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To conduct a Food Literacy Evaluation Questionnaire Chinese Version (FLEQ-Ch) through a cross-cultural validation of the original questionnaire.This was an observational, cross-sectional study undertaken in two phases: (1) translation and cross-culture adaptation, and (2) psychometric evaluation.A total of 509 residents in Yangzhou City, China were enrolled in this study.A translation and cross-cultural adaptation of the FLEQ in Chinese was developed. The psychometric characteristics of FLEQ-Ch were analyzed for internal consistency, content validity, construct validity and discriminant validity.The KMO value of the questionnaire was 0.901 and the approximate chi-square value of Bartlett's sphericity test was 8132.538. The ranges of the Cronbach's α coefficient and the test-retest coefficient of the total questionnaire and three dimensions were 0.869-0.955 and 0.941-0.952, respectively. The value of content validity index of the total questionnaire was 0.945. Construct validity: (1) Aggregation coefficient was between 0.828 and 0.955; (2) Discrimination coefficient was between 0.004 and 0.227; (3) Correlation coefficient between each factor was between 0.046 and 0.188; the correlation coefficient between each factor and the total questionnaire ranged from 0.419 to 0.788. Discriminant validity: the standardized factor loadings of all items on the corresponding factors were 0.75-0.96. The results of the model-fit indices showed RMSEA was 0.08 and GFI was 0.91.The FLEQ-Ch can effectively evaluate the food literacy of the general public in terms of foods planning and management, foods selection, and foods-making attitudes. It covers the four areas of food literacy, and shows good practicability and operability.

Some patients with cancer treated with programmed death 1 (PD-1) inhibitors experience immune-related severe adverse events (ir-SAEs), however, predictors are limited. The objective was to identify clinicopathologic features that may be associated with a higher ir-SAE risk. This was a nested case-control study. After screening a total of 832 PD-1 inhibitor-treated patients, we identified 42 ir-SAE cases. According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, ir-SAEs were defined as grade ≥3 toxic effects associated with immunotherapy. A total of 126 controls were matched. The crude and adjusted risks of ir-SAEs were estimated by odds ratio (ORs) and 95% CIs using multivariate logistic regression models. Baseline neutrophil-to-lymphocyte ratio (NLR) [per SD increment-adjusted (aOR): 1.16], lactate dehydrogenase (LDH) ≥245 U/L (aOR: 2.39), and antibiotic exposure (aOR: 4.39) were associated with a higher risk of ir-SAEs. When NLR was categorized in 3 groups, significantly higher risks of ir-SAEs (aOR: 4.95) were found in participants in group 3 (6) than in those in group 1 (3). Furthermore, NLR (per SD increment-adjusted hazard ratio:1.08) were also significantly associated with shorter overall survival (OS). Baseline LDH ≥245 U/L and antibiotic exposure were no significant association with OS. In conclusion, ir-SAEs were associated between baseline NLR, LDH ≥245 U/L and antibiotic exposure. Lower NLR was correlated with longer OS for cancer.

This study aimed to determine the cause behind the outbreak of nosocomial adenoviral conjunctivitis in the Neonatal Intensive Care Unit (NICU) and the impact of infection control measures. The objectives of the present study include investigation of the hospital-borne infection associated with adenoviral conjunctivitis, analysis of the possible risk factors, setting bundle infection control measures, which were adjusted according to the control effect. The present study also aims to observe the effect of different intervention measures on controlling adenoviral conjunctivitis. During the first and second intervention periods, overall 635 and 597 NICU patients were enrolled, respectively. Ophthalmoscopy was conducted among 188 (in the first intervention) and 184 (in the second intervention) patients (P>0.05). The times of ophthalmoscopy the patients received were 417 and 457 (P

Background. To develop an individual’s physical subhealth risk perception scale and evaluate its reliability and validity, so as to provide a measurement tool for individual physical health risk. Methods. A questionnaire on the perception risk of physical subhealth was developed. Using a random sampling method, 785 people in the Anhui provincial physical examination centre were selected as the research participants. Of the questionnaires returned, 770 were valid, giving an effective rate of 98%. Firstly, the Pearson correlation coefficient method was used to study the correlation of 35 items in the initial scale, and then, polychoric factor structure analysis was carried out by using the Pratt D matrix to optimize the item structure. The Cronbach’α coefficient method was used to test the internal consistency reliability, and a structural equation model was used to explore the construct validity of the scale. The discriminant validity of the scale was obtained by factor analysis. A general linear model was used to analyse the relationship between the clinical manifestations of physical subhealth and the level of risk perception, and the convergent validity of the scale was evaluated. Results. All the data of 35 items were significantly correlated at the 0.01 level. The correlation coefficients between a1 and a2, a3 and a4, b1 and b2, b2 and b3, c4 and c5, c5 and c6, c6 and c7, c8 and c9, d1 and d2, d2 and d3, e5 and e6, g1 and g2, g2 and g3, and g2 and g4 were greater than 0.6. The items with correlation coefficients greater than 0.6 were reduced by a Pratt D matrix. The resulting physical subhealth risk perception scale covers five factors with a total of 18 items. The Cronbach’α coefficient of the scale was 0.889, and the Cronbach’α coefficients of the five factors F1-F5 were 0.780, 0.825, 0.801, 0.736, and 0.704, respectively. Structural equation model analysis showed that χ 2 / df = 3.43 , p < 0.001 , RMSEA = 0.08 , GFI = 0.88 , NFI = 0.84 , AGFI = 0.84 , and CFI = 0.88 . Factor analysis showed that factors F1–F5 had significant correlations ( p < 0.01 ), and the correlation coefficients were less than the corresponding square root value of AVE. Based on the subhealth clinical manifestations of the participants, the general linear model was used to explore the convergent validity of the scale, and the results indicated that the scale passed the convergent validity test. Conclusions. We propose a physical subhealth risk perception scale amounting to 18 items, which includes five dimensions: health knowledge (2 items), risk perception (5 items), trust selection (4 items), information channel (4 items), and social groups (3 items). The reliability and validity of the physical subhealth risk perception scale are acceptable. Applying the scale into practice has potential to improve the overall public health level.

Background The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation. Methods A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group. Results The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1–2 lymph node metastasis (sMPN1–2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1–2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1–2 patients (P = 0.872). Conclusion As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients.

Acute kidney injury (AKI) is one of the most common severe complications among hospitalized patients. In the absence of specific drugs to treat AKI, hemodialysis remains the primary clinical treatment for AKI patients. AKI treatment has received significant attention recently due to the excellent drug delivery capabilities of low-dimensional nanomaterials (LDNs) and their unique therapeutic effects. Diverse LDNs have been proposed to treat AKI, with promising results and the potential for future clinical application. This article aims to provide an overview of the pathogenesis of AKI and the recent advances in the treatment of AKI using different types of LDNs. In addition, it is intended to provide theoretical support for the design of LDNs and implications for AKI treatment. Graphical Abstract

Purpose Long-leg-radiography (LLR) is commonly used for the measurement of lower limb alignment. However, limb rotations during radiography may interfere with the alignment measurement. This study examines the effect of limb rotation on the accuracy of measurements based on the mechanical and anatomical axes of the femur and tibia, with variations in knee flexion and coronal deformity. Methods Forty-five lower limbs of 30 patients were scanned with CT. Virtual LLRs simulating five rotational positions (neutral, ± 10$$^{\circ }$$ ∘ , and ± 20$$^{\circ }$$ ∘ internal rotation) were generated from the CT images. Changes in the hip–knee–ankle angle (HKA) and the femorotibial angle (FTA) were measured on each image with respect to neutral values. These changes were related to knee flexion and coronal deformity under both weight- and non-weight-bearing conditions. Results The measurement errors of the HKA and FTA derived from limb rotation were up to 4.84 ± 0.66$$^{\circ }$$ ∘ and 7.35 ± 0.88$$^{\circ }$$ ∘ , respectively, and were correlated with knee flexion (p < 0.001) and severe coronal deformity (p < 0.001). Compared with the non-weight-bearing position, the coronal deformity measured in the weight-bearing condition was 2.62$$^{\circ }$$ ∘ greater, the correlation coefficients between the coronal deformity and the deviation ranges of HKA and FTA were also greater. Conclusions Flexion and severe coronal deformity have a significant influence on the measurement error of lower limb alignment. Errors can be amplified in the weight-bearing condition compared with the non-weight-bearing condition. When using HKA and FTA to represent the mechanical axis and the anatomical axis on LLR, limb rotation impacts the anatomic axis more than the mechanical axis in patients with severe deformities. Considering LLR as the gold standard image modality, attention should be paid to the measurement of knee alignment. Especially for the possible errors derived from weight-bearing long-leg radiographs of patients with severe knee deformities.

