This paper summarizes Professor LU Fang's clinical experience in treating systemic lupus erythematosus （SLE） based on the differentiation and treatment of heat-toxin and blood-stasis in the collaterals. SLE is generally characterized by deficiency in origin with excess in manifestation. The core pathogenesis is heat-toxin obstructing the collaterals. During the acute active stage， the predominant pattern is blazing heat-toxin causing blood stasis， while in the chronic remitting stage， the main pattern is toxic stasis blocking the collaterals with qi and yin deficiency. Clinical treatment follows the basic principle that treat with salty-cold herbs， when heat invades internally and that assist with acrid-dispersing herbs when stasis obstructs the collaterals. The self-formulated Yimian Decoction （抑免汤） serves as the base formula and is applied in stages. During the acute active stage， it is often combined with herbs for clearing heat and detoxifying， cooling blood and resolving stasis， and unblocking the collaterals. In the chronic remitting stage， it is often combined with herbs for activating blood circulation and unblocking the collaterals， as well as tonifying qi and nourishing yin.

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective To evaluate the therapeutic effect of Shenfu injection in shock patients by using bedside critical ultrasound.Methods A total of 80 shock patients admitted to First Hospital of Nanchang from January 2022 to May 2024 were selected and divided into Shenfu group(45 cases)and control group(35 cases)according to whether Shenfu injection was applied.Patients in control group were given conventional western medical treatment,while patients in Shenfu group were treated with Shenfu injection in addition to control group.The ultrasound measurement indicators and clinical results were recorded on the 1st,3rd,and 7th days of treatment respectively,and left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),peak velocity of early diastolic flow of mitral valve(E)/peak velocity of early diastolic motion of mitral annulus(E'),tricuspid annular plane systolic excusion(TAPSE),right ventricular fractional area change(RVFAC),inferior vena cava variation rate(IVCV),heart rate(HR),mean arterial pressure(MAP),N-terminal pro-brain natriuretic peptide(NT-proBNP),lactic acid(Lac),sequential organ failure assessment(SOFA)score and 30-day survival status of two groups of patients was compared.Results After 1 day,3 days and 7 days of treatment,LVEDD and E/E'of two groups of patients gradually decreased,while LVEF,TAPSE,RVFAC and IVCV gradually increased significantly(P＜0.05).After 7 days of treatment,the LVEF,TAPSE,RVFAC and IVCV of patients in Shenfu group were significantly higher than those in control group(P＜0.05).After 7 days of treatment,the HR,NT-proBNP,Lac and SOFA scores of two groups of patients were significantly lower than those before treatment in same group,and the MAP was significantly higher than that before treatment in same group(P＜0.05).The HR,NT-proBNP,Lac and SOFA scores of patients in Shenfu group were significantly lower than those in control group,the MAP was significantly higher than that in control group,and the mechanical ventilation time and the length of stay in intensive care unit were significantly shorter than those in control group(P＜0.05).Kaplan-Meier survival analysis showed that 30-day survival rate of patients in Shenfu group was significantly higher than that in control group(82.22％vs.54.28％,P＜0.05).Conclusion Bedside critical ultrasound showed that Shenfu injection could effectively improve ventricular systolic and diastolic function in shock patients,providing a valuable real-time assessment tool for shock treatment.

OBJECTIVE To explore the diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.

