The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Fracture healing is a complex process that necessitates the synergistic action of various cells and molecules. Macrophages play an indispensable and crucial regulatory role in the process of fracture repair, influencing stages such as inflammatory modulation, angiogenesis, and tissue remodeling. This article delves into the functional characteristics of macrophages and their roles at different stages of fracture healing. Additionally, it explores the impact of aging macrophages on the healing process. Furthermore, the potential of emerging therapies, such as hydrogel-based treatments and exosomes, in modulating macrophage responses is analyzed. This study provides a theoretical foundation for the development of innovative therapies aimed at enhancing the efficacy of fracture healing.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Objective : To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis． Methods : Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results: Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ． Conclusion The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.

Objective:To investigate the correlation of sleep disorders(SD)with serum levels of amyloid β-proteins(Aβ 1-42)and tau phosphorylated at threonine(P-Tau 181)in patients with Alzheimer's disease(AD). Methods:A total of 126 patients with mild and moderate AD who met the inclusion criteria in the memory clinic, sleep clinic and geriatrics department of Jianghan Oilfield General Hospital affiliated to Yangtze University from February 2017 to January 2020 were included.The Pittsburgh Sleep Quality Index(PSQI)was used to evaluate sleep quality.Patients with PSQI scores ≥7 were included in the AD group with sleep disorders(AD-SD group), and patients with PSQI scores <7 were included in the AD group without sleep disorders(AD-NSD group). The Montreal Cognitive Assessment(MoCA), Global Deterioration Scale(GDS), Clinical Dementia Rating(CDR), Hamilton Rating Scale for Depression(HRSD)and Hamilton Anxiety Rating Scale(HAM-A)were used to evaluate cognitive and psychosocial symptoms.During the same time, biological markers such as serum Aβ 1-42, Aβ 1-40 and P-Tau 181 were detected by using enzyme-linked immunosorbent assays.Patients in the two groups received donepezil as an anti-dementia therapy, while the AD-SD group was treated additionally with a targeted sleep intervention.All patients underwent neuropsychological assessment and biochemical tests at enrollment and at the end of the 6th month, and results from all parameters at baseline and at the end of the 6th month were compared.At the end of the six-month treatment, patients in the AD-SD group were further divided into the recovery AD-SD sub-group and the no-recovery AD-SD sub-group based on the extent of sleep improvement. Results:Of the 126 AD patients, 93(73.8%)had sleep disorders.There was no statistically significant difference between the two groups in gender, age, onset age, educational level, course of disease, CDR, GDS, MoCA, Aβ 1-40 or Aβ 1-42/Aβ 1-40(all P>0.05). The scores of PSQI, HRSD and HAM-A and serum levels of Aβ 1-42 and p-Tau 181 showed statistically significant differences between the AD-ND and AD-NSD groups( P<0.05 or P<0.01). At the end of the 6th month, the scores of PSQI, GDS, HRSD and HAM-A and levels of Aβ 1-42, Aβ 1-40, and P-Tau 181 also showed statistically significant differences between the AD-ND and AD-NSD groups( P<0.05 or P<0.01). There was no statistically significant difference in results from other parameters( P>0.05). Spearman correlation analysis showed that PSQI was correlated with HRSD( r=0.271, P=0.009), HAM-A( r=0.479, P=0.000), Aβ 1-42( r=0.470, P=0.000), Aβ 1-42/ Aβ 1-40( r=0.479, P=0.000)and P-Tau 181( r=0.371, P=0.000)in the AD-SD group at baseline.Multivariate Logistic regression model showed that serum Aβ 1-42 and P-Tau 181 levels and HRSD had predictive effects on changes in sleep quality in AD patients( OR=1.897, 1.269 and 1.889, P=0.000, 0.003 and 0.000). The areas under the receiver operating characteristic(ROC)curves for Aβ 1-42, P-Tau 181 and HRSD were 0.926(95% CI: 0.860-0.991), 0.837(95% CI: 0.746-0.927)and 0.854(95% CI: 0.776-0.932), respectively. Conclusions:Sleep quality is correlated with serum Aβ 1-42and P-Tau 181 levels in AD patients.Elevated serum levels of Aβ 1-42 and P-Tau 181 and high HRSD scores are important predictors of SD in AD patients and may be used as indexes for clinical treatment efficacy.

Objective: To observe the effect of transforming growth factor-β1 (TGF-β1) on the migration of oral carcinoma associated fibroblasts (CAFs) with two-dimensional culture model and three-dimensional model. Methods : Under two-dimensional culture conditions, CAFs stimulated by TGF-β1 with the addition of 10 ng/mL medium were used as the experimental group, and untreated CAFs were used as the control group. The migration of CAFs with the stimulation of TGF-β1 was measured by cell scratch assay and transwell assay. CAFs positive for green fluorescent protein (GFP) were cultured by retrovirus transfection. Human tongue squamous cell carcinoma cells SCC25, GFP(+) CAFs and CAFs with three-dimensional cell co-culture models were established. The three-dimensional model cultured under the stimulation of TGF-β1 with 10 ng/mL medium was used as the experimental group, and the three-dimensional model without TGF-β1 was used as the control group. The migration of CAFs with the stimulation of TGF-β1 was also measured by the three-dimensional models. Results: It was verified that 10 ng/mL TGF-β1 promoted the migration of CAFs in the two-dimensional culture model. The three-dimensional co-culture models of SCC25, GFP(+) CAFs and CAFs were successfully established. The migration of SCC25 and CAFs was detected in the three-dimensional model. However, 10 ng/mL TGF-β1 had little effect on their migration. Conclusion The effect of TGF-β1 in vitro on the migration of oral CAFs was associated with different culture models in two and three dimensions.

