Search

Optical evanescent sensors can non-invasively detect unlabeled nanoscale objects in real time with unprecedented sensitivity, enabling a variety of advances in fundamental physics and biological applications. However, the intrinsic low-frequency noise therein with an approximately 1/f-shaped spectral density imposes an ultimate detection limit for monitoring many paramount processes, such as antigen-antibody reactions, cell motions and DNA hybridizations. Here, we propose and demonstrate a 1/f-noise-free optical sensor through an up-converted detection system. Experimentally, in a CMOS-compatible heterodyne interferometer, the sampling noise amplitude is suppressed by two orders of magnitude. It pushes the label-free single-nanoparticle detection limit down to the attogram level without exploiting cavity resonances, plasmonic effects, or surface charges on the analytes. Single polystyrene nanobeads and HIV-1 virus-like particles are detected as a proof-of-concept demonstration for airborne biosensing. Based on integrated waveguide arrays, our devices hold great potentials for multiplexed and rapid sensing of diverse viruses or molecules.

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against 60 Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.

Objective: To investigate the effect of acupuncture in different tissue structures on deqi and the electromyography of acupoint area., Methods: Twenty healthy subjects, respectively accepted 4 kinds of needling stimulation, i.e. stimulating skin at Zusanli (ST36), stimulating ST36 with and without skin anesthesia using compound lidocaine cream, and stimulating at Dubi (ST35) without skin anesthesia. Deqi sensation of the acupuncturist and subjects were measured according to MGH Acupuncture Sensation Scale (MASS) during needling, and the myoelectricity around the acupoints was recorded simultaneously. The occurrence rate and intensity of the different deqi sensations, the relationship between the acupuncturist's and subjects' deqi sensations, and the integrated electromyogram (iEMG) were analyzed., Results: Sharp pain and tingling were the main sensations during skin needling at ST36. Fullness, dull pain, soreness and acupuncturist's tightness were the main sensations during needling with or without skin anesthesia at ST36. Fullness was the main sensation during needling at ST35, while the intensity was lower than that during needling at ST36. A positive correlation in the intensity was found between subjects' fullness and acupuncturist's tightness during needling with or without skin anesthesia at ST36. The subjects' fullness appeared earlier about 5 seconds than acupuncturist's tightness. The iEMGs during subjects' fullness and acupuncturist's tightness were 2-3 times of that before needling., Conclusion: Deqi sensations such as subjects' fullness, dull pain, soreness and acupuncturist's tightness are mainly related to the activity of the muscles under the acupoints. Subjects' fullness and acupuncturist's tightness always appear together. Acupuncturist's tightness may be mediated by the muscle stretch reflex induced by needling stimulation.

In this commentary, we will provide a high-level introduction into LC-MS product characterization methodologies deployed throughout biopharmaceutical development. The ICH guidelines for early and late phase filings is broad so that it is applicable to diverse biotherapeutic products in the clinic and industry pipelines. This commentary is meant to address areas of protein primary sequence confirmation and sequence variant analysis where ambiguity exists in industry on the specific scope of work that is needed to fulfill the general guidance that is given in sections Q5b and Q6b. This commentary highlights the discussion and outcomes of two recent workshops centering on the application of LC-MS to primary structure confirmation and sequence variant analysis (SVA) that were held at the 2018 and 2019 CASSS Practical Applications of Mass Spectrometry in the Biotechnology Industry Symposia in San Francisco, CA and Chicago, IL, respectively. Recommendations from the conferences fall into two distinct but related areas; 1) consolidation of opinions amongst industry stakeholders on the specific definitions of peptide mapping and peptide sequencing for primary structure confirmation and the technologies used for both, as they relate to regulatory expectations and submissions and 2) development of fit-for-purpose strategy to define appropriate assay controls in SVA experiments., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations., Methods: Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed., Result: Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01)., Conclusions: The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

Scanning electron microscopy (SEM) was used to analyze and study micron-nanometer evaporite samples collected from Paleocene and Eocene drill cores in the Jiangling Depression. Accordingly, seven beds of potassium-bearing solid rocks were accurately identified. Sylvite, carnallite, syngenite, dolomite, thenardite, anhydrite, glauberite, halite, barite, celestite, and other solid salt minerals were found, and carnallite, syngenite, and thenardite were found for the first time in the Jiangling Depression. Sylvite, syngenite, and carnallite indicate that the Paleogene salt lakes in the Jiangling Depression had evolved to the sylvite stage and that prospecting for solid sylvite would be satisfactory. Micron-nanometer celestite is contained in the evaporites, from which we can infer that strontium may have been provided by deep formation water (or oil-field water). This finding is of great significance to studying the genesis of sylvite sediment in the Jiangling Depression. From the extensive development of primary glauberite beds typical of warm salt minerals in the Shashi Formation, it can be inferred that the late Paleogene paleoclimate in the Jiangling Depression of the Jianghan Basin was dry and hot. Based on the extensive distribution of micron-nanometer pyrite, siderite, iron and Fe₂O₃/FeO ratios in evaporite sediments and color analysis of mudstones, the evaporites in the study area formed in an underwater anoxic, reducing environment during sedimentation. Therefore, the evaporite sediments in the Paleocene-Eocene interval of the Jiangling Depression are proposed to have formed in a saltwater lake sedimentary environment, and the ancient lake was characterized by a deep-water salt lake sedimentary model.

In recent years, a new technique of elastic quantization imaging, the ultrasound-based shear wave elastography (SWE) is arising, which has advantages of real-time, non-invasion, rapid imaging and strong repeatability, and quantifying the elastic properties of soft tissues including thyroid gland, breast, prostate, muscle tendon, ligament, etc.. It has been gradually applied to clinical and experimental researches of acupuncture and has an extensive application prospect. The present paper briefly introduces the application of SWE in accurately locating the acupoint, Deqi from needled acupoints, acupuncture manipulations, and evaluation of efficacy of acupuncture in the treatment of musculofascial diseases.

Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE -/- mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. In vitro studies have shown that AB23A can increase cholesterol outflow in Caco-2 cells exposed to high fat concentrations and increase the expression of ATP-binding cassette transfer proteins G5/G8 (ABCG5/G8), the liver X receptor α (LXRα). Furthermore, inhibition of LXRα can significantly eliminate the active effect of AB23A on decreasing intracellular lipid accumulation. We also confirmed that AB23A has a negative effect on Acyl-CoA cholesterol acyltransferase 2 (ACAT2) in Caco-2 cells cultured in the high concentrations of fat, and we found that AB23A further reduces ACAT2 expression in cells treated with the ACAT2 inhibitor pyripyropene or transfected with ACAT2 siRNA. In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXRα-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect.

Chronic hypertension evoked aberrant myocardial remodeling is the main reason for progressive death from heart failure. It is of great clinical significance to find effective prevention and treatment methods to block this pathological process. It has been shown that imbalance of the autonomic nervous system (ANS) induced by chronic hypertension, i.e., hyper-excitation of sympathetic nerve system and suppression of parasympathetic (vagal) nerve system, activates immune cells-mediated inflammatory responses, and exacerbates the pathological remodeling of cardiac tissue. Except the negative inotropic outcomes, excitation of vagal nerves also has an anti-inflammatory effect which is mediated by activating the cholinergic anti-inflammatory pathway (CAIP). Previous studies showed that electroacupuncture (EA) could exert anti-hypertensive and systematic anti-inflammatory effects by increasing vagal activity. In addition, preliminary study from our lab demonstrated that EA was able to alleviate the pathological progress from hypertension to cardiac hypertrophy. However, the potential role of CAIP in restoring hypertension induced aberrant myocardial remodeling is still unknown. Herein, based on the alteration of ANS function in hypertension and EA's impact on vagal activity, we propose novel research ideas that EA could attenuate the pathological process of hypertension induced abnormal myocardial remodeling via activating CAIP.

