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Review
  • Jing Lin, Jun Zhu, Yan Wang, Na Zhang, Hans-Jürgen Gober, Xuemin Qiu, ...
    Volume 11 (2017) Issue 5 Pages 496-506
    Released: November 20, 2017
    JOURNALS FREE ACCESS

    Postmenopausal osteoporosis is a systemic metabolic skeletal disease generally ascribable to a dearth of estrogen. Whether traditional Chinese medicine is effective in management of postmenopausal osteoporosis remains unclear. This article reviews the experimental evidence of both in vitro and in vivo preclinical studies with the theme of the application of Chinese single herbs and active ingredients in postmenopausal osteoporosis. It includes three single herbs (Herba Epimedium, Rhizoma Drynariae, and Salvia miltiorrhiza) and eight active ingredients (saikosaponins, linarin, echinacoside, sweroside, psoralen, poncirin, vanillic acid, and osthole). The experimental studies indicated their potential use as treatment for postmenopausal osteoporosis and investigated the underlying mechanisms including osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL), extracellular-signal-regulated kinase/c-Jun N terminal kinase/mitogen-activated protein kinase (ERK/JNK/MAPK), estrogen receptor (ER), bone morphogenetic protein (BMP), transforming growth factor (TGF)-β, Wnt/β-catenin, and Notch signaling pathways. This review contributes to a better understanding of traditional Chinese medicine and provides useful information for the development of more effective anti-osteoporosis drugs.

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Original Articles
  • Xiaoning Hao, Juan Gu, Xiangji Ying, Tao Bo, Wei Fu
    Volume 11 (2017) Issue 5 Pages 507-515
    Released: November 20, 2017
    JOURNALS FREE ACCESS

    In order to describe and examine differences in social support and care needs among disabled Chinese elderly, the current study used stratified sampling to survey local residents of Beijing age 60 or over in the districts of Xicheng, Chaoyang, and Tongzhou in 2016. Structured in-person interviews were conducted with a 7-domain questionnaire. Multiple logistic regressions were used to compare social support and care needs among functioning, partially disabled, and completely disabled elderly. All statistical analyses were performed using SPSS 19.0 with a significance level of 0.05 (two-sided). One thousand and eighty-three residents completed the survey. Based on Activities of Daily Living (ADL) scores, 736 (68.0%) respondents were functioning (ADL score = 14), 167 (15.4%) were partially disabled (14 < ADL score < 22), and 180 (16.6%) were fully disabled (ADL score ≥ 22). Most of the disabled had formal financial support, they received daily care at home, and they received modest emotional support. After controlling for confounding factors, fully disabled respondents were 2.35 times (p = 0.018) more likely to receive financial support and 3.65 times (p = 0.003) more likely to receive emotional support than functioning respondents. However, the fully functioning and partially disabled did not differ significantly in terms of financial or emotional support. Compared to fully functioning respondents, partially disabled respondents were 0.49 (p < 0.001) times less likely to be fully satisfied with their daily care while fully disabled respondents were 0.37 (p < 0.001) times less likely to be fully satisfied with that care. The current study provided a thorough depiction of the current status of social support and care needs of disabled Chinese elderly. More attention should be paid to social support for the partially disabled and daily care for both the partially and fully disabled.

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  • Junling Gao, Scott R. Weaver, Hua Fu, Yingnan Jia, Jiang Li
    Volume 11 (2017) Issue 5 Pages 516-523
    Released: November 20, 2017
    [Advance publication] Released: October 11, 2017
    JOURNALS FREE ACCESS

