ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis （CAC） based on myeloid-derived suppressor cells （MDSCs）-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups： Blank group， Shaoyaotang without model group （7.12 g·kg^-1）， model group， sulfasalazine group （0.52 g·kg^-1）， Shaoyaotang low-dose group （3.56 g·kg^-1）， Shaoyaotang medium-dose group （7.12 g·kg^-1） and Shaoyaotang high-dose group （14.24 g·kg^-1）， with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline （10 mg·kg^-1）， while the other five groups were given a single intraperitoneal injection of azoxymethane （AOM） （10 mg·kg^-1）. After 1 week， the mice were given drinking water containing 2% dextran sulfate sodium （DSS） for 1 week， followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14^th day of the experiment， followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28^th and 98^th days of the experiment. After dissection， the colon length， colon weight， spleen weight， tumor size， and tumor number were measured. Hematoxylin and eosin （HE） staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs， regulatory T cells （Tregs）， CD4⁺ T cells， CD8⁺ T cells， and the CD4⁺/CD8⁺ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 （PD-1）， programmed cell death ligand 1 （PD-L1）， phosphorylated AMP-activated protein kinase （p-AMPK）， phosphorylated nuclear factor-κB （p-NF-κB）， and hypoxia-inducible factor 1α （HIF-1α） in the colon tissue. ResultsOn day 14， compared with the blank group， the body weight of the model group was significantly reduced （P<0.01）， reaching its lowest point on day 28 （23.39 ± 0.95 ） g. On days 28 and 98， compared with the blank group， the colon length in the model group was significantly shortened （P<0.01）， the colon index significantly increased （P<0.01）， the spleen index significantly increased （P<0.01）， and the tumor load significantly increased （P<0.01）. HE staining showed that in the model group， tumor cells， a large number of inflammatory cell infiltrates， goblet cell disappearance， and crypt loss were observed. In each dose group of Shaoyaotang， the damage to the colonic mucosa， inflammatory cell infiltration， and crypt structure destruction were alleviated. Compared with the model group， the body weight of mice in each dose group of Shaoyaotang increased. On day 98， the colon length was significantly increased （P<0.01）， the colon index significantly decreased （P<0.01）， the spleen index significantly decreased （P<0.01）， and the tumor burden significantly decreased （P<0.01） in each Shaoyaotang dose group. On days 28 and 98， MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced （P<0.01）， while CD4⁺ T cells and the CD4⁺/CD8⁺ T cell ratio were significantly increased （P<0.01）. The proportion of CD8⁺ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees （P<0.05， P<0.01）. On days 28 and 98， the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased （P<0.01）， while the expression of p-NF-κB and HIF-1α was significantly reduced （P<0.01）. ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.

Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death （PCD） is a kind of regulable cell death including various forms such as apoptosis， autophagy， pyroptosis， necrosis， and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years， modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation， PCD can control tumor development in time by playing a specific immune clearance role， while in the later tumorigenic stage， PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment， resulting in carcinogenic effects. Therefore， PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui， the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins''， the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis， while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis， which led to the escape and development of tumor cells. Therefore， under the guidance of ''regulating Qi and removing toxins''， the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation， the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage， the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells， with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.

Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death （PCD） is a kind of regulable cell death including various forms such as apoptosis， autophagy， pyroptosis， necrosis， and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years， modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation， PCD can control tumor development in time by playing a specific immune clearance role， while in the later tumorigenic stage， PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment， resulting in carcinogenic effects. Therefore， PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui， the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins''， the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis， while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis， which led to the escape and development of tumor cells. Therefore， under the guidance of ''regulating Qi and removing toxins''， the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation， the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage， the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells， with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.

Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.

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.

Objective: To analyze the epidemiological characteristics and trends of other infectious diarrhea among children under 18 years old in Guangzhou City from 2014 to 2020, and to explore the correlation between climatic factors and the incidence of the disease, so as to provide reference for the early prevention of infectious diseases. Methods: The data of cases of other infectious diarrhea and meteorological data of children under 18 years old in Guangzhou City from 2014 to 2020 were collected through the Chinese Infectious Disease Reporting System and the Guangzhou Meteorological Bureau. The correlation between meteorological factors and the incidence of other infectious diarrhea was analyzed using negative binomial regression. Results: A total of 104 566 cases of other infectious diarrhea among children under 18 years old were reported in Guangzhou City from 2014 to 2020, with a male to female ratio of 1.48∶1. The incidence rate was the highest in 2017 (980.83 per 100 000) and the lowest in 2020 (388.22 per 100 000). The peak of incidence occurred from October to March of the following year. Children under 5 years old accounted for 87.95% of all cases. The number of cases of other infectious diarrhea was negatively correlated with the temperature of the previous 6 days ( IRR = -0.07 ), and positively correlated with the temperature difference on the day of onset ( IRR =0.02) (both P <0.05). It was also positively correlated with the wind speed of the previous 7 days ( IRR=0.07, P <0.05), but there was no statistically significant correlation with the relative humidity on the day of onset ( IRR=-0.00, P >0.05). Conclusions Low temperature, large temperature difference, and high wind speed can increase the risk of other infectious diarrhea. It is necessary to strengthen the prediction and early warning in conjunction with meteorological changes, and warn kindergartens and schools to enhance preventive measures against the clustering of other infectious diarrhea cases.