Objective:To observe and analyze the correlation between the changes of macular microvascular structure and the level of intracocular fluid cytokines in patients with diabetic macular edema (DME).Methods:A prospective clinical study. From December 2022 to June 2024, 20 patients with 25 eyes of DME diagnosed by Department of Ophthalmology of Linyi People's Hospital were included in the study. Among them, 14 males had 17 eyes and 6 females had 8 eyes. Age was (55.08±10.34) years. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to scan the macular region at a range of 6 mm×6 mm. Central retinal thickness (CRT), blood flow density of superficial retinal capillary plexus (SCP) and area of fovea avascular zone (FAZ) were measured. The anterior aqueous humor was extracted before the first intravitreal injection of anti-vascular endothelial growth factor (VEGF), the concentrations of interleukin (IL-6), IL-8, VEGF, vascular cell adhesion molecule (VCAM), placental growth factor (PLGF) and monocyte chemotactic protein-1 (MCP-1) were detected. The correlation between macular microvascular structure and aqueous humor cytokines was analyzed by Spearman correlation analysis.Results:The CRT of the affected eyes was (617.40±167.64) μm, the SCP flow density was (39.56±1.55)%, and the FAZ area was (0.46±0.13) mm 2. The concentrations of IL-6, IL-8, VEGF, VCAM, PLGF and MCP-1 in aqueous humor were (301.36±690.52), (29.15±20.56), (71.37±29.32) and (5 621.22±7 241.06), (72.40±13.43), (464.07±163.26) pg/ml, respectively. Correlation analysis showed that there was a significant positive correlation between CRT and the concentrations of aqueous cytokines VEGF and PLGF ( r=0.460, 0.462, P<0.05). FAZ area was positively correlated with VEGF and MCP-1 concentrations ( r=0.414, 0.465; P<0.05). There was a significant negative correlation between SCP blood flow density and IL-6 ( r=0.401, P<0.05). Conclusion:There was a significant correlation between the morphological structure of macular area and the damage degree of microvessels around macular area in DME patients and the concentration of aqueous cytokines.

Objectives:To explore the correlation between angiography-derived microcirculatory resistance(AMR)and microvascular obstruction(MVO)extent,and AMR's predictive value for ventricular remodeling in patients with ST-segment elevation myocardial infarction(STEMI)post-primary percutaneous coronary intervention(PCI).Methods:This retrospective study included STEMI patients who underwent PCI at Beijing Anzhen Hospital from April 2019 to January 2023.Patients underwent acute and follow-up cardiac magnetic resonance(CMR)examinations 3-7 days and 3 months post-PCI.Ventricular remodeling was defined as a 20%or more increase in left ventricular end-diastolic volume at follow-up.Patients were divided into ventricular remodeling and non-ventricular remodeling groups.Baseline clinical characteristics,AMR values and CMR indices of both groups were compared.Pearson's correlation coefficient was used to explore the correlation between AMR and MVO extent on CMR.Logistic regression and receiver operating characteristic curve analysis were employed to evaluate the predictive performance of AMR for ventricular remodeling.Results:A total of 168 STEMI patients([56.4±11.4]years,139[82.7%]males)were included,with 49(29.2%)in the ventricular remodeling group and 119(70.8%)in the non-ventricular remodeling group.AMR was positively correlated with MVO extent on CMR(r=0.42,P<0.01).Compared to the non-ventricular remodeling group,patients in the ventricular remodeling group exhibited a higher AMR value(3.00[2.56,3.52]mmHg?s/cm vs.2.48[2.20,2.74]mmHg?s/cm,1 mmHg=0.133 kPa,P<0.01).Multivariate logistic analysis showed that AMR was independently associated with ventricular remodeling post-PCI in STEMI patients.For every 0.2 mmHg·s/cm increase in AMR,the risk for ventricular remodeling increased 45.1%(adjusted OR=1.451,95%CI:1.228-1.714,P<0.01).Area under the curve of AMR for predicting ventricular remodeling was 0.769.Conclusions:AMR is positively correlated with MVO extent and is an independent predictor for ventricular remodeling in STEMI patients post-PCI.

