Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society. METHODS AND ANALYSIS: The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers. ETHICS AND DISSEMINATION: This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.

Pan-cancer identified ARPC1B as a promising target for tumor immunotherapy and prognostic biomarker, particularly in READ.

ARPC1B encodes the protein known as actin-related protein 2/3 complex subunit 1 B (ARPC1B), which controls actin polymerization in the human body. Although ARPC1B has been linked to several human malignancies, its function in these cancers remains unclear. TCGA, GTEx, CCLE, Xena, CellMiner, TISIDB, and molecular signature databases were used to analyze ARPC1B expression in cancers. Visualization of data was primarily achieved using R language, version 4.0. Nineteen tumors exhibited high levels of ARPC1B expression, which were associated with different tumor stages and significantly affected the prognosis of various cancers. The level of ARPC1B expression substantially connected the narrative of ARPC1B expression with several TMB cancers and showed significant changes in MSI. Additionally, tolerance to numerous anticancer medications has been linked to high ARPC1B gene expression. Using Gene Set Variation Analysis/Gene Set Enrichment Analysisanalysis and concentrating on Rectum adenocarcinoma (READ), we thoroughly examined the molecular processes of the ARPC1B gene in pan-cancer. Using WGCNA, we examined the co-expression network of READ and ARPC1B. Meanwhile, ten specimens were selected for immunohistochemical examination, which showed high expression of ARPC1B in READ. Human pan-cancer samples show higher ARPC1B expression than healthy tissues. In many malignancies, particularly READ, ARPC1B overexpression is associated with immune cell infiltration and a poor prognosis. These results imply that the molecular biomarker ARPC1B may be used to assess the prognosis and immune infiltration of patients with READ.

Bioactive peptide relieves glucocorticoid-induced osteoporosis by giant macrocyclic encapsulation.

Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP (P) was selected as the representative of a bioactive peptide. Quaterphen[4]arene (4) exhibited extensive host-guest complexation with P, and the binding constant was (1.16 ± 0.10) × 107 M-1. In vitro cell experiments confirmed that P + 4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P + 4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P + 4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.

The role of robotic-assisted surgery in the management of rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Rectal cancer poses a significant global health burden. There is a lack of concrete evidence concerning the benefits of robotic-assisted surgery (RAS) for rectal cancer surgery as compared to laparoscopic and open techniques. To address this gap, we conducted a meta-analysis to assess the intraoperative, postoperative, and safety outcomes of robotic surgery in this context. METHODS: MEDLINE, Scopus, and the Cochrane library were searched till May 2023 for randomized and non-randomized studies comparing robotic surgery with either laparoscopic or open approach for rectal cancers. The outcomes of interest were operative time, blood loss, harvested lymph nodes, conversion rate, postoperative hospital stay, survival to hospital discharge, urinary retention rate, and anastomotic leakage rate. A random-effects meta-analysis was performed to pool means and dichotomous data to derive weighted mean differences and odds ratios, respectively. RESULTS: A total of 56 studies were shortlisted after the study selection process with a total of 25,458 rectal cancer patients. From the intraoperative outcomes, RAS was significantly associated with an increased operative time (WMD: 41.04, P <0.00001), decreased blood loss (WMD: -24.56, P <0.00001), decreased conversion rates (OR: 0.39, P <0.00001), lesser stay at the hospital (WMD: -1.93, P <0.00001), and no difference was found in lymph nodes harvested. Similarly, RAS group had a significantly greater survival to hospital discharge (OR: 1.90, P =0.04), decreased urinary retention rate (OR: 0.59, P =0.002), and no difference was seen in anastomotic leakage rate. CONCLUSION: Robotic-assisted surgery (RAS) demonstrates favourable outcomes for rectal cancer patients, contributing to global prevention and control efforts, health promotion, and addressing non-communicable disease risk factors. Further research and public awareness are needed to optimize RAS utilization in this context.

Road surface crack detection based on improved YOLOv5s.

