Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Objective To explore the diagnostic and prognostic values of procalcitonin(PCT),interleukin 6(IL-6)and cystatin C(CysC)combined detection in sepsis acute kidney injury(AKI).Methods A total of 100 patients with sepsis were divided into the AKI group(n=56)and the non AKI group(n=44)according to the occurrence of AKI.The prognosis of AKI patients was followed up,and patients were divided into the survival group(n=32)and the death group(n=24)according to the presence or absence of death.Enzyme-linked immunosorbent assay(ELISA)was used to detect PCT,IL-6 and CysC in different groups of patients.The Acute Physiological Function and Chronic Health Status Score(APACHEⅡ)was used to assess the condition of illness.ROC curve was used to analyze the predictive values of PCT,IL-6 and CysC in the diagnosis and death of sepsis combined with AKI.Results The male ratio,age,hypertension with diabetes ratio,APACHE Ⅱ score,serum creatinine(Scr),PCT,IL-6 and CysC levels were higher in the AKI group than those in the non AKI group,and the ratio of complications and onset time were lower in the AKI group than those in the non AKI group(P＜0.05).The ROC curve results showed that the area under the curve(AUC)of PCT,IL-6,and CysC combined for the diagnosis of sepsis complicated with AKI was 0.859,with a sensitivity of 91.07%and a specificity of 90.91%.The combined diagnostic efficacy was better than that of a single indicator.The APACHE Ⅱ score,PCT,IL-6 and CysC levels were higher in the death group than those in the survival group(P＜0.05).The ROC curve results showed that the AUC,sensitivity and specificity of PCT,IL-6 and CysC combined in predicting mortality in sepsis patients with AKI were 0.847,91.67%and 87.50%,respectively.The combined predictive efficacy was better than that of single indicator.Conclusion The combination of PCT,CysC and IL-6 indicators is more valuable in diagnosing and predicting prognosis of sepsis with AKI.

Yi Dagen was a famous physician of Xujiang School in Ming Dynasty.In the process of syndrome differentiation and treatment,Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors.His theory was based on"Yin and Yang having time rules and coordinating with pulse"in Basic Questions:The subtlety of pulse diagnosis,emphasizing the mutual reference of pulse and time,reflecting the fundamental principle of"correspondence between nature and man"in traditional Chinese medicine.The thought of mutual reference of pulse and time is mainly reflected in two levels:one is to guide syndrome differ-entiation,which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease,referring to the four-season and five-viscus pulse method to identify the cause of the disease,referring to the north-south governance to identify the nature of the disease,and choosing the time to diagnose the pulse to identify the disease situation;the second is the whole process of syndrome differentiation and treatment,including pulse and time diagnosis and treatment according to the time.The idea of mutual ref-erence of pulse and time plays an important guiding role in current clinical work.In the future,wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise applica-tion of the"mutual reference of pulse and time"theory.

Yi Dagen was a famous physician of Xujiang School in Ming Dynasty.In the process of syndrome differentiation and treatment,Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors.His theory was based on"Yin and Yang having time rules and coordinating with pulse"in Basic Questions:The subtlety of pulse diagnosis,emphasizing the mutual reference of pulse and time,reflecting the fundamental principle of"correspondence between nature and man"in traditional Chinese medicine.The thought of mutual reference of pulse and time is mainly reflected in two levels:one is to guide syndrome differ-entiation,which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease,referring to the four-season and five-viscus pulse method to identify the cause of the disease,referring to the north-south governance to identify the nature of the disease,and choosing the time to diagnose the pulse to identify the disease situation;the second is the whole process of syndrome differentiation and treatment,including pulse and time diagnosis and treatment according to the time.The idea of mutual ref-erence of pulse and time plays an important guiding role in current clinical work.In the future,wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise applica-tion of the"mutual reference of pulse and time"theory.

