ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

Objective To quantitatively analyze the effect of long-term ultrahigh-altitude and mid-high-altitude expo-sure on fundus microcirculation.Methods In the cross-sectional study,healthy residents from ultrahigh-altitude areas(＞3 500-5 500 m)and those from mid-high-altitude areas(＞1 500-3 500 m)were included as subjects.Meanwhile,healthy residents from plain areas were included as the control group.All subjects underwent optical coherence tomography angiography(OCTA)and spectral domain optical coherence tomography(SD-OCT)scans.Fundus images were quantified using ImageJ,and fundus microcirculation metrics were calculated and compared among these groups.Retinal microcircu-lation metrics included retinal vessel density(RVD),retinal skeleton density(RSD),fractal dimension(FD),foveal avas-cular zone(FAZ)area,and ganglion cell complex(GCC)thickness.Choroidal microcirculation metrics included subfoveal choroidal thickness(SFCT),luminal area(LA),total choroidal area(TCA),and choroidal vascularity index(CVI).Results In the ultra-high altitude group,the RVD was(32.52±3.57)％,the RSD was(15.05±4.24)％,and the FD was 1.68±0.08,all of which were significantly lower compared with the control group(all P＜0.001).The average thick-ness of GCC in the ultrahigh-altitude group was(98.76±10.26)μm,which was significantly thinner than the average thickness of GCC in the control group(P＜0.001).The TCA in the ultrahigh-altitude group was(2.15±0.49)mm2,the LA was(1.17±0.36)mm2,and the SFCT was(318.12±76.50)μm,all of which were significantly higher compared with the control group(all P＜0.001).However,the CVI was significantly decreased in the ultrahigh-altitude group compared with the control group(P＜0.001).There were no significant differences in fundus microcirculation metrics between the mid-high-altitude group and the control group(all P＞0.05).Conclusion Long-term ultrahigh-altitude exposure may induce ischemia and hypoxia in the fundus,primarily characterized by a decrease in the retinal and choroidal blood flow density,whereas long-term mid-high-altitude exposure cannot cause changes in the fundus microcirculation.

Objective:To explore the correlation between palm temperature,disease activity,and traditional chinese medicine syndrome types in patients with rheumatoid arthritis(RA).Methods:80 RA patients(RA group)who were admitted to our hospital from April 2022 to June 2024 were selected,they were divided into high group(DAS28 score＞5.1 score)and low to moderate group(2.6 score ≤ DAS28 score≤5.1 score)according to the 28 joint disease activity scores(DAS28).70 healthy volunteers who underwent physical examinations during the same period(control group)were selected.The palm temperature,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),and DAS28 scores between the control group and RA group were compared.The palm temperature,ESR,and CRP levels between low to moderate group and high group were compared.The correlation between palm temperature and disease activity,ESR,and CRP levels in RA patients was analyzed by Pearson correlation.The distribution of traditional chinese medicine syndrome types in RA patients was observed,the palm temperature,ESR,and CRP levels of RA patients with different traditional chinese medicine syndrome types were compared.Results:The palm temperature,ESR,CRP levels,and DAS28 score in the RA group were higher than those in the control group(P＜0.05).The palm temperature,ESR,and CRP levels in the high group were higher than those in the low to moderate group(P＜0.05).Pearson correlation analysis results showed that,the palm temperature of RA patients was positively correlated with DAS28 score,ESR,and CRP levels(P＜0.05).Among 80 RA patients,there were 17 cases(21.25％)of liver and kidney deficiency syndrome,23 cases(29.02％)of cold and dampness obstruction syndrome,14 cases(17.86％)of qi and blood deficiency syndrome,17 cases(21.47％)of damp heat obstruction syndrome,and 9 cases(11.52％)of phlegm and blood stasis obstruction syndrome.The palm temperature,ESR,and CRP levels of patients with Qi and blood deficiency syndrome,liver and kidney deficiency syndrome,and phlegm and blood stasis obstruction syndrome increased in sequence and were higher than those of patients with damp heat obstruction syndrome and cold and dampness obstruction syndrome(P＜0.05).There was no statistical difference in palm temperature,ESR,and CRP levels between the groups of damp heat obstruction syndrome and cold and dampness obstruction syndrome(P＞0.05).Conclusion:There is a certain correlation between the palm temperature and disease activity and traditional chinese medicine syndrome types of RA patients.Regular observation of palm temperature,ESR,CRP levels,and DAS28 score is helpful for assessing the condition of RA patients.

Objective:To explore the therapeutic effect of Banxia Baizhu Tianma Decoction on phlegm-dampness-blocking cervical vertigo and its influence on neck hemodynamics.Methods:96 patients with phlegm-dampness block type cervical vertigo admitted to our hospital from January 2022 to January 2024 were divided into control group and observation group,48 cases in each group.The control group was treated with conventional Western medicine,and the observation group was treated with Banxia Baizhu Tianma Decoction.Both groups were treated for 4 weeks and followed up for 6 months.The reduction time and disappearance time of vertigo were recorded.The score of cervical vertigo Symptom and Function Assessment Scale(ESCV)was performed before treatment and 1 day after treatment.The average blood flow level of basilar artery,right vertebral artery and left vertebral artery was detected,and the total clinical effective rate,recurrence rate and adverse reaction rate of the two groups were compared.Results:The reduction time and disappearance time of vertigo in the observation group were shorter than those in the control group(P＜0.05).Post-treatment,the ESCV score of both groups was higher than that before treatment;compared with the control group,the ESCV score of the observation group was higher post-treatment(P＜0.05).The total clinical effective rate of observation group was higher than that of control group,and the recurrence rate was lower than that of control group(P＜0.05).The hemodynamic index were higher after treatment than in the control group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Banxia Baizhu Tianma Decoction has certain curative effect on phlegm-dampness block type cervical vertigo,can effectively relieve vertigo symptoms,reduce recurrence,improve neck hemodynamics,and is safe,worthy of popularization and application.

