ZNF692 regulates nucleolar morphology by interacting with NPM1 and modifying its self-assembly properties.

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells.

Serum amyloid A aggravates endotoxin-induced ocular inflammation through the regulation of retinal microglial activation.

Serum amyloid A (SAA) are major acute-phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin-induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU-induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro-inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro-inflammatory factors, and increased the expression of tissue-reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll-like receptor 4 (TLR4). Collectively, our study suggested that microglial cell-expressed SAA could be a potential target in treating acute ocular inflammation.

Integrated analysis reveals NLRC4 as a potential biomarker in sepsis pathogenesis.

Sepsis remains a significant global health burden and contributor to mortality, yet the precise molecular mechanisms underlying the immune response are not fully elucidated. To gain insight into this issue, we performed a comprehensive analysis using a variety of techniques including bulk RNA sequencing, single-cell RNA sequencing, and enzyme-linked immunosorbent assay (ELISA). We performed enrichment analysis of differentially expressed genes in sepsis and healthy individuals by utilizing Gene Ontology (GO) analysis and indicated significant enrichment of immune-related response. Following Weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction analysis (PPI) were used to identify key immune-related hub genes and validated by ELISA to show that NLRC4 is highly expressed in sepsis. Additionally, an analysis of scRNA-seq data from newly diagnosed sepsis, sepsis diagnosis at 6 hours, and healthy samples demonstrates a significant increase in both the expression levels and proportions of NLRC4 in sepsis monocytes and neutrophils. In addition, using pySCENIC we identified upstream transcription factors that regulate NLRC4. Our study provides valuable insights into the identification of NLRC4 in peripheral blood as a potential candidate gene for the diagnosis and treatment of sepsis.

Single-cell analysis revealed a potential role of T-cell exhaustion in colorectal cancer with liver metastasis.

Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T-cell exhaustion on LM in CRC is unclear. Single-cell sequencing data derived from the Gene Expression Omnibus database. Data were normalized using the Seurat package and subsequently clustered and annotated into different cell clusters. The differentiation trajectories of epithelial cells and T cells were characterized based on pseudo-time analysis. Single-sample gene set enrichment analysis (ssGSEA) was used to calculate enrichment scores for different cell clusters and to identify enriched biological pathways. Finally, cell communication analysis was performed. Nine cell subpopulations were identified from CRC samples with LM. The proportion of T cells increased in LM. T cells can be subdivided into NK/T cells, regulatory T cells (Treg) and exhausted T cells (Tex). In LM, cell adhesion and proliferation activity of Tex were promoted. Epithelial cells can be categorized into six subpopulations. The transformation of primary CRC into LM involved two evolutionary branches of Tex cells. Epithelial cells two were at the beginning of the trajectory in CRC but at the end of the trajectory in CRC with LM. The receptor ligands CEACAM5 and ADGRE5-CD55 played critical roles in the interactions between Tex and Treg cell-epithelial cell, which may promote the epithelial-mesenchymal transition process in CRC. Tex cells are able to promote the process of LM in CRC, which in turn promotes tumour development. This provides a new perspective on the treatment and diagnosis of CRC.

BRIX1 promotes ribosome synthesis and enhances glycolysis by selected translation of GLUT1 in colorectal cancer.