Objective:To observe the value of heart-type fatty acid-binding protein (H-FABP) and echocardiographic indexes in the diagnosis of cardiac insufficiency in sepsis.Methods:A prospective observational study was conducted. Eighty patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of Medical College of Shihezi University from October 2016 to January 2018 were enrolled. General clinical data such as gender, age, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA) score, hospitalization time and 28-day mortality were recorded. Echocardiographic indexes at 1, 3, 7, 10 days after diagnosis, and white blood cell (WBC), neutrophilic granulocyte percentage (N%), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum H-FABP level were recorded. Sepsis patients were divided into normal cardiac function group ( n = 30) and cardiac insufficiency group ( n = 50) according to cardiac function, the differences of echocardiographic indexes and cardiac markers between the two groups at different time points were compared. Logistic regression was used to screen out cardiac ultrasound indexes and cardiac markers that affect the occurrence of cardiac dysfunction in sepsis patients, and then receiver operating characteristic (ROC) curve analysis was performed. Results:Comparing the general data of the two groups, only the SOFA score of the cardiac insufficiency group was significantly higher than that of the normal cardiac function group (6.12±4.09 vs. 4.57±2.45, P < 0.05). N% and H-FABP in cardiac insufficiency group were higher than those in normal cardiac function group at the same time (N%: F = 6.973, P = 0.010; H-FABP: F = 17.303, P = 0.000). Without considering the time factor, there were significant differences in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), left ventricular fractional shortening (LVFS), E-point of septal separation (EPSS), isovolumic relaxation time (IVRT), E peak deceleration time (EDT), A peak duration (Ad), left ventricular systolic pulmonary vein velocity (S), blood flow velocity of pulmonary vein in early left ventricular diastolic period (D), tricuspid orifice early diastolic blood flow velocity (E'), tricuspid orifice late diastolic blood flow velocity (A'), systolic velocities of the right ventricular free wall tricuspid annulus (Sm), and pulmonary valve annulus blood flow velocity (PVBV) between the two groups. ROC curve analysis of cardiac ultrasound indicators and cardiac markers screened by Logistic regression showed that the area under ROC curve (AUC) and the positive and negative predictive values were: LVEDV was 0.636, 77.30%, 56.03%; SV was 0.779, 88.82%, 71.19%; LVEF was 0.753, 92.12%, 55.21%; CO was 0.754, 88.82%, 77.19%; LVFS was 0.728, 81.25%, 66.99%; EPSS was 0.663, 96.99%, 51.56%; IVRT was 0.775, 86.97%, 73.55%; A' was 0.908, 96.58%, 89.60%; Sm was 0.738, 93.37%, 56.77%; H-FABP was 0.673, 80.26%, 57.25%, respectively. H-FABP was tested in parallel with LVEDV, SV, LVEF, CO, LVFS, EPSS, IVRT, A', Sm, and the positive predictive values were higher than the single diagnostic test (85.45%, 93.91%, 96.72%, 94.74%, 89.43%, 98.00%, 92.00%, 99.42%, 93.60%, respectively), the negative predictive values were lower than the single diagnostic test (50.89%, 57.93%, 49.15%, 58.18%, 57.05%, 45.74%, 57.92%, 64.13%, 47.78%, respectively). Conclusion:Cardiac ultrasound indicators LVEDV, SV, LVEF, CO, LVFS, EPSS, IVRT, A', and Sm combined with H-FABP are of certain value in the diagnosis of sepsis-associated heart dysfunction.

Objective:To investigate the availability, prices and affordability of essential medicines in pediatric population across China, in the hope of improving rational use of medicines.Methods:A multicenter cross-sectional survey of medicine prices, availability and affordability was conducted in 17 provinces, municipalities and autonomous region across east, south-central part, west and north of China. Data on 42 medicines used in pediatric population, both original and generic, were collected in 55 public hospitals from May 26 to June 2, 2017. Availability was expressed as the percentage of hospitals with stock of the target medicine on the day of data collection,and median price ratio (MPR) was the ratio of price upon investigation to international reference. Based on national minimum daily wage, affordability represents the number of working days needed to earn the expense which covers a standard course using the target medicine. Statistical software SPSS 13.0 was applied for descriptive analysis of availability, MPR and affordability.Results:Mean Availability of original and generic medicine was 33% and 32%, with median MPR being 5.43 and 1.55. Among the 19 medicines with price information for both original and generic product, the median MPR was 7.73 and 2.04 respectively. Regarding the five medicines used to treat four common pediatric diseases (pneumonia,peptic ulcer, congenital hypothyroidism, refractory nephrotic syndrome), the affordability was 0.63 (0.16-6.17) d for generic medicine, and 1.03 (0.16-11.53) d for its original counterpart.Conclusions:The availability to both original and generic products of the 42 medicines used in pediatric population was low in China. The prices of generic medicines seem to be lower and affordability higher than those of original medicines. There is an urgent need to improve the availability and affordability of pediatric medicines.