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Studies have compared the safety and accuracy of robot-assisted techniques for inserting conventional open pedicle screws for spinal surgery. However, no relevant studies have confirmed that robot-assisted percutaneous screw placement is better than fluoroscopic percutaneous screw placement for the treatment of thoracolumbar fractures. This study compared the accuracy and safety of TiRobot-assisted percutaneous pedicle screw placement with those of the fluoroscopy-assisted percutaneous technique for the treatment of thoracolumbar fractures.This retrospective study included 126 patients with thoracolumbar fractures who underwent percutaneous pedicle screw placement. Sixty-five patients were treated with the TiRobot-assisted technique and 61 patients were treated with the fluoroscopy-assisted technique. Patient demographics, accuracy of screw placement (according to the Gertzbein and Robbins scale of grades A to E), screw insertion angle, radiation exposure, surgical time, intraoperative blood loss, length of hospital stay, incision length, hospital expenses, surgical site infection, and neurological injury of the TiRobot-assisted and fluoroscopy-assisted groups were compared using Student's t-test, Pearson χA total of 729 screws were placed (TiRobot-assisted group: 374 screws; fluoroscopy-assisted group: 355 screws). In the TiRobot-assisted group, 82.8% of screws were optimally positioned (grade A); however, the placement grades of the remaining screws were categorized as grade B (13.3%), grade C (3.2%), and grade D (0.5%). In the fluoroscopy-assisted group, 66.7% of the screws were optimally positioned (grade A); however, the placement grades of the remaining screws were categorized as grade B (21.4%), grade C (7.6%), grade D (3.6%), and grade E (0.5%). The proportion of clinically acceptable screws (grade A or B) was greater in the TiRobot-assisted group than in the fluoroscopy-assisted group. Additionally, the TiRobot-assisted group had a significantly larger mean screw insertion angle (22.27° ± 5.48° vs 20.55° ± 5.15°), larger incision length (13.86 ± 1.24 cm vs 12.77 ± 1.43 cm), and higher hospital expenses (69061.55 ± 7166.60 yuan vs 59383.85 ± 5019.64 yuan) than the fluoroscopy-assisted group. There were no significant differences in the intraoperative blood loss, length of hospital stay, and rates of surgical site infection and neurological injury in both groups (p 0.05). However, the TiRobot-assisted group had significantly better surgical times, radiation times, and radiation exposure than the fluoroscopy-assisted group (p 0.05).Percutaneous TiRobot-assisted pedicle screw placement is a safe, useful, and potentially more accurate alternative to the percutaneous fluoroscopy-assisted technique for treating thoracolumbar fractures.

The Revised International Staging System (R-ISS) is a simple and powerful prognostic tool for multiple myeloma (MM). However, heterogeneity in R-ISS stage is still poorly characterised, hampering improvement of treatments. We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS. Plasma cells were clustered into nine groups (P1-P9) based on gene expression, where P1-P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1 was enriched in P1, and they were validated to be upregulated in the MM cell line and in 22 other patients' myeloma cells. Furthermore, in progression, PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation, while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway. Finally, a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3. A few ligand-receptor pairs (CCL3/CCL5/CCL3L1-CCR1) were obviously active in monocyte-plasma communications in stage III. Herein, this study identified novel molecules, networks and crosstalk pairs in different R-ISS stages of MM, providing significant insight for its prognosis and treatment.

Background Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) represents an important issue, as its oxacillin susceptibility has contributed to misidentification by conventional susceptibility tests and consequently potential therapeutic failure, but limited data on the current status of OS-MRSA infection in Chinese hospitals are available. Methods This multicenter study performed a battery of susceptibility tests and diagnostic tests for 956 S. aureus isolates from 10 hospitals, including automated susceptibility testing on VITEK 2, broth microdilution, disk diffusion, and detection of PBB2a, mecA gene and mecC gene. For all identified OS-MRSA, multi-locus sequence typing (MLST), together with spa typing, SCCmec typing and PVL detecting, was carried out. Results OS-MRSA, most of which were from pediatric inpatients, represented 1.8% (17/956) of total isolates. Of these 17 OS-MRSA, 10 were ST59, followed by ST965 (3/17), and 11 carried SCCmec type IV, while 5 carried SCCmec type V, but only one was Panton–Valentine leucocidin (PVL)-positive, also, 16 had one or two point mutations within mecA promoter. OS-MRSA had inducible oxacillin resistance and significantly lower MDR (Multi-Drug Resistant) rate. We observed that the VITEK 2 system exhibited some deficiency in OS-MRSA detection, whereas cefoxitin disk diffusion was shown to be a reliable and cost-saving alternative and should be supplemented in detecting S. aureus with borderline oxacillin susceptible MICs. Conclusion This study has characterized phenotypically and molecularly OS-MRSA in China, and provided insights into more effective management of OS-MRSA.

Summary Background The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. Methods We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients from two hospitals in Chongqing, China were consecutively enrolled. Eligible participants were aged 18–80 years with suspected gastric pathology and no previous surgery. Participants underwent FAMCE for screening of gastric lesions, then conventional transoral gastroscopy 2 h later, and stomach examination results were compared. The primary outcome was the rate of complete detection of gastric anatomy landmarks (cardia, fundus, body, angulus, antrum, and pylorus) by FAMCE. Secondary outcomes were the time required for gastric completion by FAMCE, the rate of detection of gastric lesions by FAMCE compared with conventional transoral gastroscopy, and the rate of complete small bowel examination. Adverse events were also evaluated. The study was registered in the Chinese Clinical Trial Registry, ChiCTR2000040507. Findings Between May 12 and Aug 17, 2020, 114 patients (mean age 44·0 years [IQR 34·0–55·0]; 63 [55%] female) were enrolled. The rate of complete detection of gastric anatomical structures by FAMCE was 100% (95% CI 99·3–100·0). The concordance between FAMCE and conventional transoral gastroscopy was 99·61% (99·45–99·78). The mean completion time of a gastroscopy with FAMCE was 19·17 min (SD 1·43; median 19·00, IQR 19·00–20·00), compared with 5·21 min (2·00; 5·18, 3·68–6·45) for conventional transoral gastroscopy. In 114 enrolled patients, 214 lesions were detected by FAMCE and conventional transoral gastroscopy. Of those, 193 were detected by both modalities. FAMCE missed five pathologies (four cases of gastritis and one polyp), whereas conventional transoral gastroscopy missed 16 pathologies (12 cases of gastritis, one polyp, one fundal xanthoma, and two antral erosions). FAMCE was able to provide a complete small bowel examination for all 114 patients and detected intestinal lesions in 50 (44%) patients. During the study, two (2%) patients experienced adverse events. No serious adverse events were recorded, and there was no evidence of capsule retention. Interpretation The performance of FAMCE is similar to conventional transoral gastroscopy in completion of gastric examination and lesion detection. Furthermore, it can provide a complete small bowel examination. Therefore, FAMCE could be effective method for examination of the gastrointestinal tract. Funding Chinese National Key Research and Development Program.

Lumbar degenerative disease (LDD) is a narrowing of the spinal canal and intervertebral foramina caused by aging and degeneration of lumbar spine tissue. Minimally invasive internal lumbar spine fixation is emerging in the treatment of LDD. However, no standard early rehabilitation protocol for orthopedic robot-assisted minimally invasive internal lumbar spine fixation exits. To investigate the effect of a nurse-led early rehabilitation program in the postoperative recovery of patients with lumbar degenerative lesions undergoing orthopedic robot-assisted minimally invasive lumbar internal fixation.Eighty patients with minimally invasive orthopedic robot-assisted lumbar degenerative lesions admitted to our hospital between January 2019 and January 2021 were recruited to this study. The patients were randomly allocated to a control group (n=40), involving conventional care, and an observation group (n=38; 40 initially and 2 later excluded) including a nurse-led early rehabilitation program added on the basis of the control group. The primary outcomes were the general postoperative conditions, scores of daily living ability, the degree of low back pain and functional recovery. Participants were also compared in terms of their compliance with the care regimen and the incidence of complications.Participants in the observation group had a significantly shorter first time on the floor after surgery (P0.001) and shorter hospital stay (P=0.003). Meanwhile, participants in the observation group had higher Barthel index (BI) scores (P=0.039), lower visual analogue scale (VAS) scores (P=0.028), and Oswestry disability index (ODI) scores (P=0.002) at 3 days postoperatively, and there was no difference in the three scores between the two groups at 1 month postoperatively (all P0.05). The compliance of participants in the observation group was significantly higher than that of the control group (P0.001). Participants in the observation group were less likely to experience constipation (P=0.043) and bloating (P=0.012) within 1 month after surgery.Implementation of a nurse-led early rehabilitation program in patients undergoing orthopedic robotic-assisted minimally invasive treatment of lumbar degenerative lesions can significantly improve patient compliance, significantly shorten postoperative flooring and hospitalization time, reduce the incidence of gastrointestinal adverse events, and accelerate postoperative recovery.Chinese Clinical Trial Registry ChiCTR2100048698.

