A fluorescent probe based on cyclochalcone for detecting peroxynitrite.

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

[Relationship Between Urbanization and Carbon Emissions in the Chang-Zhu-Tan Region at the County Level].

Urbanization is a major source of carbon emissions. A quantitative study on the dynamic relationship between urbanization and its morphological characteristics and carbon emissions is crucial for formulating urban carbon emission reduction policies. Based on the carbon metabolism model, the carbon emissions at the country level in Chang-Zhu-Tan from 1995 to 2020 were calculated. The Tapio decoupling model was used to explore the decoupling relationship between the carbon emissions of Chang-Zhu-Tan and urban land, and a geographically and temporally weighted regression(GTWR) model was used to analyze the impact mechanism of urban spatial morphology on carbon emissions. The following conclusions were drawn:① carbon emissions at the county level in the study area formed a clustered distribution centered on the city jurisdiction and showed a trend of diffusion from year to year. Compared with those in 1995, there were seven new high carbon emission districts in 2020, all of which belonged to Changsha. ② From 1995-2020, the research area as a whole changed from mainly strong decoupling to mainly dilated negative decoupling, and the spatial decoupling state fluctuated back and forth between the decoupling and negative decoupling. By 2020, except for the seven regions with the uncoupling state regressing, all of them reached the uncoupling state or were close to the uncoupling state. ③ Urban patch area(CA), urban patch number(NP), and patch combination degree(COHESION) were positively correlated with urban carbon emissions, whereas landscape shape index(LSI), maximum patch index(LPI), and Euclidean distance mean(ENN_MN) were negatively correlated with urban carbon emissions, and the impact of different urban form indicators on carbon emissions had significant spatial heterogeneity.

Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.

BACKGROUND: In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. OBJECTIVE: This study aimed to explore the potential mechanism of NMF for treating COVID-19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. METHODS: The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. RESULTS: Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. CONCLUSION: Our findings provided theoretical grounds for NMF in the treatment of COVID19.

Clinical characteristics and long-term outcomes for parapharyngeal metastases of well-differentiated thyroid cancer during 131 I therapy and follow-up.

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.

[Spatiotemporal Characteristics and Influencing Factors of Environment Emergency Incident in China from 1991 to 2018].

Research on the spatiotemporal characteristics and influencing factors of environmental emergency incidents in China in recent decades can improve the effectiveness and accuracy of risk supervision of environmental emergency incidents. Based on the data of environmental emergency incidents in 31 provincial regions in China from 1991 to 2018, this study used spatial autocorrelation analysis and a geographically and temporally weighted regression model to analyze the spatial dependence of environmental emergency incidents and the temporal and spatial heterogeneity of influencing factors. The results showed that: ① there was a significant positive spatial correlation between environmental emergency incidents during 1991-1994 and 2001-2014, and the spatial agglomeration was gradually increasing, that is, environmental emergency incidents existed in the provinces of China; clearly, the space depended on the characteristics and was not completely random. ② There was an unbalanced development pattern of environmental emergency incidents in China. The provinces with "L-L" agglomeration were concentrated in the western and northeastern regions, and the number increased and then decreased; by contrast, the ones with "H-H" agglomeration shifted from the east and south to the central and western regions, and the number increased following the decrease. The role of environmental emergency incident in different provincial regions in the spatial agglomeration was different and constantly changing. ③ The effects of various influencing factors on environmental emergency incidentshad obvious temporal and spatial heterogeneity in different periods and different provinces. The impact of the level of economic development on environmental emergency incidents was shown as a "negative-positive-negative" pattern. The impact of industrial structure on environmental emergency incidents was shown as a "negative-positive" pattern. The overall impact of pollution emissions on environmental emergency incident presented a "positive-negative-positive" pattern. Environmental letters and visits had a positive impact on the occurrence of environmental emergency incidents. The negative impact of the legal environment on environmental emergency incidents was gradually weakening. The negative impact of pollution control on environmental emergency incidents at the provincial level has gradually become apparent.

Measurement Properties of the Simplified Chinese Version of the Lumbar Spine Instability Questionnaire for Patients With Low Back Pain in Mainland China.