    It has been hypothesized that subjective well-being (SWB) is determined by a combination of individual characteristics, social environment, and physical environment. However, few studies have simultaneously examined the relationships of the social and physical attributes of a neighborhood with SWB. Accordingly, the present study aimed to examine these relationships among Chinese elders. A total of 2,719 elders aged 60 years or older were recruited from 47 neighborhoods in the Xinhua subdistrict of Shanghai by two-stage stratified random sampling and interviewed between July and September 2014. The social and physical attributes of each neighborhood were assessed using validated and psychometrically tested measures. The Chinese version of the international Personal Wellbeing Index was used to assess SWB. Control variables included sex, age, marital status, education level, years living in the neighborhood, self-rated health, chronic conditions, and leisure-time physical activity. Multilevel linear regression analysis was conducted to explore whether social and physical attributes were associated with SWB. The average level of SWB was 74.2 ± 15.7% of the scale maximum. After controlling for individual covariates, individual-level social cohesion and social interaction were positively correlated with SWB, and both individual-level and neighborhood-level aesthetic quality was positively correlated with SWB. In conclusion, both social and physical attributes of neighborhoods were associated with SWB among Chinese elderly. These findings suggest that creating aesthetic and cohesive neighborhoods may encourage Chinese elders to participate in social activities and promote their SWB.

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  • Haiyin Wang, Chunlin Jin, Qingwu Jiang
    Volume 11 (2017) Issue 5 Pages 524-532
    Released: November 20, 2017
    [Advance publication] Released: October 24, 2017
    JOURNALS FREE ACCESS

    Traditional Chinese medicine (TCM) is an important part of China's medical system. Due to the prolonged low price of TCM procedures and the lack of an effective mechanism for dynamic price adjustment, the development of TCM has markedly lagged behind Western medicine. The World Health Organization (WHO) has emphasized the need to enhance the development of alternative and traditional medicine when creating national health care systems. The establishment of scientific and appropriate mechanisms to adjust the price of medical procedures in TCM is crucial to promoting the development of TCM. This study has examined incorporating value indicators and data on basic manpower expended, time spent, technical difficulty, and the degree of risk in the latest standards for the price of medical procedures in China, and this study also offers a price adjustment model with the relative price ratio as a key index. This study examined 144 TCM procedures and found that prices of TCM procedures were mainly based on the value of medical care provided; on average, medical care provided accounted for 89% of the price. Current price levels were generally low and the current price accounted for 56% of the standardized value of a procedure, on average. Current price levels accounted for a markedly lower standardized value of acupuncture, moxibustion, special treatment with TCM, and comprehensive TCM procedures. This study selected a total of 79 procedures and adjusted them by priority. The relationship between the price of TCM procedures and the suggested price was significantly optimized (p < 0.01). This study suggests that adjustment of the price of medical procedures based on a standardized value parity model is a scientific and suitable method of price adjustment that can serve as a reference for other provinces and municipalities in China and other countries and regions that mainly have fee-for-service (FFS) medical care.

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  • Jie Zhang, Kazumitsu Nawata
    Volume 11 (2017) Issue 5 Pages 533-541
    Released: November 20, 2017
    [Advance publication] Released: October 24, 2017
    JOURNALS FREE ACCESS

    Worldwide, influenza is estimated to result in approximately 3 to 5 million annual cases of severe illness and approximately 250,000 to 500,000 deaths. We need an accurate time-series model to predict the number of influenza patients. Although time-series models with different time lags as feature spaces could lead to varied accuracy, past studies simply adopted a time lag in their models without comparing or selecting an appropriate number of time lags. We investigated the performance of adopting 6 different time lags in 6 different models: Auto-Regressive Integrated Moving Average (ARIMA), Support Vector Regression (SVR), Random Forest (RF), Gradient Boosting (GB), Artificial Neural Network (ANN), and Long Short Term Memory (LSTM) with hyperparameter adjustment. To the best of our knowledge, this is the first time that LSTM has been used to predict influenza outbreaks. As a result, we found that the time lag of 52 weeks led to the lowest Mean Absolute Percentage Error (MAPE) in the ARIMA, ANN and LSTM, while the machine learning models (SVR, RF, GB) achieved the lowest MAPEs with a time lag of 4 weeks. We also found that the MAPEs of the machine learning models were less than ARIMA, and the MAPEs of the deep learning models (ANN, LSTM) were less than those of the machine learning models. In all the models, the LSTM model of 4 layers reached the lowest MAPE of 5.4%, and the LSTM model of 5 layers with regularization reached the lowest root mean squared error (RMSE) of 0.00210.

