1.Efficacy of nicoredil and tirofiban in patients with acute myocardial infarction after PCI
Na LIU ; Hongtao ZHONG ; Miao XU ; Yue ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):164-168
Objective To explore the influence of nicorandil and tirofiban on coronary microcircula-tion and myocardial remodeling in patients with acute myocardial infarction(AMI)after percuta-neous coronary intervention(PCI).Methods A total of 118 AMI patients undergoing PCI in our hospital from January 2020 to January 2024 were enrolled,and divided into nicorandil group(n=39,nicorandil on the basis of routine treatment),tirofiban group(n=37,tirofiban on the basis of routine treatment)and combined group(n=42,nicorandil and tirofiban on the basis of routine treatment)according to their treatment regimens.The levels of the coagulation-related factors,coronary microcirculation indicators,microvascular function,myocardial remodeling indicators,oxidative stress indicators and major adverse cardiovascular events were compared among the three groups.Results In 7 d after PCI,prothrombin time(PT)value,activated partial prothrom-bin time(APTT),left ventricular ejection fraction(LVEF)value and serum levels of von Wille-brand factor(vWF),tissue factor(TF)and superoxide dismutase(SOD)were increased,while in-dex of microcirculatory resistance(IMR),left ventricular end-systolic volume(LVESV)value,left ventricular end-diastolic volume(LVEDV)value and serum endothelin(ET)level were de-creased in the three groups when compared with the corresponding levels before surgery(P<0.05).At the time point,the combined group had higher LVEF value and serum levels of vWF,TF and SOD,while lower IMR,LVESV and LVEDV values and serum ET level when compared to the nicorandil group and tirofiban group(P<0.05).The incidence of reperfusion arrhythmia(2.38%vs 16.22%and 15.38%,P<0.05),incidence of angina pectoris within 6 months after surger-y(2.38%vs 18.92%and 15.38%,P<0.05),and readmission rate of heart failure(2.38%vs 16.22%and 17.95%,P<0.05)were notably lower in the combined group than the other two groups(P<0.05).Conclusion For AMI patients after PCI,combination of nicorandil and tirofi-ban can effectively improve the postoperative coronary microcirculation,promote myocardial re-modeling,improve body's oxidative stress status and vascular endothelial function,and reduce the occurrence of cardiovascular adverse events.
2.Discussion on the Effects of Hedysarum Polybotrys Polysaccharide on Glucose Metabolism of Small Intestinal Smooth Muscle in Diabetic Gastroparesis Rats with Spleen Qi Deficiency Syndrome Based on AMPK/GLUT4 Signaling Pathway
Wenwen WANG ; Zihui ZHONG ; Shengfang WAN ; Xinxin MA ; Lei ZHANG ; Miao LIU ; Minqi XUN ; Jinyu LI ; Kang FENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):91-97
Objective To observe the effects of Hedysarum Polybotrys polysaccharide(HPS)on the glucose metabolism of small intestinal smooth muscle in rats with diabetic gastroparesis(DGP)of spleen qi deficiency syndrome;To explore its mechanism based on AMPK/GLUT4 signaling pathway.Methods Totally 72 male Wistar rats were randomly divided into 12 in the blank group and the remaining 60 rats were assigned to the model group.The DGP spleen qi deficiency syndrome model was replicated by intraperitoneal injection of streptozotocin+irregular feeding with high-fat and high sugar feed combined with swimming exhaustion method.The model rats were randomly divided into model group,metformin group and HPS high-,medium-and low-dosage groups.The metformin group was given 100 mg/kg metformin hydrochloride by gavage,while the HPS high-,medium-and low-dosage groups were given 200,100 and 50 mg/kg HPS by gavage,respectively.The blank group and model group were given purified water by gavage once a day for 8 consecutive weeks.The gastric emptying rate and small intestine propulsion rate in rats were detected,HE staining was used to observe the smooth muscle morphology of gastric antrum and ileal tissue,immunofluorescence staining was used to detect the expression of glucagon like peptide-1(GLP-1)in ileal tissue,ELISA was used to detect the contents of adiponectin(APN),glucagon(Glu)and insulin(INS)in serum,Western blot was used to detect the protein expressions of glucose transporter(GLUT)4,GLUT1,AMP-activated protein kinase(AMPK)and p-AMPK in ileal tissue.Results Compared with the blank group,the model group rats showed significantly increased random blood glucose,significantly decreased body mass,gastric emptying rate and small intestinal propulsion rate(P<0.01);the edema in the submucosal layer,loose arrangement of connective tissue,infiltration of a small number of lymphocytes,granulocytes and macrophages,reduced number of goblet cells in the ileal tissue,shedding of intestinal villous epithelial cells and widening of the gap between the