ObjectiveTo clarify the application value of nutritional scoring in patients with sepsis and explore the impact of the modified Nutritional Risk in Critically Ill （mNUTRIC） score on the in-hospital fatality of sepsis patients in the emergency intensive care unit （EICU）. MethodsA retrospective analysis was conducted on the clinical data and laboratory examination results of 436 sepsis patients treated in the EICU of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2021 to May 2024. The patients were divided into survival group （298 cases） and death group （138 cases） according to whether they died or not during hospital treatment， and then compared the two groups’ data. Logistic multi-factor regression analysis was used to analyze the risk factors for in-hospital death and the ROC curve to evaluate the predictive value of each risk factor for the prognosis of sepsis patients. ResultsThe death group exhibited higher Acute Physiology and Chronic Health EvaluationⅡ（APACHE Ⅱ） score， Nutritional Risk Screening 2002 （NRS 2002） score， mNUTRIC score， Sequential Organ Failure Assessment （SOFA） score， Padua Prediction Score for Venous Thromboembolism， the proportions of chronic kidney failure and pneumonia patients， C-reactive protein （CRP） level， lactate concentration and neutrophil count， but lower prognostic nutritional index， cholinesterase level， cholinesterase-albumin ratio and lymphocyte count than the survival group， with statistical significance （all P<0.05）. Logistic regression analysis revealed that the mNUTRIC score ［OR=1.254， 95%CI （1.109，1.417）］， CRP ［OR=1.004， 95%CI （1，1.007）］， and pneumonia ［OR=1.82， 95%CI （1.017， 3.257）］ were independent risk factors for in-hospital death in sepsis patients. ROC curve analysis showed that the area under the curve （AUC） of the mNUTRIC score for predicting in-hospital death in sepsis patients was 0.683 ［95%CI （0.623，0.742）］， with a sensitivity of 83% and a specificity of 49.3%. The AUC for CRP and pneumonia were 0.602 ［95%CI （0.533， 0.671）］， and 0.582 ［95%CI （0.516，0.647）］. ConclusionThe mNUTRIC score is an independent predictive indicator for in-hospital death in sepsis patients in the EICU.

OBJECTIVES: Injury to human cardiac microvascular endothelial cells (HCMECs) compromises myocardial microcirculation and may contribute to major cardiovascular events such as coronary heart disease, posing a serious health threat. Understanding the mechanisms of hypoxia-induced HCMEC damage is thus of great clinical relevance. This study aims to investigate the protective effects and underlying mechanisms of Li Qi Huo Xue Di Wan against hypoxia-induced HCMEC injury. METHODS: HCMECs were cultured under hypoxic conditions for 24 hours to establish a cellular model of hypoxic injury. Cells were divided into six groups: normal control, hypoxia, hypoxia + low-dose Li Qi Huo Xue Di Wan, hypoxia + medium-dose, hypoxia + high-dose, and hypoxia + salvianolic acid B (positive control). Cell viability was assessed using the MTS assay. Lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content were measured to evaluate cytotoxicity and oxidative stress. Activities of superoxide dismutase (SOD), catalase (CAT), caspase-3, and caspase-8 were determined with corresponding assay kits. Apoptosis was analyzed by flow cytometry, and expression of necroptosis-related proteins, receptor-interacting protein kinase 1 (RIPK1) and its phosphorylated form (p-RIPK1), receptor-interacting protein kinase 3 (RIPK3) and its phosphorylated form (p-RIPK3), mixed lineage kinase domain-like protein (MLKL) and its phosphorylated form (p-MLKL), was examined via Western blotting. RESULTS: Compared with the control group, hypoxia significantly decreased cell viability (P<0.01), increased MDA levels (P<0.05), and reduced CAT and SOD activity (P<0.05), accompanied by elevated apoptosis (P<0.01) and increased levels of p-RIPK1, p-RIPK3, and p-MLKL (P<0.05). High-dose Li Qi Huo Xue Di Wan significantly improved cell viability (P<0.01), reduced MDA content (P<0.05), increased CAT activity (P<0.05), and suppressed necroptosis-related protein expression (P<0.05) compared with the hypoxia group. CONCLUSIONS Li Qi Huo Xue Di Wan exerts a protective effect against hypoxia-induced injury in HCMECs. This effect is mediated by attenuation of oxidative stress, thereby reducing both apoptosis and necroptosis.
Humans ; Apoptosis/drug effects* ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Cell Hypoxia/drug effects* ; Endothelial Cells/pathology* ; Oxidative Stress/drug effects* ; Cells, Cultured ; Cell Survival/drug effects* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome, and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors, including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high-precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening in the fetal gene reprogramming in HCM.
Cardiomyopathy, Hypertrophic/metabolism* ; Humans ; Animals ; DNA Methylation ; Mice ; Transcriptome ; Chromatin/genetics* ; Early Growth Response Protein 1/metabolism* ; Male ; Epigenome ; Nucleosomes/genetics* ; Female ; Middle Aged ; Disease Models, Animal ; Adult

