[Intestinal Mantle Cell Lymphoma Complicated With Ileocecal Intussusception in Adults:Report of One Case].

Intestinal mantle cell lymphoma complicated with intussusception is rare in clinical practice,lacking specific clinical manifestations.CT and colonoscopy are helpful for the diagnosis of this disease,which need to be distinguished from colorectal cancer,Crohn's disease,and other pathological subtypes of lymphoma.The diagnosis still needs to be confirmed by pathological examination.This paper reports a case of intestinal mantle cell lymphoma complicated with ileocecal intussusception in an adult,aiming to improve the clinical and imaging doctors' understanding of this disease.

Comparative efficacy of modified Noel's technique and matrix phenolization on onychocryptosis: a retrospective study.

BACKGROUND: Onychocryptosis is a common pathological condition requiring clinical intervention. Selecting an appropriate and effective treatment based on individual patient circumstances is crucial. METHODS: We compared the efficacy and safety of the modified Noel's technique and matrix phenolization in 107 participants with onychocryptosis. Participants were divided into two groups: 75 nails (73 patients) were treated with the modified Noel's technique (modified Noel's group), while 42 nails (34 patients) were treated with matrix phenolization (Phenol group). Outcomes on clinical cure rates and postoperative complications from both groups were collected. Additionally, the efficacy of the modified Noel's technique was assessed in 31 nails with stage IV onychocryptosis. RESULTS: After 18 months, among the remaining 102 patients (110 nails), the modified Noel's group exhibited fewer complications (5.88% vs. 45.2%, P < 0.001) with similar cure rates (P = 0.62). Furthermore, there was a shorter healing time in the modified Noel's group (13.5 ± 1.4 vs. 27.6 ± 2.3 days, P < 0.001). Postoperative pain was notable in the modified Noel's group on the first postoperative day (P < 0.001), with a significant decrease in the pain score 2 weeks after surgery (P = 0.407). Postoperative nail plate narrowing was observed in the Phenol group (33%). Moreover, the modified Noel's technique achieved a 100% cure rate in stage IV patients. CONCLUSIONS: The modified Noel's technique, offering precise excision of the proliferative nail fold and strategic suturing, is suitable for stage IV patients and for those who find significant aesthetic impact unacceptable following narrowed plate postmatrix phenolization.

A fungal P450 enzyme from Fusarium equiseti HG18 with 7ß-hydroxylase activity in biosynthesis of ursodeoxycholic acid.

Cytochrome P450 enzyme with 7ß-hydroxylation capacity has attracted widespread attentions due to the vital roles in the biosynthesis of ursodeoxycholic acid (UDCA), a naturally active molecule for the treatment of liver and gallbladder diseases. In this study, a novel P450 hydroxylase (P450FE) was screen out from Fusarium equiseti HG18 and identified by a combination of genome and transcriptome sequencing, as well as heterologous expression in Pichia pastoris. The biotransformation of lithocholic acid (LCA) by whole cells of recombinant Pichia pastoris further confirmed the C7ß-hydroxylation with 5.2% UDCA yield. It was firstly identified a fungal P450 enzyme from Fusarium equiseti HG18 with the capacity to catalyze the LCA oxidation producing UDCA. The integration of homology modeling and molecular docking discovered the substrate binding to active pockets, and the key amino acids in active center were validated by site-directed mutagenesis, and revealed that Q112, V362 and L363 were the pivotal residues of P450FE in regulating the activity and selectivity of 7ß-hydroxylation. Specifically, V362I mutation exhibited 2.6-fold higher levels of UDCA and higher stereospecificity than wild-type P450FE. This advance provided guidance for improving the catalytic efficiency and selectivity of P450FE in LCA hydroxylation, indicative of the great potential in green synthesis of UDCA from biologically toxic LCA.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.

S14G-humanin confers cardioprotective effects against chronic adrenergic and pressure overload-induced heart failure in mice.

