A non-linear partial least squares based on monotonic inner relation.

A novel regression model, monotonic inner relation-based non-linear partial least squares (MIR-PLS), is proposed to address complex issues like limited observations, multicollinearity, and nonlinearity in Chinese Medicine (CM) dose-effect relationship experimental data. MIR-PLS uses a piecewise mapping function based on monotonic cubic splines to model the non-linear inner relations between input and output score vectors. Additionally, a new weight updating strategy (WUS) is developed by leveraging the properties of monotonic functions. The proposed MIR-PLS method was compared with five well-known PLS variants: standard PLS, quadratic PLS (QPLS), error-based QPLS (EB-QPLS), neural network PLS (NNPLS), and spline PLS (SPL-PLS), using CM dose-effect relationship datasets and near-infrared (NIR) spectroscopy datasets. Experimental results demonstrate that MIR-PLS exhibits general applicability, achieving excellent predictive performances in the presence or absence of significant non-linear relationships. Furthermore, the model is not limited to CM dose-effect relationship research and can be applied to other regression tasks.

Exploring the association between dietary Inflammatory Index and chronic pain in US adults using NHANES 1999-2004.

Chronic pain, a substantial public health issue, may be influenced by dietary patterns through systemic inflammation. This cross-sectional study explored the association between Dietary Inflammatory Index (DII) and chronic pain among 2581 American adults from NHANES data. The DII, ranging from - 4.98 to 4.69, reflects the inflammatory potential of the diet, with higher scores indicating greater pro-inflammatory capacity. Our findings showed no significant association between the continuous DII score and chronic pain prevalence. However, a nonlinear relationship emerged. When the DII was categorized, a significant association between higher DII scores (DII ≥ 2.5) and chronic pain prevalence was observed. The analysis uncovered a U-shaped pattern, with an inflection point at a DII score of - 0.9, indicating an association between both low and high levels of dietary inflammation are associated with higher pain prevalence. This nuanced interaction between dietary inflammation and chronic pain indicates the possibility of incorporating dietary modification into pain management strategies and underscores the need for further research into the long-term effects of diet on chronic pain.

Effective dose of intranasal remimazolam for preoperative sedation in preschool children: a dose-finding study using Dixon's up-and-down method.

Background: Most preschool children are distressed during anesthesia induction. While current pharmacological methods are useful, there is a need for further optimization to an "ideal" standard. Remimazolam is an ultra-short-acting benzodiazepine, and intranasal remimazolam for pre-induction sedation may be promising. Methods: This study included 32 preschool children who underwent short and minor surgery between October 2022 and January 2023. After pretreatment with lidocaine, remimazolam was administered to both nostrils using a mucosal atomizer device. The University of Michigan Sedation Score (UMSS) was assessed for sedation 6, 9, 12, 15, and 20 min after intranasal atomization. We used Dixon's up-and-down method, and probit and isotonic regressions to determine the 50% effective dose (ED50) and 95% effective dose (ED95) of intranasal remimazolam for pre-induction sedation. Results: Twenty-nine pediatric patients were included in the final analysis. The ED50 and ED95 of intranasal remimazolam for successful pre-induction sedation, when processed via probit analysis, were 0.65 (95% confidence interval [CI], 0.59-0.71) and 0.78 mg/kg (95% CI, 0.72-1.07), respectively. In contrast, when processed by isotonic regression, they were 0.65 (95% CI: 0.58-0.72 mg/kg) and 0.78 mg/kg (95% CI: 0.69-1.08 mg/kg), respectively. At 6 min after intranasal remimazolam treatment, 81.2% (13/16) of "positive" participants were successfully sedated with a UMSS ≧ 1. All the "positive" participants were successfully sedated within 9 min. Conclusion: Intranasal remimazolam is feasible for preschool children with a short onset time. For successful pre-induction sedation, the ED50 and ED95 of intranasal remimazolam were 0.65 and 0.78 mg/kg, respectively.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children.

