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Background The promotion of appropriate traditional Chinese medicine (TCM) techniques in primary care institutions is an important measure emphasizing the co-development of Chinese and western medicine, and enhancing the inheritance and development of TCM. Objective To analyze primary health workers'preferences for the use of appropriate TCM techniques, providing policy recommendations for the promotion and use of such techniques in primary healthcare institutions. Methods This questionnaire survey was conducted between July and August 2021. A discrete choice model with seven attributes and 18 choice sets obtained through the use of an efficient orthogonal design were used to develop the questionnaire used in the survey, and the questionnaire has three versions each version with evenly allocated six choice sets (including an opt-out option). Additionally, the three versions have a common general demographic part (sex, age, education level, professional title, etc.) and one common consistency test question. A randomized multistage stratified cluster sampling was used to select 319 health workers on duty on the survey day from a total of 23 primary healthcare institutions in three counties in eastern, central and western China (one county was extracted from each region), and each worker was required to complete one version of the questionnaire extracted sequentially by themselves. Two hundred and ninety-five cases who returned a questionnaire passing a consistency test were included for analysis, resulting in a response rate of 92.5%. Primary health workers' preferences for appropriate TCM techniques were analyzed using conditional Logit models and latent class models. Furthermore, the changes in utility of primary health workers due to attribute level changes were monetized using willingness to pay and presented accordingly. Results The conditional Logit analysis showed that medical insurance, the average duration of each operation with the TCM technique, the influence of operation with the TCM technique on income, work burden, the promotion of professional title, and patient healthcare cost, as well as effectiveness of the TCM technique were associated with primary health workers' preferences for the use of appropriate TCM techniques (P

Gastric precancerous lesions (GPL) are a special histopathological stage before the occurrence of gastric cancer. Effective treatment of GPL is the key to preventing its progression to gastric cancer. GPL has a high level of inflammation in gastric mucosa, and a large number of inflammatory cells, inflammatory factors and inflammatory mediators are metabolized at a high level, which increases oxygen consumption and leads to the formation of a hypoxia microenvironment in gastric mucosa at the GPL stage, which is conducive to the initiation of mitochondrial autophagy and glucose metabolism reprogramming. As a conserved biological process, mitochondrial autophagy exists in various tissues and cells of the body. It can form autophagosome to wrap mitochondria with damaged functions and bind with lysosomes to digest and reuse target mitochondria. Appropriate autophagy level can prevent excessive proliferation of GPL heterotype cells and inhibit the progress of GPL. However, mitochondrial autophagy activity is inhibited during the course of GPL, and the activity of glycometabolic reprogramming into glycolysis is increased during GPL. Glycolysis is a way of energy metabolism in the hypoxia state of cells, which can accelerate the energy supply of cells and the proliferation of abnormal cells, and thus accelerate the deterioration of GPL. Some evidences suggest that there may be a mutually restricting relationship between mitochondrial autophagy and glycolysis reprogramming. The inhibition of autophagy in GPL can increase glycolysis activity on the one hand, while the increase of autophagy inhibits glycolysis activity on the other hand. At present, the specific relationship and mechanism of autophagy and glycolysis are not clear, however, the complex pathological environment of GPL gastric mucosa composed of hypoxia, bacterial infection, inflammation, oxidative stress, activation disorder of signal molecules and other factors may be the key to the low autophagy level and high glycolysis activity. Hypoxia-inducible factor 1α (HIF-1α), which is involved in hypoxia adaptation, is stably expressed in gastric mucosa at the GPL stage and acts as a switch to initiate autophagy and glycolysis. However, HIF-1α seems to be more involved in the regulation of glycolysis in the pathological process of GPL. The cause of this change may be related to the above-mentioned pathological factors. H. pylori infection, activation of phosphoinositide 3-kinase (PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway and other factors inhibit autophagy. However, the continuous accumulation of reactive oxygen species (ROS) after autophagy inhibition and the aggravation of inflammation caused by H. pylori infection can promote a series of signal interactions and synergies among nuclear factor kappa-B (NF-Κb), signal transducer and activator of transcription 3 (STAT3) and PI3K/AKT/mTOR signaling pathways, and thus indirectly affect HIF-1α to promote glycolysis or directly improve glycolysis level. HIF-1α may be more involved in the activation of glycolysis due to the regulation of GPL pathological microenvironment and its upstream complex signals, thus unable to fully activate BNIP-3 mediated hypoxia-initiated autophagy, leading to the down-regulation or inhibition of autophagy level, and the inhibition of autophagy indirectly promotes the improvement of glycolysis level, forming a vicious cycle, and ultimately leading to the deterioration of GPL. This article reviewed the research progress of hypoxia-induced mitochondrial autophagy and glucose metabolism reprogramming in gastric precancerous lesions.