Background Cytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients. Methods The clinical data of the patients who underwent lung and/or heart transplantation between January 2015 and October 2020 were retrospectively collected from four transplantation centers in China. Results A total of 308 patients were analyzed. The CMV serostatus was donor positive (D+) recipient negative (R−) in 19 (6.17%) patients, D+/R+ in 233 (75.65%), D−/R+ in 36 (11.69%), and D−/R− in 20 (6.50%). CMV DNAemia was detected in 52.3% of the patients and tissue-invasive CMV disease was diagnosed in 16.2% of the patients. Only 31.8% of the patients adhered to the postdischarge valganciclovir therapy. The D+/R− serostatus (odds ratio [OR]: 18.32; 95% confidence interval [CI]:1.80-188.68), no valganciclovir prophylaxis (OR: 2.64; 95% CI: 1.05–6.64), and higher doses of rabbit anti-human thymocyte globulin (> 2 mg/kg) (OR: 4.25; 95% CI: 1.92–9.42) were risk factors of CMV disease. Conclusion CMV seroprevalence was high in Chinese thoracic organ transplant donors and recipients. The low adherence rate to the postdischarge CMV prophylaxis therapy in Chinese patients is still an unresolved issue.

(1) Background: Carbohydrate combined with dietary fiber (DF) applied as a surrogate marker of overall carbohydrate quality is a more essential determinant of cardiometabolic health. However, to date, no studies have applied this metric to analyze its associations with poor blood pressure control in hypertensive patients. (2) Methods: A cross-sectional design was implemented in one tertiary hospital and one community hospital in China. Using Feihua Nutrition Software to analyze participants’ two-day dietary log, the quantity of carbohydrate and fiber was obtained and the carbohydrate to fiber ratio (CFR) was calculated. The participants were divided into Q1, Q2, Q3, and Q4 groups by quartile method, from low to high according to CFR. The poor systolic and diastolic blood pressure (SBP and DBP) controls were defined as ≥140 mmHg and ≥90 mmHg, respectively. (3) Results: A convenience sample of 459 participants was included and the mean CFR was 29.6. Taking Q1 as reference, after adjusting for covariates, the CFR in Q4 was associated with higher poor SBP-controlled rate (OR, 4.374; 95% CI, 2.236–8.559). Taking Q2 as reference, after adjusting for covariates, the CFRs in Q3 and Q4 were associated with higher poor DBP-controlled rates [(OR = 1.964, 95% CI: 1.016–3.795) and (OR = 4.219, 95% CI: 2.132–8.637), respectively]. The CFR was the stronger protective determinant of SBP and DBP than DF or carbohydrate alone. (4) Conclusions: A higher CFR is a stronger risk factor for blood pressure (BP) control, and low CFR foods or a combination of corresponding food components, should be recommended in the dietary management of hypertensive patients.

An internal fixation composite structure of antibiotic cement plates was created. The aim of this study was to analyse the infection control effect of this structure when applied to treat a bone infection. We retrospectively analysed patients with bone infection admitted to our hospital between January 2013 and June 2019. After debridement, an antibiotic cement plate composite structure was used to fill and stabilize the defects. The treatment effect was evaluated at six months after surgery, and the infection control rate, factors associated with the recurrence of infection, and complications were analysed. If the patients had bone defects, the defect was repaired after infection control, and the infection control rate of all of the patients was re-evaluated at 12 months after surgery. A total of 548 patients were treated with this technique, including 418 men and 130 women. The infection sites included 309 tibias, 207 femurs, 16 radii and ulnae, 13 humeri, and 3 clavicles. After at least 6 months of follow-up, 92 patients (16.79%) had an infection recurrence and needed further treatment. The recurrence rate of the tibia was higher than that of the femur (P = 0.025). Eighty-nine out of 92 patients who relapsed underwent a second debridement with the same method, and the infection control rate after the second debridement was 94.71%. Complications included 8 cases of epidermal necrosis around the incision, 6 cases of internal fixation failure, and 30 cases of lower limb swelling. By the follow-up time of 12 months, another 6 patients had experienced recurrence of infection, and 4 cases were controlled after debridement. Finally, among all 548 cases, 7 patients remained persistently infected, and 6 underwent amputation. The infection control rate was 97.6% at the 1-year follow-up. The clinical efficacy of this new antibiotic cement plate composite structure for internal fixation after debridement of bone infection is stable and reliable.

Yi-Xuan Liao,1,2 Xiao-Hua Wang,3 Yu Bai,1 Fan Lin,1 Min-Xia Li,1 Wen-Jun Mi,1 Wan-Lu Sun,1 Ya-Hong Chen1 1Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Department of Radiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Ya-Hong ChenDepartment of Pulmonary and Critical Care Medicine, Peking University Third Hospital, No. 49, Huayuan bei Road, Haidian District, Beijing, 100191, People’s Republic of ChinaTel +86 139 10232918Email chenyahong@vip.sina.comObjective: To explore the relationship between endogenous hydrogen sulfide (H2S) and high-resolution computed tomography (HRCT) indexes in pulmonary vascular remodeling.Methods: A total of 94 stable chronic obstructive pulmonary disease (COPD) patients were recruited for the study．Plasma H2S levels were measured using fluorescence probe. Fluorescence quantitative polymerase chain reaction was used to measure H2S synthase cystathionine-γ-lyase (CSE) mRNA and cystathionine-β-synthesis enzyme (CBS) mRNA. The main pulmonary artery diameter (mPAD), axial diagonal mPAD, coronal mPAD, sagittal mPAD, right pulmonary artery diameter (RPAD), left pulmonary artery diameter (LPAD), and ascending aortic diameter (AAD) and the percentage of total cross-sectional area of vessels less than 5 mm2 of total lung area (%CSA < 5) on HRCT were measured. Pulmonary arterial systolic pressure (PASP) of echocardiography, blood gas analysis, and routine blood tests were performed. Correlation analysis and multivariate linear regression were performed using SPSS 22.0.Results: H2S was negatively correlated with mPAD, axial diagonal mPAD, and sagittal mPAD (r = − 0.25∼− 0.32) and positively correlated with PaO2 (r = 0.35). Relative expression of CSE mRNA was positively correlated with PASP, coronal mPAD, sagittal mPAD, white blood cell count (WBC), and neutrophil count (N) (r = 0.30∼ 0.44). The relative expression of CBS mRNA was positively correlated with PASP, WBC, and N (r = 0.34∼ 0.41). In separate models predicting pulmonary vascular indexes, a 1μmol/L increase in H2S predicted lower pulmonary artery diameter (for axial diagonal mPAD, 0.76mm lower; for mPAD/AAD, 0.68mm lower). All P values were less than 0.05.Conclusion: Endogenous H2S may be involved in pulmonary vascular remodeling, providing a new method for the diagnosis and treatment of COPD. The generation of H2S may be inhibited by hypoxia, inflammation, etc.Keywords: chronic obstructive pulmonary disease, vascular remodeling, pulmonary hypertension, multidetector computed tomography

Oligodendrocyte precursor cells (OPCs) can differentiate into myelinating oligodendrocytes during embryonic development, thereby representing an important potential source for myelin repair or regeneration. To the best of our knowledge, there are very few OPCs from human sources (human-derived OPCs [hOPCs]). In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory, transplanted into the lateral ventricles of young animals. Several acute and chronic toxicity experiments were conducted in which different doses of hOPCs were transplanted into the lateral ventricles of Sprague-Dawley rats of different ages. The toxicity, biodistribution, and tumor formation ability of the injected hOPCs were examined by evaluating the rats' vital signs, developmental indicators, neural reflexes, as well as by hematology, immunology, and pathology. In addition, the hOPCs were transplanted into the corpus callosum of the shiverer mouse to verify cell myelination efficacy. Overall, our results show that transplanted hOPCs into young mice are nontoxic to their organ function or immune system. The transplanted cells engrafted in the brain and did not appear in other organs, nor did they cause tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs were able to form myelin in the corpus callosum, alleviate the trembling phenotype of shiverer mice, and promote normal development. The transplantation of hOPCs is safe; they can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.

