Biointerface topography mediates the interplay between endothelial cells and monocytes

Endothelial cell (EC) monolayers located in the inner lining of blood vessels serve as a semipermeable barrier between circulating blood and surrounding tissues. The structure and function of the EC monolayer affect the recruitment and adhesion of monocytes, which plays a pivotal role in the development of inflammation and atherosclerosis. Here we investigate the effect of material wrinkled topographies on the responses of human umbilical vein endothelial cells (HUVECs) and adhesion of monocytes to HUVECs. It is found that HUVEC responses are non-linearly mediated by surface topographies with different dimensions. Specifically, more cell elongation and better cell orientation on the wrinkled surface with a 3.5 μm amplitude and 10 μm wavelength (W10) are observed compared to other surfaces. The proliferation rate of HUVECs on the W10 surface is higher than that on other surfaces due to more 5-ethynyl-2′-deoxyuridine (EdU) detected on the W10 surface. Also, greater expression of inflammatory cytokines from HUVECs and adhesion of monocytes to HUVECs on the W10 surface is shown than other surfaces due to greater expression of p-AKT and ICAM, respectively. This study offers a new in vitro system to understand the interplay between HUVEC monolayers and monocytes mediated by aligned topographies, which may be useful for vascular repair and disease modeling for drug testing

HORMETIC EFFECTS OF ACUTE METHYLMERCURY EXPOSURE ON GRP78 EXPRESSION IN RAT BRAIN CORTEX

This study aims to explore the expression of GRP78, a marker of endoplasmic reticulum (ER) stress, in the cortex of rat brains acutely exposed to methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA expression of Grp78 were detected by western blotting and real-time PCR, respectively. The results showed that a gradual increase in GRP78 protein expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6 mg/kg). Protein levels peaked in the 6 mg/kg group (p \u3c 0.05 vs. controls), decreased in the 8 mg/kg group, and bottomed below the control level in the 10 mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be implied that acute exposure to MeHg induced hormetic dose-dependent changes in Grp78 mRNA and protein expression, suggesting that activation of ER stress is involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78 protein expression to stimulate endogenous cytoprotective mechanisms

Efficacy and safety of traditional Chinese medicine adjuvant therapy for severe pneumonia: evidence mapping of the randomized controlled trials, systematic reviews, and meta-analyses

Background and Objective: Severe pneumonia is a critical respiratory disease with high mortality. There is insufficient evidence on the efficacy and safety of traditional Chinese medicine (TCM) adjuvant therapy for severe pneumonia. This study aims to identify, describe, assess, and summarize the currently available high-quality design evidence on TCM adjuvant therapy for severe pneumonia to identify evidence gaps using the evidence mapping approach.Methods: Systematic searches were performed on English and Chinese online databases (PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WanFang Data, CQVIP, and SinoMed) to identify papers from inception until August 2023 for inclusion into the review. Randomized controlled trials (RCTs), systematic reviews (SRs), and meta-analyses concerning TCM adjuvant therapy for severe pneumonia or its complications in adults were included. The risk of bias in RCTs was evaluated by using the Cochrane Handbook ROB tool. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Review (ROBIS) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, risk of bias, and evidence quality of SRs or meta-analyses, respectively. Then, a bubble plot was designed to visually display information in four dimensions.Results: A total of 354 RCTs and 17 SRs or meta-analyses met the inclusion criteria. The published RCTs had several flaws, such as unreasonable design, limited sample size, insufficient attention to non-drug therapy studies and syndrome differentiation, improper selection or use of outcome indicators, and failure to provide high-quality evidence. Sixteen SRs or meta-analyses of methodological quality scored “Critically Low” confidence. Twelve SRs or meta-analyses were rated as “High Risk.” Most outcomes were rated as “Low” evidence quality. We found that TCM combined with conventional treatment could improve the clinical total effective rate and the TCM syndromes efficacy. The combined approach could also shorten mechanical ventilation time, infection control time, and length of hospital and ICU stay; significantly reduce temperature, respiratory rate, heart rate, white blood cell counts, levels of C-reactive protein, procalcitonin, blood inflammatory factors, bacteriological response, and D-dimer; decrease CPIS, APACHE II score, and PSI score; improve pulmonary imaging features, arterial blood gas indicators (including arterial oxygen pressure, arterial oxygen saturation, and oxygen index), and lung function (including forced vital capacity and forced expiratory volume in the first second) for severe pneumonia compared with conventional treatment only (p < 0.05). There was no significant difference in adverse reactions and incidence of adverse events (p > 0.05). In addition, compared with conventional treatment only, most SRs or meta-analyses concluded that TCM combined with conventional treatment was “Beneficial” or “Probably beneficial.”Conclusion: TCM combined with conventional treatment had advantages in efficacy, clinical signs, laboratory results, and life quality outcomes of severe pneumonia, with no difference in safety outcomes compared with conventional treatment only. QingJin Huatan decoction is the most promising target, and Xuanbai Chengqi decoction has a “Probably beneficial” conclusion. XueBiJing injection and TanReQing injection are two commonly used Chinese herbal injections for treating severe pneumonia, and both are “Probably beneficial.” However, there was a need for multicenter RCTs with large sample sizes and high methodological quality in the future. In addition, the methodological design and quality of SRs or meta-analyses should be improved to form high-quality, evidence-based medical evidence and provide evidence for the effectiveness and safety of TCM adjuvant therapy for severe pneumonia

