Cryo-EM Structure Reveals Polymorphic Ligand-bound States of IGF1R.

Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in regulating cellular metabolism and cell growth and has been identified as an anticancer drug target. Although previous studies have revealed some structures of IGF1R with different ligands, the continuous dynamic conformation change remains unclear. Here, we report 10 distinct structures (7.9-3.6 Å) of IGF1R bound to IGF1 or insulin to reveal the polymorphic conformations of ligand-bound IGF1R. These results showed that the α-CT2, disulfide bond (C670-C670'), and FnIII-2 domains had the most flexible orientations for the conformational change that occurs when ligands bind to the receptor. In addition, we found one special conformation (tentatively named the diverter-switch state) in both complexes, which may be one of the apo-IGF1R forms under ligand-treatment conditions. Hence, these results illustrated the mechanism of how different ligands could bind to human IGF1R and provided a rational template for drug design.

Nurses' experiences regarding shift patterns in isolation wards during the COVID-19 pandemic in China: A qualitative study.

AIM AND OBJECTIVE: To explore nurses' experiences regarding shift patterns while providing front-line care for COVID-19 patients in isolation wards of hospitals in Shanghai and Wuhan during the novel coronavirus pandemic. Our findings will help to optimise shift work scheduling, use the existing nursing workforce more efficiently and improve nursing quality. BACKGROUND: Nurses are one of the main professionals fighting against COVID-19. Providing care for COVID-19 patients is challenging. In isolation wards, the workload has increased, and the workflow and shift patterns are completely different from the usual. More importantly, there is a shortage of nurses. Therefore, it is essential and urgent to arrange nurses' shifts correctly and use the existing workforce resources efficiently. DESIGN: A qualitative descriptive study of 14 nurses in Chinese hospitals was conducted. METHODS: Semi-structured interviews were used based on the phenomenological research method; data were analysed using Colaizzi's method of data analysis. This study aligns with the COREQ checklist. RESULTS: Four themes were extracted: assess the competency of nurses to assign nursing work scientifically and reasonably, reorganise nursing workflow to optimise shift patterns, communicate between managers and front-line nurses to humanise shift patterns, and nurses' various feelings and views on shift patterns. CONCLUSION: It is necessary to arrange shift patterns scientifically and allocate workforce rationally to optimise nursing workforce allocation, reduce nurses' workload, improve nursing quality and promote physical and mental health among nurses during the COVID-19 pandemic. RELEVANCE TO CLINICAL PRACTICE: This study emphasised nurses' experiences on shift patterns in isolation wards, providing useful information to manage shift patterns. Nursing managers should arrange shifts scientifically, allocate nursing workforce rationally, formulate emergency plans and establish emergency response rosters during the COVID-19 pandemic.

RNA sequencing of exosomes revealed differentially expressed long noncoding RNAs in early-stage esophageal squamous cell carcinoma and benign esophagitis.

Aim: To explore the roles of exosomal long noncoding RNAs (lncRNAs) in early-stage esophageal squamous cell carcinoma (ESCC) and benign esophagitis. Materials & methods: Exosomal lncRNAs were analyzed using RNA-seq and validated by quantitative real-time PCR, loss-of-function, co-culture and RNA pulldown assays. Results: Exosomal lncRNAs displayed tighter tissue-specificity, higher expression level and lower splicing efficiency than that of mRNAs. A total of 152 exosomal lncRNAs were differentially expressed between ESCC and controls. A total of 124 exosomal lncRNAs were dysregulated between ESCC and esophagitis. Knockdown of 13 ESCC-associated lncRNAs modified proliferation, migration, and apoptosis of ESCC cells. A novel lncRNA RP5-1092A11.2 was highly expressed in ESCC-derived exosomes, ESCC cells and tumor tissues. Exosomes released from RP5-1092A11.2-knockdown cells inhibited ESCC cell proliferation. Conclusion: Dysregulated exosomal lncRNAs were functionally associated with different disease status in esophagus.

The Effectiveness of Electrical Acupuncture Stimulation in Reducing Levels of Self-reported Anxiety of Lung Cancer Patients during Palliative Care: A Pilot Study.

