Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.

Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

OBJECTIVE: To investigate the transfusion and infusion warmer manufacturers, combine the use failures to analyze adverse events, and provide support for enterprise risk management and clinical safe use. METHODS: The sentinels from 7 manufacturing enterprises and 11 medical institutions that participated in Shandong Province's key monitoring program during the "14th Five-Year Plan" period were targeted. This was done by understanding the equipment's principles, structures, and quality control. Additionally, real-world data from January 2019 to December 2023 were collected to count adverse events. RESULTS: During production, there are risks in switching power supply stability and solder joint firmness. Fifteen kinds of faults occurred during use, and common faults such as inability to heat, unable to turn on the machine, and bubbles in the infusion tube accounted for more than 80%. CONCLUSION There are many risk points and failures for transfusion and infusion warmers, so enterprises should improve processes and quality control to address risks, and medical institutions should formulate specifications and maintenance plans to provide targeted theoretical basis for supervision.
Blood Transfusion/instrumentation* ; Risk Factors ; Quality Control ; Humans ; Risk Management ; Equipment Failure

Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective:To evaluate the specific changes and importance of the proportions of the eyebrows and eyes after surgery by analyzing and measuring the changes of the values of the eyebrows and eyes in elderly patients with aponeurotic ptosis before.Methods:A total of 54 cases (108 eyes) of elderly patients with aponeurotic ptosis who were treated in our department from 2019.01 to 2020.12 were collected preoperatively and 6 months postoperatively, and they were set as the study group. At the same time, the data of 48 cases (96 eyes) of healthy people with good face were collected and set as the young control group, and the data of 50 cases (100 eyes) of elderly healthy people without ptosis were collected and set as the elderly control group. The corresponding objective data were analyzed, and the specific changes and proportional relationship of eyebrows and eyes after surgery were evaluated.Results:Compared with the preoperative data, the marginal reflex distance 1 (MRD1), the height of the palpebral fissure (HPF) in the study group increased at 6 months after the operation, and the distance between the eyebrow and eye at each site increased or shortened ( P<0.05). Six months after the operation, the brow height from medial canthus (MBH), the central brow and eye distance (brow height from upper eyelid margin on midpupillary level, CBH), and the lateral brow and eye distance (brow height from lateral, LBH) had been changed. The change rates of canthus compared with preoperatively were that (88.29±11.69)%, (85.04±14.96)%, and (93.61±13.56)%, respectively, among which CBH shortened most significantly, and the shortened distance was (3.76±2.43) mm. The MRD1 and HPF in the group increased significantly at 6 months after operation, which were significantly greater than those in the elderly control group ( P<0.05). CBH was significantly shortened ( P<0.05); compared with preoperative, the ratio of HPF/CBH, HPF/length of the palpebral fissure (LPF) in the study group increased at 6 months after operation, and the lateral canthus brow tail line [ratio of lateral canthus to lateral end of eyebrow (LLE)]/LPF decreased ( P<0.05); HPF/CBH in the study group was lower than that in the young control group at 6 months after operation, but greater than that in the elderly control group ( P<0.05). Monthly HPF/LPF was significantly higher than that of the elderly control group ( P<0.05), and the LLE/LPF of the study group was significantly higher than that of the young control group at 6 months after operation ( P<0.05); intraoperative levator muscle shortening (LMS) was negatively correlated with postoperative MBH, CBH and LBH ( P<0.05), among which LMS had the greatest correlation with CBH ( r=-0.587). Conclusions:After ptosis correction, the palpebral fissures are larger, the distance between the eyebrows and the eyes is shortened, and there is a certain proportional relationship. After surgery, the patient's eyebrow-eye ratio is better than that of the elderly in the same age group, and it is closer to the young people, and the intraoperative LMS has a correlation with the eyebrow-eye distance, which can be used as a factor to predict the shortened distance of the eyebrow-eye distance.

Carcinoma ; Carcinoma, Papillary ; Humans ; Thyroglossal Cyst/surgery* ; Thyroid Neoplasms