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This roadmap includes the perspectives and visions of leading researchers in the key areas of flexible and printable electronics. The covered topics are broadly organized by the device technologies (sections 1–9), fabrication techniques (sections 10–12), and design and modeling approaches (sections 13 and 14) essential to the future development of new applications leveraging flexible electronics (FE). The interdisciplinary nature of this field involves everything from fundamental scientific discoveries to engineering challenges; from design and synthesis of new materials via novel device design to modelling and digital manufacturing of integrated systems. As such, this roadmap aims to serve as a resource on the current status and future challenges in the areas covered by the roadmap and to highlight the breadth and wide-ranging opportunities made available by FE technologies.

Hao Tian,1,* Tingting Zhao,1,* Yanling Li,1,* Na Sun,1 Dandan Ma,1 Qiyun Shi,1 Guozhi Zhang,1 Qingqiu Chen,1 Kongyong Zhang,1 Ceshi Chen,2,* Yi Zhang,1 Xiaowei Qi1 1Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaowei Qi; Yi Zhang, Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Gaotanyan Street 29, Chongqing, 400038, People’s Republic of China, Tel/Fax +86-23-68754160, Email qxw9908@foxmail.com; zhangyi1489@sina.comBackground: Epigenetic modification of chromatin is an important step in the regulation of gene expression. The chromobox family proteins (CBXs), as epigenetic modifier, may play a vital role in tumorigenesis and cancer progression. Herein we explored the correlation between CBXs and breast cancer (BC) via the bioinformatics approach and qRT-PCR validation.Methods: Several databases, including GEPIA, TCGA, GEO, K-M plotter, STRING, DAVID, cBioPortal, CIBERSORT, and HPA were employed to analyze the expression levels of CBXs and the correlations between CBXs and prognosis (overall and recurrence-free survival) in BC. We analyzed molecular functions, genetic variations, transcription factors of CBXs, and immune cell infiltration status. ROC curve analysis was performed to determine the predictive value of CBXs. RNA extracted from 11 human BC and paired adjacent normal tissues were subjected to qRT-PCR.Results: The mRNA expression level of CBX1– 5 was significantly upregulated, while that of CBX7 was significantly downregulated in BC; no expression disparities were observed in CBX6/8 expression. Further, high mRNA expression of CBX1/2/3/4/8 correlated with advanced BC, whereas high mRNA expression of CBX6/7 correlated with early BC. High mRNA expressions of CBX1/2/3/5 predict poor OS and RFS, while higher mRNA expressions of CBX6/7 predict better OS and RFS in patients with BC. ROC curve analysis revealed that CBX3 showed excellent discriminatory ability. Gene ontology enrichment analysis showed that CBXs primarily participated in SUMOylation and post-/transcriptional regulation. Moreover, they presented varying degrees of amplification in BC tissues and were related to the infiltration of various immune cells.Conclusion: CBXs can serve as putative biomarkers for BC. Further studies are warranted to determine the exact molecular mechanisms underlying the action of CBXs in BC, particularly CBX1/2/3/5/7.Keywords: chromobox family proteins, breast cancer, prognosis, bioinformatics, qRT-PCR

Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols.

