ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

Objective To explore the efficacy of the on-demand intermittent total androgen blockade regimen in treating cases with positive surgical margins after radical prostatectomy for pT3 stage prostate cancer. Methods A retrospective analysis was conducted on the clinical data of 21 patients with pT3 stage prostate cancer who underwent radical prostatectomy and had positive surgical margins confirmed by pathology in our hospital during Jan. 2013 and Dec. 2020. Prostate-specific antigen(PSA)was used as the indicator of observation. For those with biochemical recurrence(PSA＞0.2 μg/L), at least 2 months of androgen deprivation therapy(ADT)combined with the maximum androgen receptor antagonist was administered for maximal androgen blockade endocrine therapy. If PSA still exceeded 0.1 μg/L after 2 months of maximal androgen blockade treatment, the maximal androgen blockade was maintained and monthly follow-up was conducted until PSA reached the discontinuation criteria. During the discontinuation period, the serum PSA and testosterone levels were checked every 4 to 6 weeks. The time of application of maximal androgen blockade and the subsequent interval of discontinuation were defined as one treatment cycle. Results Postoperative pathology confirmed that among the 21 patients, 17 were pT3a and 4 were pT3b. The PSA level 1 month after surgery was(0.23±0.45)μg/L. The follow-up lasted for 48 to 126 months, with an average of(68.86 ± 20.43)months. The interval between the first application of maximal androgen blockade and radical prostatectomy was 2 to 35 months, with an average of(12.48±8.83)months. One patient died of post-cerebral infarction complications 74 months after surgery, another progressed to hormone-resistant prostate cancer(CRPC)70 months after surgery and the treatment plan was immediately changed. Up to 90.5%(19/21)of the patients completed 5 to 12 cycles of combined endocrine therapy, with no tumor progression. Conclusion Based on the postoperative PSA level monitored, intermittent administration of the maximum androgen blockade endocrine therapy can effectively control the cancer progression of patients with positive surgical margins after radical prostatectomy, which can also reduce the adverse reactions.

ObjectiveTo investigate the metabolic mechanisms of Limosilactobacillus reuteri （L. reuteri） in alleviating chemotherapy-induced intestinal mucosal injury （CIMI）. MethodsC57BL/6 mice were randomly divided into the Control group， Model group， and L. reuteri treatment group （n=8 per group）. Mice in the L. reuteri group were intragastrically administered L. reuteri （1 × 10⁹ CFU/mL） for 10 consecutive days. From day 5， mice in the Model and L. reuteri groups were intraperitoneally injected with 5-FU （65 mg/kg） for 6 consecutive days to establish a CIMI model. Body weight changes， colon length， and related indicators were recorded. Intestinal histopathological injury was assessed by HE staining with measurement of villus height and crypt depth. The expression levels of zonula occludens-1 （ZO-1）， Occludin， Claudin-4， Muc1， and Muc2 in ileal tissues were determined by RT-qPCR and immunohistochemistry to evaluate intestinal barrier function. In addition， untargeted metabolomics was performed on cecal contents from each group to analyze metabolic profiles and enrichment of differential metabolic pathways. ResultsL. reuteri intervention significantly alleviated body weight loss （P<0.001） and colon shortening （P<0.05） in CIMI mice， effectively reducing ileal tissue pathological damage， and upregulating the expression of ZO-1， Occludin， Claudin4， Muc1， and Muc2 （P<0.05）. Untargeted metabolomics analysis showed that L. reuteri treatment reversed the abnormal metabolic profile in the cecal contents of CIMI mice， bringing it closer to normal. Various differential metabolites， such as acylcarnitines and polyunsaturated fatty acids， might play an important role in L. reuteri-mediated alleviation of CIMI. These differential metabolites were primarily enriched in key pathways such as linoleic acid metabolism， tryptophan metabolism， and unsaturated fatty acid biosynthesis. ConclusionThis study reveals that L. reuteri improves intestinal barrier function and alleviates CIMI by regulating the intestinal metabolic profile， particularly lipid and amino acid metabolism. It provides a novel potential strategy for the prevention and treatment of CIMI.

