Advances in the mechanism of small nucleolar RNA and its role in DNA damage response.

Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.

Oral Decoctions Based on Qi-Yin Syndrome Differentiation After Adjuvant Chemotherapy in Resected Stage ΙΙΙA Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

OBJECTIVE: Powerful adjuvant strategies are required to improve the survival of patients with completely resected stage ΙΙΙA non-small cell lung cancer (NSCLC). We aimed to compare the efficacy of traditional Chinese medicine (TCM) treatment versus observation after adjuvant chemotherapy in these patients. METHODS: Eligible patients were randomized 1:1 to receive either oral decoctions based on Qi-Yin syndrome differentiation (TCM group) or observation (observation group). The intervention lasted for 12 months. The primary endpoint was 1-year disease-free survival (DFS). Secondary endpoints were DFS, quality of life, regulatory T cells (Tregs), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on the surface of Tregs in peripheral blood. We used EORTC QLQ-LC43 to evaluate quality of life. RESULTS: Between Apr 29, 2019, and Nov 11, 2021, 75 patients were randomly assigned to oral decoctions based on Qi-Yin syndrome differentiation (n = 38) or observation (n = 37). The full analysis set included 35 patients in the TCM group and 35 in the observation group. After a median follow-up of 24.2 months, oral decoctions based on Qi-Yin syndrome differentiation improved DFS compared with observation (HR 0.378, 95% CI: 0.157-0.912; P = .03). One-year DFS was 82.1% in the TCM group and 61.9% in the observation group (P = .06). Three months after randomization, scores of total health, role function, emotional function, and social function in the TCM group were higher than those in the observation group (P < .01 for all), scores of fatigue, pain, insomnia, appetite loss, constipation, cough, and chest pain were lower than those in the observation group (P < .05 for all); there was no significant difference in the proportion of Tregs between the TCM group and the observation group (P = .58); the proportion of CTLA-4+Tregs in the TCM group was lower than that in the observation group (P = .046). There were no adverse events that occurred in both groups. CONCLUSIONS: Oral decoctions based on Qi-Yin syndrome differentiation after adjuvant chemotherapy prolonged DFS, reduced the risk of disease recurrence and metastasis, improved quality of life, and down-regulated the proportion of CTLA-4+Tregs in completely resected stage ΙΙΙA NSCLC patients. TRIAL REGISTRATION: Chinese Clinical Trial Register, No. ChiCTR1800019396. Date of registration: 9 November 2018.

Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis.

Disulfidptosis was recently reported to be caused by abnormal disulfide accumulation in cells with high SLC7A11 levels subjected to glucose starvation, suggesting that targeting disulfidptosis was a potential strategy for cancer treatment. We analyzed the relationships between gene expression and mutations and prognoses of patients. In addition, the correlation between gene expression and immune cell infiltration was explored. The potential regulatory mechanisms of these genes were assessed by investigating their related signaling pathways involved in cancer, their expression patterns, and their cellular localization. Most cancer types showed a negative correlation between the gene-set variation analysis (GSVA) scores and infiltration of B cells and neutrophils, and a positive correlation between GSVA scores and infiltration of natural killer T and induced regulatory T cells. Single-cell analysis revealed that ACTB, DSTN, and MYL6 were highly expressed in different bladder urothelial carcinoma subtypes, but MYH10 showed a low expression. Immunofluorescence staining showed that actin cytoskeleton proteins were mainly localized in the actin filaments and plasma membrane. Notably, IQGAP1 was localized in the cell junctions. In conclusion, this study provided an overview of disulfidptosis-related actin cytoskeleton genes in pan-cancer. These genes were associated with the survival of patients and might be involved in cancer-related pathways.

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model.

Objective: Combination immunotherapy strategies targeting OX40, a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation, differentiation, and effector function of tumor-infiltrating T cells, have attracted much attention for their excellent therapeutic effects. In this study, we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core virus-like particles (HBc VLPs) therapy using a mouse colon cancer model. Methods: Humanized B-hOX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-hOX40 antibody. Tumor growth was monitored. Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors. Results: The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth, suggesting that a potent antitumor immunity was induced by the combination therapy. Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells (Teffs) and a significant decrease in regulatory T cells (Tregs) in the tumor microenvironment (TME), which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs. Conclusion: Combination therapy of anti-hOX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice, which may represent a potential design strategy for cancer immunotherapy.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

A role for the cerebellum in motor-triggered alleviation of anxiety.