Fang Zhao,1 Deyong Ma,2 Tingting Wang,3 Yan Zhang,2 Ying Dong,4 Jian Zhao2 1Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing, 100035, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking University First Hospital of Obstetrics and Gynecology, Beijing, 100034, People’s Republic of China; 3Peking University Department of Medicine, Beijing, 100191, People’s Republic of China; 4Department of Pathology, Peking University First Hospital of Obstetrics and Gynecology, Beijing, 100034, People’s Republic of ChinaCorrespondence: Jian Zhao, Email JianZhao112@outlook.comObjective: The aim of this study was to clinically evaluate the application of liquid-based cytology P16, cytologic evaluation, and high-risk human papillomavirus (HR-HPV) testing in cervical cancer screening.Methods: This study screened 900 women, who attended the outpatient clinic, according to the exclusion criteria of study participants. The study participants’ screening results of liquid-based cytology P16, cytologic evaluation, and HR-HPV testing were analyzed. According to the pathological results of the biopsy, the efficacy of different screening strategies for the identification of high-grade lesions was evaluated.Results: The positive rate of p16 expression increased with the severity of cervical lesions. P16 had the highest sensitivity and negative predictive value in identifying high-grade lesions (98.45% and 99.67%, respectively). Liquid-based Papanicolaou test (LBP), on the other hand, had the lowest sensitivity (85.27%) but the highest specificity (85.88%). HR-HPV’s positive predictive value and accuracy rate were the lowest (32.77% and 70.03%, respectively). The difference was statistically significant (P < 0.05). Dual combinations of certain tests were set up for this study; P16+LBP, HPV+LBP, and P16+HPV had sensitivities of 98.45%, 96.90%, and 99.22%, and specificities of 80.29%, 63.42%, and 64.33%, respectively. The P16 screening rates of histological and liquid-based cytology approaches were 75.74%.Conclusion: Compared with traditional LBP+HPV, the application of a test that solely screen for P16 or the combined screening method that involves the screening of P16 is more effective in identifying high-grade lesions.Keywords: biomarkers, liquid-based cytology, p16, HR-HPV, screening of high-grade cervical lesions

Qian Chen,1,2,&ast; Zhigang Qin,1,&ast; Yibing Sun,3 Xiangfeng Liu,1 Aurelie Pac Soo,2 Enqiang Chang,2 Qizhe Sun,2 Bin Yi,1 Dong-Xin Wang,3 Hailin Zhao,2 Daqing Ma,2 Jianteng Gu1 1Department of Anaesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK; 3Department of Anaesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianteng Gu, Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, People’s Republic of China, Tel +86 23 68765366, Fax +86 2365463270, Email jiantenggu@hotmail.com Daqing Ma, Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK, Tel +44 020 3315 8495, Fax +44 020 3315 5109, Email d.ma@imperial.ac.ukPurpose: This study aims to investigate the cytoprotective and anti-inflammatory effects of an α2-adrenoreceptor (α2-AR) agonist, dexmedetomidine (Dex), on lipopolysaccharides (LPS)-induced acute lung injury and underlying mechanisms with focus on alveolar macrophage polarization modulation.Methods: C57BL/6 mice were intraperitoneally injected LPS (10 mg/kg) with or without Dex (25 μg/kg) and/or α2-AR antagonist atipamezole (Atip, 500 μg/kg). Lung tissues were then analysed to determine injuries. In vitro, human pulmonary epithelial cells (A549) and mice alveolar macrophages (MH-S) were exposed to LPS (10 ng/mL) with or without different concentrations of Dex (0.1– 100 nM). Alveolar macrophage polarization, NLRP3 inflammasome activation and inflammatory responses were determined. PTEN/Akt signaling and its downstream transcriptional factors as targets for macrophage polarization were assessed.Results: Dex treatment significantly reduced pro-inflammatory M1 macrophage polarization and NLRP3 inflammasome activation in the lungs relative to the mice treated with LPS. The similar pattern reduction of NLRP3 inflammasome activation by Dex was also found in A549 cells. Atip partly reversed the anti-inflammatory effects of Dex. In cultured alveolar macrophages, Dex reduced LPS-mediated expression of IL-1, − 6 and TNF-α receptors while promoting alveolar macrophages differentiation towards a M2 anti-inflammatory phenotype. Additionally, LPS increased Akt signaling activation in a time-dependent manner, which was further activated by Dex via inhibiting phosphatase and tensin homolog (PTEN). The action of Dex on Akt signaling shifted alveolar macrophages from M1 to M2 phenotype through increasing STAT6 and IRF4 transcriptional factors.Conclusion: Dex protected against LPS-induced lung injury and suppressed LPS-induced pulmonary inflammatory responses by attenuating the NLRP3 inflammasome activation and promoting anti-inflammatory M2 macrophage polarization.Keywords: sepsis, acute lung injury, macrophage polarization, dexmedetomidine, Akt signaling

