The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways.

BACKGROUND: As reported, γ-tubulin (TuBG1) is related to the occurrence and development of various types of malignant tumors. However, its role in hepatocellular cancer (HCC) is not clear. The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients. METHODS: The correlation between TuBG1 and clinical parameters and survival in HCC patients was explored by bioinformatics analysis. Immunohistochemistry was used for the verification. The molecular function of TuBG1 was measured using colony formation, scratch assay, trans-well assay and flow cytometry. Gene set enrichment analysis (GSEA) was used to pick up the enriched pathways, followed by investigating the target pathways using Western blotting. The tumor-immune system interactions and drug bank database (TISIDB) was used to evaluate TuBG1 and immunity. Based on the TuBG1-related immune genes, a prognostic model was constructed and was further validated internally and externally. RESULTS: The bioinformatic analysis found high expressed TuBG1 in HCC tissue, which was confirmed using immunohistochemistry and Western blotting. After silencing the TuBG1 in HCC cell lines, more G1 arrested cells were found, cell proliferation and invasion were inhibited, and apoptosis was promoted. Furthermore, the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3 (ATR), phospho-P38 mitogen-activated protein kinase (P-P38MAPK), phospho-P53 (P-P53), B-cell lymphoma-2 associated X protein (Bax), cleaved caspase 3 and P21; decreased the expressions of B-cell lymphoma-2 (Bcl-2), cyclin D1, cyclin E2, cyclin-dependent kinase 2 (CDK2) and CDK4. The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively correlated with the overall survival. The constructed immune prognosis model could effectively evaluate the prognosis. CONCLUSIONS: The increased expression of TuBG1 in HCC is associated with poor prognosis, which might be involved in the occurrence and development of HCC.

Artificial Dermal Scaffold Loaded with Platelet-Rich Plasma Promotes Wound Healing in Pigs by Favoring Angiogenesis.

BACKGROUND The development of artificial dermis provides a new therapeutic method for full-thickness skin defects. However, the slow regeneration of blood vessels in the wound site still cannot be solved perfectly. In our study, we combined platelet-rich plasma (PRP) with Lando® artificial dermal scaffold to promote vascular regeneration and wound healing in pigs. MATERIAL AND METHODS First, PRP was compounded with the artificial dermal scaffold. Then, this material was co-cultured with human vascular endothelial cells (HUVECs) and the growth and proliferation of HUVECs were assessed. Bama miniature pigs wound models were fabricated, the materials were transplanted into the skin defect, and wound healing and blood vessel regeneration were assessed by HE staining and CD31 immunohistochemistry. RESULTS Scanning electron microscopy (SEM) showed that PRP formed round particles on the surface of the artificial dermis material. Cell co-culture experiments showed that the PRP composite artificial dermal scaffold can promote the growth and proliferation of HUVECs. CCK8 experiments demonstrated that the number of cells in the PRP composites group on days 2, 3, 4, and 5 was higher than that in the material alone group (P<0.01). The results of animal experiments showed that PRP composite artificial dermal material can promote wound healing. Histological staining and immunohistochemical staining indicated that the PRP composites group promoted epithelial tissue thickening and blood vessel regeneration in wounds (P<0.001). CONCLUSIONS Our experimental results showed that the artificial dermal scaffold loaded with platelet-rich plasma can promote the revascularization of wounds and accelerated wound healing.

Au@SiO2@CuInS2-ZnS/Anti-AFP fluorescent probe improves HCC cell labeling.

