Objective:To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI) and summarize the single-center experience.Methods:A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide, admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022. The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results:The study included 5 patients, 3 males and 2 females. The age of onset ranged from 1 to 90 days. Initial symptoms included poor mental state(2/5) and convulsions(3/5). Blood glucose levels were 1.1 to 2.3 mmol/L, and insulin levels ranged from 13.52 to 70.53 μIU/mL. Two cases were classified as diffuse type, and the histological type of 3 cases was unknown. Genetic testing confirmed the diagnosis, with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del). Of the five patients, three patients were treated with sirolimus after diazoxide and octreotide failed, one patient was treated after unresponsive diazoxide, and the other one was treated after diazoxide, octreotide, and even near-total pancreatectomy failed. The onset age of sirolimus therapy ranged from 1 to 20 months. The maximum dosage of sirolimus was 1.2-3.2 mg·m -2·d -1, and the duration of medication ranged from 2 to 12 months. One patient was fully responsive to sirolimus, and the other four patients were partially responsive. All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment. During follow-up, non-infectious diarrhea, elevated carcinoembryonic antigen, elevated triglycerides, and elevated liver enzymes were observed. Conclusion:This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective. However, the long-term efficacy and safety warrant further multicenter trials.

Objective:To explore the alterations in functional connectivity density (FCD) resulted from mild cognitive impairment (MCI) and their correlations with cognitive scores in various cognitive domains in patients with Parkinson's disease (PD).Methods:Forty-three PD patients admitted to Department of Neurology, Sixth Affiliated Hospital of Nantong University from January 2022 to April 2024 were selected and divided into PD-MCI group (MoCA scores<26) and PD with normal cognition (PD-NC) group (MoCA scores≥26) according to Montreal Cognitive Assessment (MoCA). Another 23 middle-aged and elderly healthy volunteers (HC group) matched with PD patients in age, gender and education level were recruited at the same period. Resting-state functional MRI (rs-fMRI) data were collected and whole brain FCD was calculated. Differences of clinical data, whole brain FCD, and FCD in brain regions with significantly different FCD among the 3 groups were compared. Efficiency of FCD in brain regions with significantly different FCD between PD-MCI group and PD-NC group in differentially diagnosing PD-MCI and PD-NC was analyzed by receiver operating characteristic (ROC) curve. Pearson correlation was used to the analyze the correlations of FCD in brain regions with significantly different FCD with MoCA score and cognitive scores in various cognitive domains.Results:Among the 43 patients, 23 were into the PD-MCI group and 20 into the PD-NC group. PD-MCI group had significantly lower scores in the visuospatial and executive function, abstraction, and delayed memory cognitive domains than PD-NC group ( P<0.05). Brain regions with significantly different FCD among the 3 groups were the right parahippocampal gyrus, left gyrus rectus, right rolandic operculum, left middle occipital gyrus, right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. Compared with the HC group, the PD-MCI group and PD-NC group had significantly increased FCD at the right parahippocampal gyrus, left gyrus rectus and right rolandic operculum, statistically decreased FCD at the right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus ( P<0.05). Compared with the HC group, the PD-MCI group had significantly increased FCD at the left middle occipital gyrus ( P<0.05). Compared with the PD-NC group, the PD-MCI group had significantly decreased FCD at the right parahippocampal gyrus, and statistically increased FCD at the left middle occipital gyrus and left middle frontal gyrus ( P<0.05). Area under ROC curve (AUC) of FCD in brain regions with significantly different FCD in discriminating PD-MCI and PD-NC was 0.878, with sensitivity of 90.0% and specificity of 91.3%. FCD at right parahippocampal gyrus, left middle occipital gyrus and left middle frontal gyrus was negatively correlated with MoCA score ( P<0.05); FCD at right parahippocampal gyrus was positively correlated with cognitive scores in the visuospatial and executive function, and delayed memory domains ( P<0.05); FCD at left middle occipital gyrus was negatively correlated with cognitive scores in the executive function and visual-spatial skills, and abstraction domains ( P<0.05); FCD at the left medial frontal gyrus was negatively correlated with cognitive scores in the visuospatial and executive function, abstraction and delayed memory domains ( P<0.05). Conclusions:Abnormal FCD can be noted in some brain regions of PD patients, enjoying differences between PD-MCI patients and PD-NC patients. Combined FCD in brain regions with significantly different FCD has high value in differentially diagnosing PD-MCI and PD-NC, and FCD in brain regions with significantly different FCD is correlated with cognitive function changes in PD patients.

Atrial fibrillation (AF) is one of the most common arrhythmias. Studies have shown that there is a significant correlation between inflammation and AF. Pathogenic microbial infection has long been considered the most likely factor to trigger and maintain the inflammatory process. In recent years, with the development of molecular biology technology, more and more evidence shows that some bacteria and viruses can cause AF. The research on AF and pathogens has gradually become a hot topic in recent years.

