A new TROP2-targeting antibody-drug conjugate shows potent antitumor efficacy in breast and lung cancers.

Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). AE and LDP can be separated and reassembled, and the reassembled LDM possesses cytotoxicity similar to that of native LDM; this has made LDM attractive in the preparation of gene-engineering drugs. We herein firstly prepared a new fusion protein hIMB1636-LDP composed of hIMB1636 and LDP by genetic engineering. This construct showed potent binding activities to recombinant antigen with a KD value of 4.57 nM, exhibited binding to Trop2-positive cancer cells and internalization and transport to lysosomes, and demonstrated powerful tumor-targeting ability in vivo. We then obtained the antibody-drug conjugate (ADC) hIMB1636-LDP-AE by molecular reconstitution. In vitro, hIMB1636-LDP-AE inhibited the proliferation, migration, and tumorsphere formation of tumor cells with half-maximal inhibitory concentration (IC50) values at the sub-nanomolar level. Mechanistically, hIMB1636-LDP-AE induced apoptosis and cell-cycle arrest. In vivo, hIMB1636-LDP-AE also inhibited the growth of breast and lung cancers in xenograft models. Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics.

hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

Effects of recorded maternal voice on anthropometric parameters and heart rate in premature infants: A pilot randomised controlled trial.

PURPOSE: To explore the benefits of a recorded maternal voice intervention on weight, recumbent length, head circumference, and heart rate of preterm infants in the neonatal intensive care unit. METHODS: A pilot randomised controlled trial was conducted in this study. Preterm infants in the neonatal intensive care unit (N = 109) were recruited and randomly assigned to an intervention or control group. Both groups received routine nursing care, while preterm infants in the intervention group received a recorded maternal voice program of 20 min, twice daily for 21 days. Preterm infants' daily weight, recumbent length, head circumference, and heart rate were collected during the 21-day intervention. Participants' heart rate in the intervention group was also recorded once a day pre-during-after the recorded maternal voice program. RESULTS: Preterm infants in the intervention group showed a significant increase in weight (-75.94, 95% CI -108.04, -43.85, P < 0.001), recumbent length (-0.54, 95% CI -0.76, -0.32, P < 0.001), and head circumference (-0.37, 95%CI -0.56, -0.18, P < 0.001) compared with the control group. Preterm infants in the intervention group also showed significant changes in heart rate pre-during-after the recorded maternal voice program. However, no significant differences were found in the heart rate scores between the two groups. DISCUSSION: The changes in heart rate pre-during-after the intervention may help explain participants' more significant increase in weight, recumbent length, and head circumference. PRACTICE IMPLICATIONS: The recorded maternal voice intervention could be incorporated into clinical practice to promote growth and development in preterm infants in the neonatal intensive care unit. STUDY REGISTRATION: Australian New Zealand Clinical Trials Register, https://www.anzctr.org.au/; (registration number: ACTRN12622000019707).

The Relationship Between eHealth Literacy and Mental Health of Adult Workers: A Cross-Sectional Study.

The current cross-sectional study aimed to investigate eHealth literacy among adult workers in China and explore the relationship between eHealth literacy and mental health in this population. Convenience sampling was used to conduct a survey among adult workers aged 18 to 60 years. Potential participants were chosen from those who completed physical examinations at the Health Management Center of one hospital in China. Participants' eHealth literacy and mental health were assessed using the eHealth Literacy Scale, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Perceived Stress Scale. Mean scores for eHealth literacy and perceived stress were 28.39 (SD = 5.78) and 5.49 (SD = 2.61), respectively. Depression and anxiety were found in 8.2% and 10.1% of participants, respectively. Multivariate logistic regression analysis showed that a 1-point increase in eHealth literacy score was associated with a 7% decrease in depressive symptoms (odds ratio [OR] = 0.93, 95% confidence interval [CI] [0.88, 0.99]) and a 6% decrease in anxiety symptoms (OR = 0.94, 95% CI [0.89, 0.99]). Furthermore, multiple linear regression analysis showed that perceived stress decreased 0.08 points (B = -0.08, 95% CI [-0.13, -0.04]) with every 1-point increase in eHealth literacy score. Thus, eHealth literacy has the potential to reduce risk of depression, anxiety, and perceived stress, and to promote the mental health of adult workers. [Journal of Psychosocial Nursing and Mental Health Services, 61(9), 40-46.].

Identifying symptom clusters among pregnant women during early and late pregnancy.

