Mechanistic insights into zinc oxide nanoparticles induced embryotoxicity via H3K9me3 modulation.

The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide nanoparticles (ZnONPs) exhibit the most significant toxicity to pre-implantation embryos in mice compared to other common NPs. In patients undergoing assisted reproduction technology (ART), a significant negative correlation was observed between Zn concentration and clinical outcomes. Therefore, this study explores the impact of ZnONPs exposure on pre-implantation embryonic development and its underlying mechanisms. We revealed that both in vivo and in vitro exposure to ZnONPs impairs pre-implantation embryonic development. Moreover, ZnONPs were found to reduce the pluripotency of mouse embryonic stem cells (mESCs), as evidenced by teratoma and diploid chimera assays. Employing multi-omics approaches, including RNA-Seq, CUT&Tag, and ATAC-seq, the embryotoxicity mechanisms of ZnONPs were elucidated. The findings indicate that ZnONPs elevate H3K9me3 levels, leading to increased heterochromatin and consequent inhibition of gene expression related to development and pluripotency. Notably, Chaetocin, a H3K9me3 inhibitor, sucessfully reversed the embryotoxicity effects induced by ZnONPs. Additionally, the direct interaction between ZnONPs and H3K9me3 was verified through pull-down and immunoprecipitation assays. Collectively, these findings offer new insights into the epigenetic mechanisms of ZnONPs toxicity, enhancing our understanding of their impact on human reproductive health.

Hyper-Selective Posterior Fusion is Recommended When the Modified S-Line is Positive in Lenke 5C Adolescent Idiopathic Scoliosis.

OBJECTIVE: Postoperative coronal decompensation and less fusion level are dilemmas and the proper selective posterior fusion (SPF) strategy should be investigated. We proposed a parameter, modified S-line, and aimed to investigate if the modified S-line could predict postoperative coronal decompensation in patients with Lenke 5C adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective radiographic study and Lenke 5C AIS patients undergoing SPF during the period from September 2017 to June 2021 were included. The modified S-line was defined as the line linking the centers of the concave-side pedicles of the upper end vertebra (UEV) and lower end vertebra (LEV) at baseline. A modified S-line tilt to the right is established as modified S-line+ (UEV being to the right of the LEV). The patients were further categorized into two groups: the Cobb to Cobb fusion group and the Cobb-1 to Cobb fusion group. Outcomes including thoracic Cobb angle, TL/L Cobb angle, coronal balance, upper instrumented vertebra (UIV) translation, lower instrumented vertebra (LIV) translation, UIV tilt, LIV tilt, LIV disc angle, thoracic apical vertebral translation, lumbar apical vertebral translation (L-AVT), L-T AVT ratio, L-T Cobb were measured at baseline, immediately after surgery, and the last follow-up. Radiographic parameters and the incidence of both proximal and distal decompensation between the two groups were compared by chi-square test. RESULTS: Among 92 patients, 48 were modified S-line+ and 44 were modified S-line-. Modified S-line+ status was identified as a risk factor for postoperative proximal decompensation (p = 0.005) during follow-up. In Cobb to Cobb group, a higher occurrence of proximal decompensation in individuals with modified S-line+ status (p = 0.001) was confirmed. Also, in the Cobb to Cobb group with baseline modified S-line+ status, patients presenting decompensation showed a significantly larger baseline of the UIV tilt and postoperative disc angle below the lower instrumented vertebra. However, In Cobb-1 group, the incidence of decompensation after surgery showed no association with baseline modified S-line tilt status (p = 0.815 and 0.540, respectively). CONCLUSION: The modified S-line could serve as an important parameter in surgical decision-making for Lenke 5C AIS patients. Cobb to Cobb SPF is not recommended with a modified S-line+ status, and the Cobb-1 to Cobb fusion may serve as a potential alternative.

Current research insights into the role of CTLA-4 in hepatitis B virus (HBV) infection.

Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV-specific T cells, which is regulated by various co-suppressor molecules. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is among these co-suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV-specific T cells. CTLA-4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA-4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA-4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA-4 may contribute to HBV infection, as well as the development of HBV-induced cirrhosis and hepatocellular carcinoma.

Mitochondrial genome transfer drives metabolic reprogramming in adjacent colonic epithelial cells promoting TGFß1-mediated tumor progression.

Although nontumor components play an essential role in colon cancer (CC) progression, the intercellular communication between CC cells and adjacent colonic epithelial cells (CECs) remains poorly understood. Here, we show that intact mitochondrial genome (mitochondrial DNA, mtDNA) is enriched in serum extracellular vesicles (EVs) from CC patients and positively correlated with tumor stage. Intriguingly, circular mtDNA transferred via tumor cell-derived EVs (EV-mtDNA) enhances mitochondrial respiration and reactive oxygen species (ROS) production in CECs. Moreover, the EV-mtDNA increases TGFß1 expression in CECs, which in turn promotes tumor progression. Mechanistically, the intercellular mtDNA transfer activates the mitochondrial respiratory chain to induce the ROS-driven RelA nuclear translocation in CECs, thereby transcriptionally regulating TGFß1 expression and promoting tumor progression via the TGFß/Smad pathway. Hence, this study highlights EV-mtDNA as a major driver of paracrine metabolic crosstalk between CC cells and adjacent CECs, possibly identifying it as a potential biomarker and therapeutic target for CC.

PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular carcinoma.

Background: The involvement of molecules associated with PANoptosis in hepatocellular carcinoma (HCC) is still not well understood. Methods: Various R packages were utilized to analyze within the R software. Data that was freely accessible was obtained from the databases of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Results: Here, we comprehensively explored the role of PANoptosis-related genes in HCC. The caspase 2 (CASP2) was identified as the interest gene for further analysis. We found that CASP2 is related to the poor prognosis and worse clinical features of HCC patients. Moreover, we explored the biological pathway CASP2 is involved in and found that CASP2 is associated with multiple carcinogenic pathways. Also, we noticed that CASP2 can significantly reshape the HCC immune microenvironment and affect the response rate of immunotherapy. Analysis of drug sensitivity suggested that individuals exhibiting elevated CASP2 levels may display increased susceptibility to doxorubicin and vorinostat while demonstrating resistance towards erlotinib, lapatinib, sunitinib, and temsirolimus. Meanwhile, we explored the single-cell distribution of CASP2 in the HCC microenvironment. To enhance the clinical application of CASP2 in HCC, we constructed a prognosis model using the molecules derived from CASP2, which demonstrated good efficiency in predicting patients prognosis. Moreover, in vitro experiments indicated that CASP2 can significantly inhibits cell proliferation, invasion and migration ability of HCC cells. Conclusions: Our study comprehensively explored the role of PANoptosis-related molecule CASP2 in HCC, which can provide directions for future studies.

Increased plasma lipocalin-2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease.

Lipocalin-2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel-based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Untargeted metabolomics reveals the regulatory effect of geniposidic acid on lipid accumulation in HepG2 cells and Caenorhabditis elegans and validation in hyperlipidemic hamsters.

