibited a markedly higher natural delivery rate and nursing satisfaction than the Con. Additionally, the Res indicated a lower incidence of adverse events ( e.g. , uterine inertia, postpartum hemorrhage, placental abruption, neonatal lung injury, and neonatal asphyxia) and shortened duration of various stages of labor. It also showed statistically lower post-interventional HAMA and HAMD scores than the Con and pre-interventional values., Conclusion: The nursing model of midwifery and postural and psychological interventions increase the natural delivery rate and reduce the duration of each labor stage. These are also conducive to improving maternal and fetal outcomes and mitigating primiparas' NEs and thus deserve popularity in clinical practice., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To observe the effect of acupotomy on the expressions of p16 Ink4a and p21 Waf1/Cip1 in knee osteoarthritis (KOA) rabbits，so as to analyze whether acupotomy can treat KOA by inhibiting the cellular senescence of chondrocytes., Methods: Twenty-four New Zealand male rabbits were randomly divided into normal, model, acupotomy and electroacupuncture (EA) groups, with 6 rabbits in each group. The KOA model was established by left hindlimb straightening fixation. After modeling, rabbits in the acupotomy group were treated with acupotomy loosening therapy on high stress points around the affected knee joints such as tendons attachment points of vastus medialis, vastus lateralis, rectus femoris, biceps femoris and pes anserine bursa, once a week for 3 weeks. In the EA group, "Xuehai"(SP10), "Liangqiu" (ST34),"Neixiyan" (EX-LE4) and "Waixiyan" (ST35) on the affected hindlimb were selected for EA treatment (3 mA, 2 Hz/100 Hz), 20 min each time, once every other day for 3 weeks. Before and after treatments, the knee Lequesne MG score and passive range of motion (PROM) of the affected knee joint were evaluated. After the treatments, the expressions of p16 Ink4a and p21 Waf1/Cip1 in the cartilage tissue of the affected knee joint were detected by immunohistochemistry and Western blot respectively., Results: Before and after treatment, compared with the normal group, the Lequesne MG score was significantly increased ( P <0.01), the PROM was significantly decreased ( P <0.01) in the model group. After treatment, compared with the normal group, the positive expression and protein expression levels of p16 Ink4a and p21 Waf1/Cip1 were significantly increased ( P <0.01) in the model group; compared with the model group, the Lequesne MG score was significantly decreased ( P <0.01), the PROM was significantly increased ( P <0.01), the positive expression and protein expression levels of p16 Ink4a and p21 Waf1/Cip1 were significantly decreased ( P <0.01， P <0.05) in the acupo-tomy and EA groups; compared with the EA group, the Lequesne MG score was decreased ( P <0.05), the PROM was increased ( P <0.05), the positive expression and protein expression levels of p16 Ink4a and p21 Waf1/Cip1 were decreased ( P <0.05， P <0.01) in the acupotomy group., Conclusion: Acupotomy intervention can down-regulate the expressions of cellular senescence markers p16 Ink4a and p21 Waf1/Cip1 in chondrocytes, indicating that acupotomy therapy may alleviate cartilage degeneration by inhibiting chondrocyte premature cellular senescence to treat KOA.

Vinyl cyclopropanes (VCPs) are among the most useful three-carbon building blocks in organic synthesis. They are commonly used as dienophiles in a range of cycloaddition reactions. However, VCP rearrangement has not received much attention since its discovery in 1959. In particular, the enantioselective rearrangement of VCP is synthetically challenging. Herein, we report the first palladium-catalyzed regio- and enantioselective rearrangement of VCPs (dienyl or trienyl cyclopropanes) for the construction of functionalized cyclopentene units in high yields and with excellent enantioselectivities and 100% atom economy. The utility of the current protocol was highlighted by a gram-scale experiment. Moreover, the methodology provides a platform for accessing synthetically useful molecules containing cyclopentanes or cyclopentenes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The development and application of botanical insecticides is important for the sustainable development of green agriculture. The abuse of chemical pesticides has caused serious problems of environment and human health. Botanical insecticides have become an environment-friendly insecticides due to their nature, low toxicity, easy degradation and other advantages, which are an important field of insecticide development in the future. Although botanical insecticides have lots of advantages, there are still problems needed to be resolved, such as insecticidal plant species, impact assessment of botanical pesticide and separation and purification of active components. To excavate the resources of highly effective insecticidal plants and understand the mechanism of botanical insecticides, here we reviewed the progress of resources and active components of botanical insecticides, the mechanisms of action of botanical insecticides, the main active components and insecticidal properties of Zingiber officinale . Finally, we analyzed the difficulties faced in the research and development of botanical insecticides, prospected future directions, and discussed the active components of ginger. This review would provide reference for the deve-lopment of new botanical insecticides.

Diarylamines and related scaffolds are ubiquitous atropisomeric chemotypes in biologically active natural products. However, the catalytic asymmetric synthesis of these axially chiral compounds remains largely unexplored. Herein, we report that a BINOL-derived chiral phosphoric acid (CPA) successfully catalyzed the atroposelective coupling of quinone esters and anilines through direct C-N bond formation to afford N-aryl quinone atropisomers with an unprecedented intramolecular N-H-O hydrogen bond within a six-membered ring in good yields and enantioselectivities with the quinone ester as both the electrophile and the oxidant. A gram-scale experiment demonstrated the utility of this synthetic protocol. Moreover, this methodology provides a platform for the synthesis of structurally diverse secondary amine atropisomers by nucleophilic addition., (© 2022 Wiley-VCH GmbH.)

