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 study the correlation and diagnostic significance of the silent information regulator 2 related enzyme 1(SIRT1)/nuclear factor kappa B(NF-κB)signaling pathway and cognitive impairment(CI)in patients with Parkinson's disease(PD).Methods A total of 119 patients with primary PD diagnosed and treated be in Taizhou Second People's Hospital from September 2017 to March 2021 were selected as PD group.According to cognitive function status of subjects,research subjects were divided into normal cognitive(NC)group(n=33),mild cognitive impairment(MCI)group(n=58),and dementia subgroup(PDD)group(n=28).In addition,50 healthy people for physical examination during the same period were selected as normal control group.After admission,the peripheral blood levels of SIRT1/NF-κB signaling pathway related molecules in all subjects were detected,and relationship between expression of SIRT1/NF-κB signaling pathway and cognitive function in PD patients was analyzed by partial correlation analysis.Cox proportional hazards regression model was used to analyze the influencing factors,and receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of the SIRT1/NF-κB signaling pathway.Results SIRT1 mRNA expression in PD group was significantly lower than normal control group,while NF-κB mRNA expression was higher than normal control group(P＜0.05).PD group was further stratified and compared,and it was found that SIRT1 mRNA expression of PDD patients was significantly lower than that of NC and MCI patients(P＜0.05).SIRT1 mRNA and NF-κB mRNA had significant correlation with MoCA score(r=0.637,-0.527,P＜0.05).Cox regression analysis showed that high H-Y staging and high expression of NF-κB mRNA were independent risk factors for occurrence of CI in PD patients,and high expression of SIRT1 mRNA and high education level were independent protective factors for PD patients.ROC curve analysis showed that SIRT 1 and NF-κB mRNA expression diagnosed secondary CI in PD patients,and both had good predictive effects(P＜0.05).Conclusion SIRT1 mRNA and NF-κB mRNA were highly expressed in the peripheral blood of patients with PD secondary to CI,and had strong correlation with cognitive function.Early enhancement of the detection of SIRT1 mRNA and NF-κB mRNA expression in peripheral blood of PD patients can play an important role in diagnosis and prognosis.

Objective To study the correlation and diagnostic significance of the silent information regulator 2 related enzyme 1(SIRT1)/nuclear factor kappa B(NF-κB)signaling pathway and cognitive impairment(CI)in patients with Parkinson's disease(PD).Methods A total of 119 patients with primary PD diagnosed and treated be in Taizhou Second People's Hospital from September 2017 to March 2021 were selected as PD group.According to cognitive function status of subjects,research subjects were divided into normal cognitive(NC)group(n=33),mild cognitive impairment(MCI)group(n=58),and dementia subgroup(PDD)group(n=28).In addition,50 healthy people for physical examination during the same period were selected as normal control group.After admission,the peripheral blood levels of SIRT1/NF-κB signaling pathway related molecules in all subjects were detected,and relationship between expression of SIRT1/NF-κB signaling pathway and cognitive function in PD patients was analyzed by partial correlation analysis.Cox proportional hazards regression model was used to analyze the influencing factors,and receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of the SIRT1/NF-κB signaling pathway.Results SIRT1 mRNA expression in PD group was significantly lower than normal control group,while NF-κB mRNA expression was higher than normal control group(P＜0.05).PD group was further stratified and compared,and it was found that SIRT1 mRNA expression of PDD patients was significantly lower than that of NC and MCI patients(P＜0.05).SIRT1 mRNA and NF-κB mRNA had significant correlation with MoCA score(r=0.637,-0.527,P＜0.05).Cox regression analysis showed that high H-Y staging and high expression of NF-κB mRNA were independent risk factors for occurrence of CI in PD patients,and high expression of SIRT1 mRNA and high education level were independent protective factors for PD patients.ROC curve analysis showed that SIRT 1 and NF-κB mRNA expression diagnosed secondary CI in PD patients,and both had good predictive effects(P＜0.05).Conclusion SIRT1 mRNA and NF-κB mRNA were highly expressed in the peripheral blood of patients with PD secondary to CI,and had strong correlation with cognitive function.Early enhancement of the detection of SIRT1 mRNA and NF-κB mRNA expression in peripheral blood of PD patients can play an important role in diagnosis and prognosis.