S14G-humanin (HNG), an analog of the mitochondria-derived peptide humanin, has demonstrated protective effects against various cardiovascular diseases. However, the specific pharmacological effects of HNG in heart failure (HF) have not been previously reported. Therefore, in this study, we aimed to investigate the potential protective effect of HNG in HF using a mouse model. HF was induced in mice through intraperitoneal injection of isoproterenol or transverse aortic constriction, followed by separate administration of HNG to assess its therapeutic impact. Our results revealed that HNG treatment significantly delayed the onset of cardiac dysfunction and structural remodeling in the HF mouse model. Furthermore, HNG administration was associated with reduced infiltration of inflammatory cells, improved myocardial fibrosis, and attenuation of cardiomyocyte apoptosis in the treated cardiac tissues. Additionally, we identified the involvement of the transforming growth factor-beta signaling pathway in the beneficial effects of HNG in isoproterenol-induced HF mice. Collectively, these findings underscore the therapeutic potential of HNG in preventing the progression of HF, as demonstrated in two distinct HF mouse models.

HDAC11 is related to breast cancer prognosis and inhibits invasion and proliferation of breast cancer cells.

OBJECTIVE: Histone deacetylases (HDACs) not only regulate histone acetylation but also participate in many pathophysiologic processes, especially the development of cancer, including breast cancer. However, whether Histone deacetylase 11 can influence breast cancer is still unknown. This study investigated the relationship between HDAC11 expression in breast cancers and clinicopathologic parameters, and used small interference RNA (siRNA) to determine the biological behavioural changes after knockdown of HDAC11. METHODS: Immunohistochemical (IHC) staining was employed to detect the expression of HDAC11 in a tissue microarray (TMA) of 145 patients with invasive ductal breast carcinoma. Transwell and wound healing assays were employed to analyze cell invasion and migration. The proliferation ability of cells was determined by Cell Counting Kit (CCK8). RESULTS: The results show that the expression of HDAC11 was positively correlated with the overall survival (OS) of breast cancer patients. Specific HDAC11 knockdown enhanced MDA-MB-231 cell proliferation, migration, and invasion. CONCLUSION: In conclusion, this study found that HDAC11 expression is positively correlated with the overall survival rate of patients. HDAC11 can inhibit the invasion and proliferation of breast cancer cells to a certain extent and can be used as a good prognosis marker.

PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers.

BACKGROUND: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8+ T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs. METHODS: Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8+ T lymphocyte infiltration is affected by the tumor microbiome of BTCs. RESULTS: We enrolled 32 patients with resected BTCs. The high CD8+ lymphocyte-infiltration (CD8hi) group had four significantly enriched taxa, and in the low CD8+ lymphocyte-infiltration (CD8low) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8hi group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8hi group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8+ lymphocyte infiltration in BTCs. CONCLUSIONS: The tumor microbiome is related to CD8+ T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8+ T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis.

A genome-wide CRISPR screen identifies the CCT chaperonin as a critical regulator of vesicle trafficking.

Vesicle trafficking is a fundamental cellular process that controls the transport of various proteins and cargos between cellular compartments in eukaryotes. Using a combination of genome-wide CRISPR screening in mammalian cells and RNAi screening in Caenorhabditis elegans, we identify chaperonin containing TCP-1 subunit 4 (CCT4) as a critical regulator of protein secretion and vesicle trafficking. In C. elegans, deficiency of cct-4 as well as other CCT subunits impairs the trafficking of endocytic markers in intestinal cells, and this defect resembles that of dyn-1 RNAi worms. Consistent with these findings, the silencing of CCT4 in human cells leads to defective endosomal trafficking, and this defect can be rescued by the dynamin activator Ryngo 1-23. These results suggest that the cytosolic chaperonin CCT may regulate vesicle trafficking by promoting the folding of dynamin in addition to its known substrate tubulin. Our findings establish an essential role for the CCT chaperonin in regulating vesicle trafficking, and provide new insights into the regulation of vesicle trafficking and the cellular function of the cytosolic chaperonin.

[Effects of serum containing Shenrong Pill on oxidative stress damage in mouse Leydig cells].