N-C Biaryl atropisomers are prevalent in natural products and bioactive drug molecules. However, the enantioselective synthesis of such molecules has not developed significantly. Particularly, the enantioselective synthesis of N-C biaryl atropisomers by stereoselective metal-catalyzed aryl amination remains unprecedented. Herein, a Pd-catalyzed cross-coupling strategy is presented for the synthesis of N-C axially chiral biaryl molecules. A broad spectrum of N-C axially chiral compounds was obtained with excellent enantioselectivities (up to 99 % ee) and good yields (up to 98 %). The practicality of this reaction was validated in the synthesis of useful biological molecules., (© 2021 Wiley-VCH GmbH.)

Nitrogen-nitrogen bonds containing motifs are ubiquitous in natural products and bioactive compounds. However, the atropisomerism arising from a restricted rotation around an N-N bond is largely overlooked. Here, we describe a method to access the first enantioselective synthesis of N-N biaryl atropisomers via a Cu-bisoxazoline-catalyzed Friedel-Crafts alkylation reaction. A wide range of axially chiral N-N bisazaheterocycle compounds were efficiently prepared in high yields with excellent enantioselectivities via desymmetrization and kinetic resolution. Heating experiments showed that the axially chiral bisazaheterocycle products have high rotational barriers.

Objective: To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG 2000 and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment., Methods: T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles in vitro was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles in vivo was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model., Results: T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. In vitro and in vivo studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G 2 /M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions., Conclusion: The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

To unify the structures of solute transport and pollutant degradation models and evaluate the wetland performance conveniently, a pollutant degradation model combining first-order kinetics with the hybrid solute transport model (plug flow with dispersion + continuous stirred-tank reactor, PFD + CSTR) was developed. Orthogonal tests revealed significant correlation between the model parameters, and the original models were optimized via linear substitution of parameters. The improved PFD + CSTR solute transport model exhibited a satisfactory fit with the original model, and the average relative errors of the determination coefficient (R 2 ) and correlation coefficient were <5%. The multiple linear regressions between the hydraulic indicators and model parameters were reconstructed and exhibited consistent structures between different stages. The degradation constant k aTN between the original and improved models exhibited high consistency (R 2  = 0.982). Conclusively, the improved models exhibited good consistency with the original models and allowed rapid and accurate performance evaluation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF- κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Tong Wang et al.)

In this study, the pressure drop obtained from physical experiments and theoretical approaches of a single horizontal wellbore is reviewed and a comprehensive wellbore pressure-drop model is derived for a multibranch well. We propose a new coupling model for fluid flow in multibranch wells and reservoirs. Based on this coupling model, we introduce a theoretical approach for the calculation of the pressure drop in a multibranch horizontal well with variable mass transfer. To facilitate the understanding of the physical model, the entire coupling model was divided into three parts: (1) the pressure-drop model of the wellbore, (2) the reservoir inflow model, and (3) the coupling model. By incorporating the acceleration, friction, mixing, confluence, and gravity pressure drops, a coupling model with a finite-conductivity multibranch horizontal well was developed. Newton-Raphson iterations and Visual Basic programming were employed to solve the coupling model and to obtain the pressure and the inflow rate of the wellbore. The wellbore pressure-drop model was verified by comparing it with different models for the same case study, which has been previously introduced in a different research work. Furthermore, the forecast and sensitivity analysis were conducted, and then the results are discussed. In the proposed new model, several factors are considered, including the wellbore structure, the wellbore completion method, the wellbore, and the fluids and formation properties. The presented approach can be used as a valuable tool to analyze the influence of the pressure drop on the productivity of complex-structured wells and vice versa, and to quantitatively investigate the various pressure drops in wellbores, including the friction, acceleration, mixing, confluence, and gravity pressure losses., Competing Interests: The authors declare no competing financial interest., (© 2020 The Authors. Published by American Chemical Society.)

In this work, well-ordered platinum (Pt) nanocubes (NCs), with precise control on the size and the spatial arrangement, are synthesized from a microemulsion overgrowth in a block copolymer (BC) nanotemplate. The nanovials on this self-assembled BC template serve as microreactors for the reduction of the HCl/H 2 PtCl 6 precursor and direct the ordered periodic arrangement of the reduced Pt nanoparticles (NPs). As the content of HCl increases from 0% to 25%, the Pt NPs evolve from quasi-spheres to NCs, for which the density functional theory (DFT) computation reveals that the different adsorption energies of Cl and HCl dominate this morphology transition. For their potential application in fuel cells, the electrochemical catalysis of the Pt NCs demonstrates a 2.8-fold mass activity in contrast to the commercial JM 40% catalyst at the same Pt loading in ethanol oxidation reaction (EOR) and a good stability of 2.2% ECSA loss over 10 000 CV cycling.

The aim of this study was to determine the effects of acupotomy on energy crises in rat trigger points (TrPs) by measuring mechanical pain thresholds (MPTs) and levels of acetylcholinesterase (AChE), free sarcoplasmic calcium (Ca 2+ ), adenosine 5'-triphosphate (ATP), adenosine 5'-monophosphate (AMP), substance P (SP), and calcitonin gene-related peptide (CGRP) in rat muscle TrP tissue. Male Sprague Dawley rats ( n  = 32) were randomly divided into four groups: control, TrP, acupotomy, and lidocaine injection. Enzyme-linked immunosorbent assays were used to measure AChE, and free sarcoplasmic Ca 2+ concentrations were determined by fluorescent staining with Fura-2 AM; high-performance liquid chromatography was used to measure ATP and AMP, and SP and CGRP were evaluated by immunohistochemistry. Compared with the control group, free sarcoplasmic Ca 2+ , AMP, SP, and CGRP were higher in the model group, while MPT, AChE, and ATP were lower. Treatment with acupotomy or lidocaine injection reduced free sarcoplasmic Ca 2+ , SP, and CGRP and increased MPTs and AChE levels compared with the model group. However, only acupotomy also led to decreased AMP and increased ATP levels relative to the model group. We conclude that acupotomy can alleviate energy crises at TrPs., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Yi Zhang et al.)