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, ß-CrossLaps (ß-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between ß-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca2+, ß-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and ß- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while ß-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

Exploration of the utility of different doses of Qingfei Dayuan granules: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.

Dose-effect relationship of linear accelerator based stereotactic radiotherapy for brain metastases.

OBJECTIVE: The purpose of this study is to reveal the dose-effect relationship of linear accelerator (LINAC)-based stereotactic radiotherapy (SRT) in patients with brain metastases (BM). MATERIALS AND METHODS: The PubMed, Cochrane, and Web of Science databases were used to identify studies that reported local tumour control after LINAC-based SRT in patients with BMs. Studies of other approaches that could affect local tumour control, such as whole brain radiotherapy, targeted therapy, and immunotherapy, were excluded from the dose-effect relationship analysis. Data extracted included patient and treatment characteristics and tumour local control. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as the statistically significant level. RESULTS: After literature screening, 19 eligible studies involving 1523 patients were included in the probit model regression analysis. There was no significant dose-effect relationship between nominal BED10 and peripheral BED10 versus 12-month local control probability. There were significant dose effect relationships between the centre BED10 and the average BED10 versus the 12-month local control probability, with P values of 0.015 and 0.011, respectively. According to the model, the central BED10 and the average BED10 corresponding to probabilities of 90% 12-month local control were 109.2 GyBED10 (95% confidence interval (CI): 88.7-245.9 GyBED10) and 87.8 GyBED10 (95% CI: 74.3-161.5 GyBED10), respectively. A 12-month local control rate of 86.9% (95% CI: 81.7-89.7%) and 85.5% (95% CI: 81.2-89.2%) can be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively. CONCLUSION: For patients with BM treated with LINAC-based SRT, more attention should be given to the central and average doses of PTV. A clear definition of the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Dose-effect of long-snake-like moxibustion for chronic fatigue syndrome: a randomized controlled trial.

BACKGROUND: The dose-effect relationship of Long-snake-like moxibustion for chronic fatigue syndrome (CFS) remains poorly understood. In order to address this gap, we designed this trial to assess the association between different treatment duration of Long-snake-like moxibustion and its effects on CFS based on the combination measurements of the subjective patient-reported scales with objective medical infrared imaging technology─Thermal Texture Maps (TTM). METHODS: From December 2020 to January 2022, 60 female CFS patients were recruited and equally allocated to two groups: Group A, receiving 60-min Long-snake-like moxibustion per treatment, and Group B, receiving 30-min Long-snake-like moxibustion per treatment. The treatment was administered 3 times per week for a total of 4 weeks. The primary outcome was defined as the improvement of symptoms measured by the Fatigue scale-14 (FS-14), and secondary outcomes were designated as the improvement in Symptoms Scale of Spleen-Kidney Yang Deficiency, Self-rating depression scale, and Self-rating anxiety scale. TTM scanning was employed twice for CFS patients (before and after 4-week treatment) and once for Healthy control subjects (HCs). RESULTS: At week 4, the scores of FS-14 and Symptoms Scale of Spleen-Kidney Yang Deficiency in Group A were significantly lower than those in Group B (physical fatigue: 5.00 vs. 6.00, with 95%CI - 2.00 to 0.00, p = 0.003; FS-14 total score: 8.00 vs. 9.00, with 95%CI - 3.00 to 0.00, p = 0.012; total score of Symptoms Scale of Spleen-Kidney Yang Deficiency: 9.80 vs. 13.07, with 95%CI - 5.78 to - 0.76, P = 0.012). All thermal radiation values of the two groups increased, and statistical differences in ΔTs between Group A and HCs were not obtained. More significant correlations between symptoms improvements and ΔT changes were observed in Group A, and its ΔT changes in Upper Jiao, Shenque (CV8), Zhongwan (CV12), Danzhong (CV17), Zhiyang (GV9), Dazhui (GV14), upper arm, thoracic segments, lumbar segments, renal region, popliteal fossa strongly correlated with the improvement of Spleen-Kidney Yang Deficiency symptoms. CONCLUSIONS: In the same course of treatment, the positive dose-effect relationship was found between the treatment duration of Long-snake-like moxibustion and CFS effect assessment. 60-min Long-snake-like moxibustion per treatment were associated with optimal clinical response and TTM improvement. TRIAL REGISTRATION: Chinese Clinical Trail Registry (No. ChiCTR2000041000, date of registration: 16 December 2020), http://www.chictr.org.cn/showproj.aspx?proj=62488.