OBJECTIVE: To explore the mechanism of Shenrong pills in improving oligoasthenospermia by inhibiting oxidative stress-induced Leydig cell apoptosis in mouse testis. METHODS: The oxidative stress model of mouse Leydig cells (TM3) was induced by 3% hydrogen peroxide (H2O2) of 600 µmol/L, and then TM3 cells were treated with 7.5%, 10% and 12.5% serum containing Shenrong pills, respectively. TM3 cells were divided into normal control group, model group, and low, medium and high dose groups of Shenrong pills containing serum. The cell viability of TM3 after treatment was detected by CCK-8 method, reactive oxygen species (ROS) were detected by DCFH probe method, and SOD-1, CAT, GSH-px, MDA and LPO in cell lysates were detected by ELISA method. The changes of apoptosis-related proteins Bcl-2, Bax in cell lysates were detected by Western Blot. RESULTS: After H2O2 treatment, compared with normal control group, cell viability was significantly decreased (P< 0.01), MDA and LPO contents were significantly increased (P<0.01), SOD-1, CAT and GSH-px contents were significantly decreased (P<0.01). Reactive oxygen species (ROS) were significantly increased, the relative expression ratio of Bcl-2 protein was significantly decreased (P<0.01, P<0.05), and the relative expression of Bax protein was increased. After the administration of Shenrong pills containing serum, the above indexes were reversed to varying degrees. CONCLUSION: Shenrong pills can resist oxidative stress, inhibit the apoptosis of TM3 cells in mice, maintain high levels of testosterone required for spermatogenic cells, and improve the sperm quality of mice with oligonasthenospermia.

5-Demethoxy-10'-ethoxyexotimarin F, a New Coumarin with MAO-B Inhibitory Potential from Murraya exotica L.

Rutaceae plants are known for being a rich source of coumarins. Preliminary molecular docking showed that there was no significant difference for coumarins in Clausena and Murraya, both of which had high scoring values and showed good potential inhibitory activity to the MAO-B enzyme. Overall, 32 coumarins were isolated from Murraya exotica L., including a new coumarin 5-demethoxy-10'-ethoxyexotimarin F (1). Their structures were elucidated on the basis of a comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via a comparison of the specific rotations and the ECD exciton coupling method. The potential of new coumarin (1) as a selective inhibitor of MAO-B was initially evaluated through molecular docking and pharmacophore studies. Compound (1) showed selectivity for the MAO-B isoenzyme and inhibitory activity in the sub-micromolar range with an IC50 value of 153.25 ± 1.58 nM (MAO-B selectivity index > 172).

The effect of dermoscopy in assisting on defining surgical margins of basal cell carcinoma.

To investigate the diagnostic value of dermoscopy in defining the tumor margin of basal cell carcinoma (BCC) for the appropriate surgical margin. A total of 107 BCC patients were enrolled for this study. The tumor boundaries were observed by naked eye and dermoscope respectively, and 5 mm outward was used as surgical margin according to the dermoscopy-defined margin. Pathological examinations were performed at 2 mm intervals in the direction previously marked and the effect was assessed accordingly. There were still 16.8% of patients whose visual margin was insufficient to the dermoscopy-detected margin. With 2 mm excision margin from the dermoscopy-guided tumor margin, excision range in 12 patients (11.2%) proved to be inadequate, but only 18 surgical margins (4.2%) in the whole 428 excision margin specimens proved to be tumor-positive. While with 4 mm margin, residual lesion was observed in 2 (0.5%) of 107 BCC patients, and positive margin was found in 2 (0.3%) of 428 margin specimen. There has been no recurrence in our study so far. Dermoscopy is superior to visual inspection for defining BCC tumor margin. Under preoperative dermoscopy detection, a 4 mm excision margin of BCC can achieve a radical resection rate of 98.1%, and 92.3% for a 2 mm excision margin of pigmented BCC.

Grab regulates transferrin receptor recycling and iron uptake in developing erythroblasts.

