Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct three-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean and standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Comparison of tropomyosin released peptide and epitope mapping after in vitro digestion from fish (Larimichthys crocea), shrimp (Litopenaeus vannamei) and clam (Ruditapes philippinarum) through SWATH-MS based proteomics.

Tropomyosin (TM) is a major shellfish allergen and a minor fish allergen. Different digestion profiles affect potential allergen anaphylaxis of protein. In this study, released peptides of fish-TM, shrimp-TM, and clam-TM by in vitro digestion of simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and gastrointestinal (GI) were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) based proteomics. Results showed that digestion products of shrimp-TM yielded a lot of peptides matched T/B cell epitopes while core regions matched epitopes were distributed along the entire chain. Pepsin or trypsin-based digestion products of shrimp-TM presented many more peptides matched T/B cell epitopes compared with those of fish-TM and clam-TM. Besides, a differentiating peptide of VEKDKALSNAEGEVAAL (72-88) overlapped T/B cell epitopes could be used as a candidate peptide marker to identify tropomyosin allergen. These findings would supply new insight into the different allergenicity of tropomyosin.

[Effect of acupuncture on dry eye and tear inflammatory factors].

OBJECTIVE: On the basis of sodium hyaluronate eye drops, to observe the clinical efficacy of acupuncture on dry eye and explore the effect mechanism of ocular surface protection. METHODS: A total of 80 patients with dry eye were randomly divided into an observation group and a control group, 40 cases in each group. The control group was treated with routine cleaning of eyelid margin, hot compress of eyes with warm towel, and external application of sodium hyaluronate eye drops for 5 weeks. On the basis of the treatment as the control group, the observation group was treated with acupuncture at Jingming (BL 1), Cuanzhu (BL 2), Chengqi (ST 1), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6), etc., once a day, 6 times a week for 5 weeks (30 times totally). Before and after treatment, SchirmerⅠtest (SⅠT), breaking up time (BUT), corneal fluorescent (FL) score, ocular surface disease index (OSDI) score, and the contents of IL-6 and TNF-α in tears were evaluated and the therapeutic effect was compared between the two groups. RESULTS: Compared with before treatment, SⅠT and BUT after treatment in the observation group were prolonged (P<0.05), the scores of FL and OSDI and the contents of IL-6 and TNF-α in tears were decreased (P<0.05). After treatment, SⅠT and BUT in the observation group were longer than the control group (P<0.05), and the scores of FL and OSDI and the contents of IL-6 and TNF-α in tears in the observation group were lower than the control group (P<0.05). The total effective rate in the observation group was 87.5% (35/40), which was higher than 45.0% (18/40) in the control group (P<0.05). CONCLUSION: On the basis of sodium hyaluronate eye drops, acupuncture could improve the clinical symptoms of dry eye, promote the secretion of tears, prolong the tear film breaking up time, and reduce corneal damage, and effect mechanism may be related to the reduction of inflammatory response.

Single-cell transcriptomic analysis reveals differential cell subpopulations and distinct phenotype transition in normal and dissected ascending aorta.

BACKGROUND: Acute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied. METHODS: Single-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings. RESULTS: We got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1+ fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs. CONCLUSION: We characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD.

Comparative Efficacy of Xianling Gubao Capsules in Improving Bone Mineral Density in Postmenopausal Osteoporosis: A Network Meta-Analysis.

OBJECTIVE: The clinical efficacy of Xianling Gubao capsule (XLGB) and its combination therapy in the treatment of postmenopausal osteoporosis (PMOP) was systematically evaluated by frequency-based network meta-analysis. METHODS: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials of XLGB for the treatment of PMOP from the establishment of each database to November 22, 2021. The quality of the included studies was evaluated by using the risk of bias assessment tool version 2.0 (Rob 2.0) recommended by Cochrane. Stata 14.0 was applied for statistical analysis of the data, and the surface under the cumulative ranking curve (SUCRA) was used to rank the intervention measures of each outcome index. RESULTS: This study included 22 clinical trials (including 19 RCTs and 3 non-RCTs) involving 12 drug therapies. According to the results of the network meta-analysis and SUCRA, the best three interventions for improving lumbar bone mineral density (BMD) are XLGB+BP+calcium (83.7%), XLGB+BP (68.5.7%) and XLGB+VD (67.1%). XLGB+calcium was the best combination regimen for improving femoral neck BMD and increasing bone Gla protein (BGP) and alkaline phosphatase (ALP) contents in serum. The SUCRA values of XLGB+calcium for improving the three outcome indicators were 68.0%, 59.5% and 82.1%, respectively. CONCLUSIONS: The results of this network meta-analysis show that combined application of XLGB can effectively improve BMD and serum BGP and ALP compared to calcium alone, VD or BP. In the future, multicenter, large-sample and double-blind clinical RCTs should be carried out to supplement and verify the results of this study.

