Objective To investigate the cardiac protective effect of Taohong Tongluo granules on coronary microvascular dysfunction(CMD)rats.Methods SD rats were randomly assigned to sham-operated group,CMD group,nicorandil group(5 mg/kg),or Taohong Tongluo granule group(50 mg/kg).Animals were administered corresponding drugs for 7 d according to the grouping,and the CMD model was prepared 2 h after the last administration.The rat CMD model was induced by injecting embolization microspheres(diameter 40-120 μm,approximately 1 000 microspheres)into the left ventricular cavity.Twenty-four hours after modeling,echocardiography was performed to measure the left ventricular ejection fraction(EF),fractional shortening(FS),and end-diastolic volume(EDV).The damaged myocardial area was assessed by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Myocardial morphological changes were observed by hematoxylin-eosin(H-E)staining.The protein expression levels of NOD-like receptor family pyrin domain containing protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),and cysteine aspartic acid specific protease(caspase)-1 in rat myocardial tissue were detected by immunohistochemical staining and Western blotting.Results Echocardiography showed that the EF and FS values in the Taohong Tongluo granule group,CMD group,and nicorandil group were significantly lower than those in the sham-operated group(all P＜0.001).The EF and FS values in the Taohong Tongluo granule group and nicorandil group were significantly higher than those in the CMD group(all P＜0.01).However,there were no significant differences in EDV among the groups(all P＞0.05).H-E staining showed no abnormalities in the myocardium in the sham-operated group.The CMD group exhibited microsphere embolism in the myocardium,myocardial cell dissolution and rupture,and inflammatory infiltration.The lesions in the nicorandil group and the Taohong Tongluo granule group were relatively milder,and the number of thrombi in both groups was lower than that in the CMD group(both P＜0.01).The results of TTC staining indicated that the areas of damaged myocardial regions in both the nicorandil group and the Taohong Tongluo granule group were smaller than that in the CMD group(P＜0.05 or P＜0.01).Moreover,the area in the Taohong Tongluo granule group was smaller than that in the nicorandil group(P＜0.05).The results of immunohistochemical staining showed that in the CMD model,the expression of ASC and caspase-1 proteins,as well as the number of positive cells for these proteins,was increased and was distributed in myocardial and interstitial cells.The numbers of ASC and caspase-1 positive cells in the Taohong Tongluo granule group were lower than that in the CMD group(both P＜0.01).The Western blotting showed that the expression levels of NLRP3,ASC,and caspase-1 proteins in the Taohong Tongluo granule group were all lower than those in the CMD group(all P＜0.05).Conclusion Taohong Tongluo granules can improve cardiac function,ameliorate hemodynamic parameters,and reduce myocardial infarction area in rats with CMD induced by microsphere embolism.The mechanism is related to the inhibition of myocardial inflammasome activation,thereby attenuating the myocardial injuries.

Objective To analyze the characteristics of TCM symptoms of aging in female insomnia patients;To provide syndrome differentiation evidence for clinical prevention and treatment of female aging.Methods A cross-sectional study method was used to include female insomnia patients who attended outpatient clinics at Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Changping District Hospital of Traditional Chinese Medicine,and the Third Affiliated Hospital of Beijing University of Chinese Medicine from August 2021 to July 2024.The patients'clinical information was collected,and frequency analysis,factor analysis,and clustering analysis of the relevant clinical information of the 107 female insomnia patients were conducted,which,together with the experts'opinions,resulted in characteristics of TCM syndrome elements and syndrome distribution of aging in female insomnia patients.Results Totally 20 core items were screened and 7 common factors were obtained from the factor analysis.There were 5 types of syndrome elements of disease location associated with aging symptoms in female patients with insomnia,including heart,liver,spleen,kidney and lung;and there were 7 types of syndrome elements of disease property,including qi deficiency,yin deficiency,qi stagnation,blood deficiency,heat,phlegm,and dampness.There were 4 types of syndromes were obtained from the systematic clustering,including heart-kidney disharmony syndrome,heart-liver stagnation syndrome,spleen deficiency and qi stagnation syndrome,lung-spleen qi deficiency syndrome.Conclusion By analyzing the TCM syndrome characteristics of aging symptoms in female patients with insomnia,four types of syndromes are obtained.The heart-kidney disharmony syndrome is the common syndrome.The internal relationship between insomnia and aging process in female patients with insomnia is revealed from the perspective of pathogenesis,which can provide a research basis for the clinical practice of TCM anti-aging guided by syndrome differentiation and treatment in the future.