Ecotoxicological effects of soil lithium on earthworm Eisenia fetida: Lethality, bioaccumulation, biomarker responses, and histopathological changes.

Lithium is an emerging environmental contaminant in the current low-carbon economy, but little is known about its influences on soil invertebrates. In this work, earthworm Eisenia fetida was exposed to soils treated with different levels of lithium for 7 d, and multiple ecotoxicological parameters were evaluated. The results showed that mortality was dose-dependent and lithium's median lethal content (LC50) to earthworm was respectively 865.08, 361.01, 139.36, and 94.95 mg/kg after 1 d, 2 d, 4 d, and 7 d exposure. The bioaccumulation factor based on measured exogenous lithium content (BFexog) respectively reached 0.79, 1.01, 1.57, and 1.27 with the increasing lithium levels, suggesting that lithium accumulation was averagely 1.16-fold to the exogenous content, and 74.42%∼81.19%, 14.54%∼18.23%, and 2.26%∼8.02% of the lithium in exposed earthworms were respectively retained in the cytosol, debris, and granule. Then, lithium stress stimulated the activity of superoxide dismutase, peroxidase, catalase, acetylcholinesterase, and glutathione S-transferase as well as the content of 8-hydroxy-2-deoxyguanosine and metallothionein, indicating the generation of oxidative damage, while the content of reactive oxygen species and malondialdehyde decreased. Finally, lithium introduced histopathological changes, including the degenerated seminal vesicle and muscle hyperplasia, as well as high or extreme nuclear DNA damage. This study confirmed the obvious bioaccumulation and toxic effects caused by soil lithium via ecotoxicological data, providing new theoretical insights into understanding the ecological risks of lithium to soil invertebrates.

Exploring the Dose-Effect Relationship of Bifidobacterium longum in Relieving Loperamide Hydrochloride-Induced Constipation in Rats through Colon-Released Capsules.

Constipation is a common disease affecting humans. Bifidobacterium longum is reportedly effective in relieving constipation. Current studies generally focus on the dose-response relationship of oral doses; however, the dose-effect relationship of B. longum in the colon, which is the primary site where B. longum exerts constipation-relieving effects, to treat constipation has not been studied. Herein, three strains of B. longum (FGSZY6M4, FJSWXJ10M2, and FSDJN6M3) were packaged in colon-released capsules to explore the dose-effect relationship in the colon. For each strain, three groups of capsules (104, 106, and 108 CFU/capsule, respectively) and one group of free probiotics (108 CFU/mL) were used to explore the colonic dose effect of B. longum. The results showed that the three strains of B. longum improved fecal water content and promoted intestinal motility by regulating gastrointestinal peptide (MTL, GAS, and VIP), aquaporin-3, and 5-hydroxytryptamine levels while promoting gastrointestinal motility and relieving constipation by regulating the intestinal flora composition of constipated rats and changing their metabolite content (short-chain fatty acids). Among the three free bacterial solution groups (108 CFU/mL), FGSZY6M4 was the most effective in relieving constipation caused by loperamide hydrochloride in rats. The optimal effective dose of each strain was 6M4 (104 CFU/day), 10M2 (106 CFU/day), and S3 (108 CFU/day) of the colon-released capsules. Therefore, for some effective strains, the dose of oral probiotics can be reduced by colon-released capsules, and constipation can be relieved without administering a great number of bacterial solutions. Therefore, investigating the most effective dose of B. longum at the colon site can help to improve the efficiency of relieving constipation.