Comparisons of the Efficacy and Safety of Total Knee Arthroplasty by Different Surgical Approaches: A Systematic Review and Network Meta-analysis.

The purpose of this network meta-analysis was to investigate the efficacy and safety of total knee arthroplasty (TKA) considering seven different surgical approaches. Four databases (PubMed, Cochrane Library, EMBASE, Web of Science) were searched for clinical randomized controlled trials (RCTs) involving TKA with different surgical approaches. STATA 14.0 was used to construct network maps and publication bias graphs and conduct inconsistency tests, network meta-analyses, and surface under the cumulative ranking (SUCRA) calculations. A total of 51 RCTs involving 4061 patients and 4179 knees from 18 countries were included. Among the seven surgical approaches, the midvastus approach (MV) was the top choice to reduce tourniquet use time, the subvastus approach (SV) had the shortest operation time, the mini-midvastus approach (Mini-SV) was associated with the least amount of time to achieve straight leg raise (SLR) after surgery, the mini-medial parapatellar approach (Mini-MP) reduced postoperative pain effects, and the medial parapatellar approach (MP) was the best approach to improve range of motion (ROM). Excluding the quadriceps-sparing approach (QS), which was not compared, the use of the mini-midvastus (Mini-MV) may shorten the hospital stay. There were no significant differences in blood loss, postoperative complications, American Knee Society Score (AKSS) objective, or AKSS functional between the seven surgical approaches (P > 0.05).

Exercise or Dietotherapy Is Not Better than Returning to a Regular Diet to Rebuild Lipid Homeostasis of Rats.

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high-fat control group, and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P < 0.001) and LDL-C (P < 0.05), but higher weight gain (P < 0.001), insulin level (P < 0.01), and pancreas AMPKα (P < 0.01) than high-fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain (P < 0.001), insulin level (P < 0.01), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.

Identification of the Dominant T-Cell Epitopes of Lit v 1 Shrimp Major Allergen and Their Functional Overlap with Known B-Cell Epitopes.

Development of efficient peptide-based immunotherapy for shrimp allergy relies on the identification of the dominant T-cell epitopes of its major allergen, tropomyosin. In this study, immunoinformatic tools, T-cell proliferation, cytokine release, IgG/IgE binding, and degranulation assays were used to identify and characterize the T-cell epitopes in Lit v 1 in comparison with previously validated B-cell epitopes. The results showed that of the six in silico predicted T-cell epitopes only one (T2: VQESLLKANIQLVEK, 60-74) promoted T-cell proliferation, the release of IL-2, and upregulated secretion of Th2-associated cytokines in the absence of IgG/IgE binding and degranulation activities. These findings support T2 as a candidate for the development of an efficient peptide-based vaccine for the immunotherapy for shrimp-allergic patients.

[Network Meta-analysis of oral Chinese patent medicine in treatment of knee osteoarthritis].