submucosal layer and the lamina propria;the expression of GLP-1 in ileal tissue was significantly decreased(P<0.05),the contents of serum APN and INS were significantly decreased,and the content of Glu significantly increased(P<0.01),the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue were significantly decreased,while the expression of GLUT1 protein significantly increased(P<0.01).Compared with the model group,rats in metformin group and HPS high-dosage group showed a random decrease in blood glucose,an increase in body mass,gastric emptying rate,and small intestine propulsion rate(P<0.05,P<0.01);a more regular arrangement of gastric antral tissue cells,a reduction of shedding cells and edema,the smooth muscle structure of the ileal tissue was relatively intact,with evenly distributed cells and reduced infiltration of inflammatory cells;the expression of GLP-1 in ileal tissue increased,the contents of serum APN and INS increased,and the content of Glu decreased,the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue increased,while the expression of GLUT1 protein decreased(P<0.05,P<0.01).Conclusion HPS may up-regulate GLUT4 and down-regulate GLUT1 expression through activates AMPK,promotes glucose uptake and utilization by small intestinal smooth muscle,and improves glucose metabolism of DGP rats with spleen qi deficiency syndrome.
3.Horticultural Therapy Combined with Intradermal Needling for Patients with Generalized Anxiety Disorder of Liver Depression Transforming into Fire Syndrome Under Transcranial Magnetic Stimulation and Psychological Therapy:Clinical Observation of 60 Cases
Wanyun ZHANG ; Jiayi YAN ; Qingyi QIU ; Yumei PENG ; Xiaoling ZHONG ; Jinwen ZHANG ; Rundong TANG ; Miao WU ; Dan HU ; Guang SU
Journal of Traditional Chinese Medicine 2025;66(1):50-58
ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs (mint and lily potted plants) combined with intradermal needling therapy for generalized anxiety disorder (GAD) of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy, and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups, horticultural therapy group, intradermal needling group, and horticultural therapy+intradermal needling group, with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment; the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment; the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy, following the same procedures and duration. Hamilton Anxiety Rating Scale (HAMA), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI) scores were assessed at baseline and after 2, 4, 6, and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured before treatment and after 8 weeks of treatment. Motor-evoked potential (MEP) baseline levels were recorded before treatment, and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels, MEP amplitude, and anxiety. ResultsIn the horticultural therapy group and intradermal needling group, HAMA, SAS and PSQI scores after 4, 6, and 8 weeks treatment were lower than baseline scores (P<0.05). In the horticultural therapy+intradermal needling group, these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment (P<0.05). The HAMA, SAS, and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2, 4, 6, and 8 weeks treatment (P<0.05). After 8 weeks of treatment, serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels (P<0.05) and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point (P<0.01). When comparing the level after 8 weeks treatment to that after 1 week treatment, under PAS10 stimulation, the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes, while in the horticultural therapy+intradermal needling group, the MEP amplitude ratio decreased at all time points (P<0.05 or P<0.001); under PAS25 stimulation, the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes, and in the intradermal needle group at 10 minutes (P<0.05). In the horticultural therapy+intradermal needling group, the MEP amplitude ratio increased significantly at all time points after treatment (P<0.001). The cure rate in the horticultural therapy+intradermal needling group (74.14%, 43/58) was significantly higher than that in the horticultural therapy group (30.00%, 18/60) and the intradermal needling group (48.28%, 28/58, P<0.05). Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores (r = 0.488, P<0.01; r = 0.428, P<0.01). Following PAS10 intervention, the MEP amplitude ratio was positively correlated with HAMA scores (r = 0.458, P<0.01), whereas after PAS25 intervention, the MEP amplitude ratio was negatively correlated with HAMA scores (r = -0.562, P<0.01). ConclusionHorticultural therapy combined with intradermal needling treatment, under transcranial magnetic stimulation and basic psychological therapy, demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and the reduction of cortical excitability.