BACKGROUND: Clear tumor imaging is essential to the resection of hepatocellular carcinoma (HCC). This study aimed to create a novel biological probe to improve the HCC imaging. METHODS: Au nano-flower particles and CuInS2-ZnS core-shell quantum dots were synthesized by hydrothermal method. Au was coated with porous SiO2 and combined with anti-AFP antibody. HCC cell line HepG2 was used to evaluate the targeting efficacy of the probe, while flow cytometry and MTT assay were used to detect the cytotoxicity and bio-compatibility of the probe. Probes were subcutaneously injected to nude mice to explore light intensity and tissue penetration. RESULTS: The fluorescence stability of the probe was maintained 100% for 24 h, and the brightness value was 4 times stronger than that of the corresponding CuInS2-ZnS quantum dot. In the targeting experiment, the labeled HepG2 emitted yellow fluorescence. In the cytotoxicity experiments, MTT and flow cytometry results showed that the bio-compatibility of the probe was fine, the inhibition rate of HepG2 cell with 60% Cu-QDs/Anti-AFP probe and Au-QDs/Anti-AFP probe solution for 48 h were significantly different (86.3%±7.0% vs. 4.9%±1.3%, t = 19.745, P<0.05), and the apoptosis rates were 83.3%±5.1% vs. 4.4%±0.8% (P<0.001). In the animal experiment, the luminescence of the novel probe can penetrate the abdominal tissues of a mouse, stronger than that of CuInS2-ZnS quantum dot. CONCLUSIONS: The Au@SiO2@CuInS2-ZnS/Anti-AFP probe can targetedly recognize and label HepG2 cells with good bio-compatibility and no toxicity, and the strong tissue penetrability of luminescence may be helpful to surgeons.

Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM-PLGA microspheres for bone cancer treatment.

To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic effect and fewer adverse side effects than direct intraperitoneal injection of ADM. The ADM-PLGA-NHAC developed in this study exhibited excellent extended-release drug properties, bone repairing and antineoplastic efficacy, which make it a promising osteoconductivity material with the capability to inhibit osteosarcoma.

Bio-compatibility and cytotoxicity studies of water-soluble CuInS2-ZnS-AFP fluorescence probe in liver cancer cells.

BACKGROUND: The oncogenesis of hepatocellular carcinoma (HCC) is not clear. The current methods of the pertinent studies are not precise and sensitive. The present study was to use liver cancer cell line to explore the bio-compatibility and cytotoxicity of ternary quantum dots (QDs) probe and to evaluate the possible application of QDs in HCC. METHODS: CuInS2-ZnS-AFP fluorescence probe was designed and synthesized to label the liver cancer cell HepG2. The cytotoxicity of CuInS2-ZnS-AFP probe was evaluated by MTT experiments and flow cytometry. RESULTS: The labeling experiments indicated that CuInS2-ZnS QDs conjugated with AFP antibody could enter HepG2 cells effectively and emit intensive yellow fluorescence by ultraviolet excitation without changing cellular morphology. Toxicity tests suggested that the cytotoxicity of CuInS2-ZnS-AFP probe was significantly lower than that of CdTe-ZnS-AFP probe (t test, F=0.8, T=-69.326, P<0.001). For CuInS2-ZnS-AFP probe, time-effect relationship was presented in intermediate concentration (>20%) groups (P<0.05) and dose-effect relationship was presented in almost all of the groups (P<0.05). CONCLUSION: CuInS2-ZnS-AFP QDs probe had better bio-compatibility and lower cytotoxicity compared with CdTe-ZnS-AFP probe, and could be used for imaging the living cells in vitro.

Complete mitochondrial genome data and phylogenetic analysis of Papilio macilentus Janson, 1877 (Lepidoptera: Papilionoidea: Papilionidae).

In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.

Sesn2 Serves as a Regulator between Mitochondrial Unfolded Protein Response and Mitophagy in Intervertebral Disc Degeneration.

Mitochondrial unfold protein response (UPRmt) can induce mitophagy to protect cell from unfold protein. However, how UPRmt induces mitophagy to protect cell is not yet clear. Herein, Sesn2 was considered to be a key molecule that communicated UPRmt and mitophagy in the intervertebral disc. Silencing of Sesn2 was able to reverse the protective effects of Nicotinamide riboside (NR) on nucleus pulposus (NP) cells and inhibit mitophagy induced by UPRmt. UPRmt upregulated Sesn2 through Eif2ak4/eIF2α/Atf4, and further induced mitophagy. Sesn2 promoted the translocation of cytosolic Parkin and Sqstm1 to the defective mitochondria respectively, thereby enhancing mitophagy. The translocation of cytosolic Sqstm1 to the defective mitochondria was dependent on Parkin. The two functional domains of Sesn2 were necessary for the interaction of Sesn2 with Parkin and Sqstm1. The cytosolic interaction of Sesn2 between Parkin and Sqstm1 was independent on Pink1 (named as PINK1 in human) but the mitochondrial translocation was dependent on Pink1. Sesn2-/- mice showed a more severe degeneration and NR did not completely alleviate the intervertebral disc degeneration (IVDD) of Sesn2-/- mice. In conclusion, UPRmt could attenuate IVDD by upregulation of Sesn2-induced mitophagy. This study will help to further reveal the mechanism of Sesn2 regulating mitophagy, and open up new ideas for the prevention and treatment of IVDD.