Objective:To report the follow-up status of patients participating phase Ⅲ clinical trial (ZGDD3) of Donafenib tosilate (abbreviated as Donafenib) in the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), and to explore its efficacy, safety and prognostic factors.Methods:This study was a randomized controlled trial, and the clinicopathological data and follow-up results of 29 patients (16 males, 13 females, age 40-68 years) who participated in the clinical trial ZGDD3 between August 2018 and March 2021 were analyzed. Patients were divided into Donafenib group and placebo group using the central dynamic randomization method with the ratio of 2∶1. Adverse reactions (AE) during the trial were observed. Independent-sample t test, Mann-Whitney U test and Fisher exact test were used to analyze the differences of baseline characteristics between the two groups. Progression-free survival (PFS) and overall survival (OS) were followed up. Kaplan-Meier method was used to draw the survival curve (log-rank test) and Cox regression analysis was used to analyze the prognostic factors. Results:There were 22 patients in Donafenib group and 7 patients in placebo group. There were no significant differences of baseline characteristics between the two groups ( t values: -0.68, Z values: from -1.47 to -0.56, all P>0.05). The follow-up was 32.07(21.07, 49.85) months. During the trial, drug-related AEs occurred in all patients in Donafenib group, mostly was grade Ⅰ-Ⅱ, no grade Ⅳ or Ⅴ AEs were found. The median PFS was significantly longer in Donafenib group than that in placebo group (13.23 vs 4.03 months; χ2=9.68, P=0.002), and the median OS was 55.00 and 24.30 months respectively ( χ2=2.07, P=0.150). Metastasis to less common sites was the independent risk factor for OS (hazard ratio ( HR)=6.789, 95% CI: 1.272-36.246, P=0.025). Conclusions:Donafenib shows good clinical application in the treatment of RAIR-DTC, demonstrating good safety and efficacy. Metastasis to less common sites is closely related to OS.

Objective To investigate the clinical effectiveness and safety of apatinib mesylate combined with gemcitabine+cisplatin(GC)and camrelizumab in the treatment of advanced gallbladder cancer,and to provide evidence for the clinical treatment of patients with advanced gallbladder cancer.Methods A total of 75 patients with advanced gallbladder cancer admitted to Henan Provincial People's Hospital and The Affiliated Cancer Hospital of Zhengzhou University from January 2022 to December 2023 were retrospectively included.According to treatment plans,they were divided into study group(apatinib mesylate combined with GC+camrelizumab)and control group(GC+camrelizumab).The 1-year survival rate,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse reactions were compared between the two groups.Inter-group comparisons were performed using the chi-square test/Fisher's exact test,the t-test,and the Mann-Whitney U test for categorical data,continuous data in normal distribution,and continuous data in non-normal distribution,respectively.The Kaplan-Meier survival curves were generated and compared using the log-rank test.Results The ORR and DCR of the study group were 35.0%and 80.0%,respectively,which were not significantly different from those of the control group(bothP>0.05).The 1-year survival rate of the study group differed significantly from that of the control group(45.0%vs 20.0%,P<0.05).The median PFS was 7.73(95%confidence interval[CI]:4.39-11.01)months in the study group and 4.17(95%CI:3.48-4.85)months in the control group,and the difference was statistically significant(P<0.01).The median OS was 11.77(95%CI:8.07-15.47)months in the study group and 7.97(95%CI:5.84-10.09)months in the control group,which were not statistically significant(P>0.05).Across all grades of adverse reactions,the study group showed significantly higher incidence rates of hand-foot syndrome(62.5%vs 34.3%,χ2=5.945,P<0.05)and elevated blood pressure(42.5%vs 20.0%,χ2=4.343,P<0.05)than the control group.There were no significant differences in the incidence rates of adverse reactions of grade Ⅲ or above between the two groups(all P>0.05).Conclusion Apatinib mesylate combined with GC+camrelizumab is superior to GC+camrelizumab in prolonging the PFS but not in terms of the OS,with controllable toxic side effects,which is a safe and effective treatment regimen.