Long-term hypertension can lead to both structural and functional impairments of the myocardium. Reversing left ventricular (LV) myocardial fibrosis has been considered as a key goal for curing chronic hypertension and has been a hot field of research in recent years. The aim of the present work is to investigate the effect of electroacupuncture (EA) at PC6 on hypertension-induced myocardial fibrosis in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA groups with WKY rats as a normal control. EA was applied once a day for 8 consecutive weeks. The cardiac fibrosis as well as the underlying mechanisms were investigated. After 8 weeks of EA treatment at PC6, the enhanced myocardial fibrosis in SHRs was characterized by an increased ratio of left ventricular mass index (LVMI), collagen volume fraction (CVF), and elevated content of hydroxyproline (Hyp) as well as the upregulated expression of collagen I and collagen III in myocardium tissue of SHRs. All these abnormal alterations in the SHR + EA group were significantly lower compared to the model group. In addition, EA at PC6 significantly improved the pathological changes of myocardial morphology. Meanwhile, the increased levels of angiotensin II (Ang II) and tumor necrosis factor-α (TNFα) and expression of transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, and MMP-9 in the serum or heart tissue of SHRs were also markedly diminished by EA. These results suggest that EA at bilateral PC6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by the regulation of the Ang II - TGF-β 1 pathway., (Copyright © 2020 Xin, Dai, Lu, Zhao, Liu, Cui, Xu, Bai, Jing, Gao and Yu.)

The effect of acupuncture-moxibustion on respiratory system and systemic immune inflammatory response were reviewed to explore the possible role of neuroimmunomodulation in the control of inflammatory response and the effect mechanism of cholinergic anti-inflammatory pathway on coronavirus disease 2019 (COVID-19). Acupuncture-moxibustion could produce the local and systemic anti-inflammatory effect on COVID-19 through the activation of cholinergic anti-inflammatory pathway. Compared with humoral anti-inflammatory pathway, the neuronal anti-inflammatory pathway has earlier initiation, rapider action, and more localization, which play a more important role in the initial stage of inflammatory response. This may be an important basis for acupuncture-moxibustion intervention in the early stage of COVID-19. In addition to cholinergic anti-inflammatory pathway, acupuncture-moxibustion may also play an anti-inflammatory role in activating sympathetic nerve, hypothalamic-pituitary-adrenal axis and other neural anti-inflammatory pathways. How acupuncture-moxibustion play its role in stimulating the vagus nerve and sympathetic nerve in different periods of inflammatory response, and whether the effect is based on the selection of acupoints and the methods of stimulation, will be the research direction of the transformation from basic research to clinical research for acupuncture-moxibustion.

Osteosarcoma is the most common primary malignant bone tumor, occurring mainly in children and adolescents, and the limbs are the main affected sites. At present, limb-salvage treatment is considered as an effective basic standard treatment for osteosarcoma of the limb. China has a vast territory, but the development of technology is not balanced,which requires sufficient theoretical coverage, strong technical guidance and the application of limb-salvage treatment guidelines to the treatment of osteosarcoma. Therefore, to standardize and promote the development of limb-salvage surgery technology and improve the success rate of limb-salvage treatment, this guide systematically introduces limb-salvage techniques for the treatment of patients with limb osteosarcoma through definition of limb-salvage treatment, surgical methods, efficacy evaluation, postoperative treatment and prevention of complications, rehabilitation guidance, and follow-up advice., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Mild [2 + 2] photodimerization of enone substrates was induced by donor-acceptor fluorophores. Enone substrates were activated efficiently for anti-head to head dimerizations with a high yield (up to 83%) and high selectivity. The adjustable excited state potential also allows donor-acceptor fluorophores to be used for isomerization of the above substrates, confirming the potential of donor-acceptor fluorophores as energy transfer photocatalysts.

Background: Due to the particularity of patients with bone tumors, the risk of periprosthetic infection following megaprosthetic replacement is much higher than that of traditional total knee arthroplasty. Unfortunately, few studies specifically reported the risk factors for periprosthetic infection following megaprosthetic replacement. The purposes of the study were to (1) establish a nomogram model, which can provide a reference for clinicians, and patients to reduce the occurrence of periprosthetic infection (2) explore the risk factors for deep infection of megaprosthesis., Hypothesis: A prediction model can be established and has favorable predictive accuracy., Patients and Methods: One hundred and seventy-seven megaprostheses were identified. There were 61 female patients and 116 male patients with a mean age of 35 years. The following risk factors were analyzed: tumor site, sex, age, material for prosthetic stem, tumor type, smoking, diabetes, length of bone resection, operation time, chemotherapy, BMI, malignant tumor staging and hematoma formation. Finally, based on the multivariate analysis, the independent risk factors were used to develop a nomogram model., Results: Univariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were risk factors for periprosthetic infection. Multivariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were significant risk factors for periprosthetic infection. The nomogram model was established using these significant risk factors, with a C-index of 0.766 and an acceptable consistency according to the internal validation, indicating that the prediction model had favorable predictive accuracy., Discussion: This study has important implications for the future investigations of prevention of periprosthetic infection. The nomogram model identifies high-risk patients for whom attached prophylaxis measures are required. Future studies regarding reduction of incidence of periprosthetic infection should pay close attention to these high-risk patients., Level of Evidence: IV, retrospective, cohort study., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

In this study, we investigated the effect of astragaloside IV on skeletal muscle energy metabolism disorder caused by statins and explored the possible mechanisms. High-fat diet-fed apolipoprotein E knockout (ApoE -/- ) mice performed aerobic exercise and were administered simvastatin, simvastatin + trimetazidine, or simvastatin + astragaloside IV by gavage. At the end of treatment, exercise performance was assessed by the hanging grid test, forelimb grip test, and running tolerance test. Moreover, plasma lipid and creatine kinase concentrations were measured. After sacrifice, the gastrocnemius muscle was used to assess muscle morphology, and energy metabolism was evaluated by determining the concentration of lactic acid and the storage capacity of adenosine triphosphate and glycogen. Mitochondrial function was assessed by measuring mitochondrial complex III and citrate synthase activity and membrane potential. In addition, oxidative stress was assessed by determining the level of hydrogen peroxide. Finally, using western blotting and reverse transcription polymerase chain reaction, we explored the mechanism of astragaloside IV in alleviating simvastatin-induced muscle injury. Our results demonstrated that astragaloside IV reversed simvastatin-induced muscle injury without affecting the lipid-lowering effect of simvastatin. Moreover, astragaloside IV promoted the phosphorylation of AMPK and activated PGC-1α, which upregulated the expression of NRF1 to enhance energy metabolism and inhibit skeletal muscle cell apoptosis., (© 2019 John Wiley & Sons, Ltd.)