BACKGROUND: Ribosome biogenesis protein BRX1 homolog (BRIX1) is critically required for the synthesis of the 60S ribosome subunit. However, the role and mechanism of BRIX1 in colorectal cancer (CRC) remain unclear. METHODS: Kyoto Encyclopedia of Gene and Genome pathway and Gene Ontology analyses were used for bioinformatics analysis. The rRNA levels were detected in CRC tissues and cells. Nascent RNA synthesis was detected via cellular immunofluorescence. The correlation was analyzed between patient Positron Emission Tomography-Computed Tomography (PET-CT) values and their BRIX1 expression. The extracellular acidification rate (ECAR) and oxygen consumption rate were determined via live metabolic analyses. Polysome fractions were collected for BRIX1 mRNA used in translation. The orthotopic model and Cell Counting Kit-8 (CCK8) assay were used to assess BRIX1 function in CRC. RESULTS: BRIX1 is a core protein involved in ribosome-related pathway changes in CRC. Gene Ontology analysis showed that BRIX1 was primarily enriched in ribosome assembly and ribosome biogenesis pathways. In fresh CRC tissue, rRNA levels (5S, 5.8S, 18S and 28S) were higher in the BRIX1 high-expression group than in the BRIX1 low-expression group. Similarly, BRIX1 knockdown significantly decreased rRNA levels for 5S, 5.8S, 18S and 28S in CRC cells, whereas overexpression of BRIX1 significantly increased these levels. In addition, BRIX1 knockdown inhibited nascent RNA synthesis in CRC cells. In clinical data analysis, BRIX1 expression was related to the glucose uptake in PET-CT. BRIX1 knockdown significantly decreased the ECAR value, glucose uptake and lactic acid production in CRC cells, whereas BRIX1 overexpression significantly increased these. Furthermore, BRIX1 knockdown significantly decreased the protein expression of GLUT1, whereas BRIX1 overexpression significantly increased this; however, expression of BRIX1 mRNA was unaffected in either case. Blocking glycolysis by si-GLUT1 or galactose reversed BRIX1 promotion of glycolysis and cell proliferation in CRC cells.

Systematic analysis of integrated bioinformatics to identify upregulated THBS2 expression in colorectal cancer cells inhibiting tumour immunity through the HIF1A/Lactic Acid/GPR132 pathway.

BACKGROUND: THBS2, a member of the extracellular matrix glycoprotein family, can effectively inhibit tumour growth and angiogenesis. This study aimed to investigate the biological role of THBS2 in various types of cancers and the mechanisms underlying the malignant progression of colorectal cancer (CRC). METHODS: THBS2 expression in pan-cancer tissues and cell lines was assessed using the HPA, TISCH and CCLE databases. The CIBERSORT, ESTIMATE, TIMER, xCell and ssGSEA (implemented using the IOBR R package) algorithms were used to calculate the proportion of tumour-infiltrating immune cells based on the expression profile of THBS2 in TCGA-COAD cohort. The clusterprofiler R package was used to implement GO and KEGG pathway enrichm SNVs were compared between the high- and low-THBS2-expression groups using the maftools R package. Additionally, immunotherapy responses were compared between the high- and low-THBS2-expression groups based on immunophenoscores (IPSs). CT26 cells were engineered to overexpress THBS2 (CT26-THBS2) to investigate its regulatory effects on HIF1 and cellular metabolism. The conditioned medium from CT26-THBS2 cells was collected to examine its effect on the M2 polarisation of RAW264.7 macrophages. Subsequently, in vitro experiments were performed to validate the inhibitory effects of M2-polarised macrophages on T-cell proliferation and cytotoxicity. A CT26-THBS2 tumour-bearing mouse model was constructed to validate the impact of high THBS2 expression in tumour cells on the tumour microenvironment in vivo. RESULTS: THBS2 expression was upregulated in a majority of tumours, including COAD, and was positively associated with ESTIMATEScore, ImmuneScore and StromalScore. Furthermore, THBS2 expression was positively associated with angiogenesis and epithelial-mesenchymal transition and negatively associated with DNA repair, cell cycle and DNA replication in most tumours. THBS2 expression was considerably associated with progression-free interval (PFI) and positively associated with MSI in COAD. THBS2 methylation levels were remarkably lower in COAD tissues than in healthy tissues. The high expression of THBS2 in CT26 cells remarkably promoted the nuclear translocation of HIF1 and consequently enhanced lactate metabolism in cells. In vitro and in vivo experiments revealed that lactate released by tumour cells promoted M2 polarisation of macrophages, leading to inhibition of T-cell proliferation and cytotoxicity. CONCLUSIONS: THBS2 expression is associated with PFI, immune cell infiltration, immune regulation, cell death, cell migration, epithelial-mesenchymal transition, angiogenesis and genomic variations in COAD. THBS2 may serve as a biomarker for immunotherapy in COAD. Upregulated THBS2 expression in CRC cells inhibits anti-tumour immunity through the HIF1A/lactic acid/GPR132 pathway.

Anti-neutrophil cytoplasmic antibody patterns can predict clinical relapse in ANCA-associated vasculitis: overall population and subgroups.