Summary: This study investigated the effects of skin‐on and skin‐off processing methods on processing efficiency, product yield and meat quality of goat carcasses. A total of twenty‐seven goats (nine/treatment, 6 months old) were processed using three methods: (1) skin‐on for ethnic consumers, (2) skin‐off for traditional consumers and (3) skin‐off‐late (skin removal after chilling) for primarily traditional consumers, with an option for ethnic consumers with skin‐on. Processing times (slaughter, chilling, fabrication) and yields (chilling and fabrication) were compared. Meat quality and appearance were evaluated using sarcomere length, Warner‐Brazler shear force, collagen content and muscle colour. Skin‐on carcasses required significantly longer chilling times to reach the internal body temperature at ≤4.4 °C (9.5 h) compared to skin‐off carcasses (7 h), presumably due to the presence of the skin. Despite this, the total processing time from stunning to fabrication showed no significant difference across treatments, although the skin‐off‐late carcasses had longer fabrication times due to the skin removal step (P < 0.05). Dressing yield was lower in the skin‐off group, and fabrication yield was reduced in the skin‐off‐late carcasses (P < 0.05). Skin‐on and skin‐off‐late carcasses showed longer sarcomere lengths and lower Warner Bratzler shear forces than skin‐off carcasses (P < 0.05). Additionally, the skin‐on group had higher collagen content than the skin‐off group. Muscle L* values were higher in skin‐on and skin‐off‐late carcasses (P < 0.05), with no significant differences in a* and b* values across treatments. This research highlights the potential benefits of the skin‐off‐late method for goat farmers, processors and consumers, offering improved dressing yield, meat tenderness and visual appearance. The skin‐off‐late method also provides an alternative processing option that could satisfy both traditional and ethnic consumer preferences. [ABSTRACT FROM AUTHOR]

Yajing Fu,1 Dan Ma,2 Fengyan Fan,3 Tongke Sun,1 Ruiqi Han,1 Yanran Yang,1 Jun Zhang1 1Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Orthodontics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Orthodontics, Hangzhou Stomatological Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, People’s Republic of China, Tel +86 139 5310 9816, Email zhangj@sdu.edu.cnPurpose: Stem cells from the apical papilla (SCAPs) are promising seed cells for tissue regeneration medicine and possess the osteogenic differentiation potential. Wnt5a, a typical ligand of the noncanonical Wnt pathway, exhibits diverse roles in the regulation of osteogenesis. The transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1) is a core regulator in the Hippo pathway and regulates stem behavior including osteogenic differentiation. This study aims to examine how Wnt5a regulates SCAPs osteogenesis and explore the precise mechanistic relationship between Wnt5a and TAZ.Methods: SCAPs were isolated from developing apical papilla tissue of extracted human immature third molars in vitro. ALP staining, ALP activity and Alizarin red staining were used to evaluate osteogenic capacity. Osteogenic-related factors were assessed by qRT-PCR or Western blotting. Additionally, the receptor tyrosine kinase-like orphan receptor 2 (ROR2) was detected by immunocytofluorescence staining and silenced by small interfering RNA to verify the function of Wnt5a/ROR2 in TAZ-mediated osteogenesis. And we constructed TAZ-overexpression and β-catenin-overexpression SCAPs generated by lentivirus to explore the precise mechanistic relationship between Wnt5a and TAZ.Results: Wnt5a (100ng/mL) significantly suppressed ALP activity, mineralization nodules formation, expression of osteogenic-related factors. Meanwhile, it decreased the expression of TAZ mRNA and protein. TAZ overexpression promoted osteogenesis of SCAPs while Wnt5a could block TAZ-mediated osteogenesis. Furthermore, ROR2 siRNA (siROR2) was found to upregulate TAZ and canonical Wnt pathway signaling related molecules such as β-catenin, GSK3β and p-GSK3β. The suppression of Wnt5a/ROR2 on osteogenesis was significantly reversed by β-catenin overexpression through Wnt5a/ROR2/β-catenin/TAZ pathway.Conclusion: Taken together, the present study demonstrates that Wnt5a suppresses TAZ-mediated osteogenesis of SCAPs and there may be a Wnt5a/ROR2/β-catenin/TAZ pathway regulating osteogenesis of SCAPs. Moreover, Wnt5a could be a candidate for regulators in tissue regeneration.Graphical Abstarct: Keywords: Wnt5a, TAZ, stem cells from the apical papilla, osteogenesis, β-catenin