BACKGROUND: Geniposidic acid (GPA) alleviates oxidative stress and inflammation in mice However, whether it can effectively regulate lipid accumulation and prevent hyperlipidemia requires further investigation. PURPOSE: This study combined the untargeted metabolomics of cells and a Caenorhabditis elegans model to evaluate the anti-hyperlipidemic potential of GPA by modulating oxidative stress and regulating lipid metabolism. A golden hamster model of hyperlipidemia was used to further validate the lipid-lowering effect and mechanism of action of GPA. METHODS: Chemical staining, immunofluorescence, and flow cytometry were performed to examine the effects of GPA on lipid accumulation and oxidative stress. Untargeted metabolomic analysis of cells and C. elegans was performed using ultra-performance liquid chromatography coupled with quadrupole electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap MS) to identify biomarkers altered by GPA action, analyze the affected metabolic pathways, and validate the mechanisms by which GPA regulates lipid metabolism and oxidative stress. A golden hamster model of hyperlipidemia was established to test the lipid-lowering effects of GPA. Body weight, biochemical markers, rate-limiting enzymes, and key proteins were assessed. Hematoxylin and eosin (H&E) and Oil Red O staining were performed. RESULTS: Phenotypic data showed that GPA decreased free fatty acid (FFA)-induced lipid buildup and high reactive oxygen species (ROS) levels, reversed the decrease in mitochondrial membrane potential (MMP), and increased the cellular reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio. GPA also reduces high glucose-induced lipid build-up and ROS production in C. elegans. Metabolomic analysis showed that GPA affected purine, lipid, and amino acid metabolism. Moreover, GPA inhibited xanthine oxidase (XOD), glutamate dehydrogenase (GLDH), fatty acid synthase (FAS), phosphorylation of P38 MAPK, and upregulated the expression of SIRT3 and CPT1A protein production to control lipid metabolism and produce antioxidant benefits in cells and golden hamsters. CONCLUSION: Current evidence suggests that GPA can effectively regulate lipid metabolism and the oxidative stress response, and has the potential to prevent hyperlipidemia. This study also provided an effective method for evaluating the mechanism of action of GPA.

Distance between the C2 vertical line and the femoral heads: a quasi-invariant global sagittal alignment parameter in both standing and sitting positions for asymptomatic adults.

Background: This study aimed to investigate whether the distance between the C2 vertical line and the femoral heads (C2-FH) is quasi-invariant for the sitting position. Methods: A cross-sectional, prospective study was conducted. A cohort of 59 asymptomatic volunteers was prospectively recruited between February 1, 2020, and February 31, 2020, at Nanjing Drum Tower Hospital of Nanjing University Medical School. The following radiographical parameters were evaluated: T4-T12 thoracic kyphosis (TK), cervical lordosis (CL), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA), T1-pelvic angle (TPA), and the C2-FH. The inclusion criteria were as follows: age between 18 and 35 years and no symptoms related to neck or back pain. The exclusion criteria were as follows: a history of any prior lower extremity or spine surgery; and a history of inflammatory arthritis, neuromuscular disorders, or congenital anomalies. Individuals were divided into the following 3 groups according to the percentile of ΔPT (PT difference between standing position and sitting position): group A (1-25% ΔPT, n=14), group B (25-75% ΔPT, n=30), and group C (75-100% ΔPT, n=15). Summary statistics calculated using analysis of variance (ANOVA) were used to provide 95% confidence intervals for measurement errors. The significance level of all statistical analyses was set as P < 0.05. Results: There was no significant difference in any of the parameters among the 3 groups in the standing position. In the sitting position, for different degrees of pelvic retroversion, there were significant differences between the 3 groups in the other parameters except for C2-FH (P=0.80; 95% CI: -20.486 to -3.893), CL (P=0.47; 95% CI: -5.645 to 4.964), TK (P=0.54; 95% CI: 17.058-25.1), and PI (P=0.44; 95% CI: 40.747-49.087). Surprisingly, C2-FH changed slightly among the 3 groups in both the standing (P=0.87) and sitting (P=0.80) positions. As ΔPT gradually increased, ΔSS, ΔLL, ΔSVA, ΔL1-L4, ΔL4-S1, ΔTPA, ΔPT/PI, and ΔPI-LL showed corresponding gradual changes (all P values <0.05). However, there was no significant difference in PI (P=0.39), CL (P=0.46), C2-FH (P=0.51), or TK (P=0.51). Conclusion: C2-FH is a quasi-invariant parameter in both the standing and sitting positions for asymptomatic adults. The mean value of C2-FH was -11.95 mm in the standing position and -1.01 mm in the sitting position. Stable C2-FH could serve as a reference during the surgical decision-making process in adult patients with spinal deformity and sagittal malalignment.

High-Strength Cell Sheets and Vigorous Hydrogels from Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells.