Insights into the Adaptation to High Altitudes from Transcriptome Profiling: A Case Study of an Endangered Species, Kingdonia uniflora.

Kingdonia uniflora is an endangered alpine herb that is distributed along an altitudinal gradient. The unique traits and important phylogenetic position make K. uniflora an ideal model for exploring how endangered plants react to altitude variation. In this study, we sampled nine individuals from three representative locations and adopted RNA-seq technology to sequence 18 tissues, aiming to uncover how K. uniflora responded to different altitudes at the gene expression level. We revealed that genes that responded to light stimuli and circadian rhythm genes were significantly enriched in DEGs in the leaf tissue group, while genes that were related to root development and peroxidase activity or involved in the pathways of cutin, suberin, wax biosynthesis, and monoterpenoid biosynthesis were significantly enriched in DEGs in the flower bud tissue group. All of the above genes may play an important role in the response of K. uniflora to various stresses, such as low temperatures and hypoxia in high-altitude environments. Furthermore, we proved that the discrepancy in gene expression patterns between leaf and flower bud tissues varied along the altitudinal gradient. Overall, our findings provide new insights into the adaptation of endangered species to high-altitude environments and further encourage parallel research to focus on the molecular mechanisms of alpine plant evolution.

The role of AGEs in pathogenesis of cartilage destruction in osteoarthritis.

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2022;11(5):292-300.

ALYREF associated with immune infiltration is a prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Although ALYREF has been demonstrated to have a role in a number of malignancies, its role in hepatocellular carcinoma (HCC) has received little attention. Our objective was to research at the prognostic value, biological role and relevance of ALYREF to the immune system in HCC. METHODS: The expression of ALYREF and its relationship with clinical parameters of HCC patients were analyzed by liver cancer cohort (LIHC) of The Cancer Genome Atlas. The expression and prognosis were verified by immunohistochemistry experiments. Gene transfection, CCK-8, scratch healing, transwell invasion and flow cytometry were used to assess the molecular function of ALYREF in vitro. The TIMER and TISIDB online data portals were used to assess the relevance of ALYREF to immunization. Stepwise regression analysis of ALYREF-related immune genes in the LIHC training set was used to construct a prognostic risk prediction model. Also, construct a nomogram to predict patient survival. The testing set for internal verification. RESULTS: Knockdown of ALYREF changed the biological phenotypes of HCC cells, such as proliferation, apoptosis, and invasion. In addition, the expression of ALYREF in HCC affected the level of immune cell infiltration and correlated with the overall survival time of patients. The constructed immune prognostic model allows for a valid assessment of patients. CONCLUSION: ALYREF is increased in HCC, has an impact on cellular function and the immune system, and might be used as a prognostic marker.

Propensity score matching study of 325 patients with spontaneous rupture of hepatocellular carcinoma.

