ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most common chronic liver disease， and it has become a major global health issue. Excessive lipid accumulation in the liver is the core pathological event of MAFLD， which triggers lipotoxicity and leads to cell apoptosis， necrosis， and inflammatory cascades by mediating endoplasmic reticulum stress， oxidative stress， organelle dysfunction， and ferroptosis， thereby promoting the progression of simple hepatic steatosis to steatohepatitis and fibrosis. In this process， very-long-chain fatty acids （VLCFAs）， as essential components of cell membranes and lipid metabolism， have attracted increasing attention for their role in lipotoxicity mechanisms. This article reviews the role of VLCFAs in lipid metabolism processes and lipotoxicity mechanisms， focusing on how VLCFAs participate in metabolic regulation through key proteins and disrupt cell membranes to induce oxidative stress， and how their metabolites and derivatives drive inflammatory responses， ultimately promoting the progression of MAFLD.

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.