BACKGROUND: Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions. METHODS: Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization. RESULTS: A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026). CONCLUSIONS In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

To investigate the epidemiology of avian infectious bronchitis virus(IBV)and study the pathogenicity of IBV isolate,we isolated the IBV field strain from a clinical sample of chickens sus-pected to be infected with infectious bronchitis virus(IBV)from Hefei,Anhui Province,named HF210416.Sequencing analysis of the S1 gene showed that HF210416 belonged to the GI-22 geno-type,which was significantly differed from that of the reference GI-22-type strains,with homology ranging only from 84.5％to 87.8％.Recombinant analysis showed that HF210416 was a recombi-nant strain,with YX10(GI-19)as the major parent and YN(GI-19)as the minor parent.2-day-old SPF chicks infected with the HF210416 isolate showed clinical symptoms such as breathing with difficulty,depression and excreting watery droppings;the infected chicks had a rapid onset of dis-ease,with mortality occurring on the second day of inoculation,and mortality persisted until the fifth day,with 33.33％(5/15)mortality rate.The infected chicks recovered the 14th day after inoculation.RT-PCR detection of pharyngeal-anal swabs showed that the virus shedding by infected chicks could be continuously detected within 14 days of the test period;Enlarged and pale kidney as well as urate deposition in the kidney were observed in infected dead and undead chicks;and the HE staining of histopathological slices showed that the cilia of trachea were removed.Immunohis-tochemistry showed that obvious viral signals were observed in the trachea,lungs,and kidneys.The viral load of various tissues was detected by RT-qPCR and it showed that HF210416 had the high-est replication efficiency in kidney tissues,then in cecum tonsils and trachea.The results of serum neutralization test showed that HF210416 had a better neutralization effect on GI-22 homologous strains,but poorer neutralization effect on other genotypes strains,suggesting that HF210416 is not suitable for vaccine candidate.In conclusion,the GI-22 isolate HF210416 is highly pathogenic and nephrotropic to chicks,and its genomic genetic characteristics and immunogenicity are differ-ent from those of other strains.This study enriches the resources of IBV strains and provides refer-ence data for understanding of the prevalence and pathogenicity of GI-22 genotypes in China.

Aim To investigate the effect of polyphyl-lin Ⅱ(PP Ⅱ)on autophagy of osteosarcoma(OS)cells and its related molecular mechanism.Methods U2OS and HOS cells were cultured in vitro and treated with different concentrations of PP Ⅱ(5,10,15,20 μmol·L-1)for 24 h.The changes of acid vesicles were detected by AO staining,the autophagosomes was ob-served by transmission electron microscopy,the ex-pressions of LC3B-Ⅱ/LC3B-Ⅰ,p62,caspase-3,cleaved caspase-3 were detected by Western blot,the intracellular reactive oxygen species(ROS)was detec-ted by DCFH-DA fluorescence probe,cell viability was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PⅠ staining.Results PP Ⅱ signifi-cantly increased the number of acidic vesicles(P＜0.05,P＜0.01)and autophagosomes.PP Ⅱ signifi-cantly up-regulated the ratio of LC3B-Ⅱ/LC3B-Ⅰ,and down-regulated the expression level of p62 protein in a concentration-and time-dependent manner(P＜0.05,P＜0.01).PP Ⅱ significantly increased intra-cellular ROS levels(P＜0.01).Autophagy inhibitor 3-MA and CQ could reverse the regulation of cell via-bility,autophagy and apoptosis related proteins by PP Ⅱ in U2OS cells,endoplasmic reticulum stress inhibi-tor 4-PBA could also reverse the regulation of autoph-agy related proteins by PP Ⅱ in U2OS cells.Conclu-sion PP Ⅱ promotes OS cell autophagy by mediating ROS and endoplasmic reticulum stress.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