Background: This study aims to find out the possible optimal therapy and assess the prognosis properly for patient with spontaneous rupture of hepatocellular carcinoma (HCC). Methods: Propensity score matching (PSM) analysis was used to study the data from 325 patients with ruptured HCC (RHCC) and 2,291 patients with non-RHCC. Results: The incidence and hospital mortality of RHCC were 5.1% and 0.8% respectively, with a median overall survival (OS) time of 17 months. There was no difference between ruptured and non-RHCC patients undergoing conservation treatment in terms of OS. Trans-arterial embolization (TAE) was carried out in 69 (21.2%) cases with RHCC, with a median OS of 7 months, which was no difference from that of non-RHCC (pre- and post-PSM). One hundred and sixty-nine (52.0%) RHCC cases underwent one-stage hepatectomy, with a median OS and disease-free survival (DFS) of 30 and 6 months respectively, which were shorter than that of non-RHCC (post-PSM). TAE plus two-stage hepatectomy was performed in 30 RHCC cases, with a median OS and DFS of 28 and 10 months respectively; these outcomes were better than that from RHCC patients undergoing TAE alone or one-stage hepatectomy (post-PSM), which were no difference from that of non-RHCC patients undergoing hepatectomy. The risk of death for RHCC patient undergoing one-stage hepatectomy is 1.545 times higher than that of one undergoing TAE + two-stage hepatectomy. Conclusions: TAE plus two-stage hepatectomy might be the optimal treatment for RHCC patient. Under the premise of the same pathological properties, there is no difference in prognosis between ruptured and non-RHCC patients if the therapy is appropriate.

High-quality reference genomes of swallowtail butterflies provide insights into their coloration evolution.

Swallowtail butterflies (Papilionidae) are a historically significant butterfly group due to their colorful wing patterns, extensive morphological diversity, and phylogenetically important position as a sister group to all other butterflies and have been widely studied regarding ecological adaption, phylogeny, genetics, and evolution. Notably, they contain a unique class of pigments, i.e., papiliochromes, which contribute to their color diversity and various biological functions such as predator avoidance and mate preference. To date, however, the genomic and genetic basis of their color diversity and papiliochrome origin in a phylogenetic and evolutionary context remain largely unknown. Here, we obtained high-quality reference genomes of 11 swallowtail butterfly species covering all tribes of Papilioninae and Parnassiinae using long-read sequencing technology. Combined with previously published butterfly genomes, we obtained robust phylogenetic relationships among tribes, overcoming the challenges of incomplete lineage sorting (ILS) and gene flow. Comprehensive genomic analyses indicated that the evolution of Papilionidae-specific conserved non-exonic elements (PSCNEs) and transcription factor binding sites (TFBSs) of patterning and transporter/cofactor genes, together with the rapid evolution of transporters/cofactors, likely promoted the origin and evolution of papiliochromes. These findings not only provide novel insights into the genomic basis of color diversity, especially papiliochrome origin in swallowtail butterflies, but also provide important data resources for exploring the evolution, ecology, and conservation of butterflies.

[Percutaneous radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta analysis].

OBJECTIVE: To evaluate the curative effect of percutaneous radiofrequency ablation (RFA) and hepatic resection (RES) for small hepatocarcinoma eligible for Milan criterion using meta analysis method. METHODS: Retrieved clinical trials comparing percutaneous radiofrequency ablation with RES for small hepatocarcinoma published from 1990 to 2010. A meta-analysis was conducted to estimate overall survival and disease free survival. A fixed random effect model or random effect model was established to collect the data. RESULTS: Four randomized controlled trials were included in this analysis. These studies included a total of 539 patients: 252 treated with percutaneous RFA and 287 treated with RES. The differences in overall survival were not statistically significant between RFA and RES (P > 0.05). In the patients treated with RES group, the 2-, 3- and 4-years disease free survival rates were significantly better than that in the patients treated with percutaneous RFA (P < 0.05). The postoperative morbidity rate was significant lower in patients treated with percutaneous RFA (OR: 0.14, 95%CI: 0.09 - 0.22, P = 0.000). But percutaneous RFA had a higher rate of tumor recurrence compared to RES (OR: 2.63, 95%CI: 1.67 - 4.15, P = 0.000). CONCLUSIONS: For small hepatocarcinoma eligible for Milan criterion, percutaneous RFA had a similar overall survival to RES. Percutaneous RFA was the invasive lesser and had a lower postoperative morbidity rate than RES, but RES may had a better prevention of the tumor recurrence than percutaneous RFA. For those patients who don't want to be treated by RES, percutaneous RFA may be a recommendable choice.

Immune implication of FAM83D gene in hepatocellular carcinoma.

