The development of novel point-to-point drugs targeting resistance mechanisms is a critical and popular research field; nevertheless, success remains challenging. Therefore, given the short survival time and heightened expectations of patients with advanced NSCLC, the design of various combination therapy strategies––integrating preclinical, clinical, and real-world evidence (such as radiotherapy, chemotherapy, targeted therapy, antibody–drug conjugates, oncolytic viruses, and cell therapy)––may be a wise and practical choice to address the disease. Resistance to immunotherapy involves almost all cell types in the body, primarily cancer cells and T cells involved in immune surveillance. As a result of space limitations, this article focuses on the progress and challenges of various combined strategies for directly eliminating cancer cells. We also emphasize the realignment of treatment goals, shifting from primarily focusing on eliminating cancer cells (via chemotherapy and radiotherapy) to fully utilizing immune regulation to overcome resistance to immune checkpoint inhibitors.

Objective: To establish a metabonomics research technique based on the combination of

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Objective:To investigate the post-traumatic growth status of patients with urinary bladder cancer after surgery and analyze its influencing factors.Methods:Using the convenient sampling method, a total of 289 patients with urinary bladder cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January to December 2019 were selected as the research objects. The general data questionnaire, Post-traumatic Growth Inventory and Psychological Resilience Scale were used for investigation. Multiple linear regression was used to analyze the influencing factors of post-traumatic growth of patients with urinary bladder cancer after surgery.Results:Post-traumatic growth score of patients with after surgery was (61.47±10.79) . Differences in post-traumatic growth scores of urinary bladder cancer patients after surgery with different ages, residences, education levels, medical payment methods, average monthly family income, degree of self-care and metastasis were statistically significant ( P<0.05) . The total score of psychological resilience and scores of various dimensions of patients with urinary bladder cancer after surgery were positively correlated with the post-traumatic growth score ( P<0.05) . The results of multiple linear regression analysis showed that psychological resilience, education level and average monthly family income were the main factors influencing post-traumatic growth of patients with urinary bladder cancer after surgery ( P<0.05) . Conclusions:Post-traumatic growth of patients with urinary bladder cancer after surgery is at a medium level. Educational level, average monthly family income and psychological resilience are the main factors affecting post-traumatic growth of patients, suggesting that nursing managers can improve the post-traumatic growth of patients with urinary bladder cancer after surgery through intervention of influencing factors.

Objective:To deeply understand needs and problems of on-site nursing service training for "network nurses", so as to provide a reference for the construction of "Internet + Nursing Service" training content system standards.Methods:Using the purposive sampling method and based on principle of maximum differentiation, a total of 12 "network nurses" in Ningbo were selected from March to May in 2020 to conduct semi-structured interviews. Braun thematic analysis method was used to analyze data and extract themes.Results:A total of 4 themes were obtained. The first was that the requirements of practicing safety education and training included risk prevention training, adverse event handling process training, emergency response plans and complication handling training. The second was the needs of humanistic care education and training, including on-site service language, code of conduct training, nurse-patient communication training and health education knowledge training. The third was the demand for diversified training forms. Fourthly, factors affecting training quality.Conclusions:"Network nurses" have a greater demand for occupational safety education and humanistic care education. It is recommended that multiple parties should cooperate to improve the "Internet +Nursing Service" emergency laws and regulations as soon as possible, provide diversified training models, reserve high-quality "Internet + Nursing Service" talents and promote continuous and standardized development of "Internet + Nursing Service".

Objective:To explore the changing characteristics of self-efficacy, social support, psychological stress in patients with osteoporotic vertebral compression fractures (OVCFs) receiving conservative treatment at different treatment stages and their correlations with the recovery of lower back function.Methods:A total of 116 patients with acute OVCFs who were admitted to the Affiliated Hospital of Medical School, Ningbo University were selected from January 2017 to May 2019. Oswestry Disability Index (ODI) Questionnaire, General Self Efficacy Scale (GSES) , Perceived Social Support Scale (PSSS) and Perceived Stress Scale (PSS) were used to assess the lower back function, self-efficacy, social support and psychological stress of OVCFs patients. Questionnaires were filled out during outpatient reexamination or in-home follow-up, and the evaluation time was at the time of treatment and 1, 3, 6, and 12 months after conservative treatment. Analysis of variance and SNK- q test were used to explore the characteristics of each score over time, and linear regression analysis was used to explore the effects of GSES, PSSS, and PSS on ODI. Results:With the prolongation of treatment time, ODI, GSES, PSSS and PSS scores of OVCFS patients under conservative treatment showed a downward trend, and the scores at 3, 6 and 12 months after treatment were lower than those at 1 month after conservative treatment ( P<0.05) . The scores at 6 and 12 months after conservative treatment were lower than those at 3 months after conservative treatment ( P<0.05) . The scores at 12 months after conservative treatment were lower than that those at 6 months after conservative treatment ( P<0.05) . GSES, PSSS (total score, in-family support, out-of-family support) and PSS were independent influencing factors of ODI at one month after treatment ( P<0.05) . GSES, PSSS (total score, in-family support) and PSS were the influencing factors of ODI at 3 months after treatment ( P<0.05) . Conclusions:The self-efficacy and social support of conservatively treated patients with OVCFs are positively correlated with their lower back function, while psychological stress will reduce lower back function of such patients. It is suggested to add these non-physical factors to the rehabilitation nursing model and take appropriate intervention measures.

