Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

Recent studies have revealed a significant association between Porphyromonas gingivalis(P.gingivalis)infection and poor prognosis in esophageal squamous cell carcinoma(ESCC).Although cer-tain circular RNAs(circRNA)have been shown to suppress ESCC tumorigenesis and progression,their regulatory mechanisms in P.gingivalis infection-associated ESCC remain elusive.In this study,RT-qPCR analysis demonstrated that P.gingivalis infection downregulated hsa_circ_0057552 expression in ESCC cells and tissues in a time-and dose-dependent manner.Actinomycin D assays further confirmed that P.gingivalis infection reduced the RNA stability of hsa_circ_0057552 in ESCC cells(P＜0.05).Functional assays in vitro and a subcutaneous tumor xenograft model in vivo revealed that hsa_circ_0057552 overexpression significantly inhibited ESCC cell proliferation,migration,invasion,and tumor growth(P＜0.05).Additionally,PCR array screening combined with RT-qPCR and Western blotting in-dicated that P.gingivalis infection markedly upregulated human antigen R(HuR)expression at both RNA and protein levels(P＜0.05).Mechanistic investigations demonstrated that HuR knockdown signifi-cantly increased hsa_circ_0057552 expression(P＜0.01),whereas hsa_circ_0057552 overexpression had no regulatory effect on HuR.Finally,si-HuR treatment reversed the inhibitory effect of P.gingivalis on hsa_circ_0057552 transcription.This study demonstrated that P.gingivalis may promote the progression of ESCC through a novel mechanism involving the regulation of HuR/hsa_circ_0057552,thereby identif-ying a novel therapeutic target and molecular marker for P.gingivalis-associated ESCC.

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Objective:To investigate causal relationship between intestinal flora and risk of developing ankylosing spondylitis(AS)by a two-sample Mendelian randomization(MR)analysis.Methods:Genome-wide association study(GWAS)data on 211 types of intestinal flora and AS were obtained,and single nucleotide polymorphism(SNP)was used as an instrumental variable and sensi-tive SNPs were selected for analysis.Two-sample MR analyses were performed by inverse variance weighted(IVW)as well as MR-Eg-ger,Weighted median,to assess causal relationship between AS and intestinal flora by OR,and results were tested for heterogeneity and pleiotropy.Results:IVW analysis showed a significant causal relationship between 11 intestinal flora and AS risk.Among them,Verrucomicrobiae,Verrucomicrobiales,Verrucomicrobiaceae,Akkermansia,Erysipelatoclostridium,Holdermannia,Holdemania,Bacillales and Verrucomicrobia had positive causal effect on AS risk,while Dialister,Howardella and Oscillospira had negative causal effect.Causal effect estimates obtained by different methods(MR-Egger,Weighted median)were consistent,and sensitivity tests did not reveal significant horizontal pleiotropy and heterogeneity.Conclusion:Intestinal flora plays an important role in pathogenesis of AS,while specific mechanism remains to be further investigated.

Objective Piperazine derivatives are a group of emerging psychoactive substances with excitatory and hallucinogenic effects on the central nervous system.This study established a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)screening method for the detection of 40 piperazine compounds in urine.Methods A 200 μL urine sample(spiked with an internal standard at 1 ng/mL)was subjected to liquid-liquid extraction with ethyl acetate.After nitrogen evaporation,the residue was redissolved in 200 μL methanol and injected for analysis.Separation was performed on a Waters Acquity UPLC? HSS T3 column(100 mm × 2.1 mm,1.8 μm).The mobile phase consisted of(A)20 mmol/L ammonium acetate buffer containing 0.1％formic acid and 5％acetonitrile,and(B)acetonitrile.Gradient elution was applied,and detection was carried out in multiple reaction monitoring(MRM)mode.Quantification was achieved using an internal standard calibration curve.Results The 40 piperazine substances demonstrated good linearity within the range of 1-50 ng/mL,with correlation coefficients of 0.995-0.998.The extraction recovery ranged from 51.51％to 104.1％.Intra-day precision was below 5％,while inter-day precision ranged from 1.61％to 10.17％.Accuracy was between-7.84％and 8.77％.The limits of detection were 0.2-1 ng/mL,and the limit of quantification was 1 ng/mL.Conclusion The proposed method requires only a small sample volume,exhibits high sensitivity,selectivity,and stability,and offers short run times.It is suitable for the qualitative and quantitative determination of piperazine derivatives in urine in forensic toxicology practice.

Uric acid is the end product of purine metabolism in the human body. In recent years, the role of uric acid in female fertility and assisted reproductive technology (ART) has gained increasing attention. Dysregulation of uric acid metabolism can lead to hyperuricemia (HUA). HUA is not only closely related to metabolic syndrome and cardiovascular diseases but may also adversely affect female fertility by influencing ovarian function and embryos development. In this review, we explored the role of uric acid in female fertility, including its association with female subfertility, infertility, adverse pregnancy outcomes and metabolic syndrome, as well as its potential impact on ART like in vitro fertilization-embryo transfer and intracytoplasmic sperm injection. Further studies are needed to clarify the threshold and clinical intervention value of uric acid levels in women of childbearing age, providing a basis for reproductive health counseling and personalized pregnancy assistance for HUA patients of childbearing age.

OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.