OBJECTIVE: To evaluate the effectiveness of orthopedic robot with modified tracer fixation (short for modified orthopedic robot) assisted percutaneous kyphoplasty (PKP) in treatment of single-segment osteoporotic vertebral compression fracture (OVCF). METHODS: The clinical data of 155 patients with single-segment OVCF who were admitted between December 2017 and January 2021 and met the selection criteria was retrospectively analyzed. According to the operation methods, the patients were divided into robot group (87 cases, PKP assisted by modified orthopedic robot) and C-arm group (68 cases, PKP assisted by C-arm X-ray fluoroscopy). There was no significant difference in gender, age, body mass index, T value of bone mineral density, therapeutic segment, grade of vertebral compression fracture, and preoperative visual analogue scale (VAS) score, midline vertebral height, and Cobb angle between the two groups (P>0.05). The effectiveness evaluation indexes of the two groups were collected and compared. The clinical evaluation indexes included the establishment time of working channel, dose of intraoperative fluoroscopy, the amount of injected cement, VAS score before and after operation, and the occurrence of complications. The imaging evaluation indexes included the degree of puncture deviation, the degree of bone cement diffusion, the leakage of bone cement, the midline vertebral height and the Cobb angle before and after operation. RESULTS: The establishment time of working channel in robot group was significantly shorter than that in C-arm group, and the dose of intraoperative fluoroscopy was significantly larger than that in C-arm group (P0.05). No severe complication such as infection, spinal cord or nerve injury, and pulmonary embolism occurred in the two groups. Five cases (5.7%) in robot group and 7 cases (10.2%) in C-arm group had adjacent segment fracture, and the difference in incidence of adjacent segment fracture between the two groups was not significant (χ(2)=1.105, P=0.293). Compared with C-arm group, the deviation of puncture and the diffusion of bone cement at 1 day after operation, the midline vertebral height and Cobb angle at 1 month after operation and last follow-up were significantly better in robot group (P

Adaptation to increased insulin demand is mediated by β cell proliferation and neogenesis, among other mechanisms. Although it is known that pancreatic β cells can arise from ductal progenitors, these observations have been limited mostly to the neonatal period. We have recently reported that the duct is a source of insulin-secreting cells in adult insulin-resistant states. To further explore the signaling pathways underlying the dynamic β cell reserve during insulin resistance, we undertook human islet and duct transplantations under the kidney capsule of immunodeficient NOD/SCID-γ (NSG) mouse models that were pregnant, were insulin-resistant, or had insulin resistance superimposed upon pregnancy (insulin resistance + pregnancy), followed by single-nucleus RNA-Seq (snRNA-Seq) on snap-frozen graft samples. We observed an upregulation of proliferation markers (e.g., NEAT1) and expression of islet endocrine cell markers (e.g., GCG and PPY), as well as mature β cell markers (e.g., INS), in transplanted human duct grafts in response to high insulin demand. We also noted downregulation of ductal cell identity genes (e.g., KRT19 and ONECUT2) coupled with upregulation of β cell development and insulin signaling pathways. These results indicate that subsets of ductal cells are able to gain β cell identity and reflect a form of compensation during the adaptation to insulin resistance in both physiological and pathological states.

TLR7 (Toll-like receptor 7), the sensor for single-stranded RNA, contributes to systemic inflammation and mortality in murine polymicrobial sepsis. Recent studies show that extracellular miR-146a-5p serves as a TLR7 ligand and plays an important role in regulating host innate immunity. However, the role of miR-146a-5p and TLR7 signaling in pulmonary inflammation, endothelial activation, and sepsis-associated acute respiratory distress syndrome remains unclear. Here, we show that intratracheal administration of exogenous miR-146a-5p in mice evokes lung inflammation, activates endothelium, and increases endothelial permeability via TLR7-dependent mechanisms. TLR7 deficiency attenuates pulmonary barrier dysfunction and reduces lung inflammatory response in a murine sepsis model. Moreover, the impact of miR-146a-5p−TLR7 signaling on endothelial activation appears to be a secondary effect because TLR7 is undetectable in the human pulmonary artery and microvascular endothelial cells (ECs), which show no response to direct miR-146a-5p treatment in vitro. Both conditioned media of miR-146a-5p−treated macrophages (Mϕ) and septic sera of wild-type mice induce a marked EC barrier disruption in vitro, whereas Mϕ conditioned media or septic sera of TLR7(−/−) mice do not exhibit such effect. Cytokine array and pathway enrichment analysis of the Mϕ conditioned media and septic sera identify TNFα (tumor necrosis factor α) as the main downstream effector of miR-146a-5p−TLR7 signaling responsible for the EC barrier dysfunction, which is further supported by neutralizing anti-TNFα antibody intervention. Together, these data demonstrate that TLR7 activation elicits pulmonary inflammation and endothelial barrier disruption by sensing extracellular miR-146a-5p and contributes to sepsis-associated acute respiratory distress syndrome.

Background and purpose To explore whether a highly refined dose volume histograms (DVH) prediction model can improve the accuracy and reliability of knowledge-based volumetric modulated arc therapy (VMAT) planning for cervical cancer. Methods and materials The proposed model underwent repeated refining through progressive training until the training samples increased from initial 25 prior plans up to 100 cases. The estimated DVHs derived from the prediction models of different runs of training were compared in 35 new cervical cancer patients to analyze the effect of such an interactive plan and model evolution method. The reliability and efficiency of knowledge-based planning (KBP) using this highly refined model in improving the consistency and quality of the VMAT plans were also evaluated. Results The prediction ability was reinforced with the increased number of refinements in terms of normal tissue sparing. With enhanced prediction accuracy, more than 60% of automatic plan-6 (AP-6) plans (22/35) can be directly approved for clinical treatment without any manual revision. The plan quality scores for clinically approved plans (CPs) and manual plans (MPs) were on average 89.02 ± 4.83 and 86.48 ± 3.92 (p mean and V18 Gy for kidney (L/R), the Dmean, V30 Gy, and V40 Gy for bladder, rectum, and femoral head (L/R). Conclusion The proposed model evolution method provides a practical way for the KBP to enhance its prediction ability with minimal human intervene. This highly refined prediction model can better guide KBP in improving the consistency and quality of the VMAT plans.

Hypothyroidism is a systemic metabolic deficiency syndrome caused by a deficiency in thyroid hormone or a decrease in the action of thyroid hormones. It has a high incidence among women of child-bearing age, and pregnant women with hypothyroidism may have a higher risk of birth defects.To explore the specific biological mechanism affecting the occurrence of hypothyroidism.This study determined key molecules by comparing and analyzing the difference in methylation levels between pre-pregnancy women and normal controls using the Illumina Infinium MethylationEPIC BeadChip.3493 Differential methylation positions (DMPs) related genes and 47 differentially methylated regions (DMRs) related genes were found between the Hypothyroidism group and the control group. Among them, miR-21 has been found to be closely related to thyroid hormone regulation. The results of enrichment analysis showed that the DMPs or DMRs-related genes are both significantly enriched in human T-cell leukemia virus 1 infection, osteoclast differentiation and sphingolipid signaling pathway, which were also closely related to the occurrence and development of hypothyroidism. In addition, the combined analysis of CNVs and DMRs showed that significant differences occurred near the regions of 16 M bp in chromosome 1 between the two groups, and the genes involved in these regions included NDUFS2, FCER1G and SHC1.This work screened molecular markers and key signaling pathways that are involved in the development of hypothyroidism in pre-pregnancy women, which may provide new targets for the research and diagnosis of hypothyroidism in the future.

