Gouty arthritis （GA） is an inflammatory disorder caused by monosodium urate （MSU） crystal deposition， accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines， resulting in joint tissue damage and intense pain. Nuclear factor E₂-related factor 2 （Nrf2）， a key transcription factor regulating the antioxidant defence system， exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 （Keap1） and activates downstream antioxidant response element （ARE）-mediated pathways. It can upregulate the expression of heme oxygenase-1 （HO-1）， NADH quinone oxidoreductase 1 （NQO1）， superoxide dismutase （SOD）， and glutathione transferase （GST） to preserve redox homeostasis. Moreover， Nrf2 can suppress activation of NOD-like receptor protein 3 （NLRP3） inflammasomes， reduce pro-inflammatory cytokine production and release， modulate nuclear factor-κB （NF-κB） transcriptional activity， regulate gut microbiota balance， enhance mitophagy， and inhibit apoptosis， so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine （TCM） for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE， Nrf2/HO-1（NQO1）， and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage， attenuate inflammatory responses， promote autophagy， and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.

The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

Objective:To investigate the clinical characteristics and prognosis of fetuses with HNF1B gene variants. Methods:Fifty-two fetuses with HNF1B gene variants diagnosed by chromosomal copy number variation sequencing and/or whole exome sequencing at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2024 were retrospectively enrolled in this study, including 47 cases of 17q12 microdeletion and five cases of HNF1B point mutations. Prenatal ultrasound features, pregnancy outcomes, and postnatal manifestations were summarized and analyzed using descriptive statistics. Results:The prenatal ultrasound features of the 52 fetuses included enhanced renal parenchymal echo in 43 cases (82.7%), renal cysts in 15 cases (28.8%), enlarged kidney volume in 14 cases (26.9%), and pyelectasis in 13 cases (25.0%). Parental verification was completed for 35 cases, with 71.4% (25/35) being de novo mutations and 28.6% (10/35) inherited from either parent. Apart from eight cases with unknown pregnancy outcome (six cases were lost to follow-up, two cases refused to be followed up), the other 44 cases were successfully followed up, among which 68.2% (30/44) terminated the pregnancies and 31.8% (14/44) continued, resulting in live births. Prenatal ultrasound indicated renal abnormalities in all 14 live births, while postnatal follow-up showed seven cases with normal kidneys, one with reduced bilateral renal cysts, one with alleviated bilateral pyelectasis, four with unimproved renal structural abnormalities, and one who did not undergo a re-examination. Conclusion:The rate of renal abnormalities diagnosed by prenatal ultrasound in fetuses with HNF1B gene variants is high, and most of the pregnancies are terminated, although the renal sturctural abnormalities may improve after birth.

Objective:To investigate the clinical characteristics and prognosis of fetuses with HNF1B gene variants. Methods:Fifty-two fetuses with HNF1B gene variants diagnosed by chromosomal copy number variation sequencing and/or whole exome sequencing at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2024 were retrospectively enrolled in this study, including 47 cases of 17q12 microdeletion and five cases of HNF1B point mutations. Prenatal ultrasound features, pregnancy outcomes, and postnatal manifestations were summarized and analyzed using descriptive statistics. Results:The prenatal ultrasound features of the 52 fetuses included enhanced renal parenchymal echo in 43 cases (82.7%), renal cysts in 15 cases (28.8%), enlarged kidney volume in 14 cases (26.9%), and pyelectasis in 13 cases (25.0%). Parental verification was completed for 35 cases, with 71.4% (25/35) being de novo mutations and 28.6% (10/35) inherited from either parent. Apart from eight cases with unknown pregnancy outcome (six cases were lost to follow-up, two cases refused to be followed up), the other 44 cases were successfully followed up, among which 68.2% (30/44) terminated the pregnancies and 31.8% (14/44) continued, resulting in live births. Prenatal ultrasound indicated renal abnormalities in all 14 live births, while postnatal follow-up showed seven cases with normal kidneys, one with reduced bilateral renal cysts, one with alleviated bilateral pyelectasis, four with unimproved renal structural abnormalities, and one who did not undergo a re-examination. Conclusion:The rate of renal abnormalities diagnosed by prenatal ultrasound in fetuses with HNF1B gene variants is high, and most of the pregnancies are terminated, although the renal sturctural abnormalities may improve after birth.