4.Efficacy analysis of plasma exchange treatment for thymoma-associated myasthenia gravis
Miao HONG ; Dongdong CAI ; Caihui WEI ; Bing HU ; Kun XIAO ; Fangming RUAN ; Piaoping HU ; Aiping LE ; Zhanglin ZHANG ; Chang ZHONG
Chinese Journal of Blood Transfusion 2025;38(9):1188-1194
Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.
5.Safety and effectiveness of lecanemab in Chinese patients with early Alzheimer's disease: Evidence from a multidimensional real-world study.
Wenyan KANG ; Chao GAO ; Xiaoyan LI ; Xiaoxue WANG ; Huizhu ZHONG ; Qiao WEI ; Yonghua TANG ; Peijian HUANG ; Ruinan SHEN ; Lingyun CHEN ; Jing ZHANG ; Rong FANG ; Wei WEI ; Fengjuan ZHANG ; Gaiyan ZHOU ; Weihong YUAN ; Xi CHEN ; Zhao YANG ; Ying WU ; Wenli XU ; Shuo ZHU ; Liwen ZHANG ; Naying HE ; Weihuan FANG ; Miao ZHANG ; Yu ZHANG ; Huijun JU ; Yaya BAI ; Jun LIU
Chinese Medical Journal 2025;138(22):2907-2916
INTRODUCTION:
Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD.
METHODS:
In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging.
RESULTS:
A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline.
CONCLUSIONS:
Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies.
REGISTRATION
ClinicalTrials.gov , NCT07034222.
Humans
;
Alzheimer Disease/drug therapy*
;
Male
;
Female
;
Aged
;
Middle Aged
;
Cognitive Dysfunction/drug therapy*
;
Aged, 80 and over
;
Amyloid beta-Peptides/metabolism*
;
Biomarkers
;
East Asian People
6.Analysis of the efficacy and influencing factors of myofunctional therapy in the treatment of adult obstructive sleep apnea
Zhenzhang LU ; Si LONG ; Wenqian ZHONG ; Meihong ZHANG ; Xiaorong GONG ; Guohui NIE ; Jing TAO ; Beiping MIAO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(4):239-243
OBJECTIVE To evaluate the efficacy of oral and facial muscle functional training in treating adult obstructive sleep apnea(OSA)and to identify clinical indicators influencing treatment outcomes.METHODS Through a prospective cohort study,patients diagnosed with OSA in the study unit were recruited to undergo a 3-month myofunctional therapy,including soft palate-related muscles,tongue muscles,buccal muscles,and labial muscles in multiple muscle groups,once a day,five times a week,with the use of offline clinic guidance,and the APP program video follow up training for effective training.Data were collected on multiple dimensions including physical signs,sleep breathing monitoring parameters,and airway measurements from imaging studies.Treatment efficacy was assessed by comparing subjective and objective sleep indicators before and after training.Patients were categorized into effective and ineffective groups based on treatment outcomes.Differences in baseline clinical indicators between these groups were analyzed using univariate and multivariate regression analyses.RESULTS The study finally included 58 people,51 males and 7 females,age(38.36±8.96)years,BMI(27.14±3.68)kg/m2,AHI of the enrolled patients was reduced from(31.27±22.28)times/h pre-training to(26.27±21.38)times/h post-training,the minimum oxygen saturation was increased from(78.43±10.07)%to(80.50±10.06)%,snoring index decreased from(62.80±75.20)times/h to(36.40±43.19)times/h,and ESS score decreased from 7.00±5.31 pre-training to 