OBJECTIVES: In anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), relapses are cause of concern as they are unpredictable and predictors of poor prognosis. We aimed to assess the characteristic and predictors of clinical relapse in AAV. METHODS: This retrospective study included 132 cases of AAV newly diagnosed from January 2016 through November 2021 in the Affiliated Hospital of Qingdao University. We reviewed clinical data of patients and analysed the risk factors for clinical relapse of overall population and subgroups by univariate and multivariate regression models and the K-M survival curve was plotted. RESULTS: The rate of relapse was highest in the positive conversion group than the others significantly (p<0.001). In overall population, ANCA patterns (p<0.001; persistent positive pattern: HR=3.352, 95%CI 1.463~7.678, p=0.004; positive conversion pattern: HR=4.760, 95%CI 2.094~10.820, p<0.001) and infections (HR =4.684, 95%CI 1.980~11.079, p<0.001) were significantly associated with clinical relapse. In myeloperoxidase (MPO)-AAV patients, ANCA patterns (p=0.001; persistent positive pattern: HR=4.495, 95%CI 1.508~13.396, p=0.007; positive conversion pattern: HR=7.404, 95%CI 2.652~20.671, p<0.001) and infections (HR=3.594, 95%CI 1.511~8.547, p=0.004) were significantly associated with clinical relapse. In renal involvement patients, ANCA patterns (p=0.004; persistent positive pattern: HR=3.618, 95%CI 1.364~9.592, p=0.01; positive conversion pattern: HR=4.492, 95%CI 1.778~11.352, p<0.001) and infections (HR=7.791, 95%CI 2.511~24.174, p<0.001) were significantly associated with clinical relapse, but were not in patients without renal involvement. CONCLUSIONS: Persistently positive and re-positive ANCA and infections predict clinical relapse in AAV, especially in patients with MPO-AAV and renal involvement. Regular ANCA monitoring should be carried out in high-risk populations.

Secondary in-the-bag Intraocular Lens Implantation in Aphakic Eyes After Vitrectomy and Silicone Oil Tamponade for Rhegmatogenous Retinal Detachment.

PURPOSE: To describe a novel technique for capsular bag reopening and secondary in-the-bag intraocular lens (IOL) implantation in aphakic eyes after vitreoretinal surgery and intraocular tamponade. METHODS: We enrolled 14 eyes of 14 patients who underwent primary vitreoretinal surgery with silicone oil tamponade for rhegmatogenous retinal detachment between September 2018 and September 2019. The novel technique was used for capsular bag reopening and foldable single-piece IOL implantation. Patients were followed up at least 24 weeks with routine ophthalmic examinations, corneal endothelial cell density, and IOL tilt and decentration measurement. RESULTS: The procedure was successfully completed in 13 cases; in one case, because of posterior capsular tear, the IOL was implanted with ciliary sulcus fixation. After a mean follow-up of 48.8 ± 14.8 (range, 24.9-65.9) weeks, the best-corrected visual acuity (before 20/76 Snellen, 0.63 ± 0.23 logarithm of the minimum angle of resolution equivalent and after 20/35 Snellen, 0.32 ± 0.32 logarithm of the minimum angle of resolution equivalent; P = 0.001) and spherical equivalent (before +8.22 ± 4.08, after -2.39 ± 1.77 D; P < 0.001) improved, intraocular pressure (before 15.93 ± 4.40, after 16.25 ± 4.25 mmHg; P = 0.743) remained unchanged. The IOL was well centered with a mean horizontal and vertical tilt of 0.5070 ± 0.3319° and 0.4652 ± 0.3465°, respectively, and decentration of 0.1705 ± 0.1334 mm and 0.1712 ± 0.1576 mm, respectively. CONCLUSION: With this technique, capsular bag reopening and secondary in-the-bag IOL implantation could be achieved in most cases with satisfactory visual outcome and IOL position.

Scleral Suture Intraocular Lens Fixation Under Microscope-Intraoperative Optical Coherence Tomography.