Background: Esophageal squamous cell carcinoma (ESCC) is one of the main causes of human death. It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage. Therefore, patients have already lost the best surgical timing when diagnosed. Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically, but the efficacy and prognosis of patients from them are still unsatisfactory. Therefore, it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients., Aim: To explore the clinical value of plasma miR-21 and miR-93 in ESCC., Methods: A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy, and other 45 healthy people during the same period were enrolled as a control group. The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction, and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed. The receiver operating characteristic (ROC) curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients, the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients, and the Cox regression analysis to identify the prognostic factors for ESCC patients., Results: The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group ( P < 0.01). The area under the ROC curve (AUC) of plasma miR-21 for diagnosing T stage, N stage, M stage, and pathological differentiation of ESCC was 0.819, 0.758, 0.824, and 0.725, respectively, and that of plasma miR-93 for diagnosing T stage, N stage, and M stage of ESCC was 0.827, 0.815, and 0.814, respectively. The AUC of combined plasma miR-21 and miR-93 for predicting radiotherapy and chemotherapy efficacy before radiotherapy and chemotherapy was 0.894, and the AUCs of them for predicting the 3-year overall survival (OS) were 0.861 and 0.807, respectively. T stage ( P < 0.05), M stage ( P < 0.05), miR-21( P < 0.01), and miR-93 ( P < 0.05) were independent risk factors for radiotherapy and chemotherapy efficacy, and T stage ( P < 0.01), N stage ( P < 0.05), M stage ( P < 0.01), miR-21 ( P < 0.01), and miR-93 ( P < 0.01) were independent prognostic factors for ESCC patients., Conclusion: MiR-21 and miR-93 can be adopted as effective biomarkers for predicting radiotherapy and chemotherapy efficacy in ESCC and the 3-year OS of ESCC patients., Competing Interests: Conflict-of-interest statement: There was no competing interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD., (© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.)

In order to study the hydrochemistry characteristics and material sources of groundwater in the Buckwheat basin, we collected 32 groundwater samples in the study area in July 2017. The chemical characteristics of groundwater were analyzed by cluster analysis, factor analysis, and path model analysis. Meanwhile, we qualitatively and quantitatively assessed the sources of groundwater hydrochemistry in the Buckwheat basin. The results showed that the groundwater in the study area was weakly alkaline, and the major ions such as Ca 2+ , Mg 2+ , SO 4 2- , HCO 3 - , and NO 3 - had high spatial variability. According to the clustering analysis, the groundwater in the study area can be divided into two categories, namely, class A and class B, and these have the following two subsets:A 1 , A 2 , B 1 , and B 2 . From A to B, the chemical types of groundwater become more complex. The hydrochemistry types of class A were all of the HCO 3 -Ca type, while those of class B 1 were HCO 3 -Ca, HCO 3 -Na·Ca, and HCO 3 -Na·Ca·Mg, and those of class B 2 were HCO 3 -Ca, HCO 3 -Ca·Mg, HCO 3 -Na·Ca. In order to further explore the influence factors of groundwater hydrochemistry, we determined that carbonate rocks, human activities, evaporite rocks, and silicate rocks were the main material sources of groundwater through factor analysis and path model analysis. Among all of the above factors, the dissolution of magnesium sulfate evaporite and the actions of human activities were found to be important reasons for the formation of carbonate rocks, which served as the main sources of groundwater chemical components and diverse hydrochemistry characteristics.

