Circular RNAs(circRNAs)are a class of closed-loop non-coding RNAs(ncRNAs)formed by head-to-tail covalent bonds.CircRNAs participate in the development of osteoarthritis by regulating extracellular matrix degrada-tion,inflammatory response and homeostasis of chondrocytes;It regulates the osteogenic differentiation of bone mar-row mesenchymal stem cells,the activity of bone microvascular endothelial cells and angiogenesis to affect femoral head necrosis;It regulates the differentiation of bone marrow stem cells,osteoblasts and osteoclasts to cause osteo-porosis and it affects the invasion,metastasis and drug resistance of osteosarcoma through different pathogenesis.CircRNAs are expected to become a new clinical diagnostic marker in the future.

Objective To investigate the intervention effects and mechanism of Danggui Shaoyao power on spontaneous abortion rats.Methods A total of 60 first-day pregnant rats were randomly divided into normal group,model group,dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups,with 10 rats in each group.The low,middle,and high dose groups were given Danggui Shaoyao power 5.175 g·kg-1,10.35 g·kg-1,20.7 g·kg-1,respectively,from 1 to 12 days of gestation,and the dydrogesterone group was given dydrogesterone tablet solution 2 mg·kg-1 once a day.On the 13th day of gestation,rats model of spontaneous abortion was established by intragastric administration of 5 mg·kg-1 of mifepristone tablet solution except for the normal group.Serum levels of GnRH,FSH,LH,E2 were measured,and abortion rates and uterine coefficients were calculated.The pathological changes of pregnant uterus were observed by haematoxylin-eosin(HE)staining.The differential proteins in rats pregnant uterus were detected by Label-Free shotgun proteomic technique,and the PPI,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis of the differential proteins were analyzed.Immunohistochemistry was used to verify the expression levels of differential proteins.Results Compared with normal group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were decreased,and the abortion rates were increased in model group(P<0.05).There were abortion lesions of spontaneous abortion in model group.Compared with model group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were increased(P<0.05),and the abortion rates were decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Proteomic results showed that a total of 550 proteins were quantified in this study.PPI analysis showed that a total of 159 proteins interacted with other proteins as hubs;the results of GO and KEGG enrichment analysis showed that the intervention effect of Danggui Shaoyao power on spontaneous abortion is related to the focal adhesion pathway,and involved upregulation of Akt2,Col6a1,Col6a2 and downregulation of Pten.Immunohistochemistry results showed that compared with normal group,the expression level of Akt2,Col6a1 and Col6a2 were decreased(P<0.05),and the expression level of Pten was increased(P<0.05)in model group.Compared with model group,the expression level of Akt2,Col6a1 and Col6a2 were increased(P<0.05),and the expression level of Pten was decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Conclusions Danggui Shaoyao power has the intervention effect on spontaneous abortion,and its mechanism may be related to by demoting the protein expressions of Pten,and promoting the protein expressions of Akt2,Col6a1 and Col6a2.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

This study aimed to elucidate the role of collagen type Ⅺ alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating im-mune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.