Maoti Wei,1,&ast; Li Dong,2,&ast; Fenghua Wang,1 Kai Cui,3 Delong Ma,2 Ning Yang,4 Yuming Li4 1Center of Clinical Epidemiology, TEDA International Cardiovascular Hospital, Tianjin, People’s Republic of China; 2Department of Pediatrics, Center Hospital of Beikuo Town, Rizhao City, Shandong Province, People’s Republic of China; 3Department of Disease Prevention and Control, Hospital of Gaoxing Town, Rizhao City, Shandong Province, People’s Republic of China; 4Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang; Yuming Li Email yangningzxdl@sina.com; cardiolab@live.comObjective: To understand the prevalence and control of type 2 diabetes mellitus (T2DM) in a rural area, a cross-sectional study was carried out.Methods: Blood glucose was determined in residents over 60 years during the National Basic Public Health Service project carrying on in a rural town of Shandong province. Combined with detail information of diabetic history, the prevalence rate of this disease was calculated with a cutoff of more than 7.0 mmol/L of fasting plasma glucose (FPG). Furthermore, according to FPG levels, the control rate of diabetes was evaluated. Basic information and clinical laboratory tests were analyzed with proper methods for univariate analysis. Multivariable logistic analysis was used to explore multiple variables associated with the control effect of T2DM.Results: The prevalence rate of T2DM was 13.5% (95% CI 12.4%∼ 14.7%) without age difference in residents over 60-year old (X2= 1.078, P = 0.898). And the rate was higher in the female (16.1%, 95% CI 14.4%∼ 17.8%) than that in the male (11.3%, 95% CI 9.7%∼ 12.9%). The control rate of diabetes was 44.5% (95% CI 39.4– 49.6%, cutoff < 6.1 mmol/L for FPG) and 59.6% (95% CI 54.5– 64.6%, cutoff < 7.0 mmol/L for FPG), respectively. Most T2DM residents had balance foods, and a high proportion of drugs or insulin were used; however, the proportion of keeping exercise and modifying behaviors was low. Nearly 80% of the diabetic individuals used at least one drug or insulin. However, the more drugs or insulin used, the higher the FPG level was.Conclusion: A relative high level of T2DM prevailed in the rural area under fast economy-transforming. T2DM was controlled poor and measures should be further optimized to achieve ideal effect, especially for the use of anti-diabetic drugs.Keywords: rural area, type 2 diabetes mellitus, the control of diabetes

Chunlei Wu, Denhua Ma, Yu Chen Department of Cardiac Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, 317000, People’s Republic of ChinaCorrespondence: Yu Chen People’s Republic of ChinaEmail chenyu5835@126.comPurpose: Here, we sought to determine the association between pulse pressure difference and the incidence of type 2 diabetes mellitus (T2DM) in Chinese people.Methods: This study involved 211,814 participants among whom 4156 had been diagnosed with T2DM. The correlation between pulse pressure difference and T2DM incidence in Chinese people was determined by multivariate analysis. A smooth curve fitting diagram was then used to explore correlation between pulse pressure difference and T2DM incidence. Finally, the inflection point in the correlation between pulse pressure difference and the T2DM incidence was located by piecewise linear regression.Results: To understand the relationship, adjustments were made for sex, age, total serum cholesterol (TC), fasting blood glucose (FPG), triglyceride (TG), alanine aminotransferase (ALT), family history of diabetes, body mass index (BMI), blood urea nitrogen (BUN), drinking status, and smoking status. Diabetes incidence increased by 0.3% [HR 1.003 (1.001, 1.005), p = < 0.05] for every 1mmHg increase in pulse pressure difference. Smooth curve analysis showed that, when pulse pressure difference was ≤ 35mmHg, diabetes incidence negatively correlated to pulse pressure difference [HR 0.972 (0.953, 0.972) p = 0.053]. However, when pulse pressure difference was > 35mmHg, diabetes incidence increased with increasing pulse pressure difference [HR 1.044 (1.042, 1.047) p = < 0.001]. And between pulse pressure difference and fasting blood glucose in the final visit, the blood glucose level increased with the elevation of pulse pressure.Conclusion: The risk of diabetes was lowest at about 35mmHg pulse pressure difference.Keywords: pulse pressure difference, diabetes mellitus incidence, Chinese population, cohort study