The thyroid nodule segmentation of ultrasound images is a critical step for the early diagnosis of thyroid cancers in clinics. Due to the weak edge of ultrasound images and the complexity of thyroid tissue structure, it is still challenging to accurately segment the delicate contour of thyroid nodules. A local and context-attention adaptive network (LCA-Net) for thyroid nodule segmentation is proposed to address these shortcomings, which leverages both local feature information from convolution neural networks and global context information from transformers. Firstly, since most existing thyroid nodule segmentation models are skilled at local detail features and lose some context information, we propose a transformers-based context-attention module to capture more global associative information for the network and perceive the edge information of the nodule contour. Secondly, a backbone module with 7×1, 1×7 convolutions and the activation function Mish is designed, which enlarges the receptive field and extracts more feature details. Furthermore, a nodule adaptive convolution (NAC) module is introduced to adaptively deal with thyroid nodules of different sizes and positions, thereby improving the generalization performance of the model. Simultaneously, an optimized loss function is proposed to solve the pixels class imbalance problem in segmentation. The proposed LCA-Net, validated on the public TN-SCUI2020 and TN3K datasets, achieves Dice scores of 90.26% and 82.08% and PA scores of 98.87% and 96.97%, respectively, which outperforms other state-of-the-art thyroid nodule segmentation models. This paper demonstrates the superiority of the proposed LCA-Net for thyroid nodule segmentation, which possesses strong generalization performance and promising segmentation accuracy. Consequently, the proposed model has wide application prospects for thyroid nodule diagnosis in clinics.

To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing, multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.A heterozygous deletion variant, c.4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. The variant was classified as pathogenic (PVS1 +PM2+PM6) according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father's TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA.The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients.

Background Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth. Objective To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells. Methods Using cell sorting technology, we obtained NG2+/−, A2B5+/− cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice. Results The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/−, A2B5+/− cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5− > NG2− > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2− > A2B5− > A2B5+ > NG2+. Conclusion In summary, NG2+ and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.

Background: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. Objectives: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. Methods: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving Results: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. Conclusion: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

The main aim of the study is to analyze the impact of Artemin on survival and prognosis in endometrial cancer (EC) patients by bioinformatics methods. As a member of the glial-derived neurotrophic factor (GDNF) family, Artemin is not only important in the repair process of nerve damage, but also involved in tumorigenesis and metastasis. In this study, we demonstrated that Artemin mRNA was overexpressed in EC tissues. Artemin expression was closely related to the FIGO stage, pathologic differentiation, deep myometrial infiltration, lymphatic metastasis, and survival status. Univariate and multivariate Cox regression analysis showed that ectopic overexpression of Artemin predicted poor survival prognosis. Artemin expression could be used as an independent risk factor for the prognosis of EC patients. The proliferation of EC cells was significantly downregulated by silencing of Artemin. Artemin promotes tumor progression by regulating the proliferation of EC cells, thereby affecting the prognosis of EC patients.

Heterozygous loss-of-function mutation of the calcium sensing-receptor (CaSR), causes familial hypocalciuric hypercalcemia type 1 (FHH1), a typically benign condition characterized by mild hypercalcemia. In contrast, homozygous mutation of this dimer-forming G-protein coupled receptor manifests as the lethal neonatal severe hyperparathyroidism (NSHPT). To investigate the mechanisms by which CaSR mutations lead to these distinct disease states, we engineered wild-type (WT) and an exon 5-deficient disease-causing mutation, and transfected expression constructs into human embryonic kidney (HEK) cells. WT protein was mainly membrane-expressed whereas the mutant CaSR protein (mCaSR) was confined to the cytoplasm. Co-expression of WT CaSR directed mCaSR to the cell membrane. In assays of CaSR function, increases in extracellular [Ca2+] ([Ca2+]o) increased intracellular [Ca2+] ([Ca2+]i) in cells expressing WT CaSR while the response was reduced in cells co-expressing mutant and WT receptor. Untransfected cells or those expressing mCaSR alone, showed minimal, equivalent responses to increased [Ca2+]o. Immunoprecipitation experiments confirmed an association between mutant and wild-type CaSR. The affinity of the WT CaSR for calcium was three times greater than that of the heterodimer. The maximal functional response to [Ca]o was dependent on localization of CaSR to the membrane level and independent of homo- or heterodimerizations. In summary, these results suggest that heterodimerization of WT and mCaSR receptors, rescues the trafficking defect of the mutant receptors and also reduces the affinity of the WT-mutant heterodimer for [Ca]o. In contrast, the homozygous mutants do not produce functional receptors on cell membrane. These data indicate how substantial differences between signaling of hetero- and homodimeric mutants may lead to profound differences in the severity of disease in heterozygous and homozygous carriers of these mutations.

Depression and anxiety often co-occur in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). This study was conducted to examine the predictive value of depression, anxiety, and their combination on the prognosis of Chinese PCI patients. A multicenter prospective study was undertaken with a sample of 309 primary PCI patients. The Hospital Anxiety and Depression Scale (HADS) was completed at baseline to assess anxiety and depression symptoms. Major adverse cardiovascular events (MACEs) were recorded for 12 months after PCI . Days from baseline to the first MACE was the outcome variable. MACEs occurred in 26 (8.4%) patients. After adjustments for socio-demographic and clinical characteristics, a Cox proportional hazards regression model revealed that depression (HR = 2.70, 95% confidence interval [CI] 1.22–5.95; p =.014) and anxiety (HR = 2.56, 95% CI 1.18–5.54; p =.017) symptoms were independent predictors of MACEs. A sub-analysis showed that the cumulative event-free survival curves did not differ among depressed and anxious patients and depressed but non-anxious patients (Log Rank p =.52). In conclusion, depression is associated with an increased risk for MACEs post-PCI, independent of anxiety. Although anxiety is associated with MACEs, it has no additional predictive value when co-occurring with depression.

Background At present, China has more than 11 million patients with stable coronary heart disease and this is becoming a major public health problem. The pathological changes of coronary heart disease can lead to dysfunction of the cardiac autonomic nervous system, which increases the risk of complications such as malignant arrhythmia (ventricular flutter, ventricular fibrillation, etc.), heart rate, systolic blood pressure, and rate-pressure product (RPP), which is highly correlated with myocardial oxygen consumption and indirectly reflects myocardial blood supply and oxygen consumption. Although the guidelines recommend that such patients take drugs to reduce heart rate and myocardial oxygen consumption, the clinical control of heart rate is still not ideal. Thus, in this trial, we will use voluntary breathing exercises as the strategy of exercise rehabilitation for patients with stable coronary artery disease (SCAD), in order to increase the vagus nerve activity and/or reduce the sympathetic nervous activity, help maintain or rebuild the balance of plant nerve system, improve the time-domain index of heart rate variability, reduce the burden on the heart, and relieve patients’ anxiety and other negative emotions. Methods This is a 6-month single-blind, randomized controlled clinical trial that will be conducted in the First Affiliated Hospital of Soochow University. A total of 140 patients who fill out the Informed Consent Form are registered and randomized 1:1 into the Voluntary Breathing Exercises (VBE)-based clinical trial monitoring group (n = 70) or the Routine follow-up group (n = 70). The VBE-based clinical trial monitoring group is given VBE training on the basis of conventional treatment and health education, while the control group received conventional health education and follow-up. The primary outcomes will be measured heart rate variability and RPP. Secondary outcomes will include changes in Self-rating Anxiety Scale, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, weight, and body mass index. Discussion This trial will carry out scientific respiratory exercise for patients with SCAD, which belongs to the category of active secondary prevention for patients, and changes from remedial to pre-protective. VBE is easy to operate and is not limited by time and place. It is important and meaningful to carry out VBE for patients with SCAD. This study will provide considerable evidence for further large-scale trials and alternative strategies for the rehabilitation nursing of patients with SCAD. Trial registration Chinese Clinical Trials Registry, 1900024043. Registered on 23 June 2019.