Objective To assess the long‐term clinical efficacy of TiRobot‐assisted percutaneous cannulated screw fixation in the treatment of femoral neck fractures. Methods This retrospective study included 50 patients with unilateral femoral neck fractures who were treated with TiRobot‐assisted percutaneous cannulated screw fixation from September 2017 to May 2018. After at least 2 years of follow‐up, the results of treatment, including operation duration, frequency of fluoroscopy use, intraoperative bleeding, hospital stay, medical expense, screw placement accuracy, rate of fracture healing and necrosis of the femoral head, and Harris hip scores at the last follow up, were recorded and compared with those of 83 matched patients who underwent conventional manual positioning surgery. Results The TiRobot group had longer operation duration (83.3 ± 31.2 min vs 44.1 ± 14.8 min) and higher medical expenses (28,407.1 ± 7498.0 yuan vs 22,672.3 ± 4130.3 yuan) than the conventional group. The TiRobot group had significantly less intraoperative bleeding (11.3 ± 7.3 mL vs 51.6 ± 40.4 mL) and shorter hospital stay (8.6 ± 2.8 days vs 11.1 ± 3.41 days) than the conventional group. Screw parallelism (1.32° ± 1.85° vs 2.54° ± 2.99° on anteroposterior radiograph; 1.42° ± 2.25° vs 3.09° ± 3.63° on lateral radiograph) and distance between screws (58.44 ± 10.52 mm vs 39.69 ± 12.17 mm) were significantly improved. No significant difference was found between the two groups in terms of the use of fluoroscopy (40.1 ± 28.5 times vs 38.6 ± 21.0 times) and Harris hip scores at the last follow‐up (93.2 ± 10.3 points vs 88.4 ± 11.9 points). Two cannulated screws penetrated the femoral head during manual insertion in the conventional group but not in the TiRobot group. The rate of nonunion and necrosis of the femoral head in the TiRobot group was reduced compared with that in the conventional group (0 vs 7.2%; 6.0% vs 24.1%). Conclusion TiRobot‐assisted percutaneous cannulated screw fixation of femoral neck fractures is accurate and minimally invasive and helps in reducing late complications, particularly necrosis of the femoral head and nonunion of fractures., TiRobot‐assisted percutaneous cannulated screw fixation of femoral neck fractures is accurate and minimally invasive, and helps in reducing late complications, particularly necrosis of the femoral head and nonunion of fracture.

Background Early prediction of patients’ deterioration is helpful in early intervention for patients at greater risk of deterioration in Intensive Care Unit (ICU). This study aims to apply machine learning approaches to heterogeneous clinical data for predicting life-threatening events of patients in ICU. Methods We collected clinical data from a total of 3151 patients admitted to the Medical Intensive Care Unit of Peking Union Medical College Hospital in China from January 1st, 2014, to October 1st, 2019. After excluding the patients who were under 18 years old or stayed less than 24 h at the ICU, a total of 2170 patients were enrolled in this study. Multiple machine learning approaches were utilized to predict life-threatening events (i.e., death) in seven 24-h windows (day 1 to day 7) and their performance was compared. Results Light Gradient Boosting Machine showed the best performance. We found that life-threatening events during the short-term windows can be better predicted than those in the medium-term windows. For example, death in 24 h can be predicted with an Area Under Curve of 0.905. Features like infusion pump related fluid input were highly related to life-threatening events. Furthermore, the prediction power of static features such as age and cardio-pulmonary function increased with the extended prediction window. Conclusion This study demonstrates that the integration of machine learning approaches and large-scale high-quality clinical data in ICU could accurately predict life-threatening events for ICU patients for early intervention.

Emerging evidence indicates that the incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions despite changing environmental factors, suggesting that genetic traits contribute to its development. Recently, long non-coding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) axis has been reported to be implicated in the pathophysiological processes of malignancies. Moreover, initial bioinformatic analysis revealed a highly expressed lncRNA Forkhead box D3 antisense RNA1 (FOXD3-AS1) for mechanistic network underlying NPC in this present study. Therefore, this study aims to delineate the ability of lncRNA FOXD3-AS1 to influence the NPC progression. The relationship among lncRNA FOXD3-AS1, miR-185-3p, and FOXD3 was identified with bioinformatics prediction, dual-luciferase reporter gene assays, RNA-binding protein immunoprecipitation, and RNA pull-down assays. Furthermore, effects of lncRNA FOXD3-AS1 on malignant phenotypes in vitro, alongside tumor formation in vivo, of transfected NPC stem-like cells were examined with gain- and loss-of-function experiments. Our findings revealed that lncRNA FOXD3-AS1 and FOXD3 exhibited increased expression levels, while miR-185-3p exhibited diminished levels in NPC. The levels of lncRNA FOXD3-AS1 and FOXD3 were further correlated with tumor node metastasis stage and pathological type of patients with NPC. LncRNA FOXD3-AS1 was also confirmed to negatively regulate the miR-185-3p expression, which further targeted the downstream gene FOXD3. In addition, lncRNA FOXD3-AS1 knockdown repressed cell stemness, colony formation, viability, invasion, migration, and in vivo tumor growth, and accelerated cell apoptosis. Moreover, FOXD3 silencing or miR-185-3p overexpression reversed the effects of lncRNA FOXD3-AS1. Our findings provide evidence indicating that lncRNA FOXD3-AS1 could bind to miR-185-3p to upregulate the FOXD3 expression, thereby promoting the development of NPC.

Background Knee osteoarthritis (OA) is a common disease condition associated with aging and a frequent cause of primary care consultations. Few longitudinal studies have been conducted to investigate the incidence of symptomatic knee osteoarthritis (OA) and to identify its risk factors among the Chinese population. Methods The China Health and Retirement Longitudinal Study (CHARLS) is a nationwide longitudinal survey of persons aged ≥45 years. Symptomatic knee OA was diagnosed when both self-reported knee pain and self-reported physician-diagnosis arthritis existed. Using the national survey data collected from the CHARLS, we estimated the incidence of symptomatic knee OA, taking into account the complex survey design and response rate. We applied weighted logistic regression analysis to identify its risk factors. Results In the 4-year follow-up, the cumulative incidence of symptomatic knee OA among middle-aged and older Chinese adults was 8.5%; the incidence was higher among females (11.2%) than males (5.6%). Female (odds ratio (OR) 1.98 [95% confidence interval (CI) 1.65–2.37]), rural area (OR 1.32 [95% CI 1.08–1.60]), and West region (OR 2.33 [95% CI 1.89–2.87]) were associated with a higher risk of incident symptomatic knee OA. Physical activities (OR 0.47 [95% CI 0.29–0.76]) and high education level (OR 0.60 [95% CI 0.41–0.88]) was associated with a lower risk of incident symptomatic knee OA, while histories of heart disease (OR 1.40 [95% CI 1.07–1.82]), kidney disease (OR 1.80 [95% CI 1.35–2.39]), and digestive disease (OR 1.54 [95% CI 1.30–1.82]) were associated with a higher risk of incident symptomatic knee OA. Conclusion The cumulative incidence of symptomatic knee OA over 4 years was relatively high, and varied by province and region. Lack of physical activities was confirmed to be risk factors of incident symptomatic knee OA. The presence of heart disease, kidney disease, and digestive disease may be associated with a higher risk of incident symptomatic knee OA, further research need to confirm these findings.

Osteosarcoma (OS) is a malignant bone cancer lacking of effective treatment target when the metastasis occurred. This study investigated the implication of MicroRNA‐326 in OS proliferation and metastasis to provide the clue for the treatment of metastatic OS. This study knocked down SP1 in MG63 and 143B cells and then performed Microarray assay to find the expression of miRNAs that were influenced by SP1. MTT, EdU, wound‐healing and cell invasion assays were performed to evaluated cell proliferation and invasion. OS metastasis to lung was detected in a nude mice model. ChIP assay and DAPA were applied to determine the regulatory effect of SP1 and histone deacetylase 1 (HDAC) complex on miR‐326 expression. Human OS tissues showed lowly expressed miR‐326 but highly expressed Sp1 and HDAC. Sp1 recruited HDAC1 to miR‐326 gene promoter, which caused the histone deacetylation and subsequent transcriptional inhibition of miR‐326 gene. miR‐326 deficiency induced the stimulation of SMO/Hedgehog pathway and promoted the proliferation and invasion of 143B and MG63 cells as well as the growth and metastasis in nude mice. SP1/HDAC1 caused the transcriptional inhibition of miR‐326 gene by promoting histone deacetylation; miR‐326 deficiency conversely stimulated SMO/Hedgehog pathway that was responsible for the proliferation and metastasis of OS.