Natural cell derivates, including cell sheets (CSs) and matrix gels, have opened new opportunities to probe questions in tissue engineering and regenerative medicine. However, the potential of CSs and hydrogels generated by current protocols is still limited by the challenges of heterogeneity and weak mechanical properties. Here, we developed a 21 day long-term serum-free culture system for human embryonic stem cell (hESC)-derived immunity-and-matrix-regulatory cells (IMRCs). The CSs formed with IMRCs (IMRC-CSs) have a much greater secretion capacity for the extracellular matrix (ECM) and stronger mechanical properties than umbilical cord-derived MSCs, with a ten thousand-fold increase in elastin, a higher elastic modulus of 1500 kPa, a thicker structure of 20.59 µm, and a higher fiber count per square millimeter. The IMRC-CSs could promote corneal chemical injury repair and could be turned into injectable temperature-sensitive hydrogels for uterine adhesion repair via a decellularization process. In summary, we have established a high-strength CS platform using human pluripotent stem cells for the first time, providing a facile and scalable engineering approach for regenerative medicine.

Synthesis and Bioactivity Evaluation of Nepetaefolin F and Its Analogues.

Nepetaefolin F (5), an abietane diterpenoid, showed significant inhibitory activity against human cancer cells in vitro with an IC50 value of 6.3 µM. The syntheses of nepetaefolin F and its analogues are presented herein. The cytotoxicity against various cancer cell lines was evaluated; notably, the cyclopropanecarboxylate ester 42 displayed significant antitumor activity against MGC 803 cells with an IC50 value of 20.9 µM. Further studies revealed that 42 could upregulate the expression of p62, microtubule-associated protein 1 light-chain 3 ß (LC3 B-I), cleaved caspase-3, and cleaved caspase-9 and downregulate the expression of Beclin-1 and LC3B-II. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 42 could modulate multiple signaling pathways, especially for peroxisome proliferator-activated receptor (PPAR) and AMP-activated protein kinase (AMPK), which are closely related to autophagy. These results suggested that compound 42 is a promising lead by inhibiting cell proliferation and autophagy, as inducing cell apoptosis in MGC 803 cells.

Tumor-derived extracellular vesicles delivering TNF-α promotes colorectal cancer metastasis via the NF-kB/LAMB3/AKT axis by targeting SNAP23.

Accumulating evidence have demonstrated that cytokines are enriched in tumor-derived extracellular vesicles (EVs) and widely involved in tumorigenesis of various types of carcinomas, including colorectal cancer (CRC). Nevertheless, the functions of cytokines in EVs secreted from colorectal cancer cells remain largely unknown. In the present study, we found that TNF-α was elevated in EVs from CRC patient serum samples and CRC cell lines, of which the expression was associated with aggressive features of colorectal cancer. EV TNF-α secretion is dependent on synaptosome-associated protein 23 (SNAP23). Functional experiments revealed that EV TNF-α promotes CRC cell metastasis via the NF-κB pathway by targeting SNAP23. Mechanistically, SNAP23 was transcriptionally upregulated by EV TNF-α/NF-κB axis to enhance the expression of laminin subunit beta-3 (LAMB3), thereby activating the PI3K/AKT signaling pathway and consequently facilitate CRC progression. Based on our findings, we could conclude that EV TNF-α plays an oncogenic role in CRC progression through SNAP23, which in turn promotes EV TNF-α secretion, suggesting that EV TNF-α/SNAP23 axis may serve as a diagnostic biomarker and potential therapeutic target for CRC.

Panaxytriol upregulates CYP3A4 expression through the interaction between nuclear regulators and DNA response elements.