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

Elucidate the influence of RFRP-3 on follicular development and steroid hormone synthe-sis in mice.Forty 6-week-old female KM mice were randomly allocated into four groups,namely the 0(control),100,500 and 2 000 ng/d treatment groups.Each group received daily intraperitoneal injections of RFRP-3 for a duration of 7 days.The ovarian coefficients were calculated and recorded by measuring the wet weight of the ovaries.The effects of RFRP-3 at different concentrations on follicular maturation in mice were investigated through HE staining.Western blot analysis was em-ployed to assess the expression of apoptosis-related proteins,steroidogenic enzymes,and oocyte se-cretion factors within the mouse ovaries.The concentrations of progesterone(P4)and estradiol(E2)in the serum of the mice were determined using radioimmunoassay techniques.The results re-vealed no significant differences in body weight between the experimental groups and the control.However,the ovarian coefficients in the 500 and 2 000 ng/d treatment groups were significantly re-duced when compared to the control(P＜0.01).A marked decrease in the numbers of secondary and antral follicles was observed in the 500 ng/d and 2 000 ng/d groups(P＜0.01),concomitant with a substantial increase in atretic follicles(P＜0.01).A significant decline in follicle count was also noted in these groups(P＜0.01).Compared to the control,the protein expression of Bax and Caspase3 was substantially upregulated in the 500 and 2 000 ng/d treatment groups(P＜0.05),while the expression of Bcl-2 protein was significantly downregulated(P＜0.01).Similarly,the protein expression of 3βHSD,StAR,CYP11a1,and CYP17a1 was significantly decreased at the 500 and 2 000 ng/d groups(P＜0.01).E2 concentrations were moderately reduced in the 500 ng/d group(P＜0.05)and significantly decreased in the 2000 ng/d group(P＜0.01),whereas P4 levels remained unchanged across all experimental groups.Notably,the expression of BMP15 and GDF9 at both the gene and protein levels was markedly attenuated in the 500 and 2 000 ng/d treatment groups compared to the control(P＜0.05).In conclusion,RFRP-3 appears to inhibit follicular de-velopment and steroid hormone secretion in mice by modulating the expression of apoptotic fac-tors,oocyte secretion factors,and steroidogenic enzymes within the ovaries.This study provides a theoretical foundation for understanding the regulatory mechanisms of RFRP-3 on mammalian follicular development and steroid hormone synthesis.

Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Objective:To study the prevalence and spatio-temporal distribution characteristics of Keshan disease in Qingyang City, Gansu Province, and provide scientific basis for formulating targeted prevention and control strategies and optimizing resource allocation.Methods:The data of patients with Keshan disease from January 2022 to December 2024 were obtained from the Qingyang Center for Disease Control and Prevention, and the population data were obtained from the Statistics Bureau of Qingyang City. Global and local spatial autocorrelation analysis was performed using GeoDa 1.16.0 software to identify four spatial clustering areas: high-high, low-low, low-high, and high-low. Spatio-temporal aggregation analysis was conducted using SaTScan 10.1.3 software.Results:The prevalence rates of Keshan disease in Qingyang City from 2022 to 2024 were 7.11/100 000, 6.68/100 000, and 6.14/100 000, respectively. Global spatial autocorrelation analysis showed that the prevalence rates of Keshan disease in Qingyang City from 2022 to 2024 showed a positive spatial correlation (Moran′s I > 0, Z > 1.96, P < 0.05), with the highest spatial correlation in 2024 (Moran′s I = 0.46, Z = 8.02, P = 0.001). Local spatial autocorrelation analysis showed that from 2022 to 2024, the number of townships (towns) exhibiting high-high clusters of Keshan disease in Qingyang City was 15, 11, and 11, respectively. These clusters were primarily concentrated in the southeastern townships (towns) of Qingyang City that boder the Ziwu Mountain. Low-low clusters were primarily concentrated in most townships (towns) of Zhenyuan County and Xifeng District of Qingyang City, as well as some townships (towns) in the northwest of Huachi County. Spatio-temporal scanning analysis showed that the high prevalence rate cluster was concentrated in 2022, covering 44 townships (towns) in 5 counties, mainly distributed in the southeast of Qingyang City. The low prevalence rate cluster was concentrated in 2024, covering 26 townships (towns) in 3 counties (districts), and distributed in the western of Qingyang City. Conclusion:There is a significant spatial clustering of Keshan disease in Qingyang City, and the high prevalence rate cluster is located in the southeast of Qingyang City, which is a key area for prevention and control of Keshan disease in the future.