Objective: To statistically analyze the association between blood donation intervals and the incidence of adverse reactions to blood donation based on blood donor data from Shenzhen. Methods: Basic data and records of adverse reactions to blood donation among voluntary whole blood donors in Shenzhen from January 2017 to June 2025 were extracted. A total of 795 404 whole blood donations were recorded, including 502 743 from males and 292 661 from females, with 1 088 and 751 cases of adverse reactions, respectively. Analyses were performed using R software, including restricted cubic spline (RCS), binary logistic regression, and generalized estimating equations (GEE) to evaluate the correlation between donation intervals and adverse reactions. Results: A total of 1 839 cases of adverse reactions were recorded, accounting for 0.23% of the total donations. Both binary logistic regression analysis and the generalized estimating equations (GEE) model showed that there was no significant difference in the incidence of adverse reactions between male and female donors with an interval of ≥6 months compared to those with an interval of ≥3 months but<6 months. Furthermore, using the 3-5 month interval group as the reference, the analysis indicated that the incidence of adverse reactions significantly increased in males with a 9-12 month interval, while no statistically significant differences were observed across any of the female subgroups. Conclusion: There was no significant correlation between adverse reactions to blood donation and the donation interval. Compared with a donation interval of ≥6 months, an interval of<6 months does not lead to an increase in the incidence of adverse reactions among male or female donors. The findings of this study may help enhance the willingness of blood donors to participate.

Objective: To statistically analyze the association between blood donor age and the incidence of adverse reactions based on whole blood donor data from Shenzhen. Methods: Data on basic characteristics and records of adverse donation reactions among voluntary whole blood donors in Shenzhen from January 2017 to June 2025 were extracted. A total of 795 404 whole blood donations were recorded, including 502 743 from males and 292 661 from females, with 1 088 and 751 cases of adverse reactions, respectively. Analyses were performed using R software, including restricted cubic spline (RCS) analysis, binary logistic regression, and generalized estimating equations (GEE) to evaluate the correlation between donor age and adverse reactions. Results: A total of 1 839 cases of adverse reactions were recorded, accounting for 0.23% of the total donations. Both binary logistic regression and GEE model revealed that, compared with the≤55 years age group, the incidence of adverse reactions was reduced in both male and female donors in the >55 years age group, with the difference being statistically significant in males. Using the <23 years age group as a reference, the incidence of adverse reactions significantly decreased in both male and female donors across the 23-30, 31-40, 41-50, and 51-60 age groups, with the differences being statistically significant. Conclusion: There is a negative correlation between the rate of adverse donation reactions and age, with the incidence of such reactions among whole blood donors over 55 years old being no higher than that among donors aged 55 years or younger. These findings carry positive significance for safeguarding the donation rights of older donors and meeting clinical blood demand.

Objective To clarify the role and underlying mechanism of macrophage-to-myofibroblast transition (MMT) in renal fibrosis that develops after acute kidney injury (AKI) induced by ischemia-reperfusion injury (IRI). Methods Mouse AKI model was generated by renal ischemia-reperfusion. Animals were randomized into control (Con), sham operated (Sham), and IRI groups sacrificed at 1 d (IRI 1 d), 3 d (IRI 3 d) and 14 d (IRI 14 d) after reperfusion (n = 5). Renal injury was assessed by renal coefficient, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1). Periodic acid-Schiff (PAS) staining was used to evaluate tubular damage and inflammatory infiltration. Masson staining and immunohistochemistry were employed to quantify collagen deposition, α-smooth muscle actin (α-SMA) and type I collagen (COL I). Flow cytometry was used to determine macrophage infiltration and phenotype. MMT was identified by flow cytometry plus immunofluorescence. Transforming growth factor (TGF)-β1/Smad3 pathway proteins were examined by Western blotting. Results Compared with Sham group, renal coefficient, Scr and KIM-1 rose in IRI 1 d group, renal coefficient and KIM-1 remained elevated in IRI 3 d group. Compared with the IRI 1 d group, the renal coefficient and KIM-1 decreased in the IRI 14 d group. Compared with the IRI 3 d group, the renal coefficient, Scr and KIM-1 decreased in the IRI 14 d group (all P < 0.05). PAS revealed the most severe tubular injury at IRI 3 d. Masson staining showed progressively increasing collagen deposition, while immunohistochemistry demonstrated α-SMA and COL I rising from day 1 and persisting to day 14 (all P < 0.05). Macrophage infiltration increased from day 1 and lasted to day 14 (P < 0.05). M1 macrophages peaked at day 1 then declined, whereas M2 macrophages increased at day 3 and remained high through day 14 (P < 0.05). MMT began to rise at day 3 and continued to day 14 and M2 macrophages were the predominant source of MMT cells (all P < 0.05). Compared with Sham group, TGF-β1 protein was up-regulated and p-Smad3/Smad3 ratio was elevated in all IRI groups (all P < 0.05). Conclusions M2 macrophages promote post-IRI-AKI renal fibrosis via MMT, a process closely linked to activation of the TGF-β1/Smad3 signaling pathway.

