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Panpan Xu,1– 3 Yu Cao,1– 3 Ruiqing Ren,1– 3 Shuai Zhang,1– 3 Cheng Zhang,1– 3 Panpan Hao,1– 3 Meng Zhang1– 3 1State Key Laboratory for Innovation and Transformation of Luobing Theory, Jinan, People’s Republic of China; 2Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Cardiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Meng Zhang; Panpan Hao, Department of Cardiology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email zhangmeng@sdu.edu.cn; panda.how@sdu.edu.cnPurpose: The systemic inflammation response index (SIRI) and the systemic immune inflammation index (SII) are indicators that reflect the body’s overall systemic inflammatory response. Inflammation plays an important role in the pathogenesis of in-stent restenosis (ISR). The aim of this study was to investigate the predictive value of preoperative SIRI and SII for the occurrence of ISR in patients undergoing coronary stent implantation.Materials and Methods: We retrospectively analyzed the clinical, hematological, and angiographic data of 387 patients who underwent coronary angiography for recurrent angina after coronary stent implantation at Qilu Hospital of Shandong University. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff values for SIRI and SII to predict ISR. Based on the optimal cutoff values for SIRI and SII, patients were categorized into high-SIRI, low-SIRI, high-SII, and low-SII groups. Multivariate logistic regression models were constructed to assess the predictive value of SIRI and SII for ISR > 50% and ISR > 70%.Results: This study included a total of 387 patients who underwent coronary angiography and follow-up at Qilu Hospital of Shandong University. Patients in the high-SIRI group had a higher incidence of ISR than those in the low-SIRI group (ISR > 50%: 44.8% vs 30.7%, p = 0.018; ISR > 70%: 41.5% vs 4.5%, p < 0.001). In addition, ISR occurred more frequently in patients with a higher SII than in patients with a lower SII (ISR > 50%: 52.6% vs 35.7%, p = 0.001; ISR > 70%: 51.9% vs 23%, p < 0.001). In multivariate logistic regression analysis, SIRI and SII were found to be independent predictive factors for ISR, both as continuous and categorical variables. In the ROC analysis, the optimal cutoff value for SIRI was set at 0.54 (sensitivity: 84.5%, specificity: 27%), and the optimal cutoff value for SII was set at 545.29 (sensitivity: 44.1%, specificity: 71.7%).Conclusion: Elevated preoperative SIRI and SII values help predict ISR and may serve as a useful screening tool to perform interventional procedures based on the patient’s risk of ISR after stent implantation.Keywords: SIRI, SII, in-stent restenosis, percutaneous coronary intervention

Lixia Li,1,&ast; Xiaohui Huang,1,&ast; Jingxian Liu,2,&ast; Chao Li,1 Zhiyan Lin,1 Rongrong Ren,3 Yan Zhang,3 Haoshu Ding,3 Jihui Chen,1 Yanfei Mao3 1Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanfei Mao; Jihui Chen, Email maoyanfei@xinhuamed.com.cn; chenjihui@xinhuamed.com.cnBackground: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety.Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis.Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L.Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.Keywords: Polymyxin B, PMB therapeutic drug monitoring, TDM, carbapenem-resistant gram-negative bacteria, CR-GNB, clinical efficacy, acute kidney injury, AKI

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, &num;1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Xujun Feng, Yuan Shi, Ye Zhang, Fei Lei, Rong Ren, Xiangdong Tang Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Rong Ren; Xiangdong Tang, Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Dian Xin Nan Jie 28&num;, Chengdu, 610041, People’s Republic of China, Tel +86-28-85422733, Email 498880651@qq.com; 2372564613@qq.comAbstract: Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system. Keywords: nanoparticles, respiratory system, lungs, nanomaterials, nanotechnology