Objective To explore artificial reconstruction vs artificial intelligence reconstruction in coronary artery volume rendering(VR).Methods A total of 110 coronary heart disease(CHD)patients were enrolled in the study,and underwent computed tomography arteriography.Artificial reconstruction(artificial group)and artificial intelligence reconstruction(intelligent group)were conducted in coronary artery VR.The image quality of VR and curved planar reconstruction(CPR),the diagnosis coincidence rate of arterial stenosis,and vascular reconstruction score were compared between two groups.Results The VR image quality of intelligent group was significantly higher than that of artificial group,with excellence rate of 90.91%vs 80.00%;and intelligent group scored higher than artificial group in CPR image quality(P<0.05).The differences in the diagnostic coincidence rates of arterial vessels(RCA,LAD,LCX)with no stenosis,slight stenosis,moderate stenosis,and vascular occlusion between two groups were trivial(P>0.05),while the two groups differed significantly in the diagnosis coincidence rates of mild stenosis and severe stenosis(P<0.05).The mean total score,the median value of the 3 main branches+posterior descending branch+intermediate branch+diagonal branch+blunt margin branch,and the median value of the other vascular branches were all significantly increased in intelligent group as compared with artificial group(P<0.05).Conclusion Artificial intelligence reconstruction has higher application value than artificial reconstruction in coronary artery VR.

Objective To explore the application of diagnostic system with artificial intelligence(AI)in the evaluation of patients with coronary heart disease(CHD)at high altitude.Methods A total of 318 pa-tients underwent coronary CT angiography(CTA)at the hospital from January to December 2022 were pro-spectively collected.According to the altitude gradient,the patients were divided into the 2 000-3 000 m group and>3 000 m group.Coronary angiography(CAG)was used as the gold standard to verify the diag-nostic performance of AI diagnostic system.Coronary artery diagnosis system with AI technology and CT de-rived fractional flow reserve(CT-FFR)measurement system were used to evaluate the plaque structure char-acteristics and hemodynamic changes in the two groups of patients.Results Calcified plaques and vulnerable plaques in the>3 000 m group were more than those in the 2 000-3 000 m group(χ2=3.976,6.482,P= 0.046,0.011).The incidence of multi-vessel coronary artery disease,moderate stenosis,severe stenosis and complete occlusion in the>3 000 m group was higher than that in the 2 000-3 000 m group,and the inci-dence of single-vessel coronary artery disease and mild stenosis in the 2 000-3 000 m group was higher than that in the>3 000 m group(P<0.05).The incidence of CT-FFR≤0.80 and<0.70 in the>3 000 m group was higher than that in the 2 000-3 000 m group(χ2=4.782,28.118,P=0.029,<0.001).The comparison with the gold standard showed that this method has high sensitivity,specificity,and diagnostic consistency(P<0.001).Conclusion The coronary diagnosis system with AI technology has certain value in the system-atic evaluation of coronary artery characteristics and hemodynamic changes in CHD patients at high altitude.

Objective To investigate the predictive value of early efficacy of neoadjuvant chemotherapy(NAC)in patient with breast cancer via full quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods Forty patients with breast cancer were selected.The 18 fluorodeoxyglucose positron emission tomography/computed tomography(18F-FDG PET/CT)and DCE-MRI were performed before and after two cycles of NAC.According to the decrease rate of maximum standardized uptake value(ΔSUVmax)of PET/CT before and after two cycles of NAC,all patients were divided into two groups,including good response group(24 cases)(ΔSUVmax>40%)and general response group(16 cases)(ΔSUVmax≤40%).The changes of full quantitative parameters of DCE-MRI between the two groups were observed and analyzed.Results There were statistically significant differences in changes of Ktrans and Kep between the two groups(P<0.05),however,there was no significant difference in the change of Ve between the two groups(P>0.05).There was a significant positive correlation between ΔKtrans and ΔSUVmax(r=0.850,P<0.001).There was a high positive correlation between ΔKtrans and ΔKep(r=0.727,P<0.001).Conclusion The full quantitative parameters of DCE-MRI are helpful to evaluate the early efficacy of NAC in breast cancer,which can reflect the changes of microcirculation in the lesion,further reflect the therapeutic effect of NAC,guide the clinical optimization of treatment plan in time,and achieve accurate evaluation and individualized treatment.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective:In order to truly realize the deep integration of ideological and political education and professional edu-cation in the course of Animal Immunology and effectively improve the comprehensive quality of students.Methods:The experiment adopts the teaching method of integrating the online and offline hybrid teaching of Animal Immunology into the ideology and politics of the course,studies the course design concept,teaching objectives,teaching design and teaching implementation,and will conduct an evaluation of the teaching effect from the examination results and ideological and political effect.Results:The results show that the teaching model has stimulated students'interest in learning and improved their overall ability.Conclusion:It shows that the teaching effect of this method is good and the basic task of moral education is realized.

