Objective To explore the mechanism of Gandou Fumu Decoction(GDFMD)for improving Wilson's disease(WD)in tx-J mice.Methods With 6 syngeneic wild-type mice as the control group,30 tx-J mice were randomized into WD model group,low-,medium-and high-dose GDFMD treatment groups,and Fer-1 treatment group.Saline(in control and model groups)and GDFMD(3.48,6.96 or 13.92 g/kg)were administered by gavage,and Fer-1 was injected intraperitoneally once daily for 14 days.Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue;ALT,AST,albumin,AKP levels were determined to assess liver function of the mice.Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4,ACSL4,ALOX15,FTH1,FLT,TFR1,FAS,SCD1,and ACOX1,and Fe2+,MDA,ROS,SOD,GSH and 4-HNE levels were analyzed to assess oxidative stress.Results The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT,AST and AKP,decreased albumin level,increased Fe2+,MDA,ROS,4-HNE levels,decreased SOD and GSH levels(P<0.05),lowered protein expressions of ACOX1,GPX4,FTH1,FLT,FAS,and SCD1,and increased protein contents of TFR1,ACSL4 and ALOX15 in the liver.Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models,decreased the levels of Fe2+,MDA and ROS,increased SOD and GSH levels,and reversed the changes in hepatic protein expressions.Conclusion GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.

Objective To design a training device of the flight crew for plateau normobaric low-oxygen acclimatization so as to enhance the flight crew's ability to adapt to the low oxygen environment after rushing into the plateau and reduce the incidence of acute plateau reaction.Methods The training device comprised a plateau environment simulation controller,a multimodal physiological acquisition system and hypoxia exercise training evaluation software.The plateau environment simulation controller was composed of an environment monitor for plateau acclimatization,two composite sensor sets,a control valve and an alarm device;the multimodal physiological acquisition system was made up of 20 groups of vital signs acquisi-tion devices,with a wearable dynamic ECG and respiration recorder,a wrist oximeter and an arm sphygmomano-meter included in each group.The hypoxia exercise training evaluation software was developed with a B/S architecture,Java language and JetBrains 2020.3.Results The training device proved to have the simulation altitude ranging from 0 to 6 000 m and facilitated simultaneous training of 20 persons for normobaric low-oxygen acclimatization,screening for hypoxia endurance,real-time monitoring of physiological parameters and assessment of training effect,with none of the trainees having acute plateau reaction.Conclusion The training device assists the flight crew for plateau normobaric low-oxygen acclimatization,and can be used for acclimatization training before plateau missions.[Chinese Medical Equipment Journal,2025,46(8):18-24]

Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P＜0.05,P＜0.01).The levels of WBC and NE in the model-A increased significantly(P＜0.01).The level of LY in model-B decreased significantly(P＜0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P＜0.01).The levels of IL-6 in model-A and model-B were significantly increased(P＜0.05,P＜0.01).The collagen volume fraction of model-A and model-B were significantly increased(P＜0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P＜0.01),and the expression levels of IκBα/β-actin were significantly decreased(P＜0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P＜0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.