Background Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive. Methods RNA-seq and qRT-PCR were performed to screen differential expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR. Cell proliferation and invasion ability were determined by CCK-8 and cell invasion assays. RNA-seq, GO-pathway, RNA pull-down and ChIRP were further applied to search for detailed mechanism. Results Here, a novel circRNA named circMRPS35, was screened out by RNA-seq in gastric cancer tissues, whose expression is related to clinicopathological characteristics and prognosis in gastric cancer patients. Biologically, circMRPS35 suppresses the proliferation and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, circMRPS35 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of FOXO1 and FOXO3a genes, which elicits acetylation of H4K5 in their promoters. Particularly, circMRPS35 specifically binds to FOXO1/3a promoter regions directly. Thus, it dramatically activates the transcription of FOXO1/3a and triggers subsequent response of their downstream target genes expression, including p21, p27, Twist1 and E-cadherin, resulting in the inhibition of cell proliferation and invasion. Moreover, circMRPS35 expression positively correlates with that of FOXO1/3a in gastric cancer tissues. Conclusions Our findings not only reveal the pivotal roles of circMRPS35 in governing histone modification in anticancer treatment, but also advocate for triggering circMRPS35/KAT7/FOXO1/3a pathway to combat gastric cancer.

Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague-Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso-Beattie-Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet-stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.

Han painting is an important art display form in Chinese history; it has a history of hundreds of years. It is the embodiment of a higher level of Chinese painting. Han paintings can also show the development of China’s political economy and culture. However, with the continuous progress of time, the patterns of Han paintings and the color characteristics of Han paintings will be greatly damaged. This limits people’s research on the civilization displayed by Han paintings. At the same time, changes in the environment also have a great relationship with the integrity of Chinese painting. Therefore, the study of the impact of environmental protection on the integrity of Han paintings is crucial to the study of Chinese civilization. It is difficult for traditional research methods to discover the quantitative relationship between environmental protection and the integrity of Han paintings. In this study, the atrous convolutional neural network (ACNN) in the artificial intelligence method and the GRU method were used to explore the relationship between environmental protection and the patterns, colors, and shapes of Chinese paintings. The research results show that the ACNN method and the GRU method can better predict the patterns, shapes, and color characteristics of Chinese paintings. Through research, it can also be found that the color and pattern features of Chinese paintings contain obvious time characteristics, which requires the GRU method for feature extraction. The prediction errors of ACNN and GRU in predicting the integrity of Chinese paintings are all within 2.5%, and the largest prediction error is only 2.45%.

To compare the incidence of xerostomia in nasopharyngeal carcinoma (NPC) patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT) and conventional IMRT (C-IMRT).Patients with histologically confirmed NPC who met the eligibility criteria were randomly assigned to receive either SPLS-IMRT or C-IMRT. The primary endpoint was the incidence of xerostomia at 12 months post-IMRT. The secondary endpoints included the xerostomia questionnaire (XQ) score, unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and survival outcomes.Ninety patients were enrolled. Eighty-two patients were included for xerostomia analysis (42 in the SPLS-IMRT group and 40 in the C-IMRT group). At 12 months post-IMRT, the incidence of xerostomia in the SPLS-IMRT group was significantly lower than that in the C-IMRT group (83.4% vs 95.0%; P = 0.007), especially the grade 3 xerostomia (0% vs 12.5%; P 0.001). The median change in XQ score was similar between the two groups (11.9 points vs 14.1 points; P = 0.194). There was a significantly higher median fractional USFR (0.67 vs 0.35; P = 0.024) and SSFR (0.66 vs 0.32; P = 0.021) in the SPLS-IMRT group than the C-IMRT group. The 3-year LRRFS, DMFS, and OS in the SPLS-IMRT and C-IMRT groups were 92.5% vs 90.9%, 83.8% vs 81.7%, and 88.9% vs 88.2% (all P 0.05).SPLS-IMRT significantly reduced the incidence of xerostomia at 12 months post-IMRT in NPC by recovering parotid gland function earlier than C-IMRT, without compromising survivals. Phase III clinical trials are warranted. (ClinicalTrials.gov, number NCT05020067).

Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8Multiple myeloma is a type of bone cancer. It affects the immune cells that make antibodies, known as plasma cells. These immune cells live in the bone marrow. As with many types of cancer, the chance of survival is highest when multiple myeloma is diagnosed early. It has three stages, labelled I, II, and III. People with stage I or II disease have better outcomes than those with stage III, but the exact reasons are unclear. Bone marrow contains lots of different types of cells, which can affect the growth of a tumour. These include cancer-targeting cells, called killer T-cells, and cancer-supporting cells called myeloid cells. Understanding these cells and how they interact could shed light on the different stages of multiple myeloma. One way to do this is to use single cell sequencing, which looks at the genes in use inside each cell at any one time. Zhong, Hao, Zhang, Jiang et al. examined the bone marrow of two healthy donors and nine people with different stages of multiple myeloma. This revealed two new groups of plasma cells. One group, highest in stage II patients, was protective, with the potential to kill cancer cells. The other, highest in people with more aggressive disease, was harmful, with the potential to divide rapidly. The sequencing also identified molecules that might be useful drug targets for the future. These included a gene that drove growth in the dangerous plasma cells, and several that might help tumours escape from the immune system. It is becoming increasingly clear that the environment around a tumour has a huge role to play in its progression. Understanding how this environment changes over time could aid in the development of more targeted treatments. The next step is to find out more about the molecules identified here.

OBJECTIVE: To investigate the effect of prophylactic C(4, 5) foraminal dilatation in posterior cervical open-door surgery on postoperative C(5) nerve root palsy syndrome. METHODS: The clinical data of patients with cervical spondylotic myelopathy (cervical spinal cord compression segments were more than 3) who met the selection criteria between March 2016 and March 2019 were retrospectively analyzed. Among them, 40 patients underwent prophylactic C(4, 5) foraminal dilatation in posterior cervical open-door surgery (observation group) and 40 patients underwent simple posterior cervical open-door surgery (control group). There was no significant difference between the two groups (P>0.05) in gender, age, disease duration, Nurick grade of spinal cord symptoms, and preoperative diameter of C(4, 5) intervertebral foramen, Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score. The occurrence of C(5) nerve root paralysis syndrome was recorded and compared between the two groups, including incidence, paralysis time, recovery time, and spinal cord drift. VAS and JOA scores were used to evaluate the improvement of pain and function before operation and at 12 months after operation. RESULTS: The incisions of the two groups healed by first intention, and there was no early postoperative complications such as cerebrospinal fluid leakage. Patients of both groups were followed up 12-23 months, with an average of 17.97 months. C(5) nerve root paralysis syndrome occurred in 8 cases in the observation group (3 cases on the right and 5 cases on the left) and 2 cases in the control group (both on the right). There was significant difference of the incidence (20% vs. 5%) between the two groups (χ(2)=4.114, P=0.043). Except for 1 case in the observation group who developed C(5) nerve root palsy syndrome at 5 days after operation, the rest patients all developed at 1 day after operation; the recovery time of the observation group and the control group were (3.87±2.85) months and (2.50±0.70) months respectively, showing no significant difference between the two groups (t=–0.649,P=0.104). At 12 months after operation, the JOA score and VAS score of cervical spine in the two groups significantly improved when compared with those before operation (P0.05). CONCLUSION: Prophylactic C(4, 5) foraminal dilatation can not effectively prevent and reduce the occurrence of postoperative C(5) root palsy, on the contrary, it may increase its incidence, so the clinical application of this procedure requires caution.

BACKGROUND To investigate the preventive effect of elastic stockings on deep vein thrombosis (DVT) after orthopedic surgery by literature search and meta-analysis. METHODS PubMed, Embase and Cochrane were selected as the search database platforms to search the literature of randomized controlled trials related to elastic stockings and DVT published from 2008 to date. Revman 5.3.5 software was used for statistical analysis of the data to obtain forest and funnel plots. RESULTS In this study, 90 studies were initially screened and 7 were finally included, covering a total of 3,116 patients. Meta-analysis showed that the 7 studies had statistical heterogeneity (I2=32%, P=0.18), so a random effect model was used. The obtained statistic was [odds ratio (OR) =0.59, 95% confidence interval (CI): (0.34, 1.03)], the statistical effect size was Z=1.84, P=0.07, and the difference was not statistically significant, so a stepwise sensitivity analysis was performed by the exclusion method. One study was excluded, and the remaining 6 showed homogeneity (I2=0%, P=0.46). They were analyzed by subgroup according to the type of operation: ankle surgery or hip and knee arthroplasty. The internal literatures of each subgroup were homogeneous: ankle surgery subgroup (I2=0%, P=0.43), hip and knee arthroplasty subgroup (I2=0%, P=0.88). Therefore, fixed effect mode analysis was used, and the effect size of elastic stockings after ankle surgery was Z=3.65, P=0.0003, while the effect size of elastic stockings in the hip and knee arthroplasty subgroup was Z=1.23, P=0.22. DISCUSSION Elastic stockings had an obvious preventive effect on DVT in patients undergoing ankle surgery, but not in patients undergoing lumbar, knee or spinal surgery. It is necessary to combine anticoagulant drugs and other physical therapies to prevent DVT.