In response to the issues of low efficiency and high cost in traditional manual methods for road surface crack detection, an improved YOLOv5s (you only look once version 5 small) algorithm was proposed. Based on this improvement, a road surface crack object recognition model was established using YOLOv5s. First, based on the Res2Net (a new multi-scale backbone architecture) network, an improved multi-scale Res2-C3 (a new multi-scale backbone architecture of C3) module was suggested to enhance feature extraction performance. Second, the feature fusion network and backbone of YOLOv5 were merged with the GAM (global attention mechanism) attention mechanism, reducing information dispersion and enhancing the interaction of global dimensions features. We incorporated dynamic snake convolution into the feature fusion network section to enhance the model's ability to handle irregular shapes and deformation problems. Experimental results showed that the final revision of the model dramatically increased both the detection speed and the accuracy of road surface identification. The mean average precision (mAP) reached 93.9%, with an average precision improvement of 12.6% compared to the YOLOv5s model. The frames per second (FPS) value was 49.97. The difficulties of low accuracy and slow speed in road surface fracture identification were effectively addressed by the modified model, demonstrating that the enhanced model achieved relatively high accuracy while maintaining inference speed.

Traumatic spinal injury-related hospitalizations in the United States, 2016-2019: a retrospective study.

BACKGROUND: Traumatic spinal injury (TSI) is associated with significant fatality and social burden; however, the epidemiology and treatment of patients with TSI in the US remain unclear. MATERIALS AND METHODS: An adult population was selected from the National Inpatient Sample database from 2016 to 2019. TSI incidence was calculated and TSI-related hospitalizations were divided into operative and nonoperative groups according to the treatments received. TSIs were classified as fracture, dislocation, internal organ injury, nerve root injury, or sprain injuries based on their nature. The annual percentage change (APC) was calculated to identify trends. In-hospital deaths were utilized to evaluate the prognosis of different TSIs. RESULTS: Overall, 95 047 adult patients were hospitalized with TSI in the US from 2016 to 2019, with an incidence rate of 48.4 per 100 000 persons in 2019 (95% CI: 46.2-50.6). The total incidence increased with an APC of 1.5% (95% CI: 0.1-3%) from 2016 to 2019. Operative TSI treatment was more common than nonoperative (32.8 vs. 3.8; 95% CI: 32.3-33.2 vs. 3.6-4%). The number of operations increased from 37 555 (95% CI: 34 674-40 436) to 40 460 (95% CI: 37 372-43 548); however, the operative rate only increased for internal organ injury (i.e. spinal cord injury [SCI])-related hospitalizations (APC, 3.6%; 95% CI: 2.8-4.4%). In-hospital mortality was highest among SCI-related hospitalizations, recorded at 3.9% (95% CI: 2.9-5%) and 28% (95% CI: 17.9-38.2%) in the operative and nonoperative groups, respectively. CONCLUSIONS: The estimated incidence of TSI in US adults increased from 2016 to 2019. The number of operations increased; however, the proportion of operations performed on TSI-related hospitalizations did not significantly change. In 2019, SCI was the highest associated mortality TSI, regardless of operative or nonoperative treatment.

Total Synthesis of the Reported Structure of Neaumycin B.

The stereoselective total synthesis of structure 1 assigned to the macrolide natural product neaumycin B is reported in a 2.3% overall yield on 90 mg scale. The synthesis features a gram-scale nickel-catalyzed reductive cross-coupling/spiroketalization tactic to construct the spiroketal core of neaumycin B. The stereostructures of the C3-C6, C8-C14, and C20-C41 segments of synthetic neaumycin B were unambiguously verified by X-ray crystallography.

Mining the vaccination willingness of China using social media data.

OBJECTIVE: Vaccination is one of the most powerful and effective protective measures against Coronavirus disease 2019 (COVID-19). Currently, several blogs hold content on vaccination attitudes expressed on social media platforms, especially Sina Weibo, which is one of the largest social media platforms in China. Therefore, Weibo is a good data source for investigating public opinions about vaccination attitudes. In this paper, we aimed to effectively mine blogs to quantify the willingness of the public to get the COVID-19 vaccine. MATERIALS AND METHODS: First, data including 144,379 Chinese blogs from Weibo, were collected between March 24 and April 28, 2021. The data were cleaned and preprocessed to ensure the quality of the experimental data, thereby reducing it to an experimental dataset of 72,496 blogs. Second, we employed a new fusion sentiment analysis model to analyze the sentiments of each blog. Third, the public's willingness to get the COVID-19 vaccine was quantified using the organic fusion of sentiment distribution and information dissemination effect. RESULTS: (1) The intensity of bloggers' sentiment toward COVID-19 vaccines changed over time. (2) The extremum of positive and negative sentiment intensities occurred when hot topics related to vaccines appeared. (3) The study revealed that the public's willingness to get the COVID-19 vaccine and the actual vaccination doses shares a linear relationship. CONCLUSION: We proposed a method for quantifying the public's vaccination willingness from social media data. The effectiveness of the method was demonstrated by a significant consistency between the estimates of public vaccination willingness and actual COVID-19 vaccination doses.

