OBJECTIVE To study the improvement effects and potential mechanisms of water extract from Chrysanthemum morifolium on skeletal muscle atrophy in rats after ischemic stroke. METHODS Sprague-Dawley rats were randomly divided into sham operation group， model group， ATP group （10 mg/kg）， C. morifolium water extract high-dose and low-dose groups （1.08， 0.54 g/kg）. Except for sham operation group， ischemic stroke models were induced in rats from the other groups using middle cerebral artery occlusion. Starting from the first day after surgery， rats in each group were given corresponding drug/normal saline intragastrically， once a day， for consecutive 7 days. On the 7th day post-surgery， the rats’ body weights were measured， and their motor functions were evaluated， including Longa scores， exercise distance， grip strength； the electrophysiological signals of the skeletal muscles in rats were measured； the pathological morphology of the soleus muscle in rats was observed； the levels of tumor necrosis factor-α （TNF-α） in serum and soleus muscle were measured； the expressions of proteins related to TNF-α/c-Jun N- terminal kinase （JNK）/mitogen-activated protein kinase （MAPK） signaling pathway in the soleus muscle were determined. RESULTS Compared with sham operation group， the body weight， grip strength and exercise distance of rats were decreased/ shortened significantly （P＜0.01）； additionally， there was a notable reduction in the interpeak value of skeletal muscle electrophysiology （P＜0.05 or P＜0.01）. Longa score， as well as the levels of TNF-α in serum and soleus muscle， and the expression levels of TNF-α， phosphorylated JNK， phosphorylated MAPK， muscle ring-finger protein-1， and muscle atrophy Fbox- 1 protein in the soleus muscle， were all significantly elevated （P＜0.01）. The skeletal muscle cells of the soleus muscle in the model group showed significant atrophy， with a markedly decreased cross-sectional area （P＜0.01）. Compared with the model group， the levels of the aforementioned indicators were significantly reversed in C. morifolium water extract groups （P＜0.05 or P＜ 0.01）， and the skeletal muscle cells of the soleus muscle were markedly enlarged. CONCLUSIONS C. morifolium water extract can improve skeletal muscle atrophy in rats after ischemic stroke， the mechanism of which may be associated with suppressing the activation of the TNF- α/JNK/MAPK E-mail：19932015@cdutcm.edu.cn signaling pathway.

ObjectiveTo observe the clinical efficacy and safety of traditional Chinese medicine （TCM） triple therapy in the treatment of spontaneous bacterial peritonitis （SBP） with damp-heat stagnation and toxin-blood stasis syndrome in liver cirrhosis patients， and to explore its potential mechanisms of action. MethodsEighty-six patients were randomly divided into the experimental group and the control group， with 43 patients in each group. Both groups received standard western medicine treatment， while the experimental group additionally received TCM triple therapy， including oral Qingre Liangxue Jiedu Decoction （清热凉血解毒汤）， retention enema with Dachengi Decoction （大承气汤）， and abdominal application of Qingre Zhitong Lishui Fomulation （清热止痛利水方） with lotus leaf. Both groups were treated for 2 weeks. Before and after treatment， various indicators were measured， such as TCM syndrome scores， ascites volume measured by abdominal ultrasound， liver function indicators including total bilirubin （TBIL）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and albumin （ALB）， infection markers， including neutrophil percentage （NEUT%）， C-reactive protein （CRP）， and procalcitonin （PCT）， inflammatory factors， such as tumor necrosis factor-alpha （TNF-ɑ）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）， intestinal mucosal barrier function markers， including endotoxin （ET）， diamine oxidase （DAO）， D-lactic acid （D-Lac）， occludin， and zonula occludens-1 （ZO-1）， and peritoneal polymorphonuclear （PMN） cell counts at 72 hours post-treatment. ResultsA total of 82 patients were included in the final analysis， with 41 patients in each group. The total effective rate for TCM syndrome in the experimental group was 92.68% （38/41）， which was significantly higher than the 80.49% （33/41） in the control group （P＜0.05）. Compared with pre-treatment values， both groups showed significant reductions in TCM syndrome scores， ascites volume， TBIL， ALT， AST， NEUT%， CRP， PCT， TNF-α， IL-6， ET， DAO， D-Lac， Occludin， and ZO-1， with an increase in IL-10 levels and a decrease in PMN count in ascites 72 hours post-treatment （P＜0.05）. Furthermore， the experimental group outperformed the control group in all the above indicators after treatment （P＜0.05）. The disappearance time of fever and abdominal pain was shorter in the experimental group than in the control group （P＜0.01）. There were no significant changes in routine urine and stool tests， renal function， electrolytes， or electrocardiogram in either group compared with pre-treatment values. ConclusionTCM triple therapy in addition to western medicine routine treatment could significantly improves clinical symptoms in patients with liver cirrhosis and SBP with damp-heat stagnation and toxin-blood stasis syndrome， alleviates liver inflammation， improves liver function， accelerates the resolution of ascites， and increases clinical efficacy. The potential mechanism may be related to the regulation of the inflammatory response and the promotion of intestinal mucosal barrier repair.

BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

OBJECTIVES: To analyze the association of CHMP2B expression level of with clinicopathological characteristics and prognosis of clear cell renal cell carcinoma (CRCC) and the possible role of CHMP2B in tumorigenesis and progression of CRCC. METHODS: RNAseq data of CRCC were downloaded from the TCGA database for analysis of CHMP2B expression levels in tumor and adjacent tissues and their correlation with clinicopathological characteristics of the patients. Survival outcomes of the patients with high and low CHMP2B expressions were analyzed using the Kaplan-Meier model, and the COX risk regression model was used for identifying the prognostic factors of the patients. The correlation between CHMP2B expression and immune infiltration, its co-expressed genes, and the effect of CHMP2B gene mutations on immunotherapy responses, and its immunohistochemical expression in CRCC and normal tissues were analyzed. Clinical samples of CRCC were collected to examine CHMP2B expressions using RT-PCR, and cell experiment was carried out to test the effect of CHMP2B overexpression on biological behaviors of CRCC cells. RESULTS: CHMP2B was significantly under-expressed in renal cancer tissues, and its overexpression obviously inhibited the proliferation of CRCC cells in vitro. CHMP2B expression level was significantly correlated with age, gender, lymph node metastasis, and tumor stage, and the patients with low CHMP2B expression had poor survival outcomes. Enrichment and co-expression gene analyses suggested that CHMP2B was mainly involved in viral outgrowth, necrotic apoptosis, endocytosis, and immune-regulatory processes in kidney cancer. CONCLUSIONS CHMP2B is lowly expressed in renal cancer tissues to affect tumor progression and tumor immune processes, and may serve as a prognostic biomarker and therapeutic target for CRCC.
Humans ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/metabolism* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Male ; Female ; Gene Expression Regulation, Neoplastic

Objective To investigate the current status of nurses'knowledge,attitude and practice regarding sleep management of critically ill children in pediatric ICU,and to analyze its impact factors.Methods A self-designed questionnaire on general information and a questionnaire on knowledge and practical behaviors of pediatric ICU nurses on child's sleep management were used.In March 2023,902 pediatric ICU nurses from 24 hospitals in China were surveyed using a convenient sampling method,and the impact factors were analyzed using multiple stepwise linear regression.Results 893 valid questionnaires were collected and the recovery rate of valid questionnaires was 99.00％.Nurses in pediatric ICU scored(33.71±7.76)in knowledge dimension,(37.38±4.86)in attitude dimension and(80.60±16.78)in practice dimension,with a total score of(151.78±24.27).The scores of knowledge and attitude,knowledge and practice,attitude and practice are all positively correlated(r=0.393,P＜0.001;r=0.495,P＜0.001;r=0.320,P＜0.001).The results of multiple stepwise linear regression analysis showed that gender,region,whether they had received sleep management training were the influencing factors of pediatric ICU nurses'total score of knowledge,attitude and practice towards children's sleep management(P＜0.05).Conclusion Nurses in pediatric ICU are positive about sleep management for critically ill children,but their knowledge and practice levels need to improve.Nursing managers should strengthen the theoretical knowledge and practical behavioral training of pediatric ICU nurses on child sleep management,develop scientific sleep management plans,and guide nurses to make reasonable evaluation and interventions to improve children's sleep quality.

Objective To explore the research hotspots on systemic lupus erythematosus(SLE)in pregnancy based on the bibliometric analysis of the related articles published from 2018 to 2023 and provide di-rections for the future research in this field.Methods PubMed,Web of Science,and Embase were searched for the articles on SLE in pregnancy that were published from January 1,2018 to December 31,2023.VOSviewer was used to visualize the high-frequency keywords in the selected articles.Results A total of 266 articles were selected,from which 25 high-frequency keywords were extracted.The bibliometric analysis showed that the available studies about SLE in pregnancy mainly focused on maternal complications,maternal and fetal outcomes,and medica-tions.The studies were limited regarding the predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring.Conclusion Maternal complications,maternal and fetal outcomes,and medications are currently hotspots in the research on SLE in pregnancy,while predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring may become future research directions.

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

Diabetic foot is one of the common chronic complications， the most common cause of hospitalization， and even the main cause of disability and death among diabetic patients. In the process of disease occurrence， development， and treatment， patients experience complex changes in physical， psychological， and social relationships. Their understanding and practice of the disease is a constant process of construction and change， which contains strategic practices influenced by factors such as disease progression， family relationships， culture and traditions of social， and doctor-patient interactions. Based on the research concepts in the field of medical anthropology， this paper applied field research methods such as survey interviews and participatory observation， and took the rich and varied and personalized narrative of diabetic foot patients as the entry point to understand their unique and detailed disease stories， as well as focused on answering the changes in the views of illness， treatment， family， society， and the body outlook experienced by diabetic foot patients. This paper aimed to provide a new perspective for understanding this group， as well as offer valuable insights for improving their treatment and management， which will help promote the overall health and quality of life with diabetic foot patients.

Objective:To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene.Methods:This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation.Results:All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days.Conclusions:The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.