ETHNOPHARMACOLOGICAL RELEVANCE: Cytochrome P3A4 (CYP3A4) is a crucial drug-metabolizing enzyme, and its expression is regulated by the pregnane X receptor (PXR), constitutive androstane receptor (CAR), steroid receptor coactivator 1 (SRC-1), and acetyltransferase P300. Panaxytriol is a naturally derived active substance extracted from the roots of Panax ginseng C. A. Mey. which is widely used clinically. Our previous studies have shown that panaxytriol induces CYP3A4 expression through PXR activation, which is antagonized by high CAR expression. However, the underlying mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the mechanism of panaxytriol in inducing CYP3A4 expression via interactions between nuclear regulators and DNA response elements. MATERIALS AND METHODS: Immunoprecipitation technique was used to assess the binding levels of PXR and CAR with the coactivators SRC-1 and P300 in HepG2 and Huh-7 cells. Furthermore, chromatin immunoprecipitation assay was used to investigate the PXR and CAR interaction with the CYP3A4 promoter response element ER-6/DR-3. RESULTS: The binding of PXR to SRC-1, P300, and the response elements ER-6 and DR-3 was improved with an increase in panaxytriol concentration (10-80 µM), and the binding affinity was further enhanced upon CAR silencing. The binding of CAR to SRC-1 and the response elements ER-6 and DR-3 was significantly higher at 80 µM panaxytriol, whereas no significant binding was observed between CAR and P300. CONCLUSION: Panaxytriol promoted the recruitment of PXR to SRC-1 and P300, binding to ER-6 and DR-3, and upregulating CYP3A4 expression. Furthermore, an interactive dialogue regulatory mechanism between PXR and CAR was observed.

Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai formula (SMF) is a well-known Chinese herbal compound preparation, which is utilized extensively for the treatment of myocardial ischemia, arrhythmia and other life-threatening conditions. Our previous researches have shown that some of the active ingredients in SMF can interact with organic anion transport polypeptide 1B1 (OATP1B1), breast cancer resistance protein (BCRP) and organic anion transporter 1 (OAT1), etc. Organic cation transporter 2 (OCT2) is a highly expressed uptake transporter in the kidney, and its interaction with the major active components in SMF remains unclear. AIM OF THE STUDY: We purposed to explore OCT2-mediated interactions and compatibility mechanisms of the main active compounds in SMF. MATERIALS AND METHODS: Fifteen active ingredients of SMF, including ginsenoside Rb1, Rd, Re, Rg1, Rf, Ro and Rc, methylophiopogonanone A and B, ophiopogonin D and D', schizandrin A and B, schizandrol A and B, were selected to investigate OCT2-mediated interactions in Madin-Darby cacine kidney (MDCK) cells stably expressing OCT2. RESULTS: Among the above 15 main active components, only ginsenosides Rd, Re and schizandrin B could significantly inhibit the uptake of 4-(4-(dimethylamino)styryl)-N-methyl pyridiniumiodide (ASP+), a classical substrate of OCT2. Ginsenoside Rb1 and methylophiopogonanone A can be transported by MDCK-OCT2 cells, and their uptake was significantly reduced when OCT2 inhibitor decynium-22 was added. Ginsenoside Rd could remarkably reduce the uptake of methylophiopogonanone A and ginsenoside Rb1 by OCT2, ginsenoside Re only decreased the uptake of ginsenoside Rb1, while schizandrin B had no effect on the uptake of both. CONCLUSIONS: OCT2 mediates the interaction of the major active components in SMF. Ginsenosides Rd, Re and schizandrin B are the potential inhibitors of OCT2, while ginsenosides Rb1 and methylophiopogonanone A are the potential substrates of OCT2. There is an OCT2-mediated compatibility mechanism among these active ingredients of SMF.

Nrf2 and its dependent autophagy activation cooperatively counteract ferroptosis to alleviate acute liver injury.