Junshuai Xue,1,&ast; Delin Ma,2,&ast; Jianjun Jiang,1 Yang Liu1 1Department of General Surgery, Vascular Surgery, Shandong University Qilu Hospital, Jinan City, Shandong Province, People’s Republic of China; 2Department of General Surgery, Shandong University Qilu Hospital, Jinan City, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang LiuDepartment of General Surgery, Vascular Surgery, Shandong University Qilu Hospital, No. 107, Road Wen Hua Xi, Jinan City, Shandong Province, 250012, People’s Republic of ChinaTel +86 18560088317Email liuyang_sdu@126.comAbstract: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), has been an important cause of sudden in-hospital death. Studies have shown that the immune/inflammatory response plays an important role in the pathogenesis of vascular disease, with representative markers in the blood including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune/inflammatory index (SII), etc. However, there is a variety of immune/inflammatory indicators. Moreover, most previous studies have been single-center investigations involving one or two indicators, with varying nature of cases, number of cases and study objectives, thereby making it difficult to reach consensus conclusions with good clinical guidelines. This article reviews the clinical value of immunoinflammatory indicators for VTE based on previous studies, including the diagnostic and prognostic capabilities. In conclusion, NLR provides promising predictive capability for the onset and prognosis of VTE and deserves extensive application in clinical practice. PLR also has certain diagnostic and prognostic value, but further studies are warranted to identify its reliability and stability. Monocytes, eosinophils and platelet-related indicators show some clinical association with VTE, although the predictive capabilities are mediocre. SII is of promising potential value for VTE and deserves further investigations. This review will provide new clues and valuable clinical guidance for the diagnosis and therapy of VTE.Keywords: venous thromboembolism, immune/inflammation biomarker, diagnosis, prognosis

Guiying Jiang,1,* Xueqian Wang,1,* Ying Zhou,1 Chenming Zou,2,3 Ling Wang,1 Wei Wang,1 Danya Zhang,1 Hanjie Xu,1 Jie Li,1 Fei Li,1 Danfeng Luo,1 Xiangyi Ma,1 Ding Ma,1 Songwei Tan,2 Rui Wei,1 Ling Xi1 1Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 2Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 3School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Xi; Rui WeiDepartment of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People’s Republic of ChinaTel/Fax +86 27 83662688Email lxi@tjh.tjmu.edu.cn; weirui2018@tjh.tjmu.edu.cnBackground and Purpose: Cisplatin–paclitaxel (TP) combination chemotherapy as the first-line therapy for numerous cancers is hindered by its inadequate accumulation in tumors and severe side effects resulting from non-specific distribution. The aim of this study is to explore whether TMTP1-modified, cisplatin and paclitaxel prodrugs co-loaded nanodrug could improve cervical cancer chemotherapy and relieve its side effects through active and passive tumor targeting accumulation and controlled drug release.Methods: TDNP, with capacities of active targeting for tumors and controlled drug release, was prepared to co-deliver cisplatin and paclitaxel prodrugs. The characteristics were investigated, including the diameter, surface zeta potential, stability and tumor microenvironment (TME) dependent drug release profiles. Cellular uptake, cytotoxicity, drug accumulation in tumors, antitumor effects and safety analysis were evaluated in vitro and in vivo.Results: The oxidized cisplatin and the paclitaxel linked to the polymer achieved a high loading effciency of over 80% and TME-dependent sustained drug release. Moreover, TMTP1 modification enhanced cellular uptake of TDNP and further improved the cytotoxicity of TDNP in vitro. In vivo, TDNP showed an extended blood circulation and increased accumulation in SiHa xenograft models with the aid of TMTP1. More importantly, TDNP controlled tumor growth without life-threatening side effects.Conclusion: Our study provided a novel TP co-delivery platform for targeted chemotherapy of cervical cancer, which was promising to improve the therapeutic effcacy of TP and may also have application in other tumors.Keywords: TME-responsive, targeted co-delivery, combined chemotherapy, cervical cancer

