Sepsis-acquired weakness (SAW) is a common complication in critically ill patients, yet significant gaps remain in both mechanistic understanding and therapeutic interventions for this condition. SAW not only prolongs the duration of mechanical ventilation and hospitalization but is also closely associated with increased mortality. Even if these SAW patients survive, they often experience long-term physical dysfunction after hospital discharge, leading to diminished quality of life. Emerging evidence suggests that sustained mitochondrial dysfunction may constitute a pivotal pathophysiological basis for the development and progression of SAW, primarily encompassing five key aspects: dysregulated mitochondrial quality control (MtQC), impaired oxidative phosphorylation (OXPHOS), exacerbated oxidative stress, disrupted Ca²⁺; homeostasis, and their mediation of diverse myofiber injuries. This article systematically elucidates the central role of mitochondrial dysfunction in the pathogenesis of SAW. Furthermore, we explore potential therapeutic strategies targeting mitochondrial function, including mitigating mitochondrial oxidative stress, optimizing nutritional support, and supplementing with muscle-derived mesenchymal stem cells. These insights provide a critical theoretical framework for understanding SAW mechanisms and developing clinical interventions, with particular emphasis on the translational value of mitochondrial-targeted therapies in improving outcomes for septic patients.
Humans ; Sepsis/metabolism* ; Mitochondria/metabolism* ; Muscle Weakness/etiology* ; Oxidative Stress ; Oxidative Phosphorylation

Objective To investigate the predictive ability of cyst fluid characteristics for malignant intraductal papillary mucinous neoplasms (IPMNs). Methods We prospectively collected fresh cyst fluid from patients undergoing pancreatic resection at the Department of Hepatobiliary Pancreatic Spleen Surgery, Changhai Hospital, Shanghai, from September 2023 to December 2024, who were ultimately pathologically confirmed with IPMN. We assessed the characteristics of cyst fluid, including viscosity, clarity, and color, and explored its predictive performance for benign or malignant. Results A total of 40 patients with IPMN were included. The sensitivity of the string sign （+） for diagnosing high-grade dysplasia/ invasive carcinoma （HGD/IC） was 90.9%, specificity was 92.9%, and accuracy was 76.0%. The cyst fluid of intestinal-type IPMN often exhibited a gelatinous consistency, and there was no significant difference in the distribution of gelatinous consistency between the HGD/IC group and the low-grade dysplasia （LGD） group. There were no significant differences in CEA, glucose, and amylase levels in the cyst fluid between the HGD/IC group and the LGD group. Conclusions The characteristics of pancreatic cyst fluid, especially viscosity, can effectively predict the benign or malignant nature of IPMN.

The 2024 World Conference on Lung Cancer (WCLC) and the European Society for Medical Oncology (ESMO) Annual Meeting, two of the most prestigious events in oncology, have concluded sequentially. As the most authoritative annual gatherings in lung cancer and the entire oncology field, the WCLC and ESMO conferences brought together top oncology experts and scientists from around the world to share, discuss, and publish the latest cutting-edge advancements in oncology. In both conferences, lung cancer immunotherapy remained a hot topic of considerable interest. This article aims to summarize and discuss the important research progress on perioperative immunotherapy for non-small cell lung cancer reported at the two conferences.

Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P＜0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P＞0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P＜0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P＜0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Objective To conduct a comprehensive review on application status and future development prospects of proton therapy for pediatric medulloblastoma.Methods A total of 218 literatures were retrieved from PubMed and CNKI database using the search terms"pediatric medulloblastoma,proton therapy,radiotherapy"(English)and"儿童髓母细胞瘤,质子治疗,放射治疗"(Chinese),with a publication timeframe from January 1,2004,to June 1,2025.Inclusion criteria were as follow:(1)proton therapy for pediatric medulloblastoma;(2)radiotherapy for pediatric medulloblastoma;(3)proton therapy for pediatric brain tumors;(4)development and applications of proton therapy.Exclusion criteria were as follow:(1)outdated literatures;(2)redundant or highly similar studies.After screening,89 literatures met the inclusion criteria.Results Compared with conventional treatments such as surgery,photon therapy,and chemotherapy,proton therapy for pediatric medulloblastoma significantly reduced acute toxicity and long-term side effects including cognitive dysfunction,endocrine disorders,and hearing loss.Additionally,proton therapy exhibited favorable cost-effectiveness.In the future,the therapeutic outcomes would be further enhanced through the optimization of proton therapy techniques,treatment planning,and equipment.Conclusion With ongoing technological advancements and growing clinical experience,proton therapy is expected to become one of the standard treatment modalities for pediatric medulloblastoma.