Objective To investigate the diagnostic efficacy of fat fraction(FF)and T2* values of infrapatellar fat pad(IPFP)based on MR mDixon-Quant technique for knee osteoarthritis(KOA),and to analyze their related influencing factors.Methods A total of 178 knee joints from 114 volunteers were included and underwent knee joints X-ray examination and MR mDixon-Quant sequence scanning.The correlation between FF and T2* values of IPFP with gender,age,body mass index(BMI),and K-L grade was analyzed by Spearman's test and multiple linear regression.Receiver operating characteristic(ROC)curves were plotted to assess the diag-nostic efficacy of FF and T2* values for KOA.Results FF value of IPFP was negatively correlated with age,BMI,and K-L grade(r=-0.470,-0.276,-0.679,P＜0.001),and T2* value was also negatively correlated with age,BMI,and K-L grade(r=-0.291,-0.173,-0.505,P＜0.001).Multiple linear regression analysis results showed that only K-L grade had a statistically significant correlation with FF and T2* values(P＜0.001).ROC curve analysis indicated that the area under the curve(AUC)for diagnosing KOA using the FF and T2* values of IPFP were 0.859 and 0.767,respectively,with sensitivity of 0.878 and 0.841,and specificity of 0.719 and 0.573,respectively.The combined diagnosis had an AUC of 0.855,a sensitivity of 0.625,and a specificity of 0.963,improving the diagnostic specificity for KOA.Conclusion FF and T2* values of IPFP can serve as objective imaging indicators for KOA assessment,and their reduction is correlated with the progress of age,BMI,and K-L grade,of which the K-L grade is an independent influencing factor.The combination of FF and T2 can improve the diagnostic specificity of KOA,and provide a quantitative basis for early KOA detection and severity stratification.

Objective To investigate the diagnostic efficacy of fat fraction(FF)and T2* values of infrapatellar fat pad(IPFP)based on MR mDixon-Quant technique for knee osteoarthritis(KOA),and to analyze their related influencing factors.Methods A total of 178 knee joints from 114 volunteers were included and underwent knee joints X-ray examination and MR mDixon-Quant sequence scanning.The correlation between FF and T2* values of IPFP with gender,age,body mass index(BMI),and K-L grade was analyzed by Spearman's test and multiple linear regression.Receiver operating characteristic(ROC)curves were plotted to assess the diag-nostic efficacy of FF and T2* values for KOA.Results FF value of IPFP was negatively correlated with age,BMI,and K-L grade(r=-0.470,-0.276,-0.679,P＜0.001),and T2* value was also negatively correlated with age,BMI,and K-L grade(r=-0.291,-0.173,-0.505,P＜0.001).Multiple linear regression analysis results showed that only K-L grade had a statistically significant correlation with FF and T2* values(P＜0.001).ROC curve analysis indicated that the area under the curve(AUC)for diagnosing KOA using the FF and T2* values of IPFP were 0.859 and 0.767,respectively,with sensitivity of 0.878 and 0.841,and specificity of 0.719 and 0.573,respectively.The combined diagnosis had an AUC of 0.855,a sensitivity of 0.625,and a specificity of 0.963,improving the diagnostic specificity for KOA.Conclusion FF and T2* values of IPFP can serve as objective imaging indicators for KOA assessment,and their reduction is correlated with the progress of age,BMI,and K-L grade,of which the K-L grade is an independent influencing factor.The combination of FF and T2 can improve the diagnostic specificity of KOA,and provide a quantitative basis for early KOA detection and severity stratification.

Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40％,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56％in the superotemporal quad-rant,58.35％in the inferotemporal quadrant,45.50％in the superonasal quadrant,and 43.17％in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71％of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00％in the superonasal quadrant and 78.41％in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.

Objective To investigate the association between brachial-ankle pulse wave velocity(baPWV)and left ventricular structure and function.Methods A total of 4864 participants who completed baPWV and transthoracic echocardiography from January 2010 to December 2021 were included.The participants were divided into three groups based on baPWV:Group T1:baPWV＜14m/s;Group T2:14m/s≤baPWV＜18m/s;Group T3:baPWV ≥18m/s.Multivariable Logistic regression and linear regression was used to examine the correlation between baPWV and interventricular septal thickness(IVS),left ventricular posterior wall thickness(LVPW),left ventricular end diastolic diameter(LVEDd),left ventricular mass index(LVMI),left ventricular ejection fraction(LVEF),and the presence of mitral e'/a'＜1.Results Increased baPWV was significantly associated with thickening of IVS(β=0.095,95％CI:0.007-0.182),thickening of LVPW(β=0.145,95％CI:0.056-0.233),and mitral e'/a'＜1(OR=2.200,95％CI:1.608-3.010)(P＜0.05).It was negatively correlated with LVEDd(β=-0.048,95％CI:-0.075--0.021)and showed no significant associa-tion with LVMI and LVEF(P＞0.05).Stratified analysis indicated that systolic blood pressure and baPWV had an interaction effect on LVEDd and mitral e'/a'＜1(P＜0.05).Conclusion BaPWV is associated with left ventricular remodeling and diastolic function.The correlation between baPWV and LVPW and LVEDd is stronger in groups with normal systolic blood pressure.In contrast,the correlation with mitral e'/a'＜1 is more prominent in groups with elevated systolic blood pressure.

