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Background Workplace heat exposure can cause a series of heat-related illnesses and injuries. Protecting workers especially those undertake work outdoors from the risk of heat strain is a great challenge for many workplaces in China under the context of climate change. The aim of this study is to investigate the perceptions and adaptation behaviors of heat exposure among construction workers and to provide evidence for the development of targeted heat adaptation strategies nationally and internationally. Methods In 2020, we conducted a cross-sectional online questionnaire survey via WeChat Survey Star in China, using a purposive snowball sampling approach. A total of 326 construction workers submitted completed questionnaires. The perceptions of workplace heat exposure were measured using seven indicators: concerns over high temperature, perception of high temperature injury, attitudes towards both heat-related training and regulations, adjustment of working habits during heat, heat prevention measures in the workplace, and reduction of work efficiency. Bivariate and multivariate regression analyses were used to identify the factors significantly associated with workers’ heat perceptions and behavioral responses. Results 33.3% of the respondents were moderately or very concerned about heat exposure in the workplace. Less than half of the workers (43.8%) were worried about heat-related injuries. Workers who have either experienced work-related injuries (OR = 1.30, 95% CI 1.03–1.62) or witnessed injuries to others during high temperatures (OR = 1.12, 95% CI 1.02–1.27) were more concerned about heat exposure compared to other workers. Most respondents (63.5%) stated that their work efficiency declined during extremely hot weather. The factors significantly associated with a reduction of work efficiency included undertaking physically demanding jobs (OR = 1.28, 95% CI 1.07–1.54) and witnessing other workers’ injuries during high temperatures (OR = 1.26, 95% CI 1.11–1.43). More than half of the workers were willing to adjust their work habits to adapt to the impact of high temperatures (81.6%). The internet was the most common method to obtain heat prevention information (44.7%), and the most frequently used heat prevention measure was the provision of cool drinking water (64.8%). Conclusions Chinese construction workers lack heat risk awareness and are not well prepared for the likely increasing heat exposure in the workplace due to global warming. Therefore, there is a need to improve their awareness of heat-related injuries, strengthen high temperature related education and training, and update the current heat prevention policies to ensure compliance and implementation.

Green investment, as a socially responsible investment, conforms to the concept of ecological civilization. It is considerable to promote enterprises to make green investment. This article is based on 211 questionnaires for employees of various enterprises in China, using STATA.14 for descriptive statistical analysis, logistical regression analysis, and trend analysis. It aims to explore the impact of government-led institutional environment on enterprises from five aspects. This study examines that the institutional environment has a positive effect on enterprise’ green investment from the legal and cultural aspects, but it has no significant impact from the political, economic, and financial aspects. Finally, this paper provides policy advice that can promote the construction of institutional environment to encourage enterprises to make green investment.

The phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa ( l -dopa) with tetrahydrobiopterin (BH 4 ) as a coenzyme. Here, we show that oral berberine (BBR) might supply H • through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH 4 from dihydrobiopterin; the increased BH 4 enhances TH activity, which accelerates the production of l -dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The l -dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus , and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of l -dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal l -dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of l -dopa in the gut microbiota through a vitamin-like effect.

Paeoniflorin, the main component of Xiaoyao Wan, presents low oral bioavailability and unclear antidepressant mechanism. To elucidate the potential reasons for the low bioavailability of paeoniflorin and explore its antidepressant mechanism from the perspective of the gut microbiota, here, a chronic unpredictable depression model and forced swimming test were firstly performed to examine the antidepressant effects of paeoniflorin. Then the pharmacokinetic study of paeoniflorin in rats was performed based on the gut microbiota; meanwhile, the gut microbiota incubated with paeoniflorin was used to identify the possible metabolites of paeoniflorin. Molecular virtual docking experiments together with the specific inhibitor tests were applied to investigate the mechanism of paeoniflorin metabolism by the gut microbiota. Finally, the intestinal microbiota composition was analyzed by 16S rRNA gene sequencing technology. The pharmacodynamics tests showed that paeoniflorin had significant antidepressant activity, but its oral bioavailability was 2.32%. Interestingly, we found paeoniflorin was converted into benzoic acid by the gut microbiota, and was mainly excreted through the urine with the gut metabolite benzoic acid as the prominent excreted form. Moreover, paeoniflorin could also regulate the composition of the gut microbiota by increasing the abundance of probiotics. Therefore, the metabolism effect of gut microbiota may be one of the main reasons for the low oral bioavailability of paeoniflorin. Additionally, paeoniflorin can be metabolized into benzoic acid via gut microbiota enzymes, which might exert antidepressant effects through the blood-brain barrier into the brain.

Trimethylamine- N -oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR’s metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (* P  < 0.05, n  = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n  = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (* P  < 0.05; * P  < 0.05), and 37 and 35% in plasma (*** P  < 0.001; * P  < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P  = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P  = 0.001; ORR, 60.1% vs. 32.0%; P  < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

It is unclear whether the magnitude and duration of elevated central venous pressure (ECVP) greater than ten mmHg has the same impact on mortality in sepsis patients. Critically ill patients with sepsis were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The duration and the magnitude of ECVP were calculated. Normalized ECVP load was defined as the ECVP load (the sum of ECVP value times its duration) divided by the total duration of ECVP. The primary endpoint was 28-day mortality. Kaplan-Meier survival analysis was used to compare survival between patients with high or low normalized ECVP load. A total of 1071 sepsis patients were included. Higher normalized ECVP load was associated with higher mortality rate; in contrast, the duration of ECVP was not associated with mortality. A linear relationship between normalized ECVP load and mortality was identified. Patients with higher normalized ECVP load had less urine output and more positive fluid balance. The magnitude, but not the duration of ECVP, is associated with mortality in sepsis patients. ECVP should be considered as a valuable and easily accessible safety parameter during fluid resuscitation.

It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota.

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

Objective Microwave ablation (MWA) has emerged as a minimally invasive technology for papillary thyroid microcarcinoma (PTMC), but it has not been widely applied to treat T1bN0M0 PTC with high-level evidence. This study was designed to compare the real-world efficacy and safety of MWA or surgery for treating T1bN0M0 PTC. Methods From December 2019 to April 2021, 123 continuous unifocal T1bN0M0 PTC patients without lymph node metastasis (LNM) or distant metastasis (DM) were included from 10 hospitals. Patients were allocated into the MWA or surgery group based on their willingness. The main outcomes were local tumour progression (LTP), new thyroid cancer, LNM, and DM. The secondary outcomes included changes in tumour size and volume, complications, and cosmetic results. Subgroup analyses were conducted to identify influencing factors. Results Fifty-two patients chose MWA, and 71 patients chose surgery. Patients had similar demographic information and tumour characteristics in the two groups. The follow-up durations after MWA and surgery were 10.6 ± 4.2 and 10.4 ± 3.4 months, respectively. The LNM rate was 5.8% in the MWA group and 1.4% in the surgery group ( p  = 0.177). No LTP, new thyroid cancer, or distant metastasis (DM) occurred in either group. Five (9.6%) of the 52 patients in the MWA group and 8 (11.3%) of the 71 patients in the surgery group had complications ( p  = 0.27). Better cosmetic results were found in the MWA group ( p  < 0.01). Conclusion MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. Clinical relevance statement MWA achieved comparable short-time treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC. Key Points • MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. • The complication rate in the surgery group was higher than that in the MWA group without a significant difference. • There was no statistically significant difference in the LNM rate between the MWA and surgery groups.