Chronic neuroinflammation is one of the pathogeneses of Alzheimer's disease(AD),and chemokines and their re-ceptors play a key role in AD pathology.Studies have shown that the expression of CCR3 is increased in AD patients and animal models,and the absence or antagonism of CCR3 can effectively improve the pathological changes of AD animal models and improve the impairment of learning and memory function,which is a potential target for AD treatment.In this review,the research progress of the role of CCR3 and its ligands in the pathogenesis of AD is reviewed,which will provide references for the in-depth disclosure of the pathogenesis of AD and the development of new drugs.

Chronic neuroinflammation is one of the pathogeneses of Alzheimer's disease(AD),and chemokines and their re-ceptors play a key role in AD pathology.Studies have shown that the expression of CCR3 is increased in AD patients and animal models,and the absence or antagonism of CCR3 can effectively improve the pathological changes of AD animal models and improve the impairment of learning and memory function,which is a potential target for AD treatment.In this review,the research progress of the role of CCR3 and its ligands in the pathogenesis of AD is reviewed,which will provide references for the in-depth disclosure of the pathogenesis of AD and the development of new drugs.

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 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 compare the efficacy of arthroscopic figure-of-eight transtibial tension-reducing technique combined with interference screw fixation versus interface screw fixation alone in the treatment of anterior cruciate ligament (ACL) rupture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 43 patients with ACL rupture admitted to Taihe Hospital between January 2022 and October 2023, including 24 males and 19 females, aged 17-61 years [(38.0±12.6)years]. Based on the tibial fixation method, 20 patients were treated with interference screw fixation alone (interference screw group) and 23 patients with figure-of-eight transtibial tension-reduction technique combined with interference screw fixation (figure-of-eight tension-reduction combined with interference screw group). An Endobutton suspension plate was used in femoral fixation in both groups. The following parameters were compared between the two groups: operative duration and graft diameter; coronal and sagittal tibial tunnel measurements by MRI within 72 hours postoperatively and at the last follow-up; knee range of motion, visual analogue scale (VAS) scores, International Knee Documentation Committee (IKDC) scores, and Lysholm scores preoperatively, at 1 month postoperatively, and at the last follow-up; perioperative complication rates.Results:All the patients were followed up for 11-28 months [(14.1±3.4)months]. There were no significant differences in operative duration or graft diameter between the two groups ( P>0.05). No significant differences were observed in coronal or sagittal tibial tunnel measurements between the two groups within 72 hours postoperatively ( P>0.05). Whereas at the last follow-up, the coronal and sagittal tibial tunnel measurements in the figure-of-eight tension-reduction combined with interference screw group were (11.6±0.7)mm and (11.7±1.1)mm, significantly lower than (13.5±0.6)mm and (13.4±1.9)mm in the interference screw group ( P<0.01). Preoperative knee range of motion, IKDC scores, Lysholm scores, and VAS scores showed no significant differences between the two groups ( P>0.05). At 1 month postoperatively and at the last follow-up, the figure-of-eight tension-reduction combined with interference screw group demonstrated significantly greater knee range of motion [100.0(95.0, 100.0)° and 130.0(120.0, 135.0)°], compared with 72.5(60.0, 95.0)° and 120.0(105.0, 133.3)° in the interference screw group ( P<0.05). VAS scores at 1 month postoperatively and at the last follow-up were 2.0(2.0, 2.0)]points and 1.0(1.0, 1.0)points in the figure-of-eight tension-reduction combined with interference screw group, significantly lower than 3.0(2.3, 4.0)points and 2.0(1.0, 2.0)points in the interference screw group ( P<0.05). IKDC scores at 1 month postoperatively and at the last follow-up were (58.8±5.7)points and (72.4±6.7)points in the figure-of-eight tension-reduction combined with interference screw group, significantly higher than (51.1±5.2)points and (67.4±7.9)points in the interference screw group ( P<0.05). Lysholm scores at 1 month postoperatively and at the last follow-up were (58.9±12.7)points and (89.1±6.0)points in the figure-of-eight tension-reduction combined with interference screw group, significantly higher than (41.2±15.0)points and (78.3±12.3)points in the interference screw group ( P<0.05). No perioperative complications were observed in either group. Conclusion:Compared with interface screw fixation alone, arthroscopic figure-of-eight transtibial tension-reduction technique combined with interference screw fixation for ACL rupture can enhance graft stability, restore knee joint range of motion, alleviate pain, and improve knee function recovery.

