Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Objective: To understand the nutritional literacy level and associated factors of primary and secondary school students in Beijing, so as to provide a scientific basis for improving student nutrition. Methods: From October 2022 to May 2023, a multi stage cluster random sampling method was employed to select a total of 14 568 primary, junior and senior high school students from 16 districts (ecluding the Economic Technological Development area) in Beijing. Through a survey questionnaire on nutritional literacy and dietary hehavior of school age children, basic information as well as data on nutritional literacy levels across four dimensions:nutrition related knowledge concepts, food selection, food preparation, and food intake dimensions were obtained. The Wilcoxon rank sum test, Kruskal-Wallis test, Spearman correlation analysis, Chi square test and binary Logistic regression were used for the analysis. Results: The median total score of nutritional literacy among primary and secondary school students in Beijing was 68.8. Approximately 26.0% of primary and secondary school students achieved nutritional literacy standards. The median scores and rates of meeting the standards for nutrition related knowledge concepts, food selection, food preparation and food intake dimensions were 23.0, 42.1%; 17.0, 27.4%; 6.5, 33.5%; 23.0, 33.3%, respectively. There were positive correlations between all pairs of the four dimensions ( r=0.33-0.49, P <0.05). The results of multiple Logistic regression analysis showed that primary school students, junior high school students, female students, suburban students, caregivers with a college education level and a bachelor s degree or above were the positive arrelation factors that promoted the achievement of nutritional literacy standards ( OR =2.21, 1.39, 1.18, 1.27, 1.42, 1.66, P <0.05). Conclusion The literacy level of primary and secondary school students in Beijing needs to be significantly improved. School stage, gender, region and caregiver s education level are associated factors.

Objective:To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model.Methods:In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn.Results:A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers ( OR=1.37, 95% CI: 1.16-1.62; OR=2.85, 95% CI: 1.56-5.20; OR=1.50, 95% CI: 1.18-1.91; OR=1.18, 95% CI: 1.02-1.37; OR=1.34, 95% CI: 1.04-1.72; OR=1.62, 95% CI: 1.21-2.17; OR=1.48, 95% CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms ( OR=0.56, 95% CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95% CI: 0.70-0.75, P<0.001) . Conclusion:The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

Objective:To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model.Methods:In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn.Results:A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers ( OR=1.37, 95% CI: 1.16-1.62; OR=2.85, 95% CI: 1.56-5.20; OR=1.50, 95% CI: 1.18-1.91; OR=1.18, 95% CI: 1.02-1.37; OR=1.34, 95% CI: 1.04-1.72; OR=1.62, 95% CI: 1.21-2.17; OR=1.48, 95% CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms ( OR=0.56, 95% CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95% CI: 0.70-0.75, P<0.001) . Conclusion:The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

Objective To observe the effect of fluorine (F) and aluminum (Al) on serum,bone,teeth,brain,kidney and liver tissues,contents of F and Al in different tissues of rats with combined F-Al toxicosis caused by drinking brick tea were determined.Methods Forty SPF grade Wistar rats of 4 weeks,including 24 females and 16 males,weighing between 40 and 50 g,were divided into control group,F group,Al group and brick tea group by random number table according to their weight,ten rats (6 females,4 males) in each group.The control group received daily drinking water.The F group drank a solution with an F content of 100 mg/L,and the Al group drank a solution with an Al content of 159 mg/L.According to the drinking habits and consumption of the herdsmen,the tea concentration and tea consumption of the rats were calculated for the brick tea group,and a tea soup was made according to the ratio,with the F content of (100 ± 2) mg/L and the Al content of (159.0 ± 1.5) mg/L.One year later,the rats were killed to determine the contents of F and Al in serum,bone,teeth,brain,kidney and liver.Results The contents of F in bone,teeth and liver of the brick tea group [(275.81 + 55.89),(283.32 ± 70.67),(15.52 ±7.57) μg/g] were significantly higher than those of the control group [(0.04 ± 0.01),(128.52 ± 12.81),(5.89 ±0.33) μg/g,P ＜ 0.01].The Al contents of teeth and liver in the brick tea group [(6.14 ± 1.69),(8.97 ± 0.85) μg/g]were significantly higher than those of the control group [(0.72 + 0.54),(5.47 + 0.83) μg/g,P ＜ 0.01].Conclusions F-Al combined toxicosis caused by drinking brick tea can cause the increases of F contents in bone,teeth and liver,and the increases of Al contents in teeth and liver.The main tissues damaged by F-Al combined toxicosis caused by drinking brick tea in rats are bone,teeth and liver.

