Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the efficacy of computed tomographic angiography (CTA) three-dimensional reconstruction technology in the repair of limb wounds using free double-leaf anterolateral thigh perforator flaps.Methods:A retrospective analysis was conducted on 30 patients with varying degrees of skin damage on their limbs who were admitted to the Hand and Foot Surgery Department of Yiwu Central Hospital in Zhejiang Province and Zhejiang Provincial People's Hospital from January 2015 to March 2022. The patients were divided into observation group ( n=15) and control group ( n=15) based on whether CTA three-dimensional reconstruction was performed preoperatively. In the observation group, CTA three-dimensional reconstruction was performed preoperatively, including 9 males and 6 females, aged 17-67 (49.7±4.2) years. In the control group, handheld Doppler ultrasound angiography was performed preoperatively, including 10 males and 5 females, aged 20-69 (50.4±5.0) years. Relevant intraoperative and postoperative indicators were compared between the two groups, including operation duration, anesthesia recovery time, blood loss, perforator localization accuracy, vascular anastomosis rate between the donor and recipient sites, flap harvesting time, flap survival rate, and incidence of adverse reactions. Follow-up visits were conducted via telephone or outpatient clinic for 3 months postoperatively, with one visit per month, to assess patient satisfaction rates. A multi-criteria decision-making model was established, and the benefit values, risk values, and stability of the decision-making model were evaluated for both groups. Results:Compared with the control group, the observation group had significantly reduced operation duration, anesthesia recovery time, blood loss, and flap harvesting time (all P<0.05). The patient satisfaction rate, perforator localization accuracy, and vascular anastomosis rate between the donor and recipient sites were significantly better in the observation group than in the control group (all P<0.05). The incidence of adverse reactions was 13.3% (2/15) in the observation group, which was lower than 53.3% (8/15) in the control group ( P=0.020). Among the benefit indicators, the vascular anastomosis rate between the donor and recipient sites and flap survival rate had the greatest impact on treatment outcomes. Among the risk indicators, venous crisis and flap necrosis had a greater impact. The benefit-risk value was 77 in the observation group and 56 in the control group, with a difference of 21 (95% CI: 14-26) between the two groups. The observation group had higher values than the control group within the range of 0-100% relative risk weight, indicating good stability of the multi-criteria decision-making evaluation model. Conclusion:CTA three-dimensional reconstruction technology can improve the vascular anastomosis rate between the donor and recipient sites and patient satisfaction rates in the repair of limb wounds using free double-leaf anterolateral thigh perforator flaps.

Objective:To investigate the genetic causal relationship of leukocyte telomere length(LTL)with prostatitis,orchi-tis and epididymitis by two-sample Mendelian randomization(MR).Methods:Using LTL as the exposure factor and prostatitis,or-chitis and epididymitis as outcome factors,we mined the Database of Genome-Wide Association Studies(GWAS).Then,we analyzed the causal relationship of LTL with prostatitis,orchitis and epididymitis by Mendelian randomization using inverse variance weighting(IVW)as the main method and weighted median and MR-Egger regression as auxiliary methods,determined the horizontal multiplicity by MR-Egger intercept test,and conducted sensitivity analysis using the leaving-one-out method.Results:A total of 121 related sin-gle nucleotide polymorphisms(SNPs)were identified in this study.IVW showed LTL to be a risk factor for prostatitis(OR=1.383,95％CI:1.044-1.832,P=0.024),and for orchitis and epididymitis as well(OR=1.770,95％CI:1.275-2.456,P=0.000 6).Conclusion:Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis,orchitis and epididymitis.