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 explore the effectiveness of free paraumbilical perforator flaps in repairing skin and soft tissue defects in children. METHODS: Between February 2018 and March 2024, 12 children with skin and soft tissue defects were treated with the free paraumbilical perforator flaps. There were 7 boys and 5 girls with an average age of 6.3 years (range, 2-12 years). The defects located on the upper limbs in 6 cases, lower limbs in 5 cases, and neck in 1 case. The causes of wounds included 7 cases of electrical burns, 1 case of thermal burn, 2 cases of scar release and excision due to scar contraction after burns, 1 case of scar ulcer at the amputation stump after severe burns, and 1 case of skin necrosis after a traffic accident injury. The size of defects after debridement ranged from 7.0 cm×4.0 cm to 18.0 cm×10.0 cm. According to the defect size, 11 cases were repaired with unilateral paraumbilical perforator flaps centered on the umbilicus, among which 3 cases with larger defects were designed as "L"-shaped flaps along the lateral and lower ends of the perforator; the donor sites were directly closed. One case with extensive defect after scar excision and release was repaired with bilateral expanded paraumbilical perforator flaps; the donor sites were repaired with autologous split-thickness skin grafts. The size of flaps ranged from 9.0 cm×4.0 cm to 20.0 cm×11.0 cm. Postoperatively, analgesia and sedation were provided, and the blood supply of the flaps was observed. RESULTS: All operations were successfully completed. The operation time was 4-7 hours, with an average of 5.0 hours. After postoperative analgesia and sedation, the visual analogue scale (VAS) score for pain in all children was less than or equal to 3, and there was no non-cooperation due to pain. All flaps and skin grafts survived completely, and the wounds healed by first intention. Ten children underwent 1-4 times of flap de-fatting, finger separation, and trimming. All children were followed up 6-48 months (mean, 26.6 months). No obvious swelling of the flaps occurred, and the texture was soft. At last follow-up, among the 6 children with upper limb defects, 2 had upper limb function grade Ⅳ and 4 had upper limb function grade Ⅴ according to the Carroll upper limb function assessment method. The 4 children with lower limb defects had no limitation of joint movement. The neck flexion and rotation in the 1 child with neck defect significantly improved when compared with that before operation. The 1 child with residual ulcer at the amputation stump could wear a prosthesis and move without limitation, and no new ulcer occurred. Linear scars were left at the donor sites, and no abdominal wall hernia was formed. CONCLUSION The free paraumbilical perforator flap has abundant blood supply and can be harvested in large size. It can be used to repair skin and soft tissue defects in children and has the advantages of short operation time, minimal injury, high safety, and minimal impact on the growth and development of children.
Humans ; Perforator Flap/transplantation* ; Child ; Male ; Female ; Soft Tissue Injuries/surgery* ; Child, Preschool ; Plastic Surgery Procedures/methods* ; Burns/surgery* ; Umbilicus/surgery* ; Skin Transplantation/methods* ; Skin/injuries* ; Cicatrix/surgery* ; Treatment Outcome

OBJECTIVES: To explore the mechanism of Pingchuanning Formula (PCN) for inhibiting airway inflammation in rats with asthmatic cold syndrome. METHODS: A total of 105 SD rats were randomized equally into 7 groups, including a control group, an asthmatic cold syndrome model group, 3 PCN treatment groups at high, medium and low doses, a Guilong Kechuanning (GLCKN) treatment group, and a dexamethasone (DEX) treatment group. In all but the control rats, asthma cold syndrome models were established and daily gavage of saline, PCN, GLCKN or DEX was administered 29 days after the start of modeling. The changes in general condition, lung function and lung histopathology of the rats were observed, and inflammatory factors in the alveolar lavage fluid (BALF), oxidative stress, lung tissue ultrastructure, cytokine levels, and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed. RESULTS: The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass, food intake, and water intake, reduced FEV_0.3, FVC, and FEV_0.3/FVC, obvious inflammatory cell infiltration in the lung tissue, and increased alveolar inflammation score and counts of neutrophils, eosinophils, lymphocytes, macrophages, and leukocytes in the BALF. The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues, where the expressions of HMGB1, Beclin-1, ATG5, TNF-α, IL-6,IL-1β, and IL-13 and the LC3II/I ratio were increased, while the levels of Bcl-2 and IFN-γ were decreased. PCN treatment significantly improved these pathological changes in the rat models, and its therapeutic effect was better than that of GLKCN and similar to that of DEX. CONCLUSIONS PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy, thereby attenuating airway inflammatory damages.
Animals ; Rats ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Asthma/pathology* ; Beclin-1 ; HMGB1 Protein/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Male ; Lung/pathology* ; Inflammation