ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

Objective To analyze the effect of Helicobacter pylori (Hp) infection on serum pepsinogen (PG) I, PGII and gastrin-17 (G-17) levels in elderly patients with chronic atrophic gastritis (CAG). Methods A total of 122 elderly patients with CAG and 85 elderly patients with CSG in the hospital were selected. According to Hp infection status, elderly patients with CAG were divided into CAG Hp (+) group (n=75) and CAG Hp (-) group (n=47). Another 122 healthy subjects with physical examination were enrolled as healthy group. The clinical data and levels of serum PGI, PGII and G-17 were compared among the three groups, and the risk factors affecting CAG with Hp infection were analyzed. Results There were significant differences in the proportion of Hp family infection history, the proportion of often spicy diet, the proportion of frequent dining out and levels of serum PGI, PGII and G-17 among CAG, CSG and healthy groups (P<0.05). Serum PGI and PGII in CAG Hp (+) group were lower than those in CAG Hp (-) group while G-17 level was higher (P<0.05). Binary logistic regression analysis showed that Hp family infection history, frequent dining out, serum PGI, PGII and G-17 levels were independent risk factors for Hp infection in elderly CAG (P<0.05). Conclusion Hp infection in elderly CAG patients is related to family aggregation, route of transmission and eating habits. Serum PGI, PGII and G-17 levels are influencing factors for elderly CAG with Hp infection.

Objective To investigate the safety and efficacy of combined confluence microdissection or balloon dilatation followed by laparoscopic transcystic common bile duct exploration (LTCBDE) in day surgery laparoscopic cholecystectomy. Methods The clinical data of 203 patients with day surgery laparoscopic cholecystectomy combined with LTCBDE from June 2021 to June 2024 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. They were divided into an observation group (59 cases, including 42 cases of confluent microdissection and 17 cases of balloon dilatation) and a conventional group (144 cases) according to the surgical technique used. Baseline characteristics, intraoperative exploration results, operation time, postoperative recovery and complications were compared between the two groups. Results The history of preoperative cholangitis or pancreatitis (P<0.001) was more common in the observation group. And total bilirubin level was significantly higher in the observation group than in the conventional group (P=0.035). The observation group had a longer operative time (P=0.014) and higher hospitalization costs (P=0.001), but there was no difference in intraoperative bleeding and postoperative discharge time. There were no serious postoperative complications in either group. Conclusions Under the premise of strict patient screening, day surgery LTCBDE combined with confluence microdissection or balloon dilatation can effectively solve the problem of difficult choledochoscopic access, with high safety and thoroughness of exploration. Both techniques provide a feasible minimally observation solution for day surgery biliary exploration.

Representative models of instruments for in vitro diagnostic (IVD) reagents simplify the performance evaluation of registration. Different from the concept of the US FDA instrument family, the domestic identification of representative models focuses on the risk analysis of instrument differences. However, there are problems such as unclear requirements for the identification of instruments, difficulties in the identification of new technology and high-risk instruments. The performance evaluation of the detection system can be partially simplified by representative models, and representative models can evaluate the performance of non-detection systems. Meanwhile, the comprehensive performance should be evaluated by representative models as conditions. Therefore, according to the analysis, performance evaluations using representative models can guarantee the safety and effectiveness of in vitro diagnostic reagents while promoting the high-quality development of the IVD industry.
Indicators and Reagents ; Reagent Kits, Diagnostic

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

AIM:To observe how total flavonoids of Pterocarya hupehensis Skan(PHSTF)affects the migra-tion and invasion of human rheumatoid fibroblast-like synoviocyte line MH7A.METHODS:The MH7A cells were divided into control group(without any treatment),low-,medium-and high-dose(6.25,12.5 and 25 mg/L,respectively)PHSTF groups,phosphatidylinositol 3-kinase(PI3K)inhibitor 740Y-P(10 μmol/L)group,and 740Y-P(10 μmol/L)+high-dose(25 mg/L)PHSTF group.The viability of the MH7A cells was determined by CCK-8 assay,while the migration and inva-sion were assessed by scratch and Transwell assays.The protein levels of matrix metalloproteinase-2(MMP-2),MMP-9,PI3K,p-PI3K,AKT and p-AKT were detected by Western blot.RESULTS:Compared with control group,the cell via-bility in PHSTF treatment groups was reduced(P<0.05),the cell wound healing area was significantly decreased(P<0.01),migratory and invasive cells in the lower chamber were significantly reduced(P<0.01),and the protein expres-sion of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT were decreased(P<0.01).Compared with high-dose PHSTF group,the addition of PI3K/AKT pathway agonist 740Y-P significantly increased the migration and invasion ability of MH7A cells(P<0.01)and elevated the protein expression of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT(P<0.01)under the treatment with PHSTF.CONCLUSION:Total flavonoids of Pterocarya hupehensis Skan could inhibit the migration and invasion of MH7A cells by regulating the PI3K/AKT signaling pathway.

This ENETS guidance for well-differentiated nonfunctioning pancreatic neuroendocrine tumours(NF-Pan-NET),which published on Journal of Neuroendocrinology(2023),has been developed by a multidisciplinary working group,and provides up-to-date and practical advice on the management of these tumours.In this guideline,the authors discussed 10 troublesome questions about clinical practice,and summarized the extensive experience of their centers treating patients with NF-Pan-NET,and suggested that multidisciplinary participation is an essential part of NF-Pan-NET diagnosis and treatment.This paper aims to interpret the key contents of the guidelines in order to provide standardized clinical diagnosis and treatment procedures in NF-Pan-NET.