Objective: To observe the effects of acupotomy intervention on the behavior, morphology and tensile mechanics of knee osteoarthritis (KOA) rabbits, and to explore the biomechanical effects of acupotomy on KOA., Methods: Twenty-four New Zealand male rabbits were randomly divided into four groups: normal group, model group, electroacupuncture group and needle-knife group, with 6 rabbits in each group. In each model group, rabbit KOA model was established by fixing Videman's left hind limb in straight position for 6 weeks. In the electroacupuncture group, rats were treated left on Liang Qiu, Xue Hai, Nei Xi Yan and Wai Xi Yan 3 times a week for 3 weeks. In the acupotomology group, the left quadriceps femoris tendon was released with acupotomology, and the treatment was once a week for 3 weeks. Behavioral tests were performed using Lequesne MG knee joint evaluation method one week after the end of modeling and one week after the end of treatment, and HE staining and mechanical tests were performed one week after the end of treatment., Results: Behavioral observation before treatment showed that there were significant differences in local pain, gait response, joint activity and joint swelling between the normal group and the model group( P <0.05), while there was no significant difference among the model group, electro-acupuncture group and needle-knife group( P >0.05). After treatment, the results showed that there were significant differences in local pain, gait response, joint activity and joint swelling among model group, electro-acupuncture group and needle-knife group compared with normal group( P <0.05); In local pain, the electro-acupuncture group was lower than the model group, and there was no significant difference( P >0.05); there was significant difference between needle knife group and model group( P <0.05); there was no significant difference between electro-acupuncture group and needle-knife group( P >0.05). In gait change, there was significant difference between model group and electro-acupuncture group( P <0.05); there was no significant difference between needle-knife group and model group( P >0.05). In joint activity, there was significant difference between electro-acupuncture group and model group( P <0.05). In joint swelling, compared with model group, there was significant difference on electro-acupuncture group and electro-knife group( P <0.01), but there was no significant difference between the electro-acupuncture group and the needle-knife group( P >0.05). Mechanics: Compared with the blank group, the ultimate load of the model group decreased significantly( P <0.01), the ultimate load of the electro-acupuncture group decreased( P >0.05), and the ultimate load of the needle-knife group increased( P >0.05). Compared with the model group, the ultimate load of the electro-acupuncture group increased significantly( P <0.05), and the ultimate load of the needle-knife group increased significantly ( P <0.01). Compared with the electro-acupuncture group, the ultimate load of the needle-knife group increased( P >0.05). Compared with the blank group, the maximum displacement of the model group decreased significantly( P <0.01), and the maximum displacement of the electro-acupuncture group and the needle-knife group decreased( P >0.05). Compared with the model group, the maximum displacement of the electro-acupuncture group increased( P >0.05), and the maximum displacement of the needle-knife group increased significantly( P <0.05). Compared with the electro-acupuncture group, the maximum displacement of the needle-knife group increased( P >0.05). There was no significant difference in stiffness among groups( P >0.05)., Conclusions: Acupotomy intervention can significantly change the behavior and morphology, significantly improve the mechanical properties of quadriceps femoris tendon stretch, and exert its biomechanical effects to achieve the purpose of treating KOA., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: We have demonstrated that needle knife (acupotomy) treatment can improve knee osteoarthritis (KOA) in rabbits. The present study was designed to examine its effect on expression of phosphorylated focal adhesion kinase (p-FAK), phosphinositides 3 kinase (p-PI 3 K) and Aggrecan genes and proteins in the knee-joint cartilage tissues of KOA rabbits, so as to explore its partial molecular mechanism underlying improvement of KOA., Methods: Forty-nine New Zealand male rabbits were randomly divided into normal control, model, model +inhibitor, needle knife, needle knife+ inhibitor, electroacupuncture (EA), EA +inhibitor groups ( n =7 in each). The KOA model was established by modified Videman method (left hindlimb extension immobilization and ankle dorsal flexion 60°). Acupotomy relaxing manipulation was applied to the lateral collateral ligament and patellar ligament of the left knee-joint, two times a week for 4 weeks, and EA (2 Hz/100 Hz, 3 mA) was applied to the left "Liangmen" (ST 21), "Xuehai" (SP 10), "Neixiyan " (EX-LE 4) and "Dubi" (ST 35) for 20 min, three times a week, for 4 weeks. About 2 h before every needle-knife or EA treatment or at the corresponding time-point, intra-articular cavity injection of PF-562271(a specific antagonist of FAK, 200 μmol/L, 0.5 mL)was performed in the three inhibitor groups. The expression levels of p-FAK, p-PI 3 K, Aggrecan genes and proteins in the cartilage tissues were measured with quantitative Real-time PCR and Western blot, separately., Results: After modeling, the expression levels of p-FAK and p-PI 3 K genes and proteins were significantly up-regulated ( P <0.05, P <0.01), while those of Aggrecan protein and mRNA considerably down-regulated in the model group in comparison with the normal group ( P <0.01). Following 4 weeks' needle-knife or EA treatment, the expression levels of p-FAK and p-PI 3 K and Aggrecan proteins in both EA and needle-knife groups, and Aggrecan mRNA in the needle knife group were significantly up-regulated ( P <0.05, P <0.01). After administration of p-FAK antagonist, modeling-induced upregulation of expression of p-FAK mRNA and protein and p-PI 3 K protein, as well as modeling-induced down-regulation of Aggrecan mRNA and protein were significantly suppressed in the model+inhibitor group ( P <0.05, P <0.01), and needle knife-induced and EA-induced up-regulation of expression of p-FAK, p-PI 3 K and Aggrecan mRNAs and proteins was notably suppressed respectively in comparison with the needle knife and EA groups ( P <0.05, P <0.01). The effect of needle knife was significantly superior to that of EA in up-regulating p-PI 3 K and Aggrecan mRNAs as well as p-FAK, p-PI 3 K and Aggrecan proteins ( P <0.05, P <0.01)., Conclusion: Needle knife intervention can up-regulate the expression levels of p-FAK, p-PI 3 K and Aggrecan proteins and mRNAs in the cartilage tissue of the knee-joint in KOA rabbits, suggesting an involvement of FAK-PI 3 K signaling in the needle knife-induced improvement of KOA.

Objective: To observe the effect of acupotomy therapy on mRNA expressions of Bcl-2, Bax , Caspase-3 in posterior cervical extensor muscles in cervical spondylosis rabbits, and explore its mechanisms for apoptosis of cervical muscles., Methods: New Zealand rabbits were randomly divided into normal, model, electroacupuncture (EA) and acupotomy groups, 6 in each group. The cervical spondylosis model was established by forced head-bowing for a long term. After model establishment, acupotomy was used at the trapezius muscle starting point and attachment site of sternocleidomastoid muscle, etc., once a week, total 3 times. EA was used at "Tianzhu" (BL 10), "Jingbailao" (EX-HN 15) and "Dazhu" (BL 11) for 3 weeks, 20 min a time, 3 times a week. Bcl-2, Bax, Caspase-3 mRNA expressions in posterior cervical extensor muscles were detected by real-time PCR., Results: There was no significant difference in the expression of Bcl-2 mRNA among all the groups ( P >0.05). Compared with the normal group, Bax mRNA increased in the model group ( P <0.01), and that in the acupotomy group was lower than that in the model group ( P <0.01). The ratio of Bcl-2/Bax mRNA in the model group decreased significantly compared with that in the normal group ( P <0.01); in comparison with the model group, the ratio in the acupotomy group increased ( P <0.01); and that in the acupotomy group was higher than the ratio in the EA group ( P <0.05). The Caspase-3 mRNA expression in the model group increased compared with that in the normal group ( P <0.05), and its expression in the acupotomy group decreased compared with those in the model and EA groups ( P <0.05)., Conclusions: Acupotomy therapy can regulate the mRNA expressions of Bax and Caspase-3, and retard apoptosis in posterior cervical extensor muscles, therefore the strained muscles are relieved, which may be one of its mechanisms for improving cervical spondylosis.

To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats (SHRs), this study used the reinforcing twirling method (1.5-2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method (1.5-2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method (1.5-2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong (LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax mRNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax mRNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR., Competing Interests: Conflicts of interest: None declared.