ObjectivesTo investigate the potential of deep learning in assessing pneumoconiosis depicted on digital chest radiographs and to compare its performance with certified radiologists.MethodsWe retrospectively collected a dataset consisting of 1881 chest X-ray images in the form of digital radiography. These images were acquired in a screening setting on subjects who had a history of working in an environment that exposed them to harmful dust. Among these subjects, 923 were diagnosed with pneumoconiosis, and 958 were normal. To identify the subjects with pneumoconiosis, we applied a classical deep convolutional neural network (CNN) called Inception-V3 to these image sets and validated the classification performance of the trained models using the area under the receiver operating characteristic curve (AUC). In addition, we asked two certified radiologists to independently interpret the images in the testing dataset and compared their performance with the computerised scheme.ResultsThe Inception-V3 CNN architecture, which was trained on the combination of the three image sets, achieved an AUC of 0.878 (95% CI 0.811 to 0.946). The performance of the two radiologists in terms of AUC was 0.668 (95% CI 0.555 to 0.782) and 0.772 (95% CI 0.677 to 0.866), respectively. The agreement between the two readers was moderate (kappa: 0.423, pConclusionOur experimental results demonstrated that the deep leaning solution could achieve a relatively better performance in classification as compared with other models and the certified radiologists, suggesting the feasibility of deep learning techniques in screening pneumoconiosis.

Dynamin-related protein-1 (Drp1) has been found to be associated with cell death. The role of Drp1 in A549 cells death has not been explored. In this study, adenovirus-mediated Drp1 overexpression was used to investigate the influence of Drp1 on A549 cell viability with a focus on F-actin and Bax. Cell viability, protein expression, oxygen consumption, energy metabolism, and growth rate were measured through ELISA, qPCR, western blots and pathway analysis. Our results indicated that Drp1 overexpression promoted A549 cell death through apoptosis. Mechanistically, cytoskeletal F-actin was impaired and Bax expression was elevated in response to Drp1 overexpression. Besides, energy metabolism was reduced and oxygen consumption was interrupted. Therefore, our results demonstrated that A549 cell viability, apoptosis and growth were regulated by the Drp1/F-actin/Bax signaling pathways. These data explain a new role played by Drp1 in regulating cell viability and also provide a potential target to affect the progression of lung cancer through induction of cell death.

Background Our aim was to investigate the clinical efficacy and complications of antibiotic treatment regimens for patients with bone infection. Methods We retrospectively analysed patients with bone infection admitted to our hospital between March 2013 and October 2018. After surgical debridement was performed, the patients were divided into three groups: IV group (intravenous antibiotics for 2 weeks); oral group (intravenous antibiotics for 2 weeks followed by oral antibiotics for 4 weeks); and rifampicin group (intravenous antibiotics for 2 weeks followed by oral antibiotics plus rifampicin for 4 weeks). The infection control rate and complications were compared among the three groups. Results A total of 902 patients were enrolled. The infection sites included 509 tibias, 228 femurs, 32 humeri, 23 radii and ulnae, 40 calcanei, and 47 miscellaneous sites, as well as 23 multiple-site infections. After at least 6 months of follow-up, 148 (16.4%) patients had an infection recurrence. The recurrence rate of the IV group was 17.9%, which was not significantly higher than the recurrence rates of the oral group (10.1%) and rifampicin group (10.5%), P = 0.051. The incidence of abnormal alanine aminotransferase (ALT) levels in the IV group was 15.1%, which was lower than that in the oral group (18.0%) and rifampicin group (27.4%), P = 0.026. The rates of proteinuria in the three groups were 3.2, 4.5, and 9.3%, respectively, P = 0.020. Conclusions After debridement of bone infection, short-term antibiotic treatment regimens might offer similar rates of infection eradication while avoiding the risk of renal and hepatic damage associated with prolonged antibiotic use. The level of clinical relevance Stage III.

This study aims to seek affordable solutions to help bus drivers reach their health goals and improve work performance. Guided by Herzberg's motivation theory and self-determination theory, the study investigates ways of reducing the psychological risks bus drivers face by conducting an experiment among them in Shenzhen, China. During the experiment, a serving of fresh fruit (e.g., an apple or a banana) was added to their lunch for 3 weeks. The enhanced lunch helped improve work performance and well-being. Specifically, eating an extra apple or banana was found to reduce depression, and improve self-efficacy and traffic safety. The results indicate that bus drivers could be motivated to work harder as a response to small attention paid to them. This research contributes to a better understanding of food impact on work performance and well-being. It also makes a theoretical contribution to the debate on how hygiene factors may alter job performance.

Introduction Our aim was to observe the efficacy of the induced membrane technique in the treatment of extremity osteomyelitis and to analyse the causes of infection recurrence and its risk factors. Methods We retrospectively analysed 424 cases of extremity osteomyelitis treated with the induced membrane technique in our department between May 2013 and June 2017. Infection recurrence time, recurrence sites and other relevant information were collected, summarized, and analysed. Results A total of 424 patients were considered as “cured” of osteomyelitis after the first stage and the induced membrane technique was performed to rebuild the bone defects. After a mean follow-up of 31.6 (16–63) months, 52 patients had recurrence of infection, including 42 tibias and 10 femurs. The recurrence rate was 12.26%. Symptoms were relieved in 16 patients after intravenous antibiotic treatment. In the remaining 36 cases (8.49%), the infection was uncontrolled by intravenous antibiotics and surgical debridement was performed. The recurrence rate of infection of the tibia (16.22%) was higher than that of the femur (8.70%). The recurrence rate of post-traumatic osteomyelitis (14.66%) was significantly higher than that of hematogenous osteomyelitis (2.41%). Patients in whom Pseudomonas aeruginosa was isolated at the first stage had a recurrence rate of 28% (7/25), which was higher than that with the other isolated bacteria. Logistic regression analysis showed that repeated operations (≥3), post-traumatic osteomyelitis, and internal fixation at the first stage were risk factors for recurrence of infection, with odds ratios (ORs) of 2.30, 5.53 and 5.28 respectively. Conclusions The induced membrane technique is an effective method in the treatment of extremity osteomyelitis, although infection recurs in some cases. Repeated operations, post-traumatic osteomyelitis, and internal fixation at the first stage were risk factors for recurrence of infection. P. aeruginosa isolated at the first stage, tibia osteomyelitis, the presence of sinus, or flaps may also be associated with recurrence of infection.

BackgroundThe induced membrane technique has achieved good clinical results in the treatment of infected bone defects, and external fixation is the main method, but it causes inconvenience and complications in patients. In this study, our objective was to investigate the outcomes of using an antibiotic cement-coated locking plate as a temporary internal fixation in the first stage of the surgical induced membrane technique for treating extremities with infected bone defects.MethodsWe retrospectively analysed patients with lower extremity infected bone defects in our department between January 2013 and December 2017. All patients were treated with the induced membrane technique. In the first stage, the defects were stabilized with an antibiotic cement-coated locking plate as a temporary fixation after debridement, and polymethyl methacrylate cement was implanted to induce the formation of a membrane. In the second stage, bone grafting rebuilt the bone defects after infection control, and the temporary fixation was changed to a stronger fixation.ResultsA total of 183 patients were enrolled, with an average follow-up duration of 32.0 (12–66) months. There were 154 males and 29 females with an average age of 42.8 (10–68) years. The infection sites included 81 femurs, 100 tibias and 2 fibulas. After the first stage of treatment (infection control), 16 (8.7%) patients had recurrence of infection. In terms of the incidence of complications, 4 patients had poor wound healing, 2 patients had fixation failure and 1 patient had femoral fracture due to a fall. After the second stage of treatment (bone reconstruction), there were 24 (13.1%) recurrences of infection, with a mean time of 9.9 months (range 0.5 to 36). Among them, 18 patients underwent bone grafting after re-debridement, 6 received permanent placement of antibiotic bone cement after debridement and 2 patients refused further treatment and chose amputation. Bone healing was achieved in 175 (95.9%) patients at the last follow-up, and the average time to bone union was 5.4 (4–12) months.ConclusionsAntibiotic cement-coated locking plates have good clinical effects in the control of bone infection, but attention must be paid to the possible difficulty of skin coverage when applied in calves.

