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Lina Du,1 Dezhi Yang,2 Lan Wu,1 Li Mei,1 Sarula Wu,1 Yasula Ba,1 Yongchang Bao,1 Rigugaqiqige Su,1 Lin Song1 1College of Mongolian Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Innovative Mongolian Medical Engineering Research Center, Inner Mongolia International Mongolian Hospital, Hohhot, Inner Mongolia, People’s Republic of ChinaCorrespondence: Lin Song, Inner Mongolia Medical University, Tel +15849163188, Email songlinwpsword@163.comObjective: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia.Methods: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot.Results: The weights of the insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses.Conclusion: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse. Keywords: Mongolian medicine sugemule-4 decoction, insomnia, metabolomics, gut microbiota, network pharmacology, molecular mechanism

Abstract The academic literature on personal experiences of climate-induced wellbeing erosion (often conceptualised as ‘non-economic losses and damages’) is still limited. This represents a serious climate policy gap that hinders support for marginalised people across the world including Indigenous People. Lately, we have seen a rapid growth in empirical studies exploring linkages between climate change and mental health among Indigenous Inuit in Canada. However, its association with human (im)mobility remains unexplored. This review article brings together the empirical evidence of Inuit experiences and perceptions of climate-related wellbeing loss and (im)mobility while providing climate policy with guidance for appropriate action. The systematic review investigates how Inuit in Arctic Canada felt that climatic changes impacted their (im)mobility and mental health while putting these feelings into a wider context of colonial violence, forced child removal, the residential schools, and other systematic human rights abuses. Twelve electronic databases (four specific to Arctic research) were searched for English and French, peer reviewed, qualitative studies published between 2000 and 2021. Fifteen selected articles were analysed using NVivo and thematic narrative analysis from a climate-violence-health nexus systems approach. Three overarching climate-related wellbeing loss themes, all strongly intertwined with feelings of immobility, emerged from the literature namely ‘identity and cultural loss’, ‘land connection as a source of healing’, and ‘changing environment triggering emotional distress’. The narratives circled around Inuit land connection and how climate-induced temporary (im)mobility interrupted this relationship. Climatic changes isolated Inuit away from the land and cut off their ability to partake in land activities. This strongly eroded Inuit wellbeing, expressed through distress, anxiety, depression, social tension, suicide ideation and deep feelings of cultural loss. The findings showed how Inuit mental health strongly depend on a sustained connection to the land. Further empirical research among other Indigenous People or nomadic groups on wellbeing loss and climate-induced involuntary immobility is urgently needed. Future research should particularly explore how such mental health impacts tie into past and present (post)colonial traumas and current suicide occurrences. This will help climate policy, research, and adaptation planning better prepare and propose more contextually and culturally appropriate health actions in the future.

Yufei Liang,1 Lina Mei,2 Qipeng Ning,2 Jiao Zhang,2 Jingying Fei,3 Jie Dong1 1Department of Gynaecology and Obstetrics, Huzhou Maternity & Child Health Care Hospital, Huzhou, People’s Republic of China; 2Department of Digestive, Huzhou Maternity & Child Health Care Hospital, Huzhou, People’s Republic of China; 3Department of Ultrasound, Huzhou Maternity & Child Health Care Hospital, Huzhou, People’s Republic of ChinaCorrespondence: Jie Dong, Department of Gynaecology and Obstetrics, Huzhou Maternity & Child Health Care Hospital, No. 2 East Street, Wuxing District, Huzhou City, Zhejiang Province, People’s Republic of China, Email 94276941@qq.comBackground: Endometriosis involves the intestine, and its clinical manifestations are nonspecific and lack of etiological manifestations. The diagnosis is difficult, which often leads to misdiagnosis. We report a case of endometriosis which was misdiagnosed as intestinal malignant tumor after colonoscopy and three biopsies.Case Presentation: We reported a 42-year-old woman who went to see a doctor because of anal distension. She was examined by three gastrointestinal endoscopists at different levels in different hospitals and underwent biopsy at the same time. Combined with clinical manifestations, imaging examination, endoscopic examination and pathological examination, she was misdiagnosed as intestinal malignant tumor, and partial intestinal resection was performed according to the surgical principle of malignant tumor.Conclusion: Although there are advanced gastrointestinal endoscopy and imaging techniques, intestinal endometriosis is still easy to be misdiagnosed. As our case report shows, after three colonoscopy and biopsy, it is still misdiagnosed as intestinal malignant tumor. Further research is needed to improve the ability of preoperative diagnosis, which deserves the attention of gastroenterologists and obstetricians and gynecologists.Keywords: endometriosis, intestinal malignant tumor, colonoscopy

