It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease （IBD）. Cold pathogens may serve as the initiating factor. When first invading the intestines， cold pathogens obstruct the flow of qi； over time， the lingering cold impairs the middle jiao （焦）， eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation， the process can be divided into three stages， active stage， remission stage， and carcinogenic stage. In the active stage， the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines； in the remission stage， cold qi impairs the spleen， disrupting its transport and transformation functions； and in the carcinogenic stage， the mechanisms include cold-induced accumulation， phlegm accumulation from cold， and stagnation of cold and blood stasis. Accordingly， the treatment strategies are proposed.In the active stage， regulating qi， relieving stagnation， and harmonizing cold and heat； in the remission stage， warming yang， dispersing cold， tonifying qi， and strengthening the spleen； and in the carcinogenic stage， promoting qi circulation， dispersing cold， resolving phlegm， activating yang， and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.

The theory of "fire and primordial qi incompatibility" was proposed by LI Gao in Clarifying Doubts about Damage from Internal and External Causes, which has important guiding significance for explaining the pathogenesis, prognosis and treatment of immune-related adverse events (irAEs). "Fire" refers to yin fire, a type of deficient fire transformed from the deficiency of the spleen and stomach, reflecting the pathological state of coexisting deficiency and heat patterns in patients with tumor after immune checkpoint inhibitor (ICI) therapy. "Primordial qi" is the most fundamental essence of human life activities and serves as the source of all bodily qi. Based on the theory of "fire and primordial qi incompatibility" and Western medicine research, we found that excessive use of ICIs can damage the spleen and stomach, leading to excessive yin fire. When yin fire becomes excessive, it consumes and injures the primordial qi; when the primordial qi is depleted, it leads to more excessive yin fire and further deficiency of the spleen and stomach, forming a syndrome in which deficiency and excess coexist. Starting from the theory of "fire and primordial qi incompatibility, "combined with our team′s clinical practice and modern pharmacological research, this study explores the application characteristics of sweet-natured herbs for irAEs during ICIs therapy and interval periods, and summarizes the treatment principles, aiming to provide new perspectives and approaches for the prevention and treatment of tumor-related irAEs with traditional Chinese medicine.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Objective:To investigate the feasibility and effect of endoscopic assisted surgery combined with sclerosing agent injection and negative pressure drainage for the treatment of microcystic lymphatic malformation in children.Methods:A retrospective analysis was conducted on clinical data of pediatric patients with microcystic lymphatic malformations between December 2021 and December 2023 in the Department of Burns and Plastic Surgery at Children’s Hospital of Nanjing Medical University. The treatment protocol consisted of endoscope-assisted surgery combined with sclerotherapy and negative pressure drainage. Preoperatively, two-dimensional ultrasound was utilized to demarcate the surface extent of the malformation. Intraoperatively, subcutaneous lymphatic malformation tissues were resected as thoroughly as possible under endoscopic guidance, and cystic cavities were interconnected. Postoperatively, a drainage tube was placed and connected to a negative pressure system. Starting on the third postoperative day, the cystic cavity was irrigated with absolute ethanol every other day. Irrigation was continued until the drainage fluid became light yellow and clear, and the daily drainage volume fell below 5 ml, at which point the drainage tube was removed. Complications were monitored, and treatment efficacy was assessed at the last follow-up using a four-tiered outcome scale: cured, markedly effective, effective, and ineffective. The overall effectiveness rate was calculated as (cured + markedly effective + effective) cases/total number of cases × 100%. Data analysis was performed using descriptive statistics.Results:A total of 20 pediatric patients were enrolled, including 8 males and 12 females. The age range was from 1 month to 13 years, with a mean age of 7 years and 7 months. All lesions were located superficially, distributed as follows: head, face, and neck (8 cases), chest (2 cases), abdomen (3 cases), back (2 cases), and limbs (5 cases). The lesion volumes ranged from 5.8 cm × 4.2 cm × 3.8 cm to 14.5 cm × 10.4 cm × 8.4 cm. No complications such as absolute ethanol intoxication, severe allergic reactions, surgical site infection, neurovascular injury, thrombosis, or pulmonary embolism occurred during the treatment period. All patients had their negative pressure drainage tubes removed on postoperative day 10. After tube removal, one case developed serous drainage from the incision, which resolved after 4 days of wound care and compressive dressing. The remaining 19 cases demonstrated satisfactory incision healing. During a follow-up period of 6 to 12 months, no significant postoperative scarring and recurrence were observed. Treatment outcomes were as follows: 4 cases of cured, 10 cases of markedly effective, 5 cases of effective, and 1 case of ineffective. The overall effective rate was 95%(19/20).Conclusion:The integrated approach of endoscope-assisted surgery combined with sclerotherapy and negative pressure drainage for the treatment of microcystic lymphatic malformations in children yields definite and favorable outcomes. This comprehensive technique is characterized by its minimal invasiveness, stable long-term result as confirmed by follow-up, absence of severe complications, and a low recurrence rate.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:It aims to systematically evaluate the current status of knowledge,attitude,and practice(KAP)regarding universal commercial medical insurance among residents of the sample province from the demand-side perspective.Methods:Utilizing a quota sampling method,face-to-face surveys were conducted via the Questionnaire Star platform to collect demographic characteristics and KAP data of the participants.Comparisons of differences among different groups were made using t-tests,analysis of variance,and chi-square tests.Furthermore,multiple linear regression and structural equation modeling were utilized to analyze the influencing factors of KAP,as well as the pathways among these three factors.Results:Out of the 415 valid questionnaires collected,there were notable differences in KAP among respondents with diverse demographic backgrounds.Regression analysis revealed that education level,frequency of health check-ups,and engagement in other commercial health insurances significantly influenced knowledge;education level,involvement in other commercial health insurances,and self-assessed health status were pivotal in shaping attitudes;whereas age,education level,frequency of health check-ups,and participation in other commercial health insurances were critical in affecting practice.The path analysis results indicate that knowledge of universal commercial medical insurance has a significant direct association with attitude(β=0.379,P＜0.001)and practice(β=0.323,P＜0.001).It also influences practice through attitude as a mediator(β=0.016,P＜0.001),but the direct effect of attitude on practice is not significant(β=0.04,P=0.403).Conclusion:While residents in the sample province exhibit a positive attitude towards universal commercial medical insurance,there is a need to enhance their level of knowledge and engagement in practice.It is recommended to strengthen targeted educational and promotional measures to promote the healthy and sustainable development of universal insurance.