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Aims: ABBV‐3373, an immunology antibody–drug conjugate composed of adalimumab conjugated to a proprietary glucocorticoid receptor modulator (the small‐molecule payload), has the potential to treat immune‐mediated inflammatory diseases. This first‐in‐human study investigated the pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) using a safety PD marker, and safety/tolerability of ABBV‐3373 in healthy adults. Methods: Fifty‐five participants were randomly assigned to single‐dose subcutaneous (SC; 30, 100 or 300 mg) or intravenous (IV; 30, 300 or 900 mg) ABBV‐3373 or placebo. Eight additional participants received a single dose of 10 mg oral prednisone for evaluation of systemic glucocorticoid effects. Blood samples were collected for up to 85 days postdose for PK, anti‐drug antibody and serum cortisol (safety PD marker) assessments. Results: ABBV‐3373 and total antibody displayed antibody‐like SC/IV PK profiles and the unconjugated/free payload in circulation exhibited formation rate‐limited kinetics with exposure several fold lower than ABBV‐3373 or total antibody. Treatment‐emergent anti‐drug antibody incidence was 69%, with loss of exposure in 6% (SC) and 5% (IV) of participants, but without any impact on safety. ABBV‐3373 up to 300 mg SC/IV had no apparent impact on serum cortisol, and only caused a transient decrease at 900 mg IV. Treatment‐emergent adverse events were primarily mild in severity, and no pattern emerged with respect to dose or route of administration. Conclusions: ABBV‐3373 had favourable PK profiles, manageable immunogenicity, and was generally well‐tolerated. Except for a transient effect at 900 mg IV, there was no apparent impact on serum cortisol. Study results supported further clinical development of ABBV‐3373. [ABSTRACT FROM AUTHOR]

Varistor coupling is recommended by International Telecommunication Union in combination wave test waveforms of surge protective devices (SPD), although the varistor coupling method and recommendation parameters for the combination wave test are not well understood. The waveform influencing characteristics introduced by varistor coupling are studied in detail in this paper. Low‐voltage varistors, with maximum operating voltages ranging from 130 to 750 V, are adopted here in the OrCAD/PSpice environment to analyze the influence of varistor coupling on the output characteristic of the combination wave generator (CWG) in test levels of 0 to 20 kV. Simulation results show that, owing to varistor coupling, the reverse oscillation phenomena will arise in the open‐circuit voltages (OCVs). Also owing to varistor coupling, compared with those generated directly by a CWG, the peak value, the front time, and the tail time for both OCV and short‐circuit current will decrease, whereas the virtual impedance will increase. Moreover, the lower the test level, or the higher the maximum operating voltage of the varistor, the more serious this effect. Experiments have also been conducted here, and our simulation results are found to match the experimental ones well. It seems that, compared with the conventional capacitor coupling, the range of the voltage of power supply networks and the levels of combination wave test by varistor coupling have to be limited to a great extent. Varistor coupling for combination wave test of SPD should be only used in special cases and special test levels where there are no strict waveform limitations. [ABSTRACT FROM AUTHOR]