PURPOSE: The aim of this study was to evaluate the accessibility and potential value of intraoperative optical coherence tomography (iOCT) during scleral suture intraocular lens (IOL) fixation. METHODS: This was a prospective cohort study in the Department of Ophthalmology, Eye and ENT Hospital, Fudan University, China. Seven eyes with insufficient capsular support and undergoing two-point scleral suture IOL fixation were included. The potential value of iOCT was evaluated, as well as the safety and efficacy of the surgery. RESULTS: Seven eyes were included. With a tailor-made iOCT, the structure of the anterior segment could be clearly visualized during the surgery. Intraoperatively, iOCT helped locate the proper place for fixation and access the position of the IOL. After an average 4.43-month follow-up, the spherical equivalent changed significantly ( P < 0.001), but the intraocular pressure, best-corrected visual acuity, and endothelial cell density remained unchanged ( P > 0.05). The IOL was well-centered with a horizontal and a vertical tilt of 0.74 ± 0.60° and 1.13 ± 0.65°, and decentration of 0.28 ± 0.12 mm and 0.30 ± 0.13 mm. The estimated IOL-induced astigmatism was -0.11 diopters (D) ± 0.46 D. CONCLUSION: Real-time high-resolution images of the anterior segment acquired by the iOCT helped the surgeon to achieve satisfactory results in scleral suture IOL fixation.

Comparison of sutureless intrascleral fixation and sutured scleral fixation for the treatment of dislocated intraocular lenses.

BACKGROUND: To compare the outcomes of sutured transscleral fixation and sutureless intrascleral fixation for the treatment of a dislocated intraocular lens (IOL). METHODS: Thirty-five eyes of 35 patients who required IOL repositioning surgery due to IOL dislocation were included in this retrospective study. Sixteen eyes underwent two-point sutured transscleral fixation, eight eyes underwent one-point sutured transscleral fixation, and 11 eyes underwent sutureless intrascleral IOL fixation. The patients were followed for ≥ 12 months after repositioning surgery, and their postoperative outcomes were recorded and analyzed. RESULTS: The major cause of IOL dislocation was ocular blunt trauma (19/35, 54.3%). The mean corrected distance visual acuity (CDVA) improved significantly after IOL repositioning (P = 0.022). The mean postoperative change in endothelial cell density (ECD) was - 4.5%. There were no significant differences in the changes in CDVA or ECD among the three groups with different repositioning techniques (both P > 0.1). The mean vertical tilt of the IOLs in all enrolled patients was significantly greater than the horizontal value (P = 0.001). The vertical tilt was greater in the two-point scleral fixation group than that in the sutureless intrascleral fixation group (P = 0.048). The mean decentration values in the one-point scleral fixation group in the horizontal and vertical directions were greater than those in the other two groups (all P < 0.01). CONCLUSION: All three IOL repositioning techniques resulted in favorable ocular prognosis.

Status quo of the public's knowledge of probiotics based on video-sharing platforms.

BACKGROUND: Probiotics have been deemed multipotent and unprecedentedly applied in the health field recently. However, there are challenges in promoting credible and reliable resources while avoiding misinformation regarding probiotics for the public. METHODS: This study analysed 400 eligible probiotic-related videos selected from YouTube, and the three most popular video-sharing platforms (Bilibili, Weibo and TikTok) in China. Video retrieval was performed on September 5th, 2022. GQS and tailored DISCERN tool assess each video's quality, usage, and reliability. A comparative analysis of videos from different sources was carried out. RESULTS: The identity distribution of probiotic video-producers was predominantly experts (n = 202, 50.50%), followed by amateurs (n = 161, 40.25%) and health-related institutions (n = 37, 9.25%). The videos' content category mainly discussed the function of probiotics (n = 120, 30%), the way to choose suitable products (n = 81, 20.25%), and the methods for taking probiotics (n = 71, 17.75%).The overall quality of videos was moderate (3/5 point) assessed by GQS, while the usage (1/6 point) and reliability (2/5 point) detailing probiotics assessed by tailored DISCERN tool were poor. The attitude of probiotic video-producers was primarily positive (n = 323, 80.75%), followed by neutral (n = 52, 13.00%) and negative (n = 25, 6.25%) (P < 0.001). CONCLUSIONS: The current study showed that videos on social media platforms publicise important information including the concepts, usage, and precautions of probiotics to the public. But the overall quality of uploaded videos about probiotics was unsatisfactory. More efforts are needed to improve the higher-quality content of probiotic-related online videos and better propagate probiotic knowledge to the public in the future.

A preliminary nomogram model for predicting relapse of patients with primary membranous nephropathy.

