A comprehensive meta-analysis comparing the effectiveness and safety of cold snare polypectomy and hot snare polypectomy in removing colorectal polyps ≤ 10 mm.

OBJECTIVE: The optimal methods for removing polyps remain controversial especially for polyps ≤10mm. We aim to combine the latest evidence to evaluate and compare the effectiveness and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP) in the removal of colorectal polyps ≤10mm in size. METHODS: We performed an extensive search across multiple databases, including PubMed, Embase, Cochrane, and Web of Science, with the search period ending in April 2023 for randomized controlled trials comparing the effectiveness and/or safety of CSP and HSP for the removal of ≤10mm colorectal polyps.The final outcomes included complete resection rate, operation time, and postoperative adverse events (including immediate bleeding, delayed bleeding, and perforation) rates. RESULTS: A total of 14 eligible randomized controlled trials were included, involving 7,460 patients and 15,829 polyps. The incidence of immediate bleeding was observed to be more prevalent in CSP in contrast to HSP, and the disparity was statistically notable (OR=2.18, 95% CI: 1.43-3.30, I2=36%, P=0.0003). The incidence of delayed bleeding was observed to be lower in CSP in contrast to HSP, and this difference was statistically significant (OR=0.30, 95% CI: 0.15-0.58, I2=0%, P=0.0003). Procedure time: both the total colonoscopy time and specific polypectomy time were shorter in CSP than in HSP (MD=-5.92, 95% CI: -9.70 to -2.14, I2=96%, P=0.002; MD=-0.56, 95% CI: -0.91 to -0.20, I2=77%, P=0.002). There were no statistically significant differences in complete resection and the polyp retrieval rate between CSP and HSP. CONCLUSION: CSP is as effective and safe as HSP for ≤10mm colorectal polyps, while effectively reducing the risk of delayed bleeding and shortening the procedure time.

Predominant control of PDGF/PDGF receptor signaling in the migration and proliferation of human adipose­derived stem cells under culture conditions with a combination of growth factors.

Human adipose-derived stem cells (hASCs) play important roles in regenerative medicine and tissue engineering. However, their clinical applications are limited because of their instability during cell culture. Platelet lysates (PLTs) contain large amounts of growth factors that are useful for manufacturing cellular products. Platelet-derived growth factor (PDGF) is a major growth factor in PLTs and a potent mitogen in hASCs. To optimize growth conditions, the effects of a combination of growth factors on the promotion of hASC proliferation were investigated. Moreover, PDGF-BB combined with vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) markedly enhanced the viability of hASCs compared with the effects of PDGF-BB alone. Neither VEGF nor HGF had any effect alone. All growth factor receptor inhibitors inhibited cell proliferation. Wound healing assays revealed that VEGF and HGF stimulated PDGF-dependent cell migration. The effects of these growth factors on the activation of their cognate receptors and signaling enzymes were assessed using immunoblotting. Phosphorylation of PDGF receptor (PDGFR)ß, VEGF receptor (VEGFR)2 and MET proto-oncogene and receptor tyrosine kinase was induced by PDGF-BB treatment, and was further increased by treatment with PDGF-BB/VEGF and PDGF-BB/HGF. The levels of phospho-ERK1/2 and phospho-p38MAPK were increased by these treatments in parallel. Furthermore, the expression levels of SRY-box transcription factor 2 and peroxisome proliferator-activated receptor g were increased in PDGF-BB-treated cells, and PDGF-BB played a dominant role in spheroid formation. The findings of the present study highlighted that PDGF/PDGFR signaling played a predominant role in the proliferation and migration of hASCs, and suggested that PDGF was responsible for the efficacy of other growth factors when hASCs were cultured with PLTs.

Activation of cell adhesion and migration is an early event of platelet-rich plasma (PRP)-dependent stimulation of human adipose-derived stem/stromal cells.

