Objective: This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Methods: Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing. Results: Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05). Conclusion QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.

Central serous chorioretinopathy(CSC), the first described pachychoroid disease, is characterized by visual distortions and loss of vision, which are commonly seen in middle-aged male. Research has demonstrated that ocular blood flow in CSC is in a state of overload, characterized by the dilation of vortex vein ampullae and choroidal vasculature. The obstruction of venous outflow is linked to scleral thickness, while the choriocapillaris exhibits perfusion deficits due to compression from the engorged vascular layer. Over time, vascular remodeling occurs, with venous anastomoses forming to create alternative drainage pathways and mitigate blood stasis. These abnormalities in vortex vein dynamics and choroidal circulation play a critical role in elucidating the underlying pathogenesis and clinical manifestations of CSC. This review highlights the alterations in vortex vein and choroidal vasculature in CSC, hoping to understand how the changes of blood flow affect the course of CSC and their correlation with treatment response. By evaluating blood flow dynamics, we aim to determine the disease stage more accurately, optimize therapeutic strategies, and ultimately enhance patient outcomes.

ObjectiveTo explore the effect and mechanism of Qigui Didang decoction， formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals， on improving metabolic memory of db/db mice with diabetic nephropathy （DN） through silent information regulator 1 signal regulator 1 （Sirt1）/p53/nuclear factor kappa-B （NF-κB） p65 pathway. MethodsFifteen db/db mice were randomly divided into model group （10 mL·kg^-1·d^-1）， resveratrol group （20 mg·kg^-1·d^-1）， and Qigui Didang decoction group （3.34 g·kg^-1·d^-1） Another five db/m mice were selected as the normal group （10 mL·kg^-1·d^-1）. After the intervention， the kidney weight of each group was measured， and the kidney index （KI） was calculated. Fasting blood glucose （FBG）， creatinine （CRE）， β2-microglobulin （β2-MG）， blood urea nitrogen （BUN）， and cystatin C （CysC） were measured. Renal pathology was observed by hematoxylin-eosin （HE） staining and Masson staining. The mRNA and protein expression levels of Sirt1， NF-κB， tumor suppressor gene p53， interleukin-1β （IL-1β）， and cysteine aspartate protease-3 （Caspase-3） were detected using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered renal structure， obvious renal damage， and markedly elevated levels of renal function indexes （CRE， β2-MG， BUN， and CysC） （P<0.01）. The KI and blood glucose were significantly increased （P<0.01）， while Sirt1 expression was markedly decreased （P<0.01）. Expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were increased significantly （P<0.05）. Compared with those in the model group， DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG， improved renal function， and markedly decreased KI （P<0.01）， along with reduced CRE， β2-MG， BUN， and CysC levels （P<0.05）. Protein expression of Sirt1 was significantly upregulated （P<0.05）， while that of NF-κB p65， p53， IL-1β， and Caspase-3 was markedly decreased （P<0.05）. The mRNA expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were significantly decreased （P<0.05）. The staining results indicate improved renal fibrosis， significantly decreased fiber deposition （P<0.05）， and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN， thereby inhibiting renal cell apoptosis and inflammatory response in mice， and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.

OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Objective To investigate the expression of 8-hydroxy deoxy guanosine(8-OHdG)and nectin-4 in the serum of primary liver cancer(PLC),and to evaluate the efficacy of transcatheter chemoembolization(TACE)for PLC.Methods From January 2021 to June 2022,180 patients with primary liver cancer with TACE were studied.According to the efficacy of TACE patients,they were separated into a good group(n=137)and an adverse group(n=43).The general clinical data and the serum expression levels of 8-OHdG and nectin-4 were compared between the two groups;multivariate Logistic regression was applied to analyze the influencing factors of postoperative efficacy in TACE for primary liver cancer;receiver operating characteristic was applied to analyze the value of serum 8-OHdG and nectin-4 levels in evaluating the efficacy of TACE for primary liver cancer.Results There were no significant differences in age,sex,BMI,Child-Pugh grade,tumor location,tumor number,tumor diameter,tumor contour,degree of differentiation,tumor envelope,vascular cancer thrombus,bile duct cancer thrombus and lymph node metastasis between the poor postoperative efficacy group and the good efficacy group after TACE for primary liver cancer(P＞0.05).The expression levels of serum 8-OHdG and nectin-4 in the poor postoperative efficacy group after TACE for primary liver cancer were obviously higher than those in the good efficacy group(P＜0.05).Multivariate Logistic regression analysis showed that serum 8-OHdG,nectin-4,tumor diameter,TNM staging and Lymph node metastasis were all independent influencing factors for the postoperative efficacy of TACE in primary liver cancer(P＜0.05).The AUC of the combined evaluation of serum 8-OHdG and nectin-4 for the postoperative efficacy of TACE in primary liver cancer was 0.930,with a sensitivity of 86.05％and a specificity of 94.16％,which was superior to their respective individual evaluations(Zcombination-8-OHdG=2.033,Zcombination-nectin-4=3.221,P=0.042,0.001).Conclusion The serum levels of 8-OHdG and nectin-4 are obviously increased in the poor postoperative efficacy group after TACE for primary liver cancer.The combination of the two has a good evaluation effect on the postoperative efficacy of TACE for primary liver cancer.