STUDY DESIGN: A prospective study. OBJECTIVE: To develop a simplified Chinese version of Lumbar Spine Instability Questionnaire (SC-LSIQ) and test its measurement properties. SUMMARY OF BACKGROUND DATA: The LSIQ has been translated into several languages. Different versions of LSIQ have proved good reliability and validity in evaluating patients with low back pain. However, there is no simplified Chinese version of LSIQ (SC-LSIQ). MATERIALS AND METHODS: The SC-LSIQ has been translated into a simplified Chinese version according to a standard procedure. A total of 155 patients with low back pain completed the SC-LSIQ along with Oswestry Disability Index, Roland-Morris disability questionnaire, Tampa Scale for Kinesiophobia, and visual analogue scale (VAS). The internal consistency, test-retest reliability, and validity of SC-LSIQ were then calculated to evaluate the measurement properties of SC-LSIQ. RESULTS: The results of SC-LSIQ demonstrated that there was no ceiling or floor effect detected. The Cronbach α coefficient of 0.911 determined a well internal consistency. The intraclass correlation coefficient (0.98) presented an excellent reliability of SC-LSIQ. The Pearson correlation coefficient (r) showed that the SC-LSIQ was excellent correlated to Oswestry Disability Index (r=0.809), Roland-Morris disability questionnaire (r=0.870), and Tampa Scale for Kinesiophobia (r=0.945,). Furthermore, it moderately correlated to visual analogue scale (r=0.586). CONCLUSION: The SC-LSIQ features good internal consistency, reliability, and validity for evaluating Chinese patients with LBP. Results suggest that the SC-LSIQ can be appropriately applied to patients with LBP in routine clinical practice.

[Analysis of Multi-scale Spatio-temporal Differentiation Characteristics of PM2.5 in China from 2011 to 2017].

It is of great significance for joint prevention and control of air pollution to understand the spatial and temporal differentiation characteristics and regional driving factors of PM2.5 in China. In this study, from a multi-scale perspective, the spatial pattern analysis and geographical detectors are used to explore the spatial and temporal distribution pattern and causes of PM2.5 pollution in China mainland from 2011 to 2017. The results show that:① the annual average PM2.5 concentration is relatively stable from 2011 to 2017, and there is no obvious trend. The change characteristics of regional PM2.5 are similar to those of national PM2.5, showing a "W" shaped fluctuation. Overall, the order of pollution degree from high to low is:central, eastern, western, and northeastern. ② From the spatial pattern analysis results, we can see that the high-value cluster mainly appears in east China, middle China, and southwest of Xinjiang, while the low-value cluster appears in Qinghai-Tibet, Yunnan, Guizhou, Plateau, and Daxinganling regions. ③ The results of geographic detector analysis show that the population factor is the leading factor nationally; meanwhile, the industrial, energy consumption, and traffic factors all contribute to the distribution pattern of PM2.5 in varying degrees. Regionally, besides the population factor, the proportion of secondary production and urban green space rate have the greatest impact on the northeast, the industrial smoke and dust and road area in the east, and the total industrial electricity and buses in the central area. The impact of social and economic factors does not significantly affect the PM2.5 in the western region.

Cardiometabolic Risk Factors and Preclinical Target Organ Damage Among Adults in Ghana: Findings From a National Study.

Background Although sub-Saharan Africa has a high prevalence of cardiovascular diseases (CVDs), there remains a lack of systematic and comprehensive assessment of risk factors and early CVD outcomes in adults in sub-Saharan Africa. Methods and Results Using a stratified multistage random sampling method, we recruited 1106 men and women, aged >18 years, from the general population in Ghana to participate in a national health survey from 2016 to 2017. In Ghanaian adults, the age-standardized prevalence of known CVD risk factors was 15.1% (95% CI, 12.9%-17.3%) for obesity, 6.8% (95% CI, 5.1%-8.5%) for diabetes mellitus, 26.1% (95% CI, 22.9%-29.4%) for hypertension, and 9.3% (95% CI, 7.1%-11.5%) for hyperuricemia. In addition, 10.1% (95% CI, 7.0%-13.2%) of adults had peripheral artery disease, 8.3% (95% CI, 6.7%-10.0%) had carotid thickening, 4.1% (95% CI, 2.9%-5.2%) had left ventricular hypertrophy, and 2.5% (95% CI, 1.5%-3.4%) had chronic kidney disease. Three CVD risk factors appeared to play prominent roles in the development of target organ damage, including obesity for peripheral artery disease (odds ratio [OR], 2.22; 95% CI, 1.35-3.63), hypertension for carotid thickening (OR, 1.92; 95% CI, 1.22-3.08), and left ventricular hypertrophy (OR, 5.28; 95% CI, 2.55-12.11) and hyperuricemia for chronic kidney disease (OR, 5.49; 95% CI, 2.84-10.65). Conclusions This comprehensive health survey characterized the baseline conditions of a national cohort of adults while confirming the prevalence of CVD risk factors, and early CVD outcomes have reached epidemic proportions in Ghana. The distinct patterns of risk factors in the development of target organ damage present important challenges and opportunities for interventions to improve cardiometabolic health among adults in Ghana.

Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway.

Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non-protein-coding RNA (lincRNA) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) against MI by targeting nuclear factor-kappa-B inhibitor alpha (NFKBIA) and mediating the nuclear factor-kappa-B (NF-κB) signalling pathway. An MI mouse model was established and idenepsied by cardiac function evaluation. It was determined that ATP2B1-AS1 was highly expressed, while NFKBIA was poorly expressed and NF-κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1-AS1 vector, NFKBIA vector, siRNA-mouse ATP2B1-AS1 and siRNA-NFKBIA. The expression of NF-κBp50, NF-κBp65 and IKKß was determined to idenepsy whether ATP2B1-AS1 and NFKBIA affect the NF-κB signalling pathway, the results of which suggested that ATP2B1-AS1 down-regulated the expression of NFKBIA and activated the NF-κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1-AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1-AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI.

Comprehensive analysis of the chemical constituents in sulfur-fumigated Lonicerae Japonicae Flos using UHPLC-LTQ-Orbitrap mass spectrometry.

Lonicerae Japonicae Flos (LJF), a kind of traditional Chinese medicines (TCMs), has functions of detoxifying and evacuating heat. In the study, a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the chemical constituent analysis of organic acids, flavonoids, iridoids and new-generated compounds in sulfur-fumigated LJF (SF-LJF). Based on the accurate mass measurement (< ± 5 ppm), chromatographic behavior and diagnostic product ions (DPIs), 113 constituents were unambiguously or tentatively characterized from SF-LJF extract, including 46 chlorogenic acids, 19 flavonoids, 29 iridoid glycosides and 19 newly-generated compounds (including 17 sulfur-containing derivatives). In addition, 5-CQA (5-caffeoylquinic acid, chlorogenic acid) was chosen to be sulfur-fumigated for the result validation. It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions, which resulted in the emergence of many new sulfur-containing components. Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF, and also an excellent guidance of quality control about LJF.

Assessment of Sagittal Spinopelvic Balance in a Population of Normal Chinese Children.

STUDY DESIGN: A retrospective study of 257 normal children at a single center from July 2016 to November 2018 was performed. OBJECTIVE: To evaluate the spinopelvic parameters in a population of normal children and adolescents in mainland China. SUMMARY OF BACKGROUND DATA: Values for sagittal parameters of the spine vary significantly by ages and different population. No study has yet quantified the normal measures for children and adolescents in China, or how these measures compare with other populations. METHODS: Pelvic incidence (PI), sacral slope, pelvic tilt, thoracic kyphosis (TK, T5-T12), lumbar lordosis (LL, L1-S1), and sagittal vertical axis were measured and evaluated by whole spine AP&lateral X-ray images. RESULTS: A total of 257 subjects, including 116 boys (45%) and 141 girls (55%) aged 3 to 12 years, were enrolled. Correlation matrix analysis demonstrated that sagittal balance is strongly correlated with age and Risser sign, including PI, a reported fixed parameter. Further investigation showed that PI could be expressed by the equation PI = 26.243+1.153×age. CONCLUSION: PI was not a fixed but a dynamic parameter in the population under 12-year old. Indeed, PI increases with age and bone maturity in childhood. We also found lower PI, pelvic tilt, and sacral slope compared with published studies of adolescents in other countries. These results may aid in the treatment of patients with spinal deformity, to help them achieve a certain degree of sagittal spinopelvic balance. LEVEL OF EVIDENCE: 2.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Low-intensity pulsed ultrasound promotes spinal fusion by regulating macrophage polarization.