[Dose-effect relationship and precise treatment of acupuncture：viewing from translational medicine].

The acupuncture treatment scheme contains several key elements including acupoint selection and prescription, duration of needle retention, treatment frequency, needling manipulation technique, etc. which have, in precision degree, an important influence on the clinical efficacy, and their precise determination needs the guidance of the dose-effect relationship of acupuncture stimulation. In the present article, we discuss the basic concept and content of the dose-effect relationship of acupuncture and analyze its relationship with the precise treatment scheme. The precision and standardization of clinical treatment scheme of acupuncture are definitely not the negation of rich clinical experience, but rather, they are the transcendence of rich clinical experience. The dose-effect relationship of acupuncture is the rule that the acupuncture effect changes with the quantitative change of each key element, and its main contents include: the dose-effect relationship of acupoint prescription, the dose-effect relationship of needling manipulation, and the time-effect relationship of acupuncture.

Dose-effect relationship of different acupuncture courses on chronic insomnia disorder: study protocol for a randomized controlled trial.

Background: Chronic insomnia disorder (CID) is increasing in prevalence year by year, is long lasting, and potentially risky. Acupuncture has been widely used in the clinical management of this condition. However, there is still a lack of direct evidence on the dose-effect relationship between different acupuncture courses and clinical efficacy. To identify this relationship, we will design a randomized controlled trial to clarify the difference in efficacy of different acupuncture courses for CID. Methods and design: This is a prospective, parallel, single center randomized controlled trial. Two hundred and one participants with CID will be randomly divided into three groups (Group A, Group B, and Group C). The three groups will be given acupuncture therapy for 4, 6, and 8 weeks, three sessions per week, with at least 1 day between sessions. Follow-up will continue until the third month after the end of treatment. The primary outcome is the Insomnia Severity Index (ISI), and secondary outcomes include percentage of ISI < 8 points, the Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Fatigue Severity Scale (FSS), medication use, and safety. Discussion: This study is expected to provide direct evidence for the optimal treatment cycle of acupuncture for CID, as well as to facilitate health economic evaluation. Clinical trial registration: https://clinicaltrials.gov/, identifier [ChiCTR2300073711].

Impact of lead oxide nanoparticle exposure on the polarization of microglia cells in mouse hippocampus / 中国职业医学

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Effect of histone H4 on polarization of alveolar macrophages in mice with acute respiratory distress syndrome / 中国职业医学

Objective To investigate the role of histone H4 in the polarization of alveolar macrophages (AM) in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in mice. Methods i) The specific pathogen free male C57BL/6 mice were randomly divided into control group and 2, 4, 6 and 8 mg/kg LPS groups, with six mice in each group. The mice in the LPS groups were intratracheally administered LPS according to their respective doses, while the mice in the control group received an equivalent volume of 0.9% saline. After 12 hours, the arterial blood gas was analyzed, and the pulmonary edema and histopathological changes in lung tissues of mice in each group were observed. The level of histone H4 in bronchoalveolar lavage fluid (BALF) of mice was detected using enzyme-linked immunosorbent assay , and mice AMs of the five group were isolated using adherent method. ii) AMs from normal mice were isolated using adherent method and randomly divided into control group, histone H4 injury group, BALF injury group and anti-histone H4 antibody (anti-H4) intervention group. In the histone H4 injury group, AMs were treated with histone H4 at a final concentration of 20 mg/L. In the BALF injury group and anti-H4 intervention group, AMs were treated with 200 μL BALF supernatant from mice intratracheally administered 6 mg/kg body weight LPS, with the latter group treated with 25 mg/L anti-H4 antibody. The control group AMs were treated with phosphate-buffered saline. iii) After 12 hours of stimulation, the cells were collected, and the relative expression of tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), differentiation antigen 206 (Cd206) and arginase 1 (Arg1) in AMs was detected using real-time quantitative polymerase chain reaction. Results i) Compared with the control group, mice in all four LPS groups exhibited rapid breathing, inflammatory reaction and lung edema in lung tissues, which were aggravated in a dose-dependent manner. The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen in mice decreased with the increase of LPS dose (P<0.05). The wet/dry weight ratio of lung, the level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs increased with the increase of LPS dose (all P<0.05). The mice in the 6 and 8 mg/kg LPS groups developed ARDS. The level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs of mice in 6 and 8 mg/kg LPS groups were higher than those in the other three groups (all P<0.05). ii) The relative expression of Tnfa and Il1b mRNA increased (both P<0.05), and the relative expression of Cd206 and Arg1 mRNA decreased (both P<0.05) in AMs of histone H4 injury group and BALF injury group compared with the control group. Compared with BALF injury group, the relative mRNA expression of Tnfa and Il1b in AMs of anti-H4 intervention group decreased (both P<0.05), while the relative expression of Arg1 mRNA increased (P<0.05). Conclusion LPS can induce a dose-dependent increase in histone H4 levels in BALF in mice. Histone H4 drives the development of ARDS by activating AMs to M1 polarization. Antagonizing histone H4 to interfere with AM polarization to M1 could be a target for the treatment of ARDS.