ObjectiveTo investigate the effect of supplemented Buyang Huanwutang on kidney tissue， nuclear factor-κB （NF-κB） pathway， and fibrosis factors in diabetic kidney disease （DKD） mice. MethodA total of 24 db/db mice （11-12 weeks old） were randomized into the model group （equivalent volume of distilled water， once/day， 8 weeks）， supplemented Buyang Huanwutang group （16.0 g·kg^-1， once/day， 8 weeks）， and irbesartan group （13.5 mg·kg^-1， once/day， 8 weeks） after adaptive feeding for 1 week and positive urinary protein monitoring， with 8 in each group. Another 8 db/m mice （11-12 weeks old） were included in the normal group （equivalent volume of distilled water， once/day， 8 weeks）. Then samples were collected， and the levels of fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （SCr）， and urinary microalbumin （mALB） were detected. The mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and monocyte chemoattractant protein-1 （MCP-1） was determined by real-time polymerase chain reaction （Real-time PCR）. The expression of nuclear factor-κB （NF-κB）， NF-κB inhibitor α （IκBα）， phosphorylated IκBα （p-IκBα）， transforming growth factor-β₁ （TGF-β₁）， α-smooth muscle actin （α-SMA）， and fibronectin （FN） in kidney tissue was measured by Western blot. The expression of NF-κB in renal tissue was detected by immunofluorescence. The pathological changes of kidney were observed under light microscope. ResultCompared with the normal group， the model group showed glomerular hypertrophy， increase in extracellular matrix， thickening of basement membrane， small cystic lumen， interstitial inflammatory cell infiltration， and some interstitial fibrosis （P<0.01）. Moreover， the model group had higher content of FBG， mALB， TC， TG， BUN， and SCr （P<0.01）， higher expression of inflammatory factors TNF-α， IL-1β， and MCP-1， and fibrosis-related proteins TGF-β₁， α-SMA， and FN （P<0.01）， and stronger activation of NF-κB pathway in renal tissue （P<0.01） than the normal group. Compared with the model group， supplemented Buyang Huanwutang alleviated the pathological injury in kidney （P<0.01）， decreased the content of mALB， TC， and TG， the content of BUN and SCr （P<0.01）， and the content of TNF-α， IL-1β， and MCP-1 （P<0.05， P<0.01）， and inhibited the activation of NF-κB pathway and the expression of fibrosis factors in renal tissue （P<0.05， P<0.01）， but had no significant effect on blood glucose level. ConclusionBy inhibiting NF-κB pathway and the expression of fibrosis factors in renal tissue， supplemented Buyang Huanwutang can exert anti-inflammatory and anti-fibrosis effect and alleviate the pathological damage in kidney tissue， thereby protecting the kidney.

Objective To investigate the clinical effect of percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy for necrosectomy and drainage in the treatment of refractory liver abscess after transcatheter arterial embolization (TACE). Methods A retrospective analysis was performed for three patients with refractory liver abscess after TACE in The Affiliated 3201 Hospital of Xi'an Jiaotong University School of Medicine from January 2018 to December 2020, and among the three patients, one had the formation of liver abscess after TACE for hepatic metastases after pancreaticoduodenectomy, one had liver abscess after repeated TACE for massive hepatocellular carcinoma, and one had secondary liver abscess after TACE for traumatic hepatic rupture. All three patients received percutaneous transhepatic drainage and sequential percutaneous nephroscopy for the treatment of refractory liver abscess, and their specific treatment process was summarized. Results All three patients were diagnosed with refractory liver abscess based on CT, routine blood test, procalcitonin, blood culture, and clinical manifestation. Percutaneous transhepatic catheterization under the guidance of conventional ultrasonography or CT and effective antibiotics had an unsatisfactory therapeutic effect, and after sequential percutaneous nephroscopy was performed for necrosectomy and drainage, liver abscess was cured and the patients had good prognosis. Conclusion For refractory liver abscess after TACE, when routine puncture treatment has an unsatisfactory therapeutic effect or a patient cannot tolerate surgical operation, percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy is safe and effective in the treatment of refractory liver abscess.

