ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

AIM To investigate the effects of Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction(GJHQHLRSD)on the pyroptosis,pathway of colonic epithelial cells in mouse models of ulcerative colitis(UC).METHODS Among the 63 C57BL/6J mice,13 were randomly selected and assigned to the model group,and the others were divided into the control group,the positive Sulfasalazine Enteric-Coated Tablets group(0.6 g/kg),and low,medium,and high dose GJHQHLRSD groups(3.9,7.8,15.6 g/kg),with 10 mice in each group.The UC mouse model was established using DSS,and the corresponding drugs were administered by gavage.The mice had their general condition observed;their disease activity index(DAI)score assessed;their colon length measured;their histopathological damage of the colon analyzed using HE staining;their colonic IL-1β,IL-8,and TNF-α levels measured by ELISA method;their colonic NLRP3,GSDMD,pro-IL-1β,pro-caspase-1,and IL-1βprotein expression detected by Western blot method;and their cell pyroptosis detected by TUNEL and GSDMD fluorescence double staining.RESULTS Compared with the control group,the model group exhibited significant decrease in body weight and a shortened colon length(P＜0.01);increases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);significant increase of colonic GSDMD and TUNEL positivity;indicating increased tissue damage and inflammatory response.Compared with the model group,the groups intervened with GJHQHLRSD showed a significant increase in body weight and colonic elongation(P＜0.05,P＜0.01);decreases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);a gradient decrease in positivity of GSDMD and TUNEL;indicating a significantly reduced colonic pathological damage.CONCLUSION GJHQHLRSD can improve the DSS-induced inflammatory reaction of colonic mucosa in UC mice,and its mechanism mainly involves the NLRP3/caspase-1,thereby the regulation of the cell pyroptosis process.

Objective To compare the capture performance differences between TruSeq? Exome and NimbleGen SeqCap EZ Human Exome kits in children with cerebral palsy(CP),and to provide a technical selection basis for clinical genetic research and diagnosis.Methods Peripheral blood samples from 48 sporadic CP patients were included.Exome libraries were constructed using TruSeq(DNA probes)and NimbleGen(RNA probes),followed by sequencing on the Illumina HiSeq 2000 platform.Bioinformatics analysis was applied to evaluate mapping rate,target region coverage,variant concordance,and clinical relevance based on a CP-related gene set(2 293 genes).The statistical analysis was performed using a paired t-test with a significance threshold of α=0.05.Results The results showed no significant differences between NimbleGen and TruSeq exome capture kits in basic data quality(alignment rate,insert size)and GC content.However,they exhibited complementary characteristics in key performance metrics:NimbleGen demonstrated superior performance in specific depth coverage(1×coverage rate,P=1.84×10-5;20×coverage rate,P=1.49×10-20).TruSeq,on the other hand,showed higher sensitivity in Indel detection(TruSeq vs.NimbleGen:11 371±1 689 vs.11 274±1 670,P=3.24×10-7)and rare variant capture(TruSeq vs.NimbleGen:3 164±766 vs.3 072±774,P=1.20×10-4),successfully identifying all 11 pathogenic variants(including 2 missed by NimbleGen).Conclusion TruSeq,with its superior variant detection rate,is more suitable for clinical diagnostic applications,while NimbleGen's coverage stability may be advantageous for research-oriented projects.

AIM To study the chemical constituents from salt-processed Litchi Semen and their antioxidant activities.METHODS The 85％ethanol extract from salt-processed Litchi Semen was isolated and purified by silica gel,Sephadex LH-20,MCI,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.DPPH and ABTS+free radical scavenging method were used to evaluate their antioxidant activities.RESULTS Fifteen compounds were isolated and identified as dehydrocostuslactone(1),ananosmoside A(2),funingensin A(3),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(4),liquiritienin(5),quercetin(6),rutin(7),isorhamnetin-3-O-β-rutinoside(8),procyanidin A2(9),procyanidin A1(10),ethyl protocatechuate(11),5-hydroxymethylfurfural(12),di(2-ethyl-hexyl)phthalate(13),nicotinamide(14),(10E,15Z)-9,12,13-trihydroxyoctadeca-10,15-dienoic acid(15).Compounds 6-7,9-10 exhibited scavenging activities against DPPH radicals with IC50 values of(12.929±1.232),(14.104±0.946),(10.417±1.736),(6.944±0.030)μmol/L,respectively.Compounds 6-10 exhibited scavenging activities against ABTS+radicals with IC50 values of(21.952±0.577),(25.683±0.625),(22.970±1.336),(20.210±1.435),(18.725±0.324)μmol/L,respectively.CONCLUSION Compounds 1,5,14-15 are isolated from Litchi genus for the first time.Compounds 6-7,9-10 have strong in vitro antioxidant activities.

