[Establishment of a predictive scoring model and preventive measures for bladder neck contracture after laparoscopic enucleation of the prostate with urethra preservation].

OBJECTIVE: To establish a predictive scoring model for bladder neck contracture (BNC) after laparoscopic enucleation of the prostate with preservation of the urethra (Madigan surgery) and explore the preventive measures against this postoperative complication. METHODS: We included 362 cases of BPH treated by laparoscopic Madigan surgery from January 2019 to March 2022 (45 with and 317 without postoperative BNC) in the training group and another 120 cases treated the same way in the verification group, collected the clinical data on the patients and evaluated the results of surgery. Using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression, we analyzed the risk factors for postoperative BNC and constructed a predictive scoring model for evaluation of the factors. RESULTS: Compared with the baseline, the IPSS, quality of life (QOL) score and postvoid residual urine volume (PVR) were significantly decreased (P < 0.05) while the maximum urinary flow rate (Qmax) remarkably increased (P < 0.05) in the BPH patients at 3 months after surgery. Eight non-zero characteristic predictors were identified by LASSO regression analysis. Multivariate logistic regression analysis showed that short clinical experience of the surgeon, concurrent prostatitis, bladder rinse solution temperature <34℃, catheter blockage, urethral balloon injection volume >40 ml and postoperative constipation were independent risk factors for postoperative BNC (P < 0.05). The best cut-off value was 2.36 points in both the training and the verification groups. The results of evaluation exhibited a high discriminability of the predictive scoring model. CONCLUSION: Laparoscopic Madigan surgery is a safe and effective method for the treatment of BPH. Short clinical experience of the surgeon, concurrent prostatitis, bladder rinse solution temperature <34℃, catheter blockage, water injected into the urethral balloon >40 ml and postoperative constipation were independent risk factors for postoperative BNC. The predictive scoring model constructed in this study has a good discriminability and is simple and feasible, contributive to the prediction of postoperative BNC in BPH patients undergoing laparoscopic Madigan surgery.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy.

Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.

XBAT31 regulates reproductive thermotolerance through controlling the accumulation of HSFB2a/B2b under heat stress conditions.

Heat shock transcription factors (HSFs) play a crucial role in heat stress tolerance in vegetative tissues. However, their involvement in reproductive tissues and their post-translational modifications are not well understood. In this study, we identify the E3 ligase XB3 ORTHOLOG 1 IN ARABIDOPSIS THALIANA (XBAT31) as a key player in the ubiquitination and degradation of HSFB2a/B2b. Our results show that the xbat31 mutant exhibits a higher percentage of unfertile siliques and decreased expression of HSPs in flowers under heat stress conditions compared to the wild type. Conversely, the hsfb2a hsfb2b double mutant displays improved reproductive thermotolerance. We find that XBAT31 interacts with HSFB2a/B2b and mediates their ubiquitination. Furthermore, HSFB2a/B2b ubiquitination is reduced in the xbat31-1 mutant, resulting in higher accumulation of HSFB2a/B2b in flowers under heat stress conditions. Overexpression of HSFB2a or HSFB2b leads to an increase in unfertile siliques under heat stress conditions. Thus, our results dissect the important role of the XBAT31-HSFB2a/B2b module in conferring reproductive thermotolerance in plants.

Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway.

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

MCU inhibition protects against intestinal ischemia‒reperfusion by inhibiting Drp1-dependent mitochondrial fission.

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.

Three-dimensional architecture of ESCRT-III flat spirals on the membrane.

The endosomal sorting complexes required for transport (ESCRTs) are responsible for membrane remodeling in many cellular processes, such as multivesicular body biogenesis, viral budding, and cytokinetic abscission. ESCRT-III, the most abundant ESCRT subunit, assembles into flat spirals as the primed state, essential to initiate membrane invagination. However, the three-dimensional architecture of ESCRT-III flat spirals remained vague for decades due to highly curved filaments with a small diameter and a single preferred orientation on the membrane. Here, we unveiled that yeast Snf7, a component of ESCRT-III, forms flat spirals on the lipid monolayers using cryogenic electron microscopy. We developed a geometry-constrained Euler angle-assigned reconstruction strategy and obtained moderate-resolution structures of Snf7 flat spirals with varying curvatures. Our analyses showed that Snf7 subunits recline on the membrane with N-terminal motifs α0 as anchors, adopt an open state with fused α2/3 helices, and bend α2/3 gradually from the outer to inner parts of flat spirals. In all, we provide the orientation and conformations of ESCRT-III flat spirals on the membrane and unveil the underlying assembly mechanism, which will serve as the initial step in understanding how ESCRTs drive membrane abscission.

