Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients

Melatonin Mitigates Salt Stress in Wheat Seedlings by Modulating Polyamine Metabolism

Melatonin, a small molecular weight indoleamine molecule, is involved in various biological processes and responses to environmental cues in plants. However, its function in abiotic stress response and the underlying mechanisms is less clear. In this study, we investigated the effect of melatonin on wheat seedlings growth under salt stress condition. Exogenous melatonin pretreatment partially mitigated the salt-induced inhibition of whole-plant growth as judged from shoot dry weight, IAA content, leaf photosynthesis rate, maximum photochemistry efficiency of photosystem II, and chlorophyll. The mitigation was also observed in reduced accumulation of H2O2 in melatonin-pretreated wheat seedlings exposed to salt stress. Exogenous melatonin increased endogenous melatonin content by evaluating the levels of TaSNAT transcript, which encodes a key regulatory enzyme in the melatonin biosynthetic pathway. Furthermore, melatonin increased polyamine contents by accelerating the metabolic flow from the precursor amino acids arginine and methionine to polyamines; melatonin also decreased the degradation of salt-induced polyamines. Taken together, these results provide the evidence that melatonin mitigates salt stress mainly through its regulation on polyamine metabolism of wheat seedlings

Intraperitoneal ropivacaine and early postoperative pain and postsurgical outcomes after laparoscoipc herniorrhaphy in toddlers: a randomized clinical trial

Background Postoperative pain can cause physiological distress, postoperative complications, and extended lengths of hospitalized stay. In children, management of postoperative pain is still recognized as being inadequate. Objective The aim of this trial was to investigate the effects of intraperitoneal ropivacaine on postoperative pain, and recovery of bowel function and emetic events after laparoscopic herniorrhaphy in toddlers. Methods Seventy-six children aged from 9 months to 3 years were recruited between August 2013 and June 2014 at Tongji Hospital and randomly assigned into two groups. One group received intraperitoneal ropivacaine right before surgery and the control group received intraperitoneal saline. A standard combined general anesthesia procedure was performed under regular monitoring. Postoperative pain was assessed by the FLACC scale. Postoperative analgesic consumption, time to flatus, time to first stool, and postoperative emetic events were also recorded. Results When compared with the control group, children who received intraperitoneal ropivacaine experienced less pain 0–4 h after surgery [P < 0.001, difference in median FLACC (95% CI) for 2 h time point is 2.00 (0.87–3.13), for 4 h time point is 1.00 (0.55–1.45)]. In addition, the number of toddlers who received analgesia 0–24 h after surgery in the ropivacaine group was lower than that in the control group [P < 0.001, difference in proportions (95% CI) is 0.575 (0.3865–0.7638)]. Compared with the control group, time to flatus in ropivacaine group was also much shorter [21.1 h vs 16.7 h, P = 0.04, difference in mean (95% CI) is 4.4 (1.49–7.28)], and the time to first stool after surgery was earlier in the ropivacaine group [30.7 h vs 25.6 h, P = 0.003, difference in mean (95% CI) is 5.1 (1.78–8.45)]. Furthermore, the incidence of emetic events in the ropivacaine group was significantly lower than the control group [32.4% vs 11.1%, P = 0.03, difference in proportions (95% CI) is 0.212 (0.0246–0.4002)]. Conclusion The present results indicate that intraperitoneal ropivacaine reduces early postoperative pain and improves recovery after laparoscopic herniorrhaphy in toddlers. Therefore, IPLA is a good stratagem for postoperative pain management after laparoscopic surgery in toddlers

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

peer reviewedCurrent therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC

Damage analysis and lifetime prediction of round-link chain of mine-used scraper conveyor

A three-dimensional model of round-link chain of scraper conveyor was established by 3D software CATIA, contact-impact process of round-link chain was simulated and analyzed by finite element analysis software ANSYS. The analysis results show that stress is concentrated on the contact area between the round-link chains and joint between straight arm and curved arm when the round-link chain is in instant startup state. The joint between the straight arm and curved arm is the weakest area of the round-link chains, and it is easy to break, so stiffness was should be strengthened in design.The contact area between the round-link chains is rubbed continuously during transmission process, and the round-link chains are broken by repeated alternating load. Lifetime of the round-link chain was predicted by theory of fatigue damage accumulation, and draw conclusion: the minimum lifetime of the round-link chain is 49 073 cycles, position of the minimum lifetime is the joint between the straight arm and curved arm. The analysis results can provide basis for optimization design of the round-link chain

Meta-Analysis of the Effect of Nitric Oxide Application on Heavy Metal Stress Tolerance in Plants

Substantial single-species studies have reported the facility of nitric oxide (NO) in alleviating heavy metal-induced stress in plants. Understanding the mechanisms of NO-involved stress alleviation is progressing; however, a quantitative description of the alleviative capacity of NO against heavy metal stress is still lacking. We combined the results of 86 studies using meta-analysis to statistically assess the responses of heavy metal-stressed plants to NO supply across several metal stresses and plant families. The results showed that plant biomass was consistently improved following NO supply to metal-stressed plants. NO played an important role in mitigating oxidative damage caused by heavy metal stress by significantly stimulating the activities of antioxidant enzymes. Moreover, NO supply consistently increased the Ca, Fe, and Mg contents in both leaves and roots. Plant tissues accumulated less heavy metals when exposed to heavy metal stress after NO addition. Additionally, the best concentration of SNP (an NO donor) for hydroponic culture is in the range of 75–150 μM. We further confirmed that NO application can generally alleviate plant heavy metal stress and its action pathway. The results presented here can help guide future applications of NO as a plant growth regulator in agriculture and breeding plants for heavy metal stress tolerance

