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.

Parkinson disease is a neurodegenerative disorder with motor and cognitive impairments as the main clinical symptoms. The disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies， which are eosinophilic inclusions composed of α-synuclein， in the remaining dopaminergic neurons. The disease predominantly affects middle-aged and elderly individuals. Oxidative stress caused by mitochondrial dysfunction can lead to the loss of dopaminergic neurons， so mitochondrial dysfunction is considered as the main cause of Parkinson disease. Mitochondrial biogenesis has an important effect on the function of mitochondria. Therefore， abnormality of the regulation system of mitochondrial biogenesis is closely related to the occurrence and development of Parkinson disease. This review focuses on the regulatory mechanism of mitochondrial biogenesis control system and aims to provide promising therapeutic targets for Parkinson disease.
Parkinson Disease

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 We aimed to assess the serum levels of the glycolysis-related protein hypoxia-inducible factor-1α(HIF-1α)and cytokines in patients with relapsing-remitting multiple sclerosis(RRMS)before and after treatment with the traditional Chinese medicine Yishen Daluo Decoction,as well as their correlation with clinical parameters,and explore the immune regulatory mechanism of Yishen Daluo Decoction on multiple sclerosis.Methods Twenty-eight patients with RRMS in remission recruited from May 2018 to January 2022 in the Multiple Sclerosis Clinic at Dongzhimen Hospital,Beijing University of Chinese Medicine were retrospectively included.Comparisons were made with paired samples from 13 of them before and after Yishen Daluo Decoction treatment.A total of 20 gender-and age-matched healthy controls(HCs)were also recruited.Clinical information was collected from all of the subjects,and the neurological impairments of RRMS patients were assessed with the Expanded Disability Status Scale(EDSS)score.ELISA and SP-X multiplex cytokine assays were used to measure the serum levels of HIF-1 α and 10 cytokines(IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-22,IFN-γ,and TNF-α),respectively.Spearman's method was used to analyze the correlation between the serum levels of HIF-1α and cytokines,and the correlation between the serum levels of HIF-1α and cytokines and patients'clinical indicators,including disease duration,the number of attacks,and the EDSS score.Results Serum HIF-1α,IL-4,IL-6,IL-8,IL-10,IL-12p70,IFN-γ,and TNF-α levels in the RRMS group were significantly higher than those in the HC group(P＜0.05).Serum levels of HIF-1α,IL-4,IL-6,and IL-12p70 in the Yishen Daluo Decoction-pre group were significantly higher than those in the Yishen Daluo Decoction-post group(P＜0.05).In addition,the serum HIF-1α level was positively correlated with IL-6(r=0.452,P=0.016)and TNF-α(r=0.524,P=0.004)levels in patients with RRMS.The IFN-γ level was negatively correlated with the EDSS score(r=-0.423,P=0.025),the IL-4 level was negatively correlated with disease duration(r=-0.385,P=0.043),and the TNF-α level was positively correlated with disease duration(r=0.397,P=0.037).Conclusion The regulatory mechanism of Yishen Daluo Decoction on immune imbalance in RRMS may be related to its ability to reduce the serum levels of the glycolysis-related protein HIF-1α in RRMS patients.It is also related to the levels of various inflammatory cytokines.

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.

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.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Background/Aims: Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321). Methods: Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated. Results: SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood. Conclusions SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

One case of periprosthetic infection after artificial joint replacement caused by Coxiella burnetii was reported. The patient was admitted to hospital due to joint pain and sinus formation after artificial knee replacement. Through medical history, physical examination, imaging examination and gene detection, it was confirmed that the infection around the prosthesis was caused by Coxiella burnetii. The patient was treated with two-stage revision surgery combined with sensitive antibiotics. Through literature review, a total of 9 cases of Coxiella burnetii infection after artificial joint replacement were reported, including 6 cases of hip joint and 3 cases of knee joint; 4 cases had clear pathogen exposure history; only one case was found protheses loosening on imaging; 7 cases with positive IgG antibody against Coxiella burnetii; 7 cases were positive for gene detection; 8 cases were negative in etiological examination, and 1 case was not cultured. All patients were treated with doxycycline and hydroxychloroquine. The serological index of 1 case without Q fever symptom turned negative after treatment. 1 case with multiple system organ dysfunction relieved symptoms after treatment, and serological antibody indicators and nuclear medicine results turned negative. All 7 patients were cured after secondary revision surgery. Coxiella burnetii infection after total joint arthroplasty is rare and lacks typical imaging manifestations and clinical features. The diagnosis of Coxiella burnetii infection after total joint arthroplasty mainly depends on gene detection and serological detection. Two-stage revision surgery combined with sufficient and long-term sensitive antibiotics is the main method of treatment.