FAM83D has been demonstrated to contribute to tumorigenesis. However, its immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify the immune role of FAM83D in HCC. FAM83D was over-expressed in HCC and contributed to poor prognosis according to the results of data analysis based on The Cancer Genome Atlas (TCGA). Afterward, the levels of immune cells infiltration were found to be correlated with the expression level of FAM83D in HCC. Through TISIDB and cBioPortal network tools, a total of 82 FAM83D-associated genes were screened out, including 12 immunoinhibitors, 20 immunostimulators and 50 tightly co-expressed genes. TCGA cohort was divided into train set and test set on the basis of the proportion of 7:3. According to FAM83D-associated immunomodulators, a four gene predicted model was established using train set via the Cox regression analysis. Survival analysis demonstrated that the overall survival (OS) of high-risk HCC patients was poor compared with the patients in low-risk group. The reliability and predicted power of the risk-score model were identified by a receiver operating characteristic (ROC) curve. A risk-score based nomogram as well as a calibration curve, which were created could be used to anticipate patient's 1-year, 3-year and 5-year survival probabilities. The test set was used to validate these results. Our findings showed that the FAM83D gene was related with HCC immunity. The immune marker chosen could be a promising biomarker for HCC prognosis.

[Indication of fusion for degenerative lumbar spinal stenosis treated by "windows technique" laminoforaminotomy].

OBJECTIVE: To explore the indications of fusion for degenerative lumbar spinal stenosis treated by "windows technique". METHODS: From December 1999 to December 2005, 145 consecutive patients who were treated by primary decompression with "windows technique" laminoforaminotomy for degenerative lumbar spinal stenosis, a retrospective study, were divided into 3 groups (A and B and C) by preoperative lumbar conditions and surgical methods. In group A, 39 patients with spinal instability or degenerative lumbar spondylolisthesis or scoliosis underwent decompression and fusion; in group B, 31 patients with spinal instability or degenerative lumbar spondylolisthesis or scoliosis underwent decompression alone; In group C, 75 patients without spinal instability or degenerative lumbar spondylolisthesis or scoliosis were treated by decompression without fusion. On hospital medical records to review, they were followed up by telephone and out-patient referral. Statistics the duration of hospitalization, operative time, estimated blood loss; Observed recrudescence and reoperation and complication; and using Oswestry Disability Index and Visual Analog Scale and satisfaction rate for efficacy assessment, application SPSS 13.0 software. RESULTS: All 145 patients had at least a 3-year follow-up (ranging 37 to 108 months). In the group C, the duration of hospitalization less than in the group A or B (P < 0.05); In the group A, the operative time and estimated blood loss greater than in the group B or C (P < 0.05); The group B treated by decompression alone in the presence of instability or spondylolisthesis or scoliosis showed the worst results by the Oswestry Disability Index or Visual Analog Scale or ate of satisfaction (P < 0.05). The same good results can be obtained in the group A and C. There were not different about recrudescence or reoperation or complication in the three groups. CONCLUSIONS: Fusion should be performed on patients with instability or degenerative lumbar spondylolisthesis or scoliosis after primary decompression with "windows technique" laminoforaminotomy. The patient with simple lumbar spinal stenosis undergone primary surgery does not require fusion.

Erratum to: A Heterologous Fibrin Glue Enhances the Closure Effect of Surgical Suture on the Repair of Annulus Fibrous Defect in a Sheep Model.

The original version of this article unfortunately contained one mistake. The institutions of the authors are wrong. The corrected institutions are given below.Zhi-cai DU1, 2, Li-xin ZHU11Department of Spinal Surgery, Orthopaedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China 2Department of Minimally Invasive Spinal Surgery, The Second Affiliated Hospital of Inner Mon-golia Medical University, Hohhot 010030, China.

Cellular senescence in recurrent tonsillitis and tonsillar hypertrophy in children.