This study aimed to elucidate the role of collagen type XI alpha 1 (COL11A1)-positive cancer-associated fibroblasts (CAFs) in modifying the tumor microenvironment of colon cancer (CC) and facilitating immune evasion through interactions with myeloid-derived suppressor cells (MDSCs). Using single-cell transcriptomic sequencing, we analyzed the interplay between COL11A 1-positive CAFs and MDSCs in the CC microenvironment, focusing on how COL11A1 impacts MDSC differentiation and activation. The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase (MMP)3 and MMP13 expression, leading to paracrine induction of MDSC differentiation and activation, which promotes immune evasion and tumor growth. Additionally, we observed that COL11A1 knockout (COL11A1^KO) suppresses tumor growth and hinders immune evasion. These findings underscore the essential role of COL11A 1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression. By elucidating the molecular pathway through which COL11A1 influences MDSC activity, this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC, particularly through modulating COL11A1 expression in CAFs.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the intervention effects and mechanism of Danggui Shaoyao power on spontaneous abortion rats.Methods A total of 60 first-day pregnant rats were randomly divided into normal group,model group,dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups,with 10 rats in each group.The low,middle,and high dose groups were given Danggui Shaoyao power 5.175 g·kg-1,10.35 g·kg-1,20.7 g·kg-1,respectively,from 1 to 12 days of gestation,and the dydrogesterone group was given dydrogesterone tablet solution 2 mg·kg-1 once a day.On the 13th day of gestation,rats model of spontaneous abortion was established by intragastric administration of 5 mg·kg-1 of mifepristone tablet solution except for the normal group.Serum levels of GnRH,FSH,LH,E2 were measured,and abortion rates and uterine coefficients were calculated.The pathological changes of pregnant uterus were observed by haematoxylin-eosin(HE)staining.The differential proteins in rats pregnant uterus were detected by Label-Free shotgun proteomic technique,and the PPI,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis of the differential proteins were analyzed.Immunohistochemistry was used to verify the expression levels of differential proteins.Results Compared with normal group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were decreased,and the abortion rates were increased in model group(P<0.05).There were abortion lesions of spontaneous abortion in model group.Compared with model group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were increased(P<0.05),and the abortion rates were decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Proteomic results showed that a total of 550 proteins were quantified in this study.PPI analysis showed that a total of 159 proteins interacted with other proteins as hubs;the results of GO and KEGG enrichment analysis showed that the intervention effect of Danggui Shaoyao power on spontaneous abortion is related to the focal adhesion pathway,and involved upregulation of Akt2,Col6a1,Col6a2 and downregulation of Pten.Immunohistochemistry results showed that compared with normal group,the expression level of Akt2,Col6a1 and Col6a2 were decreased(P<0.05),and the expression level of Pten was increased(P<0.05)in model group.Compared with model group,the expression level of Akt2,Col6a1 and Col6a2 were increased(P<0.05),and the expression level of Pten was decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Conclusions Danggui Shaoyao power has the intervention effect on spontaneous abortion,and its mechanism may be related to by demoting the protein expressions of Pten,and promoting the protein expressions of Akt2,Col6a1 and Col6a2.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To investigate the effect of tofacitinib,a pan-Janus kinase(JAK)inhibitor,on transforming growth factor-beta 1(TGF-β1)-induced fibroblast to myofibroblast transition(FMT)and to explore its mechanism.To provide a theoretical basis for the clinical treatment of connective tissue disease-related interstitial lung disease(CTD-ILD).Methods:(1)Human fetal lung fibroblast 1(HFL-1)were cultured in vitro,and 6 groups were established:DMSO blank control group,TGF-β1 in-duction group,and TGF-β1 with different concentrations of tofacitinib(0.5,1.0,2.0,5.0 μmol/L)drug intervention experimental groups.CCK-8 was used to measure the cell viability,and wound-healing assay was performed to measure cell migration ability.After 48 h of combined treatment,quantitative real-time PCR(RT-PCR)and Western blotting were used to detect the gene and protein expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),and collagen type Ⅰ(COL1).(2)RT-PCR and enzyme-linked immunosorbnent assay(ELISA)were used to detect the interleukin-6(IL-6)gene and protein expression changes,respectively.(3)DMSO carrier controls,1.0 μmol/L and 5.0 μmol/L tofacitinib were added to the cell culture media of different groups for pre-incubation for 30 min,and then TGF-β1 was added to treat for 1 h,6 h and 24 h.The phosphorylation levels of Smad2/3 and signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.Results:(1)Tofacitinib inhibited the viability and migration ability of HFL-1 cells after TGF-β1 induction.(2)The expression of α-SMA,COL1A1 and FN1 genes of HFL-1 in the TGF-β1-induced groups was signifi-cantly up-regulated compared with the blank control group(P＜0.05).Compared with the TGF-β1 in-duction group,α-SMA expression in the 5.0 μmol/L tofacitinib intervention group was significantly inhi-bited(P＜0.05).Compared with the TGF-β1-induced group,FN1 gene was significantly inhibited in each intervention group at a concentration of 0.5-5.0 μmol/L(P＜0.05).Compared with the TGF-β1-induced group,the COL1A1 gene expression in each intervention group did not change significantly.(3)Western blotting results showed that the protein levels of α-SMA and FN1 in the TGF-β1-induced group were significantly higher than those in the control group(P＜0.05),and there was no significant difference in the expression of COL1A1.Compared with the TGF-β1-induced group,the α-SMA protein level in the intervention groups with different concentrations decreased.And the differences between the TGF-β1-induced group and 2.0 μmol/L or 5.0 μmol/L intervention groups were statistically significant(P＜0.05).Compared with the TGF-β1-induced group,the FN1 protein levels in the intervention groups with different concentrations showed a downward trend,but the difference was not statistically sig-nificant.There was no difference in COL1A1 protein expression between the intervention groups com-pared with the TGF-β1-induced group.(4)After TGF-β1 acted on HFL-1 cells for 48 h,the gene ex-pression of the IL-6 was up-regulated and IL-6 in culture supernatant was increased,the intervention with tofacitinib partly inhibited the TGF-β1-induced IL-6 gene expression and IL-6 in culture supernatant.TGF-β1 induced the increase of Smad2/3 protein phosphorylation in HFL-1 cells for 1 h and 6 h,STAT3 protein phosphorylation increased at 1 h,6 h and 24 h,the pre-intervention with tofacitinib inhibited the TGF-β1-induced Smad2/3 phosphorylation at 6 h and inhibited TGF-β1-induced STAT3 phosphorylation at 1 h,6 h and 24 h.Conclusion:Tofacitinib can inhibit the transformation of HFL-1 cells into myofi-broblasts induced by TGF-β1,and the mechanism may be through inhibiting the classic Smad2/3 path-way as well as the phosphorylation of STAT3 induced by TGF-β1,thereby protecting the disease progres-sion of pulmonary fibrosis.