AIM To investigate the effects of Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction(GJHQHLRSD)on the pyroptosis,pathway of colonic epithelial cells in mouse models of ulcerative colitis(UC).METHODS Among the 63 C57BL/6J mice,13 were randomly selected and assigned to the model group,and the others were divided into the control group,the positive Sulfasalazine Enteric-Coated Tablets group(0.6 g/kg),and low,medium,and high dose GJHQHLRSD groups(3.9,7.8,15.6 g/kg),with 10 mice in each group.The UC mouse model was established using DSS,and the corresponding drugs were administered by gavage.The mice had their general condition observed;their disease activity index(DAI)score assessed;their colon length measured;their histopathological damage of the colon analyzed using HE staining;their colonic IL-1β,IL-8,and TNF-α levels measured by ELISA method;their colonic NLRP3,GSDMD,pro-IL-1β,pro-caspase-1,and IL-1βprotein expression detected by Western blot method;and their cell pyroptosis detected by TUNEL and GSDMD fluorescence double staining.RESULTS Compared with the control group,the model group exhibited significant decrease in body weight and a shortened colon length(P＜0.01);increases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);significant increase of colonic GSDMD and TUNEL positivity;indicating increased tissue damage and inflammatory response.Compared with the model group,the groups intervened with GJHQHLRSD showed a significant increase in body weight and colonic elongation(P＜0.05,P＜0.01);decreases in DAI score,levels of IL-1β,IL-8,TNF-α,as well as the protein expressions of NLRP3,GSDMD,and active-caspase-1(P＜0.05,P＜0.01);a gradient decrease in positivity of GSDMD and TUNEL;indicating a significantly reduced colonic pathological damage.CONCLUSION GJHQHLRSD can improve the DSS-induced inflammatory reaction of colonic mucosa in UC mice,and its mechanism mainly involves the NLRP3/caspase-1,thereby the regulation of the cell pyroptosis process.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.

Objective To compare the capture performance differences between TruSeq? Exome and NimbleGen SeqCap EZ Human Exome kits in children with cerebral palsy(CP),and to provide a technical selection basis for clinical genetic research and diagnosis.Methods Peripheral blood samples from 48 sporadic CP patients were included.Exome libraries were constructed using TruSeq(DNA probes)and NimbleGen(RNA probes),followed by sequencing on the Illumina HiSeq 2000 platform.Bioinformatics analysis was applied to evaluate mapping rate,target region coverage,variant concordance,and clinical relevance based on a CP-related gene set(2 293 genes).The statistical analysis was performed using a paired t-test with a significance threshold of α=0.05.Results The results showed no significant differences between NimbleGen and TruSeq exome capture kits in basic data quality(alignment rate,insert size)and GC content.However,they exhibited complementary characteristics in key performance metrics:NimbleGen demonstrated superior performance in specific depth coverage(1×coverage rate,P=1.84×10-5;20×coverage rate,P=1.49×10-20).TruSeq,on the other hand,showed higher sensitivity in Indel detection(TruSeq vs.NimbleGen:11 371±1 689 vs.11 274±1 670,P=3.24×10-7)and rare variant capture(TruSeq vs.NimbleGen:3 164±766 vs.3 072±774,P=1.20×10-4),successfully identifying all 11 pathogenic variants(including 2 missed by NimbleGen).Conclusion TruSeq,with its superior variant detection rate,is more suitable for clinical diagnostic applications,while NimbleGen's coverage stability may be advantageous for research-oriented projects.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.