Hua Xiao,&ast; Xia Yu,&ast; Yuanyuan Shang, Ruyan Ren, Yi Xue, Lingling Dong, Liping Zhao, Guanglu Jiang, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hairong Huang, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, No. 97 Ma Chang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86-10-89509159, Fax +86-10-89509160, Email huanghairong@tb123.orgBackground: Sudapyridine (WX-081) has exhibited equivalent efficacy than its counterpart parent drug bedaquiline (BDQ) but better safety profile against Mycobacterium tuberculosis (Mtb). Our study was aimed to evaluate in vitro activity of WX-081 against the clinical isolates of Mtb with different drug-resistance profiles and the intracellular bactericidal activity against the reference strain.Methods: The minimum inhibitory concentrations (MICs) of WX-081 and BDQ were tested against 114 Mtb clinical isolates. The intracellular activity of WX-081 and BDQ against the Mtb reference strain H37Rv in THP-1 cells was also evaluated in parallel.Results: The MICs for WX-081 of the enrolled isolates ranged from 0.0156 μg/mL to 1 μg/mL. The MIC50 and MIC90 of WX-081 were, respectively, 0.25 μg/mL and 0.5 μg/mL, with 95.6% of the enrolled strains having MICs ≤ 0.25 μg/mL. For a given strain, the MIC value of WX-081 was generally equivalent to or 2-fold than MIC of BDQ. The intracellular bacterial killing was acquired with the tested drug concentrations that were presumed attainable during clinical usage.Conclusion: WX-081 exhibited potent efficacy against the clinical isolates in vitro. The intracellular killing effect of sudapyridine against the reference strain supports its potential efficacy in treating TB patients.Keywords: tuberculosis, sudapyridine, bedaquiline, antibacterial activity

Lu Tan,1 Taomei Li,1 Lian Luo,1 Xiaofang Xue,2,3 Fei Lei,1 Rong Ren,1 Ye Zhang,1 Jiaming He,2,3 Konrad E Bloch,4 Xiangdong Tang1,5– 7 1Sleep Medicine Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Emergency, Diqing Tibetan Autonomous Prefectural People’s Hospital, Shangri-La, People’s Republic of China; 3Department of Intensive Care Unit, Diqing Tibetan Autonomous Prefectural People’s Hospital, Shangri-La, People’s Republic of China; 4Department of Respiratory Medicine, Sleep Disorders Center, University Hospital of Zurich, Zurich, Switzerland; 5Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 7State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiangdong Tang, Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 28 Dian Xin Nan Jie, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85422733, Fax +86-28-85422632, Email 2372564613@qq.comPurpose: Obstructive sleep apnea (OSA) is common both at low and high altitude. Since adaptations to high altitude and respiratory control may differ among Tibetans and Hans, we compared characteristics of sleep-disordered breathing in the two ethnic groups at high altitude.Materials and Methods: This was a prospective observational study including 86 Tibetan and Han long-term (> 5 years) high altitude residents with chief complaints of snoring and/or witnessed apnea underwent clinical evaluation and polysomnography at 3200 meters in Shangri-La, China.Results: In 42 Tibetans, 38 men, median (quartiles) age was 50.0 (41.0; 56.0)y, total apnea/hypopnea index (AHI) 53.9 (32.0; 77.5)/h, obstructive AHI 51.0 (28.0; 72.2)/h and central AHI 1.5 (0.2; 3.1)/h. In 44 Hans, 32 men, median (quartiles) age was 47.0 (43.5; 51.0)y, total AHI 22.2 (12.8; 39.2)/h, obstructive AHI 17.7 (12.0; 33.0)/h and central AHI 2.4 (0.5; 3.4)/h (p < 0.001 total and obstructive AHI vs Tibetans). In Tibetans, mean nocturnal oxygen saturation was lower [median 85.0 (83.0; 88.0)% vs 88.5 (87.0; 90.0)%] and obstructive apnea and hypopnea duration was longer [22.0 (19.6; 24.8) sec vs 18.3 (16.7; 20.6) sec] than in Hans (all p < 0.001). In regression analysis, Tibetan ethnicity, neck circumference and high-altitude living duration were the predictors of total AHI. We also found that with every 10/h increase in total AHI, there were an approximately 0.9 beat/min and 0.8 beat/min increase in mean heart rate during rapid eye movement (REM) and non-REM sleep and 1.9 mmHg and 2.0 mmHg increase in evening and morning systolic blood pressure.Conclusion: Our data suggest that Tibetans presented more severe obstructive sleep apnea, hypoxemia and longer apnea duration compared to Hans at 3200 meters, which was correlated with higher heart rate and blood pressure suggesting a greater cardiovascular risk.Keywords: obstructive sleep apnea, high altitude, Tibetan, long-term Han resident