Stem cell therapy is a promising treatment in regenerative medicine. Human adipose-derived stem/stromal cells (hASCs), a type of mesenchymal stem cell, are easy to harvest. In plastic and aesthetic surgery, hASC may be applied in the treatment of fat grafting, wound healing, and scar remodeling. Platelet-rich plasma (PRP) contains various growth factors, including platelet-derived growth factor (PDGF), which accelerates wound healing. We previously reported that PRP promotes the proliferation of hASC via multiple signaling pathways, and we evaluated the effect of PRP on the stimulation of hASC adhesion and migration, leading to the proliferation of these cells. When hASCs were treated with PRP, AKT, ERK1/2, paxillin and RhoA were rapidly activated. PRP treatment led to the formation of F-actin stress fibers. Strong signals for integrin ß1, paxillin and RhoA at the cell periphery of RPR-treated cells indicated focal adhesion. PRP promoted cell adhesion and movement of hASC, compared with the control group. Imatinib, an inhibitor of the PDGF receptor tyrosine kinase, inhibited the promotion of PRP-dependent cell migration. PDGF treatment of hASCs also stimulated cell adhesion and migration but to a lesser extent than PRP treatment. PRP promoted the adhesion and the migration of hASC, mediated by the activation of AKT in the integrin signaling pathway. PRP treatment was more effective than PDGF treatment in enhancing cell migration. Thus, the ability of PRPs to promote migration of hASC to enhance cell growth is evident.

Validation of reliable safe harbor locus for efficient porcine transgenesis.

Transgenic technology is now widely used in biomedical and agricultural fields. Transgenesis is commonly achieved through random integration which might cause some uncertain consequences. The site-specific integration could avoid this disadvantage. This study aimed to screen and validate the best safe harbor (SH) locus for efficient porcine transgenesis. First, the cells carrying the EGFP reporter construct at four different SH loci (ROSA26, AAVS1, H11 and COL1A1) were achieved through CRSIPR/Cas9-mediated HDR. At the COL1A1 and ROSA26 loci, a higher mRNA and protein expression of EGFP was detected, and it was correlated with a lower level of DNA methylation of the EGFP promoter, hEF1α. A decreased H3K27me3 modification of the hEF1α promoter at the COL1A1 locus was also detected. For the safety of transgenesis at different SH locus, we found that transgenesis could relatively alter the expression of the adjacent endogenous genes, but the influence was limited. We also did not observe any off-target cleavage for the selected sgRNAs of the COL1A1 and ROSA26 loci. In conclusion, the COL1A1 and ROSA26 were confirmed to be the best two SH loci with the COL1A1 being more competitive for porcine transgenesis. This work would greatly facilitate porcine genome engineering and transgenic pig production.

Porcine genome engineering for xenotransplantation.

The extreme shortage of human donor organs for treatment of patients with end-stage organ failures is well known. Xenotransplantation, which might provide unlimited organ supply, is a most promising strategy to solve this problem. Domestic pigs are regarded as ideal organ-source animals owing to similarity in anatomy, physiology and organ size to humans as well as high reproductive capacity and low maintenance cost. However, several barriers, which include immune rejection, inflammation and coagulative dysfunctions, as well as the cross-species transmission risk of porcine endogenous retrovirus, blocked the pig-to-human xenotransplantation. With the rapid development of genome engineering technologies and the potent immunosuppressive medications in recent years, these barriers could be eliminated through genetic modification of pig genome together with the administration of effective immunosuppressants. A number of candidate genes involved in the regulation of immune response, inflammation and coagulation have been explored to optimize porcine xenograft survival in non-human primate recipients. PERV inactivation in pigs has also been accomplished to firmly address the safety issue in pig-to-human xenotransplantation. Many encouraging preclinical milestones have been achieved with some organs surviving for years. Therefore, the clinical trials of some promising organs, such as islet, kidney and heart, are aimed to be launched in the near future.

Staged reconstructive treatment for extensive irregular cicatricial alopecia after burn.

For extensive irregular cicatricial alopecia after burn, effective and pleasing restoration of hair-bearing scalp remains challenging. In this article, the authors presented staged reconstructive treatment for extensive irregular cicatricial alopecia with the goal to achieve better and reliable results. A retrospective review of staged reconstructive treatment performed in 16 patients with extensive irregular cicatricial alopecia after burn was conducted. In stage 1, final flaps were designed at 1st. Tissue expanders were placed into the subgaleal plane and serially inflated with normal saline. In stage 2, scarring tissues were excised and the expanded hair-bearing flaps were advanced to the defect. Hair grafts were harvested from excessive hair-bearing scalps excised from the flaps and replanted. For patients with less satisfactory results, stage 3 was performed by hair transplantation. Cicatricial area, follicular unit density, survival rate of hair grafts, and patients' satisfaction were measured before and after each stage. Thirteen patients received 3-stage treatment, and 3 received 2-stage treatment. Significant improvements in aesthetics and patient satisfaction were achieved in all the patients. No flap necrosis, implant exposure or hematoma was observed. Ideal, aesthetic, and reliable results could be obtained using staged reconstructive treatment for patients with extensive irregular cicatricial alopecia after burn.