Objective To explore the effect and mechanism of Gegen Qinlian decoction (GQD) on myocardial injury induced by high-fat diet combined with streptozotocin in type 2 diabetic mice through network pharmacology and animal experiments. MethodsNetwork pharmacology was applied to screen the potential signaling pathways of GQD in the intervention of diabetic heart disease (DHD). A total of 36 specific pathogen-free (SPF) male C57BL/6J mice aged 8 weeks were acclimatized for 1 week and randomly divided into a normal control group (n=6) and a model group (n=30). Mice in the model group were fed a 60% high-fat diet and 5% glucose water for 4 weeks, and were intraperitoneally injected with 100 mg/kg streptozotocin after 12 h of fasting to establish the type 2 diabetes model. Mice in the normal control group were given a conventional diet and drinking water, and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model, the model mice were randomly divided into five groups according to body weight: model control group, GQD low-dose group, GQD medium-dose group, GQD high-dose group, and metformin positive control group, with 6 mice in each group. After 6 weeks of intragastric administration of corresponding doses of GQD, metformin, and ddH₂O respectively, all mice in the six groups (one normal control group and five model groups) were anesthetized with inhaled 2% isoflurane, blood samples were collected via eyeball enucleation, and heart tissues were harvested after euthanasia by cardiac exsanguination. Hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining were performed to observe the pathological damage of myocardial tissues and measure the cross-sectional area of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines in serum. Immunohistochemical staining was adopted to determine the protein expression levels of receptor for advanced glycation end products (RAGE), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), and phosphorylated nuclear factor-κB p65 (p-p65) in myocardial tissues. ResultsNetwork pharmacology analysis revealed that the targets of GQD against DHD were significantly enriched in inflammatory pathways, including the advanced glycation end products (AGEs)-RAGE axis, tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. HE and WGA staining results showed that, compared with the normal control group, the model control group exhibited myocardial fiber rupture, cardiomyocyte swelling, and significantly increased cardiomyocyte cross-sectional area (P<0.05). Compared with the model control group, GQD intervention significantly ameliorated the pathological changes, including myocardial fiber rupture, cell swelling, and cardiomyocyte hypertrophy. The results of immunohistochemical staining and ELISA indicated that compared with the model control group, GQD intervention markedly downregulated the protein expression of RAGE, NLRP3, and p-p65 in myocardial tissues, as well as the levels of serum pro-inflammatory cytokines (P<0.05). ConclusionGQD can effectively alleviate myocardial pathological injury in diet-induced type 2 diabetic mice, and its mechanism may be related to inhibiting the activation of the RAGE/p-p65/NLRP3 signaling pathway and reducing myocardial inflammatory response.