OBJECTIVE: To explore the predictive factors and establish a nomogram model for predicting relapse risk in primary membranous nephropathy (PMN). METHODS: The clinical, laboratory, pathological and follow-up data of patients with biopsy-proven membranous nephropathy were collected in the Affiliated Hospital of Qingdao University. A total of 400 PMN patients who achieved remission were assigned to the development group (n = 280) and validation group (n = 120) randomly. Cox regression analysis was performed in the development cohort to determine the predictive factors of relapse in PMN patients, a nomogram model was established based on the multivariate Cox regression analysis and validated in the validation group. C-index and calibration plots were used to evaluate the discrimination and calibration performance of the model respectively. RESULT: Hyperuricemia (HR = 2.938, 95% CI 1.875-4.605, p < 0.001), high C-reactive protein (CRP) (HR = 1.147, 95% CI 1.086-1.211, p < 0.001), and treatment with calcineurin inhibitors with or without glucocorticoids (HR = 2.845, 95%CI 1.361-5.946, p = 0.005) were independent risk factors, while complete remission (HR = 0.420, 95%CI 0.270-0.655, p < 0.001) was a protective factor for relapse of PMN according to multivariate Cox regression analysis, then a nomogram model for predicting relapse of PMN was established combining the above indicators. The C-indices of this model were 0.777 (95%CI 0.729-0.825) and 0.778 (95%CI 0.704-0.853) in the development group and validation group respectively. The calibration plots showed that the predicted relapse probabilities of the model were consistent with the actual probabilities at 1, 2 and 3 years, which indicated favorable performance of this model in predicting the relapse probability of PMN. CONCLUSIONS: Hyperuricemia, remission status, CRP and therapeutic regimen were predictive factors for relapse of PMN. A novel nomogram model with good discrimination and calibration was constructed to predict relapse risk in patients with PMN early.

Study on Ultrasonic Far-Infrared Radiation Drying and Quality Characteristics of Wolfberry (Lycium barbarum L.) under Different Pretreatments.

In order to explore the effects of different pretreatment methods on the ultrasonic far-infrared synergistic drying characteristics and quality of wolfberry, the bioactive components (polysaccharide, total phenol, total flavonoids, and antioxidants), the quality characteristics (rehydration ratio, color, vitamin C content, and betaine content), and the microstructure of the dried products were used as evaluation indices to test wolfberry treated by five different pretreatments (hot blanching; candied pretreatment; NaOH solution treatment; NaCl solution treatment; and Na2CO3 solution treatment). The results showed that hot blanching pretreatment improved the drying rate and shortened the drying time, and that the vitamin C content of dried products pretreated by hot blanching (92.56 mg/100 g) was higher than that of dried products pretreated by other methods. All five pretreatment methods increased the contents of the total phenols, vitamin C, and betaine of wolfberry. Wolfberry treated by candied pretreatment had lower color differences and higher contents of polysaccharide (0.83 g/g), total phenol (9.26 mg/g), and total flavonoids (2.61 mg/g) than wolfberry treated by the other pretreatment methods. Wolfberry pretreated by NaCl solution had the strongest antioxidant capacity (65.01%). Wolfberry pretreated by Na2CO3 solution had the highest betaine content (3.24%). The observation of the microstructure of the dried products revealed that hot blanching caused the most damage to wolfberry, while the candied pretreatment was less destructive to the tissue cells of wolfberry. On the whole, the dried wolfberry products obtained by the candied pretreatment were of a better quality than products obtained by the other pretreatment methods.

Evaluation of the Effect of Ultrasonic Pretreatment on the Drying Kinetics and Quality Characteristics of Codonopsis pilosula Slices Based on the Grey Correlation Method.

Ultrasonic (US) maltreatment was performed before the vacuum far-infrared drying (VFID) of Codonopsis pilosula (CP) slices to investigate the effects of different US parameters on the drying characteristics and nutrients of CP slices. The grey correlation method with relative correlation degree (ri) as the evaluation measure was used to construct a model for the evaluation of the pretreatment quality of CP and to determine the optimal pretreatment conditions. The results showed that with the increase in US frequency and power, the drying rate increased. Under the conditions of US power of 180 W, frequency of 60 kHz and a pre-treatment time of 30 min, the drying time reduced by 28.6%. The contents of polysaccharide and syringin in dried CP slices pretreated by US increased by 14.7% and 62.0%, respectively, compared to the non-pre-treated samples, while the total flavonoid content decreased by 10.0%. In terms of colour, pretreatment had a certain protective effect on the red colour of dried products. The highest relative correlation (0.574) and the best overall quality of performance were observed at 180 W, 60 kHz and 30 min. Overall, US technology is suitable for the pretreatment processing of CP, which is of great significance to the drying of CP.