Developing erythroblasts acquire massive amounts of iron through the transferrin (Tf) cycle, which involves endocytosis, sorting, and recycling of the Tf-Tf receptor (Tfrc) complex. Previous studies on the hemoglobin-deficit (hbd) mouse have shown that the exocyst complex is indispensable for the Tfrc recycling; however, the precise mechanism underlying the efficient exocytosis and recycling of Tfrc in erythroblasts remains unclear. Here, we identify the guanine nucleotide exchange factor Grab as a critical regulator of the Tf cycle and iron metabolism during erythropoiesis. Grab is highly expressed in differentiating erythroblasts. Loss of Grab diminishes the Tfrc recycling and iron uptake, leading to hemoglobinization defects in mouse primary erythroblasts, mammalian erythroleukemia cells, and zebrafish embryos. These defects can be alleviated by supplementing iron together with hinokitiol, a small-molecule natural compound that can mediate iron transport independent of the Tf cycle. Mechanistically, Grab regulates the exocytosis of Tfrc-associated vesicles by activating the GTPase Rab8, which subsequently promotes the recruitment of the exocyst complex and vesicle exocytosis. Our results reveal a critical role for Grab in regulating the Tf cycle and provide new insights into iron homeostasis and erythropoiesis.

Surgical repair for deformities of the nail unit.

The nail apparatus is the largest and most complex skin appendage. Defects in this unit can result in significant functional insufficiency and cosmetic disfigurement. Common nail deformities include split nail, short nail, onycholysis, nail malalignment, hooked nail, and absent nail. Currently, surgical repair is the primary treatment for such deformities. Based on the etiological and anatomical classifications, one or more appropriate operations can be selected to repair nail unit deformities. These include autologous fat grafting, longitudinal cicatrectomy, Z-plasties, nail bed elongation, split-thickness sterile matrix grafting, volar V-Y advanced flap reconstruction, sterile matrix particle grafting, germinal matrix flaps, and germinal matrix grafting. This review discusses the fundamental classification of nail unit deformities, common reconstructive surgical techniques, and their features.

Sevoflurane preconditioning prevents acute renal injury caused by ischemia-reperfusion in mice via activation of the Nrf2 signaling pathway.

Oxidative stress, caused by renal ischemia reperfusion (IR)/hypoperfusion, is one of the main causes of acute kidney injury (AKI). Previous studies have demonstrated that sevoflurane (SEV) protects organs from the damage caused by oxidative stress. In the present study, mice were randomly assigned to a sham operation group (Sham), IR-vehicle group (IR+ vehicle), IR + SEV low-dose preconditioning group and an IR + SEV high-dose preconditioning group. The effect of SEV on nuclear factor E2-related factor 2 (Nrf2), a key regulatory protein of the endogenous antioxidant defense system and, consequently oxidative stress, inflammation and apoptosis-related factors, were all quantified using commercial kits or by western blotting. SEV preconditioning was demonstrated to ameliorate kidney injury as a result of decreased blood urine nitrogen and serum creatinine levels, activated Nrf2 expression in the kidney and decreased oxidative stress and inflammatory index levels an AKI mouse model. SEV preconditioning also protected injured kidney via the downregulation of caspase-3 protein expression levels. In addition, using the Nrf2 inhibitor, Brusatol, significantly abolished the SEV preconditioning renal protective effect. Using an in vitro HK-2 cell model of hypoxia/reoxygenation, it was also demonstrated that Nrf2 pathway activation was necessary for SEV to exert its beneficial effect for tubular cell injury caused by hypoxia/reoxygenation. These results indicated that SEV may protect against renal injury caused by IR via Nrf2 upregulation.