OBJECTIVES: To investigate the status of multiple psychosomatic symptoms among women and identify symptom clusters at different gestational stages. METHODS: This was a cross-sectional study and a consecutive sample of 557 pregnant women were recruited. They were asked to complete the Memorial Symptom Assessment Scale, and to supply sociodemographic and clinical information. Spearman correlation analysis, partial correlation networks, and hierarchical cluster analysis were carried out to identify the optimal number of symptom clusters. RESULTS: The top five scores for symptoms in early pregnancy were nausea, lack of appetite, feeling drowsy, lack of energy, and vomiting. Weight gain, difficulty sleeping, sweating, lack of energy, and dry mouth scored high in late pregnancy. Four clusters were identified in early pregnancy, and three clusters were determined in late pregnancy. CONCLUSIONS: Women experience multiple psychosomatic symptoms during pregnancy, and the manifestation of symptoms varies at different stages. The present study has provided new insights into symptom clusters in pregnant women.

Psychosocial resources moderate the association between stress and insomnia among patients with digestive system cancers.

This study explored the profiles of psychosocial resources combined with resilience and family care, and analyzed their moderating effects on the relationship between stress and insomnia in patients with digestive system cancers. A total of 366 patients were recruited to participate in this study from two tertiary hospitals in China. They were assessed using the Perceived Stress Scale - 4 items, Insomnia Severity Index, Family Concern Index Questionnaire, and 10-item Connor-Davidson Resilience Scale. Latent profile analysis and the BCH (Bolck, Croon & Hagenaars) method were used to identify the subtypes and estimate the moderating role of psychosocial coping resources. About 62.3% of participants had insomnia symptoms. Insomnia was positively correlated to the stress (r = 0.25, P < 0.001). The latent classes were the low resources class (32.8%), the medium resources class (46.1%), and high resources class (21.1%). Among these, in low (estimate value = 0.563, P = 0.003) and medium (estimate value = 0.301, P = 0.029) resources class, stress had an effect on insomnia. There was no association between stress and insomnia in high resources class (estimate value = 0.165, P = 0.637). Stress might be associated with to insomnia problems, whereas patients with high psychosocial resources are more not vulnerable. Interventions to improve family function and resilience could contribute to easing the insomnia of patients with digestive system cancers.

Effects of Resilience-Promoting Interventions on Cancer Patients' Positive Adaptation and Quality of Life: A Meta-analysis.

BACKGROUND: Resilience-promoting interventions (RPIs) are increasingly used for cancer patients. However, there are few comprehensive reports on the efficacy of RPIs in cancer patients. OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was conducted to systematically evaluate the effects of RPIs on resilience, posttraumatic growth (PTG), and quality of life in cancer patients. METHODS: Two authors conducted independent literature searches in electronic databases (PubMed, Scopus, Web of Science, MEDLINE, EBSCO [ASC], Cochrane library, China National Knowledge Infrastructure, Wan Fang Data, and Chinese Scientific and Technological Journal Database) from the first available date to February 2021. Then, eligible studies were selected, data for meta-analysis were extracted, and the risk of bias was evaluated. RESULTS: Sixteen independent randomized controlled trials with 1620 participants were included. Meta-analysis showed that RPIs significantly improved the level of resilience and PTG among cancer patients. Further analysis indicated that both group and individual interventions could enhance resilience and PTG levels. However, RPIs did not significantly enhance the quality of life in cancer patients. CONCLUSIONS: Clinical evidence from current randomized controlled trials shows that RPIs can improve the positive adaptation in cancer patients through either group intervention or individual intervention methods. In the future, the impact of RPIs on the quality of life needs further validation. IMPLICATIONS FOR PRACTICE: Interventions to enhance the positive adaptation for patients with cancer are needed. Considering that both group and individual forms of RPIs can improve resilience and PTG, future clinical intervention methods can be considered in combination with the specific situation of research implementation.

The structure of menopausal syndrome: Using network analysis to understand unique symptomatic relationships.

OBJECTIVE: To explore the network structure underlying the symptoms of menopausal syndrome and to identify the central and bridge symptoms of menopause among middle-aged women. METHODS: This is a cross-sectional survey study conducted in the Chinese community with a total of 1829 women aged 40-65 years. The Menopause Rating Scale (MRS) was used to assess the menopausal syndrome, including somato-vegetative, psychological, and urogenital subdomains. The network analysis was performed to determine the central and bridge symptoms of menopause. RESULTS: In the network of menopausal symptoms, anxiety, vaginal dryness, depressive mood, and irritability were the most central symptoms. Depressive mood, anxiety, and vaginal dryness were also detected as the bridge symptoms. The estimated network between the symptoms had good stability (CS-strength = 0.75 and CS-edge = 0.75). CONCLUSION: The present network analysis provided unique insights into the inner structure of menopausal symptoms. Psychological symptoms should be considered as the core symptoms in developing relevant interventions to improve the health and well-being of middle-aged women.