Analyzing the characteristics and influencing factors of high frequency hearing loss among noise-exposed workers in an urban rail transit enterprise / 中国职业医学

{L-End}Objective To analyze the characteristics of hearing loss and the influencing factors of high-frequency hearing loss (HFHL) among noise-exposed workers in an urban rail transit enterprise over five consecutive years. {L-End}Methods A total of 1 268 noise-exposed workers, who exposed to the average noise intensity of <85.0 dB(A), in an urban rail transit enterprise was selected as the research subjects using a judgment sampling method. The pure-tone audiometry results from 2019 to 2023 were collected to analyze the result of hearing loss. The influencing factors of HFHL (average hearing threshold ≥40.0 dB at high frequencies in both ears) were analyzed using the generalized estimating equations (GEE). {L-End}Results The detection rates of threshold elevations at frequencies of 0.5-6.0 kHz increased with increasing frequency from 2019 to 2023 (all P<0.01), with the highest detection rate at 6.0 kHz. The detection rate of speech frequency hearing loss (hearing threshold weighted value≥26.0 dB in the better ear) was 0.1%, 0.0%, 0.4%, 0.2%, and 0.2%, respectively. The detection rate of HFHL from 2019 to 2023 was 2.4%, 2.8%, 2.8%, 2.1%, and 2.8%, respectively. The GEE analysis results showed that the risk of HFHL of the workers in 2022 and 2023 was lower than that in 2019 (all P<0.01), with the odds ratios and 95% confidence intervals ［OR (95%CI)］ of 0.57 (0.41-0.81) and 0.65 (0.48-0.87), respectively. The risk of HFHL was higher among vehicle maintenance worker than train drivers (P<0.05), with OR (95%CI) of 2.37 (1.18-4.77). The risk of HFHL increased with age and length of service among the workers (all P<0.05), with the OR (95%CI) of 2.05 (1.22-3.46) and 1.69 (1.12-2.54), respectively. No interaction was found between type of job and age, type of job and length of service, or age and length of service in the risk of HFHL among the research subjects(all P<0.05). {L-End}Conclusion Noise exposure below the national occupational exposure limits can lead to hearing loss in noise-exposed workers of urban rail transit enterprises, possibly affecting the hearing threshold at 6.0 kHz first. The influencing factors for HFHL in workers of rail transit are age, length of service, and type of job. There is a dose-effect relationship with age and length of service.

Association of maternal TSH and neonatal metabolism: A large prospective cohort study in China.