Background It has been reported that oral anticoagulation (OAC) is underused among Chinese patients with non-valvular atrial fibrillation (NVAF). Non-vitamin K antagonist oral anticoagulants (NOAC) have been recommended by recent guidelines and have been covered since 2017 by the Chinese medical insurance; thus, the overall situation of anticoagulant therapy may change. The aim of this study was to explore the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province. Methods This was a multi-center, cross-sectional study that was conducted in seven hospitals from January to September in 2017. The demographic characteristics and medical history of the patients were collected by questionnaire and from the medical records. Multivariate logistic regression was used to identify factors associated with anticoagulant therapy. Results A total of 593 patients were included in the analysis. A total of 35.6% of the participants received OAC (11.1% NOAC and 24.5% warfarin). Of those patients with a high risk of stroke, 11.1% were on NOAC, 24.8% on warfarin, 30.6% on aspirin, and 33.6% were not on medication. Self-paying, duration of AF ≥5 years were negatively associated with anticoagulant therapy in all patients (OR 1.724, 95% CI 1.086~2.794; OR 1.471, 95% CI 1.006~2.149, respectively), whereas, permanent AF was positively associated with anticoagulant therapy (OR 0.424, 95% CI 0.215~0.839). Among patients with high risk of stroke, self-paying and increasing age were negatively associated with anticoagulant therapy (OR 2.305, 95% CI 1.186~4.478; OR 1.087, 95% CI 1.041~1.135, respectively). Conclusions Anticoagulant therapy is positively associated with permanent AF and negatively associated with self-paying, duration of AF > 5 years. Furthermore, the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province does not appear optimistic. Therefore, further studies should focus on how to improve the rate of OAC use among NVAF patients. In addition, policy makers should pay attention to the economic situation of the patients with NVAF using NOAC. Trial registration 2,017,029. Registered 20 March 2017 (retrospectively registered).

Although a compromised epidermal permeability barrier can contribute to the development of contact dermatitis, whether subjects with hand eczema display abnormalities in baseline epidermal permeability barrier function in their uninvolved skin remains unknown. The aim of the present study was to assess epidermal permeability barrier function in subjects with and without hand eczema in clothing manufacturers. Upon approval by the institutional review board, volunteers were recruited from clothing manufacturers in Guangzhou City, China. An 11-item questionnaire was used to collect general data from the volunteers. The diagnoses of self-proclaimed hand eczema were further confirmed by a dermatologist. Epidermal biophysical properties, including transepidermal water loss (TEWL) rates, stratum corneum hydration and skin surface pH were measured on the flexural surface of the left forearm in all volunteers. Epidermal biophysical properties were compared among cohorts of subjects with active hand eczema, a prior history of hand eczema and without any history of hand eczema. A total of 650 questionnaires were collected from 462 females and 188 males, with a mean age of 36.7 ± 0.46 years (range 16–69 years; 95% CI 35.8–37.59). Thirty-five subjects (5.4%) currently had hand eczema, while 28 subjects (4.3%) reported a prior history of hand eczema that was inactive currently. The prevalence of hand eczema did not differ significantly between genders. Neither a prior personal nor a family history of allergies was associated with the prevalence of hand eczema, but certain occupations and frequent contact with disinfectants were independently associated with the prevalence of hand eczema. In the overall cohort, males displayed higher TEWL rates and stratum corneum hydration levels than did females. Both skin surface pH and TEWL rates differed significantly among normal controls and subjects with active hand eczema or a prior history of hand eczema (p < 0.05). In conclusion, the uninvolved skin site of subjects with hand eczema exhibits abnormalities in epidermal perme­ability barrier, supporting a pathogenic role of epidermal dysfunction in hand eczema. Whether subjects with hand eczema in other occupations also display altered epidermal function on uninvolved skin remains to be explored.

Background: Patients who are critically ill with COVID-19 could have impaired nutrient absorption due to disruption of the normal intestinal mucosa. They are often in a state of high inflammation, increased stress and catabolism as well as a significant increase in energy and protein requirements. Therefore, timely enteral nutrition support and the provision of optimal nutrients are essential in preventing malnutrition in these patients. Aim: This review aims to evaluate the effects of enteral nutrition in critically ill patients with COVID-19. Method: This systematic review and meta-analysis was conducted based on the preferred reporting items for systematic review and meta-Analysis framework and PICO. Searches were conducted in databases, including EMBASE, Health Research databases and Google Scholar. Searches were conducted from database inception until 3 February 2022. The reference lists of articles were also searched for relevant articles. Results: Seven articles were included in the systematic review, and four articles were included in the meta-analysis. Two distinct areas were identified from the results of the systematic review and meta-analysis: the impact of enteral nutrition and gastrointestinal intolerance associated with enteral nutrition. The impact of enteral nutrition was further sub-divided into early enteral nutrition versus delayed enteral nutrition and enteral nutrition versus parenteral nutrition. The results of the meta-analysis of the effects of enteral nutrition in critically ill patients with COVID-19 showed that, overall, enteral nutrition was effective in significantly reducing the risk of mortality in these patients compared with the control with a risk ratio of 0.89 (95% CI, 0.79, 0.99, p = 0.04). Following sub-group analysis, the early enteral nutrition group also showed a significant reduction in the risk of mortality with a risk ratio of 0.89 (95% CI, 0.79, 1.00, p = 0.05). The Relative Risk Reduction (RRR) of mortality in patients with COVID-19 by early enteral nutrition was 11%. There was a significant reduction in the Sequential Organ Failure Assessment (SOFA) score in the early enteral nutrition group compared with the delayed enteral nutrition group. There was no significant difference between enteral nutrition and parenteral nutrition in relation to mortality (RR = 0.87; 95% CI, 0.59, 1.28, p = 0.48). Concerning the length of hospital stay, length of ICU stay and days on mechanical ventilation, while there were reductions in the number of days in the enteral nutrition group compared to the control (delayed enteral nutrition or parenteral nutrition), the differences were not significant (p > 0.05). Conclusion: The results showed that early enteral nutrition significantly (p < 0.05) reduced the risk of mortality among critically ill patients with COVID-19. However, early enteral nutrition or enteral nutrition did not significantly (p > 0.05) reduce the length of hospital stay, length of ICU stay and days on mechanical ventilation compared to delayed enteral nutrition or parenteral nutrition. More studies are needed to examine the effect of early enteral nutrition in patients with COVID-19.

Background: Epidermal function is associated with diabetes and renal disease. Whether obesity can reflect the changes in epidermal function is not clear yet. Objective: We assessed here the correlation of epidermal functions with body mass index (BMI) in a large Chinese cohort. Methods and Subjects: A total of 1,405 Chinese aged 21–98 years old were enrolled in this study. Epidermal functions, including transepidermal water loss (TEWL), stratum corneum hydration, and skin surface pH, were measured on the flexor forearm and the shin. Subjects’ height and body weight were also measured. Results: Age positively correlated with both TEWL and skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin of females. Similarly, age positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of males. In females, BMI positively correlated with skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin. However, BMI correlated neither with skin surface pH on both the forearm and the shin nor with stratum corneum hydration on the shin of males. Conclusion: These results demonstrate that correlations of BMI with age and epidermal functions vary with gender.

Objective. To investigate the effect of Danggui Beimu Kushen Pills on renal cell carcinoma patients undergoing laparoscopic radical resection and their effects on renal function and immune function. Methods. 106 patients with renal cell carcinoma who underwent retroperitoneal laparoscopic radical surgery in our hospital from March 2015 to February 2017 were selected, and they were divided into control group and treatment group. The control group was treated with interferon and the treatment group was treated with Danggui Beimu Kushen pills on the basis of the control group. The clinical efficacy, incidence of adverse reactions, survival rate, and the relationship with clinical stages were detected in the two groups. The renal function index levels, immune function index levels, and quality of life levels were measured in the two groups after treatment. Results. Compared with the control group, the total clinical effective rate was increased, the abnormal renal function, abnormal liver function, and platelet decline were decreased, and the survival rate was significantly elevated in the treatment group. The patients with clinical stage I∼II’ survival rate was increased, relative to patients with clinical stage III. After treatment, the levels of β2-MG, SCr, BUN, and CD8+ in the two groups were decreased, while the levels of CD3+, CD4+, and CD4+/CD8+ were increased. Moreover, the scores of physical function, social function, emotional function, role function, cognitive function, and total score of the two groups were improved. Compared with the control group, the treatment group changes were more obvious. Conclusion. The Danggui Beimu Kushen Pill has significant clinical effects on the treatment of renal cancer, which can improve the clinical symptoms, enhance the immune function, restore the health renal function, improve the quality of life, prolong the survival time of patients, reduce the incidence of adverse reactions, and provide high safety.

