Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective To explore the diagnostic value of a combined model based on clinicopathological and MRI features in BRCA-mutated ovarian cancer.Methods The data of 132 patients with ovarian cancer who underwent pathology and BRCA gene tes-ting were analyzed retrospectively,including 52 cases of BRCA mutation group and 80 cases of BRCA wild group.The differences of MRI features and clinicopathological features between BRCA mutation group and BRCA wild group were compared.Binary logistic regression was used to construct a joint prediction model and analyze its diagnostic efficiency.Results There were significant differ-ences in cytokeratin 7(CK7),estrogen receptor(ER),Ki-67 and lymphovascular invasion(LVI)between the BRAC mutation group and the BRAC wild group(P＜0.05).Univariate analysis showed that CK7,ER,Ki-67,LVI and the apparent diffusion coefficient(ADC)value of the cystic part of tumor were risk factors for BRCA-mutated ovarian cancer.The combined model based on CK7,ER,Ki-67,LVI,and the ADC value of the cystic part of tumor for the diagnosis of BRCA-mutated ovarian cancer had an area under the curve(AUC)of 0.765.Conclusion CK7,ER,Ki-67,LVI and the ADC value of the cystic part of tumor are risk factors for BRCA-mutated ovarian cancer.The combined model based on the above characteristics demonstrates good diagnostic efficacy for BRCA-mutated ovarian cancer.

Dental caries is the most common oral disease in children,not only impairing chewing,speech,and other functions while also impacting maxillofacial development and overall health.Recent researches have established the"ecological plaque theory",which posits that an imbalance in the oral plaque microecology leads to the demineralization of teeth hard tissues,as the widely ac-cepted etiology of dental caries.However,the significant variability in the composition and function of children's plaque microorgan-isms,influenced by primary tooth eruption and replacement,changes in diet,and increase in social interactions,makes traditional culture methods inadequate for studying this complex micro-ecosystem.Advances in multi-omics technologies have recently created new opportunities for studiing complex microecology.High-throughput sequencing technologies,such as 16S rRNA gene sequencing and metagenomics,allow for the exploration of microbial diversity and the analysis of genomic functions and their associations with dental caries.Mass spectrometry-based technologies,including metabolomics and proteomics,might elucidate the molecular mecha-nisms of dental caries by analyzing differential metabolites and pathways.This review focuses on the application of multi-omics tech-nologies to explore the relationships between the structure,function,and metabolic state of oral microbial communities and pediatric dental caries.It further discusses the future of oral microorganisms as diagnosis and therapeutic targets for caries,and is expected to provide novel strategies for the prevention and treatment of pediatric dental caries.

Dental caries is the most common oral disease in children,not only impairing chewing,speech,and other functions while also impacting maxillofacial development and overall health.Recent researches have established the"ecological plaque theory",which posits that an imbalance in the oral plaque microecology leads to the demineralization of teeth hard tissues,as the widely ac-cepted etiology of dental caries.However,the significant variability in the composition and function of children's plaque microorgan-isms,influenced by primary tooth eruption and replacement,changes in diet,and increase in social interactions,makes traditional culture methods inadequate for studying this complex micro-ecosystem.Advances in multi-omics technologies have recently created new opportunities for studiing complex microecology.High-throughput sequencing technologies,such as 16S rRNA gene sequencing and metagenomics,allow for the exploration of microbial diversity and the analysis of genomic functions and their associations with dental caries.Mass spectrometry-based technologies,including metabolomics and proteomics,might elucidate the molecular mecha-nisms of dental caries by analyzing differential metabolites and pathways.This review focuses on the application of multi-omics tech-nologies to explore the relationships between the structure,function,and metabolic state of oral microbial communities and pediatric dental caries.It further discusses the future of oral microorganisms as diagnosis and therapeutic targets for caries,and is expected to provide novel strategies for the prevention and treatment of pediatric dental caries.