Analysis and Biomedical Applications of Functional Cargo in Extracellular Vesicles.

Extracellular vesicles (EVs) can facilitate essential communication among cells in a range of pathophysiological conditions including cancer metastasis and progression, immune regulation, and neuronal communication. EVs are membrane-enclosed vesicles generated through endocytic origin and contain many cellular components, including proteins, lipids, nucleic acids, and metabolites. Over the past few years, the intravesicular content of EVs has proven to be a valuable biomarker for disease diagnostics, involving cancer, cardiovascular diseases, and central nervous system diseases. This review aims to provide insight into EV biogenesis, composition, function, and isolation, present a comprehensive overview of emerging techniques for EV cargo analysis, highlighting their major technical features and limitations, and summarize the potential role of EV cargos as biomarkers in disease diagnostics. Further, progress and remaining challenges will be discussed for clinical diagnostic outlooks.

Latent profiles of emotion regulation strategies associated with alexithymia, nonsuicidal self-injury and resilience among nursing students.

The present study sought to better understand the complex nature of emotion regulation in nursing students by exploring patterns of emotion regulation strategies (ERSs), and to examine the relationships between these unique profiles with alexithymia, nonsuicidal self-injury (NSSI) and resilience. A total of 1960 nursing students (Mage  = 19.56, SD = 1.13 years) were recruited. Using latent profile analysis, nursing students were classified into four profiles based on their ERS use: high reaction profile (HRP; 11.53%), medium reaction profile (MRP; 55.46%), adaptive reaction profile (ARP; 22.86%) and low reaction profile (LRP; 10.15%). This study found that relative to HRP and MRP, ARP and LRP showed a lower incidence of NSSI and alexithymia; HRP and ARP showed a higher level of resilience than MRP and LRP. Furthermore, LRP had the lowest level of resilience. This study highlights the importance of identifying the different ERS profiles among nursing students. Targeted programs are needed to enhance adaptive strategies and reduce maladaptive strategies to improve nursing students' psychological and behavioural performance.

Baduanjin Exercise for Adults Aged 65 Years and Older: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

This study performed a systematic review and meta-analysis to evaluate the health effects of Baduanjin exercise on adults aged 65 years and older. Chinese and English databases were electronically searched using search terms related to the PICO model from inception through June 2021. The study quality assessment and meta-analysis were conducted using the PEDro scale and RevMan 5.4 software. Eleven included Chinese studies, published between 2015 and 2021, recruited participants from the mainland of China. The aggregated results showed significant benefits of Baduanjin on physical function, walking ability, balance, and anxiety. A long-term Baduanjin intervention could also improve quality of life and reduce falls and pain. Baduanjin appears to have the potential to improve the health of older adults, but conclusions are limited due to the lack of rigorous and robust studies within and outside of mainland China. Larger, well-designed RCTs are needed to confirm these findings.

Physical Activity Participation and Psychological Wellbeing in University Office Workers in China and Australia: An Online Survey.

Background and purpose: Physical inactivity and prolonged sitting have associations with adverse health. University office workers are at a high risk of psychological and pain issues. This study aimed to explore the differences in sitting time, levels of physical activity participation, stress, depression, anxiety, and pain among university office workers in China and Australia. Methods: Online surveys were distributed to university office workers over 55 years at two universities in China and Australia, respectively. Results: A total of 185 participants completed the online survey (119 in China and 66 in Australia). Significant differences were found in sitting time during workdays between the two countries (p < 0.05) with a longer sitting time in the Australian respondents (7.5 h/day) than those in China (4.6 h/day). Additionally, there were also significant differences in terms of levels of depression and pain symptoms within the two countries (p < 0.05). The Australian respondents reported high levels of depression and pain (M = 7.38, SD = 5.86 and M = 3.65, SD = 2.21, respectively) than those in China (M = 5.71, SD = 4.87 and M = 1.89, SD = 1.89, respectively). The gender, education level, and sitting time of participants were found to be associated with pain scores (p < 0.05). A significant association between marital status and pain scores was found among the Australian respondents (p < 0.05). Conclusions: Future studies with a larger population are needed to validate the results and to further explore the association between physical activity participation and psychological wellbeing among university office workers.

Identifying the different subtypes in menopausal symptoms among middle-aged women in China: a latent class analysis.