Objective: By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism., Method: 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model-inhibitors (MP), needle-knife group (D), needle-knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level., Results: Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased ( P < 0.05), while the protein and mRNA expression of Aggrecan reduced ( P < 0.05). Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased ( P < 0.05). Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased ( P < 0.05); after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced ( P < 0.05)., Conclusion: Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.

Using two-step plasmid integration in the presence of 5-fluorouracil (5-FU), we developed a stable and markerless Lactobacillus casei strain for vaccine antigen expression. The upp of L. casei, which encodes uracil phosphoribosyltransferase (UPRTase), was used as a counterselection marker. We employed the Δupp isogenic mutant, which is resistant to 5-FU, as host and a temperature-sensitive suicide plasmid bearing upp expression cassette as counterselectable integration vector. Extrachromosomal expression of UPRTase complemented the mutated chromosomal upp allele and restored sensitivity to 5-FU. The resultant genotype can either be wild type or recombinant. The efficacy of the system was demonstrated by insertion and expression of porcine rotavirus (PRV) VP4. To improve VP4 expression, we analyzed L. casei transcriptional profiles and selected the constitutive highly expressed enolase gene (eno). The VP4 inserted after the eno termination codon were screened in the presence of 5-FU. Using genomic PCR amplification, we confirmed that VP4 was successfully integrated and stably inherited for at least 50 generations. Western blot demonstrated that VP4 was steadily expressed in medium with different carbohydrates. RT-qPCR and ELISA analysis showed that VP4 expression from the chromosomal location was similar to that achieved by a plasmid expression system. Applying the recombinant strain to immunize BALB/c mice via oral administration revealed that the VP4-expressing L. casei could induce both specific local and systemic humoral immune responses in mice. Overall, the improved gene replacement system represents an efficient method for chromosome recombination in L. casei and provides a safe tool for vaccine production.

Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD], -0.54; 95% confidence intervals [CI], -0.77 to -0.30; P < 0.05). The valid duration of Tai Chi practice for osteoarthritis may be more than 5 weeks. And there were some beneficial evidences regarding the effects of Tai Chi on immediate relief of chronic pain from low back pain (SMD, -0.81; 95% CI, -1.11 to -0.52; P < 0.05) and osteoporosis (SMD, -0.83; 95% CI, -1.37 to -0.28; P = 0.003). Therefore, clinicians may consider Tai Chi as a viable complementary and alternative medicine for chronic pain conditions.

Objective: To explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof β-endorphin (β-EP) and enkephalin (ENK) contents., Methods: Totally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group. The TPSTV model was established by inserting a piece of gelatin sponge into the left transverse process of 3rd lumbar vertebrae. Rabbits in the small knife needlegroup were intervened by small knife needle. Those in the EA group were intervened by EA at bilateralWeizhong (BL40). Those in the small knife needle plus EA group were intervened by small knife needleand EA at bilateral Weizhong (BL40). Contents of β-EP and ENK in plasma, muscle, spinal cord, and hypothalamus were determined after sample collection at day 28 after modeling., Results: Compared with the normal control group, contents of β-EP and ENK in plasma and muscle increased significantly, and contents of β-EP and ENK in spinal cord and hypothalamus decreased significantly in the model group (P < 0.05, P < 0.01). Contents of β-EP and ENK approximated normal levels in the three treatment groups after respective treatment. Compared with the model group, the content of β-EP in muscle decreased, and contents of β-EP and ENK in hypothalamus increased in the three treatment groups after respective treatment (P < 0.05). There were no significant difference among the three treatment groups (P > 0.05)., Conclusions: Small knife needle treatment and EA had benign regulation on peripheral and central β-EP and ENK in TPSTV rabbits. Small knife needle treatment showed better effect than that of EA.

This study observed the local tissue homogenates in rabbits with third lumbar vertebral transverse foramen syndrome and explored the mechanism of acupotomylysis in local tissue revascularization. Thirty Japanese white rabbits were randomly divided into the following 5 groups of 6 rabbits each: normal, model, acupotomy, electroacupuncture (EA), and acupotomy-EA groups. All except the normal group were comprised of animal models of third lumbar vertebral transverse foramen syndrome prepared by embedding sponge in the left third lumbar transverse process. The rabbits in the acupotomy and EA groups underwent bilateral acupotomylysis intervention; those in the acupotomy-EA group underwent acupotomylysis and EA interventions. On the 28th day after modeling, the double-antibody ELISA was used to detect b-FGF and CD34 levels in the serum and homogenates of a muscle tissue sample from the left side of the third lumbar transverse process. The b-FGF levels in local muscle homogenates were significantly higher in the modeled rabbits than in the normal rabbits (P < 0.01), and the CD34 levels in the modeled group were significantly lower than in the normal group (P < 0.01). The b-FGF and CD34 levels in the EA, acutopomy, and acutopomy-EA groups were significantly lower than those in the modeled group (P < 0.01); the CD34 levels were significantly higher in the acupotomy-EA group than in the model group (P < 0.05); and the differences among the EA, acupotomy, and acupotomy-EA groups were not significant (P > 0.05). In conclusion, acupotomylysis regulates the levels of b-FGF and CD34 levels in serum and muscle tissue as well as local tissue revascularization.