Objectives: To investigate the contact stress and the contact area o tibial inserts and bushings with respect to different congruency designs in a spherical center axis and rotating bearing hinge knee prosthesis under gait cycle loading conditions using finite element analysis., Methods: Nine prostheses with different congruency (different degrees of tibiofemoral conformity and different distances between the spherical center and the bushing) designs were developed with the same femoral and tibial components. The models were transferred to finite element software. The peak contact stresses and contact areas on tibial inserts and bushings under the gait cycle loading conditions were investigated and compared., Results: For tibial insert, the peak contact stress was the highest in the low conformity-long group (61.4486 MPa), and it was 1.88 times higher than that in the group with the lowest stress (moderate conformity-short group, 32.754 MPa). The contact area was the largest in the low conformity-long group (420.485 mm 2 ), and it was 1.19 times larger than that in the group with the smallest area (moderate conformity-middle group, 352.332 mm 2 ). For bushing, the peak contact stress was the highest in the high conformity-long group (72.8093 MPa), and it was 3.21 times higher than that in the group with the lowest stress (high conformity-short group, 22.6928 MPa). The contact area was the largest in the low conformity-short group (2.41 mm 2 ), and it was 2.27 times larger than that in the group with the smallest area (high conformity-middle group, 1.063 mm 2 )., Conclusion: The results of our study showed that the congruency of the tibiofemoral surface and bushing surface should be considered carefully in the design of the spherical center axis and rotating bearing hinge knee prosthesis. Different levels of contact performance were observed with different congruency designs. In addition, the influence of contact stress and contact area on the polyethylene wear of rotating hinge knee prostheses should be confirmed with additional laboratory tests., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Sterilization and clarification are essential to produce wine of high quality and stability, microfiltration is a serious candidate for both purposes. In this work, microfiltration of fermented mulberry wine was evaluated for the first time. Four different commercial membranes, of two different materials (PES, PVDF) and two different nominal pore sizes (0.22 μm and 0.45 μm) were employed. Pore blocking model was used to identify the fouling mechanism, foulant constituents were revealed by FT-IR spectra. The effect of microfiltration on permeate quality of mulberry wine was also involved. The results indicated that cake formation was the dominant mechanism during steady-state of mulberry wine microfiltration, independently on the membrane property. The fouling layer was mainly composed of protein and polysaccharides, which induced basically reversible overall filtration resistance. Microfiltration delivered a superior clarity, highly polydisperse and light-color mulberry wine with a satisfactory sterilization stability. It preserved the main basic properties and organic acid contents of mulberry wine while resulted in certain loss of volatile compounds, especially esters and alcohols. This work has provided a scientific reference for producing mulberry wine, a modern functional beverage., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To collect literatures on the application of neural tracing technique in experimental acupuncture research, and summarize its application status in acupoints, meridians and Zang-fu organs., Methods: We collected papers published from databases of CNKI (1979-2017), Wan-Fang (1990-2017), VIP (1989-2017) and PubMed(1997-2017)by using keywords of "neural tracing technique" "neuroanatomic tracing" "neural tracers" and "acupuncture" "electroacupuncture" "auricular acupuncture" "eye acupuncture" "meridians" "acupuncture points" "acupoint injection", and made a summary about the current state of application of neural tracing technique in the fields of acupoint, meridian and Zang-fu organs (viscera)., Results: A total of 94 articles were collected, the most commonly used neural tracers were horseradish peroxidase and cholera toxin subunit B. The experimental animals used were rat, rabbit, cat, monkey, etc., and injection site was acupoint. After the injection of neural tracers, the survival time of animals was range from 1 day to 12 weeks, and the labelled tissues included neurons and nerve fibers of the sensory, motor, and autonomic systems. The outcomes of neural labeling mainly revealed the segmental pattern, neuroanatomical connection (neural pathways/circuits) and chemical features (shown by immunohistochemical staining) of neurons and nerve fibers innervating both the acupoints and visceral organs, suggesting their involvement in the effect of acupuncture and moxibustion treatment., Conclusion: This application of neural tracing technology help us understand the under-lying mechanisms of acupuncture and moxibustion interventions from different perspectives of neural pathways/circuits and related chemical properties, which also lays a greater role for this technology in future experimental acupuncture research.

Objective: To investigate the roles played by A2b receptor and the key Ca 2+ signaling components in the mediation of the cardioprotection of electroacupuncture pretreatment in the rats subjected to myocardial ischemia and reperfusion., Methods: SD rats were randomly divided into a normal control (NC) group, ischemia/reperfusion model (M) group, electroacupuncture pretreatment (EA) group, and electroacupuncture pretreatment plus A2b antagonist (EAG) group. The ischemia/reperfusion model was made by ligation and loosening of the left descending branch of the coronary artery in all groups except the NC group. The EA group was pretreated with electroacupuncture at the Neiguan (PC6) point once a day for three consecutive days before the modeling. The elevation of the ST segment, arrhythmia scores, and myocardial infarction size of each group was measured. The relative expression levels of A2b, RyR2, SERCA2a, NCX1, P-PLB(S16)/PLB, and Troponin C/Troponin I proteins in the injured myocardium were detected by multiple fluorescence western blot., Results: The level of ST segment, arrhythmia scores, and infarct size in the M group was significantly higher/larger than that in the NC group after ischemia and reperfusion, while all the three indices mentioned above in the EA group were significantly lower/smaller than those in the M group after reperfusion. The expression of the proteins of adenosine receptor 2b(A2b), ryanodine receptor 2(RyR2), and sarco(endo)plasmic reticulum Ca 2+ -ATPase 2a (SERCA2a) in the EA group was significantly enhanced as compared with the M group, while in the EAG group, the contents of A2b were significantly lower than those in the EA group, and RyR2 was higher in the EAG group. In comparison with the NC group, the relative expression of NCX1 protein in M, EA, and EAG groups was not changed significantly. The ratio of phosphorylated phospholamban (P-PLB) over phospholamban (PLB) in the M group was significantly lower than that in the NC group, and the ratio in the EA group was significantly increased as compared with the M group, while the ratio of Troponin C/Troponin I in the EA group was significantly decreased in comparison with that in other groups., Conclusion: Electroacupuncture pretreatment could reduce ischemia and reperfusion-induced myocardial injury via possibly increasing the A2b content and regulating the key Ca 2+ signaling components, namely inhibiting RyR2 and enhancing P-PLB(S16)/PLB ratio and SERCA2a proteins, so as to diminish the intracellular Ca 2+ overload and consequently lessen the myocardial injury., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Qiu-Fu Dai et al.)

Our previous work indicates the lymphatic network and perivascular spaces or tissues might be involved in the facial intradermal brain-targeted delivery of Evans blue (EB). In this article, we presented the detailed involvement of both, and the linkage between lymphatic network and perivascular spaces or tissues. The in-vivo imaging, the trigeminal transection and immunohistochemistry were used. In-vivo imaging indicated intradermal injection in the mystacial pad (i.d.) delivered EB into the brain at 2-, 6- and 24 h, while intranasal injection (i.n.) delivered EB into the rostral head and intravenous injection (i.v.) diffused EB weakly into the brain. Trigeminal perineurial and epineurial EB occurred along the perivascular spaces or tissues and along brain vessels. EB diffused into the lymphatic vessels and submandibular lymph nodes. Moreover, perineurial and epineurial EB co-located or overlaid with Lyve1 immuno-reactivity and VEGF antibody, and lymphatic network connected with perivascular spaces or tissues, suggesting lymphatic system-perivascular spaces might involve in the EB delivery with i.d. The trigeminal transection reduced the trigeminal epineurial and perineurial EB and brain EB along vessels. EB diffused in the fasciculus and the perineurium, blood and lymphatic vessels in the mystacial pad, mystacial EB overlaid VEGF or Lyve1 antibody. In summary, the dermal-trigeminal-brain perivascular spaces or tissues and the linkage to the lymphatic network mediated the intradermal brain-targeted delivery.