Da Ma, Zhi-Guang Yao, Yan-Ping Guo, Rui-Fa Wu Department of Pediatric General Surgery, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, 523000, People’s Republic of ChinaCorrespondence: Da MaDepartment of Pediatric General Surgery, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of ChinaTel/Fax +86 769-86186253Email mada66_doc@163.comObjective: Cryptorchidism is the most common congenital disability and is defined as the absence of one or both testicles in the scrotum during fetal development. In patients with cryptorchidism, lowered serum inhibin B levels suggest testicular dysfunction. The practical application of serum inhibin B levels in childhood remains controversial. The purpose of this study was to observe the post-operational changes of serum inhibin B levels in patients with cryptorchidism and provide evidence that serum inhibin B is a potential marker for the efficacy of testicular surgery.Methods: A total of 83 male children with cryptorchidism were enrolled in this study. All the children had blood samples taken by venipuncture on the day of surgery. The serum inhibin B levels in the blood samples were measured using an ELISA kit. Paired t-tests were used to assess differences between the groups.Results: The results show that, compared with the preoperative values, there was a statistically significant increase in serum inhibin B values one month after the operation in each group (P < 0.05). Compared with the one-month post-operation results, there were no significant changes six months after operation in each group (P> 0.05). However, serum inhibin B values decreased significantly in all groups at 12 months post-operation (P < 0.05), suggesting that serum inhibin B values are significantly correlated with age. Correlation analysis showed that serum inhibin B was negatively correlated with age from 6 to 36 months, and the correlation coefficient was − 0.488.Conclusion: Serum inhibin B can be used as a short-term evaluation index of cryptorchidism surgery rather than as a long-term indicator.Keywords: serum inhibin B, children, cryptorchidism surgery

Melanaphis sacchari is a cosmopolitan pest that causes losses in sorghum crops, so new management methods are needed. In addition, the type of fertilization used influences plant compositions and pest infestation, and allelochemicals are a promising method for the possible management of M. sacchari. In this work, we measured the preference of M. sacchari through chemical stimuli towards sorghum plants grown under greenhouse conditions without fertilization (F0), conventional fertilization (CF), and organic fertilization (OF). Leaves were collected from sorghum plants fertilized with 200 kg N ha−1 using ammonium sulfate and poultry manure. Extracts were obtained using Soxhlet extraction, and the compounds were identified using a gas chromatograph coupled with mass spectrometry (GC-MS). Sorghum extracts were individually tested through bioassays to determine M. sacchari preference. The abundance and number of compounds in sorghum differed depending on the type of fertilization used. M. sacchari showed a preference for the extract from CF sorghum plants (76.66%) over the extract from OF plants (23.34%). Therefore, the type of fertilization can be used as a tactic to prevent higher infestations of M. sacchari. The biological activity of the compounds identified here with M. sacchari should be determined for future pest management strategies using allelochemicals, given that the sugarcane aphid uses chemical signals to locate its host plant. [ABSTRACT FROM AUTHOR]