Objective:To investigate relationship between expression of ADGRG5 and clinical prognosis and immune response in pancreatic adenocarcinoma(PAAD).Methods:ADGRG5 expression in PAAD and normal tissues were compared by Wilcoxon rank sum test.Diagnostic value of ADGRG5 was evaluated by ROC curve in PAAD.Kaplan-Meier method and Cox regres-sion analysis were used to evaluate prognostic factors.Gene set enrichment analysis(GSEA)and immune infiltration analysis were applied to annotate biological function of ADGRG5.Results:ADGRG5 expression in PAAD was significantly higher than normal tissue(P=2.8e-32).ADGRG5 had significant diagnostic and prognostic ability for PAAD(AUC=0.866).High ADGRG5 expression predicted a good progress free interval(PFI)(P=0.01),and expression of ADGRG5 was independently associated with PFI(HR:0.656,95%CI:0.433～0.972,P=0.035).ADGRG5 expression was related to regulation of immunomodulatory pathway and function of some types of immune infiltrating cells.Conclusion:Increased ADGRG5 may be a potential biomarker for PAAD diagnosis and prognosis,which affects prognosis of PAAD patients and significantly correlated with immune infiltration.

Objective To compare the distribution characteristics of retinal capillary non-perfusion areas(NPAs)across different layers and regions in patients with neovascular glaucoma(NVG)secondary to proliferative diabetic retinop-athy(PDR)versus those with PDR alone through wide-field swept-source optical coherence tomography angiography(SS-OCTA)and to analyze the impacts of NPAs on the development of NVG.Methods This prospective cross-sectional study enrolled 33 patients with PDR(33 eyes,the PDR group)and 30 patients with NVG(30 eyes,the PDR+NVG group)diag-nosed at Affiliated Hospital of Shandong Second Medical University(formerly Weifang Medical University)from January 2022 to June 2023.The fundus examination was performed using SS-OCTA,and the NPA boundaries of the superficial capil-lary plexus(SCP)and deep capillary plexus(DCP)of the retina were manually delimited with the aid of ImageJ.The reti-na was divided based on two methods.Specifically,according to different concentric circles,the retina could be divided in-to the foveal area,parafoveal area,perifoveal area,annulus6-9,annulus9-12,annulus12-retinal boundary;besides,the ret-ina could also be divided into four quadrants(supratemporal,infratemporal,supranasal,and infranasal quadrants)based on the horizontal and vertical lines centered on the macular fovea.Based on that,the NPA area and ischemia index(ISI)in each layer and subdivision of the two groups of patients were counted.Additionally,the NPA and ISI in different concentric circles and different quadrants of the SCP and DCP were compared between the two groups.Moreover,the distribution characteristics of NPAs as well as the effect of NPAs on NVG were analyzed.Results(1)The NPA area and ISI in the DCP were larger than those in the SCP in both groups(all P＜0.001);the NPA area and ISI in the SCP and DCP of patients in the PDR+NVG group were larger than those in the PDR group(all P＜0.001).(2)In the supratemporal,infratemporal,supranasal,and infranasal quadrants,the NPA area and ISI in the SCP and DCP of patients in the PDR+NVG group were larger than those in the PDR group(all P＜0.01).The NPA area in the inferotemporal quadrant was the largest in the SCP and DCP,respectively,within each group(all P＜0.01).(3)The differences in the NPA area and ISI between the two groups were statistically significant in the annulus6-9,annulus9-12,and annulus12-retinal boundary in the SCP and DCP(all P＜0.01).The differences in the NPA area and ISI were statistically significant between different annular subdivisions in the SCP and DCP within each group(all P＜0.001).The multiple comparison results showed that the NPA area and ISI of the annulus12-retinal boundary in the SCP and DCP were larger than those in other annuli in both groups(all P＜0.05).The NPA area and ISI of the annulus9-12 were larger than those of the parafoveal and perifoveal areas;the NPA area and ISI of the annulus6-9 were larger than those of the parafoveal area(all P＜0.05).There was no statistically significant differ-ence in the NPA area and ISI in the remaining annuli(all P＞0.05).(4)The multivariate logistic regression analysis showed that the NPA area and ISI in the subnasal quadrant of the SCP were negatively correlated with the risk of NVG sec-ondary to PDR(P=0.036 and 0.038).The increased NPA area and ISI in the subnasal quadrant of the DCP were risk fac-tors for NVG secondary to PDR,and they may increase the risk of NVG(P=0.029 and 0.028).Conclusion The in-creased NPA area and ISI in the subnasal quadrant of the DCP were risk factors for secondary NVG in patients in the PDR group.