Long non-coding RNA nuclear paraspeckle assembly transcript 1 downregulation protects lens epithelial cells from oxidative stress-induced apoptosis by regulating the microRNA-124-3p/death-associated protein kinase 1 axis in age-related cataract.

Oxidative stress plays a significant role in cataract development. It causes the apoptosis of lens epithelial cells (LECs), resulting in lens opacification and accelerating cataract progression. Long non-coding RNAs (lncRNAs) and microRNAs have been linked to cataract development. Notably, lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in LEC apoptosis and cataract formation. However, the molecular mechanism by which NEAT1 causes age-related cataracts remains unknown. In this study, LECs (SRA01/04) were exposed to 200 µM H2O2 to generate an in vitro cataract model. The apoptosis and viability of cells were determined using flow cytometry and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assays, respectively. Additionally, western blotting and quantitative polymerase chain reaction were used to determine the miRNA and lncRNA expression levels. When LECs were treated with hydrogen peroxide, lncRNA NEAT1 expression levels were significantly upregulated, which contributed to LEC apoptosis. Notably, lncRNA NEAT1 suppressed the expression of miR-124-3p, a critical regulator of apoptosis, whereas NEAT1 inhibition increased miR-124-3p expression and alleviated apoptosis. However, this effect was reversed when miR1243p expression was inhibited. Additionally, the miR1243p mimic effectively inhibited the death-associated protein kinase 1 (DAPK1) expression and apoptosis of LECs, while the DAPK1 mimic reversed these effects. In conclusion, our findings indicate that the lncRNA NEAT1/miR-124-3p/DAPK1 signaling loop is involved in the regulation of LEC apoptosis induced by oxidative stress, which can be exploited to develop potential treatment strategies for age-related cataracts.

Utility of transversus abdominis plane block on patients undergoing transanal total mesorectal excision.

Objective: To evaluate the analgesic effect of transversus abdominis plane block (TAPB) on patients undergoing transanal total mesorectal excision (taTME). Methods: Medical records of patients who were eligible to receive proctectomy surgery in Renji Hospital, Shanghai Jiao Tong University School of Medicine (From January 2019 to December 2021) were retrospectively reviewed. Propensity score matching (PSM) was applied to the included cases. A total of 120 cases were divided into three groups based on the different operation and anesthesia methods used. Group-A (Lap, n=40) included patients that underwent laparoscopic surgery under general anesthesia. Group- B (ta, n=40) included patients who received taTME surgery under general anesthesia. Group-C (ta+TAPB, n=40) included patients who received taTME surgery under general anesthesia combined with TAPB. The dosage of sufentanil, time of postoperative revival and extubation, anal exhaust time and other adverse events were recorded. Pain assessment using the visual analogue scale (VAS) was performed at 12, 24,48 and 72 hours after the operation. Results: There were no significant differences in the general parameters, operative conditions, and anesthetic administration between the three groups (P>0.05). The dosage of sufentanil was significantly reduced in Group-C, compared with Group-A and Group-B, with no difference between the groups A and B. There was no significant difference between the three groups in postoperative recovery time and extubation time. VAS score was lower in Group-C than Group-A and Group-B. This difference was more obvious in the early postoperative period and gradually diminished with time. VAS score became similar in all three groups 72 hours after the surgery. Conclusion: Transanal total mesorectal excision was associated with less pain, compared to laparoscopic TME. TAPB with general anesthesia in patients undergoing taTME is safe and effective. It can significantly reduce the use of sufentanil and has optimal analgesic effect.