OBJECTIVE: Many studies have focused on the severity and prevalence of menopausal symptoms among middle-aged women, which are limited by heterogeneity and diversity of subtypes. Subtyping facilitates the adaptation to prevention and clinical intervention strategies that target women. To determine the existence of significant subgroups of women with similar menopausal symptoms, a person-centered approach was used to identify potential profiles of women during the menopausal transition. In addition, we aimed to examine the association between latent subtypes and individual factors. METHODS: This cross-sectional study included 797 middle-aged women, aged 40 to 60 years, who were recruited from Shandong Province, China, between December 2017 and August 2018. We identified the subtypes in menopausal symptoms by performing a latent class analysis according to the self-reported Menopause Rating Scale and evaluated the robustness of our identified subtypes using a sensitivity analysis. Multinomial logistic regression was performed to explore the association between emergent latent subtypes and sociodemographic, clinical, and psychosocial characteristics. RESULTS: The mean age of participants was 49.83 ± 5.05 years. (1) Four potential classes were identified in middle-aged women: "severe symptoms" (14.9%), "dominant sleep-emotion symptoms" (31.4%), "physical/mental exhaustion symptoms" (32.5%), and "no symptoms" (21.2%). The four classes were also verified using a sensitivity analysis according to age and menopause status subgroups, which revealed the robust subtypes of menopausal symptoms. (2) The odds ratio of neuroticism, chronic diseases, and gynecological diseases were significantly higher for the "severe symptoms," "dominant sleep-emotion symptoms," and "physical/mental exhaustion symptoms" classes, compared to the "no symptoms" class, while the odds ratio of mindfulness and social support were lower. CONCLUSIONS: A person-centered approach for middle-aged women could address the unmet need to understand the heterogeneity of menopausal symptoms. Subtyping facilitates the identification of the potential causes of menopausal symptoms and the development of personalized interventions.

Video Summary:http://links.lww.com/MENO/A830 .

A CRISPR/Cas13a-powered catalytic electrochemical biosensor for successive and highly sensitive RNA diagnostics.

Rapid and specific quantitation of a variety of RNAs with low expression levels in early-stage cancer is highly desirable but remains a challenge. Here, we present a dual signal amplification strategy consisting of the CRISPR/Cas13a system and a catalytic hairpin DNA circuit (CHDC), integrated on a reusable electrochemical biosensor for rapid and accurate detection of RNAs. Signal amplification is accomplished through the unique combination of the CRISPR/Cas13a system with CHDC, achieving a limit of detection of 50 aM within a readout time of 6 min and an overall process time of 36 min, using a measuring volume of 10 µL. Enzymatic regeneration of the sensor surface and ratiometric correction of background signal allow up to 37 sequential RNA quantifications by square-wave voltammetry on a single biosensor chip without loss of sensitivity. The reusable biosensor platform could selectively (specificity = 0.952) and sensitively (sensitivity = 0.900) identify low expression RNA targets in human serum, distinguishing early-stage patients (n = 20) suffering from non-small-cell lung carcinoma (NSCLC) from healthy subjects (n = 30) and patients with benign lung disease (n = 12). Measurement of six NSCLC-related RNAs (miR-17, miR-155, TTF-1 mRNA, miR-19b, miR-210 and EGFR mRNA) shows the ability of the electrochemical CRISPR/CHDC system to be a fast, low-cost and highly accurate tool for early cancer diagnostics.

Individual and additive-effect relationships of sleep problems and severe menopausal symptoms among women in menopausal transition.

OBJECTIVE: Sleep problems and menopausal symptoms are both common complaints among midlife women. However, the associations of the quality and quantity of sleep problems with the severity of menopausal symptoms have not been well studied. Thus, this study aims to examine the relationships between individual sleep problems and the additive number of sleep problems with severe menopausal symptoms among women during the menopausal transition. METHODS: Using the convenience sampling, a total of 848 middle-aged women in China were investigated from December 2017 to August 2018. All participants completed a questionnaire on sleep problems, Menopause Rating Scale, and the general information questionnaire. Based on the cutoff of the Menopause Rating Scale, participants were divided into the nonsevere menopausal symptom group and severe menopausal symptoms group. Propensity score matching was used to balance covariates between the two groups. Stepwise binary logistic regression and restricted cubic spline were applied to analyze the associations of individual and additive sleep problems with severe menopausal symptoms. RESULTS: After propensity score matching, no significant difference was observed between the nonsevere menopausal symptoms group and severe menopausal symptoms group (Ps > 0.05). Logistic regression analysis showed that five sleep problems ("feeling too hot," "having pain," "restless legs syndrome," "taking medicine to help sleep," and "having trouble staying awake") were closely associated with severe menopausal symptoms. The restricted cubic spline curve showed an upward trend in odds ratios between the number of these five sleep problems and severe menopausal symptoms, and women were more than twice as likely to suffer severe menopausal symptoms when they experienced more than three of these individual sleep problems. CONCLUSION: Both the individual and additive number of sleep problems exerted significant effects on severe menopausal symptoms. It might be useful for healthcare providers to set guidelines to support a healthy menopausal transition for midlife women.