To evaluate the efficacy and safety of Chinese patent medicine in the treatment of knee osteoarthritis(KOA) with network Meta-analysis, and provide evidence-based medicine evidences for clinical practice. PubMed, Cochrane Library, EMbase, CNKI, Wanfang, VIP and CBM were used to search for clinical randomized controlled trials(RCTs) on Chinese patent medicines for treatment of knee osteoarthritis, with a time limit from the establishment of each database to March 2020. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. The network Meta-analysis was performed by Stata 14.0 software. A total of 5 788 patients in 58 RCTs were included, involving 9 kinds of Chinese patent medicines. The results of the network Meta-analysis indicated that in terms of total effective rate, the top three optimal medication regimens were Jinwu Gutong Capsules + Amino Acid Glucose(AAG), Xianling Gubao + AAG and Biqi Capsules; the top three interventions to reduce the VAS score were Panlongqi Tablets > Xianling Gubao + AAG > Xianling Gubao + non steroidal anti-inflammatory drugs(NSAIDs); the top three interventions to reduce the total score of WOMAC were Jintiange Capsules+NSAIDs> Jinwu Gutong Capsules + AAG > Biqi Capsules + NSAIDs; the top three medication schemes with better curative effect to reduce Lequesnse index were Xianling Gubao + NSAIDs > Biqi Capsules + NSAIDs > Jintiange Capsules + NSAIDs; the top three interventions to reduce TNF-α level Xianling Gubao + AAG > Jintiange Capsules > Jintiange Capsules + AAG=Jinwu Gutong Capsules + AAG. In terms of safety, the top five interventions with the least adverse reactions were Biqi Capsules > Jinwu Gutong Capsules > Biqi Capsules + NSAIDs > Xianling Gubao + NSAIDs > Jintiange Capsules. The combined application of Chinese patent medicine and NSADIs or AAG can improve the clinical treatment effect and reduce adverse reactions in KOA patients.

Effect of selective lymph node dissection on immune function in patients with T1 stage non-small cell lung cancer: a randomized controlled trial.

BACKGROUND: Many lymph nodes resected from early-stage non-small cell lung cancer (NSCLC) patients haven't metastasis. Selective lymph node dissection (SLND) can reduce surgical trauma by retaining non-metastatic lymph nodes, we aimed to investigate whether SLND could reduce immune impairment compared with systematic lymph node dissection. METHODS: According to the selection criteria, patients with no metastasis in hilar and regional lymph nodes were selected as the research subjects. The patients were randomly divided into 2 groups: the SLND group (Group SD) and the systematic lymph node dissection group (Group CD). At 24 hours before surgery and on the 1st and 3rd postoperative days (POD), fasting venous blood was sampled to detect cytokine indicators [interleukin-6 (IL-6), C-reactive protein (CRP)], cellular immune indicators [lymphocytes, natural killer cells (NK cells), CD4+, CD8+, CD4+/CD8+], and humoral immune indicators (IgG, IgA, IgM). At the same time, clinically indicators of the patients were recorded. All indicators between the 2 groups were compared. RESULTS: The comparison of clinical indicators between the two groups showed that SLND is more conducive to patients' rapid recovery after surgery. CRP and IL-6 levels in Group CD were significantly higher than those in Group SD after surgery (P<0.05). There were no statistical differences between the 2 groups in the proportions of lymphocytes and NK cells after surgery (P>0.05). The proportions of CD4+ cells and CD4+/CD8+ in Group CD were significantly lower than those in Group SD at POD1 (P<0.05). The proportion of CD8+ cells was significantly higher in Group CD than in Group SD at POD3 (P<0.05). There were no significant differences in IgG, IgA, and IgM levels between the 2 groups at the same point in time (P>0.05). CONCLUSIONS: Compared with systematic lymph node dissection, SLND has the following advantages: (I) it is more conducive to patients' rapid recovery after surgery; (II) it can reduce the body's acute inflammatory response and non-specific immune damage; (III) it can reduce the damage to cellular immune function caused by surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045893.

Experimental Study on the Bone Morphogenetic Protein 1-Modified Bone Marrow Mesenchymal Stem Cell Sheets to Promote Mandibular Distraction Osteogenesis.

OBJECTIVE: The present study aims to increase the concentration of genetically modified bone marrow mesenchymal stem cells (BMSCs) in the distraction osteogenesis (DO) interstitial space and induce the conversion of BMSCs to osteoblasts to improve the osteogenic efficiency in DO and shorten the treatment period. METHODS: Bone morphogenetic protein 1 (BMP-1) and green fluorescent protein (GFP) gene-modified cell sheets of BMSCs were constructed by tissue engineering. Thirty-six New Zealand white rabbits were randomly divided into three groups: group A (the blank control group), group B (the GFP group) with the injection of GFP gene-modified BMSC sheets into the DO gap, and group C (the BMP-1 group) with the injection of BMP-1 gene-modified BMSC sheets into the DO gap. Rabbits in all three groups were distracted for 5 days at a distraction rate of 2.0 mm/d, once/day. After distraction, the above-mentioned cell sheet suspension was injected into the distraction gap to observe osteogenesis, which was observed by gross specimen observation, micro-computed tomography (Micro-CT) scanning, and histomorphology. RESULTS: The gross specimen observation showed that all animals had smooth and continuous bone cortex in the distraction region with relatively high hardness. The osteogenesis quality or hardness was ranked from the highest to the lowest, as Group C > Group B > Group A. Micro-CT and histomorphological observation revealed that group C had better maturation and bone volume of the new bone in the DO region at weeks 3 and 6 than groups B and A. CONCLUSION: BMP-1 gene-modified BMSC sheets could effectively promote the formation of new bone during rapid DO in the mandible, compensating for the poor osteogenesis caused by rapid distraction and providing a new approach to shorten the DO treatment period in clinical practice.