Objectives: To evaluate treatments and prognostic factors for the myxoid liposarcoma in extremities., Methods: We retrospectively reviewed 34 patients histologically diagnosed with myxoid liposarcoma arising in the extremities, treated in our hospital from 2010 to 2017. We recorded tumor locations, max diameter, operations, complications, radiation, chemotherapy, survival, recrudescence, and metastases. Overall survival, treatments, and prognostic factors were subsequently analyzed., Results: The mean age of 34 patients with myxoid liposarcoma in extremities was 49.1 years, and the mean follow-up period was 65.1 months. The median survival time was 190 months. Five of 14 patients accepted recrudescence resection and two patients of 20 patients who underwent primary tumor resection or unplanned operation died of tumor progression. Although no statistical difference was found (X 2 = 3.331, P = 0.068), the lower mortality was confirmed in the patients who accepted primary tumor resection or unplanned operation. Eleven patients with a tumor diameter of 8.6 ± 4.7 cm accepted wide resection, while 23 patients with 17.2 ± 8.8 cm tumors accepted marginal resection. Statistical difference was found between the size of tumors with relatively wide resection and those with relatively marginal resection (F = 9.130, P = 0.005). No recurrence or metastasis occurred in patients who accepted wide resection, while 14 patients presented with local recurrence and 8 patients developed distant metastases among the 23 patients with marginal resection. Seven patients died of metastases, while one patient lived with metastases. No significant difference in survival was found between different surgical methods (X 2 = 0.9460, P = 0.3307). The average diameter of eight patients with distant metastases was 21.7 cm, which was considerable larger than the 12.1 cm of patients without metastasis. This difference was proven significant upon the statistical analysis (F = 9.412, P = 0.004)., Conclusions: Wide resection achieved good local control but was not unambiguously superior in long-term survival. Myxoid liposarcoma tumors with larger diameters were more difficult to be submitted to wide resection and were more likely to present with distant metastasis., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To observe the process of sacroiliac joint invasion by primary malignant tumors of sacrum and iliac bone, and to explore the methods of surgical resection and reconstruction., Methods: From January 2009 to November 2017, there were nine patients with primary malignant bone tumors involving sacroiliac joints, five males and four females, aged from 16 to 63 years, with an average age of 35 years. Of these there were three cases of primitive neuroectodermal tumors, three cases of chondrosarcoma, and three cases of osteosarcoma. Pelvic ring reconstruction was performed with longitudinal half sacrum, sacroiliac joint and partial iliac bone block excision and screw-rod system combined with bone grafting., Results: The operation time was 155-310 min, with an average of 245 ± 55 min, and the bleeding volume was 1400-8500 ml, with an average of 3111 ± 2189 ml. Follow-up ranged from 5 to 108 months, with a median follow-up of 24 months. Three patients (33.3%) had local recurrence, three patients (33.3%) survived without tumors, and one patient had lung metastasis 2 years after operation, and survived with tumors. Five patients (55.6%) died, of which four died of lung metastasis and one died of brain metastasis. Survival analysis showed that the 3-year overall survival rate was 57%. Bone grafts did not heal in four patients, and bone grafts healed in five patients. The healing time ranged from 5 to 7 months, with an average of 6.2 months., Complications: one patient developed deep infection 2 months after operation; one patient had skin edge necrosis; titanium rod loosening and displacement were found in two patients with nonunion of bone graft, and no fracture of nail rod was found. The MSTS 93 functional score of nine patients ranged from 20% to 50%, with an average of 34%., Conclusion: The tumors around the sacroiliac joint often invade the contralateral bone by ligament, and the en bloc resection and pelvic ring reconstruction for primary malignant bone tumors involving sacroiliac joint was feasible., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Aseptic loosening has become the main cause of prosthetic failure in medium- to long-term follow-up. The objective of this study was to establish and validate a nomogram model for aseptic loosening after tumor prosthetic replacement around knee., Methods: We collected data on patients who underwent tumor prosthetic replacements. The following risk factors were analyzed: tumor site, stem length, resection length, prosthetic motion mode, sex, age, extra-cortical grafting, custom or modular, stem diameter, stem material, tumor type, activity intensity, and BMI. We used univariate and multivariate Cox regression for analysis. Finally, the significant risk factors were used to establish the nomogram model., Results: The stem length, resection length, tumor site, and prosthetic motion mode showed a tendency to be related to aseptic loosening, according to the univariate analysis. Multivariate analysis showed that the tumor site, stem length, and prosthetic motion mode were independent risk factors. The internal validation indicated that the nomogram model had acceptable predictive accuracy., Conclusions: A nomogram model was developed for predicting the prosthetic survival rate without aseptic loosening. Patients with distal femoral tumors and those who are applied with fixed hinge and short-stem prostheses are more likely to be exposed to aseptic loosening.

Background: The incidence of giant cell tumors in the proximal humerus is low. We evaluated 2 surgical treatments for giant cell tumors of the proximal humerus and postoperative upper-extremity function., Methods: This study retrospectively analyzed the clinical data of 27 cases of giant cell tumors of the proximal humerus at 4 Chinese medical centers specializing in bone oncology collected between January 2002 and June 2015. All patients were followed up for more than 2 years. The surgical procedures performed for treatment included curettage in 14 patients and segmental resection in 13. The Campanacci grade, occurrence of pathologic fracture, surgical method, complications, and Musculoskeletal Tumor Society score were recorded for each cohort., Results: The recurrence rate was 7.1% in the curettage group and 15.4% in the segmental resection group. Other postoperative complications occurred in 4 patients with segmental resection, including resorption of the osteoarticular allograft in 2, subluxation of the glenohumeral joint in 1, and prosthetic loosening and exposure in 1. A significant difference in postoperative upper-extremity function was noted between the 2 groups (P < .001)., Conclusions: Postoperative upper-extremity function in the curettage group was significantly better than that in the segmental resection group. Segmental resection and reconstruction with a large segmental osteoarticular allograft were considered unadvisable. We suggest that extensive curettage should be selected to treat proximal humerus giant cell tumors as much as possible., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the expression of serotonin (5-HT) in local tissue of different acupoint regions at the hind limbs of rats., Methods: A total of 6 male SD rats were used in the present study. The local tissues of "Neiting"(ST44), "Zusanli"(ST36) and "Futu"(ST32) at the hindlimbs were dissected after transcardiac perfusion with fixative solution containing 4% paraformaldehyde, phosphate buffer, etc., fixed again in 4% paraformaldehyde and cut into sections (at 20 µm thick). Then, the tissue sections were subjective into immunofluorescence stain for displaying 5-HT positive cells and calcitonin gene-related peptide (CGRP) -positive fibers, vessel-like structure (labelled with phalloidin) and cellular nucleus (labelled with DAPI), separately. After that, the tissue samples were observed and recorded using a laser confocal microscope., Results: The 5-HT labeled cells presented flat or round form in the local tissues of the 3 acupoint regions. These cells were mainly located in the dermis and subcutaneous tissue, and concentrated around the vessel-like structure and CGRP-positive nerve fibers. The number of cutaneous 5-HT positive cells was most in ST44 (156.6±12.1), and fewer in ST36 (83.5±18.2)and ST32(53.3±5.2)in turn., Conclusion: 5-HT-positive cell is an important member in local tissue of acupoints (ST44, ST36 and ST32), and varies in number according to their locations, suggesting an involvement of different densities of 5-HT-positive cells in different levels of regulatory effects of acupuncture stimulation of these acupoints.