Objective: To observe the effect of acupotomy (needle-knife) therapy on local pathological changes and cartilage-mechanics related protein expression in rabbits with knee osteoarthritis (KOA) so as to study its mechanisms underlying improving KOA., Methods: Forty New Zealand rabbits were randomly divided into normal control group, model group, acupotomy group, and electroacupuncture (EA) group (n = 10 in each group). The KOA model was established by immobilization of the left knee-joint (modified Videman method) for 6 weeks. After modeling, acupotomy relaxing was applied to the lateral collateral ligament and patellar ligament of the left knee-joint, once a week for 3 times, and EA (2 Hz/100 Hz, 3 mA) was applied to the left "Yanglingquan" (GB 34), "Yinlingquan" (SP 9), "Neixiyan" (EX-LE 4) and "Waixiyan" (ST 35) for 20 min, 3 times a week for three weeks. The expression levels of Integrin β1, type II collagen (Col-II), matrix metalloproteinase (MMP)-3 and Aggrecan proteins of the cartilage tissue of the left femoral medial and external condyles were observed by Western blot. Pathological changes of the knee-joint by X-ray scanning and those of the femoral condyle tissue were evaluated by Mankin's scores under light microscope after H. E. staining., Results: X-ray showed successful modeling, and pathological changes of the articular cartilage belonged to the early and moderate lesion of knee osteoarthritis. The Mankin's score was significantly higher in the model group than in the control group (P < 0.01) , and after the treatment, the Mankin's scores were significantly decreased in the acupotomy. group (P < 0.01), rather than in the EA group (P > 0.05). The results of Western blot showed that after modeling, the expression levels of Integrin β 1, Col-II and Aggrecan proteins of the femoral articular cartilage were considerably decreased (P < 0.01), while that of MMP-3 protein was significantly increased (P < 0.01). Compared with the model group, the decreased expression levels of Integrin β 1, Col-II and Aggrecan proteins in the acupotomy group and Integrin β 1 protein in the EA group were notably up-regulated (P < 0.01 , P < 0.05), and MMP-3 expression in the acupotomy group was significantly down-regulated (P < 0.01). No significant changes were found in the EA group in the expression levels of Col-II , Aggrecan and MMP-3 proteins compared with the model group (P > 0.05)., Conclusion: Acupotomy intervention can relieve KOA-induced injury of the knee-joint in KOA rats, which is associated with its actions in raising expression levels of Integrin β 1, Col-II and Aggrecan proteins and in lowering the expression of MMP-3 proteins in the articular cartilage, probably by adjusting the mechanics-related signal pathway of the articular chondrocytes.

Pond wetlands have been widely used in the treatment of drainage water from paddy fields. However, wetland hydraulic performance and purification effects are affected by many factors, such as water depth, flow rate, aspect ratio and vegetation distribution, and the better understanding of these factors would be helpful to improve the quality of wetland design, operation and management. This paper analyzed the effect of three different water depths (20, 40 and 60 cm) on the hydraulic performance of pond wetland through the dye tracer experiments with Rhodamine WT. The hydraulic indices, i. e., effective volume ratio, nominal serial complete mixing tanks (N), hydraulic efficiency (λ), were selected for analysis through the hydraulic residence time distribution (RTD) curve. The results showed that the effective volume rate rose from 0.421 to 0.844 and the hydraulic efficiency from 0.281 to 0.604 when the water depth declined from 60 cm to 20 cm. This indicated that the wetland hydraulic performance improved as the water depth decreased. In addition, the hydraulic performance of the first half of the wetland was significantly better than that of the second half. The flow regime of the first half approached complete mixing because of the mixing index (N) approaching 1 and its effective volume rate was above 0.9 when the water depth was relatively low (20 and 40 cm). The normalized RTD curves demonstrated a good agreement between moment analysis parameters and hydraulic parameters, and a great consistency between the hydraulic parameters and moment index which was not affected by tail truncation error. The experimental study concluded that a lower water depth was favorable to improve the hydraulic performance of pond wetlands.

Purpose: The purpose of this study was to investigate the associated between serum total bilirubin (STB) levels and long-term outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI)., Methods: A total of 1,273 consecutive patients were enrolled. Patients were grouped according to their baseline STB levels: Group 1 (STB < 3.4 μmol/L), Group 2 (3.4 μmol/L ≤ STB ≤ 10.3 μmol/L), Group 3 (10.3 μmol/L < STB ≤ 17.1 μmol/L), and Group 4 (STB < 17.1 μmol/L) and the rate of major adverse cardiovascular events (MACE) was determined, Results: A total of 1,152 patients were successfully followed up (90.5%) for a mean period of 30 ± 5 months, including 187 patients experiencing a major adverse cardiovascular event (MACE: death from any cause, myocardial infarction, repeat revascularization or readmission). The MACE rate in Groups 3 and 4 was lower than in Groups 1 and 2 (P < 0.01). After adjusted the confounding factors with Cox regression analysis, the MACE rates in Groups 2-4 were still lower than in Group 1 (Group 2, RR=0.293, 95% CI 0.167-0.517, P < 0.01; Group 3, RR=0.142, 95% CI 0.065-0.312, P < 0.01; Group 4, RR=0.134, 95% CI 0.071-0.252, P < 0.01). The cumulative survival rates of Groups 3 and 4 were higher than that of Groups 1and 2 (P < 0.01)., Conclusions: High STB concentration is associated with lower MACE in patients with ACS after PCI.

Objective: To evaluate the effectiveness of manual therapy and traction for lumbar disc herniation and analyze the current status of this kind of randomized clinical trial (RCT)., Methods: Database of CNKI, VIP, WANFANG, PubMed and OVID were searched. Some relevant journals were manually retrieved. A total of 2 874 literatures on manual therapy and traction for lumbar disc herniation were collected, of which 17 articles met the inclusion criteria. The Jadad score scale was used to evaluate the quality,and RevMan5.0 was used for meta-analysis of literatures., Results: The results of the meta-analysis of all trials involved were as followed:the combined effect of the effective rate was RR = 1.10, 95% CI [1.06, 1.14], the combined effect of the cure rate was RR = 1.36, 95% CI [1.21,1.52], the combined effect of the VAS was RR = 1.37, 95% CI [1.28, 1.45], the combined effect of the JOA was RR = 4.75, 95% CI [4.40, 5.09]., Conclusion: The overall quality of the current RCT researches about manual therapy for lumbar disc herniation was lower,and did not support the conclusion that manual therapy was more effective than traction for lumbar disc herniation.

