Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

Preeclampsia (PE) is a severe gestational disorder characterized by hypertension and proteinuria, with a subset of cases exhibiting an immune-driven phenotype marked by placental overexpression of proinflammatory cytokines and chronic inflammatory damage, profoundly impacting fetal development. To elucidate the pathophysiology of this PE subtype, we established an inflammation-driven PE mouse model via lipopolysaccharide (LPS) intraperitoneal injection, systematically evaluating histopathological changes in maternal heart, liver, lung, kidney, and placenta, and integrating transcriptomic profiling to uncover molecular mechanisms. LPS administration robustly induced maternal hypertension and proteinuria, hallmarks of PE, without significantly altering organ or fetal weights. Histological analyses revealed pronounced inflammatory damage in the maternal lung, kidney, and placenta, with the lung exhibiting the most severe pathology, characterized by inflammatory cell infiltration, alveolar wall thickening, and interstitial edema-challenging the conventional focus on placental and renal primacy in PE. Placental labyrinth and junctional zones displayed extensive structural disruption and necrosis, indicating functional impairment. Transcriptomic analysis identified 27 inflammation-related genes consistently upregulated across tissues, with protein-protein interaction networks pinpointing Il1β, Il6, Ccl5, Ccl2, Cxcl10, Tlr2, and Icam1 as hub genes. Quantitative PCR validation confirmed Tlr2 as a central regulator, evidenced by significant upregulation of Tlr2 in lung, kidney, and placenta of LPS-induced PE mice, while Cxcl10 exhibited placenta-specific upregulation, suggesting a synergistic inflammatory axis in placental pathology. These findings highlight the lung as a critical, yet underappreciated, target in inflammation-driven PE, reframe the multi-organ inflammatory landscape of the disease, and nominate Tlr2 and Cxcl10 as potential diagnostic biomarkers and therapeutic targets, offering new avenues for precision intervention in PE.
Animals ; Female ; Pregnancy ; Mice ; Pre-Eclampsia/genetics* ; Inflammation ; Lipopolysaccharides/adverse effects* ; Disease Models, Animal ; Transcriptome ; Placenta/pathology* ; Phenotype

In accordance with the theory of'treating the skin diseases with the skin',skin-related Chinese medicinals are usually used for the treatment of skin diseases,which reflects the thinking mode of holistic syndrome differentiation and classification according to the manifestations in traditional Chinese medicine.With ying-yang theory as the principle of differentiation and treatment of diseases and based on the core pathogenesis of'yin-yang imbalance causing the manifestations of the skin'for the skin diseases,Chinese medical master XU AN Guo-Wei has used skin-related Chinese medicinals in the treatment of skin diseases and has given full play to their unique advantage by following the theory of'treating the skin diseases with the skin'and'balanced regulation of yin and yang'.In the clinical practice,allergic skin diseases were usually treated with Cicadae Periostracum plus Dictamni Cortex for dispelling wind and relieving itching,hypopigmentation related skin diseases were usually treated with Sojae Semen Nigrum skin plus Dictamni Cortex for dispelling wind and tonifying kidney,autoimmune skin diseases were usually treated with Moutan Cortex plus Lycii Cortex for nourishing yin,clearing heat and activating blood,and skin diseases associated with abnormal sebum secretion were usually treated with Mori Cortex plus Lycii Cortex for purging lung and nourishing kidney.Skin-related Chinese medicinals have the actions of expelling wind and promoting eruption of papules,tonifying kidney and nourishing yin.The medication method of'treating the skin diseases with the skin'will provide reference for the treatment of skin diseases.

AIM To study the protective effects and mechanism of pueraria isoflavones on myocardial injury in ovariectomized rats.METHODS Thirty-six rats were randomly divided into the sham operation group,the model group,the estradiol valerate group(0.1 mg/kg)and the low,medium and high dose pueraria isoflavones groups(55,110,220 mg/kg).In contrast to the rats of the sham operation group having their small pieces of adipose tissue removal around the ovaries,rats of the other groups had their bilateral ovaries excised,followed by the 16-week corresponding oral drug administration 2 weeks later at a once daily frequency for,6 days a week.At the end of the 16th week,the rats had their hemodynamics[systolic pressure(SBP),diastolic pressure(DBP),mean pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVMP),and the maximum rate of increase and decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)]detected by PowerLab;their cardiac pathological changes observed by HE staining;their levels of creatine kinase(CK),lactate dehydrogenase(LDH),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and glucose(Glu)in plasma detected by biochemical analyzer;their myocardial level of adenosine triphosphate(ATP)detected by colorimetry;their mRNA expressions of glucose transporter 4(GLUT4),lactate dehydrogenase A(LDHA),carnitine palmitoyl transferase-1(CPT-1α),acyl coenzyme A carboxylase(ACC),liver kinase B1(LKB1),adenylate-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor γ coactivator factor 1α(PGC-1α)detected by RT-qPCR;and their myocardial expressions of energy metabolism related proteins LKB1,p-AMPK/AMPK and PGC-1α detected by Western blot.RESULTS Compared with the model group,the pueraria isoflavones groups displayed decreased levels of SBP,DBP,MBP,LVSP,LVMP(P＜0.05,P＜0.01);increased-dp/dtmax(P＜0.05,P＜0.01);improved myocardial fibrinolysis,gap widening and inflammatory infiltration caused by ovariectomy;decreased activities of LDH and CK(P＜0.05);increased myocardial ATP level(P＜0.05,P＜0.01);decreased levels of TC,TG,LDL-C and Glu(P＜0.05,P＜0.01);increased HDL-C level(P＜0.05,P＜0.01);increased myocardial mRNA expressions of GLUT4,LDHA,CPT-1α,ACC,LKB1,AMPK and PGC-1α(P＜0.05,P＜0.01);and increased protein expressions of myocardial LKB1,p-AMPK/AMPK and PGC-1α(P＜0.05,P＜0.01).CONCLUSION Pueraria isoflavones are protective to myocardial injury in ovariectomized rats,and the mechanism may lie in the improvement of energy metabolism-related myocardial proteins via LKB1/AMPK/PGC-1α signaling pathway.