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  • Qiwei Guo, Yanjun Si, Mi Su, Mei Fan, Jia Lin, Nazakat H Memon, Dingzh ...
    Volume 11 (2017) Issue 5 Pages 542-549
    Released: November 20, 2017
    [Advance publication] Released: October 29, 2017
    JOURNALS FREE ACCESS

    To explain the inconsistent relationship between proprotein convertase subtilisin/kexin type 9 (PCSK9) rs7552841 and plasma lipids profiles, we hypothesized that interplays might occur among gender, PCSK9 rs7552841 and posttraumatic stress disorder (PTSD) on plasma lipids levels. To test this hypothesis, a population of 704 Chinese Han high school students was used, which had been recruited after the 2008 Wenchuan Earthquake. In this population, the plasma levels of glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) had been measured by routine methods. PTSD had been assessed by the PTSD Checklist Civilian Version (PCL-C). PCSK9 rs7552841 was analyzed by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. The T allele carriers had significantly higher levels of TG, TC, LDL-C, and glucose than the CC homozygotes of PCSK9 rs7552841 after the adjustment for age and BMI in the female students, but not in the male students. When PTSD was taken into consideration, the female T allele carriers had significantly higher TG, TC, LDL-C and glucose than the female CC homozygotes after the adjustment for age and BMI only in the subjects without PTSD, but not in the PTSD patients. No significant differences were observed in the male students regardless of PTSD and the adjustment for age and BMI. These results suggest that PCSK9 rs7552841 is associated with plasma lipids profiles only in female adolescents, but not in male students. This association can be modified and negated by PTSD.

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  • Kun Yin, Chao Xu, Gui-Hua Zhao, Ye Liu, Ting Xiao, Song Zhu, Ge Yan
    Volume 11 (2017) Issue 5 Pages 550-556
    Released: November 20, 2017
    [Advance publication] Released: October 16, 2017
    JOURNALS FREE ACCESS

    C35 is a novel tumor biomarker associated with metastasis progression. To investigate the interaction factors of C35 in its high expressed breast cancer cell lines, we constructed bait recombinant plasmids of C35 gene and T47D cell cDNA library for yeast two-hybrid screening. Full length C35 sequences were subcloned using RT-PCR from cDNA template extracted from T47D cells. Based on functional domain analysis, the full-length C351-348bp was also truncated into two fragments C351-153bp and C35154-348bp to avoid auto-activation. The three kinds of C35 genes were successfully amplified and inserted into pGBKT7 to construct bait recombinant plasmids pGBKT7-C351-348bp, pGBKT7-C351-153bp and pGBKT7-C35154-348bp, then transformed into Y187 yeast cells by the lithium acetate method. Auto-activation and toxicity of C35 baits were detected using nutritional deficient medium and X-α-Gal assays. The T47D cell ds cDNA was generated by SMARTTM technology and the library was constructed using in vivo recombination-mediated cloning in the AH109 yeast strain using a pGADT7-Rec plasmid. The transformed Y187/pGBKT7-C351-348bp line was intensively inhibited while the truncated Y187/pGBKT7-C35 lines had no auto-activation and toxicity in yeast cells. The titer of established cDNA library was 2 × 107 pfu/mL with high transformation efficiency of 1.4 × 106, and the insert size of ds cDNA was distributed homogeneously between 0.5-2.0 kb. Our research generated a T47D cell cDNA library with high titer, and the constructed two C35 "baits" contained a respective functional immunoreceptor tyrosine based activation motif (ITAM) and the conserved last four amino acids Cys-Ile-Leu-Val (CILV) motif, and therefore laid a foundation for screening the C35 interaction factors in a BC cell line.