Does Routine Anti-Osteoporosis Medication Lower the Risk of Fractures in Male Subjects? An Updated Systematic Review With Meta-Analysis of Clinical Trials.

Background: Several epidemiological articles have reported the correlations between anti-osteoporosis medication and the risks of fractures in male and female subjects, but the specific efficacy of anti-osteoporosis medication for male subjects remains largely unexplored. Objective: The aim of this study was to evaluate the correlation between anti-osteoporosis medication and the risk of fracture in relation to low bone mass [including outcomes of osteoporosis, fracture, and bone mineral density (BMD) loss] in male subjects analyzed in studies within the updated literature. Methods: Randomized controlled trials (RCTs) that analyzed the effectiveness of a treating prescription for male subjects with osteoporosis (or low BMD) and that focused on the outcomes of fracture were included. Relevant studies from Embase, Web of Science, PubMed, and Chinese database of CNKI were retrieved from inception to January 30th, 2019. Two staff members carried out the eligibility assessment and data extraction. The discrepancies were settled by consultation with another researcher. We calculated the pooled relative risks (RRs) based on 95% confidence intervals (CIs). Results: Twenty-seven documents (28 studies) with 5,678 subjects were identified. For the category of bisphosphonates, significant results were observed in pooled analyses for decreased risk of the vertebral fracture domain (RR, 0.44 [95% CI, 0.31-0.62]), nonvertebral fracture domain (RR, 0.63 [95% CI, 0.46-0.87]), and clinical fracture domain (RR, 0.59 [95% CI, 0.48-0.72]) compared with those of controls. Participants with bisphosphonates had a 56% (95% CI = 38-69%) lower risk of vertebral fractures, 37% (95% CI = 13-54%) lower risk of nonvertebral fractures, and 41% (95% CI = 28-52%) lower risk of clinical fractures. Furthermore, meta-analyses also demonstrated a decreased risk of the vertebral fracture domain via treatment with risedronate (RR, 0.45 [95% CI, 0.28-0.72]) and alendronate (RR, 0.41 [95% CI, 0.23-0.74]), but not with calcitriol, calcitonin, denosumab, ibandronate, monofluorophosphate, strontium ranelate, teriparatide, or zoledronic acid, compared with that of controls. Conclusions: This systematic review confirms that bisphosphonates were connected with a decreased risk of vertebral fractures, nonvertebral fractures, and clinical fractures for male subjects with osteoporosis. Future research is needed to further elucidate the role of nonbisphosphonates in treating fractures of osteoporosis subjects.

Selective lymph node dissection for clinical T1 stage non-small cell lung cancer.

BACKGROUND: More and more pulmonary nodules are detected by CT scan, and postoperative pathology reveals many lymph nodes without metastasis. The purpose of this study was to investigate the characteristics of T1 stage lymph node metastasis in non-small cell lung cancer (NSCLC) and to explore the indications for selective lymph node dissection (SLND). METHODS: A total of 841 patients with stage T1 of NSCLC were performed lobectomy and systemic lymphadenectomy. We analyzed the types of lymph node metastases and the relationship between lymph node metastasis and pulmonary pleural invasion, thrombosis of vascular carcinoma and tumor size in all patients. RESULTS: Among them, 257 cases of tumor in the right upper lobe (RUL) and 186 cases in the left upper lobe (LUL), and no metastasis was found in the inferior mediastinal lymph nodes. Tumor metastases occurred in subcarinal lymph nodes, with hilar and/or mediastinal lymph node metastasis. Among the 171 cases with right lower lobe (RLL) tumors and the 151 cases with left lower lobe (LLL) tumors, patients with superior lymph node metastasis were all associated with hilar and/or subcarinal lymph node metastasis. Among the 76 cases with right middle lobe (RML) tumors, no metastasis with inferior mediastinal lymph node was observed. Lymph node metastasis is much easier in patients with pulmonary pleural invasion or thrombosis of vascular cancer. The larger the tumor diameter, the greater the possibility of lymph node metastasis. CONCLUSIONS: SLND is a feasible treatment for clinical T1 stage NSCLC under the guidance of intraoperative frozen results of lobe-specific lymph nodes.