OBJECTIVE: To observe the difference in cellular senescence patterns between recurrent tonsillitis and tonsillar hypertrophy. METHODS AND MATERIALS: Forty-three patients diagnosed with recurrent tonsillitis or tonsillar hypertrophy, based on medical history and symptoms, underwent tonsillectomy. The specimens were collected and examined using senescence ß-galactosidase staining for cellular senescence. Macrophages were detected by immunochemistry. RESULTS: Cellular senescence was found in both recurrent tonsillitis and tonsillar hypertrophy groups. The comparison of cellular senescence in microcompartments of tonsil tissue (germinal centre, mantle zone, subepithelial and intraepithelial) revealed a significant increase of senescent cells in germinal centres in tonsillar hypertrophy compared with that in tonsillar hypertrophy. The majority of senescent cells in both groups were CD68-positive. CONCLUSIONS: Different cellular senescence patterns were found between the two studied paediatric tonsillar diseases. Macrophage senescence may play a role in the pathogenesis of these diseases.

Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice.

AIMS: Liraglutide, a glucagon-like peptide-1(GLP-1) analog, is effective for the treatment of type II diabetes and nonalcoholic fatty liver disease (NAFLD). It was proved that gut microbiome plays a role in the development of NAFLD. This study aims to observe the therapeutic effect of liraglutide on nonalcoholic fatty liver (NAFL) in mice and effect on the gut microbial community. MAIN METHODS: The db/db mice were used as the NAFL model, and lactulose was used as the positive control drug. Hepatic triglyceride, liver histopathology, and indices of glucolipid metabolism, including fasting blood glucose, fasting insulin, insulin resistance index and blood lipids were evaluated after treatment of liraglutide or lactulose for four weeks. The colonic microbiome of the mice was analyzed by 16S rRNA gene sequencing. KEY FINDINGS: Liraglutide significantly reduced the hepatic triglyceride (TG) content, alanine aminotransferase (ALT) activity, fasting blood glucose, insulin resistance and serum low density lipoprotein (LDL) in the db/db mice. In terms of hepatic pathologies, hepatic steatosis was significantly improved after liraglutide treating. Microbiome analysis revealed that liraglutide significantly increased the abundance of Akkermansia, Romboutsia, norank_f_Bacteroidales_S24-7_group, and decreased the abundance of Klebsiella, Anaerotruncus, Bacteroides, Lachnospiraceae_UCG-001, Lachnospiraceae_NK4A136_group, Ruminiclostridium, uncultured_f__Ruminococcaceae, and Desulfovibrio. SIGNIFICANCE: The results of the present study suggested that liraglutide had a certain therapeutic effect on fatty liver in db/db mice and had an impact on the composition of the intestinal microflora, especially some bacteria related to glucolipid metabolism and intestinal inflammation. Affecting gut microbiome might be a potential mechanism of liraglutide in treating NAFL.

A Novel Surgery Classification for Endoscopic Approaches to Middle Ear Cholesteatoma.

This study aimed to develop a novel surgery classification for an endoscopic approach to middle ear cholesteatoma. We retrospectively analyzed the surgical approaches and outcomes of patients with middle ear cholesteatoma. Middle ear cholesteatoma surgeries were divided into four types and two special types as follows: type I, attic retraction pocket, which only requires tympanostomy tube placement or retraction pocket resection and cartilage reconstruction; type II, cholesteatoma which is limited to the attic or in which endoscopy can confirm complete removal of mastoid cholesteatoma lesions, including type II a, requiring only use of a curette, and type II b, requiring use of an electric drill or chisel; type III, cholesteatoma not limited to the attic, in which endoscopy cannot confirm complete removal of mastoid cholesteatoma lesions, requiring the combined use of endoscope and microscope to perform endoscopic tympanoplasty and "Canal Wall Up" mastoidectomy; type IV, extensive involvement of mastoid cavity cholesteatoma lesions and/or cases with a potential risk of complications, removal of which can only be performed under a microscope for "Canal Wall Down" mastoidectomy. In addition, there were two special types: "difficult external auditory canal" and congenital cholesteatoma in children. In our system, type I and type II middle ear cholesteatoma surgery was completely performed under an endoscope alone. However, estimating the extent of the lesions, determining the choice of mastoid opening and reestablishing ventilation are the key points for an endoscopic approach to middle ear cholesteatoma. The classification of endoscopic middle ear cholesteatoma surgery may benefit the selection of surgical indications.