Aims: Neonatal metabolites are very important in neonatal disease screening, and maternal thyroid hormones play an important role in fetal and neonatal health. Our study aimed to explore the association of maternal thyroid hormones with neonatal metabolites and identify an important time windows. Methods: Pregnant women were recruited in Jinan Maternity and Child Care Hospital and followed up until delivery. Multivariate generalized linear regression models (GLMs) and restricted cubic spline (RCS) regression analysis models were used to investigate the associations of maternal TSH and FT4 with neonatal metabolites. Results: In total, 6,653 pairs of mothers and newborns were enrolled in our study. We identified 5 neonatal metabolites, including arginine/ornithine (Arg/Orn), C14:1/C2, C18:1, C3DC+C4OH and C8:1, that were significantly associated with maternal serum TSH during the whole pregnancy (P < 0.05), especially in the first trimester. Moreover, 10 neonatal metabolites were significantly associated with maternal serum FT4 (P < 0.05), most of which had positive correlations with maternal FT4 in the first trimester (P < 0.05). Some neonatal metabolites also had linear or nonlinear dose-effect relationships with maternal serum TSH and FT4 during the whole pregnancy, particularly in the first trimester. Conclusions: Our study, for the first time, provides epidemiological evidence that maternal serum TSH and FT4, especially during the first trimester, are associated with linear or nonlinear variations in neonatal metabolites. Efforts to identify newborn metabolism levels should carefully consider the effects of maternal thyroid function.

Dose-effect relationship of stereotactic body radiotherapy in non-small cell lung cancer patients.

OBJECTIVE: To establish the dose effect relationship between the dose parameters of stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) and the local tumor control rate. MATERIALS AND METHODS: A comprehensive literature search was conducted using PubMed, the Web of Science and the Cochrane databases to determine the articles treated with SBRT in early-stage NSCLC. Original studies with complete prescription dose information, tumor local control rate and other important parameters were screened and reported. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as a statistically significant level. RESULTS: After literature screening, 22 eligible studies were included in probit model regression analysis, involving 1861 patients. There is no significant dose effect relationship between nominal BED10 and peripheral BED10 versus 3 years local control probability. There were significant dose effect relationships between the center BED10 and the average BED10 versus the 3 years local control probability, with P values are 0.001 and < 0.0001, respectively. According to the results of this model, the 3 years local control rate of 90.5% (87.5-92.1%) and 89.5% (86.7-91.0%) can be expected at the center BED10 of 180 Gy or the average BED10 of 140 Gy, prospectively. CONCLUSIONS: For NSCLC treated with SBRT, more attention should be paid to the central dose and average dose of PTV. A set of clear definition in the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Bromophenol Induced Multiple Stress Responses in Rice Plants: Impact of Doses and Congener Structures.

Bromophenols (BPs) have both natural and artificial sources in the environment and are frequently detected in plants. Herein, the ubiquitous 2,4,6-TriBP was hydroponically exposed to rice seedlings at two concentrations (0.2 and 2.0 mg/L) to characterize the dose-dependent abiotic stress responses of rice plants to BPs. The 2,4,6-TriBP induced oxidative damage to rice roots and subsequently inhibited plant transpiration and growth at the end of exposure in both concentrations. Moreover, the gene expression of OsUGT72B1 and the activity of glycosyltransferases of exposed rice roots were 2.36-to-4.41-fold and 1.23-to-1.72-fold higher than that of the blank controls after 24 h, following the formation of glycoconjugates in response to 2,4,6-TriBP exposure. It was notable that the glycosylation rates also showed a dose-effect relationship in rice roots. One and six glycoconjugates of 2,4,6-TriBP were detected in 0.2 and 2.0 mg/L exposure groups, respectively. Considering the detected species of glycoconjugates for four other types of BPs, the numbers of bromine atoms were found to dramatically affect their glycosylation process in rice plants. These results improve our fundamental understanding of the impact of congener structures and exposure concentrations of organic contaminants on the glycosylation process in response to phytotoxicity.

The response of bacterial community to UVB was significantly different between immature periphyton and mature periphyton, but not for physiological indicators.