Slope one is a popular recommendation algorithm due to its simplicity and high efficiency for sparse data. However, it often suffers from under-fitting since the global information of all relevant users/items are considered. In this paper, we propose a new scheme called enhanced slope one recommendation through local information embedding. First, we employ clustering algorithms to obtain the user clusters as well as item clusters to represent local information. Second, we predict ratings using the local information of users and items in the same cluster. The local information can detect strong localized associations shared within clusters. Third, we design different fusion approaches based on the local information embedding. In this way, both under-fitting and over-fitting problems are alleviated. Experiment results on the real datasets show that our approaches defeats slope one in terms of both mean absolute error and root mean square error., Competing Interests: The authors have declared that no competing interests exist.

Background: Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis. However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear., Purpose: The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/lpr mice and its regulatory function on Tfh cells., Study Design and Methods: MRL/lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2-Stat3 signaling pathway., Results: Upon oral administration, ART significantly prolonged the survival of MRL/lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment, T-cell compartment in the spleen of MRL/lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/lpr mice., Conclusion: ART showed therapeutic effects on lupus-prone MRL/lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2-Stat3 signaling cascade., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Polysorbate 20 (PS20), a widely used surfactant in protein therapeutics, has been reported to undergo hydrolytic degradation during product storage, causing the release of free fatty acids. The accumulation of free fatty acids in protein therapeutics was found to result in the formation of particles due to their limited aqueous solubility at 2°C-8°C. Quantitation of free fatty acids originating from PS20 degradation is thus important during bioprocess optimization and stability testing in formulation development to ensure optimum PS20 stability as well as product and process consistency in final drug products. This work reports the development of a simple and robust, high-throughput, reversed-phase ultra high performance liquid chromatography mass spectrometry method for high-sensitivity quantitation of lauric acid and myristic acid by using isotope-labeled fatty acid internal standards. The high sensitivity (<100 ng/mL for lauric acid) and suitable precision (intermediate precision relative standard deviation of 11%) of this method enable accurate detection of lauric acid produced from the degradation of less than 1% of PS20 in a 0.2-mg/mL formulation. Using accelerated thermal stability testing, this method identifies processes that exhibit fast PS20 degradation within only days and consequently allows faster iterative optimization of the process., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Meiosis is a specialized type of cell division that creates haploid germ cells and ensures their genetic diversity through homologous recombination. We show that the H3K4me3 reader ZCWPW1 is specifically required for meiosis prophase I progression in male but not in female germ cells in mice. Loss of Zcwpw1 in male mice caused a complete failure of synapsis, resulting in meiotic arrest at the zygotene to pachytene stage, accompanied by incomplete DNA double-strand break repair and lack of crossover formation, leading to male infertility. In oocytes, deletion of Zcwpw1 only somewhat slowed down meiosis prophase I progression; Zcwpw1 -/- oocytes were able to complete meiosis, and Zcwpw1 -/- female mice had normal fertility until mid-adulthood. We conclude that the H3K4me3 reader ZCWPW1 is indispensable for meiosis synapsis in males but is dispensable for females. Our results suggest that ZCWPW1 may represent a previously unknown, sex-dependent epigenetic regulator of germ cell meiosis in mammals.

Objective: Calcium dobesilate (CaD), an effective drug for the treatment of diabetic microvascular complications, especially diabetic retinopathy, is widely used in the clinic. Interestingly, several studies have indicated that CaD is therapeutic for diabetic kidney disease (DKD). Recently, evidence has indicated that altered vascular endothelial growth factor (VEGF) expression and decreased autophagy are the main pathological mechanisms of proteinuria. Thus, this study was conducted to explore the effect of CaD on restoring autophagy in DKD and the possible signaling pathway between VEGF and autophagy. Methods: Obese mice with spontaneous diabetes (KK-Ay) and high-fat diet- and streptozotocin-induced diabetic mice (HFD/STZ) were used in this study. Biochemical staining, western blotting, and immunohistochemistry were conducted to determine the angioprotective effect of CaD and the underlying mechanism between autophagy and VEGF/VEGFR. Results: Our results showed that CaD was capable of reducing albuminuria and restoring renal histological changes in KK-Ay and HFD/STZ-induced diabetic mice. CaD restored autophagy by decreasing the protein expression of LC3 II, Atg5, and beclin 1 and increasing the expression of P62. Moreover, CaD reduced the activation of the autophagy-related PI3K/AKT/mTOR pathway possibly via decreasing VEGF and downregulating VEGF receptor 2. Conclusion: Overall, CaD, as a novel potential therapeutic drug for DKD, plays a key role in protecting renal function and restoring autophagy by blocking VEGF/VEGFR2 and inhibiting the PI3K/AKT/mTOR signaling pathway.

Objectives: To evaluate the validity of a modified scoring system (MSS) for inferring the bony quality of tumor-bearing diaphyses and predicting the risk of reconstructive failure after devitalized bone replantation (DBR)., Methods: In this retrospective cohort study, we reviewed the records of 30 patients surgically treated for diaphyseal malignancies between 1996 and 2015. There were 18 male and 12 female subjects; the average age was 34.0 ± 24.5 years (8-82 years). Tumor locations comprised the femur (21), the humerus (4), the tibia (3), the radius (1), and the fibula (1). Histological diagnoses included osteosarcoma (13), metastases (4), Ewing sarcoma (3), chondrosarcoma (3), malignant fibrohistiocytoma (2), periosteal osteosarcoma (1), Langerhans cell sarcoma (1), lymphoma (1), rhabdomyosarcoma (1), and malignant giant cell tumor (1). All primary tumors were rated as stage IIB. Twenty patients underwent DBR. Prosthetic procedures and segmental autografting/allografting were performed in 7 and 3 cases, respectively. MSS (comprising 5 elements: pain, tumor location, bone destruction, localized dimension, and longitudinal dimension) for each patient was calculated in accordance with their preoperative presentations. Outcome measurements included oncological results, outcomes of reconstructions, complications, and functional preservation, presented using the musculoskeletal tumor society (MSTS) scale., Results: Follow up was available in 29 cases for an average duration of 61.0 ± 49.9 months (12-152 months). Infection occurred in 2 patients (6.9%), primary nonunion in 6 (27.3%), metastases in 9 (31.9%), recurrences in 4 (13.8%), and deaths in 7 (24.1%); 1 subject underwent amputation due to recurrence following endoprosthetic replacement (3.4%). In the DBR group, fractures occurred in 4 cases (21.1%) and nonunion in 5 (25%); internal fixation was related to nonunion (nails, 44.4% vs plates, 9.1%, P = 0.02). MSS was associated with fractures of devitalized autografts (11.0 ± 1.2 vs 8.3 ± 1.8, P = 0.01); the system was efficacious in predicting chances of fractures of these grafts (P = 0.02). MSS ≥ 10 (with false positive rate ≤ 6.7%) suggested increased fracture probability (≥22.7%) after DBR; therefore, 10 was considered a cutoff value., Conclusions: Diaphyseal malignancies with MSS ≥10 may contraindicate DBR for increased chances of reconstructive failure. In this situation, alternative procedures are advisable. Further investigations are warranted to assess the efficacy of MSS in implying the validity of DBR for diaphyseal malignancies., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: The optimal reconstructive method after diaphyseal malignant bone tumor resection remains controversial. This multicenter clinical study was designed to investigate the clinical value and complications of segmental prosthesis in the repair of diaphyseal defects., Methods: We present 49 patients from three clinical centers treated with wide resection for primary or metastatic bone tumors involving the diaphysis of the femur, tibia, humerus, or ulna, followed by reconstruction using a modular intramedullary segmental prosthesis., Results: Enrolled patients included 23 men and 26 women with a mean age of 63.3 years. Of these, seven patients had primary bone tumors and 42 patients had metastatic lesions. At the mean follow-up of 13.7 months, 17 patients were alive, 31 patients were deceased due to tumor progression, and one patient was dead of another reason. There were eight nononcologic complications (two with radial nerve injury, three with delayed incision healing, two with aseptic loosening in the proximal humerus prosthetic stem and one with structural failure) and three oncologic complications (three with primary tumor recurrence) among all patients. The incidence of complications in primary tumor patients (4/7, 57.1%) was higher than that in patients with metastatic tumors (7/42, 16.7%) (p = 0.036). Aseptic loosening and mechanical complications were not common for patients with primary tumors, although the reconstruction length difference was statistically significant (p = 0.023). No statistically significant differences were observed in limb function, while the mean musculoskeletal tumor society score was 21.2 in femora, 19.6 in humeri, and 17.8 in tibiae (p = 0.134)., Conclusions: Segmental prostheses represent an optional method for the reconstruction of diaphyseal defects in patients with limited life expectancy. Segmental prostheses in the humerus experienced more complications than those used to treat lesions in the femur.