OBJECTIVE:To prepare anti-tumor drug H6(lactone compound)polymeric micelles,and to investigate its in vitro anti-tumor effects. METHODS:Using mPEG2000-PCL4000 as carrier,H6/mPEG2000-PCL4000 micelles were prepared. Using particle size, PDI and 48 h whether to produce precipitation as indexes,feeding ratio,H6 concentration,volume ratio of organic solvent were screened. The encapsulation efficiency and drug-loading amount of micelle were all detected. MTT assay was used to detect the tox-icity of micelles and H6 solution to human non-small cell lung cancer cell A549 and human lung cancer cell H460. RESULTS:The screened formulation was as follows as feeding ratio of 1∶25,H6 concentration of 2 mg/mL,the ratio of ethanol to chloroform of 1∶1(V/V). The parameters of prepared H6/mPEG2000-PCL4000 micelles were as follows as particle size of(40.74±0.116 3)nm,PDI of(0.101±0.006),encapsulation efficiency of(94.87±0.016 3)%,drug-loading amount of(7.07±0.001 5)%(n=3). IC50 of mi-celles and H6 solution to A549 cell were 15.62 and 12.57 nmol/L;IC50 of micelles and H6 solution to H460 cell were 27.68 and 15.19 nmol/L. CONCLUSIONS:H6/mPEG2000-PCL4000 micelles are prepared successfully and show in vitro anti-tumor effects.

OBJECTIVE:To establish the detection method for anti-inflammatory compound HB0314 in plasma of rats,and study on its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC-MS/MS was performed on the column of Waters Ac-quity UPLCTM BEH C18 with mobile phase of 0.1% formic acid aqueous solution(A)-methanol(B)by gradient elution(0-2 min, 70%-90% B) at flow rate of 0.25 mL/min,column temperature was 30 ℃,and injection volume was 5 μL. Electrospray ion source was used,capillary voltage was 3 kV,ion source temperature was 150 ℃,desolvation gas temperature was 450 ℃,desol-vent air flow volume was 600 L/h,cone air flow volume was 45 L/h,and the inner standard was tetrahydropalmatine. 12 rats were randomly divided into iv group and ig group,6 in each group. Rats were intravenously injected and intragastrically administrated HB0314 solution 5,10 mg/kg. Sample blood 0.4 mL were taken from the jugular vein blood before administration and after 5,15, 30,60,120,240,360,480,600,720,1440 min of administration to determine the HB0314 plasma concentration. DAS 2.0 software was used to calculate the pharmacokinetic parameters and absolute bioavailability. RESULTS:The linear range of HB0314 was 1-1000 ng/mL(r=0.9955),and the lower limit of quantification was 1 ng/mL. RSDs of extra-day and daytime precision,sta-bility were not higher than 8.45%(n=5);recovery were 68.21%-90.29%(RSD≤11.20%,n=5),and matrix effects were 82.63%-106.90%(RSD≤6.75%,n=5). After intravenous injection and intragastric administration,AUC0-24 h were (270.267 ± 21.164), (252.755 ± 26.169)μg·h/L (n=6);t1/2z were (8.722 ± 2.266),(11.877 ± 4.517) h (n=6);and absolute bioavailability was 56.79%. CONCLUSIONS:The method is rapid,simple,and can be used for the determination of HB0314 content in plasma of rats. HB0314 shows high oral absolute bioavailability in rats in vivo,indicating that post-dosage form design may be considered as oral anti-inflammatory drugs.