Prodromal symptoms of Autism Spectrum Disorder (ASD) have been detected within the first year of life. This review evaluated evidence from randomized controlled trials (RCTs) of parent-mediated interventions for infants under 24 months who are at risk for ASD. Electronic databases, including grey literature, were searched up till November 2019. Seven RCTs were identified. There was substantial heterogeneity in recruitment, outcome measures and effect size calculations. Interventions did not reduce the risk of later ASD diagnosis and post-intervention effects on infant outcomes were inconsistent, with five studies reporting significant improvements across both treatment and control groups. Moderate level of evidence of intervention effects on parental interaction skills and the small number of RCTs, and significant limitations restrict generalizability across studies.

Prodromal symptoms of Autism Spectrum Disorder (ASD) have been detected within the first year of life. This review evaluated evidence from randomized controlled trials (RCTs) of parent-mediated interventions for infants under 24 months who are at risk for ASD. Electronic databases, including grey literature, were searched up till November 2019. Seven RCTs were identified. There was substantial heterogeneity in recruitment, outcome measures and effect size calculations. Interventions did not reduce the risk of later ASD diagnosis and post-intervention effects on infant outcomes were inconsistent, with five studies reporting significant improvements across both treatment and control groups. Moderate level of evidence of intervention effects on parental interaction skills and the small number of RCTs, and significant limitations restrict generalizability across studies., Author(s): Mei L. Law [sup.1] [sup.2] , Jatinder Singh [sup.1] [sup.2] , Mathilde Mastroianni [sup.1] [sup.2] , Paramala Santosh [sup.1] [sup.2] Author Affiliations: (1) grid.13097.3c, 0000 0001 2322 6764, Department [...]

Background: Neglected Tropical Diseases (NTDs) disproportionately affect marginalised groups within impoverished communities, conferring devastating physical, financial and psychosocial effects. Skin-NTDs (SNTDs) are uniquely stigmatising due to their visible nature, rendering affected individuals vulnerable to psychosocial risk and the associated decline in social participation, quality of life and mental health. In response to knowledge gaps identified by current global efforts for integrated control of SNTDs this review gathers existing evidence on the psychosocial effects of SNTDs, with consideration given to the influence of gender. Methods: The study protocol is registered with PROSPERO (CRD42022336676). Data was collected from Embase, Global Health, Medline and Web of Science, with additional articles identified through Google Scholar and bibliography tracking. Qualitative studies published in English between 2005 and 2024 reporting men's and women's experiences with SNTDs were searched. Appropriate data from each included study were inputted into NVivo software to facilitate thematic synthesis. Descriptive and analytic themes were generated through line-by-line coding using an inductive approach. Results: 27 articles of high and moderate quality were included. They pertained to buruli ulcer, cutaneous leishmaniasis, leprosy, lymphatic filariasis, tungiasis, onchocerciasis, schistosomiasis and podoconiosis. Men and women across SNTDs and contexts reported debilitating physical symptoms which impaired their ability to work, socialise and carry out usual daily activities. Some felt (at least initially) well supported by partners and relatives, whereas most experienced avoidance, abandonment and even violence, with women incurring worse SNTD-related social consequences. Many men and most women experienced stigma, with discriminatory behaviours largely attributed to fear of infection, decreased ability to perform gender-specific daily activities, and the perceived association between SNTDs and sinfulness. Self-reported impacts of SNTDs on men's and women's mental wellbeing included low mood, anxiety, low self-esteem, and suicidal ideation. Disease-specific knowledge, early treatment, social support, and disease acceptance were mentioned as protective factors. Conclusion: SNTDs cause significant psychosocial harms, particularly for women. Implementing myth-busting and contact-based educational campaigns and improving access to treatment and to livelihood opportunities and social protection schemes for men and women with a SNTD will help prevent and mitigate these. Author summary: Neglected Tropical Diseases (NTDs) mostly affect marginalised groups in deprived communities, and are known to have harmful physical, financial, social, and mental health consequences. Skin-NTDS (SNTDs) are particularly damaging because they are noticeable, rendering the affected individuals vulnerable to discrimination. This systematic review of the published literature aims to understand the socio-economic and emotional effects of SNTDs and how these are influenced by individuals' gender. Our review includes 27 studies. Men and women experience physical suffering which reduces their ability to work, socialise, and carry out usual daily activities. Some feel well supported by partners, friends, and family, at least initially, while most are avoided, abandoned, and even suffer from verbal and physical violence, particularly women. The reported impacts of SNTDs on individuals' emotional wellbeing include low mood, anxiety, low self-esteem, and suicidal thoughts. Early treatment, disease knowledge, social support networks, and disease acceptance were mentioned as protective factors. We conclude that SNTDs increase individuals' psychosocial suffering, with women being particularly at risk. Ensuring treatment access and socio-economic support for men and women with SNTDs and developing culturally appropriate educational interventions designed to foster more positive attitudes towards people with SNTDs will help prevent and reduce these harms. [ABSTRACT FROM AUTHOR]