An innovative thread-lift technique for facial rejuvenation and complication management: A case report.

RATIONALE: Aging of face is an unavoidable process. Traditional procedures for facial rejuvenation have multiple disadvantages. In this case report, we used an innovative technique combining thread lift with small incision rhytidectomy for facial rejuvenation. Management for complication was also reported. PATIENT CONCERNS: We presented a 52-year-old male with facial ptosis and wrinkles. DIAGNOSES: The patient was diagnosed as facial aging including skin laxity, mid-face and mandibular jowl ptosis, static crows-feet wrinkles, and deepening nasolabial fold. INTERVENTIONS: We used an innovative technique combining thread lift with small incision rhytidectomy to treat facial aging. OUTCOMES: Improvements of the crow's feet, nasolabial fold, mid-face and lower face ptosis were observed. Complication of subcutaneous nodule was corrected with cosmetic effect of thread lift remained. LESSONS: The innovative technique combining thread lift with small incision rhytidectomy is a good alternative for the treatment of facial aging.

Phoenixin: A Newly Discovered Peptide with Multi-Functions.

Phoenixin (PNX), a newly identified peptide cleaved from the C-terminus of protein C4orf52, mainly exists in two active isoforms, phoenixin-14 (PNX-14) amide and phoenixin-20 (PNX-20) amide that were first isolated from the rat hypothalamus and bovine heart, respectively. Initial studies demonstrated that PNX is a reproductive peptide, which affects the hypothalamus pituitary genital (HPG) axis through regulating the expression of kisspeptin, GnRH, GnRH receptor, LH and oestrus process. However, further studies indicated that PNX might play a wide range of roles in additional physiological process such as inhibiting visceral pain and eliciting pruritus, inducing anxiety, improving memory retention. Recently, Gpr173, also designated as SREB3, was identified as the cognate receptor of PNX. Whereas, the regulatory mechanism of PNX has not been fully clarified. This review aims to provide the current knowledge of PNX and propose some study directions for future research.

[Effect of intermittent hypoxia on lipid metabolism in liver cells and the underlying mechanism].

OBJECTIVE: To determine the effect of intermittent hypoxia on lipid metabolism in liver cells and to explore the possible molecular pathways involved in this process. METHODS: An intermittent hypoxia cell model system was established by incubating the human hepatic cell lines L02 and HepG2 in an atmosphere of 2% O2, 5% CO2 and 93% N2 for 8 hours per day over a period of 1, 2, 3, 4 or 5 days. Cells cultured in normoxia conditions (21% O2) served as controls. Changes in intracellular lipid droplets and triglyceride (TG) levels were assessed by biochemical assays and oil red staining. Changes in intracellular reactive oxygen species (ROS) were assessed by inverted fluorescence microscopy and flow cytometry. Changes in expression of hypoxia-inducible factor (HIF)-1a and HIF-2a proteins, and the downstream ADFP, SREBP-1c and FAS proteins, were detected by western blotting. RESULTS: For both L02 and HepG2 cell lines, the cells grown under hypoxic conditions showed significantly higher lipid droplet accumulation and TG content than the cells grown under normoxic conditions (F(L02) =61.83, FHepG2 =104.19, P less than 0.01). Both oxygen concentration and time appeared to be correlated with these lipid-related changes (F(L02) =39.60, FHepG2 =76.39, P less than 0.01). The ROS fluorescence index was significantly increased after 2 days of intermittent hypoxia L02: 0.703 ± 0.129 vs. 3.310 ± 0.198, t =22.0637 and HepG2:0.617 ± 0.156 vs. 2.33 ± 0.42, t =7.2003, P < 0.05); in addition, increasing trends were observed in the ROS content and intensity of green fluorescence in conjunction with increased time of exposure to intermittent hypoxia (F(L02) =1021.84, FHepG2 =49.89, P less than 0.01). Compared with their respective control groups, the L02 and HepG2 cells both showed significantly upregulated expression of HIF-1a ADFP, SREBP-1c and FAS (L02:FHIF-1a =371.19, FsREBP-1c =204.49, FFAS =38.20, FADFP =154.31, P less than 0.05 and HepG2:FHF-1a =150.84, FSRERBP-1c =107.35, FFAs =279.71, FADFP =352.06, P less than 0.01). In contrast, the HIF-2a level was markedly decreased in the cells after 4 and 5 days of exposure to intermittent hypoxia (F(L02) =125.29, FHcpG2 =10.68, P less than 0.05). CONCLUSION: Under intermittent hypoxic conditions, ROS may regulate the expression of hypoxia-inducible factors and the adipose differentiation-related protein,as well as influence fatty acid metabolism via a HIF-1 a-SREBP-1 c-FAS signal and upregulation of the ADFP protein, in liver cells.

