ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

OBJECTIVE To explore the effects of isorhamnetin on the development of gastric cancer through up-regulation of solute carrier family 25 member 25 antisense RNA 1（SLC25A25-AS1）. METHODS Using BALB/c nude mice as the subjects， the xenograft tumor model was established by subcutaneously inoculating human gastric cancer MKN28 cells into the axillary region. The effects of low and high doses of isorhamnetin （20 and 40 mg/kg） on the tumor volume and mass in nude mice were investigated. MKN28 cells were selected and divided into control group， isorhamnetin group （70 μmol/L， similarly hereinafter）， isorhamnetin+knocking down negative control group， isorhamnetin+knocking down SLC25A25-AS1 group， isorhamnetin+ overexpression negative control group and isorhamnetin+overexpressing SLC25A25-AS1 group. Effects of knocking down/ overexpressing SLC25A25-AS1 on viability， apoptosis， migration and invasion ability of isorhamnetin-treated cells were detected. After verifying the targeting relationships between microRNA-212-3p （miR-212-3p） and SLC25A25-AS1， as well as phosphatase and tensin homologue deleted on chromosome 10 （PTEN）， the effects of knocking down/overexpressing SLC25A25-AS1 on the expression of miR-212-3p， PTEN mRNA， and PTEN protein in isorhamnetin-treated cells were investigated. RESULTS Compared with the model control group， tumor volume and mass of nude mice in the isorhamnetin low-dose and high-dose groups were reduced significantly， and the isorhamnetin high-dose group was significantly lower than the isorhamnetin low-dose group （P＜0.05）. miR-212-3p had targeting relationships with SLC25A25-AS1 and PTEN. Compared with the control group， the cell viability （intervened for 24， 48 h）， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin group， isorhamnetin+knocking down negative control group and isorhamnetin+overexpressing negative control group were significantly reduced or decreased or down-regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly increased or up-regulated （P＜0.05）. Compared with isorhamnetin group and isorhamnetin+knocking down negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in the isorhamnetin+knocking down SLC25A25-AS1 group were significantly increased or up- regulated， while the apoptosis rate， mRNA and protein expressions of PTEN were significantly reduced or down-regulated （P＜ 0.05）. Compared with isorhamnetin group and isorhamnetin+overexpressing negative control group， the cell viability， migration number， invasion number and miR-212-3p expression of cells in isorhamnetin+overexpressing SLC25A25-AS1 group were significantly reduced or decreased or down-regulated， while the apoptosis rate， PTEN mRNA and protein expressions were significantly increased or up-regulated （P＜0.05）. CONCLUSIONS Isorhamnetin may inhibit the development of gastric cancer by up-regulating the expression of SLC25A25-AS1， down-regulating miR-212-3p， and up-regulating the expression of PTEN， which is a downstream target of miR-212-3p.

OBJECTIVE To explore the effects of limonin on renal lesions， glucose metabolism， inflammation， and oxidative stress in gestational diabetic rats and its possible mechanisms. METHODS The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group （intragastrical administration and tail vein injection of equal volume of normal saline）， limonin low-， medium-， and high-dose groups （intragastrical administration of limonin， at doses of 12.5， 25.0 and 50.0 mg/kg， and equal volume of normal saline into the tail vein）， and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun N-terminal kinase （JNK） activator Anisomycin 2 mg/kg ]， with 12 rats in each group. In addition， 12 pregnant rats were selected as the control group （intragastrical administration and tail vein injection of equal volume of normal saline）. They were given relevant medicine， once a day， for 14 consecutive days. After the last administration， fasting blood glucose （FBG）， the levels of fasting insulin （FINS）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum were detected； the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， blood urea nitrogen （BUN）， and creatinine （Cr） in the renal tissue were detected； the pathological changes of renal tissue were observed； the expressions of proteins related to the JNK/nuclear factor-κB （NF-κB） signaling pathway in the renal tissue were detected. RESULTS Compared with control group， in model group， the rats showed pathological injuries in the kidney tissue， such as glomerular atrophy， edema of renal tubular epithelial cells； the levels of FBG， FINS， IL-1β， IL-6， TNF-α， MDA， BUN and Cr， HOMA-IR， as well as the phosphorylation levels of JNK and NF-κB 0453-6602005。E-mail：mcvi45@163.com p65 proteins were increased significantly （P＜0.05）， while the levels of SOD and GSH-Px were decreased significantly （P＜0.05）. Compared with model group， in each dose group of limonin， the degree of renal tissue lesions in rats was alleviated， and the above-mentioned indicators were significantly improved （P＜0.05）， showing an obvious dose-effect relationship （P＜0.05）. Compared with high-dose limonin group， in the combination group， the degree of renal tissue lesions in rats was relatively aggravated， and the changes in the above-mentioned indicators were significantly reversed （P＜0.05）. CONCLUSIONS Limonin has a certain improvement effect on renal lesions， glucose metabolism， inflammation， and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To investigate the effect and mechanism of Jiedu Xiaoying Patch in rats with Hashimoto's thyroiditis (HT).Methods:Totally 32 rats were randomly divided into a blank group of 8 rats and a model group of 24 rats. The HT rat model was prepared by freely drinking 0.064% sodium iodide solution in the modeling module. 24 successfully modeled rats were randomly divided into model group, selenium yeast group, and patch group, with 8 rats in each group. Starting from the 9th week, the application group applied Jiedu Xiaoying Patch to the surface projection area of the thyroid gland in the neck of rats for 6 hours, once a day, for a total of 6 weeks; the selenium yeast group was orally administered with 21 μg/ml selenium yeast solution at a dose of 0.5 ml/100 g, while the blank group, model group, and patch group were orally administered with equal volumes of physiological saline solution once a day for a total of 6 weeks. The levels of TGAb,TPOAb, Sema 5A, and IL-17A in rat serum were detected by ELISA. The changes of thyroid tissue was observed with HE staining. The relative expression levels of plexin-A1 and plexin-B3 were determined through RT-PCR.Results:Compared with the model group, the levels of TPOAb, TGAb, Sema 5A, and IL-17A decreased ( P<0.05), and the expressions of plexin-A1 and plexin-B3 decreased in the selenium yeast group and the patch group ( P<0.05). The thyroid follicles in the model group were severely damaged, with a large number of lymphocytes infiltrating the interstices; the thyroid follicular structure of the selenium yeast group was relatively intact, and lymphocyte infiltration was reduced compared to the model group. The thyroid follicular structure of the patch group was basically intact, with a small amount of lymphocyte infiltration observed. Conclusion:Jiedu Xiaoying Patch can significantly reduce the levels of TPOAb and TGAb in HT rats. The mechanism may be related to reducing the content of Sema 5A, inhibiting the expressions of receptors plexin-A1 and plexin-B3, reducing the production of inflammatory cytokines such as IL-17A, and inhibiting immune and inflammatory responses.