Performance appraisal of well-facilitated farmland projects has positive significance for promoting the development of modern agriculture in rural areas and carrying out rural revitalization. Based on the AHP-object metatopological model, a well-facilitated farmland project performance appraisal system is proposed to analyze the county performance of well-facilitated farmland construction. In this study, Fangcheng County, Henan Province, is selected as the research sample area and evaluated by applying the established index system. The results show that the overall performance grade of the well-facilitated farmland project in Fangcheng County is at an excellent level with both excellent and good rates reaching more than 90%, the output is slightly lower with excellent and good rates reaching 73%, and the benefit is the worst with excellent and good rates at 53%. These indicate that the construction effect of the well-facilitated farmland project in Fangcheng County is at a good level, but the benefits are not as satisfactory as expected. In the overall appraisal, excellent accounts for 48.1%, good accounts for 26.9%, average accounts for 16.3%, and poor accounts for 8.7%. Fangcheng County has achieved a good performance level in the construction of a well-facilitated farmland project in 2019, with almost full completion of project objectives and compliance with implementation standards. This study provides a system of county performance appraisal methods for well-facilitated farmland as well as its practical application in county-level units.

Severe hypertriglyceridemia (sHTG) is an independent risk factor of atherosclerotic heart disease (ASHD) and acute pancreatitis (AP). The aim was to evaluate the efficacy and safety of DFPP in sHTG patients (TG1,000 mg/dL).This was a prospective single-center study in which patients with severe symptomatic drug and diet refractory HTG were recruited. Peripheral venous access of upper extremities was used for DFPP. Blood flow rate was 100 - 120 mL/min and plasma separation rate was 800 - 1,000 mL/h. Plasma volume to treat in each case was calculated with the Kaplan formula. Anticoagulation was achieved by low molecular weight heparin. Treatment goal was triglyceride level decreased to normal (1.7 mmol/L). Epidemiological data, lipid, hematological parameters as well as side effects were evaluated before and after DFPP.Seven patients (6 males and 1 female) were consecutively enrolled to this trial. There was diabetes mellitus type 2 in four patients and obesity-associated nephropathy in one patient. The mean age was 42.5 years. The average TG level before plasmapheresis was 17.41 mmol/L (range 10.93 - 26.33 mmol/L). After one session, the levels of triglyceride, total cholesterol, LDL-c, HDL-c decreased significantly by 58.3%, 43.2%, 41.9%, 20.7%, respectively. The mean number of treatment sessions was 1.5 (range 1 - 3). DFPP was well-tolerated. Except for transient decrease of albumin, globulin and fibrinogen, liver and renal functions, hematological parameters did not change significantly.According to our own experience, DFPP may be used safely and effectively in sHTG patients at risk of acute coronary events and AP. However, further randomized controlled trials are necessary to explore the long-term effect.

Ferroptosis is caused by lipid peroxidation and iron accumulation and can cause cell death. Abnormally expressed iron transporters are involved in ferroptosis in a variety of diseases. ZRT/IRT-like protein 14 (ZIP14) is a transport protein that can mediate cellular uptake of iron, zinc, and manganese. Herein, we have tested the hypothesis that the divalent metal transporter ZIP14 is involved in the initiation of ferroptosis in diabetic nephropathy (DN). DN was induced in 8-week-old male rats by streptozotocin before analysis of the degree of renal tubular injury. In addition, an in vitro model of DN in human kidney proximal tubular cell line was used. We showed that ZIP14 was up-regulated and ferrous iron (Fe2+) levels increased both in vivo and in vitro. Expression of glutathione peroxidase 4 and the level of glutathione were reduced, whereas that of malondialdehyde (MDA) increased. Ferrostatin-1 (Fer-1) treatment reduced the expression of ZIP14 and the levels of Fe2+ and MDA, which is consistent with ferroptosis. Fer-1 improved kidney function in DN rats. This was characterized by urine levels of protein-to-creatinine ratio, α1-microglobulin, and N-acetyl-β-D-glucosaminidase. Our study demonstrates a novel role for ZIP14 in diabetic kidney injury mediated by ferroptosis, and suggests a potential new therapeutic approach for the treatment of diabetic nephropathy.

BackgroundVitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency.MethodsWe studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function.ResultsWe demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver.ConclusionsBecause FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

ObjectivesWe examined the relationship between statin use during hospitalisation and mortality in patients with intracerebral haemorrhage (ICH).DesignRetrospective propensity-matched cohort study.SettingPatients with ICH (≥18 years old) admitted to Beth Israel Deaconess Medical Center (Boston, Massachusetts, USA) from 2001 to 2012 registered in the Medical Information Mart for Intensive Care III database.Participants1043 patients with ICH (≥18 years) were evaluated for the relationship between statin use during hospitalisation and mortality.InterventionsStatin use.Primary and secondary outcome measuresThe primary outcome was 90-day mortality. We used multivariable Cox regression analyses to calculate the adjusted HR with 95% CI and used propensity score analysis and an inverse probability weighting (IPW) model to ensure the robustness of our findings.ResultsWe included 1043 patients with ICH (362 and 681 were statins and non-statin users, respectively) between 2001 and 2012. The overall 90-day mortality was 29.8% (311/1043); it was 33.3% (227/681) and 23.2% (84/362) for non-statin and statin users, respectively. After adjusted for potential confounders, we found that statin use was associated with 29% lower of 90-day mortality (HR=0.71, 95% CI 0.52 to 0.97, pConclusionStatin use during hospitalisation may be associated with reduced risk-adjusted mortality in patients with ICH. Further randomised controlled trials are needed to clarify this association.

Elevated expressions of transforming growth factor β1 (TGF-β1) have been implicated in the pathogenesis of liver fibrosis, thus attenuating the excessive TGF-β1's activity by TGF-β1-binding peptide is an ideal strategy for the treatment of liver fibrosis. However, the application of small peptide as a pharmaceutical agent is obstacle due to difficult preparation and non-selective delivery. The I-plus sequences of circumsporozoite protein (CSP-I) possesses high affinity for heparan sulfate proteoglycans, which are primarily located on liver tissues. TGF-β1-binding peptide P15 holds specific ability of binding to TGF-β1. In this study, we describe an approach to efficiently preparing liver-targeting peptide P15-CSP-I, which is conjugation of the sequences of P15 to the N-terminus of CSP-I, from the cleavage of biological macromolecule SUMO-tagged P15-CSP-I. In vitro and ex vivo binding assay showed that P15-CSP-I specifically targeted to the hepatocytes and liver tissues. Moreover, P15-CSP-I inhibited cell proliferation, migration and invasion, and decreased fibrosis-related proteins expression in TGF-β1-activated HSCs in vitro. Furthermore, P15-CSP-I ameliorated liver morphology and decreased the fibrosis responses in vivo. Taken together, P15-CSP-I may be a potential candidate for targeting therapy on liver fibrosis due to its high efficient preparation, specific liver-targeting potential and improved anti-liver fibrotic activity.

Acute kidney injury (AKI), a major health burden, lacks effective therapy. Anti-inflammatory actions of a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13) may provide a new treatment option for AKI. Along with inflammation, oxidative stress is critical for AKI development, yet the impact of ADAMTS13 on oxidative stress in AKI remains to be fully elucidated.We assess recombinant human ADAMTS13 (rhADAMTS13) actions on oxidative stress in a murine ischaemia/reperfusion (IR) model. Antioxidant stress-enzyme activities, renal morphology, kidney function markers and vascular function of isolated afferent arterioles are quantified.rhADAMTS13 provided after IR, reduces blood urea nitrogen (BUN) by 33% and serum creatinine (Scr) by 73% in 24 hours post-IR. rhADAMTS13 reduces BUN (40.03 ± 20.34 mmol/L vs 72.35 ± 18.74 mmol/L, P .01), Scr (75.67 ± 51.19 μmol/L vs 176.17 ± 55.38 μmol/L, P .01) and proteinuria by 41% in 48 hours post-IR as well. Moreover, rhADAMTS13 administration decreases malondialdehyde (MDA) and increases the activity of antioxidant stress enzymes, and attenuates reactive oxygen species production. rhADAMTS13 also upregulates nuclear factor-erythroid-2-related factor 2/haem oxygenase-1, enhances antioxidant enzymes activity and alleviates endothelial dysfunction. Finally, treatment with rhADAMTS13 mitigates severe functional and morphological injury present in IR mice. Extracellular signal-regulated kinase (ERK) phosphorylation is limited by rhADAMTS13 and PPARγ expression is partly restored in ischaemic kidneys. Co-administration of von Willebrand factor (VWF) impairs rhADAMTS13's antioxidant capacity and its protective role in IR.rhADAMTS13 alleviates renal IR injury through antioxidant effects by cleaving VWF.