Symptom clusters in head and neck cancer patients with endotracheal tube: Which symptom clusters are independently associated with health-related quality of life?

PURPOSE: The point of view of symptom clusters (SCs) may develop an efficient symptom management strategy to enhance health-related quality of life (HRQoL) in head and neck (HNC) patients with endotracheal tube (ETT). The study aims to investigate the possible SCs in HNC patients with ETT and determine whether there was an independent relationship between one or more SCs and HRQoL. METHODS: A cross-sectional study design was adopted, and 203 HNC patients with ETT were recruited. They took measurements of General Information Questionnaire, MD Anderson Symptom Inventory-Head & Neck, and Twelve-Item Short-Form Health Survey (SF-12). Spearman correlations, partial correlations, and hierarchical cluster analysis were performed to determine latent number of SCs, and covariance analyses were used to determine independent associations between SCs and SF-12. This study followed STROBE Statement. RESULTS: Pain SCs (pain, distressed, short of breath, and sadness), fatigue SCs (fatigue/weakness, restless, and sleepy), digestive SCs (appetite loss, constipation, and nausea), HNC-specific SCs (dry mouth and mucus), and tracheostomy-related SCs (difficulty swallowing and difficulty with voice and speech) were found. After adjusting covariant variables, this study found independent relationships of pain SCs and fatigue SCs with physical component summary of SF-12, and between fatigue SCs and mental component summary of SF-12. CONCLUSIONS: Multiple SCs were found in those HNC patients. Pain SCs and fatigue SCs were independently associated with HRQoL. In process of caring HNC patients with ETT, it is vital to focus on SCs, especially on pain SCs and fatigue SCs, which might effectively improve patients' HRQoL.

Fusarihexins A and B: Novel Cyclic Hexadepsipeptides from the Mangrove Endophytic Fungus Fusarium sp. R5 with Antifungal Activities.

Two novel cyclic hexadepsipeptides, fusarihexin A (1: ) and fusarihexin B (2: ), and two known compounds, cyclo-(L-Leu-L-Leu-D-Leu-L-Leu-L-Val) (3: ) and cyclo-(L-Leu-L-Leu-D-Leu-L-Leu-L-Ile) (4: ), were isolated from the marine mangrove endophytic fungus Fusarium sp. R5. Their chemical structures were elucidated on the basis of spectroscopic data and Marfey's analysis. In an in vitro bioassay, fusarihexin A (1: ) remarkably inhibited three plant pathogenic fungi: Colletotrichum gloeosporioides (Penz.) Sacc., which causes anthracnose in many fruits and vegetables, Colletotrichum musae (Berk. and M. A. Curtis) Arx, which causes crown rot and anthracnose in bananas, and Fusarium oxysporum Schlecht. f. sp. lycopersici (Sacc.) W. C. Snyder et H. N. Hansen, which causes Fusarium wilt and fruit rot in tomatoes. Fusarihexin B (2: ) strongly inhibited C. gloeosporioides and C. musae. The compounds were more potent than carbendazim, which is widely used as an agricultural and horticultural fungicide worldwide.

New Antimicrobial Cyclopentenones from Nigrospora sphaerica ZMT05, a Fungus Derived from Oxya chinensis Thunber.

Six new cyclopentenone derivatives (+)-nigrosporione A (+)-1, (-)-nigrosporione A (-)-1, nigrosporione B (2), nigrosporione C (3), (+)-nigrosporione D (+)-4, and (-)-nigrosporione D (-)-4 were isolated from an endophytic fungus Nigrospora sphaerica ZMT05, collected from the rice grasshopper ( Oxya chinensis Thunberg), which is an insect pest in rice and which is also used as a food for people in some countries. Their planar and spatial structures were determined by spectroscopic analyses and eletronic circular dichroism (ECD) calculations. Compounds (+)-1, (-)-1, and 2 inhibited the plant pathogens Fusarium oxysporum, Colletotrichum musae, Penicillium italicum, and Fusarium graminearum, compounds 3 and (-)-4 inhibited F. oxysporum, C. musae, and P. italicum, and compound (+)-4 inhibited F. oxysporum, C. musae, and F. graminearum, showing antifungal activities stronger than triadimefon. Additionally, compounds (+)-1, (-)-1, 2, and 3 displayed moderate antibacterial activities against Staphyloccocus aureus and Escherichia coli.