Objective:To investigate the effects of Porphyromonas gingivalis derived outer membrane vesicles (Pg OMV) on osteoclast differentiation of macrophages and its underlying mechanisms. Methods:The morphology and the size distribution of Pg OMV were analyzed by transmission electron microscopy and nanoparticle tracing analysis, respectively. The osteoclast precursors were treated with 1, 3 and 10 mg/L Pg OMV (1, 3 and 10 mg/L OMV treatment group) or phosphate buffer solution (PBS)(control group). The formation of osteoclasts was analyzed by tartrate-resistant acid phosphase (TRAP) staining and F-actin staining and real-time quantitative PCR (RT-qPCR) were used to detect the expression of Fos and matrix metallopeptidase 9 (MMP9). Polymyxin B (PMB) was used to block lipopolysaccharide (LPS) and then Pg OMV was used to treat osteoclast precursor (PMB-OMV treatment group), and OMV treatment group was used as control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The effect of Pg OMV on the expression of Toll-like receptor (TLR) 2 and TLR4 in preosteoclasts was detected by Western blotting. The osteoclast precursors were pretreated with 10, 50, 100 and 200 μmol/L C29, an inhibitor of TLR2, and then treated with Pg OMV(OMV+10, 50, 100 and 200 μmol/L C29 treatment group) and OMV treatment group without C29 pretreatment was control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The osteoclast precursor cells were treated with OMV (OMV treatment group) and OMV incubated with PMB (PMB-OMV treatment group) and the expression of TLR2 in osteoclast precursor was detected by Western blotting.Results:Pg OMV showed classical vesicular structures, and the average particle size of Pg OMV were 179.2 nm. A large number of actin rings were observed in the 3 and 10 mg/L OMV treatment groups. The percentages of TRAP-positive osteoclast area in 3 mg/L OMV treatment group [(22.6±2.1)%] and 10 mg/L OMV treatment group [(32.0±2.3)%] were significantly increased compared with control group [(4.9±0.5)%] ( P<0.001). Compared with the control group (1.000±0.029), the mRNA relative expression of Fos in 3 mg/L OMV treatment group (1.491±0.114) and 10 mg/L OMV treatment group (1.726±0.254) was significantly increased ( P=0.013, P=0.001). Compared with the control group (1.007±0.148), the mRNA relative expression of MMP9 in the group of 10 mg/L OMV (2.232±0.097) was significantly increased ( P<0.001). Actin ring formation was less in PMB-OMV treatment groups than in OMV treatment groups. The proportion of TRAP-positive osteoclasts area [(14.8±3.8)%] in PMB-OMV treatment group was significantly lower than OMV treatment group [(31.5±6.7) %] ( P=0.004). The relative expression of TLR2 in OMV treatment group (1.359±0.134) was significantly higher than that in the control group (1.000±0.000) ( t=4.62, P=0.044). Compared with the OMV treatment group [(29.4±1.7)%], 50, 100 and 200 μmol/L C29 significantly decreased the formation of osteoclasts [(24.0±1.7)%, (18.5±2.1)%, (9.1±1.3) %] ( P=0.026, P<0.001, P<0.001). TLR2 protein expression in PMB-OMV group (0.780±0.046) was significantly lower than that in OMV group (1.000±0.000)( t=8.32, P=0.001). Conclusions:Pg OMV can promote osteoclast differentiation by carrying LPS, TLR2 plays an important role in Pg OMV mediated osteoclast differentiation.

AIM:To investigate the mechanism of action of Wenweiyang decoction(WWYD)in treating func-tional dyspepsia in rats based on mast cell activation and stem cell factor(SCF)/receptor tyrosine kinase c-Kit signaling pathway.METHODS:Sixty SD rats were randomly divided into control group,model group,ranitidine hydrochloride capsule group,and low-,medium-and high-dose WWYD groups,with 10 rats in each group.The rat model of functional dyspepsia was established by tail clamping and irregular feeding compound senna method.After modeling,the rats in con-trol group and model group were given normal saline,while those in low-,medium-and high-dose(0.743 g/mL,1.485 g/mL and 2.970 g/mL)WWYD groups and ranitidine hydrochloride capsule(3 g/L)group were treated with corresponding drugs by intragastric administration.After treatment,the propulsion rate of the small intestine was measured by the carbon ink propulsion method.Rat duodenal mast cells were observed and counted by toluidine blue staining.ELISA was used for determination of mast cell tryptase(MCT)and histamine(HA)content in rat duodenum.The mRNA levels of SCF and c-Kit in duodenum were detected by RT-qPCR.Western blot and immunohistochemistry were employed to determine the ex-pression levels of SCF and c-Kit in the duodenum.RESULTS:Compared with model group,WWYD treatment signifi-cantly increased the propulsion rate of the small intestine in rats(P<0.05).ELISA results showed that WWYD reduced the number of mast cells and the content of MCT and HA in the duodenal mucosa tissue of rats(P<0.05).Western blot and immunohistochemistry results suggested that WWYD up-regulated the protein expression levels of c-Kit and SCF in the duodenal tissue of rats(P<0.05),and increased the numbers of SCF and c-Kit positive cells.RT-qPCR results indicated that WWYD up-regulated the mRNA expression of c-Kit and SCF in the duodenum of rats(P<0.05).Moreover,the small intestinal propulsion rate was negatively correlated with MCT and HA content,and positively correlated with the expres-sion of SCF and c-Kit.CONCLUSION:Wenweiyang decoction promotes rat duodenal motility,and its mechanism may be related to the inhibition of rat duodenal MCT and HA production and activation of SCF/c-Kit signaling pathway.