Objective To investigate the clinical effectiveness and safety of apatinib mesylate combined with gemcitabine+cisplatin(GC)and camrelizumab in the treatment of advanced gallbladder cancer,and to provide evidence for the clinical treatment of patients with advanced gallbladder cancer.Methods A total of 75 patients with advanced gallbladder cancer admitted to Henan Provincial People's Hospital and The Affiliated Cancer Hospital of Zhengzhou University from January 2022 to December 2023 were retrospectively included.According to treatment plans,they were divided into study group(apatinib mesylate combined with GC+camrelizumab)and control group(GC+camrelizumab).The 1-year survival rate,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse reactions were compared between the two groups.Inter-group comparisons were performed using the chi-square test/Fisher's exact test,the t-test,and the Mann-Whitney U test for categorical data,continuous data in normal distribution,and continuous data in non-normal distribution,respectively.The Kaplan-Meier survival curves were generated and compared using the log-rank test.Results The ORR and DCR of the study group were 35.0%and 80.0%,respectively,which were not significantly different from those of the control group(bothP>0.05).The 1-year survival rate of the study group differed significantly from that of the control group(45.0%vs 20.0%,P<0.05).The median PFS was 7.73(95%confidence interval[CI]:4.39-11.01)months in the study group and 4.17(95%CI:3.48-4.85)months in the control group,and the difference was statistically significant(P<0.01).The median OS was 11.77(95%CI:8.07-15.47)months in the study group and 7.97(95%CI:5.84-10.09)months in the control group,which were not statistically significant(P>0.05).Across all grades of adverse reactions,the study group showed significantly higher incidence rates of hand-foot syndrome(62.5%vs 34.3%,χ2=5.945,P<0.05)and elevated blood pressure(42.5%vs 20.0%,χ2=4.343,P<0.05)than the control group.There were no significant differences in the incidence rates of adverse reactions of grade Ⅲ or above between the two groups(all P>0.05).Conclusion Apatinib mesylate combined with GC+camrelizumab is superior to GC+camrelizumab in prolonging the PFS but not in terms of the OS,with controllable toxic side effects,which is a safe and effective treatment regimen.

Objective To compare the distribution characteristics of retinal capillary non-perfusion areas(NPAs)across different layers and regions in patients with neovascular glaucoma(NVG)secondary to proliferative diabetic retinop-athy(PDR)versus those with PDR alone through wide-field swept-source optical coherence tomography angiography(SS-OCTA)and to analyze the impacts of NPAs on the development of NVG.Methods This prospective cross-sectional study enrolled 33 patients with PDR(33 eyes,the PDR group)and 30 patients with NVG(30 eyes,the PDR+NVG group)diag-nosed at Affiliated Hospital of Shandong Second Medical University(formerly Weifang Medical University)from January 2022 to June 2023.The fundus examination was performed using SS-OCTA,and the NPA boundaries of the superficial capil-lary plexus(SCP)and deep capillary plexus(DCP)of the retina were manually delimited with the aid of ImageJ.The reti-na was divided based on two methods.Specifically,according to different concentric circles,the retina could be divided in-to the foveal area,parafoveal area,perifoveal area,annulus6-9,annulus9-12,annulus12-retinal boundary;besides,the ret-ina could also be divided into four quadrants(supratemporal,infratemporal,supranasal,and infranasal quadrants)based on the horizontal and vertical lines centered on the macular fovea.Based on that,the NPA area and ischemia index(ISI)in each layer and subdivision of the two groups of patients were counted.Additionally,the NPA and ISI in different concentric circles and different quadrants of the SCP and DCP were compared between the two groups.Moreover,the distribution characteristics of NPAs as well as the effect of NPAs on NVG were analyzed.Results(1)The NPA area and ISI in the DCP were larger than those in the SCP in both groups(all P＜0.001);the NPA area and ISI in the SCP and DCP of patients in the PDR+NVG group were larger than those in the PDR group(all P＜0.001).(2)In the supratemporal,infratemporal,supranasal,and infranasal quadrants,the NPA area and ISI in the SCP and DCP of patients in the PDR+NVG group were larger than those in the PDR group(all P＜0.01).The NPA area in the inferotemporal quadrant was the largest in the SCP and DCP,respectively,within each group(all P＜0.01).(3)The differences in the NPA area and ISI between the two groups were statistically significant in the annulus6-9,annulus9-12,and annulus12-retinal boundary in the SCP and DCP(all P＜0.01).The differences in the NPA area and ISI were statistically significant between different annular subdivisions in the SCP and DCP within each group(all P＜0.001).The multiple comparison results showed that the NPA area and ISI of the annulus12-retinal boundary in the SCP and DCP were larger than those in other annuli in both groups(all P＜0.05).The NPA area and ISI of the annulus9-12 were larger than those of the parafoveal and perifoveal areas;the NPA area and ISI of the annulus6-9 were larger than those of the parafoveal area(all P＜0.05).There was no statistically significant differ-ence in the NPA area and ISI in the remaining annuli(all P＞0.05).(4)The multivariate logistic regression analysis showed that the NPA area and ISI in the subnasal quadrant of the SCP were negatively correlated with the risk of NVG sec-ondary to PDR(P=0.036 and 0.038).The increased NPA area and ISI in the subnasal quadrant of the DCP were risk fac-tors for NVG secondary to PDR,and they may increase the risk of NVG(P=0.029 and 0.028).Conclusion The in-creased NPA area and ISI in the subnasal quadrant of the DCP were risk factors for secondary NVG in patients in the PDR group.