Percutaneous transforaminal endoscopic surgery combined with mini-incision OLIF and anterolateral screws rod fixation vs. MIS-TLIF for surgical treatment of single-level lumbar spondylolisthesis

ObjectiveOblique lumbar interbody fusion (OLIF) has been used to treat lumbar spine spondylolisthesis. However, it usually needs posterior pedicle screws fixation for biomechanical stability and possible posterior direct decompression for relieving neurologic symptoms. We use percutaneous transforaminal endoscopic surgery (PTES) combined with mini-incision OLIF and anterolateral screws rod fixation for surgical treatment of lumbar spondylolisthesis. The purpose of study is to evaluate the feasibility, efficacy, and safety of this method compared with minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF).MethodsFrom July 2016 to May 2018, 65 patients of lumbar spondylolisthesis (L2–4) with neurologic symptoms were treated using PTES combined with mini-incision OLIF and anterolateral screws rod fixation (31 cases, group A) or MIS-TLIF (34 cases, group B) in this study. Operative duration, blood loss, incision length, fluoroscopy frequency, and hospital stay are compared. Preoperative and postoperative visual analog scale (VAS) pain scores of back and legs, Oswestry disability index (ODI), intervertebral space height, lumbar lordotic angle, operative segmental lordotic angle, and complications are recorded. The fusion status is assessed according to Bridwell's fusion grades.ResultsThe VAS score of back and leg pain and ODI significantly dropped after surgery in both groups (p < 0.001). There was no statistical difference of back and leg VAS score and ODI between two groups except that back VAS scores in group A were significantly lower than that of group B immediately after surgery (p = 0.000). Group A had significantly more intervertebral space height and operative segmental lordotic angle than group B postoperatively (p = 0.022, p = 0.002). Twenty-three segments (74.2%) were grade I and 8 segments (25.8%) were grade II in group A; 20 segments (58.8%) were grade I and 14 segments (41.2%) were grade II in group B at a 2-year follow-up (p = 0.194). No difference was observed in the complication rate between the two groups (6.5% vs. 5.9%, p = 0.924).ConclusionThe long-term clinical efficacy and complication rates of both groups are comparable. PTES combined with mini-incision OLIF and anterolateral screws rod fixation is a good choice of minimally invasive surgery for lumbar spondylolisthesis, which hardly destroys the paraspinal muscles and bone structures