Objective To study the effect of scalp acupuncture plus facilitation technique on the temporal and spatial parameters of gait in spastic cerebral palsy. Method Thirty eligible patients with spastic cerebral palsy were randomized into a treatment group and a control group based on the inter-group balance in age, palsy type, and the Gross Motor Function Classification System (GMFCS), 15 cases in each group. The treatment group was intervened by scalp acupuncture, together with the facilitation technique during the retaining of the needles; the control group was also by scalp acupuncture and facilitation techniques but with over 1 h interval between the two methods. The treatment was given once a day, totally for 3 months. The walking, running, and jumping items (E category) of the Gross Motor Function Measure-66 (GMFM-66), temporal and spatial parameters of gait, and vertical ground reaction force during stance were compared before and after the treatment. Result There were no significant inter-group differences in comparing the rates of E category of the GMFM-66 before the treatment (P>0.05), the rates were significantly changed after the treatment in both groups (P<0.05), and there were significant differences in comparing the rates between the two groups after the intervention (P<0.05);after the intervention, the step length, walking speed, and step frequency were increased significantly in both groups (P<0.05), while the double-stance phase was decreased significantly, and swing phase was increased significantly (P<0.05); after the intervention, the step length, walking speed, and step frequency of the treatment group were significantly better than that of the control group (P<0.05). Conclusion Acupuncture plus facilitation technique can mitigate the spasticity in spastic cerebral palsy, improve the gross motor function, especially the function of standing and walking, enhance the activities, and benefit the improvement of the step length, step width, and walk speed.

Objective To investigate the clinical outcomes of the medial displacement calcaneal osteotomy with reconstruction of posterior tibial tendon insertion on navicular for the flatfoot related with accessory navicular.Methods From March 2009 to October 2011,13 patients (16 feet) with flatfoot related with accessory navicular received treatment by the medial displacement calcaneal osteotomy with reconstruction of posterior tibial tendon insertion on navicular.There were 4 males and 9 females,with an average age of 41.3 years (range,18-64 years).All patients had obvious valgus calcaneus,the angle of which was 11.3°± 1.4°.According to AOFAS ankle-hindfoot scores,the arch height,calcaneus inclination angle (CI),talocalcaneal angle (TC),talar first metatarsal angle (TMT) on the lateral weight-bearing radiograph of foot,and the talocalcaneal angle (TC),talar first metatarsal angle (TMT) on the AP view of the weight-bearing radiograph of foot,and the heel valgus alignment on axial radiographs of the hindfoot were measured on the X-ray film.Results All patients were followed up for 12 to 31 months,with the average of 16.8 months.Eleven patients (13 feet) felt no pain 6 months after operation,while 2(3 feet) felt pain after long walking.There was no complication,including infection,nerve injury,un-union,and so on.The average AOFAS ankle-hindfoot score improved from 56.4-±6.4 preoperatively to 88.1±2.8 at the last follow-up.Radio graphically,all parameters were statistically significant between pre-operation and the last follow-up,including the arch height,CI,TC,TMT modifying from 3.8±0.3 mm,9.5°±1.1°,47.3°±2.5°,17.6°±1.6° to 12.0±1.1 mm,20.1°±1.5°,32.3°±2.5°,6.8°±1.0° respectively on the lateral weight-bearing view; TC improving from 39.5°±2.3° to 26.2°±2.0°and TMT improving from 15.2°±1.7° to 6.3°±1.0° on the AP weight-bearing view.Conclusion The medial displacement calcaneal osteotomy with reconstruction of posterior tibial tendon insertion on navicular is a good choice for the treatment of flatfoot related with accessory navicular with excellent clinical outcomes.

OBJECTIVE: To discuss the development direction for hospital pharmacists in the medical reform and to promote rational use of drugs.METHODS: The status quo for the medical reform was analyzed based on the practicality of hospital and the author's perspectives on how to improve pharmaceutical care level was presented.RESULTS & CONCLUSIONS: Hospital pharmacists should change pharmaceutical care model to face up to the challenges in the medical reform by establishing clinical pharmacists' team and setting up pharmaceutical care center to improve pharmaceutical care level and adapt to the development of medical reform.