Lin Mei,1,* Xiaodan Li,1,* Shengcai Wang,1,* Run Si,2 Tingting Ji,1 Zhifei Xu,3 Yun Peng,4 Yue Liu,4 Hongbin Li,1 Jie Zhang,1 Yongli Guo,5 Jinghong Tian,6 Guifei Zhou,2 Huifang Huang,2 Jun Tai,1,7,* Jiangang Liu,8,9 Xin Ni1 1Department of Otolaryngology, Head and Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2School of Computer and Information Technology, Beijing Jiaotong University, Beijing, People’s Republic of China; 3Department of Respiration, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing, People’s Republic of China; 4Department of Radiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, People’s Republic of China; 6Department of Neurorehabilitation, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 7Department of Otorhinolaryngology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 8Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 9Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiangang LiuBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail jgliu@buaa.edu.cnXin NiDepartment of Otolaryngology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishilu, Beijing, People’s Republic of ChinaTel +86-139-1011-1999Email nixin@bch.com.cnObjective: To investigate the impacts of obstructive sleep apnea (OSA) on white matter (WM) integrity and cognitive functions of pediatric patients with different levels of OSA severity.Methods: Fifty-eight children with OSA and thirty-four healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) examination, polysomnography (PSG), and neurocognitive assessments. Patients were divided into mild OSA (MG) and moderate-severe OSA (SG) groups. WM integrity, PSG data, and neurocognitive assessment scores were compared among those groups.Results: For apnea hypopnea index (AHI), obstructive apnea hypopnea index (OAHI), arousal index, SpO2 nadir, and attention, SG was worse than both MG and HC with MG worse than HC. For baseline SpO2 and intelligence, SG was worse than both MG and HC with no significant difference between MG and HC. Impaired WM integrity was observed in bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, right superior longitudinal fasciculus, right hippocampus, left cingulate gyrus, right uncinate fasciculus, callosum forceps major, and callosum forceps minor only for SG than for HC. WM integrity was significantly correlated with OSA severity and neurocognitive assessment scores only for SG, but not for MG.Conclusion: Decreased baseline SpO2, WM impairment, and intelligence decline were all observed only for SG, but not for MG, implying an associated relationship among decreased SpO2, WM impairment and WM impairment. Thus, for SG, additional assessments of brain damage and cognitive function decline are needed for prognostic evaluation of OSA.Keywords: diffusion tensor imaging, obstructive sleep apnoea, children, tract-based spatial statistics, white matter