OBJECTIVE: To evaluate the safety of TiRobot-guided percutaneous transpedicular screw implantation. METHODS: The medical records of 158 patients with thoracolumbar fractures and lumbar degenerative diseases who underwent percutaneous transpedicular screw implantation were retrospectively analyzed between January 2018 and December 2020. The patients were divided into trial group (TiRobot-guided screw implantation, 86 cases) and control group (fluoroscopy-guided screw implantation, 72 cases). There was no significant difference in gender, age, pathology, lesion segment, and the average number of screw implantation per case (P>0.05). The operation time, fluoroscopic dose, fluoroscopic time, and fluoroscopic frequency were compared between the two groups. One day postoperatively, the convergence angle was measured and the penetration of the pedicle cortex was evaluated according to Gertzbein-Robbins classification standard. RESULTS: The operation time, fluoroscopic dose, fluoroscopic time, and fluoroscopic frequency of the trial group were significantly lesser than those of control group (P

OBJECTIVE: To compare the effectiveness of robot assisted internal fixation and traditional open reduction and internal fixation for calcaneal fractures. METHODS: The clinical data of 44 patients (44 feets) with calcaneal fracture admitted between October 2017 and December 2018 who met the selection criteria were retrospectively analyzed. According to different operation methods, they were divided into trial group (19 cases, treated with robot assisted percutaneous reduction and cannulated screw fixation through tarsal sinus incision) and control group (25 cases, treated with open reduction and internal fixation via traditional tarsal sinus incision). There was no significant difference in gender, age, injured side, cause of injury, fracture type, time from injury to operation, and preoperative Böhler angle, Gissane angle, calcaneus width, American Orthopedic Foot and Ankle Association (AOFAS) score, and other general data between the two groups (P>0.05). The operation time, intraoperative fluoroscopy frequency, and fracture healing time were recorded and compared between the two groups. Before operation and at 6 months after operation, the Böhler angle and Gissane angle were measured on the lateral X-ray film, and the calcaneal width was measured on the axial X-ray film of the calcaneus to evaluate the recovery of the deformity and collapse after surgical treatment; the AOFAS score was used to evaluate the function of the affected foot and ankle joint. RESULTS: The operation time of the trial group was significantly longer than that of the control group (P0.05); the fractures in the two groups were healed, there was no significant difference in healing time (t=–1.890, P=0.066); the AOFAS scores of the two groups were significantly higher than those before operation (P

Background High risk of embolic events exists in both patients with chronic atrial fibrillation (AF) and patients in the perioperative period of ablation (effective treatment for AF). Therefore, anticoagulant therapy is important. Oral anticoagulants can be divided into two major categories: vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs). VKAs, represented by warfarin, have been widely used as traditional anticoagulants, whereas NOACs have been used in clinical practice, but their anticoagulant effects and side effects are still the focus of research. We used a meta-analysis to compare the incidence of left atrial thrombi (LAT) between different anticoagulants. Methods We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases for observational studies that compared the transesophageal echocardiography (TEE) findings for patients treated with NOACs and VKAs. The incidence of LAT and dense spontaneous echocardiographic contrast (dense SEC) were extracted as the basis of the meta-analysis. Results Fifteen studies were included in the meta-analysis. We found that patients anticoagulated with NOACs and VKAs had similar incidence of LAT (OR = 0.74, 95%CI: 0.55–1.00). After excluding the heterogeneous article by sensitivity analysis, we found the incidence of LAT in patients anticoagulated with NOACs is lower than VKAs (OR = 0.59, 95%CI: 0.42–0.84). The results of subgroup analysis showed that the incidence of LAT among three types of NOACs have no significant difference (dabigatran vs. rivaroxaban, OR = 1.16 [0.75, 1.81]; rivaroxaban vs. apixaban, OR = 0.97 [0.54, 1.74]; dabigatran vs. apixaban, OR = 1.09 [0.55, 2.16]). Conclusion Patients anticoagulated with NOACs may have lower incidence of LAT than VKAs. The incidence of LAT among different type of NOACs are similar.

Thalassemia is one of the most common genetic diseases in southern China. Accurate population frequency data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies of thalassemia.The aim of this study is to reveal the prevalence and the mutation spectrum of thalassemia in neonates in the Wuhan region of central China.About 3796 neonates in Wuhan area of China were analyzed by hematological and genetic analysis.About 2174 subjects were genetically diagnosed as thalassemia carriers or patients, including 1415 cases of α-thalassemia (65.89%), 731 cases of β-thalassemia (33.62%), and 28 cases of α-composite β-thalassemia (1.29%). A total of 11 genotypes and 6 gene mutations were identified in α-thalassemia anomalies, with -There was high heterogeneity and extensive spectrum of thalassemia in the neonates in Wuhan populations. The findings will be useful for genetic counseling and prenatal diagnosis of thalassemia in the Wuhan region.

Background Congenital heart disease (CHD) is among the leading causes of infant death worldwide. Although shortage of folate has been found potentially to contribute to CHD in the embryo, the aetiology of CHD was not completely understood. Inflammation and altered immune processes are involved in all forms of cardiac malformation, including CHD. Tumour necrosis factor-α (TNF-α), was involved in the pathogenesis of multiple kinds of heart diseases. However, no studies have systematically evaluated the associations of genetic variants of TNF-α with susceptibility of CHD. Methods A case-control study was conducted to evaluate the associations between tagSNPs of TNF-α and CHD susceptibility. Serum level of TNF-α was assessed using ELISA. The dual luciferase reporter assay was used to evaluate the functional significance of variant rs1800629 on TNF-α transcriptional activity. Results We found rs1800629 was significantly correlated with increased CHD susceptibility (OR: 1.72, 95% CI 1.26 to 2.36, p=0.001). Serum levels of TNF-α were significantly higher in CHD group (9.09±1.90 pg/mL) than that in control group (6.12±1.56 pg/mL, p Conclusion These results indicate that higher level of serum TNF-α increases risk of CHD, while TNF-α rs1800629 A allele might contribute to higher risk for CHD due to the increase in TNF-α expression.

Type 1 diabetes (T1D) is characterized by pancreatic islet infiltration by autoreactive immune cells and a nearly complete loss of β cells1. Restoration of insulin-producing β cells coupled with immunomodulation to suppress the autoimmune attack has emerged as a potential approach to counter T1D2–4. Here we report that enhancing β-cell mass early in life, in two models of female non-obese diabetic (NOD) mice, results in immunomodulation of T cells, reduced islet infiltration and lower β-cell apoptosis, which together protect them from developing T1D. The animals displayed altered β-cell antigens; islet transplantation studies showed prolonged graft survival in the NOD-liver-specific insulin receptor knockout (LIRKO) model. Adoptive transfer of splenocytes from NOD-LIRKO mice prevented development of diabetes in prediabetic NOD mice. A substantial increase in the splenic CD4+CD25+Foxp3+ regulatory T cell (Treg) population was observed to underlie the protected phenotype since Treg-cell depletion rendered NOD-LIRKO mice diabetic. An increase in Treg cells coupled with activation of transforming growth factor-β/SMAD family member 3 signalling pathway in pathogenic T cells favoured reduced ability to kill β cells. These data support a previously unidentified observation that initiating β-cell proliferation, alone, before islet infiltration by immune cells alters the identity of β cells, decreases pathological self-reactivity of effector T cells and increases Treg cells to prevent the progression of T1D. Type 1 diabetes (T1D) involves immune-mediated destruction of pancreatic β cells. Here, the authors show that inducing β-cell replication before immune cell infiltration of the pancreas alters β-cell antigen expression and prevents T1D disease progression in female NOD mice in a regulatory-T-cell-dependent manner.