Objective:To explore the feature of FOS expression in oxytocin-and vasopressin-positive neurons in the hypothalamic paraventricular nucleus(PVN)under different status of diabetes mellitus(DM).Methods:Intraperito-neal injection of vehicle or STZ in mice was conducted to establish control or diabetes model.Mechanical sensitivity was evaluated by von Frey filament tests to distinguish diabetic neuropathic pain(DNP)from without-pain group(DWP).The expression of FOS,oxytocin(OXT)-and vasopressin(VP)-positive neurons,as well as their double labeling was detected by immunohistochemical and immunofluorescent staining.Cell counting and comparison were made in groups.Results:FOS expression was easily detected in the PVN in the three groups(Control group,DNP group and DWP group)at 7 days,while that in DWP and DNP groups at 28 days was hardly detectable,with the number being signifi-cantly different from the 7 days group(P＜0.05 or 0.001).Likewise,compared with the control group,immunofluo-rescent signals for VP and OXT staining in the DNP and DWP groups also showed a trend of weakening as the modeling time increased(P＜0.05).The cell counting after double staining for VP or OXT with FOS showed that,in the DWP group at 7 days,the number of VP and FOS double-labeled neurons was 74.33±22.10,accounting for(56.64± 7.52)％of VP-positive cells,whereas the double labeling rate for OXT and FOS was only(10.44±3.14)％.In the DNP group at 7 days,the number of OXT and FOS double-labeled neurons was 51.00±31.80,accounting for(18.50 ±9.51)％of OXT-positive neurons,whereas the double labeling rate for VP and FOS was only(9.34±3.27)％.In contrast to these changes in 7 days group,the expression of FOS decreased sharply in the group of 28 days,thereby al-most no double-labeled neurons.Conclusion:The plasticity changes of oxytocin-and vasopressin-positive neurons in the PVN are different depending on the status of pain and non-pain,and the stage of disease progression.Understanding the changes is of great significance for unravelling the neural mechanism of diabetes and its complications.

Objective:To investigate the impact of body mass index (BMI) on delayed extubation of patients with acute Stanford type A aortic dissection (ATAAD).Methods:A total of 400 ATAAD patients who were admitted to our hospital from October 2021 to October 2023 and underwent surgical treatment were selected as the research objects. According to BMI, they were divided into obese group (BMI≥28 kg/m 2, 119 cases) and non-obese group (BMI<28 kg/m 2, 281 cases). The differences of preoperative clinical characteristics, intraoperative and postoperative data between the two groups were compared. Starting from transferring to the ICU and ending with the first successful extubation, The risk factors of postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients were analyzed, and the predictive efficacy of related factors for postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients was evaluated. Results:Compared with the non-obese group, the proportion of hypertension, diabetes, admission heart rate, admission systolic blood pressure, admission diastolic blood pressure and preoperative white blood cell count in the obese group were significantly increased, and the differences were statistically significant ( P<0.05). The cardiopulmonary bypass time, aortic cross-clamp time, operation time, red blood cell transfusion volume, invasive mechanical ventilation time, secondary operation rate and total hospitalization cost in the obese group were significantly higher than those in the non-obese group, and the differences were statistically significant ( P<0.05). Univariate logistic regression analysis showed that BMI, cardiopulmonary bypass time, ascending aortic cross-clamp time, operation time, age, hypertension, and red blood cell transfusion were related factors for postoperative invasive mechanical ventilation time ≥48 h in ATAAD patients ( P<0.05). Logistic multivariate regression analysis showed that increased BMI ( OR=1.213, P<0.05) and increased age ( OR=1.020, P<0.05) were independent risk predictors of postoperative invasive mechanical ventilation time≥48 h in ATAAD patients. Receiver operating characteristic curve ( ROC) analysis showed that the area under the ROC curve ( AUC) of BMI for predicting the duration of postoperative invasive mechanical ventilation in ATAAD patients≥48 h was 0.682 ( P<0.05), and the best predictive cut-off value was 25.64 kg/m 2. Conclusion:BMI≥28kg/m 2 increases the difficulty of surgery and the duration of invasive mechanical ventilation in ATAAD patients. BMI has a high predictive value for the duration of invasive mechanical ventilation in ATAAD patients after surgery ≥48 h, and effective intervention measures can be formulated to improve the treatment effect of patients.