Objective:It aims to systematically evaluate the current status of knowledge,attitude,and practice(KAP)regarding universal commercial medical insurance among residents of the sample province from the demand-side perspective.Methods:Utilizing a quota sampling method,face-to-face surveys were conducted via the Questionnaire Star platform to collect demographic characteristics and KAP data of the participants.Comparisons of differences among different groups were made using t-tests,analysis of variance,and chi-square tests.Furthermore,multiple linear regression and structural equation modeling were utilized to analyze the influencing factors of KAP,as well as the pathways among these three factors.Results:Out of the 415 valid questionnaires collected,there were notable differences in KAP among respondents with diverse demographic backgrounds.Regression analysis revealed that education level,frequency of health check-ups,and engagement in other commercial health insurances significantly influenced knowledge;education level,involvement in other commercial health insurances,and self-assessed health status were pivotal in shaping attitudes;whereas age,education level,frequency of health check-ups,and participation in other commercial health insurances were critical in affecting practice.The path analysis results indicate that knowledge of universal commercial medical insurance has a significant direct association with attitude(β=0.379,P＜0.001)and practice(β=0.323,P＜0.001).It also influences practice through attitude as a mediator(β=0.016,P＜0.001),but the direct effect of attitude on practice is not significant(β=0.04,P=0.403).Conclusion:While residents in the sample province exhibit a positive attitude towards universal commercial medical insurance,there is a need to enhance their level of knowledge and engagement in practice.It is recommended to strengthen targeted educational and promotional measures to promote the healthy and sustainable development of universal insurance.

Objective:To investigate the feasibility and effect of endoscopic assisted surgery combined with sclerosing agent injection and negative pressure drainage for the treatment of microcystic lymphatic malformation in children.Methods:A retrospective analysis was conducted on clinical data of pediatric patients with microcystic lymphatic malformations between December 2021 and December 2023 in the Department of Burns and Plastic Surgery at Children’s Hospital of Nanjing Medical University. The treatment protocol consisted of endoscope-assisted surgery combined with sclerotherapy and negative pressure drainage. Preoperatively, two-dimensional ultrasound was utilized to demarcate the surface extent of the malformation. Intraoperatively, subcutaneous lymphatic malformation tissues were resected as thoroughly as possible under endoscopic guidance, and cystic cavities were interconnected. Postoperatively, a drainage tube was placed and connected to a negative pressure system. Starting on the third postoperative day, the cystic cavity was irrigated with absolute ethanol every other day. Irrigation was continued until the drainage fluid became light yellow and clear, and the daily drainage volume fell below 5 ml, at which point the drainage tube was removed. Complications were monitored, and treatment efficacy was assessed at the last follow-up using a four-tiered outcome scale: cured, markedly effective, effective, and ineffective. The overall effectiveness rate was calculated as (cured + markedly effective + effective) cases/total number of cases × 100%. Data analysis was performed using descriptive statistics.Results:A total of 20 pediatric patients were enrolled, including 8 males and 12 females. The age range was from 1 month to 13 years, with a mean age of 7 years and 7 months. All lesions were located superficially, distributed as follows: head, face, and neck (8 cases), chest (2 cases), abdomen (3 cases), back (2 cases), and limbs (5 cases). The lesion volumes ranged from 5.8 cm × 4.2 cm × 3.8 cm to 14.5 cm × 10.4 cm × 8.4 cm. No complications such as absolute ethanol intoxication, severe allergic reactions, surgical site infection, neurovascular injury, thrombosis, or pulmonary embolism occurred during the treatment period. All patients had their negative pressure drainage tubes removed on postoperative day 10. After tube removal, one case developed serous drainage from the incision, which resolved after 4 days of wound care and compressive dressing. The remaining 19 cases demonstrated satisfactory incision healing. During a follow-up period of 6 to 12 months, no significant postoperative scarring and recurrence were observed. Treatment outcomes were as follows: 4 cases of cured, 10 cases of markedly effective, 5 cases of effective, and 1 case of ineffective. The overall effective rate was 95%(19/20).Conclusion:The integrated approach of endoscope-assisted surgery combined with sclerotherapy and negative pressure drainage for the treatment of microcystic lymphatic malformations in children yields definite and favorable outcomes. This comprehensive technique is characterized by its minimal invasiveness, stable long-term result as confirmed by follow-up, absence of severe complications, and a low recurrence rate.

Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bis-pecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed tech-niques in elucidating the inherent structural characteristics of novel therapeutics and their conforma-tional stability.