Objective To investigate the association between brachial-ankle pulse wave velocity(baPWV)and left ventricular structure and function.Methods A total of 4864 participants who completed baPWV and transthoracic echocardiography from January 2010 to December 2021 were included.The participants were divided into three groups based on baPWV:Group T1:baPWV＜14m/s;Group T2:14m/s≤baPWV＜18m/s;Group T3:baPWV ≥18m/s.Multivariable Logistic regression and linear regression was used to examine the correlation between baPWV and interventricular septal thickness(IVS),left ventricular posterior wall thickness(LVPW),left ventricular end diastolic diameter(LVEDd),left ventricular mass index(LVMI),left ventricular ejection fraction(LVEF),and the presence of mitral e'/a'＜1.Results Increased baPWV was significantly associated with thickening of IVS(β=0.095,95％CI:0.007-0.182),thickening of LVPW(β=0.145,95％CI:0.056-0.233),and mitral e'/a'＜1(OR=2.200,95％CI:1.608-3.010)(P＜0.05).It was negatively correlated with LVEDd(β=-0.048,95％CI:-0.075--0.021)and showed no significant associa-tion with LVMI and LVEF(P＞0.05).Stratified analysis indicated that systolic blood pressure and baPWV had an interaction effect on LVEDd and mitral e'/a'＜1(P＜0.05).Conclusion BaPWV is associated with left ventricular remodeling and diastolic function.The correlation between baPWV and LVPW and LVEDd is stronger in groups with normal systolic blood pressure.In contrast,the correlation with mitral e'/a'＜1 is more prominent in groups with elevated systolic blood pressure.

Objective To investigate the role of Taohong Siwu Decoction(THSWD)in microglia pyroptosis mediated neuronal injury in PC12 under oxygen-glucose deprivation/reperfusion(OGD/R)and related mechanisms.Methods PC12 and BV2 cells were co-cultured using the OGD/R model to simulate ischemia-reperfusion injury of in vitro.The experiment was grouped as follows:control(PC12,PC12+BV2),OGD/R group(PC12,PC12+BV2),and OGD/R+10％THSWD-containing serum group(PC12,PC12+BV2).Oxygen and glucose was restored for 24h after 4-6h of deprivation.The severity of damage to PC12 cells was evaluated by cell counting kit-8(CCK-8)and flow cytometry.BV2 cells were used for the experiments and were divided into control,OGD/R and OGD/R+THSWD-containing serum(5％,10％,15％)groups,which were moulded and administered in the same way,and cell py-roptosis proteins proteinscysteinyl aspartate specific proteinase-1(caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC),gasdermin D(GSDMD),interleukin-1β(IL-1β),interleukin-18(IL-18)and nucleotide-binding oligomeriza-tion domain-like receptor protein 3(NLRP3)inflammasome-associated proteins were detected by Western blot.Results In the pres-ence of BV2 cells,THSWD was able to further restore the morphology,increase cell viability(P＜0.05)and reduce apoptosis of PC12 cells after OGD/R injury(P＜0.05).In addition,THSWD was able to reduce the expression of OGD/R-induced pyroptosis proteins(caspase-1,ASC,GSDMD,IL-1β,IL-18)in BV2 microglia cells(P＜0.05).In contrast,the inhibitory effects of THSWD on BV2 cells pyroptosis proteins and NLRP3 inflammasome were reversed by NLRP3/caspase-1 agonist(P＜0.05).Conclusion THSWD protects PC 12 cells against OGD/R injury via inhibiting microglia pyroptosis mediated by the NLRP3/caspase-1 pathway.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.