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  • Hong Yao, Lichun Zhou, Linlin Tang, Yanhui Guan, Shang Chen, Yu Zhang, ...
    Volume 11 (2017) Issue 5 Pages 557-564
    Released: November 20, 2017
    [Advance publication] Released: October 16, 2017
    JOURNALS FREE ACCESS

    Cardiomyocyte nutrient deprivation is a common clinical event that mediates various cardiac ischemic processes and is associated with autophagy activation and cell survival or death. Luteolin-7-O-glucoside (LUTG) was one of the flavonoid glycosides isolated from Dracocephalum tanguticum. Previous research had showed that LUTG pretreatment had significant protective effects against doxorubicin-induced cardiotoxicity. However, whether LUTG could protect cardiomyocytes from starvation-induced injury was not clear. In this study, cardioprotection and mechanisms of LUTG against starvation-induced injury were investigated in vitro. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay showed starvation-induced autophagy is a homeostatic and protective response for H9c2 cell survival. LUTG could protect against injury induced by starvation in H9c2 cells. Acridine orange (AO) staining showed that pretreatment with LUTG enhanced lysosomal autophagy. Western blotting indicated that LUTG enhanced autophagy by down-regulating the expression of phospho-extracellular signal regulated kinase1/2 (p-ERK), phospho-protein kinase B (p-Akt) and phospho-mammalian target of rapamycin (p-mTOR). These results suggest that LUTG might act as a promising therapeutic agent for preventing starvation-induced cardiotoxicity by upregulation of autophagy through the Akt/mTOR and ERK signal pathway.

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  • Kyu Im Ahn, Eun Ok Choi, Da He Kwon, Hyun HwangBo, Min Yeong Kim, Hong ...
    Volume 11 (2017) Issue 5 Pages 565-573
    Released: November 20, 2017
    [Advance publication] Released: October 24, 2017
    JOURNALS FREE ACCESS

    Citrus unshiu peel has been used to prevent and treat various diseases in traditional East-Asian medicine including in Korea. Extracts of C. unshiu peel are known to have various pharmacological effects including antioxidant, anti-inflammatory, and antibacterial properties. Although the possibility of their anti-cancer activity has recently been reported, the exact mechanisms in human cancer cells have not been sufficiently studied. In this study, the inhibitory effect of ethanol extract of C. unshiu peel (EECU) on the growth of human bladder cancer T24 cells was evaluated and the underlying mechanism was investigated. The present study demonstrated that the suppression of T24 cell viability by EECU is associated with apoptosis induction. EECU-induced apoptosis was found to correlate with an activation of caspase-8, -9, and -3 in concomitance with a decrease in the expression of the inhibitor of apoptosis family of proteins and an increase in the Bax:Bcl-2 ratio accompanied by the proteolytic degradation of poly(ADP-ribose) polymerase. EECU also increased the generation of reactive oxygen species (ROS), collapse of mitochondrial membrane potential, and cytochrome c release to the cytosol, along with a truncation of Bid. In addition, EECU inactivated phosphatidylinositol 3-kinase (PI3K) as well as Akt, a downstream molecular target of PI3K, and LY294002, a specific PI3K inhibitor significantly enhanced EECU-induced apoptosis and cell viability reduction. However, N-acetyl cysteine, a general ROS scavenger, completely reversed the EECU-induced dephosphorylation of PI3K and Akt, as well as cell apoptosis. Taken together, these findings suggest that EECU inhibits T24 cell proliferation by activating intrinsic and extrinsic apoptosis pathways through a ROS-mediated inactivation of the PI3K/Akt pathway.

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  • Yoshikuni Kawaguchi, Yoshihiro Sakamoto, Daisuke Ito, Kyoji Ito, Junic ...
    Volume 11 (2017) Issue 5 Pages 574-580
    Released: November 20, 2017
    [Advance publication] Released: October 29, 2017
    JOURNALS FREE ACCESS