Ferroptosis has been implicated in the pathophysiological progression of a variety of diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant response and can counteract ferroptosis by inducing autophagy and targeting genes involved in iron metabolism and glutathione (GSH) synthesis/metabolism. This study investigated how Nrf2 and autophagy interact to prevent ferroptosis in acute liver injury under sulforaphane (SFN) intervention. The results showed that SFN could activate Nrf2 signaling pathway and its downstream target genes, promote cell autophagy, and then combat ferroptosis to alleviate liver injury. After inhibiting Nrf2, the autophagy activated by SFN almost disappeared, and the anti-ferroptosis effect was greatly weakened. After inhibiting autophagy, SFN can still activate Nrf2 and its downstream target gene, but solute carrier family 7 member 11 (SLC7A11) membrane transfer and its cystine transport ability are significantly weakened, thus ultimately attenuating the anti-ferroptosis effect of SFN. Further studies showed that Nrf2-dependent autophagy activation disrupted SLC7A11 binding to S93-phosphorylated coiled-coil myosin-like BCL2-interacting protein (BECN1) and increased SLC7A11 membrane transfer to combat ferroptosis. In conclusion, Nrf2-dependent autophagy activation is essential for promoting SLC7A11 membrane localization to inhibit ferroptosis. Activation of Nrf2 not only upregulates the expression of SLC7A11, glutathione peroxidase 4 (GPX-4) and autophagy-related proteins, but also destroys the binding of SLC7A11 and BECN1 by inducing autophagy, thereby promoting SLC7A11 membrane transfer and GSH synthesis, and finally suppressing ferroptosis. However, inhibition of autophagy had no significant effect on the expression of Nrf2 and downstream genes during SFN anti-liver injury intervention.

Proximal junctional kyphosis is a compensation for post-operative negative C2-FH in ASD patients: a cross-sectional study.

BACKGROUND: Recent studies have found that C2-FH is close to 0 cm in both standing and sitting position for asymptomatic adults. We hypothesize that the thoracic spine may compensate with PJK when the immediate post-operative C2-FH was not ideally restored in adult spinal deformity (ASD). METHODS: The inclusion criteria were as follows: ASD patients over 45 years old; Cobb angle > 30°; with posterior spinal correction surgery; at least 2 years follow-up. C2-FH was defined as the distance between the femoral heads to the C2 vertical line. All participants were divided into two groups according to the occurrence of PJK at the last follow-up: PJK group and non-PJK group. RESULTS: 68 ASD patients, with a minimum follow-up of 2.5 years, were included. PJK was found in 24 patients (35.3%) while the rest 44 patients remained no sagittal malalignment. Immediately post-operative C2-FH showed significant difference between PJK group and non-PJK group (p = 0.015). However, at the last follow-up, C2-FH showed no significant difference between PJK and non-PJK group and the mean value of C2-FH in both groups was approximately - 1 cm, indicating that ASD patients could develop various compensatory mechanisms to maintain sagittal global balance. The AUC was 0.84 (95%CI 0.68-0.97), indicating the well effectiveness of ROC curve and cut-off value in predicting occurrence of PJK in ASD patients. Based on the ROC curve, the optimal cut-off value of C2-FH as indicators for occurrence of PJK was - 42.3 mm. CONCLUSION: Immediate postoperative negative global malalignment (C2-FH < - 42.3 mm) may predict proximal junctional kyphosis in ASD patients. The normal value of C2-FH, - 1 cm, may be the target of global sagittal compensation, and PJK is a compensatory mechanism. TRIAL REGISTRATION: 2021-LCYJ-DBZ-05, 2021.07, Retrospective study.

Laparoscopic single-layer running "trapezoid-shaped" suture versus mechanical stapling for esophagojejunostomy after total gastrectomy for gastric cancer: cost-effect analysis of propensity score-matched study cohorts.