Ghrelin alleviates intestinal ischemia-reperfusion injury by activating the GHSR-1α/Sirt1/FOXO1 pathway.

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.

Structures of the mumps virus polymerase complex via cryo-electron microscopy.

The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses (nsNSVs), while structures corresponding to these activities remain obscure. Here, we resolved two L-P complex conformations from the mumps virus (MuV), a typical member of nsNSVs, via cryogenic-electron microscopy. One conformation presents all five domains of L forming a continuous RNA tunnel to the methyltransferase domain (MTase), preferably as a transcription state. The other conformation has the appendage averaged out, which is inaccessible to MTase. In both conformations, parallel P tetramers are revealed around MuV L, which, together with structures of other nsNSVs, demonstrates the diverse origins of the L-binding X domain of P. Our study links varying structures of nsNSV polymerase complexes with genome replication and transcription and points to a sliding model for polymerase complexes to advance along the RNA templates.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

Bibenzyl-Phenylpropane Hybrids with Immunosuppressive Activities from Dendrobium Nobile Lindl.

Fifteen bibenyls and four fluorenones, including five new bibenzyl-phenylpropane hybrids, were isolated from the aerial part of Dendrobium nobile Lindl. Their structures were determined by spectroscopic methods. Bioassay on the LPS-induced proliferations of mouse splenic B lymphocytes, and Con A-induced T lymphocytes showed that compounds 1, 2, and 14 showed excellent immunosuppressive activities with IC50 values of 1.23, 1.01, and 3.87 µM, respectively, while compounds 3-4, 7, 10, 13, and 15 exhibited moderate immunosuppressive activities with IC50 values ranging from 6.89 to 14.2 µM.

Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

Regulation of metal homoeostasis by two F-group bZIP transcription factors bZIP48 and bZIP50 in rice.

Zinc (Zn) deficiency not only impairs plant growth and development but also has negative effects on human health. Rice (Oryza Sativa L.) is a staple food for over half of the global population, yet the regulation of Zn deficiency response in rice remains largely unknown. In this study, we provide evidence that two F-group bZIP transcription factors, OsbZIP48/50, play a crucial role in Zn deficiency response. Mutations in OsbZIP48/50 result in impaired growth and reduced Zn/Fe/Cu content under Zn deficiency conditions. The N-terminus of OsbZIP48/OsbZIP50 contains two Zn sensor motifs (ZSMs), deletion or mutation of these ZSMs leads to increased nuclear localization. Both OsbZIP48 and OsbZIP50 exhibit transcriptional activation activity, and the upregulation of 1117 genes involved in metal uptake and other processes by Zn deficiency is diminished in the OsbZIP48/50 double mutant. Both OsbZIP48 and OsbZIP50 bind to the promoter of OsZIP10 and activate the ZDRE cis-element. Amino acid substitution mutation of the ZSM domain of OsbZIP48 in OsbZIP50 mutant background increases the content of Zn/Fe/Cu in brown rice seeds and leaves. Therefore, this study demonstrates that OsbZIP48/50 play a crucial role in regulating metal homoeostasis and identifies their downstream genes involved in the Zn deficiency response in rice.

Sestrin2 reduces ferroptosis via the Keap1/Nrf2 signaling pathway after intestinal ischemia-reperfusion.

Sestrins are metabolic regulators that respond to stress by reducing the levels of reactive oxygen species (ROS) and inhibiting the activity of target of rapamycin complex 1 (mTORC1). Previous research has demonstrated that Sestrin2 mitigates ischemia-reperfusion (IR) injury in the heart, liver, and kidneys. However, its specific role in intestinal ischemia-reperfusion (IIR) injury remains unclear. To elucidate the role of Sestrin2 in IIR injury, we conducted an experimental study using a C57BL/6J mouse model of IIR. We noticed an increase in the levels of Sestrin2 expression and indicators associated with ferroptosis. Our study revealed that manipulating Sestrin2 expression in Caco-2 cells through overexpression or knockdown resulted in a corresponding decrease or increase, respectively, in ferroptosis levels. Furthermore, our investigation revealed that Sestrin2 alleviated ferroptosis caused by IIR injury through the activation of the Keap1/Nrf2 signal pathway. This finding highlights the potential of Sestrin2 as a therapeutic target for alleviating IIR injury. These findings indicated that the modulation of Sestrin2 could be a promising strategy for managing prolonged IIR injury.

Dysregulated inter-mitochondrial crosstalk in glioblastoma cells revealed by in situ cryo-electron tomography.