Objective To explore the diagnostic value of a combined model based on clinicopathological and MRI features in BRCA-mutated ovarian cancer.Methods The data of 132 patients with ovarian cancer who underwent pathology and BRCA gene tes-ting were analyzed retrospectively,including 52 cases of BRCA mutation group and 80 cases of BRCA wild group.The differences of MRI features and clinicopathological features between BRCA mutation group and BRCA wild group were compared.Binary logistic regression was used to construct a joint prediction model and analyze its diagnostic efficiency.Results There were significant differ-ences in cytokeratin 7(CK7),estrogen receptor(ER),Ki-67 and lymphovascular invasion(LVI)between the BRAC mutation group and the BRAC wild group(P＜0.05).Univariate analysis showed that CK7,ER,Ki-67,LVI and the apparent diffusion coefficient(ADC)value of the cystic part of tumor were risk factors for BRCA-mutated ovarian cancer.The combined model based on CK7,ER,Ki-67,LVI,and the ADC value of the cystic part of tumor for the diagnosis of BRCA-mutated ovarian cancer had an area under the curve(AUC)of 0.765.Conclusion CK7,ER,Ki-67,LVI and the ADC value of the cystic part of tumor are risk factors for BRCA-mutated ovarian cancer.The combined model based on the above characteristics demonstrates good diagnostic efficacy for BRCA-mutated ovarian cancer.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective To investigate the difference of the disease progression in patients with chronic obstructive pulmonary disease (COPD) with different muscle mass levels and the influence of related factors on the disease progression. Methods A total of 308 newly diagnosed patients with COPD from February 2021 to February 2022 were selected for this study. All patients were below moderate COPD. The patients were divided into two groups according to their muscle mass levels: sarcopenia group (98 cases) and control group (210 cases). The diagnostic criteria for sarcopenia were based on sarcopenia diagnostic thresholds: RSMI <7.0kg/m² in men and <5.4kg/m² for women. All subjects were followed up for 4 months to observe the progress of the patient's condition. The correlation between the muscle mass level and pulmonary function level, as well as the results of 6-minute walking test and CAT score was evaluated, and the influence of muscle mass level on the patient's disease progress was analyzed. At the same time, the potential influence of related factors (body fat rate, vitamin D level, etc.) on the condition of patients with different muscle mass levels was discussed. SPSS 19.0 software was used to perform statistical analysis. Results Under the same treatment intervention, the baseline and follow-up lung function improvement levels of patients in the sarcopenia group were lower than those in the control group, and the difference was statistically significant (P<0.05). At the same time, the baseline and follow-up 6-minute walk test results of the patients in the sarcopenia group were also worse than those of the control group, and the difference was statistically significant (P<0.05). Further correlation analysis was carried out between the patient's muscle mass level and the post-treatment pulmonary function indicators and 6MWD test level. The results showed that the muscle mass level was positively correlated with several pulmonary function indicators (FEV1, FEV1% predict) and 6MWD (both P<0.05). Considering the possible influence of other factors on the control and progress of the patient's condition, the present study used follow-up CAT score results to distinguish the prognosis of the patient's condition improvement, and used improvement and non-improvement as dependent variables to analyze the influence of various potential influencing factors. The results of regression model analysis showed that lower baseline muscle mass, women, lower body fat percentage, and lower vitamin D level were the main risk factors. Conclusion Under the same treatment condition, COPD patients with different muscle mass levels improve more slowly when complicated with sarcopenia and have poor prognosis. Women, lower body fat percentage and lower vitamin D level are potential risk factors for poor prognosis.

Objective To explore the efficiency and safety of trans-sheath intraluminal forceps biopsy under digital subtraction angiography(DSA)guidance for assisting diagnosis of pulmonary artery obstructive diseases.Methods Data of 16 patients who underwent trans-sheath intraluminal forceps biopsy for pulmonary artery obstructive diseases were retrospectively analyzed,and the clinical manifestations were recorded.The technical success of biopsy was defined as tissue obtained met the needs of pathology diagnosis.For patients with malignant pathology results,the final diagnosis was malignant,for those with benign pathology results after biopsy and no obvious changes after 6-month or longer follow-up,or benign pathology results after surgical resection,the final diagnosis was benign,otherwise was no clear diagnosis.The operation time,technical success rate,diagnostic efficiency,complications and changes of pulmonary artery pressure before and after the biopsy were observed.Results Among 16 patients,9 complained of intermittent chest tightness,4 complained of chest pain with chest tightness,2 complained of chest pain but 1 denied any symptoms.The lesions located in the left lung in 10 cases and in the right lung in 6 cases,all with enhanced CT showed filling defects of the involved branch of pulmonary artery.Totally 16 trans-sheath intraluminal forceps biopsies were performed in 16 patients,with an average operation time of(31.02±6.02)min and technical success rate of 100%.Malignant tumors were finally diagnosed in 10 cases,including 1 case of lung cancer with false-negative biopsy result,while biopsy correctly diagnosed benign lesions in the other 6 cases.Transient worsening chest pain with chest tightness occurred in 2 cases and relieved after symptomatic treatments.No statistically significant difference of pulmonary artery pressure was found before([53.38±14.28]mmHg)and after([53.69±14.15]mmHg)biopsy(P＞0.05).Conclusion DSA-guided trans-sheath intraluminal forceps biopsy was relatively safe and valuable for assisting diagnosis of pulmonary artery obstructive diseases.

Objective To observe the value of dual-source CT(DECT)virtual monoenergetic imaging(VMI)for differentiating prostate cancer(PC)and benign prostatic hyperplasia(BPH).Methods Thirty-three patients with PC(PC group)and 44 patients with BPH(BPH group)were retrospectively enrolled,and 40-100 keV(with 10 keV interval)VMI were reconstructed based on arterial phase DECT images,respectively.Clinical data,focal CT value and contrast-to-noise ratio(CNR)of VMI with different energy levels and conventional linear fusion images of arterial phase were compared between groups.Binary logistic regression models were constructed based on clinical data being significantly different between groups,focal CT value of VMI with energy level with the highest CNR,also focal CT value of conventional linear fusion images of arterial phase,respectively.The area under the receiver operating characteristic curve(AUC)was calculated to evaluate the efficacy of each model for differentiating PC and BPH.Results Free prostate-specific antigen(f-PSA),total prostate-specific antigen(t-PSA),focal CT value of 40-100 keV VMI and conventional linear fusion images of arterial phase in PC group were all higher,while short diameter in PC group was smaller than those in BPH group(all P＜0.05).Logistic regression models were constructed based on f-PSA,t-PSA,short diameter,CT value at 40 keV VMI and CT value at conventional linear fusion images of arterial phase,respectively,with AUC for differentiating PC and BPH of 0.879,0.902,0.701,0.911 and 0.857,respectively.Conclusion DECT VMI could be used as a supplementary examination for prostate diseases,and 40 keV VMI had the best efficacy for differentiating PC and BPH.

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.