Can Dietary Intake of Vitamin C-Oriented Foods Reduce the Risk of Osteoporosis, Fracture, and BMD Loss? Systematic Review With Meta-Analyses of Recent Studies.

Background: Several epidemiological studies have been performed to evaluate the association of dietary intake of vitamin C-oriented foods (DIVCF) with risk of fracture and bone mineral density (BMD) loss, but the results remain controversial. Therefore, we conducted a systematic meta-analysis to assess this correlation. Methods: We searched EmBase, PubMed, Web of Science, and the Chinese database CNKI for relevant articles published up to August 2019. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random- or fixed-effects model. Discrepancies were resolved by consultation with a third expert. Results: A total of 13 eligible articles (including 17 studies) with 19,484 subjects were identified for the present meta-analysis. The pooled RR of hip fracture for the highest vs. lowest category was 0.66 (95% CI, 0.47-0.94) for DIVCF, i.e., people with a greater frequency of Vitamin C uptake had a 34% (95% CI, 6%-53%) lower prevalence of hip fracture. In subgroup analyses stratified by study design, gender, and age, the negative associations were statistically significant. Furthermore, the statistical analysis of the association between DIVCF and risk of osteoporosis (RR, 0.66; 95% CI, 0.48-0.92), BMD at the lumbar spine (pooled r, 0.15; 95% CI, 0.09-0.23), and BMD at the femoral neck (pooled r, 0.20; 95% CI, 0.11-0.34) showed beneficial effects of DIVCF. Conclusion: Our meta-analysis indicates that DIVCF is negatively associated with the risk of hip fracture, osteoporosis, and BMD loss, suggesting that DIVCF decreases the risk of hip fracture, osteoporosis, and BMD loss.

[Dihydromyricetin ameliorates chronic social defeat stress induced cognitive and affective disorder in mice].

OBJECTIVE: To investigated the effects of dihydromyricetin on cognitive and affective disorders induced by chronic social defeat stress and its possible mechanism in mice. METHODS: C57BL/6J mice were randomly divided into control group (Control), chronic social defeat stress group (CSDS) and chronic social defeat stress + DHM group (CSDS+DHM) (14 mice in each group). The mice received chronic social defeat stress and were injected with DHM or vehicle intraperitoneally. A part of mice were subjected to (10 mice of each group) novel object recognition test (NOR), Y maze test, open field test (OFT), social interaction test (SIT), forced swimming test (FST) and tail suspension test (TST). The other mice (4 mice of each group) were decapitated and the expression levels of SIRT1 in hippocampus were detected by Western blot. RESULTS: Compared with the control group, the learning and memory of the CSDS group were reduced significantly, the anxiety level was increased significantly, the immobility time in TST and FST was increased significantly, and the SIRT1 protein level in hippocampus was reduced significantly (P＜ 0.05 or P＜ 0.01); Compared with the CSDS group, the learning and memory of the CSDS + DHM group were improved significantly, the anxiety level of the mice was reduced significantly, and the immobility time in TST and FST was reduced significantly. The protein level of SIRT1 in hippocampus was increased significantly (P＜ 0.05 or P＜ 0.01). CONCLUSION: DHM ameliorates the cognitive impairment, anxiety like behavior and depression like behavior of mice induced by CSDS and up-regulates the expression of SIRT1 protein.

Hypoxia-inducible factor-1 promotes cancer progression through activating AKT/Cyclin D1 signaling pathway in osteosarcoma.