The aim of this article is to study how andrographolide-releasing collagen scaffolds influence rabbit articular chondrocytes in maintaining their specific phenotype under inflammatory environment. Physical blending combined with vacuum freeze-drying method was utilized to prepare the andrographolide-releasing collagen scaffold. The characteristics of scaffold including its surface morphology and porosity were detected with environmental scanning electron microscope (ESEM) and a density instrument. Then, the release of andrographolide from prepared scaffolds was measured by UV-visible spectroscopy. Rabbit chondrocytes were isolated and cultured and seeded on andrographolide-releasing collagen scaffolds. Following culture with normal medium for 3 d, seeded chondrocytes were cultured with medium containing interleukin-1 beta (IL-1β) to stimulate inflammation for 7 d. The proliferation, morphology and gene transcription of tested chondrocytes were detected with Alamar Blue assay, fluorescein diacetate (FDA) staining and reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) test respectively. The results showed that the collagen scaffolds prepared by vacuum freeze-dry possess a high porosity close to 96%, and well-interconnected chambers around (120.7±17.8) μm. The andrographolide-releasing collagen scaffold continuously released andrographolide to the PBS solution within 15 d, and collagen scaffolds containing 2.22% andrographolide significantly inhibit the proliferation of chondrocytes. Compared with collagen scaffolds, 0.44% andrographolide-containing collagen scaffolds facilitate chondrocytes to keep specific normal morphologies following 7 d IL-1β induction. The results obtained by RT-qPCR confirmed this effect by enhancing the transcription of tissue inhibitor of metalloproteinase-1 ( ), collagen II ( ), aggrecan ( ) and the ratio of / collagen I( ), meanwhile, reversing the promoted transcription of matrix metalloproteinase-1 ( ) and matrix metalloproteinase-13 ( ). In conclusion, our research reveals that andrographolide-releasing (0.44%) collagen scaffolds enhance the ability of chondrocytes to maintain their specific morphologies by up-regulating the transcription of genes like , and , while down-regulating the transcription of genes like and which are bad for phenotypic maintenance under IL-1β simulated inflammatory environment. These results implied the potential use of andrographolide-releasing collagen scaffold in osteoarthritic cartilage repair.

Objective To compare signal characteristics and image qualities of MR diffusion-weighted imaging (DWI)at 1.5T and 3.0T in patients with the complex adnexal masses.Methods Magnetic resonance imaging including routine MRI and DWI(b=0 s/mm2 ,400 s/mm2 , 600 s/mm2 ,800 s/mm2 ,1 000 s/mm2 )of 1.5T (50 patients with 31 benign and 1 9 malignant lesions )and 3.0T (53 patients with 29 benign and 24 malignant lesions )were performed in 103 patients with histopathologically proved adnexal masses.The optimal b value was analyzed,and the apparent diffusion coefficient (ADC)value and signal intensity (SI)value and contrast to noise ratio (CNR)of solid and cystic components in adnexal masses from both 1.5T and 3.0T MR were respectively compared statistically.Results The 800 s/mm2 was the optimal b value in demonstrating adnexal masses at 1.5T and 3.0T.The CNR of solid and cystic components in adnexal masses were significantly higher at 3.0T than at 1.5T on all b values(all P =0.000).The difference in ADC value of solid lesions between 1.5T and 3.0T on all b values DWI had no statistically significant (all P >0.05),nor did the difference in SI value of solid lesions as well as ADC value of cystic lesions on b800 DWI(P >0.05).Conclusion MR diffusion-weighted imaging at 3.0T compared with 1.5T has quantitative and qualitative advantages of evaluating for adnexal masses,while the 800 s/mm2 is the optimal b value for both of them.

OBJECTIVETo determine the survival rates of liver cancer in Qidong during the years 1972-2011, according to the data from a population-based cancer registry, in order to assess the long-term trends for prognosis of this cancer type.