Yuyu Lv,1,2 Ru Ren,1– 3 Chengxiang Tang,4 Kuimeng Song,5 Shunping Li,1– 3 Haipeng Wang1,2 1Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, People’s Republic of China; 3Center for Health Preference Research, Shandong University, Jinan, People’s Republic of China; 4Macquarie University Centre for the Health Economy, Macquarie University Business School & Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia; 5School of Health Care Security, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaCorrespondence: Shunping Li; Haipeng Wang, Centre for Health Management and Policy Research, Wenhua Xi Road 44, Jinan, Shandong Province, 250012, People’s Republic of China, Tel +86-131-8893-4998, +86-186-6899-6362, Email lishunping@sdu.edu.cn; wanghaipeng@sdu.edu.cnPurpose: To evaluate preferences for medications among patients with type 2 diabetes mellitus (T2DM) from urban community health stations or rural village clinics in Shandong province, China.Methods: We use a discrete choice experiment (DCE) to measure the medication preferences. Each patient completed six DCE choice sets. The attributes for the DCE questionnaire include mode of administration, out-of-pocket medication cost per month, fasting blood glucose control effect and frequency of hypoglycemia events. The conditional logit model (Clogit) and mixed logit model (MXL) were used to evaluate choice data.Results: A total of 887 patients with T2DM completed the survey. The mean age of participants was 64 years, 36.42% experienced complications, and the mean duration of diabetes was about 8 years. Overall, patients’ ideal medication would not have hypoglycemia events, provide normal fasting glucose levels, have oral medication three times a day and lower monthly medication cost. Patients prioritized the frequency of hypoglycemia events (β=15.055, P < 0.01) and were willing to spend CNY 393.10 per month to avoid hypoglycemia events. For patients with higher educational levels and with longer diagnosis time, the effect of fasting blood glucose was more relevant than all other outcomes.Conclusion: This study provides information on T2DM patients’ preference for medications. Our results suggest that clinical doctors should present patients with a variety of pharmaceutical characteristics and include their preference into medication decision, which will improve patient adherence and health outcomes.Keywords: type 2 diabetes mellitus, patients’ preference, medication, discrete choice experiment

Rongxin Ren, Shiwei Bao, Wenjiang Qian, Hongyi Zhao Department of Plastic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hongyi ZhaoDepartment of Plastic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel/Fax +86 10 65238573Email zhaohongyi991@yeah.netObjective: Post-inflammatory hyperpigmentation (PIH) is a reactive hypermelanosis of various skin types, which occurs as a sequela of cutaneous inflammation or injury. Despite generally a self-limited and temporary condition, PIH is still a frustrating problem that can have significant psychosocial effects on patients, especially those with darker skin types. Laser therapy is one of the effective treatments for PIH, and various wavelength lasers and light devices have been utilized in PIH therapy. Nonetheless, data on the long-term efficacy of the 755-nm alexandrite picosecond laser are limited.Methods: This study analyzed two cases of PIH treated with a combination of a 755-nm alexandrite picosecond laser and a diffractive lens array or zoom handpiece. Efficacy of the treatment was determined by the images of skin lesions under a fixed light source before and after each treatment, which were independently reviewed by two plastic-surgery specialists blinded to the clinical data. Improvement was classified as complete (> 75%), significant (50– 75%), mild (25– 50%), and inefficient (< 25% or no obvious change). Skin imaging analysis was carried out using the VISIA system (Canfield, USA), and dermoscopy was performed at the same time.Results: After two to three courses of treatment, all cases showed significant or complete improvement, and no recurrence was observed during the three years of follow-up.Conclusion: A 755-nm alexandrite picosecond laser in combination with a diffractive lens array or zoom handpiece had significant and long-term efficacy for the treatment of PIH caused by trauma. However, attention should be paid to the problem of transient deepening of pigmentation during treatment.Keywords: 755 nm, picosecond laser, long-term effect, post-inflammatory hyperpigmentation