Objective To understand the recognition and coping strategies of ICU nurses on post-ICU syndrome in family members of patients during hospitalisation so as to provide a reference for handling post-ICU syndrome of the family members of patients.Methods A phenomenological approach within qualitative research was adopted.Semi-structured in-depth interviews were conducted with 15 ICU nurses from 3 wards of the Second Affiliated Hospital of South China University.Colaizzi 7-step method was applied to analyse and refine the interview data themes.Results Three main themes and nine sub-themes were identified and they were insufficient cognition of post-ICU syndrome of the family members(limited understanding of post-ICU syndrome in family members,difficulty in recognising or ignoring symptoms,uncertainty about the impact of post-ICU syndrome),active coping with post-ICU syndrome of the family members(coping mainly through listening and explaining,coping mainly through verbal and physical actions,diligent patient care)and various factors hindering nurses'coping with post-ICU syndrome of the family members(compassion fatigue,high ICU work intensity,limited contact time with family members).Conclusion ICU nurses have insufficient understanding of post-ICU syndrome with the family members of patients during hospitalisation.It requires to enhance a comprehensive understanding in ICU nurses about post-ICU syndrome of the family members of patients and to optimise coping strategies to alleviate negative emotions of the family members.Additionally,efforts should be made to overcome factors that hinder nurses'coping with post-ICU syndrome of the family members of patients and to promote a harmonious relationship between medical staff and patients.

ObjectiveHemoglobin is the iron-containing protein in the red blood cells of many animals. The primary function of hemoglobin is to transport oxygen from lung to tissues. It is composed of two identicalα‑globin subunits and two identical β‑globin subunits. Hemoglobin has unique magnetic properties. The paramagnetism of deoxyhemoglobin, and the diamagnetism of oxyhemoglobin and carboxyhaemoglobin have been reported previously. Studies have also shown that external magnetic field affected blood flow rate, but whether magnetic field may affect the oxygenation rate of hemoglobin remains unknown. Here in this study, we are aiming to address this question with recombinant hemoglobin. Human hemoglobin and yak hemoglobin were selected as the research objects, and a recombinant protein expression and purification system was established to explore the magnetic field effects on the oxygenation rate of hemoglobin, as well as the differences in the oxygenation rate between human hemoglobin and yak hemoglobin under external magnetic field. MethodsThe recombinant expression and purification system of human and yak hemoglobin was established. The recombinant hemoglobin expression was further optimized and appropriated inducing temperature and IPTG concentration were screened. Recombinant human hemoglobin and yak hemoglobin were purified to homogeneity by affinity chromatography and further by size-exclusion chromatography. SDS-PAGE was used to validate the purification, and UV-Vis spectrum and EPR were used to characterize the biochemical properties of recombinant hemoglobin. Deoxyhemoglobin of human and yak were placed under 0.3 T external magnetic field to test the magnetic field effects on oxygenation rate, and geomagnetic field condition was used as a sham control. The UV-Vis spectrum data were measured every 10 min, and the concentration and proportion of oxygenated hemoglobin, deoxyhemoglobin and methemoglobin were calculated to analyze the effects of magnetic field on the oxygenation rate of hemoglobin. The magnetic properties of human oxygenated hemoglobin and human deoxygenated hemoglobin have been measured by SQUID, a superconducting quantum interference magnetic measurement system. Three biological replications were performed for each experiment. The possible mechanism of the effect of magnetic field on the oxygenation rate of hemoglobin has been investigated and discussed. ResultsHuman and yak hemoglobin were successfully expressed and purified by E.coli prokaryotic expression system. The optimal expression temperature was 30℃, and the most suitable IPTG concentration was 1 mmol/L. EPR results suggested that trace amount of methemoglobin existed both in the purified human hemoglobin and yak hemoglobin proteins. The oxygenation rate of yak hemoglobin appeared to be faster than that of human hemoglobin, and the additional magnetic field treatment significantly increased the oxygenation rate of both human and yak hemoglobin, and yak hemoglobin was more sensitive to magnetic field than human hemoglobin. The paramagnetism of deoxyhemoglobin was verified by SQUID measurement. However, the diamagnetism of oxygenated hemoglobin remains uncertain, probably due to the presence of trace amount of methemoglobin in the sample of oxygenated hemoglobin, which was consistent with EPR results. ConclusionIn this study, human and yak hemoglobin were successfully expressed and purified. The purified hemoglobin proteins have similar function and conformational states as native protein. External static magnetic field facilitates hemoglobin oxygenation, and yak hemoglobin seems more sensitive to magnetic field compared with human hemoglobin. These findings provide theoretical basis for the potential applications of applying magnetic field to improve hypoxia symptoms in clinical practice in the future.