Objective:To observe the neuroanatomical properties of the projection pathway from the nucleus reuniens(Re)to the dorsal(dHC)and ventral(vHC)hippocampus.Methods:Adeno-associated virus SV40 was injected into the Re of C57BL/6 mice and the profile of downstream projection in the whole brain was examined and ranked.Retro-grade tracer Fluoro-Gold(FG)was injected into the whole hippocampus(wHC),dorsal hippocampus(dHC)or ven-tral hippocampus(vHC),and the distribution of the retrogradely labeled neurons and its relationship with calretinin(CR)in the Re were analyzed.Results:After injection of SV40 virus into the Re,we observed projection fibers or ter-minals in 18 areas across the brain.Among the areas,those to the hippocampus(HC)were mainly distributed in the dorsal and ventral lacunosum molecular layer,which ranked No.2 with regard to the projection intensity.Following injection of FG into the hippocampus,we observed that the retrogradely labeled neurons projecting to the wHC were densely distributed in the rostrocaudal segments of Re,with a more concentrated aggregation in the ventromedial part.FG+CR+double labeled neurons accounted for(47.47±0.07)％of FG labeled neurons,and for(67.13±0.10)％of CR+neurons in this case.The retrograde labeled neurons projecting to the dHC were sparse and mainly distributed in the dorsolateral part of Re.FG+CR+double labeled neurons accounted for(24.11±0.06)％of FG labeled neurons,and for(32.99±0.19)％of CR+neurons.The retrogradely labeled neurons projecting to the vHC were mainly distrib-uted in the ventralmedial part of Re.FG+CR+double labeled neurons accounted for(49.55±0.03)％of FG labeled neurons,and for(69.14±0.12)％of CR+neurons.Conclusion:Hippocampus is an essential target of the Re.The projections to the dHC and vHP differ in the location of projection neurons and the positive ratio with CR,which may re-flect the differential pathophysiological functions of the two pathways in vivo.

Objective:To observe the neuroanatomical properties of the projection pathway from the nucleus reuniens(Re)to the dorsal(dHC)and ventral(vHC)hippocampus.Methods:Adeno-associated virus SV40 was injected into the Re of C57BL/6 mice and the profile of downstream projection in the whole brain was examined and ranked.Retro-grade tracer Fluoro-Gold(FG)was injected into the whole hippocampus(wHC),dorsal hippocampus(dHC)or ven-tral hippocampus(vHC),and the distribution of the retrogradely labeled neurons and its relationship with calretinin(CR)in the Re were analyzed.Results:After injection of SV40 virus into the Re,we observed projection fibers or ter-minals in 18 areas across the brain.Among the areas,those to the hippocampus(HC)were mainly distributed in the dorsal and ventral lacunosum molecular layer,which ranked No.2 with regard to the projection intensity.Following injection of FG into the hippocampus,we observed that the retrogradely labeled neurons projecting to the wHC were densely distributed in the rostrocaudal segments of Re,with a more concentrated aggregation in the ventromedial part.FG+CR+double labeled neurons accounted for(47.47±0.07)％of FG labeled neurons,and for(67.13±0.10)％of CR+neurons in this case.The retrograde labeled neurons projecting to the dHC were sparse and mainly distributed in the dorsolateral part of Re.FG+CR+double labeled neurons accounted for(24.11±0.06)％of FG labeled neurons,and for(32.99±0.19)％of CR+neurons.The retrogradely labeled neurons projecting to the vHC were mainly distrib-uted in the ventralmedial part of Re.FG+CR+double labeled neurons accounted for(49.55±0.03)％of FG labeled neurons,and for(69.14±0.12)％of CR+neurons.Conclusion:Hippocampus is an essential target of the Re.The projections to the dHC and vHP differ in the location of projection neurons and the positive ratio with CR,which may re-flect the differential pathophysiological functions of the two pathways in vivo.