Objectives: To investigate the association between the number of metastases to the spine and survival in patients with metastatic spinal cord compression (MSCC), as well as the prognosis difference between patients with solitary spinal metastasis (SSM) and multiple spinal metastases (MSM)., Methods: Three institutional databases were searched to identify all patients who had undergone spinal surgery for metastatic spinal tumors between March 2002 and June 2010. As well as age and gender, preoperative medical conditions were collected from medical records, including primary tumor, preoperative Frankel score, other bone metastases, preoperative Karnofsky performance status (KPS), number of involved vertebrae, pathological fracture metastasis site, serum albumin, sphincter dysfunction and the time of developing motor deficits before surgery. Survival data were obtained from medical records or via telephone follow-ups. Univariate and multivariate predictors of overall survival for each group were assessed using the Cox proportional hazards model., Results: The median postoperative survival time was 6.0 ± 0.6 months (95% confidence interval [CI] 4.8-7.2) in patients with SSM and 7.0 ± 1.0 months (95% CI 5.1-8.9) in patients with MSM (P = 0.238). The difference in survival was not significant between groups. Furthermore, univariate analysis showed that the number of spinal metastases had no significant association with survival (P = 0.075). Primary tumor (P = 0.004) and preoperative KPS (P < 0.001) were independent prognostic factors in the whole cohort; primary tumor (P = 0.020), time of developing motor deficit (P = 0.041) and preoperative KPS (P = 0.038) were independent prognostic factors in patients with SSM; while preoperative KPS (P = 0.001) and serum album level (P < 0.001) were independent prognostic factors in patients with MSM., Conclusion: The number of spinal metastases has not proven to be useful in predicting the prognosis for patients with MSCC. Consequently, more aggressive operations should be considered for patients with multiple spinal metastases., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To investigate whether visceral metastases have a significant impact on survival in patients with metastasis-related spinal cord compression (MSCC), and to determine the difference in prognosis between patients with and without visceral metastases., Methods: Three institutional databases were searched to identify all patients who had undergone spinal surgery for spinal metastases between March 2002 and June 2010. Data on patient characteristics including pre- and post-operative medical conditions, were collected from medical records or by telephone follow-up. Survival data were obtained either from medical records or by searching a governmental cancer registry., Results: The mean age of study patients was 59.6 ± 10.5 years (range, 18-84 years), of whom 102 were male and 67 female. The median and mean postoperative survival times were 7.0 ± 0.5 (95% CI 6.0-8.0) months and 12.6 ± 1.2 (95% CI 10.1-15.0) months, respectively, in all patients, being 5.0 ± 0.5 (95% CI 4.0-6.0) months and 10.8 ± 2.4 (95% CI 6.1-15.5) months, respectively, for patients with visceral metastases and 7.0 ± 0.8 (95% CI 5.4-8.6) months and 13.0 ± 1.4 (95%CI 10.3-15.6) months, respectively, for patients without visceral metastases (P = 0.87). These survival times did not differ significantly between groups. Multivariate Cox proportional hazard regressions showed that visceral metastases had no statistically significant association with survival (P = 0.277), whereas rate of growth of primary tumor (P = 0.003), preoperative Karnofsky performance status (KPS) (P < 0.001), change in KPS (P < 0.001), and Frankel grade (P = 0.091) were independent prognostic factors in the whole cohort (P = 0.005). Changes in KPS (P = 0.001) and major complications (P = 0.003) were significantly associated with survival in patients with visceral metastases, whereas rate of growth of primary tumor (P = 0.016), change in KPS (P = 0.001), and preoperative KPS (P < 0.001) were significantly associated with survival in patients without visceral metastases., Conclusions: Visceral metastases do not appear to predict the prognosis of patients with MSCC; thus, more aggressive surgery should be considered in patients with MSCC who have visceral metastases. Additionally, prognostic factors differ according to visceral metastases status in these patients., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Optical microcavities have been widely applied as sensitive detectors due to ultrahigh quality factors and small mode volumes. Besides considering the optical mode as the sensing signal, the optomechanical oscillations induced by the optical spring effect also perform as an elegant sensing signal. However, the minimal size of a detectable analyte is limited by the relatively weak light-matter interaction compared to the experimental noises. To improve the detection limit, many methods have been developed to either enhance device sensitivities or suppress experimental noises. In this work, we present a way to lower the detection limit by suppressing experimental noises of the mechanical frequency by 3 orders of magnitude. Utilizing a fiber tip as a benchmark analyte attaching onto the cavity, the mechanical frequency shift reflects the changes of the optical mode detuning of the cavity, predicting an effective tool for ultrasensitive detection.

Acupuncture sensation, as one of the essential signs of deqi (arrival of qi ), is closely associated with curative effect. With systematically reviewing the literature regarding relationship between acupuncture sensations of deqi and different organizational structures of acupoint area (skin, connective tissue, muscles, nerves and blood vessels), it is believed that acupuncture sensation of deqi is the product of various organizational structures in acupoint area, which is closely related to the nervous system. The deqi sensations sensed by the hands of acupuncturists, which is called sense of needle stagnation, maybe caused by the contraction of muscles in the acupoint area during the process of needle manipulation. By system review, this paper puts forward a new research idea to explore the role of different manipulations of needling in generating the sense of qi -generating needle based on different acupoint structure and brain function response system, which could provide some reference for clarifying the scientific mechanism and clinical application of acupuncture sensations of deqi .

