ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

Objective:To understand the knowledge, attitudes, and behaviors of residents in areas endemic for severe fever with thrombocytopenia syndrome (SFTS) and the factors influencing these aspects, to provide a scientific basis for the prevention and control of SFTS among residents in endemic areas.Methods:A multi-stage sampling method was used to select subjects for a questionnaire survey, and the collected data were analyzed and compared.Results:The awareness rate of SFTS-related knowledge among residents in the endemic areas of Qingdao was 14.38%, while the awareness rate of tick-related knowledge was 69.78%. The mean score for protective attitudes among residents in the endemic areas was 24.50±4.09, and the mean score for protective behaviors was 11.20±2.76. Among residents of different ages, occupations, and educational levels, comparisons of SFTS-related knowledge awareness rates ( χ2=293.553, P<0.001; χ2=495.216, P<0.001; χ2=677.272, P<0.001), tick-related knowledge awareness rates ( χ2=29.986, P<0.001; χ2=23.239, P=0.002; χ2=41.003, P<0.001), protective attitude scores ( H=52.094, P<0.001; H=33.446, P<0.001; H=81.715, P<0.001), and protective behavior scores ( H=52.344, P<0.001; H=28.465, P<0.001; H=67.061, P<0.001) showed statistically significant differences. Comparisons of these same factors among residents of different genders showed no statistically significant differences ( χ2=1.159, P=0.282; χ2=0.298, P=0.585; t=-0.808, P=0.419; t=-1.229, P=0.219). Comparisons of tick-related knowledge awareness rates among residents with different frequencies of outdoor work showed no statistically significant differences ( χ2=5.367, P=0.147); however, comparisons of SFTS-related knowledge awareness rates, protective attitude scores, and protective behavior scores among residents with different frequencies of outdoor work showed statistically significant differences ( χ2=117.010, P<0.001; F=4.127, P=0.006; H=56.280, P<0.001). Multivariate linear regression analysis revealed that older age, lower educational level, and less frequent outdoor work were associated with lower protective behavior scores ( t=-3.479, P<0.001; t=4.861, P<0.001; t=-7.753, P<0.001). Conclusions:Residents in the epidemic areas of SFTS have a low level of knowledge, attitude and practice. Factors influencing protective behaviors include age, occupation, educational level, and frequency of outdoor work. Farmers are a group that requires particular attention.

Objective:To design and develop a cone-beam CT imaging system for small animals with continuously adjustable spatial resolution.Methods:The imaging system used an X-ray source with a focal spot size of 30 μm and a flat panel detector with a pixel size of 100 μm. On this premise, a " stepping-focusing-rotating" image acquisition mode was proposed, in which the " focusing" and " stepping" systems were sequentially embedded in the " rotating" system. In this acquisition mode, the X-ray source and flat panel detector were relatively stationary to form the " focusing" system. When the " stepping" system accurately transported the object to the scanning position, the " focusing" system could achieve adjustable spatial resolution by making linear motion around the object to be scanned according to different experimental requirements. Finally the " rotating" system achieve high-quality imaging.Results:The variable spatial resolution of small animal CBCT ranges from 35.7 μm to 71.4 μm, and the FOV ranges from 39.6 mm to 108.0 mm. The conversion time for the limit spatial resolution is 19.125 s, which allowed accurate 3D reconstruction of normal mice at different resolutions with high reproducibility.Conclusions:A cone-beam CT suitable for small animals has been developed, whose spatial resolution and FOV can be adjusted arbitrarily within a certain range, which can meet the different imaging requirements in rodent experiments.

Objective:To investigate the effectiveness of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision in the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ.Methods:A retrospective case series study was conducted to analyze the clinical data of the 18 patients who had been treated at Department of Minimally Invasive Orthopedics, Zhengzhou Orthopaedic Hospital from February 2020 to July 2023 for chronic Achilles tendon rupture of Myerson type Ⅲ by means of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision. There were 15 males and 3 females, with an age of (37.2±6.8) years. All patients suffered from unilateral injury, involving 13 left sides and 5 right sides. Their body mass index was (22.6±2.5) kg/m 2. The operation time, blood loss, incision length, wound healing and complications were documented. The ankle dorsiflexion and plantar flexion at the last follow-up were compared between the affected side and the healthy side. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) before operation were compared with those at the last follow-up. Results:All the 18 patients were followed up for (18.0±5.5) months. Their operation time was (69.1±5.2) minutes, blood loss (71.6±9.2) mL, incision at the broken end of the Achilles tendon (12.4±2.6) cm and incision at the proximal end (2.5±0.4) cm. At the last follow-up, the ankle dorsiflexion was 12.7°±1.9° and the ankle plantar flexion 35.2°±2.0° at the affected side, showing no significant difference from those at the healthy side (13.0°±2.1° and 34.7°±1.8°) ( P>0.05). The AOFAS ankle-hindfoot score was (89.4±3.4) points and the ATRS (85.3±3.2) points for the affected side at the last follow-up, showing significant improvements compared with the preoperative values [(54.2±4.2) points and (51.1±4.6) points] ( P<0.05). All the incisions healed at one stage after operation, with no such complications as incision infection or re-rupture of the Achilles tendon. One patient experienced mild pain at the anchor insertion site, but the pain disappeared 6 months after operation without any treatment. One patient had the symptoms of sural nerve injury which responded to 3 months of oral neurotrophic medication. Conclusion:In the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ, gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision can result in limited invasion, a low incidence of complications, and definite effectiveness.