Risk factors for peripherally inserted central catheterization-associated bloodstream infection in neonates. / ç»å¤–å‘¨é™è„‰ç©¿åˆºä¸­å¿ƒé™è„‰ç½®ç®¡æ‚£å„¿ç›¸å ³æ€§è¡€æºæ„ŸæŸ“çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the features of catheter-related bloodstream infection (CRBSI) or central line-associated bloodstream infection (CLABSI) after peripherally inserted central catheterization (PICC) in neonates admitted to the neonatal intensive care unit (NICU) and the risk factors for CRBSI or CLABSI. METHODS: A retrospective analysis was performed on the medical data of the neonates who were treated and required PICC in the NICU of the Children's Hospital, Zhejiang University School of Medicine from June 1, 2018 to May 1, 2020. The catheterization-related data were collected, including placement time, insertion site, removal time, and antimicrobial lock of PICC. The multivariate logistic regression model was used to investigate the risk factors for CRBSI or CLABSI in the neonates. RESULTS: A total of 446 neonates were enrolled, with a mean gestational age of (30.8±4.0) weeks, a mean birth weight of (1 580±810) g, a median age of 9 days, and a median duration of PICC of 18 days. The incidence rates of CLABSI and CRBSI were 5.6 and 1.46 per 1 000 catheter days, respectively. Common pathogens for CLABSI caused by PICC included Staphylococcus epidermidis (n=19) and Klebsiella pneumoniae (n=11), and those for CRBSI caused by PICC included Klebsiella pneumoniae (n=6). The risk of CLABSI caused by PICC increased significantly with prolonged durations of PICC and antibiotic use, and the PICC-related infection probability at head and neck was significantly lower than that in the upper and low limbs (P<0.05), while the above conditions were more obvious in neonates with a birth weight of <1 500 g. The risk of CRBSI caused by PICC decreased with the increase in gestational age (P<0.05). CONCLUSIONS: CRBSI and CLABSI remain serious issues in NICU nosocomial infection. The identification of the risk factors for CRBSI and CLABSI provides a basis for improving the quality of clinical care and management.

[Effect of moxibustion with wheat-grain-sized moxa cones on uterine natural killer cells and deci-dualization in rats with thin endometrium].

OBJECTIVE: To observe the effect of moxibustion at "Shenshu"(BL23) and "Guanyuan" (CV4) on decidua-lization and uterine natural killer cells in rats with thin endometrium, so as to explore its mechanism underlying promotion of embryo implantation. METHODS: Female SD rats were randomly divided into normal control, model and wheat-grain-sized moxa cone moxibustion (moxibustion) groups, with 14 rats in each group. The thin endometrium model was established by bilaterally intrauterine perfusion of 95% ethanol (first) and saline (later) during estrus. For rats of the moxibustion group, the ignited wheat-grain-sized moxa cones were applied to bilateral BL23 and CV4, with 7 moxa cones for each acupoint, once a day, continuously for 3 estrous cycles. Then the male and female rats were raised in the same cage. On the 5th day of pregnancy, the rats were killed under anesthesia and the uterus tissue was collected for measuring the endometrium thickness and the numbers of blood vessels and glands after H.E. staining, detecting the levels of the proportion of natural killer cells with flow cytometry. After the uterine natural killer cells were sorted by the immunomagnetic bead method, the expression levels of insulin-like growth factor binding protein (IGFBP-1), interferon(INF-γ), tumor necrosis factor(TNF-α), transforming growth factor(TGF-ß), interleukin 4(IL-4) and IL-10 mRNAs were detected by using fluorescence quantitative real-time PCR. RESULTS: Compared with the normal control group, the endometrium thickness, number of glands and blood vessels, and the expression levels of IGFBP-1, TGF-ß, IL-4 and IL-10 mRNAs were significantly decreased (P<0.01, P<0.05), while the expression levels of IFN-γ and TNF-α mRNAs were significantly increased (P<0.05，P<0.01) in the model group. In contrast to the model group, the endometrium thickness, number of glands and blood vessels, and the expression levels of IGFBP-1, TGF-ß, IL-4 and IL-10 mRNAs were significantly increased (P<0.05, P<0.01), while the expression levels of IFN-γ and TNF-α mRNAs were considerably down-regulated (P<0.05, P<0.01) in the moxibustion group. No significant difference was found among the 3 groups in the proportion of natural killer cells in the endometrium (P>0.05). CONCLUSION: Moxibustion of BL23 and CV4 with wheat-grain-sized moxa cones can improve the degree of thin endometrial decidualization, which may be related with its functions in regulating the levels of cytokines secreted from natural killer cells in the uterus.