Adlay (Coix lacryma-jobi L.), a crop closed related to maize (Zea mays L.) and sorghum (Sorghum bicolor L.), originated in tropical/subtropical regions of Asia and Africa; southwest China primary center of this plant’s origin, evolution and migration. Adlay is a traditional high-value minor crop used for both medicinal and dietary purposes. Adlay has anti-tumor, anti-bacterial, anti-inflammatory, analgesic, blood sugar-lowering, and blood lipid-lowering effects. To clarify the main bioactive components and phytochemical compounds and to fully explore their utility, this review summarizes the research done on the main functional ingredients of adlay, including amino acids and proteins, oils, vitamins and minerals, polysaccharides, and polyphenols. This study also highlighted the application of genome sequencing to tailor nutrient-rich adlay cultivars and nutraceutical product development. Additionally, the acquisition of high-density genomic data combined with next-generation phenotypic analysis will undoubtedly improve our understanding of the potential genetic regulation of adlay nutraceutical traits. This review provides new insights and ideas for the research of adlay in comparison and evolutionary genomics, and a useful reference for molecular breeding and genetic improvement of this important minor crop.

Lingfei Hu, Yinping Liu, Chaobing Wei, Huixiang Jin, Lixin Mei, Changfan Wu Department of Ophthalmology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, People’s Republic of ChinaCorrespondence: Changfan Wu Tel +86- 13909632351Email wuchangfan1971@sohu.comAim: In the present study, we performed bioinformatics studies and in vitro functional assays to explore the underlying role of serpin family H member 1 (SERPINH1) in the diabetic retinopathy.Methods: Common differentially expressed genes (DEGs) between diabetic retinal tissues and normal retinal tissues were analyzed using Gene Expression Omnibus (GEO) database. The proliferation and migration of human retinal endothelial cells (HRECs) was evaluated by MTS, EdU and wound healing assays, respectively; the miRNA and mRNAs expression levels of hub genes in HRECs were determined using quantitative real-time PCR (qRT-PCR). Protein levels were determined using a Western blot assay.Results: A total of 189 common DEGs were screened between two GEO datasets (GSE60436 and GSE94019), and ten potential hub genes that may link to the progression of diabetic retinopathy were detected. The qRT-PCR results showed that collagen, type I, alpha 1 (COL1A1), Collagen, type I, alpha 2 (COL1A2) and serpin family H member 1 (SERPINH1) mRNA expression levels were up-regulated in the HRECs after being exposed to high glucose for 48 h. Silence of SERPINH1 repressed the high glucose-induced increase in proliferation and migration of HRECs. SERPINH1 was a target of miR-29b and was suppressed by miR-29 in HRECs. SERPINH1 overexpression promoted HREC proliferation and migration. Furthermore, miR-29b suppressed HREC proliferation and migration under high-glucose stimulation, which was significantly attenuated by enforced expression of SERPINH1.Conclusion: In conclusion, by performing the integrated bioinformatics analysis, the present study suggested that 3 hub genes (COL1A1, COL1A2 and SERPINH1) may be associated with diabetic retinopathy pathophysiology. Further mechanistic studies indicated that miR-29b/SERPINH1 signaling participated in high glucose-induced enhancement in the proliferation and migration of HRECs.Keywords: diabetic retinopathy, bioinformatics analysis, HRECs, SERPINH1, proliferation, migration

Abstract Background Cutaneous leishmaniasis (CL), endemic in Guatemala, mostly affects poor people living in the northern region. A national control program that includes surveillance, diagnose, and treatment offered free of cost by the Ministry of Health (MoH) has been in place since 2003. However, the incidence is increasing and treatment rates are not optimal, suggesting that current efforts are not being effective. This study aimed to understand barriers and facilitators of CL control in Guatemala as experienced and perceived by key stakeholders in order to comprehend what works well and does not and suggest evidence-informed interventions. Methods The study was conducted in the Cobán municipality, the most endemic of Guatemala, situated in the Department of Alta Verapaz. Data were collected during May and June 2019 via focus groups and semi-structured interviews with key stakeholders, including local and national health personnel and residents of four communities of the endemic region. Thematic and content analysis of the collected data was conducted using NVIVO. Results Three overarching issues hamper the effectiveness of current CL efforts: resource scarcity, treatment challenges, and knowledge-action gaps. Scarce economic resources from the MoH and community residents negatively impact incidence, detection of cases and treatment rates in that preventive action is insufficient and healthcare access is low. In addition, local health workers often lack specialized CL training and access to the national CL control guidelines. With regards to the population living in the study area, misunderstanding of disease causation, shame associated with CL lesions, treatment pain fear, and long (often uncertain) waiting times for diagnose and treatment negatively affect people’s willingness to seek help, treatment adherence, and their trust on the healthcare provided. Conclusions Culturally sensitive CL preventive action must be developed. Given the scarce economic resources available for CL control in the country, the involvement of trained community health workers and the inclusion of thermotherapy as a treatment option is also advised. Other cost-effective actions include: ensuring all health workers receive CL training and have access to national CL control guidelines, improving national procurement system to avoid treatment shortages, and provision of motorized vehicles to increase active surveillance and treatment rates. Graphical abstract