Endoplasmic reticulum stress leads to lipid accumulation through upregulation of SREBP-1c in normal hepatic and hepatoma cells.

Endoplasmic reticulum stress (ERS) has been found in non-alcoholic fatty liver disease. The study was to further explore the mechanistic relationship between ERS and lipid accumulation. To induce ERS, the hepatoblastoma cell line HepG2 and the normal human L02 cell line were exposed to Tg for 48 h. RT-PCR and Western blot were performed to evaluate glucose-regulated protein (GRP-78) expression as a marker of ERS. ER ultrastructure was assessed by electron microscopy. Triglyceride content was examined by Oil Red O staining and quantitative intracellular triglyceride assay. The hepatic nuclear sterol regulatory element-binding protein (SREBP-1c), liver X receptor (LXRs), fatty acid synthase (FAS), and acetyl-coA carboxylase (ACC1) expressions were examined by real-time PCR and Western blot. 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF) was used to inhibit S1P serine protease inhibitor, and SREBP-1c cleavage was evaluated under ERS. SREBP-1c was knockdown and its effect on lipid metabolism was observed. Tg treatment upregulated GRP-78 expression and severely damaged the ER structure in L02 and HepG2 cells. ERS increased triglyceride deposition and enhanced the expression of SREBP-1c, FAS, and ACC1, but have no influence on LXR. AEBSF pretreatment abolished Tg-induced SREBP-1c cleavage. Moreover, SREBP-1c silencing reduced triglycerides and downregulated FAS expression. Pharmacological ERS induced by Tg leads to lipid accumulation through upregulation of SREBP-1c in L02 and HepG2 cells.

N-heterocyclic carbene-catalyzed cascade annulation reaction of o-vinylarylaldehydes with nitrosoarenes: one-step assembly of functionalized 2,3-benzoxazin-4-ones.

The NHC-catalyzed reactions of ortho electron-deficient vinyl substituted arylaldehydes with nitrosoarenes were studied. The reactions produced multifunctional 2,3-benzoxazin-4-ones in good to excellent yields via a cascade aza-benzoin reaction between aldehyde and nitroso groups followed by an intramolecular oxo-Michael addition. The resulting 1-acetate substituted 2,3-benzoxazinones were transformed into a new type of ß-hydroxycarboxylate derivatives or 3-oxo-1-isobenzofuranacetates, respectively, under different reductive conditions. This work not only provides a simple and efficient method for the construction of multifunctional 2,3-benzoxazin-4-ones of potential pharmacological interest, but also expands the application of NHC-catalyzed cascade reactions in the formation of carbon-heteroatom and heteroatom-heteroatom bonds.

The multicomponent reaction of imidazo[1,5-a]pyridine carbenes with phthalaldehydes and dimethyl acetylenedicarboxylate: a facile construction of benzo[d]furo[3,2-b]azepines.

A study on the multicomponent reaction comprising both N-heterocyclic carbenes and substituted phthalaldehydes is reported. The imidazo[1,5-a]pyridine carbenes, namely imidazo[1,5-a]pyridine-3-ylidenes, reacted with phthalaldehydes and DMAD under very mild conditions to produce novel fused tricyclic benzo[d]furo[3,2-b]azepine derivatives. The resulting fused heterocyclic compounds are fluorescent and they give an emission around 500 nm with quantum yields (Φ(F)) being up to 0.81. This study provides not only a unique approach to fused azepine derivatives that are not easily accessible by other methods, but also opens a new avenue to complicated molecular skeletons. The fluorescence properties of long emission wavelength and high fluorescence quantum yields of some products predict their potential applications as optical sensors.