    Effective adjuvant therapies have not been established for hepatocellular carcinoma (HCC). The study aimed to determine prognostic influence of statin against HCC recurrence after initial resection. From 2003 to 2013, 734 patients underwent initial HCC resection. Exposure to statins was defined as the use at the recommended daily dosage for > 90 days after surgery. Outcomes were compared between patients who did and did not receive statins. Of 734 patients, 31 (4.2%) received statins for dyslipidemia (statin group) and 703 (95.8%) did not (non-statin group). The proportions of hepatitis B (6.5% vs. 22.8%, P = 0.032), C (19.4% vs. 45.0%, P = 0.005), and a fibrosis score of F3-4 (16.1 % vs. 39.8%, P = 0.008) were significantly lower in the statin than non-statin group. The recurrence-free survival rate was significantly higher in the statin than non-statin group (P < 0.001), without significant difference of the overall survival rate (P = 0.142). A multivariable Cox proportional hazards model revealed that the use of statins (hazard ratio, 0.34; P = 0.005) was associated with a significantly lower risk of HCC recurrence. After one-to-two propensity score matching, the RFS rate was also significantly higher in the statin group (n = 31) than in the non-statin group (n = 62) (P = 0.008). In conclusion: The statins use reduced the risk of HCC recurrence after initial resection. Statins may have protective influences on HCC recurrence in patients who undergo initial liver resection.

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  • Tokio Higaki, Shintaro Yamazaki, Masamichi Moriguchi, Hisashi Nakayama ...
    Volume 11 (2017) Issue 5 Pages 581-587
    Released: November 20, 2017
    [Advance publication] Released: October 11, 2017
    JOURNALS FREE ACCESS

    Major portal vein invasion (MVI) by hepatocellular carcinoma (HCC) carries an extremely poor prognosis. Our aim was to clarify the indications of hepatic resection in the presence of MVI by HCC. Between 2001 and 2015, 1,306 patients undergoing primary treatment for HCC were analyzed (866 hepatic resections and 440 transarterial therapies). Significant prognostic factors were identified by retrospectively analyzing tumor status, liver function and treatment. Overall survival was compared in terms of the degree of vascular invasion and treatment. The 5-year survival rates according to the degree of vascular invasion (Vp) were Vp0: 51.9%, Vp1: 33.0%, Vp2: 16.7%, Vp3: 21.8%, and Vp4: 0%, respectively. Overall survival (OS) did not differ significantly between patients with Vp3 and Vp4 MVI (p = 0.153). Median survival following hepatic resection of Vp3 cases was significantly better than that for Vp4 cases (1,913 vs. 258 days, p = 0.014), while OS following transarterial therapy was not significantly different (164 vs. 254 days in Vp3 vs. Vp4, p = 0.137). Multivariate analysis revealed hepatic resection (Odds: 2.335 [95%CI: 1.236-4.718], p = 0.008) and multiple tumors (1.698 [1.029-2.826], p = 0.038) as independent predictors of survival. Hepatic resection in HCC patients with MVI should be indicate in patients with Vp3 invasion.

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  • Toshitaka Sugawara, Junichi Shindoh, Yujiro Nishioka, Masaji Hashimoto
    Volume 11 (2017) Issue 5 Pages 588-594
    Released: November 20, 2017
    [Advance publication] Released: October 24, 2017
    JOURNALS FREE ACCESS

    The ratio of the bilirubin concentration in abdominal drainage fluid to the serum bilirubin concentration (d-Bil/s-Bil) has been used as a predictor of biliary fistula (BF) formation after hepatobiliary surgery. The d-Bil/s-Bil ratio is highly influenced by the amount of drainage and is not always reliable, especially when the amount of drainage is large. In this study, the usefulness of the d-Bil/s-Bil ratio and total bilirubin amount in the drainage fluid (TBA) (bilirubin concentration in the drainage fluid x the amount of drainage) as predictors of severe BF (sBF) formation was evaluated retrospectively from the data of 306 patients who had undergone hepatobiliary surgery. Of the 306 patients, 201 patients were included in the training set and the remaining 105 in the validation set, to determine the best parameter to predict sBF formation after hepatobiliary surgery. Receiver-operating characteristic curve analysis revealed that the predictive power of TBA was superior to that of the d-Bil/s-Bil ratio throughout the postoperative period, and that the TBA on postoperative day (POD) 1 showed the highest discriminatory power in the training set (area under the curve, 0.789; cutoff value, 470 mg/day). The TBA on POD 1 also showed the highest predictive power for sBF formation in the validation set, with a sensitivity of 100%, specificity of 97.1%, and accuracy of 97.1%. In conclusion, TBA may be a more reliable predictor of sBF than the conventionally used d-Bil/s-Bil ratio. Early prediction of sBF may be useful for early removal of unnecessary prophylactic drainage tubes after hepatobiliary surgery.