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

Four new constituents from the fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1-2), two new geranyl glucosides (3-4), and nine known compounds (5-13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

Metabolomics unveils the mechanism of Bufei Huayu decoction in combination with cisplatin against non-small cell lung cancer (NSCLC).

Introduction: Bufei Huayu Decoction (BFHY) is a clinical prescription with reported efficacy in enhancing the therapeutic outcomes of chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, the underlying metabolic mechanism of BFHY's action remains unexplored. Objective: The objective of this study is to investigate the global metabolic effects of cisplatin and cisplatin plus BFHY on NSCLC. Methods: Three groups (NSCLC, cisplatin, and cisplatin + BFHY) underwent a serum metabolomics procedure based on UHPLC-QE-MS. Then, a pathway analysis was carried out using MetaboAnalyst 3.0 to elucidate the therapeutic action routes of cisplatin and cisplatin plus BFHY in NSCLC. Results: In the subcutaneous NSCLC model, both cisplatin and cisplatin + BFHY reduced the tumor volume and caused cell death. In comparison to cisplatin alone, cisplatin + BFHY showed a stronger tumor-suppressing impact. Furthermore, the same 16 metabolic signaling pathways were shared by the cisplatin and cisplatin + BFHY treatments. These typical metabolites are mainly involved in amino acid metabolism, lipid mobilization, nucleic acid metabolism and carbohydrate metabolites. Conclusions: Potential biomarkers and metabolic networks of cisplatin and cisplatin + BFHY's anti-tumor actions are revealed in our investigation.

Association of Breastfeeding Duration with Body Composition in Children Aged 3-5 Years.

Objective: This study aimed to assess the relationship between the body composition of children aged 3-5 years and breastfeeding status and duration. Methods: The study was conducted using data from the National Nutrition and Health Systematic Survey for children 0-17 years of age in China (CNHSC), a nationwide cross-sectional study. Breastfeeding information and potential confounders were collected using standardized questionnaires administered through face-to-face interviews. The body composition of preschool children was measured using bioelectrical impedance analysis. A multivariate linear regression model was used to assess the relationship between breastfeeding duration and body composition after adjusting for potential confounders. Results: In total, 2,008 participants were included in the study. Of these, 89.2% were ever breastfed and the median duration of breastfeeding was 12 months (IQR 7-15 months). Among children aged 3 years, the height-for-age Z-score (HAZ) for the ever breastfed group was lower than that for never breastfed group (0.12 vs. 0.42, P = 0.043). In addition, the weight-for-age Z-score (WAZ) of the ever breastfed group was lower than that of the never breastfed group (0.31 vs. 0.65, P = 0.026), and the WAZ was lower in children aged 4 years who breastfed between 12 and 23 months than in those who never breastfed. Compared to the formula-fed children, the fat-free mass of breastfed infants was higher for children aged 3 years (12.84 kg vs. 12.52 kg, P = 0.015) and lower for those aged 4 years (14.31 kg vs. 14.64 kg, P = 0.048), but no difference was detected for children aged 5 years (16.40 kg vs. 16.42 kg, P = 0.910) after adjusting for potential confounders. No significant difference was detected in the weight-for-height Z-score (WHZ), body mass index (BMI)-for-age Z-score (BAZ), fat-free mass index, and body fat indicators in the ever breastfed and never breastfed groups and among various breastfeeding duration groups for children aged 3-5 years. Conclusion: No obvious associations were detected between breastfeeding duration, BMI, and fat mass indicators. Future prospective studies should explore the relationship between breastfeeding status and fat-free mass.

Combination of BFHY with Cisplatin Relieved Chemotherapy Toxicity and Altered Gut Microbiota in Mice.