Objective To investigate the clinical effect of two-step percutaneous transhepatic choledochoscopic lithotomy (PTCSL) in the treatment of complex hepatolithiasis. Methods A retrospective analysis was performed for the clinical data of 118 patients with complex hepatolithiasis who were admitted to 3201 Hospital of Xi'an Jiaotong University Health Science Center from January 2018 to June 2020, and according to the surgical procedure, they were divided into PTCSL group with 60 patients and surgery group with 58 patients. All patients were followed up for half a year to 3 years via telephone and outpatient service. The two groups were compared in terms of general information, perioperative indicators (including time of operation, intraoperative blood loss, incision length, time to first flatus and time to first defecation after surgery, time to extraction of abdominal drainage tube, and length of hospital stay), changes in liver function and inflammatory indicators, postoperative complications (bile leakage, acute cholangitis, wound infection, and venous thrombosis of lower extremities), stone clearance rate and recurrence rate, and quality of life. The two-independent-samples t -test was used for comparison of continuous data between two groups; the paired t -test was used for comparison between different periods of time within group; the chi-square test was used for comparison of categorical data between two groups. Results Compared with the surgery group, the PTCSL group had significantly shorter time of operation, time to first flatus and time to first defecation after surgery, and time to extraction of abdominal drainage tube, a significantly lower intraoperative blood loss, and a significantly shorter incision length (all P < 0.05). On day 1 after surgery, both groups had significant reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ( P < 0.05) and a significant increase in white blood cell count (WBC) ( P < 0.05), and the PTCSL group had significantly lower levels of ALT, AST, and WBC than the surgery group (all P < 0.05). Compared with the surgery group, the PTCSL group had significantly lower incidence rates of postoperative bile leakage (5.0% vs 17.2%, P < 0.05), acute cholangitis (3.3% vs 13.8%, P < 0.05), wound infection (1.7% vs 10.3%, P < 0.05), and venous thrombosis of lower extremities (1.7% vs 12.1%, P < 0.05). Compared with the surgery group, the PTCSL group had a significantly higher stone clearance rate (58.3% vs 37.9%, P < 0.05) and a significantly lower long-term stone recurrence rate (10.0% vs 20.7%, P < 0.05). The PTCSL group had significantly higher quality of life scores than the surgery group (all P < 0.05). Conclusion For the treatment of complex hepatolithiasis, two-step PTCSL can effectively remove stones, with the advantages of fast postoperative recovery, low recurrence rate and incidence rate of complications, and high quality of life, and therefore, it is an effective alternative surgical procedure.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in developed and developing countries.NAFLD is considered to be the manifestation of metabolic syndrome in the liver and an important risk factor for cardiovascular diseases as well.Studies have shown that NAFLD patients have significantly increased the prevalence rates of the diseases including ischemic heart disease and heart failure.Therefore,whether the changes in cardiac structure and impaired cardiac function occur before the development of organic heart diseases in NAFLD patients has attracted scholars' attention.With reference to the published literature,this article reviews the research advances in the association between NAFLD and cardiac changes in adults,children,and patients with diabetes and hypertension.

Background and purpose: MicroRNAs (miRNAs) play an important role in tumor biological behavior. miRNAs are down-regulated or up-regulated in various cancer types, triggering abnormal cell differentiation, proliferation and apoptosis. This study was designed to investigate the expression and clinical signiifcance of miR-187*in colorectal cancer (CRC), and further to investigate its roles in promoting cell apoptosis. Methods:The expressions of miR-187* in 40 CRC cases were examined by real-time quantitative reverse transcription-PCR (qRT-PCR). The relationship between miR-187*expression and clinical features of CRC was analyzed. HCT116 cells were transfected with a miR-187*mimic and the apoptosis of the transfected cells were examined by lfow cytometry (FCM). Results:The expression of miR-187*was down-regulated in CRC tissues 0.165 (0.106, 0.428) compared with those in normal tissues 0.334 (0.211, 0.712) (P<0.05), especially in mucinous carcinoma and older age CRC (P<0.05). Transfection of HCT116 cells with a miR-187*mimic up-regulated the expression of miR-187*and increased cell early apoptosis (P<0.05). Conclusion: The expression level of miR-187* was lower in CRC. miR-187* expression correlates with histological type and age. Transfection of HCT116 cells with a miR-187*mimic accelerates apoptosis of tumor cells, suggesting that miR-187*is a potent tumor suppressor.