Background: The parasitic filariae responsible for onchocerciasis and lymphatic filariasis are host to an endosymbiotic bacterium, Wolbachia, which is essential to the fertility and development of the parasites. We performed a Phase-I pharmacokinetic, safety and food-effect study on single and multiple ascending doses of flubentylosin (ABBV-4083), a macrolide antibacterial with activity against Wolbachia, intended to sterilize and eliminate the parasites. Methods: Seventy-eight healthy adults were exposed to flubentylosin; 36 were exposed to single ascending 40, 100, 200, 400 or 1000 mg doses; 12 received 1000 mg in the food-effect part; and 30 received multiple ascending daily doses of 100 mg for 7 days, 200 mg for 7 or 14 days, or 400 mg for 7 or 14 days. Twenty-two subjects received placebo. Results: Maximum concentrations (Cmax) of flubentylosin were reached after 1–2 hours, with a half-life < 4 hours at doses ≤ 400 mg. Cmax and AUC increased in a more than dose-proportional manner, with similar exposure after multiple dose administration. The most frequently reported adverse events were nausea (8/78, 10%) and headache (6/78, 8%). Two subjects given a single dose of flubentylosin 1000 mg in the food-effect part experienced reversible asymptomatic ALT and AST elevations at Grade 2 or Grade 4, with no elevation in bilirubin, deemed related to study drug. The effect of food on exposure parameters was minimal. No treatment-related serious adverse events were reported. Discussion: Flubentylosin 400 mg for 14 days was the maximum tolerated dose in this first-in-human, Phase-I study in healthy adults. Based on preclinical pharmacokinetic/pharmacodynamic modeling, flubentylosin 400 mg once daily for 7 or 14 days is expected to be an effective dose. A Phase-II, proof-of-concept study with flubentylosin using these regimens is currently ongoing in patients with onchocerciasis in Africa. Author summary: Onchocerciasis and lymphatic filariasis are neglected tropical diseases caused by parasitic filarial nematodes. Current efforts to eliminate these diseases are hindered by a lack of drugs that permanently sterilize and/or kill the adult worms. Antibacterials, including doxycycline, have been shown to deplete Wolbachia, an endosymbiotic bacterium essential to the fertility and development of the adult worms, leading to their permanent sterilization and death. However, doxycycline is contraindicated in women of child-bearing age, breastfeeding women, and children, and must be given for 4–6 weeks to be effective. There is a need for agents with fewer contraindications and a shorter treatment regimen. Flubentylosin is an antibacterial with demonstrated anti-Wolbachia activity in several animal models of filarial disease. The present first-in-human Phase-I clinical study investigated the safety and pharmacokinetics of flubentylosin in healthy male and female subjects after single and multiple ascending doses, as well as the effect of food on the pharmacokinetics of flubentylosin, in order to identify appropriate regimens for Phase-II studies. Treatment regimens with 400 mg flubentylosin for 7 or 14 days were selected for further investigation. [ABSTRACT FROM AUTHOR]

A simulation model composed of an interfering cable and a disturbed cable is established for studying the lightning inductive characteristics between parallel cables. Effects of the horizontal distance between cables (5–40 cm), their height difference (−6–32 cm), as well as the length of disturbed cable (1–100 m) are investigated for the cable induced voltage, which is measured at the resistive load connected between one terminal of the disturbed cable and the ground, when various lightning surge currents (8/20 μs, 5/320 μs, and 0.5 μs/100 kHz) are delivered into the interfering cable. Our findings show that an increase of horizontal distance between cables can give rise to an exponential decrease of the cable induced voltage, and that there exist linear correlations between either the height difference of two cables or the length of disturbed cable and the cable induced voltage, which reaches maximum when the cables are located at the same height and of equal length. Verification experiments for the effect of horizontal distance have also been made, and, in general, they all show a reasonable agreement with the simulations. A detailed theoretical explanation of obtained findings is provided as well. [ABSTRACT FROM AUTHOR]

As the height of wind turbine increases, the lightning strike accident has become a non‐negligible issue. In this paper, the lightning attachment characteristic of a 2‐MW wind turbine generator (WTG) is investigated using a model with a reduced scale of 100. The WTG model is equipped with receptors on the blades and a lightning rod on the nacelle, both serving as its external lightning protection system (LPS). The high‐voltage electrode, which delivers a lightning impulse voltage from a Marx generator, is used to simulate the final stage of downward negative lightning strikes from 29 coming‐leader positions. The experimental results indicate that lightning leaders from either front directions or side directions could be intercepted effectively by LPS, whereas the back‐direction lightning could not. Moreover, with the increase of striking distance, the capture ratio for the insulation part of blade decreases. Electric field intensity distribution simulations for the full‐scale WTG model, using conditions similar to their experimental counterparts, are conducted and compared with the lightning attachment distribution. Based on classical electro‐geometrical model, a simulative method is proposed to predict the lightning attachment distribution of WTG. Our results indicate that it is feasible with this method to produce a satisfactory approximation to the experimentally obtained lightning attachment distribution. [ABSTRACT FROM AUTHOR]