Objective:To compare the efficacy of arthroscopic figure-of-eight transtibial tension-reducing technique combined with interference screw fixation versus interface screw fixation alone in the treatment of anterior cruciate ligament (ACL) rupture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 43 patients with ACL rupture admitted to Taihe Hospital between January 2022 and October 2023, including 24 males and 19 females, aged 17-61 years [(38.0±12.6)years]. Based on the tibial fixation method, 20 patients were treated with interference screw fixation alone (interference screw group) and 23 patients with figure-of-eight transtibial tension-reduction technique combined with interference screw fixation (figure-of-eight tension-reduction combined with interference screw group). An Endobutton suspension plate was used in femoral fixation in both groups. The following parameters were compared between the two groups: operative duration and graft diameter; coronal and sagittal tibial tunnel measurements by MRI within 72 hours postoperatively and at the last follow-up; knee range of motion, visual analogue scale (VAS) scores, International Knee Documentation Committee (IKDC) scores, and Lysholm scores preoperatively, at 1 month postoperatively, and at the last follow-up; perioperative complication rates.Results:All the patients were followed up for 11-28 months [(14.1±3.4)months]. There were no significant differences in operative duration or graft diameter between the two groups ( P>0.05). No significant differences were observed in coronal or sagittal tibial tunnel measurements between the two groups within 72 hours postoperatively ( P>0.05). Whereas at the last follow-up, the coronal and sagittal tibial tunnel measurements in the figure-of-eight tension-reduction combined with interference screw group were (11.6±0.7)mm and (11.7±1.1)mm, significantly lower than (13.5±0.6)mm and (13.4±1.9)mm in the interference screw group ( P<0.01). Preoperative knee range of motion, IKDC scores, Lysholm scores, and VAS scores showed no significant differences between the two groups ( P>0.05). At 1 month postoperatively and at the last follow-up, the figure-of-eight tension-reduction combined with interference screw group demonstrated significantly greater knee range of motion [100.0(95.0, 100.0)° and 130.0(120.0, 135.0)°], compared with 72.5(60.0, 95.0)° and 120.0(105.0, 133.3)° in the interference screw group ( P<0.05). VAS scores at 1 month postoperatively and at the last follow-up were 2.0(2.0, 2.0)]points and 1.0(1.0, 1.0)points in the figure-of-eight tension-reduction combined with interference screw group, significantly lower than 3.0(2.3, 4.0)points and 2.0(1.0, 2.0)points in the interference screw group ( P<0.05). IKDC scores at 1 month postoperatively and at the last follow-up were (58.8±5.7)points and (72.4±6.7)points in the figure-of-eight tension-reduction combined with interference screw group, significantly higher than (51.1±5.2)points and (67.4±7.9)points in the interference screw group ( P<0.05). Lysholm scores at 1 month postoperatively and at the last follow-up were (58.9±12.7)points and (89.1±6.0)points in the figure-of-eight tension-reduction combined with interference screw group, significantly higher than (41.2±15.0)points and (78.3±12.3)points in the interference screw group ( P<0.05). No perioperative complications were observed in either group. Conclusion:Compared with interface screw fixation alone, arthroscopic figure-of-eight transtibial tension-reduction technique combined with interference screw fixation for ACL rupture can enhance graft stability, restore knee joint range of motion, alleviate pain, and improve knee function recovery.

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.

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 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.