METHODSThe deadline of the last follow-up for survival status of the 28, 398 registered cases was April of 2012. Cumulative observed survival (OS) and relative survival (RS) rates were calculated using Hakulinen's method performed by the SURV3.01 software developed by the Finnish Cancer Registry.

RESULTSThe 1-, 3-, 5-, 10-and 15-year OS rates were 15.18%, 6.23%, 4.26%, 2.79% and 2.39%, respectively; the 1-, 3-, 5-, 10-and 15-year RS rates were 15.47%, 6.60%, 4.69%, 3.41% and 3.29%, respectively. For males, these OS rates were 14.95%, 6.05%, 4.06%, 2.67% and 2.26%, and these RS rates were 15.23%, 6.41%, 4.47%, 3.26% and 3.12%, respectively. For females, these OS rates were 15.89%, 6.79%, 4.87%, 3.17% and 2.80%, and these RS rates were 16.20%, 7.20%, 5.37%, 3.87% and 3.82%, respectively. No statistical differences were found between the male and female groups (P>0.05). The 5-year RS rates for age groups 15-34, 35-44, 45-54, 55-64, 65-74 and 75+ years-old were 4.42%, 4.29%, 4.96%, 4.67%, 4.67% and 6.35%, and the 10-year RS rates were 3.17%, 2.98%, 3.44%, 3.47%, 3.75% and 11.27%, respectively. Remarkable improvement was seen for the 1-, 3-, 5-, 10-and 15-year OS rates in this setting since the 1980s.

CONCLUSIONThe survival outcome from Qidong registered cases with liver cancer has shown gradual progress over the past four decades. Early detection and improvement of therapies may be responsible for the improved prognosis of liver cancer. While the disparity gap of survival between this area and developed countries is narrowing, there is still a need for improving the survival in Qidong.

Adolescent ; Adult ; Aged ; Female ; Humans ; Liver Neoplasms ; Male ; Middle Aged ; Prognosis ; Software ; Survival Rate ; Time Factors ; Young Adult

Objective: This research explores the relationship between the immuno-suppression function of regulatory T cells (Treg) in the ascites of ovarian cancer (OC) patients, the clinico-pathologic features of these patients, and the correlation of the function of Treg with initial treatment and relapse status of the patients to further investigate the specific mechanism of immuno-regulatory func-tion of CD4+ CD25+ Treg in the ascites of OC. Methods: Immuno-magnetic activated cell sorting (MACS) was conducted to sort CD4+CD25+Treg and autologous CD4+CD25-Treg from the ascites of 28 OC patients. Carboxyfluorescein-diacetate succinimidyl ester (CFSE) was used to label the autologous CD4+CD25-Treg. These labeled cells were then used as controls and co-cultured with autologous CD4+CD25+Treg at the ratio of 1∶1 or 1∶2. The mean inhibition ratio of Treg in specimens to the proliferation of autolo-gous CD4+ CD25-Treg was calculated after the flow cytometry of the CFSE expression and Modfit software analysis of the CD4+CD25-Treg proliferation index (PI) were performed. Anti-IL-10 and/or anti-TGF-β1 antibodies were neutralized to investigate whether the CD4+CD25+Treg-mediated immuno-suppression escaped through the ascites can produce a marked effect by the inhibitory cyto-kine IL-10 or TGF-β1. Results: The mean inhibition ratio of CD4+ CD25- Treg in the ascites of stage Ⅲ to Ⅳ OC patients was (75.72±17.04)%, which is significantly higher than that of stageⅠtoⅡOC patients (59.61±16.97)%;P<0.05. In addition, Treg in the as-cites of OC patients with recurrent disease showed a significantly higher inhibition ratio than that of patients with primary disease;P<0.001. Moreover, Treg in groups added into neutralizing anti-IL-10 and/or anti-TGF-β1 antibodies displayed significantly lower depres-sant effect than the control group;P<0.05. Conclusion:The immuno-suppression of CD4+CD25+Treg in the ascites of OC patients is correlated with the tumor staging and status of the primary or recurrent diseases. Moreover, Treg may indicate a suppressor function by secreting cytokine IL-10 and TGF-β1.