The measurement of heart rate variability (HRV) has the advantages of noninvasiveness and simple operation and is widely used in clinical trials and scientific research for assessing reactions of the autonomic nervous system. More and more studies on acupuncture also take HRV as an important index. In addition to the definition, origin, analytical methods, and significance of time domain and frequency domain parameters of HRV, we reviewed the situations of application of HRV to acupuncture research in recent years, analyzed the influence of acupuncture and sham acupuncture, different acupuncture methods, and different acupoints on HRV, and confirmed the role of HRV in reflecting the effect of acupuncture on the vagal and sympathetic systems. However, various interference factors for HRV measurement and diverse methods for data analysis may lead to great differences in the experimental results of HRV and the interpretation of parameters. Therefore, careful analysis is needed in future studies on acupuncture with HRV as an observation index.

The role of protein structural disorder in biological functions has gained increasing attention in the past decade. The bacterial acid-resistant chaperone HdeA belongs to a group of "conditionally disordered" proteins, because it is inactive in its well-structured state and becomes activated via an order-to-disorder transition under acid stress. However, the mechanism for unfolding-induced activation remains unclear because of a lack of experimental information on the unfolded state conformation and the chaperone-client interactions. Herein, we used advanced solution NMR methods to characterize the activated-state conformation of HdeA under acidic conditions and identify its client-binding sites. We observed that the structure of activated HdeA becomes largely disordered and exposes two hydrophobic patches essential for client interactions. Furthermore, using the pH-dependent chemical exchange saturation transfer (CEST) NMR method, we identified three acid-sensitive regions that act as structural locks in regulating the exposure of the two client-binding sites during the activation process, revealing a multistep activation mechanism of HdeA's chaperone function at the atomic level. Our results highlight the role of intrinsic protein disorder in chaperone function and the self-inhibitory role of ordered structures under nonstress conditions, offering new insights for improving our understanding of protein structure-function paradigms., (© 2019 Yu et al.)

Acupuncture therapy has a positive role in the prevention and treatment of some related diseases by regulating autonomic nervous function. But it has been found in experimental researches that the modulatory effects of acupuncture on autonomic nervous system are not always consistent with each other. Because in the animal studies on the mechanism of acupuncture intervention, the anesthetic agent has to be used and definitely affects the activities of the autonomic nervous system while playing its pharmacological effects. Hence, it is very significant to explore the rational application of anesthetic agents and minimize their unfavorable impacts on the research outcomes. In the present paper, we make a retrospective analysis on (1) the effect of acupuncture intervention on activities of the autonomic nerve in animal models of myocardial ischemia, gastrointestinal mobility, and urinary system; (2) the effect of anesthetics as isoflurane, urethane, pentobarbital sodium, ketamine, α-chloralose, propofolum, etc. on activities of the autonomic nerve system. In terms of different anesthetic modes and various depths of anesthesia by using isoflurane inhalation, mixed solution of urethane and chloralose, etc., some approaches for assessing the state of anesthesia in accordance with the pupillary reflex, righting reflex, footboard reflex, swallowing reflex, heart rate, blood pressure, body temperature, respiration frequency, ventilation volume, oxygen saturation, partial pressure of carbon dioxide, neuromuscular blo-ckade, etc. in combination with the indexes directly and indirectly reflecting functions of the sympathetic and vagus nerves are proposed to analyze the impact of different anesthetic states on the therapeutic effect of acupuncture in various models of dysfunction of the autonomic nerve system. Under the circumstances, it is possible to provide a reference for rational use of anesthetic agents and dosages in the acupuncture research of autonomic nerve regulation.

Objective: To try to re-map an acupoint atlas in vector mode in the experimental rat by using a new-generation drawing tool., Methods: A total of 5 SD rats were used in the present study. In reference to the current acupoint locations and anatomical structure of rats as well as those of the human body, an acupoint atlas having a stereoscopic mode was re-mapped by using Adobe photoshop/illustrator CS6 imaging processing and drawing system., Results: According to the skeletal structure and body surface landmarks, an acupoint atlas consisting of Shuigou (GV26), Baihui (GV20), Tianmen (i.e. Cuanzhu, BL2), Erjian (MA-H6), Dazhui (GV14), Feishu (BL13), Xinshu (BL15), Geshu (BL17), Jizhong (GV6), Pishu (BL20), Shenshu (BL23), Houhui (SI3), Huantiao (GB30), Houhai, Yanglingquan (GB34), Housanli (ST36), Zhaohai (KI6), Sanyinjiao (SP6), Genduan point, Shenmai (BL62), Taichong (LR3), Zhijian (foot), Yongquan (KI1), Guanyuan (CV4), Xiqian, Weijian, Shenque (CV8), Zhongwan (CV12), Qiansanli (LI10), Waiguan (SJ5), Neiguan (PC6), Quchi (CV6), Zhoujie (EX-UE1), Hegu (LI4), Zhijian (hand), Houxi (SI3), Shenmen (HT7), Taiyuan (LU9), Shaohai (HT3), Chize (LU5), Danzhong (CV17), and Chengjiang (CV24) which have been positioned in plane graph mode by Professor HUA Xing-bang and colleagues in 1991. The newly re-mapped acupoint atlas displayed more clearly in the anatomic locations relevant to the traditional one., Conclusion: A new acupoint atlas with 3 dimension image mode is accomplished in the rat, being more convenient and applicable for researchers to edit the relevant graph materials in paper writing, and playing a possibly useful guidance for the standardization of acupoint selection in experimental acupuncture researches.

We aimed to explore changes in basic soil productivity (BSP) under different fertilization regimes in the Poyang Lake region, Jiangxi Province, China. Soil samples were collected from a long-term fertilization experiment (since 1981) that included treatments of no fertilization (CK), chemical fertilization (NPK), and combined chemical and organic fertilization (NPKM). Then, a three-year pot experiment (from 2012 to 2014) with double rice cropping was conducted with two different fertilization regimes (no fertilization, F 0 ; fertilization, F 1 ) using CK, NPK and NPKM soils. Grain yield and BSP were analyzed among soils with different fertilization regimes to identify the key factors driving changes in BSP. Results showed that grain yields in NPKM soil were higher than in NPK and CK soils regardless of fertilization in the pot experiment. Under the F 0 condition, annual grain yields of NPKM soil were 37.7%-143.9% and 20.8%-66.7% higher than CK and NPK soils, respectively. The BSP values of CK, NPK and NPKM soils in three years were 41.8%-53.1%, 45.2%-62.6% and 59.1%-88.1%, respectively. NPKM soil had significantly higher BSP than NPK and CK soils. Furthermore, there were significant positive correlations between soil organic matter and BSP as well as between organic carbon balance and BSP. These results suggested that long-term application of chemical and organic fertilizers could improve BSP in the double rice cropping system of the Poyang Lake region. In addition, soil organic matter and organic carbon balance are important factors for improving BSP in this region.

Methodologies employing LC-MS/MS have been increasingly used for characterization and identification of residual host cell proteins (HCPs) in biopharmaceutical products to ensure their consistent product quality and safety for patients. To improve the sensitivity and reliability for HCP detection, we developed a high pH-low pH two-dimensional reversed phase LC-MS/MS approach in conjunction with offline fraction concatenation. Proof-of -concept was established using a model in which seven proteins spanning a size range of 29-78 kDa are spiked into a purified antibody product to simulate the presence of low-level HCPs. By incorporating a tandem column configuration and a shallow gradient through the second-dimension, all seven proteins were consistently identified at 10 ppm with 100% success rate following LC-MS/MS analysis of six concatenated fractions across multiple analysts, column lots and injection loads. Using the more complex Universal Proteomic Standard 1 (UPS-1) as an HCP model, positive identification was consistently achieved for 19 of the 22 proteins in 8-12 ppm range (10 ppm ±20%). For the first time, we demonstrate an effective LC-MS/MS strategy that not only has high sensitivity but also high reliability for HCP detection. The method performance has high impact on pharmaceutical company practices in using advanced LC-MS/MS technology to ensure product quality and patient safety.