Glioblastomas (GBMs) are the most lethal primary brain tumors with limited survival, even under aggressive treatments. The current therapeutics for GBMs are flawed due to the failure to accurately discriminate between normal proliferating cells and distinctive tumor cells. Mitochondria are essential to GBMs and serve as potential therapeutical targets. Here, we utilize cryo-electron tomography to quantitatively investigate nanoscale details of randomly sampled mitochondria in their native cellular context of GBM cells. Our results show that compared with cancer-free brain cells, GBM cells own more inter-mitochondrial junctions of several types for communications. Furthermore, our tomograms unveil microtubule-dependent mitochondrial nanotunnel-like bridges in the GBM cells as another inter-mitochondrial structure. These quantified inter-mitochondrial features, together with other mitochondria-organelle and intra-mitochondrial ones, are sufficient to distinguish GBM cells from cancer-free brain cells under scrutiny with predictive modeling. Our findings decipher high-resolution inter-mitochondrial structural signatures and provide clues for diagnosis and therapeutic interventions for GBM and other mitochondria-related diseases.

Using autogenous tooth sticky bone graft repair mandibular third molar dentigerous cyst osseous defects.

BACKGROUND: Dentigerous cyst are most common odontogenic cyst and they frequently occur at the mandibular third molar. Their asymptomatic long medical history always resulted in severe bone resorption at the distal aspect of the adjacent second molar. BonMaker® ATB demonstrate an excellent autogenous bone graft candidacy. The aim of this study is to share a single team's experience of dentigerous cyst osseous defect repairing by applying autogenous tooth sticky bone graft. METHOD: In total, 18 patients with dentigerous cyst, which was arised from mandibular third molar unilaterally, were enrolled in this study. Enucleation of dentigerous cyst was performed extracting with involving teeth under general anesthesia. Autogenous tooth sticky bone graft was prepared using extracted tooth and autogenous fibrin glue. Subsequently, grafting was performed above covering with concentrate growth factors. Patients were followed up at sixth months. RESULTS: They were eleven male and seven female patients. Their ages ranged from 20 to 40 years, with a mean of 31 years. Primary wound healing of all sites was achieved in all the patients. Sixth months postoperative radiographic assessment show that dentigerous cysts osseous defects of seventeen patients were good bone filling and ossification. One patient occurred slight bone resorption at the distal aspect of the adjacent second molar. CONCLUSION: Within the limitation of sample size and retrospective nature of the present study, autogenous tooth sticky bone graft demonstrates one of the best alternative alveolar bones repairing graft.

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Acupuncture has a positive effect in the treatment of ischemic stroke (IS). A number of studies have confirmed that the role of acupuncture in the treatment of IS, which is closely related to its functions of regulating mitochondrial functions. In the present article, we review the mechanisms of acupuncture underlying improvement of mitochondria in the treatment of IS from 4 aspects： 1) protecting mitochondrial structure integrity, 2) regulative effect on mitochondrial functional activities, including regulating energy metabolism, reducing oxidative stress, suppressing calcium overload, and regulating mitochondrial membrane potential changes, 3) regulating mitochondrial quality control system, including promoting mitochondrial biosynthesis, regulating mitochondrial dynamics and apoptosis, and 4) regula-ting mitochondria-related apoptosis pathways. All of these may provide a theoretical basis for acupuncture in the treatment of IS and a reference for further research.

Machine learning-based nonlinear regression-adjusted real-time quality control modeling: a multi-center study.

OBJECTIVES: Patient-based real-time quality control (PBRTQC), a laboratory tool for monitoring the performance of the testing process, has gained increasing attention in recent years. It has been questioned for its generalizability among analytes, instruments, laboratories, and hospitals in real-world settings. Our purpose was to build a machine learning, nonlinear regression-adjusted, patient-based real-time quality control (mNL-PBRTQC) with wide application. METHODS: Using computer simulation, artificial biases were added to patient population data of 10 measurands. An mNL-PBRTQC was created using eight hospital laboratory databases as a training set and validated by three other hospitals' independent patient datasets. Three different Patient-based models were compared on these datasets, the IFCC PBRTQC model, linear regression-adjusted real-time quality control (L-RARTQC), and the mNL-PBRTQC model. RESULTS: Our study showed that in the three independent test data sets, mNL-PBRTQC outperformed the IFCC PBRTQC and L-RARTQC for all measurands and all biases. Using platelets as an example, it was found that for 20 % bias, both positive and negative, the uncertainty of error detection for mNL-PBRTQC was smallest at the median and maximum values. CONCLUSIONS: mNL-PBRTQC is a robust machine learning framework, allowing accurate error detection, especially for analytes that demonstrate instability and for detecting small biases.