Objective To compare the surgical effects and long-term efficacy of hand-assisted laparoscopic surgery (HALS) and open surgery (OS) in radical gastrectomy for advanced distal gastric cancer. Methods One hundred twenty-four patients who were admitted to the Department of Gastrointestinal Surgery of the West War Zone General Hospital from May 2008 to April 2012 were randomly divided into a HALS group (n = 62) and an OS group (n = 62). After surgery, 113 patients were followed up for 5 and 8 years, and 11 patients were lost to follow-up. The 5- and 8-year overall survival and disease-free survival rates of the two groups were compared and analyzed. Results The 5- and 8-year overall survival rates were 31.90% and 18.40% in the HALS group and 32.50% and 18.60% in the OS group, respectively. The 5- and 8-year disease-free survival rates were 21.50% and 13.00% in the HALS group and 21.90% and 13.10% in the OS group, respectively. No significant differences were found. Conclusion Hand-assisted laparoscopic radical gastrectomy for advanced distal gastric cancer has the advantages of less severe trauma, less intraoperative blood loss, more rapid postoperative recovery, and equivalent long-term efficacy compared with OS.

The use of nutritional interventions for managing diabetes is one of the effective strategies aimed at reducing the global prevalence of the condition, which is on the rise. Almonds are the most consumed tree nut and they are known to be rich sources of protein, monounsaturated fatty acids, essential minerals, and dietary fibre. Therefore, the aim of this review was to evaluate the effects of almonds on gut microbiota, glycometabolism, and inflammatory parameters in patients with type 2 diabetes. Methods: This systematic review and meta-analysis was carried out according to the preferred reporting items for systematic review and meta-analysis (PRISMA). EBSCOhost, which encompasses the Health Sciences Research Databases; Google Scholar; EMBASE; and the reference lists of articles were searched based on population, intervention, control, outcome, and study (PICOS) framework. Searches were carried out from database inception until 1 August 2021 based on medical subject headings (MesH) and synonyms. The meta-analysis was carried out with the Review Manager (RevMan) 5.3 software. Results: Nine randomised studies were included in the systematic review and eight were used for the meta-analysis. The results would suggest that almond-based diets have significant effects in promoting the growth of short-chain fatty acid (SCFA)-producing gut microbiota. Furthermore, the meta-analysis showed that almond-based diets were effective in significantly lowering (p < 0.05) glycated haemoglobin (HbA1c) levels and body mass index (BMI) in patients with type 2 diabetes. However, it was also found that the effects of almonds were not significant (p > 0.05) in relation to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and Tumour necrosis factor α, TNF-α), glucagon-like peptide-1 (GLP-1), homeostatic model assessment of insulin resistance (HOMA–IR), and fasting insulin. The biological mechanisms responsible for the outcomes observed in this review in relation to reduction in HbA1c and BMI may be based on the nutrient composition of almonds and the biological effects, including the high fibre content and the low glycaemic index profile. Conclusion: The findings of this systematic review and meta-analysis have shown that almond-based diets may be effective in promoting short-chain fatty acid-producing bacteria and lowering glycated haemoglobin and body mass index in patients with type 2 diabetes compared with control. However, the effects of almonds were not significant (p > 0.05) with respect to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and TNF-α), GLP-1, HOMA–IR, and fasting insulin.

Background Exposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that the receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma. Histone deacetylase (HDAC) has been reported to be important in asthmatic pathogenesis. However, its effect on TDI-induced asthma is not known. The aim of this study was to determine the role of RAGE and HDAC in regulating airway inflammation using a TDI-induced murine asthma model. Methods BALB/c mice were sensitized and challenged with TDI to establish an asthma model. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitors) were administered intraperitoneally before each challenge. In vitro, the human bronchial epithelial cell line 16HBE was stimulated with TDI-human serum albumin (TDI-HSA). RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was also used in the experiments. Results In TDI-induced asthmatic mice, the expression of RAGE, HDAC1, and p-AKT/t-AKT was upregulated, and these expressions were attenuated by FPS-ZM1. Airway reactivity, Th2 cytokine levels in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by JNJ-26482585 and romidepsin. In addition, JNJ-26482585 and romidepsin ameliorated the redistribution of E-cadherin and β-catenin in TDI-induced asthma. In TDI-HSA-stimulated 16HBE cells, knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT). Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. Conclusions These findings indicate that RAGE modulates HDAC1 expression via the PI3K/AKT pathway, and that inhibition of HDAC prevents TDI-induced airway inflammation.

Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing (NESTS) program to screen 11,484 babies in eight Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85% (902/11,484). With 45.89% (414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07% (50/414), estimating an average of 0.95% (7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3,923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period less than 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

Somatic hypermutation (SHM) and class-switch recombination (CSR) of the immunoglobulin (Ig) genes allow B cells to make antibodies that protect us against a wide variety of pathogens. SHM is mediated by activation-induced deaminase (AID), occurs at a million times higher frequency than other mutations in the mammalian genome, and is largely restricted to the variable (V) and switch (S) regions of Ig genes. Using the Ramos human Burkitt’s lymphoma cell line, we find that H3K79me2/3 and its methyltransferase Dot1L are more abundant on the V region than on the constant (C) region, which does not undergo mutation. In primary naïve mouse B cells examined ex vivo, the H3K79me2/3 modification appears constitutively in the donor Sμ and is inducible in the recipient Sγ1 upon CSR stimulation. Knockout and inhibition of Dot1L in Ramos cells significantly reduces V region mutation and the abundance of H3K79me2/3 on the V region and is associated with a decrease of polymerase II (Pol II) and its S2 phosphorylated form at the IgH locus. Knockout of Dot1L also decreases the abundance of BRD4 and CDK9 (a subunit of the P-TEFb complex) on the V region, and this is accompanied by decreased nascent transcripts throughout the IgH gene. Treatment with JQ1 (inhibitor of BRD4) or DRB (inhibitor of CDK9) decreases SHM and the abundance of Pol II S2P at the IgH locus. Since all these factors play a role in transcription elongation, our studies reinforce the idea that the chromatin context and dynamics of transcription are critical for SHM.

Objective The study examined the association between resting heart rate (RHR) of early pregnancy and risk of gestational diabetes mellitus (GDM) in Chinese population. Methods As retrospective study, medical data of 15,092 pregnant women gave birth in 2019 was collected and analyzed. The pregnant women's age, educational level, pre-pregnancy body weight, height, parity, family history of diabetes, lipid profile, blood pressure and RHR were recorded during 11 ∼ 13+6 weeks. Multivariate logistic regression analysis was used to estimate the association between maternal characteristics and RHR and GDM. And we further evaluated the predictive roll of RHR in different sub-groups defined by their body mass index (BMI), age, fasting plasma glucose (FPG), total cholesterol and triglyceride. Results 2313 women (15.33%) were diagnosed as GDM according to 75 g OGTT. According to the quartile value of RHR, the subjects were divided into four groups. Risk of GDM increased significantly as RHR increased. In the fully adjusted model, ORs(95%CI) for the lowest vs highest quartiles of heart rate were 1(as reference), 1.14(0.97 ∼ 1.33), 1.25(1.05 ∼ 1.40), 1.41(1.21 ∼ 1.62), respectively. In the subgroup's analysis, we found the relationship between RHR and risk of GDM was evident in women with low and normal BMI; with normal fasting plasma; and normal serum lipid level. Conclusion The current study shows early-pregnancy maternal RHR is associated with potential risk of developing GDM.

