ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

Renal interstitial fibrosis （RIF） is a common pathological change process from the development of various chronic nephropathies to the end stage， and it is an important histological manifestation of renal function decline. At present， no effective anti-fibrosis drugs have been found in clinical practice. In recent years， with the continuous development of traditional Chinese medicine （TCM） pharmacology， molecular biology， system biology， and network pharmacology， the research on regulating RIF with TCM monomer， single TCM， TCM compound， Chinese patent medicine， and TCM injection is deepening. Among them， Jianpi Yishen recipe， Shendi Bushen capsules， Jianzhong Bushen Xiaozheng decoction， Liuwei Dihuangtang， and Lycium barbarum polysaccharides can regulate transforming growth factor-β/small mother against decapentaplegic （TGF-β₁/Smads）， Wnt/β-catenin， and neurogenic locus notch homolog protein （Notch） signaling pathways. Wulingsan， Zhenwutang， pachymic acid ZA， pachymic acid ZC， and pachymic acid ZD， which mainly induce diuresis， can regulate the Wnt/β-catenin signaling pathway. Hirudin， curcumin， and Fuzheng Huayu recipe， which mainly promote blood circulation， can inhibit inflammation-related pathways such as p-nuclear transcription factor-κB （NF-κB）， Toll-like receptor 4/p-nuclear transcription factor-κB （TLR4/NF-κB）， and Janus kinase 2/signal transducer and activator of transcription 3 （JAK/STAT）， so as to achieve anti-inflammatory and anti-oxidation effects and alleviate the progression of RIF. Shenshuai Xiezhuo decoction， Shenkang injection， and Shenshuai recipe， which are mainly used for invigorating Qi， removing blood stasis， and removing turbidity， can inhibit transdifferentiation of pericytes-myofibroblasts through vascular endothelial growth factor receptor （VEGFR） signaling pathway. At present， there are many studies on the regulation of the RIF signaling pathway by TCM， but there is a lack of a systematic summary. In this study， by combing the signaling pathway of TCM in the treatment of RIF， the effective target of TCM treatment is screened， and its possible mechanism is found， which provides new ideas for clinical treatment and new drug research and development.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Cerebral hyperperfusion syndrome (CHS) is a rare but serious complication after cerebral revascularization, which may lead to catastrophic consequences. The mechanism of CHS is not fully understood, and it may be related to cerebral autoregulation dysfunction and the increase of blood pressure after operation. Timely detection and treatment of cerebral hyperperfusion can avoid CHS. This article reviews the pathogenesis, diagnosis, clinical manifestations, prevention and treatment of CHS.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective:To survey the child health service capacity of community health service institutions in Shenzhen city.Methods:This was a cross-sectional study. An online survey was conducted among 559 community health service centers, stations and clinics in Shenzhen from January 23, 2024 to February 3, 2024. The questionnaire contents included the development of child health management, vaccination, diagnosis and treatment of common diseases in children, management of children′s chronic diseases, appropriate technology, availability of children′s special drug dosage forms, provision of special Chinese patent medicine and appropriate technology of traditional Chinese medicine for children, referral and remote consultation in 2019 and 2023. The reasons of unavailable service items were asked in the questionnaire and the questionnaire also contained an open-ended question about the suggestions for improving the capacity of child health services.Results:A total of 559 valid questionnaires were collected, accounting for 64.48% (559/867) of the community health service centers, stations and health clinics in Shenzhen in 2023. Compared to 2019, there was a significant increase in the rate of pediatric health services provided in 2023, including the diagnosis and treatment of common diseases in children under 6 years (96.06%, 537 institutions), nebulized inhalation therapy (96.60%, 540 institutions), influenza and other respiratory pathogen detection (90.70%, 507 institutions), rotavirus and other intestinal pathogen detection (34.53%, 193 institutions), allergen detection (81.75%, 457 institutions), blood oxygen saturation monitoring (84.44%, 472 institutions), pediatric-specific formulations of Western medicine (90.52%, 506 institutions), pediatric-specific formulations of traditional Chinese medicine (89.27%, 499 institutions), appropriate Chinese medicine techniques (88.19%, 493 institutions), relatively fixed referral hospitals (95.17%, 532 institutions), and remote consultation service (19.14%, 107 institutions); and the differences were statistically significant ( P<0.01). The reasons for unavailable service items were lack of space and personnel for the basic public health services, lack of space, personnel and a deficiency in knowledge and technical capabilities for diagnostic tests, and lack of equipment and personnel for remote consultation service. Suggestions made by 394 respondent institutions (70.48%) for further improvement included: conducting and strengthening various training (44.42%, 175/394), consultation and teaching by expert visiting (18.53%, 73/394), increasing the space and equipment (9.39%, 37/394), and further study at higher-level units (98.88%, 35/394). Conclusions:The child health services have been greatly improved in community health service institutions in Shenzhen, but there are still rooms for further improvement such as the ability of child health management, vaccination, chronic disease managements and provision of remote consultation.

Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.

Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

Objective:To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in patients with mild carotid artery stenosis.Methods:A retrospective study was conducted to select 30 cases of patients with unilateral mild carotid artery stenosis and moderate intensity aerobic exercise for more than 1 year in the Central Hospital of Dalian University of Technology from July 2022 to November 2023 as the exercise group (study group), and 30 cases of patients with unilateral mild carotid artery stenosis without exercise habits matched by age, gender and other factors as the non-exercise group (control group). Transcranial Doppler ultrasound (TCD) examination was performed in both groups, and the recumbent-upright-test, breath holding test and breath exchange test were performed to calculate the occurrence rate of "w" wave in recumbent-upright position, the slope of "w" wave in recubitus position, the change rate of pulse index (PI) before and after breath holding, resistance index (RI), breath holding index (BHI), and cerebral blood flow velocity before and after breath exchange. The blood pressure and heart rate difference in the recumbent-upright position were calculated, and the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation function in patients with mild carotid artery stenosis was evaluated by statistical analysis. The correlation analysis between the exercise years and BHI in the study group was carried out to explore the relationship between the exercise years and cerebrovascular reactivity.Results:The occurrence rate and slope of "w" wave in the study group were higher than those in the control group: 93.3%(28/30) vs. 86.7%(26/30), 2.27 ± 1.14 vs. 1.28 ± 0.23, 2.67 ± 0.63 vs. 1.41 ± 0.69, there were statistically significant ( P<0.05). The change rates of PI and RI before and after breath holding and ventilation in the study group were higher than those in the control group: 21.23 ± 7.67 vs. 13.89 ± 9.67, 14.62 ± 6.63 vs. 11.17 ± 1.78 and 26.26 ± 12.46 vs. 18.36 ± 12.13, 14.91 ± 4.91 vs. 10.83 ± 2.35, and the average cerebral blood flow velocity before and after ventilation was higher than that in the control group: (31.26 ± 4.92) cm/s vs. (24.89 ± 6.34) cm/s, there were statistically significant ( P<0.01). The exercise years of the study group was negatively correlated with the breath holding index. Conclusions:Moderate intensity exercise is associated with cerebral blood flow regulation in patients with mild carotid artery stenosis. Exercise years are negatively correlated with cerebral blood flow regulation. Impaired cerebral blood flow regulation may be one of the potential mechanisms of poor prognosis of stroke in carotid artery stenosis population.

Objective:To perform optical surface monitoring-based three-dimensional (3D) in vivo dose verification for patients with left breast cancer undergoing deep inspiration breath-hold surface-guided radiation therapy (DIBH-SGRT) and to investigate the dosimetric differences in the target volumes and related factors affecting γ pass rates. Methods:Totally 20 patients with left breast cancer who received DIBH-SGRT at the Department of Radiation Oncology, Women′s Hospital, School of Medicine, Zhejiang University were selected. The optical surface monitoring-based intrafractional displacement deviations of the patients during DIBH were recorded. Meanwhile, electronic portal imaging device (EPID)-based in vivo dosimetry (EIVD) verification was performed for patients during the DIBH-SGRT, and γ pass rates were measured with the criteria of 2 mm/2%, 3 mm/3%, and 3 mm/5%. The dosimetric differences between planning target volumes (PTVs) and organs at risk (OARs) were analyzed based on dose-volume histograms (DVHs). Furthermore, Pearson correlation analysis was employed to determine the correlation of three γ pass rates with dosimetric differences and displacement deviations. Results:The average pass rates with the criteria of 2 mm/2%, 3 mm/3%, and 3 mm/5% were determined at 73.43%, 86.00%, and 92.96%, respectively, and the average deviations between EIVD measured doses and planned doses in PTV_TB and PTV Dmean were proved to be 0.23% and 0.59%, respectively ( P > 0.05). Pearson analysis revealed that the γ pass rates exhibited a weak correlation with dosimetric differences in PTVs( R<0.7) but strong correlations with intrafractional displacement deviations in Lat and Vert directions during DIBH ( R > 0.7). Conclusions:EIVD verification can ensure the high accuracy of dose delivery in PTVs during DIBH-SGRT for left breast cancer. Additionally, the EIVD verification system has the potential to detect displacement deviations during breath holding.