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 compare and analyze the differences in positioning errors and placement outside the target area between two different image-guided systems(Halcyon and Synergy)in radiotherapy for cervical cancer.Methods:The data of 40 patients with cervical cancer who received treatment in Dezhou People's Hospital from March 2023 to June 2023 were retrospectively selected.Each patient was treated respectively with Halcyon linear accelerator and Synergy linear accelerator,with 20 cases for each treatment method.All patients underwent cone beam computed tomography(CBCT)at kV level to conduct image scanning before radiotherapy,and the obtained CBCT images were matched with the positioned CT images by online.The registration results of left and right(x),head and foot(y)and front and back(z)of three translation direction,and pitch(Rx),rotation(Ry)and deflection(Rz)directions of rotation direction were respectively obtained.The margin of planning target volume(MPTV)was calculated according to positioning expansion formula.The differences of positioning errors and target area expansion between Halcyon and Synergy image-guided systems were compared and analyzed.Results:Halcyon and Synergy image-guided systems obtained respectively 479 and 447 sets of CBCT images.The translational errors of Halcyon image-guided system on x,y,and z directions were respectively(-0.03±0.21),(0.12±0.63)and(0.02±0.15)cm,and the rotational errors of that on Rx,Ry and Rz directions were respectively(0.38±1.26)°,(-0.40±1.02)°,and(0.07±1.07)°.The translational errors of Synergy image-guided system were respectively(-0.07±0.18),(0.08±0.49)and(0.11±0.22)cm on the three directions,and the rotational errors of that were respectively(0.28±1.29)°,(-0.29±1.29)° and(-0.16±1.20)°.The translational error values on the y direction of both image-guided system were larger than that on x and z directions,and the absolute values of the range of translational errors of them were basically within 5 mm.There were no statistically significant difference in the positioning errors of rotation on Rx and Ry directions between Halcyon and Synergy image-guided systems(P＞0.05),while there was a statistically significant difference in the positioning error of rotation on Rz direction between them(t=-3.06,P＜0.05).The MPTV values of Halcyon image-guided system on x,y and z directions were respectively 0.4,1.4 and 0.3 cm,and those of Synergy image-guided system were respectively 0.4,0.9 and 0.5 cm.The expansion boundary of target area of Halcyon image-guided system on the y direction was larger than that of Synergy image-guided system,and that on other directions were all less or equal to 0.5 cm.Conclusion:The MPTV values of Halcyon and Synergy image-guided systems can meet clinical requirements in radiotherapy.The positioning errors and the tube current of the scan of Halcyon image-guided system were larger than those of Synergy image-guided system,but the scanning time and treatment time of that were significantly lower than those of Synergy image-guided system.Different treatment systems can be selected individually for patients according to their different conditions.

Objective:To systematically evaluate the predictive value of the reverse shock index multiplied by the Glasgow coma scale score (rSIG) for mortality of trauma patients.Methods:A comprehensive literature search was conducted to identify studies on the predictive value of rSIG for mortality of trauma patients in the following databases from inception to April 2025, including CNKI, Wanfang Data, SinoMed, PubMed, Cochrane Library, Web of Science, and Embase. Two investigators independently screened the literature, extracted data, and assessed study quality according to predefined inclusion and exclusion criteria. The Quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used to evaluate the risk of bias in the included studies. Meta analysis was performed using Stata 17.0 software with a bivariate mixed-effects model. The following metrics were used to assess the predictive value of rSIG for mortality in trauma patients, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (SROC) curve (AUC). The influence of various factors on the predictive performance of rSIG was examined, including injury type, study design, region, sample size, cut-off value, rSIG measurement time, and outcome measures. Additionally, sensitivity analysis, Fagan′s nomogram, and Deeks′ funnel plot were employed to assess the robustness of the findings, clinical applicability, and publication bias.Results:A total of 15 studies involving 710 612 trauma patients were included, 26 105 of whom were deceased. Meta analysis results showed that rSIG had a pooled sensitivity of 0.78(95% CI 0.71, 0.84), a pooled specificity of 0.78(95% CI 0.68, 0.86), a pooled PLR of 3.60(95% CI 2.46, 5.27), a pooled NLR of 0.28(95% CI 0.22, 0.36), a pooled DOR of 12.70(95% CI 8.10, 19.91), and an AUC of 0.85(95% CI 0.81, 0.87) for predicting mortality of trauma patients. Subgroup analysis identified injury type as one of the major sources of heterogeneity, and the predictive specificity of rSIG was significantly higher in patients with multiple trauma (0.82) than in those with isolated traumatic brain injury (0.65) ( P<0.05). Sensitivity analysis indicated that the findings were robust and stable. Fagan′s nomogram showed that when the pre-test probability was 7%, the post-test probability of death increased to 21% in patients with low rSIG and decreased to 2% in those with high rSIG. Deeks′ funnel plots suggested no significant publication bias among the included studies ( P>0.05). Conclusion:Low rSIG has good predictive performance for mortality of trauma patients and can serve as an effective tool for early and rapid prognosis assessment with superior predictive performance in patients with multiple trauma compared to those with traumatic brain injury.