OBJECTIVES: Totally laparoscopic total gastrectomy has been developed with difficulty in intracorporeal esophagojejunostomy. Although mechanical stapling has been widely used for intracorporeal esophagojejunostomy, manual suture holds great promise with the emergence of high-resolution 3D vision and robotic surgery. After exploration of how to improve the safety and efficiency of intracorporeal suture for esophagojejunostomy, we recommended the technique of single-layer running "trapezoid-shaped" suture. The cost-effectiveness was analyzed by comparing with conventional mechanical stapling. METHODS: The study retrospectively reviewed the patients undergoing laparoscopic gastrectomy for gastric cancer from January 2010 to December 2021. The patients were divided into two cohorts based on the methods of intracorporeal esophagojejunostomy: manual suture versus stapling suture. Propensity score matching was performed to match patients from the two cohorts at a ratio of 1:1. Then group comparison was made to determine whether manual suture was non-inferior to stapling suture in terms of operation time, anastomotic complications, postoperative hospital stay, and surgical cost. RESULTS: The study included 582 patients with laparoscopic total gastrectomy. The manual and stapling suture for esophagojejunostomy were performed in 50 and 532 patients, respectively. In manual suture cohort, the median time for the whole operation and digestive tract reconstruction were 300 min and 110 min. There was no anastomotic bleeding and stenosis but two cases of anastomotic leak which occurred at 3 days after surgery. The median length of postoperative hospital stay was 11 days. After propensity score matching, group comparison yielded two variables with statistical significance: time for digestive tract reconstruction and surgery cost. The manual suture cohort spent less money but more time for esophagojejunostomy. Intriguingly, the learning curve of manual suture revealed that the time for digestive tract reconstruction was declined with accumulated number of operations. CONCLUSIONS: Laparoscopic single-layer running "trapezoid-shaped" suture appears safe and cost-effective for intracorporeal esophagojejunostomy after total gastrectomy. Although the concern remains about prolonged operation time for beginners of performing the suture method, adequate practice is expected to shorten the operation time based on our learning curve analysis.

The effectiveness of percutaneous endoscopic lumbar discectomy combined with external lumbar drainage in the treatment of intervertebral infections.

Objective: To analyze the effect of percutaneous endoscopic lumbar discectomy in treating lumbar intervertebral infections. Methods: A total of 13 patients with lumbar intervertebral infections who underwent percutaneous endoscopic lumbar discectomy combined with external drainage between November 2016 and December 2019 were enrolled in the present study. After the operation, sensitive antibiotics were used based on the results of the bacterial culture. If no pathogens were detected in the biopsy culture of the infected tissues, empirical antibiotics were administrated to these patients. The clinical efficacy was evaluated by using a visual analog scale (VAS), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and standard Macnab's evaluation. Postoperative computed tomography (CT) and MRI were also used to evaluate clinical efficacy. Results: The follow-up time was 10-18 months, and the average time was (13.69 ± 2.63) months. Causative bacteria were isolated in 7 of 13 infected tissue biopsy cultures. Systemic antibiotics and anti-tuberculous chemotherapy were administered according to sensitivity studies for identified. There were no pathogens isolated from the other six patients. Empiric antibiotics were administrated in these patients. One week after the operation, WBC, a fractional fraction of medium granulocytes, ESR and CRP were significantly lower compared to before the operation (all P < 0.05). At the last follow-up visit, the above-mentioned markers were all within normal range, which differed compared to the pre-operative data (P < 0.05). The VAS and ODI of the patients at 1 week and 3 months after operation were significantly lower compared to preoperative data (all P < 0.05). During the last follow-up visit, seven patients were excellent, five were good, and one was poor according to standard Macnab's evaluation. No serious complications were recorded. Conclusions: Percutaneous lumbar discectomy combined with external drainage resulted as an effective method for treating lumbar intervertebral infections and was associated with fewer injuries, less pain, low cost, and low recurrence rate.

Plasma arylsulfatase A levels are associated with cognitive function in Parkinson's disease.

BACKGROUND: Arylsulfatase A (ARSA), a lysosomal enzyme, has been shown to inhibit the aggregation and propagation of α-synuclein (α-syn) through its molecular chaperone function. The relationship between ARSA levels and Parkinson's disease (PD) in the Chinese Han population remains controversial, and few quantitative research studies have investigated the relationship between plasma ARSA levels and PD. OBJECTIVES: The purpose of this study was to investigate the relationships between ARSA levels and cognitive function in PD patients and to evaluate the association of ARSA and α-syn levels with nonmotor symptoms. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma ARSA and α-syn levels in 50 healthy controls, 120 PD patients (61 PD patients with no cognitive impairment (PD-NCI) and 59 PD patients with cognitive impairment (PD-CI)). Motor symptoms and nonmotor symptoms (cognitive function, Unified Parkinson's Disease Rating Scale (UPDRS) score, depression, anxiety, constipation, olfactory dysfunction, sleep disruption, and other symptoms) were assessed with the relevant scales. The Kruskal-Wallis H test was used for comparison between groups, and Pearson/Spearman analysis was used for correlation analysis. RESULTS: The plasma ARSA concentrations were lower in the PD-CI group than in the PD-NCI group. The plasma α-syn levels in the PD-CI group were higher than those in the healthy control group, and the plasma ARSA levels were correlated with the Mini-Mental State Examination (MMSE scores) and Hoehn and Yahr (H-Y) stage. CONCLUSION: We used a quantitative assessment method to show that low plasma ARSA levels and high α-syn levels are related to cognitive impairment in PD patients. Plasma ARSA levels gradually decrease with PD progression.