ObjectiveTo establish blood stasis models in zebrafish using three inducers and select the optimal model for evaluating the activity of Notoginseng Radix et Rhizoma in promoting blood circulation. MethodArachidonic acid （AA）， ponatinib， and isoprenaline （ISO） were used to induce blood stasis models in zebrafish. A normal group， a model group， a positive drug group， and Notoginseng Radix et Rhizoma water extract freeze-dried powder groups at different concentrations were set up. The staining intensity of cardiac erythrocytes and the fluorescence intensity of cardiac apoptotic cells were calculated， the anti-thrombotic effect and anti-myocardial hypoxia activity of Notoginseng Radix et Rhizoma were evaluated. The activities of water extract and 70% methanol extract of Notoginseng Radix et Rhizoma were compared based on the preferred AA- and ISO-induced blood stasis models in zebrafish and the difference in the chemical composition was analyzed by UHPLC LTQ-Orbitrap MS/MS. ResultAfter induction by AA and ponatinib， the staining intensity of cardiac erythrocytes was reduced （P<0.01）， and the fluorescence intensity of cardiac apoptotic cells increased after the induction by ISO （P<0.01）. The freeze-dried powder of the water extract of Notoginseng Radix et Rhizoma could antagonize the thrombosis in the AA-induced model （P<0.01） and the myocardial apoptosis in the ISO-induced model （P<0.05）， while no significant improvement in the thrombosis was observed in the ponatinib-induced model. The freeze-dried powder of 70% methanol extract of Notoginseng Radix et Rhizoma could inhibit myocardial apoptosis in the ISO-induced blood stasis model （P<0.01）， and the effect was stronger than that of the freeze-dried powder of Notoginseng Radix et Rhizoma water extract. The difference in chemical composition lay in some saponins （such as ginsenoside Re）， amino acids， and acetylenic alcohols. ConclusionAA， ponatinib， and ISO all can serve as inducers for the blood stasis model in zebrafish. AA- and ISO-induced models can be used to evaluate the activity of freeze-dried powder of Notoginseng Radix et Rhizoma water extract in promoting blood circulation. The chemical compositions of the freeze-dried powders of Notoginseng Radix et Rhizoma extracted with water and 70% methanol are quite different. For the ISO-induced blood stasis model， the freeze-dried powder of Notoginseng Radix et Rhizoma extracted with 70% methanol has a stronger ability against myocardial hypoxia. Saponins and acetylenic alcohols may be closely related to the effects of promoting blood circulation and resolving blood stasis.

Objective:To develop and validate a visualized computed tomography nomogram for differentiating focal-type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC).Methods:This retrospective review included 42 consecutive patients with fAIP diagnosed according to the International Consensus Diagnostic Criteria and 242 consecutive patients with PDAC confirmed by pathology between January 2011 and December 2018 in the First Affiliated Hospital of Naval Medical University. Among them, 209 consecutive patients (25 fAIP and 184 PDAC) were enrolled in the development cohort; Seventy-five consecutive patients (17 fAIP and 58 PDAC) were enrolled in the validation cohort. CT image characteristics, including lesion location, size, enhancement mode and degree of mass enhancement in portal vein phase, pancreatic parenchymal atrophy, main pancreatic duct dilation, common bile duct dilation, cyst, acute obstructive pancreatitis, and vascular invasion were compared. Univariate and multivariate analysis were used to screen the independent predictive factors for fAIP and PDAC, based on which the nomogram was constructed and visualized. The receiver operating characteristic curve (ROC) was drawn and area under the curve (AUC) was calculated to evaluate the differential efficacy of the nomogram. The clinical usefulness of the nomogram was evaluated by decision curve analysis.Results:There were statistically significant differences on common bile duct dilation and the mode and degree of enhancement in portal phase between fAIP group and PDAC group in training set and validation set ( P<0.05). Univariate regression analysis showed that common bile duct dilation and degree of mass enhancement in portal vein were closely correlated with fAIP and PDAC phase between the two groups in training set and validation set; mass enhancement mode in portal vein phase and main pancreatic duct dilation were closely correlated with fAIP and PDAC in training set. Multivariate logistic regression analysis showed that common biliary duct dilatation ( OR=0.26, 95% CI 0.06-1.10, P=0.07), main pancreatic duct dilation ( OR=9.46, 95% CI 1.60-56.04, P<0.01) and mass mild hyper-enhancing in portal vein phase ( OR=0.003, 95% CI 0.0003-0.0278, P<0.0001) were the three independent predictors for fAIP and PDAC. Thus, the equation for predicting the probability of PDAC was 4.51-1.33× no dilatation of the common bile duct+ 2.25× the main pancreatic duct dilated-5.84× mass mild hyper-enhancing during the portal phase. The individualized prediction nomogram using these predictors of the fAIP achieved an AUC of 0.97 (95% CI 0.95-0.99) in the development set and 0.97(95% CI0.94-1.00) in the validation set. The sensitivity, specificity and accuracy of the model were 87.5%, 100% and 89% in the training set; and 94.83%, 94.12% and 94.67% in the validation set, respectively. The decision curve analysis demonstrated that the nomogram was clinically useful when the nomogram differentiated fAIP and PDAC at a rate of >0.2. Conclusions:The nomogram based on common bile duct dilation, main pancreatic duct dilation and mass enhancement in portal vein phase can be used as a useful tool for predicting fAIP and PDAC and provide valuable evidence for clinical decision.