Aim: We sought to profile gut microbiota's role in combination of Bu Fei Hua Yu (BFHY) with cisplatin treatment. Methods: Non-small cell lung cancer (NSCLC) mice model were constructed followed by treatment with cisplatin alone or combined with BFHY. Mice weight and tumor volume were measured during the experiment. And mice cecum were detected by hematoxylin and eosin, cecum contents were collected for Enzyme Linked ImmuneSorbent Assay, and stool were profiled for metagenomic sequencing. Results: Combination of BFHY with cisplatin treatment decreased the tumor growth and relieved the damage of cecum. Expressions of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), monocyte chemotactic protein 1 (MCP), and interferon-γ (IFN-γ) were decreased compared with cisplatin treatment alone. Linear discriminant analysis effect size analysis showed that g_Parabacteroides was downregulated and g_Escherichia and g_Blautia were upregulated after cisplatin treatment. After combination with BFHY, g_Bacteroides and g_Helicobacter were decreased. g_Klebsiella, g_Unclssified_Proteobacteria, and g_Unclssified_Clostridiates were increased. Moreover, heatmap results showed that Bacteroides abundance was increased significantly after cisplatin treatment; BFHY combination treatment reversed this state. Function analysis revealed that multiple functions were slightly decreased in cisplatin treatment alone and increased significantly after combination with BFHY. Conclusion: Our study provided evidence of an efficacy of combination of BFHY with cisplatin on treatment of NSCLC and revealed that gut microbiota plays a role in it. The above results provide new ideas on NSCLC treatment.

Oxytocin Receptor in Cerebellar Purkinje Cells Does Not Engage in Autism-Related Behaviors.

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.

Simultaneous development of pneumonitis and autoimmune diabetes secondary to immune checkpoint inhibitor treatment with durvalumab in an advanced small cell lung cancer patient: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed. PATIENT CONCERNS: In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab. DIAGNOSES: According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus. INTERVENTIONS: Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed. OUTCOMES: After the cessation of durvalumab and comprehensive treatment, the patient's respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy. LESSONS: With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients.

Hemorrhagic shock due to ruptured lower limb vascular malformation in a neurofibromatosis type 1 patient: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF-1) is a common autosomal dominant genetic disorder. It is characterized by café-au-lait spots and cutaneous neurofibromas. Although NF-1 typically involves the skin, nerves, bones, and eyes, vascular manifestation in the form of devastating hemorrhage can occur rarely. CASE SUMMARY: We present the case of a 47-year-old female with NF-1 who had a ruptured right lower limb arterial malformation. She presented with sudden right lower limb swelling for two hours and symptoms of hemorrhagic shock on admission. The physical examination revealed a right lower limb presenting as elephantiasis and visible dark-brown pigmentation over a large area. Computed tomography angiography showed right lower limb arteriovenous malformation. Therefore, the patient underwent emergency right lower limb digital subtraction angiography (DSA) and vascular embolization after blood transfusions. However, after DSA, vascular embolization, and repeated blood transfusions, the anemia and right lower limb swelling and tenderness did not improve. As a result, the patient underwent right lower extremity above-knee amputation. After amputation, the patient's hemoglobin level improved significantly without blood transfusion, and she was discharged from the hospital after the incision healed. Postoperative pathological examination suggested neurogenic tumors. No other complications had occurred 1-year follow-up. CONCLUSION: Vascular malformation and rupture are fatal complications of NF-1. Embolization may not provide complete relief, the patient might need to undergo neurofibroma resection or amputation.

Strumal Carcinoid Tumor of the Ovary: Report of Rare Occurrence with Review of Literature.