Risk factors for peripherally inserted central catheterization-associated bloodstream infection in neonates / 中国当代儿科杂志

OBJECTIVES@#To study the features of catheter-related bloodstream infection (CRBSI) or central line-associated bloodstream infection (CLABSI) after peripherally inserted central catheterization (PICC) in neonates admitted to the neonatal intensive care unit (NICU) and the risk factors for CRBSI or CLABSI.@*METHODS@#A retrospective analysis was performed on the medical data of the neonates who were treated and required PICC in the NICU of the Children's Hospital, Zhejiang University School of Medicine from June 1, 2018 to May 1, 2020. The catheterization-related data were collected, including placement time, insertion site, removal time, and antimicrobial lock of PICC. The multivariate logistic regression model was used to investigate the risk factors for CRBSI or CLABSI in the neonates.@*RESULTS@#A total of 446 neonates were enrolled, with a mean gestational age of (30.8±4.0) weeks, a mean birth weight of (1 580±810) g, a median age of 9 days, and a median duration of PICC of 18 days. The incidence rates of CLABSI and CRBSI were 5.6 and 1.46 per 1 000 catheter days, respectively. Common pathogens for CLABSI caused by PICC included Staphylococcus epidermidis (n=19) and Klebsiella pneumoniae (n=11), and those for CRBSI caused by PICC included Klebsiella pneumoniae (n=6). The risk of CLABSI caused by PICC increased significantly with prolonged durations of PICC and antibiotic use, and the PICC-related infection probability at head and neck was significantly lower than that in the upper and low limbs (P<0.05), while the above conditions were more obvious in neonates with a birth weight of <1 500 g. The risk of CRBSI caused by PICC decreased with the increase in gestational age (P<0.05).@*CONCLUSIONS@#CRBSI and CLABSI remain serious issues in NICU nosocomial infection. The identification of the risk factors for CRBSI and CLABSI provides a basis for improving the quality of clinical care and management.

TRIM21 suppresses invasion of hepatocellular carcinoma cells by promoting β-catenin ubiquitylation and degradation / 南方医科大学学报

OBJECTIVE@#To explore the role of TRIM21 in modulating the invasive phenotype of hepatocellular carcinoma (HCC) cells and its mechanism of action.@*METHODS@#RNA interference technique was used to knock down the expression of TRIM21 and β-catenin, alone or in combination, in HCC cell lines 97H and LM3, and the interfering efficiency and the activity of closely related pathways were determined using Western blotting. The two cells with TRIM21 knockdown (siTRIM21 97H and siTRIM21 LM3 cells) were assessed for their invasion ability in vitro using Transwell invasion assay, and the lung metastasis capacity of siTRIM21 LM3 cells following tail vein injection was evaluated in nude mice. The binding of TRIM21 with β-catenin and the ubiquitylation level of β-catenin in TRIM21-overexpressing HEK293 cells were determined with Western blotting and co-immunoprecipitation assay. We also compared the overall survival of patients with CTNNB1highTRIM21high and CTNNB1highTRIM21low HCC subtypes using Kaplan-Meier method based on filtrated and grouped HCC clinical data from TCGA database.@*RESULTS@#TRIM21 knockdown significantly enhanced the invasion ability of 97H and LM3 cells in vitro (P < 0.01 or 0.05) and the lung metastasis ability of LM3 cells in nude mice (P < 0.01), and simultaneous knockdown of β -catenin obviously suppressed the in vitro invasiveness of the cells (P < 0.0001 or 0.05). Co-immunoprecipitation assay showed that TRIM21 was capable of directly binding with β-catenin protein to accelerate the ubiquitination and degradation of the latter, leading to inhibition of nuclear translocation of β-catenin and hence reduced invasiveness of HCC cells. Bioinformatic analysis showed that compared patients with CTNNB1highTRIM21low HCC subtype where Wnt pathway was activated, the patients with CTNNB1highTRIM21high HCC subtype had a significantly better survival outcomes (P < 0.05).@*CONCLUSION@#A high expression of TRIM21 suppresses the invasion of HCC cells by promoting β-catenin ubiquitylation and degradation, which possibly explains the poor prognosis of CTNNB1highTRIM21low HCC patients.