Objective:To investigate the clinical efficacy of Shashen Maidongtang plus total glucosides of paeony capsule on primary Sjogren's syndrome (pSS) based on the theory of fluid metabolism. Method:In this study, 84 patients of Qi-Yin deficiency type pSS admitted in Zhengzhou Chinese Medicine Hospital from January 2018 to January 2019 were divided into observation group (42 cases) and control group (42 cases) on the basis of random number table. The control group was orally given total glucosides of paeony capsule and iguratimod tablet, while the observation group was orally given Shashen Maidongtang combined with glucosides of paeony capsule. After 3 months of continuous treatment to all subjects, the clinical efficacy was evaluated, and side effects were recorded. Before and after the treatment, the saliva flow rate and basal tear secretion Schirmer I test (SIt) value were measured, European League Against Rheumatism Sjogren's syndrome patient reported index and Sjogren's syndrome disease activity index (ESSPRI and ESSDAI) were scored, the erythrocyte sedimentation rate (ESR) was determined by Westergren, and the levels of serum rheumatoid factor (RF) and immunoglobulin (Ig) G were tested by immunoturbidimetry and rate scattering turbidimetry, respectively. Result:The overall effective rate of the observation group was 90.48% (38/42), which was much higher than 69.05% (29/42) of the control group (χ²=5.974，P<0.05). After treatment, the saliva flow rates and SIt values of both groups got significantly increased compared with those before the treatment (P<0.05), but the saliva flow and SIt of the observation group were significantly better than those of the control group over the same period after treatment (P<0.05). After treatment, both groups had a great decrease in ESSPRI and ESSDAI scores compared with those before the treatment (P<0.05), and the above scores of the observation group were dramatically lower than those of the control group over the same period (P<0.05). After treatment, ESR, serum RF, and IgG levels of both groups were significantly lower than those before the treatment (P<0.05), and the observation group showed higher levels of ESR, serum RF and IgG than the control group over the same period after treatment (P<0.05). Side effects were few and mild in both groups. Conclusion:In treating patients of Qi-Yin deficiency type pSS, Shashen Maidongtang plus total glucosides of paeony capsule was proven to be effective generally. It could significantly inhibit excessive inflammation and hyperhumoral immunity in patients, and control their disease activity. This may be related to the effect of Shashen Maidong decoction and its decomposed recipes in correcting body fluid infusion and metabolic disorder in patients of Qi-Yin deficiency type pSS.