Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To explore the clinicopathological features of rectal neuroendocrine tumor (R-NET) G2, identify prognostic factors, and summarize treatment experience.Methods:The clinical data of patients diagnosed with R-NET G2 by pathological diagnosis admitted to Cancer Hospital of the Chinese Academy of Medical Sciences from January 2003 to September 2023 were retrospectively analyzed. The Fisher's exact test and Kaplan-Meier curves were performed to analyze the association between pathological features and prognosis.Results:A total of 22 patients were enrolled in this study and 21 patients were followed up for a period of 6-98 months with a median follow-up time of 42 months. 5 patients died due to tumor progression during the follow-up period. The 1-, 3-, and 5-year cancer-specific survival (CSS) of the whole group were 100.0%, 92.9%, and 69.6%, respectively. Of the 22 patients, 20 underwent surgical treatment, of which 15 underwent postoperative adjuvant therapy; 2 underwent medical treatment for liver and bone multiple metastases. The 5-year survival rates of patients with tumours ≥2 cm in length, T2-3 stage, lymph node metastasis, and distant metastasis (57.1%, 68.8%, 66.7%, and 63.6%, respectively) were shorter than those of patients with tumours <2 cm in length, T1 stage, no lymph node metastasis, and no distant metastasis (all 100.0%, P＜0.001). In addition, patients with liver metastases had larger primary tumor diameters and higher T-stages compared with those without distant metastasis ( P＜0.05). Conclusions:R-NET G2 has a high degree of malignancy compared with G1 and a high propensity for metastasis. Clinicians should formulate appropriate diagnostic and treatment strategies based on factors such as tumor size, depth of invasion, lymph node status, presence of distant metastasis, and the location and extent of distant metastasis.

Objective To study how lipid bilayer fluidity modulates the interaction between β1 integrin and CD40L,as well as the formation of CD40L-mediated tumor cell contact interfaces.Methods Supported lipid bilayers(SLB)with different fluidities were prepared through adjusting the 1,2-dioleoyl-sn-glycero-3-[N-(5-amino-l-carboxypentyl)iminodiacetic acid]succinyl nickel salt(DGS-NTA)content.The functionalization of lipid bilayers was achieved by anchoring fluorescently labeled CD40L molecules onto the membrane surface.The contact interface formation of PC9 cells on the functionalized lipid bilayers was observed through confocal fluorescence imaging and fluorescence recovery after photobleaching(FRAP)experiments,and data of two dimensional(2D)reaction kinetics of β1 integrin and CD40L were extracted from Zhu-Golan plots.Results The diffusion coefficient of molecules in lipid bilayer was negatively correlated with DGS-NTA content.High fluidity of lipid bilayer promoted CD40L accumulation at cell contact interface and expanded the cell contact area.The 2D dissociation constants(2D Kd)of β1 integrin-CD40L complexes were approximately 13,31 and 65 molecules/μm2 for the three lipid bilayers with high,moderate and low fluidities,respectively.Conclusions High fluidity of lipid bilayers significantly facilitates diffusion and aggregation of CD40L to the cell contact interface,thus enhancing β1 integrin-CD40L interaction and the stability of cell contact interfaces.

Objective To study how lipid bilayer fluidity modulates the interaction between β1 integrin and CD40L,as well as the formation of CD40L-mediated tumor cell contact interfaces.Methods Supported lipid bilayers(SLB)with different fluidities were prepared through adjusting the 1,2-dioleoyl-sn-glycero-3-[N-(5-amino-l-carboxypentyl)iminodiacetic acid]succinyl nickel salt(DGS-NTA)content.The functionalization of lipid bilayers was achieved by anchoring fluorescently labeled CD40L molecules onto the membrane surface.The contact interface formation of PC9 cells on the functionalized lipid bilayers was observed through confocal fluorescence imaging and fluorescence recovery after photobleaching(FRAP)experiments,and data of two dimensional(2D)reaction kinetics of β1 integrin and CD40L were extracted from Zhu-Golan plots.Results The diffusion coefficient of molecules in lipid bilayer was negatively correlated with DGS-NTA content.High fluidity of lipid bilayer promoted CD40L accumulation at cell contact interface and expanded the cell contact area.The 2D dissociation constants(2D Kd)of β1 integrin-CD40L complexes were approximately 13,31 and 65 molecules/μm2 for the three lipid bilayers with high,moderate and low fluidities,respectively.Conclusions High fluidity of lipid bilayers significantly facilitates diffusion and aggregation of CD40L to the cell contact interface,thus enhancing β1 integrin-CD40L interaction and the stability of cell contact interfaces.

Objective:To construct a health education checklist for safety management of oral antitumor drugs in tumor patients, so as to provide a guidance for clinical nurses in practice, thereby improving the drug safety of patients taking oral antitumor drugs.Methods:Based on the cognition-behavior theoretical framework, a preliminary draft of a health education checklist for safety management of oral antitumor drugs in tumor patients was developed through literature review. The Delphi method was used to conduct consultations with 17 experts from July to September 2024 to revise and add or delete the contents of the checklist based on the experts' assignments of importance to the indicators at each level and the textual comments made.Results:A total of two rounds of expert consultation were conducted. The final established health education checklist for safety management of oral antitumor drugs in tumor patients included 4 primary and 28 secondary indicators. In the two rounds of consultation, the positive coefficient of experts was 100.0%, the coefficient of expert authority was 0.93, the coefficients of variation for the two rounds of expert ratings were 0 to 0.173 and 0 to 0.151, and the coefficients of Kendall's concordance were 0.141 (χ 2=74.461, P<0.001) and 0.113 (χ 2=59.549, P=0.002) , respectively. Conclusions:The health education checklist for safety management of oral antitumor drugs in tumor patients has good scientific, reliable and clinical practical value, which can provide scientific, standardized and convenient practical guidance for clinical nurses to implement health education on drug safety management for patients taking oral antitumor drugs.

Objective:To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC).Methods:Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared.Results:The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20.Conclusions:Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.

Objective:To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC).Methods:Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared.Results:The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20.Conclusions:Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.

Objective:To construct a health education checklist for safety management of oral antitumor drugs in tumor patients, so as to provide a guidance for clinical nurses in practice, thereby improving the drug safety of patients taking oral antitumor drugs.Methods:Based on the cognition-behavior theoretical framework, a preliminary draft of a health education checklist for safety management of oral antitumor drugs in tumor patients was developed through literature review. The Delphi method was used to conduct consultations with 17 experts from July to September 2024 to revise and add or delete the contents of the checklist based on the experts' assignments of importance to the indicators at each level and the textual comments made.Results:A total of two rounds of expert consultation were conducted. The final established health education checklist for safety management of oral antitumor drugs in tumor patients included 4 primary and 28 secondary indicators. In the two rounds of consultation, the positive coefficient of experts was 100.0%, the coefficient of expert authority was 0.93, the coefficients of variation for the two rounds of expert ratings were 0 to 0.173 and 0 to 0.151, and the coefficients of Kendall's concordance were 0.141 (χ 2=74.461, P<0.001) and 0.113 (χ 2=59.549, P=0.002) , respectively. Conclusions:The health education checklist for safety management of oral antitumor drugs in tumor patients has good scientific, reliable and clinical practical value, which can provide scientific, standardized and convenient practical guidance for clinical nurses to implement health education on drug safety management for patients taking oral antitumor drugs.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.