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 observe the clinical efficacy and safety of external application of Piyan Formula in treating epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs)-related rashes.Methods Sixty cases of EGFR-TKIs-related rash patients were randomly allocated into either a treatment group or a control group.The treatment group received external application of Piyan Formula to the rash area twice daily for 14 days.The control group received external application of fucidic acid cream to the rash area twice daily for 14 days.Changes in rash grading,itching grading,quality of life scores and adverse event were observed and recorded in both groups.At the same time,levels of hypersensitive C-reactive protein,interleukin(IL)-6,and IL-1β were measured before treatment and 24 hours after treatment.Results After treatment,the rash severity,itching severity,and quality of life scores were notably lower in the treatment group compared to the control group(P<0.05).The levels of hypersensitive C-reactive protein,IL-6,and IL-1β exhibited a significant decrease compared to their pre-treatment values.(P<0.05).Compared with the control group,the levels of hypersensitive C-reactive protein,IL-6,and IL-1β decreased in the treatment group,with statistically significant differences(P<0.05).No adverse events related to Piyan Formula or fucidic acid cream occurred during the treatment process.Conclusion External application of Piyan Formula in treating EGFR-TKIs-related rashes shows significant clinical efficacy,can effectively reduce the levels of inflammatory factors,and has high safety,thus warranting clinical promotion.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective To study the effect of interleukin-15(IL-15)on lipopolysaccharide(LPS)-induced apoptosis of septic cardiomyocytes and its related mechanism.Methods H9C2 cells were divided into control group(H9C2 cells in conventional culture),apoptosis group(LPS-induced myocardial cell injury model was established),and intervention group(10 ng/ml recombinant rat IL-15 was used in myocardial H9C2 cell injury model for 6 h).The effects of IL-15 on H9C2 cell proliferation and apoptosis were detected by methyl thiazolyl tetrazolium(MTT)assay and flow cytometry,the level of mitochondrial membrane potential was detected by staining of tetramethylrhodamine ethyl ester(TMRE).The sepsis mouse model was established by intraperitoneal injection of 10 mg/kg LPS,and 100 μl of normal saline containing 100 μg/ml IL-15 was injected intraperitoneally.HE staining was used to evaluate the pathological injury of mouse myocardium.The indexes of oxidative stress in mouse myocardium were detected by ELISA.The effects of IL-15 on the expression of heme oxygenase 1(HO-1)and NF-E2-related factor 2(Nrf2)mRNAs and proteins in myocardium of mouse sepsis model were detected by real-time fluorescence quantitative PCR and Western bloting.Results The apoptosis rate of H9C2 cells in the apoptosis group was significantly higher than that in the control group(47.9%±5.1%vs.2.1%±0.3%,P<0.05).The apoptosis rate of H9C2 cells in the intervention group was 20.7%±2.7%,which was significantly lower than that in the apoptosis group(P<0.05).LPS could significantly inhibit the proliferation of myocardial cells,while IL-15 could inhibit LPS-induced decrease in myocardial cell viability(P<0.05).The relative mitochondrial membrane potential of myocardial H9C2 cells in the apoptosis group was significantly lower than that in the control group(2.6±4.6 vs.7.4±5.2,P<0.05).The relative mitochondrial membrane potential of myocardial H9C2 cells in the intervention group was 4.2±4.9,which was significantly higher than that in the apoptosis group(P<0.05).LPS significantly enhanced the loss of mitochondrial membrane potential of myocardial H9C2 cells,and IL-15 intervention weakened the loss of mitochondrial membrane potential of H9C2 cells induced by LPS(P<0.05).HE staining revealed obvious myocardial tissue damage and inflammatory cell infiltration in mouse sepsis model.IL-15 ameliorated LPS-induced myocardial injury in mice.The expression levels of superoxide dismutase(SOD)and total antioxidant capacity(T-AOC)in myocardium of sepsis mice were significantly lower than those in normal mice,while the expression level of malondialdehyde(MDA)in sepsis mice was significantly higher than that in normal mice(P<0.05).After IL-15 intervention,the expression of SOD and T-AOC in myocardium of sepsis mice was increased,and the expression of MDA was decreased(P<0.05).The mRNA and protein expression levels of HO-1 and Nrf2 were low in myocardium of normal mice.The mRNA and protein expression levels of HO-1 and Nrf2 in myocardium of sepsis mice were significantly higher than those in normal mice(P<0.05).After IL-15 intervention,the mRNA and protein expression levels of HO-1 and Nrf2 were significantly increased in myocardium of sepsis mice(P<0.05).Conclusion IL-15 can protect cardiomyocyte apoptosis induced by sepsis and decrease myocardial injury in sepsis mice.The mechanism may be related to the activation of HO-1/Nrf2 signaling pathway and the inhibition of myocardial oxidative stress in septic mice.

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg^-1•d^-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg^-1•d^-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.
Animals ; Rats ; Rats, Sprague-Dawley ; Propionates ; Serotonin ; Depression/therapy* ; Electroacupuncture ; Fatty Acids, Volatile ; Stroke/complications* ; Acetic Acid ; Butyric Acid ; Water

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β₂-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
Humans ; Multiple Myeloma/drug therapy* ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Treatment Outcome ; Hematologic Diseases

ObjectiveThis study aimed to analyze the difference in setup error before and after correction of systematic error. To determine the most appropriate image-guided strategy during HT treatment， we use different scanning ranges and image-guidance frequencies in patients with nasopharyngeal carcinoma （NPC） treated with helical tomotherapy （HT）. MethodsFifteen patients with NPC who received HT treatment in Sun Yat-sen University Cancer Center from October 2019 to February 2020 were selected. Megavoltage computed tomography （MVCT） scanning was performed before each treatment. After five times of radiotherapy， system-error correction was performed to adjust the setup center. The setup errors before and after the correction of systematic errors， as well as the setup errors of different scanning ranges and different scanning frequencies， were collected for analysis and comparison. ResultsWhen comparing the setup errors before and after the correction of systematic error， the differences in setup errors in the left–right （LR）， superior–inferior （SI）， and anterior–posterior （AP） directions were statistically significant （P<0.05）.The different scanning ranges of "nasopharynx + neck" and "nasopharynx" were compared， and a statistically significant difference was found in yaw rotational errors （P<0.05）. In the comparison of daily and weekly scan frequency after system-error correction， a significant difference was found in AP direction （P<0.05）. ConclusionDuring radiotherapy for NPC， the systematic error can be corrected according to the first five setup errors， and then small-scale scanning was selected for image-guided radiotherapy every day.