Radiographic study of peak velocity of pelvic incidence in adolescent idiopathic scoliosis.

BACKGROUND: Pelvic incidence (PI), a parameter related to the ideal spinopelvic alignment, is a morphological parameter that is usually considered fixed, but the PI's growth during adolescence has been reported. We investigated the peak PI velocity during adolescence and describe the relationship between increasing PI and changes in the morphology of the pelvis and sacrum. METHODS: We measured standing height (SH) and radiological anatomical parameters including pelvic height (PH), pelvic width (PW), sacral width (SW), femoral head-sacrum (FH-S), sacrum-coccyx (S-C) length, and S-C distance at each follow-up of 76 adolescent idiopathic scoliosis (AIS) patients. ΔParameter was the difference between the next measurement and the previous one. Growth velocity was ΔParameter divided by time interval. All ΔParameters were compared between different Risser stages using repeated-measures analysis of variance (ANOVA). The Pearson coefficients of correlation were calculated to assess the relationships between PI and ΔParameters. RESULTS: PI reached peak growth with a 1.6°/year growth in females and 1.8°/year in males at Risser stage 1. PI tended to grow rapidly with Risser 0 and closed triradiate cartilage (female: 1.3°/year and male: 1.4°/year) and to slow down at Risser 2 (female: 1.2°/year and male: 1.3°/year). ΔPI strongly correlated with ΔFH-S (R>0.508, P<0.05) and also correlated with ΔSH, ΔPH, ΔPW, ΔSW, and ΔS-C length (R>0.192, P<0.05) but not correlated with ΔS-C distance and ΔS-C ratio. CONCLUSIONS: In patients with AIS, the peak PI velocity is at Risser 1, and it is still increasing at Risser 5. Our result suggested that the growth of the PI may be associated with SH and changing pelvic morphology during skeletal growth of adolescence.

The long noncoding RNA GAS5 potentiates neuronal injury in Parkinson's disease by binding to microRNA-150 to regulate Fosl1 expression.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been the focus of recent studies of neurodegenerative disorders, including Parkinson's disease (PD). However, the specific mechanism of action of growth arrest-specific 5 (GAS5) in PD has not yet been characterized. First, the GSE8030 and GSE16658 datasets were analyzed to obtain differentially expressed genes (DEGs), followed by the development of a PD mouse model. The effects of shRNA targeting fos-like antigen-1 (shFosl1) and microRNA (miR)-150 agomiR on PD mouse behavior and neuronal injury were evaluated in vitro and in vivo. After the determination of target lncRNAs using bioinformatics tools, cell models were developed in SH-SY5Y and N2a cells using MPP+ to verify the effects of GAS5, miR-150 and Fosl1 on cell viability. Knockdown of Fosl1 and GAS5 or overexpression of miR-150 alleviated neuronal injury in mice after MPTP treatment and significantly increased the activity of SH-SY5Y and N2a cells after MPP treatment. GAS5 bound to miR-150, while miR-150 targeted Fosl1. Fosl1 activated the PTEN/AKT/mTOR pathway, thus promoting apoptosis and inhibiting neuronal activity in the PD model. Overall, our findings illuminated that GAS5 accelerated PD progression by targeting the miR-150/Fosl1 axis.