Rongxin Ren, Shiwei Bao, Wenjiang Qian, Hongyi Zhao Department of Plastic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hongyi Zhao Email zhaohongyi991@yeah.netObjective: The present study aims to explore the effect of acne debridement + meticulous nursing on 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in adolescent patients with moderate–severe acne.Methods: A total of 60 adolescent patients with moderate–severe acne who were admitted to our plastic surgery outpatient clinic between January 2018 and January 2020 were selected as the subjects of the present retrospective study. The patients were divided into two groups: the observation group and the control group (n = 30, each). Patients in the control group were treated with standardized ALA-PDT and conventional nursing, while patients in the observation group were treated with ALA-PDT and acne debridement + meticulous nursing intervention. The treatment’s therapeutic effect, adverse reaction incidence, and patient satisfaction 6 months after treatment were compared between the two groups.Results: The acne debridement + meticulous nursing effectiveness was 86.7% in the observation group and 60% in the control group, and the adverse reaction incidence was 20% in the observation group and 46.7% in the control group. There existed statistically significant differences in the above-stated indicators between the two groups (p < 0.05). The difference in the visual analogue scores (VASs) for pain, which were measured immediately after the operations, between the two groups was not statistically significant (p > 0.05); however, the respective VAS differences between the two groups at 30 min and 60 min after the operation were statistically significant (p < 0.05). There was a statistically significant difference in patient satisfaction between the two groups (p < 0.05).Conclusion: In adolescent patients with ALA-PDT-treated moderate–severe acne, the application of acne debridement + meticulous nursing could improve the clinical treatment efficacy and patient comfort as well as reduce the adverse reaction incidence. For these reasons, the treatment method could be worth promoting in clinical practice.Keywords: photodynamics, 5-aminolevulinic acid, psychology, pain, meticulous nursing, acne debridement

Bo Deng,1,* Yi Yuan,1,* Miao Zhong,1,* Rui Ren,1 Wuquan Deng,1 Xiaodong Duan2 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400014, People’s Republic of China; 2Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Duan Email duanxiaodong2032@sina.comAim: The relationship between thyroid status and metabolic factors was investigated as well as iodine nutrition in the general population and among the elderly population.Methods: We performed a cross-sectional survey of 2483 subjects to assess the status of national iodine nutrition and incidence of thyroid disease. The general and elderly populations were divided into normal thyroid function (NTF) and subclinical hypothyroidism (SCH) groups. The anthropometric parameters and biochemical indicators were then analyzed.Results: Overall, 327 participants were diagnosed with thyroid diseases, 73 (22.32%) of whom were 65 years or older. For the general population, compared with the NTF group, individuals in the SCH group were older, presented with higher systolic blood pressure, fasting blood glucose, serum cholesterol, and urinary iodine concentration (all p< 0.05) but lower blood uric acid (UA) (p< 0.05). Linear regression analysis further revealed that age and triglyceride (TG) serum levels positively correlated with serum thyroid-stimulating hormone (TSH) levels. Multiple regression analyses revealed that age, TG, waist circumference (WC), and body mass index were independent predictors for abnormal TSH serum levels. For the elderly population, compared with NTF group, individuals in the SCH group were substantially older (p< 0.05) but presented with lower UA (p< 0.05). Pearson linear regression analysis revealed a positive correlation between age (p=0.003) as well as TG levels (p< 0.001) and serum TSH levels. In contrast, WC (p=0.003) was negatively related to TSH serum levels. Further multiple regression analysis revealed that age, TG, WC and heart rate were independent predictors of blood TSH.Conclusion: The large-scale national study of iodine nutrition, thyroid disease has shown a vital relationship between metabolic indicators and serum TSH levels. Age and metabolic diseases increase the likelihood of developing thyroid diseases, both the general population and among the elderly.Keywords: thyroid function, metabolic status, aging