BACKGROUND:Liuwei Dihuang Wan takes"three tonifying and three reducing effects"as its compatibility feature to nourish yin and tonify the kidneys,while Zuogui Wan takes"seeking yin in yang"as its compatibility feature to nourish yin and tonify the kidneys by promoting yang.Both of them belong to the same method of nourishing yin and tonifying the kidneys,and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE:To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism,and to explore their mechanism of action in the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)osteoblastic pathway. METHODS:Thirty-two Sprague-Dawley rats were randomized into model,Liuwei Dihuang Wan,Zuogui Wan,and sham operation group,with eight rats in each group.Osteoporosis models were prepared using removal of both ovaries in the first three groups.Starting at 30 days postoperatively,rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d;rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d;and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d.After 12 weeks of gavage,the rat tibia was taken to measure bone mineral density.The serum levels of estrogen,bone alkaline phosphatase,and cAMP/cGMP were measured using ELISA,and the expression of OPG/RANKL in the femur was detected using western blot. RESULTS AND CONCLUSION:Compared with the sham operation group,the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase(P＜0.05)and an increase in cAMP/cGMP level(P＜0.05).Compared with the model group,the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density(P＜0.05)and bone alkaline phosphatase levels(P＜0.05);the Zuogui Wan group significantly decreased cAMP/cGMP levels(P＜0.05)and upregulated OPG expression(P＜0.05);the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression(P＜0.05);and both groups were unable to significantly increase estrogen levels(P＞0.05).To conclude,Zuogui Wan,which seeks yin from yang,can effectively increase the expression of OPG but cannot downregulate the expression of RANKL.However,Liuwei Dihuang Wan,which has three tonifying and three reducing effects,can bidirectionally regulate the expression of OPG and RANKL.This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan,and further research is needed to verify this conclusion.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Objective:To evaluate the efficacy of dexzopiclone combined with repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders (PSSD) and its effects on sleep electroencephalography and neuroelectrophysiological parameters.Methods:180 PSSD patients admitted to Yulin First Hospital (December 2019-December 2020) were randomized into medication group ( n=90, dexzopiclone) and rTMS group ( n=90, dexzopiclone+rTMS). Outcomes included clinical efficacy, sleep quality [Pittsburgh Sleep Quality Index (PSQI), Self-Rating Scale for Sleep (SRSS)], electroencephalogram parameters [sleep latency (SL), total sleep time (TST), sleep efficiency], neuroelectrophysiological indices [bilateral motor thresholds], biochemical markers [S100β protein, brain-derived neurotrophic factor (BDNF)], adverse reactions, and 1-year recurrence rate. Results:After treatment, the rTMS group had a significantly higher efficacy (92.22%, 83/90) compared to the medication group (81.11%, 73/90) ( χ2=4.81, P=0.028). Compared to post-treatment, PSQI decreased to [7.47 (6.63,8.69) points vs. 13.56 (3.15,19.51) points] in the rTMS group and [9.56 (8.59,11.11) points vs. 14.01 (2.58,20.55) points] in the medication group ( U=8.82, 8.38; both P<0.001). SRSS scores decreased to [(15.23±2.88) points vs. (28.81±4.99) points) ( t=32.74, P<0.001) and (19.54±3.59) points vs. (28.15±4.71) points) ( t=19.68, P<0.001)], respectively. Compared to before treatment, the rTMS group had lower scores than the medication group ( U=7.80, t=8.88; P<0.01). SL reduced to (27.65±5.12) min vs. (44.92±8.21) min ( t=24.58, P<0.001) in rTMS group and (38.78±6.34) min vs. (45.23±8.56) min ( t=8.24, P<0.001) in medication groups. TST increased to (348.50±56.27) min vs. (299.21±52.14) min ( t=8.63, P<0.001) and (311.42±55.39) min vs. (275.65±52.23) min ( t=6.31, P<0.001), sleep efficiency improved to (70.96±12.33%) vs. (57.43±10.98%) ( t=11.01, P<0.001) and (62.37±11.28%) vs. (56.78±10.72%) ( t=4.82, P<0.001), while the rTMS group showed greater improvement ( t=4.46, 4.88; P<0.001). Compared to before treatment, left motor thresholds decreased to (55.65±2.48)% vs. (64.37±3.12)% and (61.76±3.17)% vs. (65.12±3.45)% post-treatment ( t=29.54, 9.63; P<0.001), with significant intergroup differences ( t=14.40, P<0.001). Right motor thresholds decreased to (56.28±3.45)% vs. (67.42±3.61)% and (60.89±3.39)% vs. (66.62±3.54)% ( t=29.94, 15.69; P<0.001), with intergroup differences ( t=9.04, P<0.01). Compared to before treatment, serum S100β levels decreased in both group post-treatment (23.65±3.23) ng/L vs. (65.37±7.89) ng/L and (29.76±3.61) ng/L vs. (63.48±7.34) ng/L ( t=71.19, 58.43; P<0.001), with lower levels in the rTMS group ( t=11.97, P<0.001). Compared to before treatment, BDNF increased to (554.48±69.78) ng/L vs. (502.82±64.11) ng/L and (524.90±67.66) ng/L vs. (505.12±64.45) ng/L post-treatment ( t=7.32, 2.84; P=0.001, 0.030), with higher levels in the rTMS group ( t=2.89, P=0.004). Adverse reaction rates were 4.44% (4/90) and 3.33% (3/90), respectively ( χ2=0.15, P=0.700). Recurrence rates were 1.18% (1/85) in the rTMS group and 3.90% (3/77) in the medication group ( χ2=0.37, P=0.544). Conclusion:The combination of dexzopiclone and repetitive transcranial magnetic stimulation (rTMS) demonstrates significant advantages and efficacy in treating post-stroke sleep disorders (PSSD). This approach comprehensively improves patients' sleep quality, EEG parameters and neuroelectrophysiological indicators while enhancing the regulatory effects of brain-derived neurotrophic factor (BDNF). Additionally, the therapy exhibits a favorable safety profile and prognosis.

Pancreatic β-cell dysfunction is a critical factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Recent studies have identified iron overload as a significant risk factor for T2DM, wherein excess iron contributes to β-cell dysfunction through multiple pathways, including oxidative stress, mitochondrial dysfunction, and a reduction in the number of pancreatic β-cells.These mechanisms adversely affect insulin synthesis, secretion, and release.This review aims to summarize the recent advancements in understanding the relationship between iron overload and pancreatic β-cell dysfunction.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Granulomatous vasculitis is a kind of necrotizing granulomatous vasculitis with the prominent feature of detectable anti-neutrophil cytoplasmic antibodies in serum, which often involves the respiratory tract and kidneys, and the onset of symptoms in the digestive tract is rare, and we now report a rare case of granulomatous vasculitis in which the gastrointestinal tract was involved as the first symptom in order to improve the clinician's understanding of this disease.