The primary ovarian carcinoid tumor is a very rare ovarian tumor, which accounts for approximately 0.5% to 1.7% of all carcinoids and 1% of ovarian cancer. According to its histopathological features, it can be divided into four categories: insular, trabecular, strumal, and mucinous, among which insular carcinoid is common in Western countries. By comparison, the chain-typed and trabecular carcinoid seem to be common in Asian countries. To date, about 150 cases have been reported in the world, and 40% of them are strumal carcinoid tumor of the ovary (SCTO), which is a highly specialized teratoma differentiated from the monomer, and often characterized by the coexistence of thyroid follicular tissue and carcinoid tissue with the neuroendocrine function. Preoperative diagnosis may be difficult due to the very insidious nature of the disease and its multiple imaging manifestations. We reported the case of a 39-year-old woman with a 5-year clinical history. Gynecologic examination and ultrasonic testing revealed an enlarged ovary with a diameter of about 60 mm, accompanied by a hypoechoic area, which was suspected to be a benign teratoma. Ca-125, AFP, free T4, TSH, and other diagnostic indicators were normal. During the laparoscopic oophorocystectomy of the left ovary, a smooth and solid tumor with the size of 6 × 6 × 5 cm was found in the right ovary. During the operation, a mature cystic teratoma containing a struma was frozen, then the oophorocystectomy of the left ovary was performed. According to the Federation International of Gynecology and Obstetrics (FIGO) in 2014, histopathological examination showed a mature teratoma with thyroid carcinoid stage Ic, and Douglas's cystic hygroma cytopathology was negative. One year after the operation, the patient was tumor-free, with Ca-125, FT4, and TSH being within the normal range. Specific diagnostic tools and serological monitoring of malignant tumors of the ovary have low specificity and sensitivity in the diagnosis of this rare malignant tumor of the ovary. Female patients with habitual constipation, chronic abdominal colic, diarrhea, and endocrine dysfunction also need to be alert to this rare malignant tumor of the ovary.

Pathogenicity and Immunogenicity of a Serially Passaged Attenuated Genotype 2c Porcine Epidemic Diarrhea Virus Cultured in Suspended Vero Cells.

In this study, one G2c-subtype strain of porcine epidemic diarrhea virus (PEDV) (SHXX1902 strain) was isolated from clinical samples in suspended Vero cells, which was different from the genotype of the commercial AJ1102 vaccine. As a result, we determined the pathogenicity of different passages' isolates (SHXX1902 strain) and compared the immunogenicity of G2c-subtype strain (SHXX1902 strain) with the commercial AJ1102 vaccine. The viral titer reached 107 50% tissue culture infectious dose (TCID50)/ml, which met the requirement for seed virus replication during vaccine development. Five-day-old piglets were orally infected with viruses from passages P5 and P35 to determine the pathogenicity and immunogenicity of different passages. Pregnant sows were immunized with inactivated SHXX1902-P5 or the commercial AJ1102 vaccine (first immunized with an attenuated vaccine and then boosted with an inactivated vaccine) to study the influence of the culture method on the immunogenicity of the strain. The median pig diarrhea dose (PDD50) and the median lethal dose (LD50) of the P5 virus were 102.00 and 102.84 TCID50/ml, respectively. All five piglets infected with the SHXX1902-P5 virus shed the virus 24 h after vaccination, whereas only two of the five piglets treated with the SHXX1902-P35 virus shed the virus 48 h after vaccination. The SHXX1902-P35 virus was partially attenuated in the 5-day-old piglets. Inactivated SHXX1902-P5 induced PEDV-specific immunoglobulin G (IgG) antibody responses equivalent to those induced by AJ1102 after infection in sow serum. However, the IgA titer induced by AJ1102 was much higher than that induced by inactivated SHXX1902-P5 since the boost immunization. On days 5 and 7 after farrowing, the IgA titers were similar among the immunized groups. Our study highlights that serial passage can lead to the attenuation of G2c-subtype strain. The immunogenicity of the inactivated strain was similar to the commercial vaccine. Our observation helped conceptualize appropriate study designs for the PEDV vaccine.

Rice Cell Division Cycle 20s are required for faithful chromosome segregation and cytokinesis during meiosis.

Chromosome segregation must be under strict regulation to maintain chromosome euploidy and stability. Cell Division Cycle 20 (CDC20) is an essential cell cycle regulator that promotes the metaphase-to-anaphase transition and functions in the spindle assembly checkpoint, a surveillance pathway that ensures the fidelity of chromosome segregation. Plant CDC20 genes are present in multiple copies, and whether CDC20s have the same functions in plants as in yeast and animals is unclear, given the potential for divergence or redundancy among the multiple copies. Here, we studied all three CDC20 genes in rice (Oryza sativa) and constructed two triple mutants by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated genome editing to explore their roles in development. Knocking out all three CDC20 genes led to total sterility but did not affect vegetative development. Loss of the three CDC20 proteins did not alter mitotic division but severely disrupted meiosis as a result of asynchronous and unequal chromosome segregation, chromosome lagging, and premature separation of chromatids. Immunofluorescence of tubulin revealed malformed meiotic spindles in microsporocytes of the triple mutants. Furthermore, cytokinesis of meiosis I was absent or abnormal, and cytokinesis II was completely prevented in all mutant microsporocytes; thus, no tetrads or pollen formed in either cdc20 triple mutant. Finally, the subcellular structures and functions of the tapetum were disturbed by the lack of CDC20 proteins. These findings demonstrate that the three rice CDC20s play redundant roles but are indispensable for faithful meiotic chromosome segregation and cytokinesis, which are required for the production of fertile microspores.