Objective: To observe the effect of acupotomy, electroacupuncture (EA) or round-sharp acupuncture needle intervention on the expression of Bcl-2,Bax and Caspase-3 proteins in the rectus femoris in rabbits with knee ostarthritis (KOA), so as to explore their mechanisms underlying improvement of braking-induced joint damage from the cellular apoptosis., Methods: Forty-five New Zealand rabbits were equally and randomized into control group, model group, acupotomy (AP) group, EA group and round-sharp acupuncture needle (RSAN) group (n = 9 in each group). The knee-joint injury model was established by fixing the left knee joint in extention position with plaster bandage. EA (2 Hz/100 Hz, 3 mA, 20 min each time) was applied to the left "Yanglingquan" (GB 34)- "Yinlingquan" (SP 9) and left "Neixiyan" (EX-LE 4)- "Waixiyan"(ST 35) for rabbits in the EA group. The EA treatment was given once daily, 3 times a week, 3 weeks in total. For rabbits of the AP group, a needle-knife was held to insert into the front edge of the midpoint, the starting point and the stopping point of the left medial collateral ligamen, lateral collateral ligament and the patellar ligament of the knee to make a loosening manipulation for 5 times in a session of treatment, once a week, 3 times altogether. For rabbits of the RSAN group, a round-sharp needle was performed in the same way to the needle-knife including the stimulation point, the manipulation method and treatment sessions. At the end of the experiment, the left rectus femoris was taken out for detecting the expression of Bcl-2, Bax and Caspase-3 proteins with Western blot., Results: In comparison with the control group, the passive range of motion (PROM) level was significantly decreased 4, 8 and 12 weeks after modeling (P < 0.01), and the expression levels of Bax and Caspase-3 proteins in the rectus femoris were considerably upregulated in the model group (P < 0.05), while the ratio of Bcl-2/Bax was notably down-regulated (P < 0.05) in the model group. Compared with the model group, the PROM level at week 12 after modeling in the AP, EA and RSAN groups were significantly increased (P < 0.01); while Bax and Caspase-3 expression levels in both AP and RSAN groups were considerably downregulated (P < 0.05). No significant differences were found among the five groups in Bcl-2 expression levels (P > 0.05), and between the EA and model groups in Bax and Caspase-3 expression levels and the ratio of Bcl-2/Bax (P > 0.05)., Conclusion: AP, RSAN and EA interventions are effective in improving the knee-joint motion range in KOA rabbits, and this effect of both AP and RSAN is closely associated with their actions in lowering the expression of Bax and Caspase-3 proteins of the rectus femoris and in raising ratio of Bcl-2/Bax protein (reducing muscular cellular apoptosis). The mechanism of EA intervention in improving PROM may be different.

Objective: To observe the effect of acupotomy therapy on cervicomuscular apoptosis and apoptosis regulator Bax protein expression in cervical spondylosis (CS) rabbits so as to investigate its mechanisms underlying improvement of CS., Methods: Twenty-four New Zealand rabbits were randomly divided into normal control, model, acupotomy and electroacupuncture (EA) groups, with 6 rabbits in each group. The CS model was made by forced head-bowing for 5 hours in a restrained chamber, once daily for 12 weeks. Acupotomy was performed at the starting point of trapezius, the mastoid process attaching point of sternocleidomastoid, the cerverical vertebrae joint process or the local induration or cord-like mass (2 or 3 points of them were used as the needle-knife entering points), once a week for 3 weeks. For animals of the EA group, EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Tianzhu" (BL 10), "Jingbailao" (EX-HN 15), "Dazhu" (BL 11) for 20 min, once daily and 3 times a week for 3 weeks. The number of apoptotic cells in the cervical muscle was observed by light microscope after TUNEL staining and muscular Bcl-2 and Bax protein expression was detected by Western blot., Results: In comparison with the control group, the number of cervicomuscular apoptotic cells, and the expression level of cervicomuscular Bax protein were significantly increased, and the Bcl-2/Bax was obviously decreased in the model group (P < 0.01, P < 0.05). Compared to the model group, the number of apoptotic cells and the expression level of muscular Bax protein were notably decreased in the acupotomy group (P < 0.01, P < 0.05), while the ratio of Bcl-2 and Bax was apparently increased in the acupotomy group (P < 0.05). The effects of acupotomy were significantly superior to those of EA in lowering apoptotic cell number and in up-regulating Bcl-2/Bax (P < 0.01, P < 0.05). No significant differences were found between the EA and model groups in the apoptotic cell number and among the four groups in Bcl-2 protein expression levels (P > 0.05)., Conclusion: Acupotomy therapy can reduce cervicomuscular cellular apoptosis and Bax protein expression in CS rabbits, which may be one of its mechanism underlying improving CS.

The aim of this paper was to explore the long-term effects and pain relief mechanism of acupuncture knife on third lumbar vertebrae (L3) transverse process syndrome. Forty SD rats were randomized into control, model, electroacupuncture (EA), and acupuncture knife (AK) group. Except control rats, other rats were subjected to an operation to emulate L3 transverse process syndrome. Fourteen days after the operation, EA and AK rats were given electroacupuncture and acupuncture knife treatments, respectively. Fifty-six days after the operation, enzyme-linked immunosorbent assay was used to measure substance P (SP), 5-hydroxytryptamine (5-HT), interleukin-1β (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) in peripheral blood. The tail flick test was used to observe pain threshold. We found that rats with the simulation operation had significantly higher levels of SP, 5-HT, IL-1, IL-10, TNF-α, and TGF-β, while the AK rats had lower levels. In addition, the pain threshold of AK rats was similar to that of control rats. AK pretreatment could alleviate pain through modulating inflammatory response.