Although behavioral and neuropsychological studies have suggested two distinct routes of phonological access, their neural substrates have not been clearly elucidated. Here, we designed an artificial language (based on Korean Hangul) that can be read either through addressed (i.e., whole word mapping) or assembled (i.e., grapheme-to-phoneme mapping) phonology. Two matched groups of native English-speaking participants were trained in one of the two conditions, one hour per day for eight days. Behavioral results showed that both groups correctly named more than 90% of the trained words after training. At the neural level, we found a clear dissociation of the neural pathways for addressed and assembled phonologies: There was greater involvement of the anterior cingulate cortex, posterior cingulate cortex, right orbital frontal cortex, angular gyrus and middle temporal gyrus for addressed phonology, but stronger activation in the left precentral gyrus/inferior frontal gyrus and supramarginal gyrus for assembled phonology. Furthermore, we found evidence supporting the strategy-shift hypothesis, which postulates that, with practice, reading strategy shifts from assembled to addressed phonology. Specifically, compared to untrained words, trained words in the assembled phonology group showed stronger activation in the addressed phonology network and less activation in the assembled phonology network. Our results provide clear brain-imaging evidence for the dual-route models of reading. © 2014 Mei et al.

Cong Hao,1–3 Xuewen Wu,1–3 Ruoyu Zhou,1–3 Hao Zhang,1,2 Yulai Zhou,1,2 Xinxing Wang,1,2 Yong Feng,1–3 Lingyun Mei,1–3 Chufeng He,1–3 Xinzhang Cai,1–3 Lisha Wu1–3 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital Central South University, Changsha 410008, Hunan, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha 410008, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of ChinaCorrespondence: Lisha WuDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital Central South University, Changsha 410008, Hunan, People’s Republic of ChinaEmail ENTLisaWu@163.comBackground: p66Shc, a Src homologue and collagen homologue (Shc) adaptor protein, mediates oxidative stress signaling. The p66Shc-null mice have increased lifespan and enhanced resistance to oxidative stress. Studies have also indicated its potential role in inner ear aging, which can lead to deafness.Objective: The aim of this study was to determine the effects of p66Shc down-regulation on the marginal cells (MCs) of the inner ear stria vascularis.Methods: Primary MCs were isolated from neonatal rats and treated with glucose oxidase to induce oxidative stress. The cells were transduced with adenovirus expressing siRNA, and the knockdown was verified by Western blotting. The reactive oxygen species (ROS) levels and apoptosis were analyzed using the DCFH-DA probe and Annexin-V/7-AAD staining respectively. The ultrastructure of the differentially-treated cells was examined by transmission electron microscopy (TEM).Results: The in vitro oxidative stress model was established successfully in rat MCs. Knockdown of p66Shc alleviated the high ROS levels and apoptosis in the glucose oxidase-treated cells. In addition, glucose oxidase significantly increased the number of peroxisomes in the MCs, which was decreased by p66Shc inhibition.Conclusion: Oxidative stress increases p66Shc levels in the marginal cells of the inner ear, which aggravates ROS production and cellular injury. Blocking p66Shc expression can effectively reduce oxidative stress and protect the MCs.Keywords: p66Shc, marginal cells of stria vascularis, oxidative stress, peroxisome