OBJECTIVE: Osteosarcoma is an aggressive malignant neoplasm, which commonly afflicts patients of 20-30 years of age, and its morbidity has increased markedly in recent years. Certain genes and signal pathways have been identified to exert key roles in osteosarcoma progression. Here, we set out to characterize in more detail of the role of HIF-1/AKT/Cyclin D1 pathway in the progression of osteosarcoma. METHODS: Immunohistochemistry, western blot and qPCR were used to test the protein or mRNA levels of HIF-1 in osteosarcoma tissues or adjacent nontumor tissues. MTT, clone formation, wound healing, Transwell, in vivo tumorigenesis, flow cytometry and western blot analysis were used to determine cell proliferation, clone formation ability, migration, invasion, tumorigenesis, and cell apoptosis in MG63 and U2OS cells, respectively. Immunoprecipitation and immunofluorescence assays were performed to investigate the protein-protein interaction between HIF-1α and proteins related to signal pathways. RESULTS: HIF-1 was overexpressed in osteosarcoma tissues and cell lines, which promoted cell proliferation, clone formation, migration, invasion and inhibited cell apoptosis. Results also demonstrated that HIF-1 combined with AKT, and there might be a positive loop between the two proteins of HIF-1 and AKT, then the protein-protein interaction up-regulated the expression of Cyclin D1 in protein level, but not mRNA level, made Cyclin D1 protein more stable, triggered cell proliferation, clone formation, tumorigenesis, but inhibited cell apoptosis. CONCLUSIONS: The present study showed that HIF-1 modulated Cyclin D1 expression might through shaping a positive loop with AKT proteins. Additionally, HIF-1α promoted the tumor cells growth, migration and invasion in osteosarcoma through the activation of the AKT/Cyclin D1 signal cascade. We proposed that HIF-1 could be served as a marker for distinguishing osteosarcoma and an effective therapeutic target for osteosarcoma.

Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r2) and cross-validation coefficient (q2) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r2 and q2 of CoMSIA (comparative molecular similarity analysis) are 0.992 and 0.863, respectively. Molecular docking and MD simulations were conducted to confirm the detailed binding mode of enzyme-inhibitor system. The new NA inhibitors had been designed, synthesized, and their inhibitory activities against group-1 neuraminidase were determined. One agent displayed excellent neuraminidase inhibition, with IC50 value of 39.6 µM against NA, while IC50 value for oseltamivir is 61.1 µM. This compound may be further investigated for the treatment of infection by the new type influenza virus.

Scaffold-Based Delivery of Bone Marrow Mesenchymal Stem Cell Sheet Fragments Enhances New Bone Formation In Vivo.

PURPOSE: Stem cell therapy is becoming a potent strategy to shorten the consolidation time and reduce potential complications during distraction osteogenesis (DO). However, the conventional local injection or scaffold-based delivery of bone marrow mesenchymal stem cell (BMSC) suspension deprives the cells of their endogenous extracellular matrix, which might dampen cell differentiation and tissue regeneration after implantation. Therefore, in our study, a BMSC sheet was established and was then minced into fragments and loaded onto a hydroxyapatite (HA) scaffold for grafting. MATERIALS AND METHODS: The purified and characterized BMSCs were grown into a cell sheet, and bone formation and mineralization capacity, as well as the cell sheet composition, were analyzed. Afterward, the in vivo osteogenic ability of cell sheet fragments (CSFs) was evaluated in immunocompromised mouse and rabbit models of DO. RESULTS: The BMSC sheet exhibited higher alkaline phosphatase activity than osteogenic cell suspension cultures. Alkaline phosphatase activity and mineral particles in the cell sheet increased further after osteogenic induction. Moreover, calcium and phosphorus were present only in the osteogenic cell sheet, along with the common elements carbon, oxygen, chlorine, sodium, and sulfur, as indicated by x-ray photoelectron spectroscopy analysis. In a mouse model, the CSF-HA complex was injected subcutaneously. Micro-computed tomography analysis showed that the osteogenic CSF-HA complex led to a considerably higher bone volume than the BMSC-HA or CSF-HA complex. The osteogenic CSF-HA specimens showed increased angiogenesis and deposition of type I collagen compared with the non-osteogenic CSF-HA or BMSC-HA specimens. Moreover, the osteogenic CSF-HA markedly improved bone consolidation and increased bone mass in DO rabbits. CONCLUSIONS: Collectively, the incorporation of osteogenic BMSC sheets into HA particles greatly promoted bone regeneration, which offers therapeutic alternatives for DO.

Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion.

OBJECTIVES: Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. MATERIALS AND METHODS: Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman's rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. RESULTS: In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01)/clinical staging (r = -0.41, P<0.01)/tumor stage (r = -0.28, P = 0.02)/nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. CONCLUSION: Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.