The prevalence of hip fracture and associated risk factors in China were evaluated in a Health and Retirement Longitudinal Study. There is an apparent geographic variation in the prevalence of hip fracture in China. Advanced age, West region, lower education, under-weight, having self-reported history of chronic lung diseases, heart diseases, stroke, and arthritis appear to be associated with risk of hip fracture.The aim of this study is to estimate the prevalence of hip fracture and to identify its risk factors in China.Using the national survey data collected from the China Health and Retirement Longitudinal Study (CHARLS), we estimated the prevalence of hip fracture, considering the complex survey design and response rate. We applied the weighted logistic regression analysis to identify risk factors associated with hip fracture employing cross-sectional study designs.Among 20,110 respondents included in the analysis, there were 431 hip fractures. The overall prevalence of hip fracture among middle-aged and older Chinese adults was 2.36%. From those aged50 years to 60-69 years, the prevalence of hip fracture did not increase with age, but significantly increased after the age of 70; 1.62% for those aged50 years and 5.42% for those aged ≥70 years. East, South-Central, South-West, and North-West region had a higher prevalence of hip fracture than North and North-East region. Compared with underweight, obesity (OR 0.37 [95% CI 0.20-0.69]) was associated with a lower likelihood of hip fracture. A self-reported history of chronic lung diseases (OR 2.11 [95% CI 1.51-2.96]), heart diseases (OR 1.36 [95% CI 1.00-1.85]), stroke (OR 2.30 [95% CI 1.08-4.92]), and arthritis (OR 2.30 [95% CI 1.08-4.92]) were significantly correlated with hip fracture.There is an apparent geographic variation in the prevalence of hip fracture in China. Advanced age, West region, lower education, under-weight, having self-reported history of chronic lung diseases, heart diseases, stroke, and arthritis appear to be associated with risk of hip fracture. Understanding the geographic variations in hip fracture prevalence is important for allocation of healthcare resources. Knowing the reasons for hip fracture is necessary to implement a comprehensive policy for hip fracture prevention in China.

To evaluate DNA methylation sites and gene expression associated with coronary artery disease (CAD) and the possible pathological mechanism involved, we performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood datasets from the Gene Expression Omnibus repository of CAD samples and controls; (2) functional enrichment analysis and differential methylation gene regulatory network construction; (3) validation tests of 11 differential methylation positions of interest and the corresponding gene expression; and (4) correlation analysis for DNA methylation and mRNA expression data. A total of 669 differentially expressed mRNAs were matched to differentially methylated genes. After disease ontology, Kyoto Encyclopedia of Genes and Genomes pathway, gene ontology, protein-protein interaction and network construction and module analyses, 11 differentially methylated positions (DMPs) corresponding to 11 unique genes were observed: BDNF – cg26949694, BTRC - cg24381155, CDH5 - cg02223351, CXCL12 - cg11267527, EGFR - cg27637738, IL-6 - cg13104385, ITGB1 - cg20545410, PDGFRB - cg25613180, PIK3R1- cg00559992, PLCB1 - cg27178677 and PTPRC - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that CXCL12 was less hypomethylated in the CAD group, whereas the relative expression of ITGB1, PDGFRB and PIK3R1 was lower in CAD samples, and CXCL12 and ITGB1 methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of CXCL12 in CAD pathogenesis.

In the U.S., 30% of adults suffer joint pain, most commonly in the knee, which severely limits mobility and is often attributed to injury of cartilage and underlying bone in the joint. Current treatment methods such as microfracture result in less resilient fibrocartilage with eventual failure; autografting can cause donor site morbidity and poor integration. To overcome drawbacks in treatment, tissue engineers can design cell-instructive biomimetic scaffolds using biocompatible materials as alternate therapies for osteochondral defects. Nanofibrous poly (l-lactic acid) (PLLA) scaffolds of uniform, spherical, interconnected and well-defined pore sizes that are fabricated using a thermally-induced phase separation and sugar porogen template method create an extracellular matrix-like environment which facilitates cell adhesion and proliferation. Herein we report that chondrogenesis and endochondral ossification of rabbit and human bone marrow stromal cells (BMSCs) can be controlled by scaffold pore architecture, particularly pore size. Small-pore scaffolds support enhanced chondrogenic differentiation in vitro and cartilage formation in vivo compared to large-pore scaffolds. Endochondral ossification is prevented in scaffolds with very small pore sizes; pore interconnectivity is critical to promote capillary ingrowth for mature bone formation. These results provide a novel strategy to control tissue regenerative processes by tunable architecture of macroporous nanofibrous scaffolds. STATEMENT OF SIGNIFICANCE: Progress in understanding the relationship between cell fate and architectural features of tissue engineering scaffolds is critical for engineering physiologically functional tissues. Sugar porogen template scaffolds have uniform, spherical, highly interconnected macropores. Tunable pore-size guides the fate of bone marrow stromal cells (BMSCs) towards chondrogenesis and endochondral ossification, and is a critical design parameter to mediate neotissue vascularization. Preventing vascularization favors a chondrogenic cell fate while allowing vascularization results in endochondral ossification and mineralized bone formation. These results provide a novel strategy to control tissue regenerative processes by tunable architecture of macroporous nanofibrous scaffolds.

Growing evidence indicates an important link between gut microbiota, obesity, and metabolic syndrome. Alterations in exocrine pancreatic function are also widely present in patients with diabetes and obesity. To examine this interaction, C57BL/6J mice were fed either a chow diet, high-fat diet (HFD) or HFD plus oral vancomycin or metronidazole to modify the gut microbiome. HFD alone leads to a 40% increase in pancreas weight, decreased glucagon-like peptide-1 and peptide YY levels, and increased glucose-dependent insulinotropic peptide in the plasma. Quantitative proteomics identified 138 host proteins in fecal samples of these mice, of which 32 were significantly changed by HFD. The most significant of these were the pancreatic enzymes. These changes in amylase and elastase were reversed by antibiotic treatment. These alterations could be reproduced by transferring gut microbiota from donor C57BL/6J mice to germ-free. By contrast, antibiotics had no effect on pancreatic size or exocrine function in C57BL/6J mice fed a chow diet. Further, one week vancomycin administration significantly increased amylase and elastase levels in obese prediabetic men. Thus, the alterations in gut microbiota in obesity can alter pancreatic growth, exocrine function and gut endocrine function, and may contribute to the alterations observed in patients with obesity and diabetes.

To detect the level of vascular endothelial growth factor (VEGF) in bone marrow of patients with non-M3 acute leukemia (AL), and estimate its relationship with prognosis.From January 2016 to December 2019, 114 patients with AL in department of Hematology, Wuwei People's Hospital were selected as study group, and 25 healthy volunteers were enrolled as control group. The concentration of VEGF in bone marrow was detected by ELISA. The patients were divided into high and low concentration group according to the level of VEGF. The overall survival (OS) and event-free survival (EFS) were compared among different groups.The level of VEGF in patients with AL was significantly higher than that in the control group. The median OS and EFS in the low concentration group was 34.5 and 32 months, respectively, while, in the high concentration group was 30 and 26 months, respectively. The differences between the two groups were statistically significant (P=0.010). There were significant differences in OS rate (P=0.035) and EFS rate (P=0.026) between low and high concentration group. Multivariate analysis showed that high VEGF concentration was an independent risk factor affecting OS (HR=2.619, 95%CI 1.070-6.406, P=0.035) and EFS (HR=2.221, 95%CI 1.074-4.552, P=0.031) in AL patients.VEGF highly expresses in the bone marrow of patients with AL at initial diagnosis and relapse, and shows adverse effects on the prognosis.急性白血病患者骨髓VEGF高表达及其与预后的相关性分析.检测非M3型急性白血病（AL）患者的骨髓血管内皮生长因子（VEGF）水平，探讨VEGF的表达水平与预后的关系.选取2016年1月至2019年12月在武威市人民医院血液内科住院的AL患者共114例，以本课题组25名健康志愿者为对照组，用ELISA方法分别检测骨髓VEGF的浓度，依据VEGF表达水平进行分组，比较不同组间总生存期（OS）和无事件生存期（EFS）的差异.AL患者VEGF的表达水平明显高于对照组。VEGF低浓度组的中位OS和EFS分别为34.5和32个月，高浓度组分别为30和26个月，比较差异有统计学意义（P=0.010）。VEGF低浓度组与高浓度组的OS率与EFS率比较，差异均有统计学意义（P=0.035，P=0.026）。多因素分析显示，高浓度VEGF是影响患者OS（HR=2.619，95%CI 1.070-6.406，P=0.035）和EFS（HR=2.221，95%CI 1.074-4.552，P=0.031）的独立危险因素.AL患者初诊及复发时骨髓高表达VEGF，并对患者预后产生不良影响.