5.50±3.17.By comparing the effective and ineffective groups,it was found that there was a statistically significant difference in the tongue position and ESS scores between the two groups(both P<0.05),while no significant differences were found in gender,age,neck circumference,posterior soft palate area,uvula area,posterior tongue area,or posterior epiglottic area(all P>0.05).Univariate logistic regression analysis indicated that tongue position,AHI,and ESS scores were factors affecting the efficacy of oral and facial muscle function training.Multivariate regression analysis revealed that AHI was an independent prognostic factor for this training in OSA patients.CONCLUSION Oral and facial muscle function training can improve both subjective and objective sleep breathing indices in OSA patients.Tongue position,AHI,and ESS scores may serve as prognostic factors for OSA treatment,aiding in guiding subsequent individualized intervention therapies.
7.Experimental study of magnetic tracer technique in the localization of pulmonary nodules in dogs
Huan-chen SHA ; Miao-miao ZHANG ; Jia-hui WAN ; Qiu-ye ZHONG ; Rui-min GONG ; Yi LYU ; Xiao-peng YAN
Journal of Regional Anatomy and Operative Surgery 2025;34(10):841-845
Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.
8.Studies on the Design and Activity of Anticancer Peptides Based on the Weak Acidic Microenvironment of Tumors
Yue-Qi NIE ; Miao JIANG ; Hui-Yan WU ; Chang-Hao DING ; Wei REN ; Jun-Yi CHANG ; Ke CHEN ; Shao-Long DU ; Peng ZHANG ; Zhong-Hua LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1380-1391
Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38%)and primary myocardial cells(the inhibition rate was 49.7%,with P<0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P<0.01),decreasing the hy-drated particle size(P<0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.
9.The influence of two-way referral model on treatment and prognosis of patients with chronic heart failure
Yijun SUN ; Xinyu ZHANG ; Yue HU ; Zongwei LIN ; Jie XIAO ; Peng LI ; Xin ZHAO ; Huafang ZHANG ; Bo QIN ; Dequan JIA ; Tao ZHANG ; Jian MA ; Hongping CHEN ; Chunju ZHANG ; Xinwei GENG ; Kaiyan ZHANG ; Man ZHENG ; Fenglei ZHANG ; Yan LANG ; Hegong HOU ; Peng LIU ; Haifeng JIA ; Jianjun LU ; Kai ZHAO ; Hui ZHAO ; Jiechang XU ; Mi ZHANG ; Xiuxin LI ; Dongxia ZHANG ; Lin ZHONG ; Hui ZHAO ; Fangfang LIU ; Yan LIU ; Dongxia MIAO ; Chengwei WANG ; Hui ZHANG ; Chen WANG ; Fen WANG ; Xuejuan ZHANG ; Huixia LYU ; Xiaoping JI
Chinese Journal of Cardiology 2025;53(11):1244-1253
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.
10.Studies on the Design and Activity of Anticancer Peptides Based on the Weak Acidic Microenvironment of Tumors
Yue-Qi NIE ; Miao JIANG ; Hui-Yan WU ; Chang-Hao DING ; Wei REN ; Jun-Yi CHANG ; Ke CHEN ; Shao-Long DU ; Peng ZHANG ; Zhong-Hua LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1380-1391
Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38%)and primary myocardial cells(the inhibition rate was 49.7%,with P<0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P<0.01),decreasing the hy-drated particle size(P<0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

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