The Effects of Sidt2 on the Inflammatory Pathway in Mouse Mesangial Cells.

In patients with chronic kidney disease, the abnormal activation of inflammatory pathways is usually an important factor leading to renal fibrosis and further deterioration of renal function. Finding effective intervention targets of the inflammatory signaling pathway is an important way to treat chronic kidney disease. As a newly discovered lysosomal membrane protein, the correlation between SID1 transmembrane family member 2 (Sidt2) and the inflammatory signaling pathway has not been reported. The aim of this study was to investigate the effect of Sidt2 on inflammation by inhibiting the expression of the Sidt2 gene in a mouse mesangial cell line mediated by a lentiviral CRISPR/Cas9 vector. Hematoxylin and eosin staining and microscopy found that the mesangial cells lost their normal morphology after inhibiting the expression of Sidt2, showing that the cell body became smaller, the edge between the cells was unclear, and part of the nucleus was pyknotic and fragmented, appearing blue-black. The expressions of IKK ß, p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the NF-κB pathway of the Sidt2 -/- group were higher than those of the Sidt2 +/+ group. p-Jak2 and IL6 increased in the Jak/Stat pathway, and p-ERK and p-P38 increased in the MAPK pathway. The expressions of IKK ß, p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the NF-κB pathway of the Sidt2 +/++LPS group were significantly higher than those in the Sidt2 +/+ group. The expressions of IKK ß, p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the Sidt2 -/-+LPS group were higher than those in the Sidt2 -/- group. The expressions of p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the Sidt2 -/-+LPS group were higher than those in the Sidt2 +/++LPS group. In the Jak/Stat pathway, the protein expressions of p-Jak2 and IL6 in the Sidt2 +/++LPS group were higher than those in the Sidt2 +/+ group. The expressions of p-Jak2 and IL6 in the Sidt2 -/-+LPS group were higher than those in the Sidt2 -/- group. The expressions of p-Jak2 and IL6 in the Sidt2 -/-+LPS group were higher than those in the Sidt2 +/++LPS group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the MAPK pathway in the Sidt2 +/++LPS group were higher than those in the Sidt2 +/+ group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the Sidt2 -/-+LPS group were higher than those in the Sidt2 -/- group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the Sidt2 -/-+LPS group were higher than those in the Sidt2 +/++LPS group. These data suggested that deletion of the Sidt2 gene changed the three inflammatory signal pathways, eventually leading to the damage of glomerular mesangial cells in mice.

An Alternate Route of Transforming meso-Tetraarylporphyrins to Porpholactams, and Their Conversion to Amine-Functionalized Imidazoloporphyrins.

A novel and efficient synthetic pathway toward known meso-tetraphenylporpholactams, also applicable to the synthesis of hitherto unknown and inaccessible meso-C6F5-substituted porpholactam, is detailed (dioxochlorin → dioxochlorin urea adduct → porpholactam). meso-Tetraphenylporpholactam was converted to an imidazoloporphyrin-α-triflate derivative that was demonstrated to be of utility for the generation of functionalized imidazoloporphyrins with a substituted amine adjacent to the outside N atom of the imidazole moiety (using pyridine, Et2NH, diethyliminodiacetic acetate, dipicolylamine (DPA), and cyclen). The DPA- and iminodiacetate-imidazoloporphyrin conjugates were structurally characterized. The chemosensing potential of the metal chelate-imidazoloporphyrin conjugates was evaluated, though their constrained metric parameters led to muted chemosensing responses to various divalent metal ions. The accessibility of the meso-arylporpholactams and the meso-tetraphenylimidazoloporphyrin triflate enables the continued exploration of porphyrin-like pyrrole-modified porphyrins that incorporate a nitrogen atom in place of a ß-carbon atom in their macrocycles.

Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis.

1,1'-Spirobiindane has been one type of privileged skeleton for chiral ligand design, and 1,1'-spirobiindane-based chiral ligands have demonstrated outstanding performance in various asymmetric catalysis. However, the access to enantiopure spirobiindane is quite tedious, which obstructs its practical application. In the present article, a facile enantioselective synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished, in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation of α,α'-bis(arylidene)ketones and TiCl4 promoted asymmetric spiroannulation of the hydrogenated chiral ketones. The protocol can be performed in one pot and is readily scalable, and has been utilized in a 25 g scale asymmetric synthesis of cyclohexyl-fused spirobiindanediol (1 S,2 S,2' S)-5, in >99% ee and 67% overall yield for four steps without chromatographic purification. Facile derivations of (1 S,2 S,2' S)-5 provided straightforward access to chiral monodentate phosphoramidites 6a-c and a tridentate phosphorus-amidopyridine 11, which were evaluated as chiral ligands in several benchmark enantioselective reactions (hydrogenation, hydroacylation, and [2 + 2] reaction) catalyzed by transition metal (Rh, Au, or Ir). Preliminary results from comparative studies showcased the excellent catalytic performances of these ligands, with a competency essentially equal to the corresponding well-established privileged ligands bearing a regular spirobiindane backbone. X-ray crystallography revealed a close resemblance between the structures of the precatalysts 20 and 21 and their analogues, which ultimately help to rationalize the almost identical stereochemical outcomes of reactions catalyzed by metal complexes of spirobiindane-derived ligands with or without a fused cyclohexyl ring on the backbone. This work is expected to stimulate further applications of this type of readily accessible skeletons in development of chiral ligands and functional molecules.

A new synthetic method for non-symmetric pillar[5]arenes with simple isolation and improved yield.

The conventional method to synthesize non-symmetric pillar[n]arenes (PA[n]s) generally results in a low yield and requires laborious isolation. We developed a new synthetic method to prepare non-symmetric PA[5]s with various substitutions. Monomers were synthesized starting from commercially available chemicals. The desired products could be easily isolated with an improved yield.

Improved Solubility and Bioactivity of Camptothecin Family Antitumor Drugs with Supramolecular Encapsulation by Water-Soluble Pillar[6]arene.

Water-soluble pillar[6]arene (WP6) was used to solubilize camptothecin family antitumor drugs. In the presence of WP6, the solubility of camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) was enhanced by 380 and 40 times, respectively. The solubility enhancement is proved to be the result of the host-guest encapsulation by WP6. WP6 has a low cytotoxicity against normal MC 3T3-E1 cells, whereas the bioactivity of CPT and HCPT is substantially improved as a result of the solubility enhancement.

[Reference values of semen parameters for normal fertile men in Shanghai].

OBJECTIVE: To analyze the distribution characteristics of the main semen parameters of healthy semen donors and normal fertile men in Shanghai, compare the semen quality between the two groups, and investigate the normal reference values of the semen parameters of the fertile population in Shanghai. METHODS: We obtained semen samples from 100 healthy donors and 41 fertile men, performed semen analyses according to the WHO (2010) guidelines, and determined the semen volume, sperm concentration, sperm progressive motility, total sperm count and total progressively motile sperm count. We analyzed the distribution of the semen parameters of the normal fertile men, and obtained the lower limits of their normal reference values. RESULTS: There were no statistically significant differences in the main semen parameters between the healthy donors and normal fertile men (P < 0.05). The lower reference limits for the semen parameters of normal fertile men in Shanghai (P < 0.05) were as follows: sperm concentration > or = 27.3 x 10(6)/ml, sperm progressive motility > or = 8.1%, semen volume > or = 0.82 ml, total sperm count > or = 44.73 x 10(6) per ejaculate, and total progressively motile sperm count > or = 24.68 x 10(6) per ejaculate. CONCLUSION: For the evaluation of male fecundity, total sperm count and total progressively motile sperm count may be two better predictors than others.