The manipulating methods among the traditional needling manipulation other than lifting-thrusting and twirling are analyzed, their manipulations and curative effect are explored in combination with acupotomy. It is believed that there's a certain kind of prizing manipulation, which plays an important part in elasatolysis, circulation of qi promotion and arrival of qi stimulation. The elastic and flexible characteristic of modern acupuncture needle has made it difficult to play the role of prizing puncture. On the contrary, the high stiffness and inflexible needle like acupotomy and leverage needle can effectively complete the prizing puncture.

Objective: To explore the mechanism of acupotomy lysis in treatment of the third lumbar vertebrae transverse process syndrome., Methods: One hundred and eighty patients were randomly assigned into an acupotomy group and an electroacupuncture (EA) group, 90 cases in each group. The acupotomy group was treated with acupotomy on the tip of the 3rd lumbar vertebrae transverse process (tender point) combination with massage manipulation of hyperflexion and hyperextension on the waist, once a week for 3 weeks. The EA group was treated with EA at bilateral Shenshu (BL 23), Yaoyangguan (GV 3), Ashi point (local tender point) and ipsilateral Weizhong (BL 40), 3 times a week for 3 weeks. The 500 g pressure displacement and the energy absorption ratio were measured by JZL-II soft tissue tension meter and the clinical effect was evaluated by JOA low back pain scale before treatment, after treatment and 6 months after treatment., Results: After treatment and at follow-up visit, the 500 g pressure displacement in the acupotomy group increased significantly (both P < 0.01), but it was decreased significantly in the EA group (P < 0.05, P < 0.01). The energy absorption ratio in the acupotomy group after treatment and at follow-up visit increased significantly (both P < 0.01), and in the EA group, there was no significant difference after treatment as compared with that before treatment (P > 0.05), but it was increased significantly at follow-up visit (P < 0.01). The total therapeutic level distribution in the acupotomy group was better than that in the EA group after treatment and 6 months after treatment (P < 0.05, P < 0.01)., Conclusion: Acupotomy therapy can significantly increase the 500 g pressure displacement and the energy absorption ratio of the local soft tissue around the third lumbar vertebrae transverse process, decrease the local soft tissue tension so as to alleviate pain. The clinical effect of the acupotomy is superior to that of electroacupuncture.

Acupotomology is a technique of percutaneous minimally invasive soft tissue releasing. It can be found in traditional acupuncture, but is deemphasized in modern times. Therefore, the development of acupotomology is held as restoring of ancient ways of acupuncture. Compared with traditional acupuncture, acupotomology makes modern interpretations on the theory of muscle regions, absorbs theories of anatomy and pathology as well as techniques of asepsis and anaesthesia. It improves traditional needling tool. Therefore, it is also held as an innovation of acupuncture. The development of acupotomology makes up for the deficiency of acupuncture study. It. will promote the differentiation and crossing of acupuncture discipline, and become a new trend of acupuncture.

Objective: To study the analgesia mechanism of needle-knife lysis in spinal cord and other parts of central nervous system by comparing the changes of Leu-Enkephalin (L-ENK) content in different parts of centrium of rats undergone needle-knife lysis and electro-acupuncture respectively., Methods: Sixty healthy SD rats were randomly devided into normal control group, model group, needle-knife lysis (NKL) group and electro-acupuncture (EA) group. 4% papain solution mixed with 0.3 mol/L cysteine solutin in the ratio of 1:1, paused for 0.5 h,injected the mixture, 20 microl each time,into the left knee joint cavities of rats in model, NKL, EA groups at the 1st, 4th, 7th day. After 4 weeks in NKL group and EA group were treated with needle-knife lysis and electro-acupuncture, respectively. Three weeks after treatment, samples of spinal cord of the swollen part of rat waists and rat brains were taken from and the content of L-ENK of medulla oblongata, midbrain, pituitary gland, and hippocampus were measured., Results: L-ENK content of model group increased higher than that of normal control group in spinal cord, hippocampus and midbrain (P < 0.01); there were no significant difference between normal control group and modle group on L-ENK in medulla oblongata and thalamus (P > 0.05). After intervening of NKL or EA, L-ENK content of NKL group increased higher in hippocampus than that of model group and EC group (P < 0.05); but L-ENK content of NKL group in midbrain was lower than that of model group (P < 0.05)., Conclusion: Needle-knife lysis has characteristic of regulation for the L-ENK content in different parts of central nervous system of rats with knee osteoarthritis, and analgesic effect of needle-knife was possibly related with regulation of center L-ENK.

Formins have been paid much attention for their potent nucleating activity. However, the connection between the in vivo functions of AtFHs (Arabidopsis thaliana formin homologs) and their effects on actin organization is poorly understood. In this study, we characterized the bundling activity of AtFH8 in vitro and in vivo. Biochemical analysis showed that AtFH8(FH1FH2) could form dimers and bundle preformed actin filaments or induce stellar structures during actin polymerization. Expression of truncated forms of AtFH8 and immunolocalization analysis showed that AtFH8 localized primarily to nuclear envelope in interphase and to the new cell wall after cytokinesis, depending primarily on its N-terminal transmembrane domain. GUS histochemical staining showed AtFH8 was predominantly expressed in Arabidopsis root meristem, vasculature, and outgrowth points of lateral roots. The primary root growth and lateral root initiation of atfh8 could be decreased by latrunculin B (LatB). Analysis of the number of dividing cells in Arabidopsis root tips showed that much fewer dividing cells in Lat B-treated atfh8 plants than wild-type plants, which indicates that AtFH8 was involved in cell division. Actin cytoskeleton in root meristem of atfh8-1 was more sensitive to LatB treatment than that of wild-type. Altogether, our results indicate that AtFH8 is an actin filament nucleator and bundler that functions in cell division and root development.