Bin Zheng,1,* Yakun Yang,1,* Jinghan Li,1 Jing Li,1 Saijie Zuo,1 Xi Chu,2 Shan Xu,3 Donglai Ma,1 Li Chu1,4 1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Hebei Province Hospital of Chinese Medicine, Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donglai Ma; Li ChuSchool of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of ChinaTel/Fax +86 311 89926719Email mdl_hebei@aliyun.com; chuli0614@126.comPurpose: Magnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through anti-inflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism.Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection.Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased.Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.Keywords: magnesium isoglycyrrhizinate, arsenic trioxide, cardiotoxicity, Nrf2, TLR4/NF-κB

Qingli Cui, Yanhui Hu, Dongyang Ma, Huaimin Liu Department of Integrated Traditional and Western Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People’s Republic of ChinaCorrespondence: Huaimin LiuDepartment of Integrated Traditional and Western Medicine, The Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, People’s Republic of ChinaEmail huaiminliu@sina.comObjective: Anlotinib, an oral small-molecular tyrosine kinase inhibitor (TKI) on tumor angiogenesis and growth, has a wide spectrum of inhibitory effects on targets such as vascular endothelial growth factor receptors 2/3 (VEGFR2/3), etc. The efficacy and safety of anlotinib in the treatment of platinum-resistant or platinum-refractory ovarian cancer were evaluated.Patients and Methods: Patients with platinum-resistant or platinum-refractory ovarian cancer that treated with anlotinib in the Affiliated Cancer Hospital of Zhengzhou University from May 2018 to March 2020 were included. Medical records were reviewed in terms of objective response, survival outcomes, and safety.Results: A total of 38 patients were analyzed. The median progression-free survival and the median overall survival were 7.7 months (95% CI: 6.7– 8.7) and 16.5 months (95% CI: 13.3– 19.7), respectively. About 17 patients received anlotinib monotherapy, and the median progression-free survival was 7.7 months (95% CI: 6.3– 9.1). A total of 19 cases received anlotinib plus chemotherapy with a median progression-free survival of 8.0 months (95% CI: 4.8– 11.2). A total of 2 cases received anlotinib plus anti-PD-1 antibody pembrolizumab, and 1 case had partial response, the other progressive disease. The objective response rate was 42.1% while the disease control rate was 86.8%. A total of 5 patients experienced dose reduction from 12 mg to 10 mg because of adverse effects. The most common adverse effects were hypertension (31.6%), fatigue (28.9%), anorexia (26.3%) and hand-foot syndrome (23.7%). No treatment-related deaths were recorded.Conclusion: Anlotinib produced moderate improvements in progression-free survival and overall survival in patients with platinum-resistant or platinum-refractory ovarian cancer. It indicates that anlotinib maybe a new treatment option for patients with platinum-resistant or platinum-refractory ovarian cancer.Keywords: angiogenesis, anlotinib, ovarian cancer, platinum-resistant

