Ethical utilitarianism is a consequence-oriented ethical theory that pursues the maximization of happiness and fully considers the long-term impact of behavior. In the ethical review of human organ donation and transplantation, this theory is mainly applied in three aspects, ethical review supervision, process and content. However, in practice, it faces challenges such as the difficulty and subjectivity of utility calculation, the balance between individual rights and social welfare, the long-term impact of decision-making, and international cooperation under a global perspective. Therefore, governance strategies such as improving ethical review policy rules, refining the ethical review system by drawing on international experience, and strengthening public education and publicity are proposed. Despite many challenges, ethical utilitarianism still provides an important theoretical framework for the ethical review of human organ donation and transplantation. Therefore, this article reviews the application of ethical utilitarianism in the ethical review of human organ donation and transplantation and its challenges, aiming to provide a reference for related research on the ethical review of human organ donation and transplantation.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

To elucidate the genomic characteristics of Salmonella strains derived from sheep,this study employed various methods,including bacterial isolation and identification,biochemical identi-fication,pathogenicity test,whole-genome sequencing,and BLAST comparison,along with the screening of integrative conjugative elements(ICE)using ICEfinder and EasyFig for comparative analysis,as well as plasmid comparisons utilizing PlasmidBrig.The results revealed the isolation of a Gram-negative,non-spore-forming bacillus from nasal swabs of diseased sheep,which formed gray-white,smooth-surfaced,and neatly edged circular colonies on TSA sheep blood agar.On XLT-4 agar medium,it produced smooth-surfaced,white,circular colonies.The bacterium was identified as Salmonella enterica through 16S rRNA sequencing and biochemical identification.This bacteri-um induces hemorrhaging in the intestines of guinea pigs,resulting in their demise within a 48-hour period.The pathogen exhibits high virulence.Whole-genome alignment demonstrated a high degree of homology with Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7).ICE screen-ing and comparative analysis indicated the presence of a novel ICE in this strain,characterized by a core structural framework that includes an integrative shear module,a mobilizable processing mod-ule,a conjugative pair formation module,and a regulatory module.Notably,ICE from different spe-cies containing the same integrase exhibited identical inverted repeat sequences and insertion sites at tRNAPhe.Plasmid homology comparisons revealed that plasmid sequences from different strains of Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)also showed high homology;however,the homology with plasmid sequences from other Salmonella and Escherichia coli strains was only 50％.These findings indicate that the isolated strain is Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)and contains a novel ICE as well as a plasmid.This study fur-ther enriches the molecular epidemiology of Salmonella and provides a theoretical basis for the prevention and control of infections caused by this pathogen.

To elucidate the genomic characteristics of Salmonella strains derived from sheep,this study employed various methods,including bacterial isolation and identification,biochemical identi-fication,pathogenicity test,whole-genome sequencing,and BLAST comparison,along with the screening of integrative conjugative elements(ICE)using ICEfinder and EasyFig for comparative analysis,as well as plasmid comparisons utilizing PlasmidBrig.The results revealed the isolation of a Gram-negative,non-spore-forming bacillus from nasal swabs of diseased sheep,which formed gray-white,smooth-surfaced,and neatly edged circular colonies on TSA sheep blood agar.On XLT-4 agar medium,it produced smooth-surfaced,white,circular colonies.The bacterium was identified as Salmonella enterica through 16S rRNA sequencing and biochemical identification.This bacteri-um induces hemorrhaging in the intestines of guinea pigs,resulting in their demise within a 48-hour period.The pathogen exhibits high virulence.Whole-genome alignment demonstrated a high degree of homology with Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7).ICE screen-ing and comparative analysis indicated the presence of a novel ICE in this strain,characterized by a core structural framework that includes an integrative shear module,a mobilizable processing mod-ule,a conjugative pair formation module,and a regulatory module.Notably,ICE from different spe-cies containing the same integrase exhibited identical inverted repeat sequences and insertion sites at tRNAPhe.Plasmid homology comparisons revealed that plasmid sequences from different strains of Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)also showed high homology;however,the homology with plasmid sequences from other Salmonella and Escherichia coli strains was only 50％.These findings indicate that the isolated strain is Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)and contains a novel ICE as well as a plasmid.This study fur-ther enriches the molecular epidemiology of Salmonella and provides a theoretical basis for the prevention and control of infections caused by this pathogen.

[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching ⁶⁸Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT.