Objective: To analyze the association between poor sleep characteristics and the coexistence of negative emotions and overweight/obesity among college students, so as to provide a scientific basis for improving their physical and mental health. Methods: From November to December 2023, a convenience sampling method was used to survey 6 600 college students from nine universities in Jiangxi, Hunan, and Hubei provinces. The Depression Anxiety and Stress Scale-21 (DASS-21), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and physical examinations were employed to assess negative emotions, poor sleep characteristics, and overweight/obesity. Chi square test and Logistic regression were used to analyze the impact of poor sleep characteristics on the coexistence of negative emotions and overweight/obesity. Results: The coexistence rates of different categories of negative emotions (depression, anxiety, stress) and overweight/obesity were 6.1% ( n= 405), 8.0% ( n =529), and 3.3% ( n =217), respectively. Gender, grade level, major, maternal education level, annual family income, physical activity level, only child status, and carbonated beverage consumption were statistically associated with the coexistence rates of different categories of negative emotions and overweight/obesity ( χ 2=4.01-35.18, all P <0.05). Logistic regression analysis showed that after adjusting for gender, grade level, major, only child status, maternal education level, annual family income, physical activity level, and carbonated beverage consumption, poor sleep characteristics were significantly associated with an increased risk of the coexistence of negative emotions and overweight/obesity ( OR =1.41-6.65); moderate and poor sleep quality levels were significantly associated with an increased risk of the coexistence of different categories of negative emotions and overweight/obesity among female students ( OR =1.99-4.71) (all P <0.05). Conclusions Poor sleep characteristics are associated with the coexistence of negative emotions and overweight/obesity among college students. Greater attention should be paid to sleep issues in this population, and sleep education should be actively promoted to reduce the risk of comorbid negative emotions and overweight/obesity.

AIM: To compare the effectiveness of foldable capsular body(FCB)with traditional scleral buckling(SB)in the treatment of experimental retinal detachment animal models.METHODS: After successfully establishing rhegmatogenous retinal detachment(RRD)animal models, 24 New Zealand white rabbits were randomly divided into three groups(RRD models group, SB group, and FCB group), with 8 rabbits in each group. The FCB and SB groups underwent SB and FCB surgeries for the RRD animal models, while the RRD models group only consists of RRD models without any surgical intervention during the follow-up period. The follow-up duration was 3 mo. Wide-field neonatal fundus imaging system and ophthalmic B-ultrasound were used to assess the fundus conditions before and after surgery. The Icare® TONOVET Plus tonometer was utilized to evaluate intraocular pressure changes before and after surgery. The Eaton and Draize scoring systems were selected to monitor postoperative inflammatory reactions.RESULTS: The retinal reattachment rates in the FCB and SB groups were 87.5% and 75.0%, respectively, with no statistically significant difference between the groups(P>0.05). The intraocular pressure in both the FCB and SB groups increased postoperatively compared to preoperative levels(P<0.01), and there were no significant differences in intraocular pressure at any time points during the follow-up period between the groups(P>0.05). The intraocular pressure in the RRD models group remained at a low level throughout the follow-up period. The average surgical time for the FCB group was 16.87±2.29 min, which was shorter than 46.25±4.74 min in the SB group(t=-15.166, P<0.001). According to the Eaton and Draize scoring systems, the FCB group had lower grades of conjunctival hyperemia and edema in the early postoperative period compared to the SB group, indicating milder inflammatory reactions(P<0.05).CONCLUSION: Both FCB and SB are effective in treating experimental RRD. Compared to SB, FCB is simpler to operate, and also has a shorter surgical time and milder postoperative inflammatory reactions.