Luoning Gou,1,* Ming Xiang,2,* Xiao Ran,3,* Fen Wang,1 Shujun Zhang,1 Shusheng Li,3 Kun Dong,1 Xi Chen,1 Yangxin Huang,4 Chengzhen Meng,2 Qian Fan,2 Yan Yang,1 Xuefeng Yu,1 Delin Ma,1 Ping Yin2 1Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4College of Public Health, University of South Florida, Tampa, Florida, The United States*These authors contributed equally to this workCorrespondence: Ping Yin; Delin MaTongji Medical College, Huazhong University of Science and Technology, 13 Hongkong Road, Wuhan, 430030 Hubei, People’s Republic of ChinaTel + 86-27-83692832Fax +86-27-83692333Email pingyin2000@126.comDelin Ma Email maderine4@163.comPurpose: Recently, a cluster of pneumonia caused by SARS-CoV-2 were identified in Wuhan and spread throughout the world. More information about risk factors for mortality of critically ill patients infected with SARS-CoV-2 remain to be evaluated.Methods: We included adult patients confirmed with SARS-CoV-2 infection who were critically ill and admitted to the intensive care unit (ICU) of Tongji Hospital in Wuhan from Feb 4, 2020 to Feb 20, 2020. Data were collected and compared between patients who died and improved. Logistic regression was used to explore the risk factors for death of SARS-CoV-2-infected critically ill patients.Results: A total of 160 critically ill patients with SARS-CoV-2 infection were included, of which 146 patients with appeared outcomes were included into the final analysis. The random blood glucose, serum sodium and effective plasma osmolarity were higher in deceased patients, especially in patients with diabetes. There were 7 patients with diabetes with hyperosmolar status and all of them were deceased. Multivariable regression revealed that older age (odds ratio 4.28, 95% CI 1.01– 18.20; p = 0.049), higher C-reactive protein (odds ratio 1.01, 1.00– 1.03; p = 0.024), higher interleukin-6 (odds ratio 1.01, 1.00– 1.03; p = 0.0323), and d-dimer greater than 1 μg/mL (odds ratio 1.10, 1.01– 1.20; p = 0.032) at admission were associated with increased odds of death.Conclusion: In conclusion, hyperosmolarity needs more attention and may contribute to mortality in critically ill patients with COVID-19, especially in those with diabetes. Older age, inflammatory response, and thrombosis may be risk factors for death of critically ill patients with SARS-CoV-2 infection.Keywords: SARS-CoV-2, critically ill, hyperosmolarity, diabetes, risk factors, mortality

Xin Zheng,1,2,* Yun Chen,3,* Danyan Ma,4 Mulin Zhang,1,2 Yinxiang Huang,1,2 Meifeng Tong,1,2 Bing Yan,1,2 Shaowei Lin,5 Xiaohong Yan,6 Changqin Liu1– 3 1Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; 2Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen Clinical Medical Center for Endocrine and Metabolic Diseases, Xiamen, China; 3The School of Clinical Medicine, Fujian Medical University, Fuzhou, China; 4School of Medicine, Xiamen University, Xiamen, China; 5Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China; 6Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China*These authors contributed equally to this workCorrespondence: Changqin LiuDepartment of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaTel +86-592-2137796Fax +86-592-2137189Email liuchangqin@xmu.edu.cnXiaohong YanReproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, ChinaTel +86-592-2662318Fax +86-592-2662318Email xmyxh1224@sina.comObjective: The aim of the present study was to investigate the possible correlation between the percentage of daily energy intake from fat (PEF) with insulin resistance (IR) in women with polycystic ovary syndrome (PCOS).Methods: In this cross-sectional study, a total of 186 females with PCOS were screened. Daily dietary intake data were collected by a trained nutritionist using the 24-h dietary recall method over three consecutive days. A total of 111 subjects who had complete data were divided into two groups based on the percentage of daily energy intake from fat (PEF): the normal PEF (NPEF) group (PEF < 30%) and the high PEF (HPEF) group (PEF ≥ 30%). Pearson’s correlation analysis and stepwise multivariate linear regression analysis were used to analyze the correlation of PEF with homeostasis model assessment of insulin resistance (HOMA-IR).Results: The total prevalence rate of overweight/obesity was 80.2%. There were significant differences in waist circumference (WC), body mass index (BMI), fasting insulin, and HOMA-IR (P < 0.001) among the normal weight, the overweight, and the obese groups, but no significant differences were observed in total energy and dietary macronutrients intake in the three groups. The daily intake of fat and protein, fasting insulin, and HOMA-IR in the NPEF group were significantly higher than those in the HPEF group. Pearson’s correlation analysis showed PEF in PCOS women was negatively correlated with BMI (r= − 0.189, p=0.047) and HOMA-IR (log-transformed) (r= − 0.217, p=0.022). Further, stepwise multivariate linear regression analysis showed PEF was negatively correlated with HOMA-IR (p< 0.05).Conclusion: The percentage of daily energy intake from fat is negatively correlated with IR in women with PCOS.Keywords: the percentage of daily energy intake from fat, polycystic ovary syndrome, insulin resistance, daily dietary intake, obesity