To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival.Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3The ratio of CD3Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.髓白1号方联合化疗对急性髓系白血病患者骨髓中Th17细胞的调控作用研究.探索髓白1号方联合化疗对AML患者骨髓液中Th17细胞的调控作用，为提高AML患者治疗效果与长期生存提供指导.选取2017年4月- 2019年8月在武威市人民医院血液科住院的AML患者70例，并以25名健康志愿者纳入对照组；然后AML患者根据治疗方案分为联合治疗组（髓白1号方联合化疗）和非联合治疗组（单纯化疗）。采用流式细胞术检测骨髓液中CD3初诊及复发的AML患者CD3初诊及复发的AML患者骨髓中Th17细胞的表达水平明显升高，治疗后显著减低。髓白1号方联合化疗治疗AML可明显提高CR率，降低复发率.

Globally, the tenth most common cancer is the oral squamous cell carcinoma (OSCC) and the treatment strategy for improving of OSCC patients survival rate still remains a challenging one. Aberrant regulation of cell to extracellular matrix protein interactions leads to progression of human cancers. The focal adhesion kinase (FAK) and its downstream target paxillin have been implicated in cancer growth, migration, invasion and metastasis of different cancers. However, the clinical significance of FAK and paxillin in OSCC is not well characterized so far. In the present work, we showed that relative mRNA and protein expressions of FAK and paxillin are significantly higher in side population (SP) cells of OSCC cell line SCC-55. Concomitantly, the matrix metalloproteinase-11 (MMP-11) level is also significantly elevated in SP cells. The enhanced expression of paxillin is strongly correlated with increased chemoresistance, proliferation rate, migration and invasion potential of SP cells. In addition, inhibition of paxillin expression by RNAi makes SP cells more sensitive to chemotherapy drugs. Therefore, our results suggest that paxillin over expression might play a significant role in cancer progression, invasion and chemoresistance of OSCC.

Some events of hepatotoxicity have been linked to consumption of green tea supplements. The association between consumption of green tea or green tea supplements and abnormal liver biomarkers in adults was investigated using cross-sectional data from the 2009–2014 United States National Health and Nutrition Examination Survey (U.S. NHANES). Individuals with levels of either bilirubin or GGT, ALT, AST, and/or ALP in excess of the age- and gender-specific upper limits of normal ranges were classified as having abnormal liver biomarkers. Associations between green tea or green tea supplement use (consumption vs. not) and liver function were determined using multiple logistic regression modelling. 12,289 persons were included in the green tea analyses and 12,274 in the green tea supplement analyses. The odds of having one or more abnormal liver biomarkers were significantly reduced (p = 0.01) with consumption of green tea (OR: 0.49; 95% CI: 0.28, 0.85), while no significant association (p = 0.78) was determined for consumption of green tea supplements (OR: 0.92; 95% CI: 0.52, 1.64). Based on data from the 2009–2014 U.S. NHANES, green tea consumption was associated with reduced odds of having one or more abnormal liver biomarkers; whereas, no significant association was determined with consumption of green tea supplements.

OBJECTIVE: To evaluate the safety and effectiveness of robot-guided percutaneous kyphoplasty (PKP) in treatment of multi-segmental thoracolumbar osteoporotic vertebral compression fracture (OVCF). METHODS: A clinical data of 63 cases with multi-segmental thoracolumbar OVCF without neurologic deficit treated with PKP between October 2017 and February 2019 were analyzed retrospectively. The patients were divided into robot-guided group (33 cases) and traditional fluoroscopy group (30 cases). There was no significant difference in gender, age, fracture segment, bone mineral density, and preoperative visual analogue scale (VAS) score, midline vertebral height, and Cobb angle between the two groups (P>0.05). The time to establish the tunnel, the times of fluoroscopy, the dose of fluoroscopy, the deviation of puncture, the distribution of bone cement, the leakage of bone cement, the puncture angle, and the postoperative VAS score, midline vertebral height, and Cobb angle were recorded and compared. RESULTS: The patients in two groups were followed up 11-13 months (mean, 12 months). Compared with traditional fluoroscopy group, the time to establish the tunnel, the times and dose of fluoroscopy in robot-guided group were significantly lower, the deviation of puncture was slighter, the distribution of bone cement was better, and the puncture angle was larger, the differences between the two groups were significant (P0.05). CONCLUSION: Robot-guided PKP in treatment of multi-segmental thoracolumbar OVCF can shorten the operation time, improve the accuracy of puncture, reduce the times and dose of fluoroscopy, reduce the leakage of bone cement, and achieve better cement distribution.

No international consensus has been reached regarding delineation of postoperative intensity-modulated radiotherapy (PO-IMRT) clinical target volumes (CTV) for major salivary gland carcinoma (SGC). The purpose of this article was to report our experience according to surgical principles. Between June 2010 and June 2018, 54 consecutive patients were enrolled. Reserved tissues around the margin of resection that were less than 5 mm from the invasive tumour edge before surgery were defined as high-risk clinical target volumes (CTV-HD), those less than 10 mm away were defined as medium-risk CTV (CTV1), and those 10–20 mm away were defined as low-risk CTV (CTV2), and were irradiated with 63–65 Gy, 59.5–61 Gy, and 45–54 Gy, respectively. Target volume distributions of reserved tissues were analysed and actuarial estimates of overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were obtained with the Kaplan–Meier method. In parotid gland tumours, the percentages of defined CTV-HD in the styloid process, mandibular ramus, posterior venter of the digastric muscle, carotid sheath and stylomastoid foramen reached 34.29%, 25.71%, 54.29%, 40.00%, and 37.10%, respectively. The median follow-up was 33 months (range, 5–98 months). The 3-year and 5-year Kaplan–Meier estimates of OS, RFS and DMFS were 85.4% and 77.8%, 97.4%, and 97.4%, and 82.0% and 82.0%, respectively. It is feasible to delineate CTVs according to distances between various reserved tissues and the primary tumour edge before operation.

Purpose: The aim was to investigate the associations between maternal thyroid parameters within the normal ranges during early pregnancy and birth outcomes, and further to examine whether the associations were modified by gestational weight gain (GWG). Methods: Maternal serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations within the normal ranges during early pregnancy were measured from 8,107 pregnant women in Wuhan, China. The associations between maternal thyroid parameters and birth outcomes (birth weight, birth length, and low birth weight) were analyzed using multivariable adjusted regression models, and effect modification by pre-pregnancy body mass index (BMI) category and GWG were further evaluated. Results: Maternal TSH and FT4 concentrations were negatively associated with birth weight, and the latter only occurred in normal weigh women with inadequate and excessive GWG, as well as in both underweight and overweight women with excessive GWG (e.g., β = -359.33 g, 95% CI: -700.95, -17.72 in underweight women with excessive GWG for per unit increase of FT4 concentrations). Moreover, maternal FT4 and FT3 concentrations were associated with increased risk for low birth weight, and the latter only occurred in normal weigh women with inadequate GWG (OR = 2.52, 95% CI: 1.00, 6.36 for per unit increase of FT3 concentrations). These associations still persist when maternal thyroid parameters were modeled as quintiles. Main conclusion: Maternal normal thyroid function during early pregnancy with excessive and inadequate GWG may adversely influence fetal growth.

OBJECTIVE: To compare short-term effectiveness between robot-guided percutaneous minimally invasive pedicle screw internal fixation and traditional open internal fixation in the treatment of thoracolumbar fractures. METHODS: The clinical data of 52 cases of thoracolumbar fracture without neurological injury symptoms admitted between January 2018 and May 2018 were retrospectively analyzed. According to the different surgical methods, they were divided into minimally invasive group (24 cases, treated with robot-assisted percutaneous minimally invasive pedicle screw internal fixation) and open group (28 cases, treated with traditional open internal fixation). There was no significant difference between the two groups in the general data such as gender, age, cause of injury, fracture segment, thoracolumbar injury classification and severity score (TLICS), preoperative back pain visual analogue scale (VAS) score, Oswestry disability index (ODI) score, fixed segment height, and fixed segment kyphosis Cobb angle (P>0.05). The operation time, intraoperative blood loss, and hospitalization time of the two groups were recorded and compared; as well as the VAS score, ODI score, fixed segment height, and fixed segment kyphosis Cobb angle of the two groups before operation and at 3 days, 1 month, 6 months, and 10 months after operation. CT scan was reexamined at 1-3 days after operation, and the pedicle screw insertion accuracy rate was determined and calculated according to Gertzbein-Robbins classification standard. RESULTS: The operation time of the minimally invasive group was significantly longer than that of the open group, but the intraoperative blood loss and hospitalization time were significantly shorter than those of the open group (P0.05). CONCLUSION: Robot-assisted percutaneous minimally invasive pedicle screw internal fixation for thoracolumbar fractures has significant advantages in intraoperative blood loss, hospitalization time, and early postoperative effectiveness and other aspects, and the effect of fracture reduction is good.