Yuanpeng Gao,1,* Haixia Ma,2,* Yan Gao,3 Kai Tao,4 Liyan Fu,5 Ruimin Ren,6 Xingui Hu,7 Min Kou,8 Bin Chen,1 Junjun Shi,1 Yunpeng Wen9 1Department of Orthopaedics,The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Tumor Hospital of Shanxi, Taiyuan, People’s Republic of China; 3Department of VitreoretinalSurgery, Shanxi Eye Hospital, Taiyuan, People’s Republic of China; 4Department of Digestive Minimally Invasive Surgery, Tumor Hospital of Shanxi, Taiyuan, People’s Republic of China; 5Comprehensive Examination Department, Children’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China; 6Department of Urology Surgery, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 7Department of Cardiology, Taiyuan Iron and Steel Group General Hospital, Taiyuan, People’s Republic of China; 8Department of Nephrology, Children’s Hospital of Shanxi Province, Taiyuan, People’s Republic of China; 9Department of Rehabilitation, Shanxi Huajin Orthopedic Hospital, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun Shi Tel/fax +86 0351 6125623Email gypfly147852@163.comYunpeng Wen Tel/fax +86 0351 6185361Email nmepvb@163.comBackground: Osteosarcoma (OS) is the most common bone tumor. Many studies have reported that circular RNAs (circRNAs) play an important role in the development of a variety of human cancers. However, the underlying mechanism of circ_0001721 in regulating osteosarcoma progression remains unknown.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001721, miR-372-3p, and mitogen-activated protein kinase 7 (MAPK7) in osteosarcoma tissues and cells. Besides, glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, separately. Cell migration and invasion were determined by transwell assay. Moreover, the protein levels of HK2 and epithelial-to-mesenchymal transition (EMT) markers were determined by Western blot analysis. The relationship between miR-372-3p and circ_0001721 or MAPK7 was predicated by starbase v3.0 and confirmed by dual-luciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assay. Murine xenograft model was established to investigate the role of circ_0001721 in vivo.Results: The levels of circ_0001721 and MAPK7 were upregulated in osteosarcoma tissues and cells, while miR-372-3p was downregulated. Knockdown of circ_0001721 inhibited glycolysis, cell proliferation, cell migration, invasion and epithelial-to-mesenchymal transition (EMT), and promoted apoptosis. Circ_0001721 was validated as a sponge of miR-372-3p and mediated glycolysis, cell proliferation, apoptosis, migration, invasion, and EMT of osteosarcoma cells through miR-372-3p. MAPK7 was a target of miR-372-3p and overexpression of MAPK7 attenuated anti-cancer role of miR-372-3p in OS cells. Further studies revealed that circ_0001721 regulates MAPK7 expression via sponging miR-372-3-p. Finally, knockdown of circ_0001721 inhibited tumor progression in vivo.Conclusion: Circ_0001721 promoted osteosarcoma development through the miR-372-3p/MAPK7 axis.Keywords: circ_0001721, miR-372-3p, MAPK7, osteosarcoma

Yangmengfan Chen,1,* Ming Guan,1,* Ranyue Ren,1 Chenghao Gao,1 Hao Cheng,2 Yong Li,1 Biao Gao,3 Yong Wei,3 Jijiang Fu,3 Jun Sun,4 Wei Xiong1 1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, People’s Republic of China; 4Department of Biochemistry and Molecular Biology, Basic Medical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun SunDepartment of Biochemistry and Molecular Biology, Basic Medical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of ChinaTel +86 189 7128 0215Email sunjun99@hotmail.comWei XiongDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, People’s Republic of ChinaTel +86 132 1273 6006Email 1996tj0558@hust.edu.cnIntroduction: The bone regeneration of endosseous implanted biomaterials is often impaired by the host immune response, especially macrophage-related inflammation which plays an important role in the bone healing process. Thus, it is a promising strategy to design an osteo-immunomodulatory biomaterial to take advantage of the macrophage-related immune response and improve the osseointegration performance of the implant.Methods: In this study, we developed an antibacterial silver nanoparticle-loaded TiO2 nanotubes (Ag@TiO2-NTs) using an electrochemical anodization method to make the surface modification and investigated the influences of Ag@TiO2-NTs on the macrophage polarization, osteo-immune microenvironment as well as its potential molecular mechanisms in vitro and in vivo.Results: The results showed that Ag@TiO2-NTs with controlled releasing of ultra-low-dose Ag+ ions had the excellent ability to induce the macrophage polarization towards the M2 phenotype and create a suitable osteo-immune microenvironment in vitro, via inhibiting PI3K/Akt, suppressing the downstream effector GLUT1, and activating autophagy. Moreover, Ag@TiO2-NTs surface could improve bone formation, suppress inflammation, and promote osteo-immune microenvironment compared to the TiO2-NTs and polished Ti surfaces in vivo. These findings suggested that Ag@TiO2-NTs with controlled releasing of ultra-low-dose Ag+ ions could not only inhibit the inflammation process but also promote the bone healing by inducing healing-associated M2 polarization.Discussion: Using this surface modification strategy to modulate the macrophage-related immune response, rather than prevent the host response, maybe a promising strategy for implant surgeries in the future.Keywords: silver nanoparticle, TiO2 nanotubes, immune response, glucose transport, autophagy