Standard liver weight model in adult deceased donors with fatty liver: A prospective cohort study.

BACKGROUND: Standard liver weight (SLW) is frequently used in deceased donor liver transplantation to avoid size mismatches with the recipient. However, some deceased donors (DDs) have fatty liver (FL). A few studies have reported that FL could impact liver size. To the best of our knowledge, there are no relevant SLW models for predicting liver size. AIM: To demonstrate the relationship between FL and total liver weight (TLW) in detail and present a related SLW formula. METHODS: We prospectively enrolled 212 adult DDs from West China Hospital of Sichuan University from June 2019 to February 2021, recorded their basic information, such as sex, age, body height (BH) and body weight (BW), and performed abdominal ultrasound (US) and pathological biopsy (PB). The chi-square test and kappa consistency score were used to assess the consistency in terms of FL diagnosed by US relative to PB. Simple linear regression analysis was used to explore the variables related to TLW. Multiple linear regression analysis was used to formulate SLW models, and the root mean standard error and interclass correlation coefficient were used to test the fitting efficiency and accuracy of the model, respectively. Furthermore, the optimal formula was compared with previous formulas. RESULTS: Approximately 28.8% of DDs had FL. US had a high diagnostic ability (sensitivity and specificity were 86.2% and 92.9%, respectively; kappa value was 0.70, P < 0.001) for livers with more than a 5% fatty change. Simple linear regression analysis showed that sex (R2, 0.226; P < 0.001), BH (R2, 0.241; P < 0.001), BW (R2, 0.441; P < 0.001), BMI (R2, 0.224; P < 0.001), BSA (R2, 0.454; P < 0.001) and FL (R2, 0.130; P < 0.001) significantly impacted TLW. In addition, multiple linear regression analysis showed that there was no significant difference in liver weight between the DDs with no steatosis and those with steatosis within 5%. Furthermore, in the context of hepatic steatosis, TLW increased positively (non-linear); compared with the TLW of the non-FL group, the TLW of the groups with hepatic steatosis within 5%, between 5% and 20% and more than 20% increased by 0 g, 90 g, and 340 g, respectively. A novel formula, namely, -348.6 + (110.7 x Sex [0 = Female, 1 = Male]) + 958.0 x BSA + (179.8 x FLUS [0 = No, 1 = Yes]), where FL was diagnosed by US, was more convenient and accurate than any other formula for predicting SLW. CONCLUSION: FL is positively correlated with TLW. The novel formula deduced using sex, BSA and FLUS is the optimal formula for predicting SLW in adult DDs.

Electroacupuncture Improves Pregnancy Outcomes in Rats with Thin Endometrium by Promoting the Expression of Pinopode-Related Molecules.

A thin endometrium affects the success of assisted reproduction due to low endometrial receptivity. Acupuncture improves endometrial receptivity and promotes the formation of pinopodes, the ultrastructure marker implantation window. However, the specific underlying mechanisms remain unclear. In this study, the efficacy of acupuncture treatment and its underlying mechanism were investigated by analyzing pregnancy rate, pinopode formation, and related molecular markers in thin endometrium model rats. Absolute ethanol (95%) was injected into the uteruses of female Sprague-Dawley rats to construct a thin endometrium model. In this model, acupuncture stimulation at EX-CA1, SP6, and CV4 ameliorated the pregnancy rate. Significantly increased embryo implantation, endometrial thickness, numbers of glands, and blood vessels were observed in the electroacupuncture (EA) group compared to the model group. The number of pinopodes in the EA group was abundant, with a shape similar to that of the control group. Additionally, significantly higher expression levels of pinopode-related markers, including integrin αvß3, homeobox A10 (HOXA10), heparin-binding EGF-like growth factor (HBEGF), estrogen receptor alpha (ERα), and progesterone receptor (PR), were observed in the EA group than those in the model group. In conclusion, EA had a positive effect on the endometrial receptivity of thin endometrium model rats by improving pinopode formation through multiple molecular targets.