A chemical investigation on the 95% ethanol extract of the aerial part of

A chemical investigation on the 80% EtOH extract of the aerial parts of Kopsia fruticosa led to five new indole alkaloids, kopsifolines G-K (1–5), and one known alkaloid, kopsifoline A (6). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated components were evaluated in vitro for cytotoxic activities against seven tumor cell lines, antimicrobial activities against two Gram-positive bacteria and five Gram-negative bacteria, and antifungal activities against five pathogens. As a result, alkaloids 3–5 exhibited some cytotoxicity against all of seven tested tumor cell lines (HS-1, HS-4, SCL-1, A431, BGC-823, MCF-7, and W480) with IC50 values of 11.8–13.8, 10.3–12.5, and 7.3–9.5 μM, respectively. Alkaloids 3–5 also possessed significant antimicrobial and antifungal activities which was reported for the first time for the alkaloids isolated from Kopsia genus.

The regulation of islet cell biology is critical for glucose homeostasis1.N6-methyladenosine (m6A) is the most abundant internal messenger RNA (mRNA) modification in mammals2. Here we report that the m6A landscape segregates human type 2 diabetes (T2D) islets from controls significantly better than the transcriptome and that m6A is vital for β-cell biology. m6A-sequencing in human T2D islets reveals several hypomethylated transcripts involved in cell-cycle progression, insulin secretion, and the Insulin/IGF1-AKT-PDX1 pathway. Depletion of m6A levels in EndoC-βH1 induces cell-cycle arrest and impairs insulin secretion by decreasing AKT phosphorylation and PDX1 protein levels. β-cell specific Mettl14 knock-out mice, which display reduced m6A levels, mimic the islet phenotype in human T2D with early diabetes onset and mortality due to decreased β-cell proliferation and insulin degranulation. Our data underscore the significance of RNA methylation in regulating human β-cell biology, and provide a rationale for potential therapeutic targeting of m6A modulators to preserve β-cell survival and function in diabetes.

To investigate the common genotypes of thalassemia of the pregnant woman in Wuhan area of China, and to make the prenantal gentic diagnosis for the fetus at high risk of thalassemia.A total of 357 pregnant woman with the primary positive screening in Wuhan area were included in this study. Genotypes were measured with PCR-flow cytometry, and fluorescence hybridization was used for detecting thalassmia gene. The husbands of the pregnant women with thalassmia were recalled for genetic analysis of thalassemia, and 9 cases of fetuses with high risk of thalassemia were detected by amniocontesis after genetic counseling.In 357 cases of the pregnant women in Wuhan area, the 214 cases were diagnosed as thalassemia, 80 cases were diagnosed as alpha thalassemia (up to 90%), whose genotypes were determind as --Minor and static thalassemia were very common in Wuhan area. Genetic detection after primary screening, genetic counseling and prenatal diagnosis in pregnant women could provide a theoretical basis for the development of regional specific prevention of intermedius and critical thalassemia which is meaning for rearing and bearing better children.中国武汉地区孕妇地中海贫血基因检测及产前诊断.调查中国武汉地区孕妇地中海贫血（地贫）常见基因突变类型，并对地中海贫血高风险胎儿进行地中海贫血基因产前诊断.采用PCR-流式荧光杂交法对产检疑似地中海贫血的357例孕妇进行地中海贫血基因检测，召回阳性孕妇的丈夫进行地中海贫血基因检测。经遗传咨询，对9例孕有地中海贫血高风险胎儿的孕妇抽取羊水进行地中海贫血基因产前诊断.在357例疑似地中海贫血孕妇中，经基因确诊214例，其中α-地中海贫血孕妇80例，基因型--武汉地区孕妇地中海贫血以静止型和轻型最为常见；对疑似地中海贫血阳性的孕妇进行基因检测、遗传咨询、并对孕有高风险胎儿的孕妇进行地中海贫血基因产前诊断，能有效防止中间型和重型地中海贫血患儿出生，对优生优育具有重大意义.

A phytochemical investigation on the 90% ethanol aqueous extract of the aerial part of

Pin1 is the only known peptidyl-prolyl cis–trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.

Phytochemical investigation on the stems of Schisandra glaucescens resulted into the isolation of three new lanostane triterpenoids, 12-hydroxyschiglausin B (1), 12-hydroxykadsuphilactone B (2), and 20R-hydroxyschinalactone C (3). Structural elucidation of all the compounds was accomplished by spectral methods. The isolated compounds were tested in vitro for cytotoxic activities. As a result, triterpenoids 1 and 2 showed cytotoxic activities for all six tested tumor cell lines with IC

Background: A normal thyroid physiology is crucial for the maintenance of male reproductive health. Changes in thyroid hormones may represent an intermediate biological mechanism linking phthalate exposure and potential adverse health effects on male reproduction. Objective: To investigate the mediating role of thyroid function on the association between phthalate exposure and semen quality. Method: Serum thyroid hormones, semen quality and repeated measures of urinary phthalate metabolites were determined among 509 reproductive-aged men in Wuhan, China. Cross-sectional associations between urinary phthalate metabolites, serum thyroid hormones and semen quality were explored using multivariable linear regressions. A mediation analysis was conducted to explore the role of thyroid function on the association of phthalate exposure with semen quality. Results: Significant dose-dependent relationships were found across quartiles of monoethyl phthalate (MEP) with decreasing serum free thyroxine (FT4), which, in turn, was negatively associated with percentage of normal morphology (p for trend = 0.04). Also, we found that the proportions of di-(2-ethylhexyl)-phthalate metabolites excreted as mono-(2-ethylhexyl) phthalate (%MEHP) were negatively associated with serum thyroid-stimulating hormone (TSH) (all p for trends

A systematic review of published toxicology and human intervention studies was performed to characterize potential hazards associated with consumption of green tea and its preparations. A review of toxicological evidence from laboratory studies revealed the liver as the target organ and hepatotoxicity as the critical effect, which was strongly associated with certain dosing conditions (e.g. bolus dose via gavage, fasting), and positively correlated with total catechin and epigallocatechingallate (EGCG) content. A review of adverse event (AE) data from 159 human intervention studies yielded findings consistent with toxicological evidence in that a limited range of concentrated, catechin-rich green tea preparations resulted in hepatic AEs in a dose-dependent manner when ingested in large bolus doses, but not when consumed as brewed tea or extracts in beverages or as part of food. Toxico- and pharmacokinetic evidence further suggests internal dose of catechins is a key determinant in the occurrence and severity of hepatotoxicity. A safe intake level of 338 mg EGCG/day for adults was derived from toxicological and human safety data for tea preparations ingested as a solid bolus dose. An Observed Safe Level (OSL) of 704 mg EGCG/day might be considered for tea preparations in beverage form based on human AE data.

Non-small cell lung cancer (NSCLC) is a common malignant tumor. Although the abnormal expression and potential clinical prognostic value of histone deacetylase 1 (HDAC1) were recently discovered in many kinds of cancer, the roles and molecular mechanisms of HDAC1 in NSCLC is still limited. The CCK-8 assay is used to evaluate the viability of NSCLC cells. Downregulation of HDAC1 by shRNA. The TUNEL assay was used to evaluate the role of HDAC1 in NSCLC apoptosis. To evaluate the role of HDAC1 in NSCLC cells migration, the Boyden chamber transwell assay and wound healing assay were used. To evaluate the cells invasion, the matrigel precoated Transwell assay was used. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the level of vascular endothelial growth factor (VEGF) and IL-8 in NSCLC. To investigate the role of HDAC1 in angiogenesis, the tube formation assay was investigated. In this study, we showed that HDAC1 expression was elevated in NSCLC lines compared to that in normal liver cells LO2. Furthermore, downregulation of HDAC1 inhibited cell proliferation, prevented cell migration, decreased cell invasion, reduced tumor angiogenesis and induced cell apoptosis. In summary, HDAC1 may be regarded as a potential indicator for NSCLC patient treatment.