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 compare and analyze the differences in positioning errors and placement outside the target area between two different image-guided systems(Halcyon and Synergy)in radiotherapy for cervical cancer.Methods:The data of 40 patients with cervical cancer who received treatment in Dezhou People's Hospital from March 2023 to June 2023 were retrospectively selected.Each patient was treated respectively with Halcyon linear accelerator and Synergy linear accelerator,with 20 cases for each treatment method.All patients underwent cone beam computed tomography(CBCT)at kV level to conduct image scanning before radiotherapy,and the obtained CBCT images were matched with the positioned CT images by online.The registration results of left and right(x),head and foot(y)and front and back(z)of three translation direction,and pitch(Rx),rotation(Ry)and deflection(Rz)directions of rotation direction were respectively obtained.The margin of planning target volume(MPTV)was calculated according to positioning expansion formula.The differences of positioning errors and target area expansion between Halcyon and Synergy image-guided systems were compared and analyzed.Results:Halcyon and Synergy image-guided systems obtained respectively 479 and 447 sets of CBCT images.The translational errors of Halcyon image-guided system on x,y,and z directions were respectively(-0.03±0.21),(0.12±0.63)and(0.02±0.15)cm,and the rotational errors of that on Rx,Ry and Rz directions were respectively(0.38±1.26)°,(-0.40±1.02)°,and(0.07±1.07)°.The translational errors of Synergy image-guided system were respectively(-0.07±0.18),(0.08±0.49)and(0.11±0.22)cm on the three directions,and the rotational errors of that were respectively(0.28±1.29)°,(-0.29±1.29)° and(-0.16±1.20)°.The translational error values on the y direction of both image-guided system were larger than that on x and z directions,and the absolute values of the range of translational errors of them were basically within 5 mm.There were no statistically significant difference in the positioning errors of rotation on Rx and Ry directions between Halcyon and Synergy image-guided systems(P＞0.05),while there was a statistically significant difference in the positioning error of rotation on Rz direction between them(t=-3.06,P＜0.05).The MPTV values of Halcyon image-guided system on x,y and z directions were respectively 0.4,1.4 and 0.3 cm,and those of Synergy image-guided system were respectively 0.4,0.9 and 0.5 cm.The expansion boundary of target area of Halcyon image-guided system on the y direction was larger than that of Synergy image-guided system,and that on other directions were all less or equal to 0.5 cm.Conclusion:The MPTV values of Halcyon and Synergy image-guided systems can meet clinical requirements in radiotherapy.The positioning errors and the tube current of the scan of Halcyon image-guided system were larger than those of Synergy image-guided system,but the scanning time and treatment time of that were significantly lower than those of Synergy image-guided system.Different treatment systems can be selected individually for patients according to their different conditions.

Objective:To systematically evaluate the predictive value of the reverse shock index multiplied by the Glasgow coma scale score (rSIG) for mortality of trauma patients.Methods:A comprehensive literature search was conducted to identify studies on the predictive value of rSIG for mortality of trauma patients in the following databases from inception to April 2025, including CNKI, Wanfang Data, SinoMed, PubMed, Cochrane Library, Web of Science, and Embase. Two investigators independently screened the literature, extracted data, and assessed study quality according to predefined inclusion and exclusion criteria. The Quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used to evaluate the risk of bias in the included studies. Meta analysis was performed using Stata 17.0 software with a bivariate mixed-effects model. The following metrics were used to assess the predictive value of rSIG for mortality in trauma patients, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (SROC) curve (AUC). The influence of various factors on the predictive performance of rSIG was examined, including injury type, study design, region, sample size, cut-off value, rSIG measurement time, and outcome measures. Additionally, sensitivity analysis, Fagan′s nomogram, and Deeks′ funnel plot were employed to assess the robustness of the findings, clinical applicability, and publication bias.Results:A total of 15 studies involving 710 612 trauma patients were included, 26 105 of whom were deceased. Meta analysis results showed that rSIG had a pooled sensitivity of 0.78(95% CI 0.71, 0.84), a pooled specificity of 0.78(95% CI 0.68, 0.86), a pooled PLR of 3.60(95% CI 2.46, 5.27), a pooled NLR of 0.28(95% CI 0.22, 0.36), a pooled DOR of 12.70(95% CI 8.10, 19.91), and an AUC of 0.85(95% CI 0.81, 0.87) for predicting mortality of trauma patients. Subgroup analysis identified injury type as one of the major sources of heterogeneity, and the predictive specificity of rSIG was significantly higher in patients with multiple trauma (0.82) than in those with isolated traumatic brain injury (0.65) ( P<0.05). Sensitivity analysis indicated that the findings were robust and stable. Fagan′s nomogram showed that when the pre-test probability was 7%, the post-test probability of death increased to 21% in patients with low rSIG and decreased to 2% in those with high rSIG. Deeks′ funnel plots suggested no significant publication bias among the included studies ( P>0.05). Conclusion:Low rSIG has good predictive performance for mortality of trauma patients and can serve as an effective tool for early and rapid prognosis assessment with superior predictive performance in patients with multiple trauma compared to those with traumatic brain injury.

Objective:To analysis the laws and regulations related to human genetic resources, this study analyzed the current management status and trends at home and abroad, explored the related issues of human genetic resources data management, and provided reference for further promoting and standardizing the management of human genetic resources data in my country.Methods:This article analyzed the current management status of human genetic resources data from three levels: relevant policies, management frameworks, data platforms and sample databases through literature review and expert consultation and policy research.Results:Countries paid more and more attention to human genetic resources, and the construction of my country′s human genetic resources management system is constantly advancing and improving. In the data era, the management of human genetic resources was facing new problems and challenges, requiring further strengthening the research and management of relevant data.Conclusions:At present, the management of human genetic resource data in my country needs to be strengthened. On the one hand, it is necessary to promote the implementation and coordinated management of specific systems on human genetic resources data. On the other hand, it is necessary to strengthen the effective protection and sharing of human genetic resource data.

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.