Pancreatic cancer is one of the most prevalent malignant tumors of the digestive system， and its incidence and mortality rates are increasing year by year. Most patients with pancreatic cancer are unable to receive surgery due to the advanced stage. Although chemotherapy regimens based on gemcitabine and fluorouracil have prolonged the survival time of patients to some extent， some patients cannot tolerate chemotherapy and hence lose the opportunity for treatment. With the advent of the era of precision medicine， molecular-targeted therapy has exhibited an excellent therapeutic efficacy and has thus become one of the most important treatment techniques for tumors； however， due to the high heterogeneity of pancreatic cancer and its complicated tumor microenvironment， molecular-targeted therapy for pancreatic cancer has not achieved notable results. Therefore， it is imperative to seek new therapeutic targets and medications to overcome this issue. This article reviews the latest advances in the research on molecular-targeted therapy for unresectable pancreatic cancer based on common molecular targets and tumor immunity-related therapeutic targets， in order to provide new treatment strategies for patients with pancreatic cancer.

Objective:To investigate the sedative effect of remimazolam on ICU elderly patients undergoing mechanical ventilation and its influence on circulatory system.Methods:Using a prospective research approach, 189 ICU elderly patients undergoing mechanical ventilation in Hebei Petro China Central Hospital from October 2021 to June 2023 were selected. The patients were divided into remimazolam group, dexmedetomidine group and propofol group by random number table method with 63 cases in each group. The patients in remimazolam group, dexmedetomidine group and propofol group were sedated with remimazolam, dexmedetomidine and propofol, respectively. The sedation standard time, sedation standard rate, sedation maintenance time and recovery time after drug withdrawal were compared among the three groups. The heart rate, mean arterial pressure (MAP), respiratory rate and pulse oxygen saturation (SpO 2) before medication (T 0) and medication for 15 min (T 1), 30 min (T 2), 1 h (T 3), 6 h (T 4), 12 h (T 5) were recorded. The incidences of bradycardia, hypotension, respiratory depression, body movement and delirium during sedation were recorded. Results:The sedation standard time and recovery time after drug withdrawal in remimazolam group were significantly shorter than those in dexmedetomidine group and propofol group: (22.27 ± 5.31) min vs. (29.45 ± 6.24) and (30.12 ± 5.87) min, (28.66 ± 7.06) min vs. (32.22 ± 6.85) and (34.34 ± 7.24) min, and there were statistical differences ( P<0.05); there were no statistical difference between dexmedetomidine group and propofol group ( P>0.05). The sedation standard rate in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group: 87.43% (661/756) and 83.60% (632/756) vs. 72.49% (548/756), and there was statistical difference ( P<0.016 7); there was no statistical difference between remimazolam group and dexmedetomidine group ( P>0.016 7). There was no statistical difference in sedation maintenance time among the three groups ( P>0.05). There were no statistical difference in T 0 heart rate, MAP, respiratory rate and SpO 2 among the three groups ( P>0.05). The T 1 to T 5 heart rate and MAP in remimazolam group were significantly higher than those in dexmedetomidine group and propofol group, the T 2 to T 5 heart rate and MAP in dexmedetomidine group were significantly lower than those in propofol group, and there were statistical differences ( P<0.05). The T 2 to T 5 respiratory rate in remimazolam group was significantly lower than that in dexmedetomidine group, the T 1 to T 5 respiratory rate in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group, and there were statistical differences ( P<0.05). The T 2 to T 5 SpO 2 in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group, and there was statistical difference ( P<0.05). The incidence of bradycardia in remimazolam group was significantly lower than that in dexmedetomidine group: 7.94% (5/63) vs. 25.40% (16/63), the incidence of hypotension was significantly lower than that in propofol group: 6.35% (4/63) vs. 23.81% (15/63), and there were statistical differences ( P<0.016 7). The incidence of respiratory depression in remimazolam group and dexmedetomidine group was significantly lower than that in propofol group: 4.76% (3/63) and 1.59% (1/63) vs. 22.22% (14/63), and there was statistical difference ( P<0.016 7). There was statistical difference in incidence of delirium among the three groups ( P<0.05), but there was no statistically significant difference in pairwise comparison ( P>0.016 7). There was no statistical difference in the incidence of body movement among the three groups ( P>0.05). Conclusions:The effect of remimazolam sedation in ICU elderly patients undergoing mechanical ventilation is satisfactory, with little influence on circulation and respiratory system and few adverse reactions.