Objective To explore the diagnostic and prognostic values of procalcitonin(PCT),interleukin 6(IL-6)and cystatin C(CysC)combined detection in sepsis acute kidney injury(AKI).Methods A total of 100 patients with sepsis were divided into the AKI group(n=56)and the non AKI group(n=44)according to the occurrence of AKI.The prognosis of AKI patients was followed up,and patients were divided into the survival group(n=32)and the death group(n=24)according to the presence or absence of death.Enzyme-linked immunosorbent assay(ELISA)was used to detect PCT,IL-6 and CysC in different groups of patients.The Acute Physiological Function and Chronic Health Status Score(APACHEⅡ)was used to assess the condition of illness.ROC curve was used to analyze the predictive values of PCT,IL-6 and CysC in the diagnosis and death of sepsis combined with AKI.Results The male ratio,age,hypertension with diabetes ratio,APACHE Ⅱ score,serum creatinine(Scr),PCT,IL-6 and CysC levels were higher in the AKI group than those in the non AKI group,and the ratio of complications and onset time were lower in the AKI group than those in the non AKI group(P＜0.05).The ROC curve results showed that the area under the curve(AUC)of PCT,IL-6,and CysC combined for the diagnosis of sepsis complicated with AKI was 0.859,with a sensitivity of 91.07%and a specificity of 90.91%.The combined diagnostic efficacy was better than that of a single indicator.The APACHE Ⅱ score,PCT,IL-6 and CysC levels were higher in the death group than those in the survival group(P＜0.05).The ROC curve results showed that the AUC,sensitivity and specificity of PCT,IL-6 and CysC combined in predicting mortality in sepsis patients with AKI were 0.847,91.67%and 87.50%,respectively.The combined predictive efficacy was better than that of single indicator.Conclusion The combination of PCT,CysC and IL-6 indicators is more valuable in diagnosing and predicting prognosis of sepsis with AKI.

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Objective:To explore the effect of discharge preparation service based on timing theory on the care readiness and benefit finding of caregivers for elderly dementia patients.Methods:From January 2021 to December 2022, 100 caregivers of elderly dementia patients from the Neurology Department and Rehabilitation Department of Jingjiang People's Hospital were selected as the subject by convenient sampling. Caregivers were divided into a control group and a study group based on their enrollment time, with 50 cases in each group. The control group received routine nursing, while the study group was treated with discharge preparation services based on timing theory. The effect was evaluated using the Caregiver Preparedness Scale (CPS) and Caregiver Benefit Finding Questionnaire.Results:After intervention, the CPS score of the study group was (22.80±2.83), which was higher than the control group's (17.92±2.60), and the difference was statistically significant ( P<0.05). After three months of discharge, the score of the Caregiver Benefit Finding Questionnaire in the study group was (117.50±6.25), which was higher than the control group's (109.98±9.89), and the difference was also statistically significant ( P<0.05) . Conclusions:The discharge preparation service based on timing it right can improve the care readiness and benefit finding of caregivers for elderly dementia patients.

The Yin-Fire theory is the core content of Li Dongyuan's academic thought and has profound and extensive clinical guidance value.This paper analyzes the connotation and background of the Yin-Fire theory,and proposes that the core pathogenesis of Yin-Fire syndrome is qi deficiency without movement,and stagnation turning into fire;qi deficiency without rise,and dampness and turbidity flowing downward;qi deficiency without astringent,and Xiang-Fire rushing upward;qi deficiency and fire hyperactivity,which hurts body fluid and burns blood.This article summarizes the key points of diagnosis and treatment of various diseases by sorting out the commonly used prescriptions and medicines of Yin-Fire theory and its clinical application in miscellaneous internal medicine diseases,and deepens the understanding of the connotation of Yin-Fire syndrome.

Objective:To explore the obstacle factors and promoting factors of exercise guidance and implementation after breast cancer surgery, so as to provide reference and basis for the formulation of exercise program after breast cancer patients.Methods:Using the objective sampling method, a total of 10 medical staff and 10 patients with breast cancer after operation from the breast surgery department of the Seven People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine hospital in Shanghai were selected as research objects from July to September 2022. A semi-structured interview was conducted. The interview outline was developed based on the knowledge transformation framework, and the results were analyzed by the content analysis method.Results:The study extracted three levels of influencing factors. The system level included caregiver workload, educational materials, norms and responsibilities and trust in evidence-based evidence. The practitioner level included the level of exercise knowledge, the concern about patient compliance and the emphasis on exercise. The patient level included sports knowledge level, personality and interest, venous line, adverse reaction of treatment, psychological state, weather environment, attention to health and concern of family members.Conclusions:The medical staff need to consider the postoperative exercise guidance for breast cancer patients from the department, themselves and patients, and should fully consider the patients' conditions and subjective experience to improve the patients' exercise compliance.