BACKGROUND: Spinal fusion is considered the gold standard procedure for treating spinal degeneration, tumors, and trauma. An inflammatory response is an important part of bone repair. We investigated the polarization change of inflammatory macrophages (M1) and resident macrophages (M2) during low-intensity pulsed ultrasound (LIPUS) treatment. METHODS: Thirty male Sprague Dawley rats (age: 12 weeks; weight: 300 g) were used in the study. A rat spinal fusion model was established by surgical procedures. LIPUS treatment (20 min. d, 5 d/wk) was begun 3 days after surgery. The rats were randomly divided into a control group (5 subgroups, 3 rats in each subgroup) and LIPUS group (5 subgroups, 3 rats in each subgroup), and sacrificed on day 3, 5, 7, 10, and 14 after spinal fusion surgery for further evaluation. Bone volume was measured by micro-CT, fusion region was examined by histological analyses, types of macrophages in the fusion area were examined by immunohistochemical staining. Raw264.7 cells and bone marrow-derived macrophages (BMDM) were used in cell experiments. Cells were divided into a control group and LIPUS group. Flow cytometry was used to examine the rate of resident macrophages, and real-time PCR was used to examine the mRNA expression of anti-inflammation genes. RESULTS: LIPUS promoted spinal fusion and stimulated the transition of F4-80+/Mac-2+ (M1) to F4-80+/Mac-2- (M2), leading to the early appearance of resident macrophages. Cell experiments showed CD206+ macrophages (M2) were significantly increased after LIPUS treatment. M2-related genes and anti-inflammation factors (Arg-1, PPAR-γ, and IL-4) were increased after LIPUS treatment. CONCLUSION: The earlier transition from inflammatory to resident macrophage might be one reason for the positive effect of LIPUS on spinal fusion.

Novel breeding approach for Japanese flounder using atmosphere and room temperature plasma mutagenesis tool.

BACKGROUND: Artificial induction of mutagenesis is effective for genetic resource innovation and breeding. However, the traditional mutation methods for fish breeding are not convenient or safe for daily use. Hence, development of a simple, safe and effective mutagenesis method with a high mutation rate and applicability to multiple fish species, is needed. RESULTS: We reported the first successful mutagenesis in a marine aquaculture fish species, Japanese flounder, Paralichthys olivaceus, using a novel atmosphere and room temperature plasma (ARTP) mutagenesis tool. ARTP treatment time was optimized for the fertilized eggs and sperm, respectively. Eggs fertilized for 60 min were treated by ARTP with a radio-frequency power input of 120 W, and the ARTP treatment time was 25 min. Under an ARTP radio-frequency power input of 200 W, the optimal treatment time for sperm diluted with Ringer's solution by 1:40 v/v was 10 min. The ARTP-treated group presented differences in morphological traits such as body height, total length among individuals at day 90 after hatching. Whole-genome sequencing was used to reveal the mutation features of ARTP-treated individuals collected at day 120 after hatching. In total, 69.25Gb clean data were obtained from three controls and eight randomly selected ARTP-treated individuals, revealing 240,722 to 322,978 SNPs and 82,149 to 86,798 InDels located in 17,394~18,457 and 12,907~13,333 genes, respectively. The average mutation rate reached 0.064% at the genome level. Gene ontology clustering indicated that genes associated with cell components, binding function, catalytic activity, cellular process, metabolic process and biological regulation processes had higher mutation rates. CONCLUSIONS: ARTP mutagenesis is a useful method for breeding of fish species to accelerate the selection of economically important traits that would benefit the aquaculture industry, given the variety of mutations detected.

MiR-128-3p accelerates cardiovascular calcification and insulin resistance through ISL1-dependent Wnt pathway in type 2 diabetes mellitus rats.

Vascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality. In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR-128-3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet ß-cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR-128-3p, ISL1, and the Wnt signaling pathway- and apoptosis-related genes. Finally, apoptosis of islet ß-cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet ß-cell function were decreased. Furthermore, upregulation of miR-128-3p and ISL1 gene silencing promoted the expression of Wnt-1, ß-catenin, GSK-3ß, and Bax and the phosphorylation of ß-catenin and GSK-3ß, inhibited c-fos, PDX-1, and Bcl-2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR-128-3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR-128-3p may serve as a potential target for the treatment of T2DM.