GPR37 promotes cancer growth by binding to CDK6 and represents a new theranostic target in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is associated with poor prognosis. Identifying novel cancer targets and helpful therapeutic strategies remains a serious clinical challenge. This study detected differentially expressed genes in The Cancer Genome Atlas (TCGA) LUAD data collection. We also identified a predictive DNA biomarker, G protein-coupled receptor 37 (GPR37), which was verified as a prognostic biomarker with a critical role in tumor progression. In human LUAD specimens and microarray analyses, we determined that GPR37 was significantly upregulated and associated with a poor prognosis. GPR37 downregulation markedly inhibited the proliferation and migration of LUAD both in vitro and in vivo. Mechanistically, GPR37 could bind to CDK6, thereby facilitating tumor progression in LUAD by inducing cell cycle arrest at the G1 phase. GPR37 also facilitates tumorigenesis in xenograft tumors in vivo. High-throughput screening for GPR37-targeted drugs was performed using the Natural Products Library, which revealed the potential of Hypocrellin B to inhibit GPR37 and cell growth in LUAD. We demonstrated that Hypocrellin B suppressed LUAD cell proliferation and migration both in vitro and in vivo via GPR37 inhibition. Collectively, our findings reveal the role of GPR37 in LUAD progression and migration and the potential of GPR37 as a target for the treatment of LUAD. Thus, the specific inhibition of GPR37 by the natural product Hypocrellin B may possess the potential for the treatment of LUAD.

Visible-Light-Promoted Cross Dehydrogenative/Decarboxylative Coupling Cascades of Glycine Ester Derivatives and ß-Keto Acids.

A visible-light-induced dehydrogenative/decarboxylative coupling reaction of arylglycine derivatives and ß-keto acids is described. This photocatalyst- and additive-free protocol can be applied in the efficient synthesis of γ-keto glycine derivatives under ambient conditions. Further uses of this methodology and a plausible mechanism are also demonstrated.

Change in axial length after vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment.

BACKGROUND: We aimed to explore the changes in the axial length and related factors after vitrectomy for rhegmatogenous retinal detachment (RRD). METHODS: This study retrospectively evaluated patients who underwent vitrectomy with silicone oil (SO) tamponade for RRD and subsequent silicone oil removal at our clinic. Using a Zeiss IOLMaster 700, axial length was measured before vitrectomy for RRD and SO removal. The change in axial length (ΔAL) was calculated, and multivariate binary logistic regression analysis was performed to investigate the potential correlation between ΔAL and clinical factors, such as preoperative hypotony, extreme myopia, age, macular involvement, choroidal detachment, operation duration, and operation history. RESULTS: In total, 213 eyes from 213 patients were included. The mean axial length changed significantly pre- and post-vitrectomy (25.98 ± 2.87 mm and 26.25 ± 3.07 mm, respectively, P < 0.001); the mean ΔAL was 0.37 ± 0.62 mm. Multivariate binary logistic regression analysis showed that preoperative hypotony and extreme myopia were significantly correlated with the ΔAL (P = 0.001 and P = 0.001, respectively). A higher proportion of hypotonic eyes had ΔAL ≥ 0.3 mm (33/76 in hypotony eyes and 32/137 in others; P = 0.003). A higher proportion of extremely myopic eyes also had a ΔAL ≥ 0.3 mm (23/46 in extremely myopic eyes and 42/167 in others; P = 0.002). CONCLUSION: For patients with RRD and cataracts, as axial length changed significantly after vitrectomy in those with hypotony or extreme myopia, secondary lOL implantation should be considered.

Rare-Earth-Catalyzed Selective 1,4-Hydrosilylation of Branched 1,3-Enynes Giving Tetrasubstituted Silylallenes.

Allenes are versatile synthons in organic synthesis and medicinal chemistry because of their diverse reactivities. Catalytic 1,4-hydrosilylation of 1,3-enynes may present the straightforward strategy for synthesis of silylallenes. However, the transition-metal-catalyzed reaction has not been successful due to poor selectivity and very limited substrate scopes. We report here the efficient and selective 1,4-hydrosilylation of branched 1,3-enynes enabled by the ene-diamido rare-earth ate catalysts using both alkyl and aryl hydrosilanes, leading to the exclusive formation of tetrasubstituted silylallenes. Deuteration reaction, kinetic study, and DFT calculations were conducted to investigate the possible mechanism, revealing crucial roles of high Lewis acidity, large ionic radius, and ate structure of the rare-earth catalysts.