In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

Objective To observe the effect of dulaglutide combined with insulin aspart and metformin on blood glucose,pancreatic beta-cell status and physique in elderly patients with type 2 diabetes mellitus(T2DM)and obesity.Methods Elderly patients with T2DM and obesity were divided into the control group and the treatment group according to the queue method.Both groups were given intensive insulin therapy with insulin aspart injection at 0.4-0.6 U·kg-1·d-1 and oral administration of 0.5 g of metformin tablets,tid.A week later,the treatment of control group was switched to sequential therapy with insulin glargine injection at an initial dose of 0.4-0.6 U·kg-1·d-1,qn.The dose was adjusted according to blood glucose concentration.During this period,0.5 g of metformin tablets was administrated,tid,for 12 consecutive weeks.Meanwhile,treatment of the treatment group was switched to sequential therapy with 1.5 mg of dulaglutide injection,once a week.During this period,0.5 g of metformin tablets was administrated,tid,for 12 consecutive weeks.The two groups were compared in terms of clinical efficacy,blood glucose level[glycosylated hemoglobin(HbAlc),fasting plasma glucose(FPG)],pancreatic beta-cell status[fasting insulin(FINS),homeostasis model assessment-β(HOMA-β)and homeostasis model assessment-insulin resistance index(HOMA-IR)],and physical parameters[waist circumference and body mass index(BMI)].Safety was evaluated.Results Fifty-three cases and fifty-one cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 98.11％(52 cases/53 cases)and 84.31％(43 cases/51 cases),and the difference was statistically significant(P＜0.05).After treatment,HbAlc in the treatment and the control group were(7.01±0.75)％and(7.63±0.82)％;FPG levels were(6.23±0.70)and(6.62±0.74)mmol·L-1;FINS levels were(5.25±1.06)and(6.48±1.12)mU·L-1;HOMA-β were 32.62±6.53 and 27.19±5.18;HOMA-IR were 1.31±0.25 and 1.65±0.28;waist circumference were(82.31±6.04)and(85.79±6.82)cm;BMI were(27.14±1.23)and(27.91±1.15)kg·m-2.The differences in above indicators between the treatment group and the control group were statistically significant(all P＜0.05).Adverse drug reactions in the treatment group mainly included nausea,vomiting and skin rash.Adverse drug reactions in the control group mainly included nausea and vomiting.The total incidence rates of adverse drug reactions in the treatment and the control group were 11.32％and 9.80％,without statistically significant difference(P＞0.05).Conclusion Dulaglutide combined with insulin aspart and metformin can effectively improve blood glucose,lipids,inflammation and pancreatic β-cell status in elderly patients with T2DM and obesity,reduce glycemic excursions,and promote decreases in waist circumference and BMI,with good safety.

Post-acute pancreatitis diabetes is one of the most common distant complications of acute pancreatitis. However, its incidence has been underestimated for a long time, indicating that it has not been taken seriously by healthcare professionals in clinical practice. This article provides a review of the urgent need for healthcare professionals to focus on the current status, adverse outcomes, screening and management aspects of diabetes after acute pancreatitis, and aims to provide a reference for healthcare professionals in their relevant clinical work.

Objective To explore the effect of gender,training duration and type of sports on electro-cardiographic changes in Chinese elite athletes by performing electrocardiography(ECG).Methods A to-tal of 891 Chinese elite athletes who underwent ECG examinations between 2016 and 2019 were in-cluded in the study.The ECGs were divided into three groups according to the guidelines of the Euro-pean Society of Cardiology(ESC)in 2010:group 0(normal ECG),group 1(common and training-relat-ed ECG)and Group 2(uncommon and training-unrelated ECG).The effect of gender,training dura-tion(4 to 6 years,7 to 10 years and more than 11 years)and sports types(skill,strength,endur-ance and mixed categories)on the ECG changes was assessed.Results No significant differences were found in Group 2 in sex,training duration or sports types.However,the prevalence of common train-ing-related ECG changes was significantly higher in male athletes than in female athletes(58.9%vs.47.4%).Moreover,the highest prevalence was found in athletes with more than 11 years of training,significantly higher than those with 4-6 years of training(P<0.05).A highly significant difference was also observed among athletes of different sports(P<0.01),with the highest in those of the mixed cate-gory at 64.6%.Moreover,sinus bradycardia occurred with significantly higher incidence in athletes un-dertaking mixed and endurance training than others(P<0.05).Conclusion The training-related ECG changes of Chinese elite athletes is closely correlated to their gender,training duration and sports types.