BACKGROUND: Lung cancer is a serious threat to human health and life worldwide. Anxiety is common amongst palliative care patients with lung cancer and adversely affects quality of life. Acupuncture is an effective and safe treatment method used for the treatment of depressive mood status. We aimed to assess the influence of electrical acupuncture stimulation on self-reported anxiety in palliative care among patients with lung cancer. METHODS: This pilot study had an experimental, 3-group, research plan. A total of 188 participants were enrolled from the Shanghai Pulmonary Hospital, Tongji University, Shanghai, China from 2014-2015. This pilot study had an experimental, 3-group, research plan. In TEAS group, participants received standardized palliative care and electrical acupuncture stimulation in Zusanli, Sanyinjiao and Hegu acu-points. Group MS received standardized palliative care and muscle stimulation nearby nonacupoint. Controlled group received standardized palliative care. The patients maintained their assigned acupuncture stimulation for 7 days. Demographic Instrument, Karnofsky Performance Scale Index, SF-16 health questionnaire and Self-Rating Anxiety Scale (SAS) were used. RESULTS: The mean SAS scores in TEAS Group before and after electrical intervention in palliative care intervention were 31.17±7.55,34.58±13.98 and 27.86±6.73, (P=0.00) QoL score showed elevation from 57.13 in 8th day to 60.12 in 28th day, rising further to 5%. Comfort Score showed continuous elevation trend for 28 days. CONCLUSION: Electric acupuncture stimulation could reduce the anxiety of patients, promote rehabilitation and increase the quality of life among patients with lung cancer in palliative care.

Transcutaneous electrical acupoint stimulation (TEAS) relieved cancer-related fatigue in non-small cell lung cancer (NSCLC) patients after chemotherapy.

BACKGROUND: To explore the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) approach on cancer-related fatigue (CRF) in non-small cell lung cancer (NSCLC) chemotherapy patients. METHODS: A total of 162 participants who treated with gemcitabine combined with platinum-based drugs (GP chemotherapy) were randomly assigned to three groups: Control (Group A, n=56), Sham TEAS (Group B, n=49), and TEAS (Group C, n=57). The following acupoints were used in this study: Qihai (CV6), Keshu (UB17), and Zusanli (ST36). The Revised Piper Fatigue Scale (RPFS) were used to measure CRF on the day before chemotherapy (P1), days 8 (P2) and 28 (P3) separately. The Differences among three groups were analyzed. RESULTS: At the 28th day, the outcomes of the fatigue scores for Group C, Group B and Group A were 2.06±0.90, 2.80±1.34, 3.00±1.29 respectively. There were significantly different among three groups (F=9.784, P<0.01). At the 28th day, the outcomes of the affective fatigue (F=8.161, P<0.01), sensory fatigue (F=3.06, P=0.05) and cognitive fatigue (F=8.06, P<0.01) for Group C, Group B and Group A were significantly different among three groups. CONCLUSIONS: Chemotherapy may increase the fatigue from P1 to P2 and P3 in NSCLC patients. And TEAS could help to relived CRF, especially at P3.

Self-reported depression among patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is a disease with a poor prognosis and psychological impact. Lung cancer causes both physical and psychological burdens on patients, and financial burdens on families and society. The aim of this study was to examine the relationship between depression and influencing factors in non-small-cell lung cancer (NSCLC) patients. METHODS: A quantitative study was applied. Data was obtained from the Shanghai Pulmonary Hospital in China. One hundred and four patients with NSCLC were surveyed. Self-rating depression scale (SDS), social support rating scale (SSRS), and visual analog scale (VAS) were used. RESULTS: Among the 104 patients, 48 (46.1%) were diagnosed with depression. Gender (P = 0.000), disease duration (P = 0.006), self-care ability (P = 0.004), and pain (P = 0.003) were statistically significant predictors of self-reported depression in non-small-cell lung cancer patients. CONCLUSIONS: Self-reported depression is highly prevalent in NSCLC patients. In addition, gender, disease duration, self-care ability, pain and social support may increase self-reported depression.

Mechanism study of chitosan on lipid metabolism in hyperlipidemic rats.

It has been reported that plasma and liver cholesterol concentrations decrease when animals are fed with chitosan, but the mechanism is unclear. Four wk old male SD (Sprague-Dawley) rats were fed a commercial rat diet (cholesterol-free diet, negative control, NC), cholesterol-enriched diet containing 5% of chitosan (CH) or cholesterol-enriched diet containing 5% of cellulose (CE) and 5% of lard for 12 weeks. We would investigated the effects of chitosan on plasma and liver cholesterol levels, liver weight, bile acids concentrations of fecal and hepatic LDL receptor mRNA expression. The results showed that chitosan could decrease levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) in plasma (p<0.05), and TC, total triglyceride (TG) in liver (p<0.05), and increase fecal bile acids excretion (p<0.05), but the levels of TG and HDL-C in plasma was unchanged (p>0.05). In addition, the result of RT-PCR test showed that saturated fat and cholesterol fed could significantly induce the reduction of LDL receptor mRNA levels, while chitosan could increase hepatic LDL receptor mRNA levels. This study suggested that chitosan improve lipid metabolism by regulating TC and LDL-C by upregulating of hepatic LDL receptor mRNA expression, increasing the excretion of fecal bile acids.