One-stage total hip arthroplasty for advanced hip tuberculosis combined with developmental dysplasia of the hip: A case report.

BACKGROUND: A patient with advanced tuberculosis of the hip joint combined with Crowe type IV developmental dysplasia of the hip (DDH) and a drainage sinus is a rare condition. There are no previous reports of this condition, and it is a complex challenge for surgeons to develop a treatment scheme. CASE SUMMARY: We report a 73-year-old male patient with severe hip pain and drainage sinus of the left hip for one month. Approximately 40 years ago, a drainage sinus occurred at the lateral left hip was healed at the local hospital with anti-infectious therapy. After the sinus healed, gradual pain occurred in the left hip for 40 years. Approximately one month prior, hip pain was sharply aggravated, and a drainage sinus reoccurred in the left hip. The X-ray and computed tomography examinations showed destruction of the head and neck of the left femur, as well as an acetabular deformity. The results of Mycobacterium tuberculosis antibody and Xpert were positive. Therefore, the patient was diagnosed with advanced TH combined with Crowe type IV DDH. After 22 d of treatment with anti-tuberculosis chemotherapy, the sinus healed, and the patient underwent one-stage total hip arthroplasty (THA) surgery consisting of debridement, osteotomy, and joint replacement. After surgery, the patient received anti-tuberculosis chemotherapy drugs for nine months, with no recurrent infection. After one year of follow-up, the Harris score of the patient increased from 21 pre-THA to 86. CONCLUSION: Although drainage sinuses are a contraindication to one-stage THA, one-stage THA is still an effective and safe surgical method after the sinus heals.

MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-ß/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7.

BACKGROUND: Various stimuli, including Clonorchis sinensis infection, can cause liver fibrosis. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) with massive production of extracellular matrix (ECM). Our previous study showed that the TGF-ß1-induced Smad signaling pathway played a critical role in the activation of HSCs during liver fibrosis induced by worm infection; however, the mechanisms that modulate the TGF-ß/Smad signaling pathway are still poorly understood. Accumulating evidence demonstrates that miRNAs act as an important regulator of activation of HSCs during liver fibrosis. METHODS: The target of miR-497 was determined by bioinformatics analysis combined with a dual-luciferase activity assay. LX-2 cells were transfected with miR-497 inhibitor and then stimulated with TGF-ß1 or excretory/secretory products of C. sinensis (CsESPs), and activation of LX-2 was assessed using qPCR or western blot. In vivo, the mice treated with CCl4 were intravenously injected with a single dose of adeno-associated virus serotype 8 (AAV8) that overexpressed anti-miR-497 sequences or their scramble control for 6 weeks. Liver fibrosis and damage were assessed by hematoxylin and eosin (H&E) staining, Masson staining, and qPCR; the activation of the TGF-ß/Smad signaling pathway was detected by qPCR or western blot. RESULTS: In the present study, the expression of miR-497 was increased in HSCs activated by TGF-ß1 or ESPs of C. sinensis. We identified that Smad7 was the target of miR-497 using combined bioinformatics analysis with luciferase activity assays. Transfection of anti-miR-497 into HSCs upregulated the expression of Smad7, leading to a decrease in the level of p-Smad2/3 and subsequent suppression of the activation of HSCs induced by TGF-ß1 or CsESPs. Furthermore, miR-497 inhibitor delivered by highly-hepatotropic (rAAV8) inhibited TGF-ß/smads signaling pathway by targeting at Smad7 to ameliorate CCL4-induced liver fibrosis. CONCLUSIONS: The present study demonstrates that miR-497 promotes liver fibrogenesis by targeting Smad7 to promote TGF-ß/Smad signaling pathway transduction both in vivo and in vitro, which provides a promising therapeutic strategy using anti-miR-497 against liver fibrosis.