Objective:To explore status of quality of life of elderly patients with benign prostatic hyperplasia and analyze the influencing factors.Methods:A total of 300 elderly patients with benign prostatic hyperplasia who were admitted to the First Affiliated Hospital of Zhengzhou University from September 2018 to October 2019 were selected as the research subjects by the convenient sampling method. The general information questionnaire, Benign Prostatic Hyperplasia Patients Quality of Life Scale and Health Behavior Ability Self-Rating Scale were used to investigate. Pearson correlation analysis method was used to analyze the correlation between health behavior and quality of life in elderly patients with benign prostatic hyperplasia. Multiple linear regression was used to analyze the factors affecting quality of life of elderly patients with benign prostatic hyperplasia. In this study, a total of 300 questionnaires were distributed, and 289 valid questionnaires were returned. The effective response rate was 96.33%.Results:The score of the Benign Prostatic Hyperplasia Patients Quality of Life Scale for 289 elderly patients with benign prostatic hyperplasia were (106.83±20.27) , and score of Health Behavior Ability Self-Rating Scale was (56.19±18.64) . Univariate analysis showed that there were statistically significant differences in scores of Benign Prostatic Hyperplasia Patients Quality of Life Scale for patients with different age, education background, marital status, family per capita monthly income, residence, disease course and other chronic diseases ( P< 0.05) . The results of Pearson correlation analysis showed that the health behavior of elderly patients with benign prostatic hyperplasia was positively correlated with the quality of life ( P<0.01) . The results of multiple linear regression analysis showed that educational background, healthy behavior ability and marital status were influencing factors of quality of life of elderly patients with benign prostatic hyperplasia ( P<0.01) , a total of 40.4% of the total variation was explained. Conclusions:The quality of life of elderly patients with benign prostatic hyperplasia is not high, and the educational background, health behavior ability and marital status can affect the quality of life of patients. It is recommended that clinical nursing workers take targeted and effective measures to improve the quality of life of elderly patients with benign prostatic hyperplasia.

Objective:To analyze the real work experience of "online nurses" door-to-door services under the Internet model so as to provide a basis for the government and management departments to carry out "Internet + nursing services" work.Methods:According to the phenomenological research method, intentional sampling and the principle of maximum differentiation were used to select 20 nurses who had provided home care services in Class Ⅲ Grade A hospital and hosted community health service center in Ningbo for the semi-structured interview from August to November 2019. The interview data was organized and analyzed using the Colaizzi data analysis method.Results:There were two themes that affected the work experience of "online nurses" nursing service. Among them, the positive factors included the obvious increase in professional values, policy support guarantee, the surge in patient demand, insurance protection and first aid safety guarantee; the negative factors included the unbalanced input and harvest, service costs not included in medical insurance, improper disposal of medical waste, lack of team support, insufficient publicity of "online" nursing services, weak multidisciplinary nursing knowledge, and lack of standardization of "online" nursing medical records.Conclusions:The "online nurses" have positive experiences such as increased professional values in their service experience. At the same time, there are also difficulties such as imbalance in income and expenditure, and insufficient team support. It is necessary to further strengthen the government-hospital-community-enterprise collaboration, gradually improve the "online" nursing service standards from multiple angles and directions, provide a good working environment and the security for online nurses so as to serve society well.

The " Internet+ Nursing Service" has been explored in localities as a new type of medical service. The paper introduced the innovation and excellence in the operation of Ningbo in the past four years, namely a unified operation platform to save resources, marked-based pricing to care for interests of three parties, nursing qualifications to safeguard quality of service, contracting with hospital entities to clarify responsibilities and rights, government leadership to determine assessment goals, and Ningbo Nursing Association in guidance to ensure homogeneous service. Thanks to the above measures, no disputes and complaints were recorded among 3 088 person-times ever since. Experiences in Ningbo may serve as a reference for such model to be implemented smoothly and orderly in other places.

Objective To investigate inner experience of junior nurses after a serious adverse event.Methods A total of 7 junior nurses undergoing a serious adverse event were interviewed from June to August 2016, using the phenomenological approach in qualitative research. The interview was analyzed by phenomenological methodology. The information was dealt with Colaizz 7 steps analysis method.Results The perception of junior nurses experiencing a serious adverse event could be classified into 3 themes: emotional changes in different periods, family attitude having an impact, the pursuit of nursing work having some changes. Conclusions The interview of junior nurses can help them undergoing a serious adverse event to express inner feelings, which shorten the time of mental health and provide the basis for the research on nursing adverse event management system.