Gut microbiota produce Trimethylamine N-oxide (TMAO) by metabolizing dietary phosphatidylcholine, choline, l-carnitine and betaine. TMAO is implicated in the pathogenesis of chronic kidney disease (CKD), diabetes, obesity and atherosclerosis. We test, whether TMAO augments angiotensin II (Ang II)-induced vasoconstriction and hence promotes Ang II-induced hypertension. Plasma TMAO levels were indeed elevated in hypertensive patients, thus the potential pathways by which TMAO mediates these effects were explored. Ang II (400 ng/kg−1min−1) was chronically infused for 14 days via osmotic minipumps in C57Bl/6 mice. TMAO (1%) or antibiotics were given via drinking water. Vasoconstriction of renal afferent arterioles and mesenteric arteries were assessed by microperfusion and wire myograph, respectively. In Ang II-induced hypertensive mice, TMAO elevated systolic blood pressure and caused vasoconstriction, which was alleviated by antibiotics. TMAO enhanced the Ang II-induced acute pressor responses (12.2 ± 1.9 versus 20.6 ± 1.4 mmHg; P, Graphical abstract Image 1, Highlights • Orally administered TMAO aggravates Ang II-induced hypertension. Antibiotics alleviate Ang II-induced hypertension by reducing TMAO generation. • High concentrations of TMAO constrict afferent arterioles and mesenteric arteries and increase blood pressure. • Low concentrations of TMAO enhance Ang II-induced vasoconstriction and acute pressor response via activating PERK/ROS/CaMKII/PLCβ3/Ca2+ pathway.

Vaginal microbiota-host interactions are linked to preterm birth (PTB), which continues to be the primary cause of global childhood mortality. Despite the majority of PTB occuring in Asia, studies of the pregnancy vaginal microbiota are largely limited to Northern American and European populations. Here, we characterised the vaginal microbiome of 2689 pregnant Chinese women using metataxonomics and in a subset (n=823), the relationship between vaginal microbiota composition, sialidase activity and leukocyte presence and pregnancy outcomes. Vaginal microbiota were most frequently dominated by Lactobacillus crispatus or L. iners, with the latter associated with vaginal leukocyte presence. Women with high sialidase activity were enriched for bacterial vaginosis-associated genera including Gardnerella, Atopobium and Prevotella. Vaginal microbiota composition, high sialidase activity and/or leukocyte presence was not associated with PTB risk suggesting underlying differences in the vaginal microbiota and/or host immune responses of Chinese women, possibly accounting for low PTB rates in this population.ImportanceSpecific vaginal microorganisms or ‘vaginal microbiota’, are associated with preterm birth, which is the primary cause of death in children under 5yrs of age worldwide. Despite most preterm births occuring in Asia, almost all studies of the pregnancy vaginal microbiota have been limited to Northern American and European women. Here, we studied the vaginal microbiota in a large cohort of 2689 pregnant Chinese women and showed that it was most frequently dominated by Lactobacillus crispatus or L. iners. The latter was associated with leukocyte infiltration of vaginal secretions. Women with high activity of the enzyme sialidase, were frequently colonised by species associated with the common condition bacterial vaginosis, including Gardnerella, Atopobium and Prevotella species. Vaginal microbiota, high sialidase activity and/or leukocyte presence was not associated with preterm birth risk indicating differences in the microbe-host immune responses of Chinese women, possibly explaining why preterm birth rates in this population are low.

Background While clinical signs, symptoms, as well as etiology of sensitive skin in general populations have been extensively studied over the last decades, characteristics of sensitive skin in normal subjects, particularly gender-related characteristics, still remain unknown. Objective In the present study, we characterize facial sensitive skin in normal young Chinese. Subjects and methods A questionnaire was given to each participant aged 10-30 years. Clinical signs, symptoms, and associated trigger factors of facial sensitive skin were compared in normal young Chinese males versus females. Results After excluding subjects with pre-existing skin disorders, 475 females and 429 males out of 954 responders were included in the analyzes. Prevalence of self-reported facial sensitive skin was significantly higher in females than in males. Yet, while more females experienced various symptoms, symptoms were more severe in males than in females. However, both the prevalence and severity of clinical signs were similar in females and males. Skin care products appeared to be the major contributors to facial sensitive skin in both genders. Moreover, it appeared that females were more sensitive to environmental factors such as low humidity and sun-exposure while males were more sensitive to emotional factors. Taken together, these results demonstrate that characteristics of sensitive skin are associated with gender, while the underlying mechanisms remain to be explored. Conclusions There are gender differences in prevalence, symptoms, and trigger factors of facial sensitive skin in normal young Chinese.

Objective: Osteosarcoma is one of the most common malignancies in children and adolescents. Studies have shown that miR-34c-5p is involved in the progression of various cancers. To explore the effects of miR-34c-5p on the proliferation, migration and invasion of osteosarcoma cells and its potential mechanism. Methods: qRT-PCR was used to detect the expression levels of miR-34c-5p and FLOT2 mRNA in osteosarcoma tissues and cells. Western Blot was used to detect protein expression. MTT assay used to detect cell viability. Transwell was used to detect cell migration and invasion in each group. Dual luciferase reporter gene assay was used to detect luciferase activity. Results: The expression of miR-34c-5pwas significantly decreased in osteosarcoma tissues and cells and the expression level of FLOT2 mRNA was significantly increased. Overexpression of miR-34c-5p and inhibition of FLOT2 inhibited the proliferation, migration and invasion of osteosarcoma cells and inhibited the expression of Cyclin D1, MMP-2 and MMP-9 proteins and promoted the expression of p21 protein. miR-34c-5p targeted to regulate the expression of FLOT2. Overexpression of FLOT2 reversed the inhibitory effect of miR-34c-5p overexpression on proliferation, migration and invasion of osteosarcoma cell lines. Conclusion: miR-34c-5p can inhibit the proliferation, migration and invasion of osteosarcoma cells. The mechanism may be related to targeting FLOT2, which will provide a new target for the prevention and treatment of osteosarcoma.

Paraoxonase-2 (PON2) belongs to the paraoxonase (PON) protein family. Unlike paraoxonase-1 (PON1), the expression and significance of PON2 remained largely unknown in gastric cancer (GC). Thus, the purpose of our study was to investigate the role of PON2 in GC. First, we found PON2 expression was obviously increased in GC samples compared with paired normal tissue samples at The Cancer Genome Atlas (TCGA) database. Then the high expression status of PON2 mRNA and protein in GC tissues was confirmed by RT-qPCR and immunohistochemistry. Furthermore, we performed the immunohistochemical analysis to study the correlation between PON2 expression and clinicopathological parameters of GC patients, and found high PON2 expression had significantly positive association with diffuse type, clinical stage, tumor invasion, lymph node metastasis and distant metastasis in GC patients. Moreover, survival analysis suggested GC patients with high PON2 expression resulted in a remarkably shorter overall survival compared with GC patients with low PON2 expression, and high expression of PON2 acted as an unfavorable predictor for overall survival. The in vitro studies indicated that silencing of PON2 expression inhibited GC cell proliferation, migration and invasion. In conclusion, our findings give first evidence that PON2 serves as oncogene in GC.

BACKGROUND The aim of this study was to investigate the effect of using osteoprotegerin (OPG) to treat bone defects mediated by endothelial progenitor cell (EPC) recruitment and migration through the CXCR4 signaling pathway. MATERIAL AND METHODS The EPCs extracted from human peripheral blood were cultured in vitro and the expression of CXCR4 and its downstream p-AKT was monitored by the Western blot analysis after OPG treatment. Using the scratch wound healing test and Transwell assay, we assessed the variables influencing the effect of OPG on EPCs after pre-treatment with CXCR4 blocker (AMD3100) and PI3K blocker (Ly294002). After 4 weeks, the bone defect repair condition was estimated via micro-CT and staining with HE and Masson trichrome. Then, immunofluorescence staining was performed to assess angiogenesis in bone defects, while the expression of EPC marker and vascular endothelial growth factor receptor 2 (VEGFR2) was detected by immunohistochemical staining. RESULTS The EPCs treated with OPG had increased levels of CXCR4 and p-AKT. Moreover, the difference in EPC levels among groups in the scratch wound healing experiment and migration experiment indicated that the OPG treatment promoted cell migration and AMD3100 and LY294002 inhibited the function of OPG. In addition, OPG promoted angiogenesis and repair of bone defect in rats, and these effects were abolished by AMD3100 and LY294002 administration. CONCLUSIONS OPG enhanced the proliferation and migration of EPCs through the CXCR4 pathway and promoted angiogenesis and bone formation at bone defect sites.