Periphyton has important ecological functions. It can even exist in environments with strong ultraviolet radiation. However, knowledge of periphyton under ultraviolet is limited, which limits the understanding and application of periphyton in environments with high ultraviolet radiation. In this study, immature periphyton (IMP) and mature periphyton (MP) under ultraviolet B (UVB) irradiation were investigated and compared in terms of physiological characteristics and bacterial community. Analysis of the physiological characteristics showed that the response patterns of IMP and MP to UVB were similar. IMP and MP could adapt to UVB of 1 W/m2 well. However, high-intensity UVB (2 and 3 W/m2) reduced the periphyton biomass, inhibited photosynthesis and antioxidant enzyme activity and caused severe lipid peroxidation in both IMP and MP. Integrated Biological Response (IBR) analysis and toxicological model fitting showed that the ED50 values of UVB for IMP and MP were 1.25 and 1.50 W/m2, respectively. 16 S rRNA gene analysis showed that in both IMP and MP, bacterial community composition, assembly and function were affected by UVB. In addition, the response of the bacterial community in IMP to UVB was stronger than that in MP. The diversity of the IMP community was inhibited by UVB, but that of the MP community was not. Proteobacteria and Deinococcus-Thermus are key microorganisms responsible for tolerance to UVB stress. Neutral community model fitting showed that both UVB and the development process caused the determinism of bacterial succession. However, UVB may weaken the deterministic process caused by development. Functional prediction showed that many metabolic functions of periphyton were inhibited by UVB in IMP and MP. However, UVB caused different changes (enhancement or inhibition) of some ecological functions in them. This study provides valuable information for understanding periphyton in environments with UVB radiation, which may be used to improve the application of periphyton in these environments.

[Effective Dose of Prophylactic Norepinephrine for Preventing Hypotension under Combined Spinal and Epidural Anesthesia during Cesarean Section in Singleton Versus Twin Pregnancies].

Objective: To determine and compare the 90% effective dose (ED 90) of prophylactic infusion of norepinephrine for preventing hypotension during combined spinal-epidural anesthesia for cesarean section in singleton versus twin pregnancies. Methods: A randomized controlled trial was conducted, enrolling 200 pregnant women, 100 of which were of singleton pregnancies while the other 100 were of twin pregnancies, at West China Second University Hospital, Sichuan University between November 3, 2020 and June 2, 2021. All 200 subjects were to have Cesarean section under combined spinal-epidural anesthesia. By using a random number table, they were randomly assigned to five groups, receiving norepinephrine at the infusion dosage of 0.025, 0.050, 0.075, 0.100, and 0.125 µg/(kg·min), with 20 subjects of singleton pregnancy and 20 subjects of twin pregnancy in each group. Norepinephrine infusion started when the anesthesiologist initiated the spinal anesthetic injection and lasted until the delivery of the fetus. The primary outcome measure was the incidence of maternal hypotension during combined spinal-epidural anesthesia, up until the delivery of the fetus. Survival analysis, with survival being defined as not having hypotension, of the incidence of hypotension among the subjects was conducted. Probit regression was used to determine the ED 90 of norepinephrine, as well as the corresponding 95% confidence interval ( CI), for preventing hypotension during cesarean delivery under combined spinal-epidural anesthesia in women with singleton and twin pregnancies. Results: There was no significant difference in the baseline data or the anesthesia and operation data between pregnant women of singleton pregnancy and those of twin pregnancy ( P>0.05). In singleton pregnant women receiving 0.025, 0.05, 0.075, 0.1 and 0.125 µg/(kg·min) of norepinephrine, the incidence of hypotension was 50% (10/20), 35% (7/20), 20% (4/20), 10% (2/20) and 5% (1/20), respectively. The estimated ED 90 of prophylactic norepinephrine for preventing hypotension during anesthesia was 0.100 (95% CI, 0.082-0.130) µg/(kg·min). In twin pregnant women receiving 0.025, 0.05, 0.075, 0.1 and 0.125 µg/(kg·min) of norepinephrine, the corresponding incidence of hypotension was 60% (12/20), 20% (4/20), 20% (4/20), 10% (2/20) and 5% (1/20). The estimated ED 90 of norepinephrine for preventing hypotension during anesthesia was 0.098 (95% CI, 0.080-0.127) µg/(kg·min). Survival analysis showed significant difference in the incidence of hypotension among the five groups receiving different infusion doses in singleton pregnancy subjects, and the same is true of the twin pregnancy subjects ( P<0.05). The incidence of reactive hypertension increased with increasing dosage of norepinephrine in both singleton pregnancy subjects and twin pregnancy subjects ( P<0.05). There was no significant difference in the incidence of other maternal adverse reaction or in neonatal outcomes in singleton and twin pregnancy subjects receiving different dosage of norepinephrine ( P>0.05). The gestational weeks, weight, and BMI were significantly different ( P<0.05), while the other characteristics, including age and height, were comparable ( P>0.05) between singleton and twin pregnancy subjects receiving norepinephrine at the same dosage. There was no significant difference in the incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, and dizziness between singleton and twin pregnancy subjects receiving the same dose ( P>0.05). Survival analysis displayed no significant difference in the incidence of hypotension between singleton and twin pregnancy subjects receiving norepinephrine at the same dosage ( P>0.05). There was no significant difference in the ED 90 of norepinephrine between women with singleton pregnancies and those with twin pregnancies ( P>0.05). Conclusion: There was no significant difference in the ED 90 of norepinephrine for preventing hypotension during combined spinal-epidural anesthesia between women with singleton pregnancy and those with twin pregnancy. Interference of other factors, including gestational age, body mass, and BMI should be considered in clinical practice.