Rui Ren,1,2 Yu Ma,2 Fang Deng,1 Tao Li,1 Hongyan Wang,2 Jing Wei,3 Xiaoyan Jiang,2 Min He,1 Mingyuan Tian,4 Dongfang Liu,4 Bing Chen,1 Wuquan Deng1,21Department of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China; 2Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Department of Endocrinology, General Hospital of Xinjiang Military Region, PLA, Urumqi, People’s Republic of China; 4Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wuquan DengDepartment of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No. 1 Jiankang Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 236 369 2185Email wuquandeng@gmail.comBackground: Whether a relationship exists between various metabolic factors and thyroid-stimulating hormone (TSH) levels in euthyroid persons remains unknown. This study aims to explore the relationship between TSH levels and metabolic factors in euthyroid individuals.Methods: A total of 2,663 subjects were enrolled from a nationwide population-based cross-sectional survey of iodine nutrition, thyroid disease and diabetes in China (2014–2017). Euthyroid individuals were divided into four groups according to quartiles of TSH levels: group A (n=305, 0.3–1.3 mIU/L), group B (n=829, 1.3–2.2 mIU/L), group C (n=673, 2.2–3.2 mIU/L) and group D (n=349, 3.2–4.2 mIU/L). Anthropometric parameters, biochemical indicators and TSH levels were determined.Results: A total of 2,156 euthyroid subjects with serum TSH levels within the normal range accounted for 86.8% of the sample. The systolic blood pressure (SBP) in group D was significantly higher than that in the other three groups. Group C displayed significantly lower thyroid peroxidase antibody (TPOAb) levels than the other three groups. Group C also had lower anti-thyroglobulin antibody (TgAb) levels than groups A and D, whereas the TgAb levels in group B were only lower than those in group A. Spearman’s or Pearson’s linear regression analysis showed that SBP (r=0.054; P=0.013) was positively correlated with TSH, but cholesterol (TC) (r=−0.043, P=0.047) was negatively correlated with TSH. Multiple stepwise regression analysis revealed that SBP, the urinary iodine concentration (UIC), waist circumference (WC), body mass index (BMI), TC, triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of serum TSH levels.Conclusion: This large population-based study demonstrates a significant interaction between metabolic factors and TSH levels. An adverse weight status, high blood pressure levels, blood lipid metabolism disorder and excessive iodine intake may be early manifestations of thyroid disease in euthyroid subjects.Keywords: thyroid-stimulating hormone, metabolic syndrome, iodine nutrition, euthyroid state

Tao Li,1 Yu Ma,2 Min Wang,1 Tao Wang,3 Jing Wei,4 Rui Ren,1 Min He,1 Guixue Wang,2 Johnson Boey,5 David G Armstrong,6 Wuquan Deng,2 Bing Chen1 1Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Endocrinology and Nephrology, Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Affiliated Central Hospital of Chongqing University, Chongqing, People’s Republic of China; 3Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, People’s Republic of China; 4Department of Endocrinology, General Hospital of Xinjiang Military Region, The Chinese People’s Liberation Army, Urumqi, People’s Republic of China; 5Department of Podiatry, Singapore General Hospital, Singapore; 6Southwestern Academic Limb Salvage Alliance (SALSA), Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA Aim: This study was designed to examine the potential mechanism underlying these roles of platelet-rich plasma in treating diabetic foot ulcers (DFUs). Methods: Staphylococcus aureus and HaCaT were co-cultured under high glucose conditions to serve as an in vitro model for infected cells in DFUs. Platelet-rich gel (PRG) or extract liquid of platelet-rich gel (EPG) were used to interfere with the model to observe the growth of HaCaT cells and S. aureus, and the effect of miR-21 changes in HaCaT cells on PDCD4, NF-κB activity and related inflammatory factors. Results: Incubation of HaCaT cells with S. aureus promoted the decline of cell proliferation. Under this condition, the level of PDCD4 and the activity of NF-κB were increased in HaCaT cells with concomitant increased of IL-6, TNF-α and decreased IL-10, TGF-β1 in cultured supernatant. Both of PRG and EPG exhibited specific anti-S. aureus activity where they protect HaCaT cells from bacterial damage and promote cell proliferation. Meanwhile, EPG was observed to increase intracellular miRNA-21 while reduce PDCD4 expression and inhibit NF-κB activity to suppress the inflammation in HaCaT cells. Conclusion: This in vitro model provides a valuable tool for study of wound healing in the treatment of DFUs. Our results suggest that miRNA-21 may regulate the expression of NF-κB through PDCD4 where it plays an anti-inflammatory role and promote proliferation in infected DFUs treated by PRP. These findings could provide novel therapeutic targets for refractory wounds. Keywords: platelet-rich plasma, antibacterial, anti-inflammatory, cell proliferation-promoting, diabetic infected wound