Objective To investigate the effects of Gandou Fumu Decoction on liver fibrosis,iron metabolism,and ferroptosis in patients with hepatolenticular degeneration(Wilson disease,WD).Methods Seventy-eight hospitalized patients with WD characterized by kidney and liver deficiency,with phlegm and blood stasis,from the Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,were randomly assigned to two groups using a random number table method.The control group(n=39)received sodium dimercaptosulfonate in combination with a low-copper and high-protein diet.The observation group(n=39)received the same treatment as the control group,with the addition of Gandou Fumu Decoction(one dose per day,taken twice daily,in the morning and evening).Both groups underwent six treatment cycles,each lasting eight days.Ultrasonographic parameters,including portal vein main trunk diameter(PVMD),portal vein velocity(PVV),shear wave velocity(SWV),liver stiffness measurement(LSM),serum liver fibrosis markers(hyaluronic acid[HA],laminin[LN],procollagen typeⅢN-terminal peptide[PⅢNP],collagen type Ⅳ[CⅣ],aspartate aminotransferase to platelet ratio index[APRI],fibrosis-4 index[FIB-4]),and iron metabolism indicators(serum iron[SI],ferritin[FT])were compared before and after treatment.The relationship between baseline iron metabolism markers and ultrasonographic parameters,as well as serum liver fibrosis markers,was analyzed.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,and adverse reactions were also compared between the groups.Additionally,bioinformatics analysis was performed to identify potential targets of Gandou Fumu Decoction for WD treatment.Peripheral blood mononuclear cells were collected from a normal group of 20 healthy individuals,as well as from both the control and observation groups before and after treatment.Real time fluorogenic quantitative PCR was performed to validate the expression changes of these targets across the groups.Results Compared with pre-treatment values,no significant changes were observed in PVMD levels in either group after treatment.No significant change in PVV was observed in the control group,whereas a significant decrease was noted in the observation group(P＜0.01).SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels were significantly reduced compared to pre-treatment levels(P＜0.05,P＜0.01),whereas SI remained unchanged.Compared with the control group,the observation group had no significant difference in PVMD but had significantly lower PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels(P＜0.05,P＜0.01),whereas SI remained unchanged.The total effective rate of treatment in the observation group was significantly higher than that in the control group(P＜0.05).Both groups showed a significant reduction in TCM syndrome scores after treatment(P＜0.01),with a significantly greater reduction observed in the observation group(P＜0.01).No significant adverse reactions were reported during treatment.Before treatment,there was no significant correlation between the SI of both groups and PVMD,PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,and FIB-4.In the observation group,FT showed a positive correlation with SWV,LSM,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.05,P＜0.01),while in the control group,FT showed a positive correlation with HA,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.01).After treatment,in the control group,SI showed a positive correlation with APRI and FIB-4(P＜0.05,P＜0.01),but there was no significant correlation between SI in the observation group and FT in both groups with the above-mentioned indicators.Bioinformatics analysis identified four potential targets of Gandou Fumu Decoction for treating WD,namely heme oxygenase 1(HMOX1),peroxisome proliferator-activated receptor alpha(PPARα),small heat shock protein B1(HSPB1),and mitogen-activated protein kinase 3(MAPK3).Compared to the normal group,both the control and observation groups had significantly lower PPARαand HSPB1 expression and significantly higher HMOX1 and MAPK3 expression before treatment(P＜0.01).Compared to before treatment within the same group,both groups showed significantly increased PPARα and HSPB1 expression and significantly decreased HMOX1 and MAPK3 expression after treatment(P＜0.05,P＜0.01).After treatment,the observation group had significantly higher PPARα and HSPB1 expression and lower HMOX1 and MAPK3 expression than the control group(P＜0.05,P＜0.01).Conclusion Gandou Fumu Decoction demonstrates remarkable advantages in improving clinical efficacy,Chinese medicine syndrome scores,iron metabolism,liver fibrosis progression,ultrasound imaging parameters,and ferroptosis-related biomarkers expression in patients with WD,with a favorable safety profile.

Objective:To discuss the diagnostic value of levels of growth stimulation expressed gene 2 protein(ST2),carbohydrate antigen 125(CA125),and human epididymis protein 4(HE4)in serum of the ovarian cancer patients,and to clarify their relationships with clinicopathological parameters of the ovarian cancer patients.Methods:A total of 136 patients with ovarian benign lesions or primary ovarian malignancies in our hospital confirmed by postoperative histopathology were randomly selected,including 53 cases in ovarian benign ovarian disease group and 83 cases in ovarian cancer group.Additionally,55 healthy female volunteers during the same period were enrolled as healthy control group.The fasting venous blood from all the subjects was collected on the first day of admission,and serum was retained;cyclic enhanced fluorescence immunoassay was used to detect ST2 levels of the subjects in various groups;chemiluminescence method was used to detect serum CA125 and HE4 levels of the subjects in various groups;receiver operating characteristic(ROC)curve was used to assess the diagnostic performance of each indicator;the Cut-off value and area under the ROC curve(AUC)were calculated,with AUC representing the diagnostic performance;Kendall's method was used to analyze the correlations between serum ST2 levels and TNM stage,maximum tumor diameter,distant metastasis,lymphnode metastasis,peritoneal metastasis,carcinoembryonic antigen(CEA),CA125,carbohydrate antigen 199(CA199),HE4,P53,and Kiel-67(Ki67)in the ovarian cancer patients.Results:Compared with healthy control group,the serum CA125 level of the patients in ovarian benign ovarian disease group was significantly increased(P<0.05).Compared with healthy control group and ovarian benign group,the serum levels of ST2,CA125,and HE4 of the patients in ovarian cancer group were significantly increased(P<0.05).The AUC values were 0.719(95%CI:0.616-0.822)for ST2,0.868(95%CI:0.794-0.942)for CA125,and 0.867(95%CI:0.793-0.942)for HE4.The combined detection of ST2+CA125+HE4 yielded an AUC of 0.894(95%CI:0.832-0.955).Significant differences were observed in serum ST2,CA125,and HE4 levels among ovarian cancer patients with different TNM stages,lymph node metastasis,distant metastasis,and peritoneal metastasis(P<0.05),while there were no significant differences in the patients with different ages or maximum tumor diameters(P>0.05).The ST2 level in serm of the ovarian cancer patients was positively correlated with TNM stage,distant metastasis,lymph node metastasis,peritoneal metastasis,CA125 level,HE4 level,and Ki67 level(P<0.05),but was not correlated with maximum tumor diameter,CEA,CA199 level,or P53 level(P>0.05).Conclusion:ST2,CA125,and HE4 are highly expressed in the serum of the ovarian cancer patients.Combined detection of serum ST2,CA125,and HE4 exhibits good sensitivity and specificity for ovarian cancer screening and improves diagnostic efficacy.ST2 is associated with advanced TNM stage and metastasis in ovarian cancer and may participate in the occurrence and progression of ovarian cancer.

ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease（AD） using bioinformatics and machine learning methods， validate them at the clinical specimen level， and predict potential traditional Chinese medicine（TCM）. MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus （GEO） database， and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected， and the relative gene expression was clinically verified by real-time polymerase chain reaction（Real-time PCR）. Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained， mainly involved in pathways of tricarboxylic acid cycle， 2-oxocarboxylic acid metabolism， and carbon metabolism. Five core cuproptosis-related genes， dihydrolipoamide dehydrogenase （DLD）， glutaminase （GLS）， pyruvate dehydrogenase E1 subunit beta （PDHB）， full name nuclear factor （erythroid-derived 2）-related factor 2 （NFE2L2）， and dihydrolipoamide branched-chain transacylase E2 （DBT） were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group， minimum mental state examination （MMSE） and Montreal cognitive assessment （MoCA） were significantly decreased in the AD group （P<0.01）， Homocysteine（Hcy）， interleukin（IL）-6， C-reactive protein（CRP） ， and β amyloid protein（Aβ） indexes were significantly increased （P<0.01）， and malondialdehyde（MDA） indexes were decreased （P<0.05）. Superoxide dismutase（SOD） levels were significantly decreased （P<0.01）. The mRNA relative expressions of NFE2L2 and DBT were up-regulated （P<0.05）， and those of DLD， GLS， and PDHB were significantly down-regulated （P<0.01）. The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth， calmness， and cold， and the five flavors including bitterness， sweetness， and pungency， and it was attributed to the meridians of the liver， spleen， stomach， and kidney， with the efficacy of tonifying Qi， activating blood， eliminating phlegm， and resoling dampness. ConclusionDLD， GLS， NFE2L2， PDHB， and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes， and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.

Objective To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency,which was based on G protein-coupled receptor 41(GPR41)/GPR43-mediated mitogen-activated protein kinase(MAPK)signaling pathway.Methods The three-factor composite modeling method of eating disorder,diarrhea and fatigue was used to establish a model of spleen qi deficiency,and the rats were randomly divided into model,honey-processed Hedysari Radix,probiotics and blank groups with 15 rats per group.The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix.The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage.The blank and model groups were given the same dose of distilled water by gavage.Four groups were treated for 15 d with once a day.The expression levels of GPR41,GPR43,P38 MAPK,c-Jun N-terminal kinase(JNK)and extracellular regulatory protein kinase 1/2(ERK1/2)in colon tissues were detected by Western blotting.Results The relative expression levels of GPR41 in the blank,model,honey-processed Hedysari Radix and probiotics groups were 0.95±0.07,0.45±0.03,0.84±0.19 and 0.86±0.20;the relative expression levels of GPR43 were 1.17±0.11,0.41±0.06,0.66±0.03 and 0.57±0.01;the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01,0.43±0.01,0.39±0.01 and 0.36±0.02;the phosphorylated JNK/JNK ratios were 0.58±0.05,1.47±0.10,0.90±0.11 and 0.90±0.11;the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33,3.19±0.03,2.01±0.17 and 2.23±0.59,respectively.Compared with the model group,the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups(P＜0.05,P＜0.01).Conclusion The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.

For HCQ retinopathy with CME, acupuncture combined with periocular injection can be used to improve the CME and protect the central vision. Subsequent research endeavors involving a more extensive cohort and extended observation periods are warranted to evaluate the effectiveness and safety profile of the intervention.
Humans ; Macular Edema/drug therapy* ; Acupuncture Therapy/methods* ; Hydroxychloroquine/therapeutic use* ; Female ; Retinal Diseases/chemically induced* ; Middle Aged ; Combined Modality Therapy ; Male

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice. METHODS: With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe²⁺, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress. RESULTS: The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe²⁺, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe²⁺, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions. CONCLUSIONS GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Hepatolenticular Degeneration/drug therapy* ; Hepatocytes/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Fatty Liver/metabolism* ; Arachidonate 15-Lipoxygenase/metabolism* ; Coenzyme A Ligases/metabolism* ; Liver/metabolism* ; Male