Cinnamaldehyde regulates mitochondrial quality against hydrogen peroxide induced apoptosis in mouse lung mesenchymal stem cells via the PINK1/Parkin signaling pathway

Background Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease without effective treatments. Mitochondrial dysfunction weakens the ability of mesenchymal stem cells (MSCs) to repair the distal lung epithelium, which is a probable pathogenesis of IPF. In previous research, we found that cinnamaldehyde (CA) can maintain the mitochondrial morphology of MSCs. Methods This present study evaluated the effect and mechanism of CA on murine lung MSCs using the hydrogen peroxide model. Antioxidant effects and mitochondrial function were determined using flow cytometry. The mRNA levels of mitochondrial dynamics and the expressions of autophagy-related proteins were also detected. Results CA can increase the levels of SOD, MMP and ATP, decrease the rate of ROS and apoptosis, and restore the mitochondrial structure. CA can also improve the mRNA expression of MFN1, MFN2, FIS1, DRP1, OPA1, and PGC-1α, increase the expression of LC3 II and p62 and promote the PINK1/Parkin signaling pathway. Our results demonstrated that CA can control mitochondrial quality and avoid apoptosis, which may be associated with the regulation of the PINK1/Parkin signaling pathway

Multiform-based Baduanjin exercise prevention and treatment for idiopathic pulmonary fibrosis: study protocol for a randomized controlled trial

Abstract Introduction In this study, we will combine the traditional Baduanjin with Yijin Jing and Wuqinxi to create an optimized Baduanjin exercise program with three different forms (vertical, sitting, and horizontal) to adapt to idiopathic pulmonary fibrosis (IPF) patients in vairous stages of the disease. The purpose of this study is to explore and compare the therapeutic effects of this multi-form Baduanjin, traditional Baduanjin, and resistance training on lung function and limb motor function in IPF patients. The goal of this study is to prove a novel optimal exercise prescription strategy of Baduanjin exercise for improving and protecting lung function in IPF patients. Methods/design A single-blind and randomized controlled trial is used to conduct this study, while the randomization list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. It will be strictly followed to blind the outcome assessors. and until the experiment’s conclusion, participants won’t know which group they are enrolled in. Patients between the ages of 35 and 80 who have stable diseases and have not regularly practiced Baduanjin exercise in the past will be included. They are divvied up into the following five groups at random: (1) The conventional care group (control group, CG), (2) The traditional Baduanjin exercise group (TG), (3) The modified Baduanjin exercise group (IG), (4) The resistance exercise group (RG) (5) The modified Baduanjin exercise combined with resistance exercise group (IRG). Those CG participants only received the usual treatment, while TC, IG, and RG participants exercised 1 h twice a day for 3 months. MRG participants will have a 3-month intervention with 1 h of Modified Baduanjin Exercise and 1 H of Resistance Training for each day. Every week, all groups underwent will supervis one-day training, with the exception of the control group. The Pulmonary Function Testing (PFT), HRCT, and 6MWT are the main outcome variables. The St. George Respiratory Questionnaire and mMRC are used as secondary outcome measures. Discussion This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. Because it consists of three forms, including vertical, sitting, and horizontal, it is more adaptable to the various disease stages and actual situations of IPF patients and may compensate for the shortcomings of conventional pulmonary rehabilitation and traditional Baduanjin. Trial registration Chinese Clinical Trial Registry, ChiCTR2200055559 . Registered on 12 January 2022

Estimation of Short-Term and Long-Term Ozone Exposure Levels in Beijing–Tianjin–Hebei Region Based on Geographically Weighted Regression Model

In recent years, ozone (O3) concentration has shown a decreasing trend in the Beijing–Tianjin–Hebei (BTH) region in China. However, O3 pollution remains a prominent problem. Accurate estimation of O3 exposure levels can provide support for epidemiological studies. A total of 13 variables were combined to estimate short- and long-term O3 exposure levels using the geographically weighted regression (GWR) model in the BTH region with a spatial resolution of 1 × 1 km from 2017 to 2020. Five variables were left in the GWR model. O3 concentration was positively correlated with temperature, wind speed, and SO2, whereas is was negatively correlated with precipitation and NO2. Results showed that the model performed well. Leave-one-out cross-validation (LOOCV) R2 for short- and long-term simulation results were 0.91 and 0.71, and the values for RMSE were 11.14 and 3.49 μg/m3, respectively. The annual maximum 8 h average O3 concentration was the highest in 2018 and the lowest in 2020. Decreasing concentrations of major precursors of O3 due to the regional joint prevention and control may be the reason. O3 concentration was high in the southeast of the BTH region, including in Hengshui, Handan, Xingtai and Cangzhou