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7}  cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5  MeV/c^{2} to 100  TeV/c^{2}) and cover a wide range of βγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with βγ as small as 0.1 for the first time.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst)  eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140  MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

ObjectiveRecent advances in light-sheet fluorescence microscopy (LSFM) enable 3-dimensional (3-D) imaging of cardiac architecture and mechanics in toto. However, segmentation of the cardiac trabecular network to quantify cardiac injury remains a challenge.MethodsWe hereby employed "subspace approximation with augmented kernels (Saak) transform" for accurate and efficient quantification of the light-sheet image stacks following chemotherapy-treatment. We established a machine learning framework with augmented kernels based on the Karhunen-Loeve Transform (KLT) to preserve linearity and reversibility of rectification.ResultsThe Saak transform-based machine learning enhances computational efficiency and obviates iterative optimization of cost function needed for neural networks, minimizing the number of training datasets for segmentation in our scenario. The integration of forward and inverse Saak transforms can also serve as a light-weight module to filter adversarial perturbations and reconstruct estimated images, salvaging robustness of existing classification methods. The accuracy and robustness of the Saak transform are evident following the tests of dice similarity coefficients and various adversary perturbation algorithms, respectively. The addition of edge detection further allows for quantifying the surface area to volume ratio (SVR) of the myocardium in response to chemotherapy-induced cardiac remodeling.ConclusionThe combination of Saak transform, random forest, and edge detection augments segmentation efficiency by 20-fold as compared to manual processing.SignificanceThis new methodology establishes a robust framework for post light-sheet imaging processing, and creating a data-driven machine learning for automated quantification of cardiac ultra-structure.

We present an analysis of electron recoils in cryogenic germanium detectors operated during the SuperCDMS Soudan experiment. The data are used to set new constraints on the axioelectric coupling of axionlike particles and the kinetic mixing parameter of dark photons, assuming the respective species constitutes all of the galactic dark matter. This study covers the mass range from 40 eV/c2 to 500 keV/c2 for both candidates, excluding previously untested parameter space for masses below ∼1 keV/c2. For the kinetic mixing of dark photons, values below 10-15 are reached for particle masses around 100 eV/c2; for the axioelectric coupling of axionlike particles, values below 10-12 are reached for particles with masses in the range of a few-hundred eV/c2.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) searches for interactions between dark matter particles and germanium nuclei in cryogenic detectors. The experiment has achieved a low energy threshold with improved sensitivity to low-mass (

Background EuroQoL EQ-5D-5L is a commonly used measure of health-related quality of life in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D-5L is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. Methods A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. Results EQ-5D-5L mean index and VAS score changes between patients who had cognitive failure and those who had preserved cognition showed no statistically significant differences at any timepoint. In contrast, VAS changes at 4 months (1.61 vs -5.13, P  = .05) and 6 months (8.17 vs −0.14, P  = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were improved in the cohort of patients with preserved neurocognitive function at 2 months (1.68 vs 2.08, P  = .05) and 4 months (1.35 vs 1.83, P  = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. Conclusion EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a quality of life metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. Trial Registration NCT# 02360215. [ABSTRACT FROM AUTHOR]