Background: There is a high aseptic loosening rate for intercalary prosthetic reconstruction for malignant tumors. We evaluated outcomes and complications of intercalary prosthetic reconstruction for pathologic diaphyseal humeral fractures and report the application of an extracortical plate that can prevent early loosening., Methods: We retrospectively analyzed 9 patients who underwent intercalary prosthetic reconstruction for pathologic diaphyseal humeral fractures secondary to metastatic diseases between March 2011 and September 2017. Procedures were intercalary prosthetic reconstruction in 4 patients (group A) and an implanted intercalary prosthesis with a plate in 5 patients (group B). Operative time, blood loss, complications, and functional score were noted., Results: Mean operative time for group A and B was 80 ± 14 and 94 ± 5 minutes, respectively; blood loss was 115 ± 26 and 120 ± 31 mL respectively; and follow-up was 11.5 ± 10.1 and 6.2 ± 4.4 months, respectively. At final follow-up, all patients in group A had died, and 3 patients in group B had died; mean survival was 11.5 ± 10.1 and 9.3 ± 1.2 months, respectively. The mean postoperative Musculoskeletal Tumor Society score was 24.5 ± 2.4 and 26.2 ± 0.8, respectively. The mean postoperative American Shoulder and Elbow Surgeons score was 85.5 ± 4.20 and 87 ± 2.6, respectively. There were no significant differences between the 2 groups (P > .05). There was 1 aseptic loosening and 1 radial nerve injury in group A; there were no complications in group B., Conclusions: The intercalary prosthesis yielded satisfactory outcomes in patients with pathologic diaphyseal humeral fractures, and an extracortical plate can prevent early aseptic loosening., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

The aim of the present study was to evaluate the prognostic potential of postoperative scores of inflammation indexes and the dynamic changes of scores before and after tumor resection in colorectal cancer patients. The study included 516 colorectal cancer patients with primary colorectal tumor resection. Cox regression was applied to estimate the associations of postoperative and dynamic changes of inflammation indexes with progression-free survival and overall survival. As results, we found that higher postoperative neutrophil to lymphocyte ratio (NLR), neutrophil and monocyte to lymphocyte ratio (NMLR), platelet to lymphocyte ratio (PLR) and systemic immune inflammation index (SII) were associated with shorter progression-free survival. The increased NLR, NMLR, PLR, SII and C-reaction protein (CRP) to albumin (ALB) ratio (CAR) were associated with poor progression-free survival, with HRs (95% CIs) of 1.92 (1.27-2.90), 1.46 (1.11-2.09), 2.10 (1.34-3.30), 1.81 (1.22-2.70) and 1.65 (1.03-2.67), respectively. Postoperative NMLR, SII, CAR, and their dynamic changes were also significantly correlated with overall survival, with the HRs (95% CIs) of 2.63 (1.30-3.97), 2.44 (1.43-4.17), 2.74 (1.31-5.74), 2.08 (1.21-3.60), 1.97 (1.12-3.45) and 2.55 (1.21-5.38) respectively. In conclusion, postoperative inflammation indexes and their dynamic changes, particularly for NMLR, SII and CAR are promising prognostic predictors of CRC patients.

It has been shown that ischemia preconditioning (IPC) can attenuate the myocardial injury induced by ischemic and reperfusion. But it was rarely used in clinic due to its inoperability. Previous studies indicate that electroacupuncture (EA) pretreatment can mimic myocardial ischemia preconditioning (MIPC) to produce cardioprotective effect. The activated adenosine A 2 b receptor has been proven to be involved in mediating the cardioprotection of IPC. In the studies on acupuncture analgesia, it was reported that adenosine receptor was activated by acupuncture stimulation, and acupuncture pretreatment can affect the acti-vities of intracellular A 2 b receptor. Based on those mentioned above, it is highly likely that the A 2 b receptor may also participate in the cardioprotection produced by acupuncture pretreatment. In this paper, we comprehensively reviewed relevant studies regarding 1) the cardioprotective effect of IPC and its limitations, 2) the similar cardioprotection produced by both acupuncture pre-treatment and IPC, 3) the mechanism underlying myocardial ischemic injury and intracellular calcium regulation, 4) the acti-vation of adenosine receptors and effects of acupuncture, 5) the relationship between adenosine receptors and intracellular calcium ion, and 6) the effect of acupuncture on adenosine receptors, so as to provide a novel assumption that A 2 b receptor may be a key factor in mediating the cardioprotection of acupuncture pretreatment. Our future research will systematically explore the me-chanism of acupuncture pretreatment in protecting ischemic myocardium from myocardial cell adenosine A 2 b receptor and intracellular calcium signal transduction related factors.

N 6 -methyladenosine (m 6 A) messenger RNA methylation is a gene regulatory mechanism affecting cell differentiation and proliferation in development and cancer. To study the roles of m 6 A mRNA methylation in cell proliferation and tumorigenicity, we investigated human endometrial cancer in which a hotspot R298P mutation is present in a key component of the methyltransferase complex (METTL14). We found that about 70% of endometrial tumours exhibit reductions in m 6 A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3, another component of the methyltransferase complex. These changes lead to increased proliferation and tumorigenicity of endometrial cancer cells, likely through activation of the AKT pathway. Reductions in m 6 A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator mTORC2. Together, these results reveal reduced m 6 A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m 6 A methylation as a regulator of AKT signalling.

Ultrasensitive and rapid detection of nano-objects is crucial in both fundamental studies and practical applications. Optical sensors using evanescent fields in microcavities, plasmonic resonators, and nanofibers allow label-free detection down to single molecules, but practical applications are severely hindered by long response time and device reproducibility. Here, an on-chip dense waveguide sensor to monitor single unlabeled nanoparticles in a strong optical evanescent field is demonstrated. The spiral nanowaveguide design enables two orders of magnitude enhancement in sensing area compared to a straight waveguide, significantly improving the particle capture ability and shortening the target analysis time. In addition, the measurement noise is suppressed to a level of 10 -4 in the transmitted power, pushing the detection limit of single particles down to the size of 100 nm. The waveguide sensor on the silicon-on-isolator platform can be fabricated reproducibly by the conventional semiconductor processing and compatible with surface functionalization chemistries and microfluidics, which could lead to widespread use for sensing in environmental monitoring and human health., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although an accurate evaluation of the distribution of ultrafine particulate matter in air is of utmost significance to public health, the usually used PM 2.5 index fails to provide size distribution information. Here we demonstrate a low-profile and cavity-free size spectrometer for probing fine and ultrafine particulate matter by using the enhanced particle-perturbed scattering in strong optical evanescent fields of a nanofiber array. The unprecedented size resolution reaches 10 nm for detecting single 100-nm-diameter nanoparticles by employing uniform nanofibers and controlling the polarizations of the probe light. This size spectrometry was tested and used to retrieve the size distribution of particulate matter in the air of Beijing, yielding mass concentrations of nanoparticles, as a secondary exercise, consistent with the officially released data. This nanofiber-array probe shows potential for the full monitoring of air pollution and for studying early-stage haze evolution and can be further extended to explore nanoparticle interactions., Competing Interests: The authors declare no conflict of interest.

Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.