Objective To evaluate the therapeutic effect of Shenfu injection in shock patients by using bedside critical ultrasound.Methods A total of 80 shock patients admitted to First Hospital of Nanchang from January 2022 to May 2024 were selected and divided into Shenfu group(45 cases)and control group(35 cases)according to whether Shenfu injection was applied.Patients in control group were given conventional western medical treatment,while patients in Shenfu group were treated with Shenfu injection in addition to control group.The ultrasound measurement indicators and clinical results were recorded on the 1st,3rd,and 7th days of treatment respectively,and left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),peak velocity of early diastolic flow of mitral valve(E)/peak velocity of early diastolic motion of mitral annulus(E'),tricuspid annular plane systolic excusion(TAPSE),right ventricular fractional area change(RVFAC),inferior vena cava variation rate(IVCV),heart rate(HR),mean arterial pressure(MAP),N-terminal pro-brain natriuretic peptide(NT-proBNP),lactic acid(Lac),sequential organ failure assessment(SOFA)score and 30-day survival status of two groups of patients was compared.Results After 1 day,3 days and 7 days of treatment,LVEDD and E/E'of two groups of patients gradually decreased,while LVEF,TAPSE,RVFAC and IVCV gradually increased significantly(P＜0.05).After 7 days of treatment,the LVEF,TAPSE,RVFAC and IVCV of patients in Shenfu group were significantly higher than those in control group(P＜0.05).After 7 days of treatment,the HR,NT-proBNP,Lac and SOFA scores of two groups of patients were significantly lower than those before treatment in same group,and the MAP was significantly higher than that before treatment in same group(P＜0.05).The HR,NT-proBNP,Lac and SOFA scores of patients in Shenfu group were significantly lower than those in control group,the MAP was significantly higher than that in control group,and the mechanical ventilation time and the length of stay in intensive care unit were significantly shorter than those in control group(P＜0.05).Kaplan-Meier survival analysis showed that 30-day survival rate of patients in Shenfu group was significantly higher than that in control group(82.22％vs.54.28％,P＜0.05).Conclusion Bedside critical ultrasound showed that Shenfu injection could effectively improve ventricular systolic and diastolic function in shock patients,providing a valuable real-time assessment tool for shock treatment.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objectives:To explore the correlation between angiography-derived microcirculatory resistance(AMR)and microvascular obstruction(MVO)extent,and AMR's predictive value for ventricular remodeling in patients with ST-segment elevation myocardial infarction(STEMI)post-primary percutaneous coronary intervention(PCI).Methods:This retrospective study included STEMI patients who underwent PCI at Beijing Anzhen Hospital from April 2019 to January 2023.Patients underwent acute and follow-up cardiac magnetic resonance(CMR)examinations 3-7 days and 3 months post-PCI.Ventricular remodeling was defined as a 20%or more increase in left ventricular end-diastolic volume at follow-up.Patients were divided into ventricular remodeling and non-ventricular remodeling groups.Baseline clinical characteristics,AMR values and CMR indices of both groups were compared.Pearson's correlation coefficient was used to explore the correlation between AMR and MVO extent on CMR.Logistic regression and receiver operating characteristic curve analysis were employed to evaluate the predictive performance of AMR for ventricular remodeling.Results:A total of 168 STEMI patients([56.4±11.4]years,139[82.7%]males)were included,with 49(29.2%)in the ventricular remodeling group and 119(70.8%)in the non-ventricular remodeling group.AMR was positively correlated with MVO extent on CMR(r=0.42,P<0.01).Compared to the non-ventricular remodeling group,patients in the ventricular remodeling group exhibited a higher AMR value(3.00[2.56,3.52]mmHg?s/cm vs.2.48[2.20,2.74]mmHg?s/cm,1 mmHg=0.133 kPa,P<0.01).Multivariate logistic analysis showed that AMR was independently associated with ventricular remodeling post-PCI in STEMI patients.For every 0.2 mmHg·s/cm increase in AMR,the risk for ventricular remodeling increased 45.1%(adjusted OR=1.451,95%CI:1.228-1.714,P<0.01).Area under the curve of AMR for predicting ventricular remodeling was 0.769.Conclusions:AMR is positively correlated with MVO extent and is an independent predictor for ventricular remodeling in STEMI patients post-PCI.