Background and purpose:There are few studies on the quality of life after transanal total mesorectal excision(TaTME)for rectal cancer,and there is a lack of evidence-based research.This study aimed to evaluate the impact of TaTME in comparison to laparoscopic total mesorectal excision(LaTME)on postoperative quality of life in patients.Methods:A retrospective analysis was conducted on clinical and pathological data from rectal cancer patients who underwent LaTME and TaTME between September 2019 and September 2022 at Renhe Hospital,Baoshan District,Shanghai,and Fudan University Shanghai Cancer Center.All the patients completed a set of validated questionnaires one year postoperatively,including the EORCT QLQ-C30,Low Anterior Resection Syndrome(LARS)score,International Prostate Symptom Score(IPSS),Generalized Anxiety Disorder-7(GAD-7),and Patient Health Questionnaire-9(PHQ-9).Comparative analysis of these survey results was performed.The study was approved by the Ethics Committee of Renhe Hospital,Baoshan District,Shanghai.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:A total of 39 patients in the TaTME group and 38 patients in the LaTME group were included.There were no statistically significant differences between two groups regarding demographic variables such as gender and age,as well as clinical factors including tumor distance from the anal verge,tumor stage,and preoperative neoadjuvant treatment protocols.Analysis of EORCT QLQ-C30 results indicated equivalent overall quality of life between the two groups;however,the TaTME group reported significantly more severe insomnia(P=0.020).No significant differences were observed in LARS severity or total scores between the groups,though the TaTME group demonstrated superior functional outcomes in terms of incontinence for liquid stools and clustering of stools(P=0.007,P=0.004).Additionally,both groups exhibited comparable results in IPSS,and levels of depression and anxiety.Conclusion:The findings suggest that TaTME and LaTME yield similar outcomes in terms of anal and urinary function,overall quality of life,and psychological health,indicating that it is a viable and safe alternative to LaTME in terms of postoperative quality of life.

Objective To conduct a comprehensive review on application status and future development prospects of proton therapy for pediatric medulloblastoma.Methods A total of 218 literatures were retrieved from PubMed and CNKI database using the search terms"pediatric medulloblastoma,proton therapy,radiotherapy"(English)and"儿童髓母细胞瘤,质子治疗,放射治疗"(Chinese),with a publication timeframe from January 1,2004,to June 1,2025.Inclusion criteria were as follow:(1)proton therapy for pediatric medulloblastoma;(2)radiotherapy for pediatric medulloblastoma;(3)proton therapy for pediatric brain tumors;(4)development and applications of proton therapy.Exclusion criteria were as follow:(1)outdated literatures;(2)redundant or highly similar studies.After screening,89 literatures met the inclusion criteria.Results Compared with conventional treatments such as surgery,photon therapy,and chemotherapy,proton therapy for pediatric medulloblastoma significantly reduced acute toxicity and long-term side effects including cognitive dysfunction,endocrine disorders,and hearing loss.Additionally,proton therapy exhibited favorable cost-effectiveness.In the future,the therapeutic outcomes would be further enhanced through the optimization of proton therapy techniques,treatment planning,and equipment.Conclusion With ongoing technological advancements and growing clinical experience,proton therapy is expected to become one of the standard treatment modalities for pediatric medulloblastoma.

Background and purpose:There are few studies on the quality of life after transanal total mesorectal excision(TaTME)for rectal cancer,and there is a lack of evidence-based research.This study aimed to evaluate the impact of TaTME in comparison to laparoscopic total mesorectal excision(LaTME)on postoperative quality of life in patients.Methods:A retrospective analysis was conducted on clinical and pathological data from rectal cancer patients who underwent LaTME and TaTME between September 2019 and September 2022 at Renhe Hospital,Baoshan District,Shanghai,and Fudan University Shanghai Cancer Center.All the patients completed a set of validated questionnaires one year postoperatively,including the EORCT QLQ-C30,Low Anterior Resection Syndrome(LARS)score,International Prostate Symptom Score(IPSS),Generalized Anxiety Disorder-7(GAD-7),and Patient Health Questionnaire-9(PHQ-9).Comparative analysis of these survey results was performed.The study was approved by the Ethics Committee of Renhe Hospital,Baoshan District,Shanghai.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:A total of 39 patients in the TaTME group and 38 patients in the LaTME group were included.There were no statistically significant differences between two groups regarding demographic variables such as gender and age,as well as clinical factors including tumor distance from the anal verge,tumor stage,and preoperative neoadjuvant treatment protocols.Analysis of EORCT QLQ-C30 results indicated equivalent overall quality of life between the two groups;however,the TaTME group reported significantly more severe insomnia(P=0.020).No significant differences were observed in LARS severity or total scores between the groups,though the TaTME group demonstrated superior functional outcomes in terms of incontinence for liquid stools and clustering of stools(P=0.007,P=0.004).Additionally,both groups exhibited comparable results in IPSS,and levels of depression and anxiety.Conclusion:The findings suggest that TaTME and LaTME yield similar outcomes in terms of anal and urinary function,overall quality of life,and psychological health,indicating that it is a viable and safe alternative to LaTME in terms of postoperative quality of life.

Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P＜0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P＞0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P＜0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P＜0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.