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Brief Report
  • Xiaoqiong Peng, Wei Qian, Jiangang Hou
    Volume 11 (2017) Issue 5 Pages 595-599
    Released: November 20, 2017
    [Advance publication] Released: October 16, 2017
    JOURNALS FREE ACCESS

    This report aims to evaluate the usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's disease for achieving maximum tumor resection. Between January 2014 and December 2015, 5 patients underwent surgical resection of a penile-scrotal extramammary Paget's disease in department of urology, Huashan hospital, Fudan University. All patients were coated with 5-ALA (concentration of 20%) throughout the scrotum and the visible range of the lesion plus a 2cm margin 3 hours before the induction of anesthesia. 5-ALA fluorescence was visualized using an ultraviolet (UV) light at 405 nm. Surgical margin was determined in a standardized manner. The extent of resection was evaluated on the basis of frozen and histology sections. If the fluorescence positive punctate lesions were found outside the resection range, we removed the lesions and sent them for pathological examination. All data were prospectively collected, and the short- and long-term outcomes of the treatment strategy were analyzed. Lesions in the blue light turns red after irradiation, the fluorescence-guided surgery delineated range is less than the naked eye, intraoperative frozen prompted negative margins, postoperative pathological diagnosis. A total of 31 scattered lesions were found. After biopsy pathology prompted four were positive. In conclusion, 5-ALA fluorescence-guided minimum range can be completely removed in penile-scrotal Paget's lesions, and it is able to detect distant scattered lesions.

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Letter
  • Gotaro Kojima, Steve Iliffe, Ann Liljas, Kate Walters
    Volume 11 (2017) Issue 5 Pages 600-602
    Released: November 20, 2017
    [Advance publication] Released: October 11, 2017
    JOURNALS FREE ACCESS

    A recent systematic review and meta-analysis study suggested that higher alcohol consumption is associated with lower risks for frailty. However the apparent protective effect may not be true because of some limitations. Therefore we further explored potential linear and non-linear associations using a two-stage dose-response meta-analysis. Restricted cubic splines were applied with three fixed knots at percentiles (10%, 50%, and 90%). A two-stage dose-response meta-analysis showed a significant non-linear association (p for non-linearity < 0.001); incident frailty risk decreased until around 15 g/day of alcohol consumption and increased thereafter. This suggests that while moderate alcohol consumption is associated with a lower risk of frailty, at higher consumption levels this apparent protect effect is lost. Given these findings, non-linear associations should be considered in future research on alcohol and frailty.

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  • Yuhong Niu, Na Li, Chunlin Jin, Duo Chen, Yitong Yang, Hansheng Ding
    Volume 11 (2017) Issue 5 Pages 603-605
    Released: November 20, 2017
    JOURNALS FREE ACCESS

    Elderly individuals benefit from frequently engaging in activities outside the home because such activities sustain the overall health and functioning of an aging body. However, environmental barriers can limit participation in activities outside the home by elderly individuals. The current study examined the factors that influence the frequency with which elderly individuals living in China engage in activity outside the home. Data were collected from 2,402 elderly individuals residing in the Jiangning district of Shanghai, China in 2015. Face-to-face interviews were conducted based on a questionnaire, and multiple regression analysis was used to measure influencing factors. Results revealed that elderly respondents with a better self-reported health status (p = 0.2499) engaged in activities outside the home more frequently. In addition, elderly respondents residing on higher floors of multi-floor residential buildings (p < 0.001) were less likely to participate in activities outside of the home. This effect was virtually eliminated, however, when the residence in question was equipped with an elevator (p < 0.001).

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