Objective:To investigate relationship between expression of ADGRG5 and clinical prognosis and immune response in pancreatic adenocarcinoma(PAAD).Methods:ADGRG5 expression in PAAD and normal tissues were compared by Wilcoxon rank sum test.Diagnostic value of ADGRG5 was evaluated by ROC curve in PAAD.Kaplan-Meier method and Cox regres-sion analysis were used to evaluate prognostic factors.Gene set enrichment analysis(GSEA)and immune infiltration analysis were applied to annotate biological function of ADGRG5.Results:ADGRG5 expression in PAAD was significantly higher than normal tissue(P=2.8e-32).ADGRG5 had significant diagnostic and prognostic ability for PAAD(AUC=0.866).High ADGRG5 expression predicted a good progress free interval(PFI)(P=0.01),and expression of ADGRG5 was independently associated with PFI(HR:0.656,95%CI:0.433～0.972,P=0.035).ADGRG5 expression was related to regulation of immunomodulatory pathway and function of some types of immune infiltrating cells.Conclusion:Increased ADGRG5 may be a potential biomarker for PAAD diagnosis and prognosis,which affects prognosis of PAAD patients and significantly correlated with immune infiltration.

Objective To analyze the characteristics of TCM symptoms of aging in female insomnia patients;To provide syndrome differentiation evidence for clinical prevention and treatment of female aging.Methods A cross-sectional study method was used to include female insomnia patients who attended outpatient clinics at Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Changping District Hospital of Traditional Chinese Medicine,and the Third Affiliated Hospital of Beijing University of Chinese Medicine from August 2021 to July 2024.The patients'clinical information was collected,and frequency analysis,factor analysis,and clustering analysis of the relevant clinical information of the 107 female insomnia patients were conducted,which,together with the experts'opinions,resulted in characteristics of TCM syndrome elements and syndrome distribution of aging in female insomnia patients.Results Totally 20 core items were screened and 7 common factors were obtained from the factor analysis.There were 5 types of syndrome elements of disease location associated with aging symptoms in female patients with insomnia,including heart,liver,spleen,kidney and lung;and there were 7 types of syndrome elements of disease property,including qi deficiency,yin deficiency,qi stagnation,blood deficiency,heat,phlegm,and dampness.There were 4 types of syndromes were obtained from the systematic clustering,including heart-kidney disharmony syndrome,heart-liver stagnation syndrome,spleen deficiency and qi stagnation syndrome,lung-spleen qi deficiency syndrome.Conclusion By analyzing the TCM syndrome characteristics of aging symptoms in female patients with insomnia,four types of syndromes are obtained.The heart-kidney disharmony syndrome is the common syndrome.The internal relationship between insomnia and aging process in female patients with insomnia is revealed from the perspective of pathogenesis,which can provide a research basis for the clinical practice of TCM anti-aging guided by syndrome differentiation and treatment in the future.