The median effective doses of propofol combined with two different doses of nalbuphine for adult patients during painless gastroscopy.

Objective: Propofol is the most widely administered intravenous anesthetic to induce deep sedation for gastroscopy procedures. Coadministration of nalbuphine can provide analgesia and sedation to patients experiencing visceral pain, thereby decreasing the amount of propofol needed and reducing the risk of propofol-induced adverse events. We carried out this study to determine the median effective dose (ED50) of propofol in combination with different dosages of nalbuphine and the optimal dosage of nalbuphine during painless gastroscopy. Methods: We recruited sixty-five patients aged 18-60 years who underwent elective painless gastroscopy. A total of sixty-one patients were allocated randomly to the N1 group (nalbuphine 0.1 mg/kg) or N2 group (nalbuphine 0.15 mg/kg). Three minutes after administration of nalbuphine, patients received a preset dose of propofol at 2.0 mg/kg with a dose gradient of 0.2 mg/kg according to Dixon's "up-and-down" method. The primary outcome was the ED50 of propofol in combination with nalbuphine. Hemodynamic parameters, recovery time, pain score, and adverse events were recorded as secondary outcomes. Results: The ED50 of propofol in the N2 group was significantly lower than that observed in the N1 group (p < 0.01). Using probit analysis, the ED50 and ED95 of propofol were 1.632 mg/kg and 2.759 mg/kg in the N1 group and 1.111 mg/kg and 2.243 mg/kg in the N2 group, respectively. The incidence of hypotension in the N2 group was lower than that in the N1 group (p < 0.05), and the recovery time was shorter than that of the N1 group (p < 0.05). Conclusion: In adult patients, 0.15 mg/kg nalbuphine led to a significant reduction in the ED50 and ED95 of propofol during gastroscopy. This dose of nalbuphine also reduced the incidence of hypotension and shortened the recovery time. Therefore, nalbuphine (0.15 mg/kg) combined with propofol is a safe option for enhancing recovery after painless gastroscopy in adult patients. Clinical Trial Registration: [https://www.chictr.org.cn/edit.aspx?pid=126699&htm=4], identifier [ChiCTR2100053204].