OBJECTIVE: To investigate the clinical effect of electroacupuncture (EA) in preventing chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Fifty-two patients with breast cancer in the regimen of taxane-assisted/neoadjuvant chemotherapy, were randomly divided into an EA group (26 cases, 3 cases dropped out) and a usual care (UC) group (26 cases, 1 case dropped out). In the UC group, on the basis of standard chemotherapy regimen, the routine nursing was administered. In the EA group, on the intervention as the UC group, EA was added, the acupoints included Yintang (GV 24⁺), Baxie (EX-UE 9, the second one), Waiguan (TE 5), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), Yinlingquan (SP 9), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3), Xuanzhong (GB 39) and Bafeng (EX-LE 10, the fourth one). Electric stimulation was attached to Taichong (LR 3) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave and the frequency of 2 Hz/10 Hz, for 30 min. EA started one day before the first cycle of chemotherapy, twice weekly in the first two weeks and once weekly in the rest weeks of chemotherapy. The duration of the intervention with EA was 12 weeks. The incidence of CIPN was compared in week 24 of the trial between the two groups. At the baseline and in week 12 and 24 of the trial, the score of EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer on chemotherapy-induced peripheral nerve toxicity quality of life questionnaire 20), the score of TCM syndrome scale and the score of EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer on quality of life scale) were observed in the two groups. At the baseline and in week 12 of the trial, the sensory nerve conduction velocity (SCV) and the motor nerve conduction velocity (MCV) was detected. RESULTS: In week 24 of the trial, the incidence of CIPN was 17.4% (4/23) in the EA group, lower than that (72.0%, 18/25) in the UC group (P<0.001). The incidence of high-grade CIPN was 0% (0/23) in the EA group, lower than that (28.0%, 7/25) in the UC group (P<0.05). In week 12 and 24 of the trial, the scores for the sensory nerve symptom of EORTC QLQ-CIPN20 and the total scores were higher when compared with the baseline in the UC group (P<0.001, P<0.05, P<0.01). In week 24 of the trial, the score for the sensory nerve symptom of EORTC QLQ-CIPN20 in the EA group was lower than that of the UC group (P<0.05). In week 12 of the trial, SCV of the right superficial peroneal nerve was reduced when compared with the baseline in the UC group (P<0.05), and SCV of the left median nerve and the right superficial peroneal nerve was higher in the EA group when compared with the UC group (P<0.05, P<0.01). In week 12 and 24 of the trial, the scores for the secondary symptoms of TCM scale were decreased in the EA group compared with the baseline (P<0.05), and the scores for the primary and secondary symptoms, as well as the total scores of TCM scale were all higher than those of the baseline in the UC group (P<0.01, P<0.001, P<0.05). In week 12 of the trial, the scores for the primary and secondary symptoms, as well as the total score of TCM scale in the EA group were lower than those of the UC group (P<0.05, P<0.01). In week 24 of the trial, the score for the secondary symptoms and the total score of TCM scale in the EA group were lower than those of the UC group (P<0.05). In week 12 of the trial, the scores for fatigue, pain, nausea and vomiting in EORTC QLQ-C30 were increased in comparison with the baseline in the UC group (P<0.05, P<0.01); in week 24 of the trial, the score of the general health in EORTC QLQ-C30 was elevated when compared with the baseline in the EA group (P<0.001), and the scores for nausea and vomiting, loss of appetite were decreased in comparison with the baseline (P<0.01). In week 12 of the trial, the score of the general health in EORTC QLQ-C30 in the EA group was higher compared with the UC group (P<0.01), and the scores for pain, nausea and vomiting were lower (P<0.01, P<0.05). In week 24 of the trial, the score of the general health in EORTC QLQ-C30 was higher in the EA group compared with the UC group (P<0.001), and the score for loss of appetite was lower (P<0.05). CONCLUSION Electroacupuncture reduces the incidence and severity of CIPN, ameliorates nerve conduction velocity and improves the quality of life of the patients.
Humans ; Electroacupuncture ; Female ; Peripheral Nervous System Diseases/prevention & control* ; Middle Aged ; Adult ; Breast Neoplasms/therapy* ; Antineoplastic Agents/adverse effects* ; Aged

Adoptive cell immunotherapy has been a hot spot in tumor research in recent years. Chimeric antigen receptor T cells (CAR-T) have achieved great success in hematological tumors and have changed the current tumor treatment landscape to a certain extent. However, the application of CAR-T therapy in clinics is limited due to its serious side effects and high treatment costs. Natural killer (NK) cells are important immune cells in the body and have native cytotoxicity and well safety. NK cells based on CAR engineering (CAR-NK) have shown powerful anti-tumor activity and safety in preclinical research and could be the next generation of CAR platform-based cellular immunotherapy. This review will systematically introduce the current research status of CAR-NK cells in lymphoma.