Cross-cultural Adaptation and Validation of the Simplified-Chinese Version of Neck Bournemouth Questionnaire for Patients in Mainland China.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to develop and assess the internal reliability and structure validity of a simplified Chinese version of the Neck Bournemouth Questionnaire (SC-NBQ) for evaluation of patients with nonspecific neck pain (NP) in mainland China. SUMMARY OF BACKGROUND DATA: The NBQ has been cross-culturally translated into several languages with good internal consistency and construct validity to evaluate low back pain and NP. However, the NBQ has been not translated or validated for Chinese-speaking patients. METHODS: The SC-NBQ was developed by standard cross-translation procedures, and completed by 106 patients with nonspecific NP, along with other self-reported questionnaires, including the Neck Disability Index (NDI), Hospital Anxiety and Depression Scale (HADS), Functional Rating Index (FRI), and 36-Item Short Form Health Survey (SF-36). The internal consistency, test-retest reliability, and construct validity of the SC-NBQ were determined. RESULTS: The NBQ was successfully translated into Chinese. All patients completed the SC-NBQ twice, and the other instruments. Score distribution demonstrated that there was no floor or ceiling effects of the SC-NBQ. Cronbach α coefficient (α = 0.89) and intraclass correlation coefficient (ICC = 0.97) showed good internal consistency and test-retest reliability. A good construct validity was shown by strong correlation with HADS (r = 0.75), NDI (r = 0.82), FRI (r = 0.90) and SF-36 physical functioning (r = 0.75), and bodily pain (r = 0.75) subscales. CONCLUSION: The SC-NBQ demonstrated good internal consistency, test-retest reliability, and construct validity, and may be used for the evaluation of NP in Chinese-speaking patients. LEVEL OF EVIDENCE: 2.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

Effects of Low-Intensity Pulsed Ultrasound on Knee Osteoarthritis: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Osteoarthritis (OA) is a common degeneration disease characterized with joint pain. The aim of the present study was to systemically review the effects of LIPUS on pain relief and functional recovery in patients with knee osteoarthritis (OA). METHODS: PubMed, Embase, and Cochrane Library were searched manually for researches on LIPUS treatment in patients with knee OA from 1945 to July 2017. Two investigators independently selected the studies according to the inclusion and exclusion criteria, extracted the concerned data, and assessed the included studies. Meta-analysis was performed to evaluate VAS, WOMAC, and ambulation speed between control and LIPUS groups. RESULTS: Five studies were selected in this study. Compared with control group, LIPUS group received a decrease of pain intensity with moderate heterogeneity (-0.79, 95% CI, -1.57 to 0.00; I2 = 65%, P = 0.04) by VAS and improvement in knee function by WOMAC (-5.30, 95% CI, -2.88 to -7.71; I2 = 44%, P = 0.17). No significant improvement was found in ambulation speed (0.08 m/s, 95% CI, -0.02 to 0.18 m/s; I2 = 68%, P = 0.03). CONCLUSION: The present study includes 5 high quality randomized controlled trials. The result indicated that LIPUS, used to treat knee OA without any adverse effect, had a beneficial effect on pain relief and knee functional recovery. More evidence is needed to prove whether LIPUS is effective in improving walking ability.

Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway.

Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. This study showed that LIPUS treatment after spinal fusion surgery increased bone formation. The increased bone mass under LIPUS treatment appeared to result from the increased migration and proliferation of osteoblasts, resulting from upregulation of the Shh signaling pathway. In contrast, inhibition of Shh reduced the migratory and proliferative ability of osteoblast-like MG63 cells and blocked the efficacy of LIPUS treatment.

Circulating Serum Fatty Acid-Binding Protein 4 Levels Predict the Development of Diabetic Retinopathy in Type 2 Diabetic Patients.

PURPOSE: Fatty acid-binding protein 4 (FABP4) has been implicated in the pathology of diabetes and macrovascular diseases. Serum FABP4 levels were determined in type 2 diabetic patients without diabetic retinopathy (DR) at admission in order to investigate a possible contribution of FABP4 to the increased risk of 5-year incidence of DR. DESIGN: Cohort study. METHODS: A total of 738 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists in the following 5 years. Multivariate analyses were performed using logistic regression models. RESULTS: During the follow-up period, 152 (20.60% [95% CI: 17.68%-23.51%]) patients developed DR and 60 (8.13% [95% CI: 6.16%-10.10%]) patients developed vision-threatening DR (VTDR). Nonparametric Spearman rank correlation revealed a statistically significant positive correlation between serum FABP 4 level and international Clinical Diabetic Retinopathy Severity Scales (r = 0.348; P < .001). After adjustment for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the FABP4, levels of FABP4 were associated with DR and the adjusted risk of DR increased by 124% (OR = 2.24 [95% CI 1.65-3.68], P = .006) and 227% (3.27 [2.04-5.56], P < .001), respectively. Similarly, the adjusted risk of VTDR increased by 140% (OR = 2.40 [95% CI 1.32-3.82], P = .001) and 278% (3.78 [2.17-6.59], P < .001), respectively. CONCLUSION: FABP4 shows potential as a novel biomarker for DR prediction in Chinese patients with T2DM, and strict glycemic control and more frequent retinal examination should be highlighted for T2DM patients with the highest quartile range of FABP4.