Systemic sclerosis is an autoimmune rheumatic disease that often leads to multisystem diseases,frequently resulting in pulmonary interstitial fibrosis.According to the theory of sanjiao(triple energizers)membranous channels,sanjiao connects the five zang-organs and six fu-viscera internally and the skin,muscles,and bones externally.It serves as a four-way membranous channel that connects internal organs and external structures,linking with the micromembranes of organs and blood vessels.The pathogenesis of pulmonary interstitial fibrosis secondary to systemic sclerosis involves external cold obstructing the skin and interstitial layers,impairing the defense qi and defense yang,which originate in the essence of the kidney.This leads to weak defensive qi and kidney deficiency,causing stagnation in sanjiao's energy flow and disruption of water and gasification and loss of fluid,resulting in accumulation of dampness,phlegm,and blood stasis.These obstructive factors spread along sanjiao's membranous channels,leading to multiorgan micromembrane involvement and systemic damage.The lungs,which are in direct contact with the external environment,are particularly susceptible to invasion by external pathogens.When combined with stagnation of dampness,phlegm,and blood in the lungs,this leads to secondary pulmonary fibrosis,resulting in lung dysfunction.Continuous stagnation of sanjiao exacerbates the overall condition of the patient,leading to a mixed cold-heat imbalance.Treatment focuses on"unblocking,transforming,and regulating"to restore sanjiao function,promote qi and fluid circulation,invigorate blood,and adjust the cold-heat imbalance,ultimately restoring the overall condition of the patient.

Objective To observe the efficacy and safety of Yifei Sanjie Decoction in the treatment of multiple pulmonary nodules.Methods A prospective randomized controlled clinical study was conducted to select 189 patients with multiple pulmonary nodules who saught medical attention at the Pulmonary Nodule Diagnosis and Treatment Center of Dongfang Hospital,Beijing University of Chinese Medicine and the Department of Thoracic Surgery of Beijing Shijitan Hospital Affiliated to Capital Medical University from January 2023 to March 2025.According to the random number table method,126 cases were randomly divided into the trial group and 63 cases in the blank control group at a ratio of 2∶1.The trial group was treated with modified Yifei Sanjie Decoction,and the blank control group was only followed up without intervention.The course of treatment was 3 months.The patients in the two groups were reexamined with lung CT after 3 months.The efficacy was evaluated by the area reduction rate of the major pulmonary nodules and the cumulative multiple pulmonary nodules in patients with multiple pulmonary nodules combined with the average diameter and malignant signs.According to the property of the major pulmonary nodules,we divided the patients into ground glass,solid,and mixed ground glass subgroups to evaluate the efficacy of different types of pulmonary nodules.We evaluated the change of malignant risk of pulmonary nodules according to the change of Mayo score.We evaluated the safety of the treatment medicine by blood routine,urine routine,and liver and kidney function.Results A total of 175 patients completed the study,117 in the trial group and 58 in the blank control group.The total effective rates of the major pulmonary nodules and the cumulative multiple pulmonary nodules in the trial group were 41.03%and 42.74%,respectively,the total effective rate of nodule number change was 29.91%which were significantly higher than those in the blank control group(P<0.05).In the trial group,the total effective rates of the major pulmonary nodules in the ground glass(72 cases),solid(28 cases),and mixed ground glass(17 cases)subgroups were 40.28%,32.14%,and 58.82%,respectively,the total effective rates of the cumulative multiple pulmonary nodules were 38.89%,42.86%,and 58.82%,respectively,which were significantly higher than those in corresponding subgroups of ground glass(37 cases),solid(14 cases),and mixed ground glass(7 cases)of the blank control(P<0.05).After treatment,the average diameter,area,and Mayo score of the major pulmonary nodules and the cumulative multiple pulmonary nodules in the trial group were significantly lower than those in the blank control group and before treatment(P<0.05),the average diameter,area,and Mayo score of the major pulmonary nodules and the cumulative multiple pulmonary nodules in the ground glass,solid,and mixed ground glass subgroups were lower than those in corresponding subgroups of the blank control group,and significantly lower than those before treatment(P<0.05).The number of nodules and malignant signs in the trial group were lower than before,while those in the blank control group were higher than before.There were no serious adverse events in the two groups during the study.Conclusion Yifei Sanjie Decoction can effectively treat the major pulmonary nodules and the cumulative multiple pulmonary nodules in patients with multiple pulmonary nodules,reduce the average diameter and area of nodules,reduce the Mayo score,and reduce the malignant signs and number of nodules.In the ground glass,solid,and mixed ground glass groups,the curative effect is well,and the safety is high,it can be used for the clinical treatment of multiple pulmonary nodules.

Objective:To comprehensively retrieve and evaluate the best available evidence on perioperative fluid management in patients undergoing hepatectomy for liver cancer, and to provide references for clinical practice.Methods:A systematic search was conducted across multiple platforms, including UpToDate, BMJ Best Practice, Guidelines International Network, National Institute for Health and Care Excellence, PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data, for clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and randomized controlled trials related to perioperative fluid management in patients undergoing hepatectomy for liver cancer. The search period was from database inception to March 13, 2024. The 2014 version of the Joanna Briggs Institute evidence pre-grading and recommendation grading system was used to classify the evidence.Results:A total of 14 articles were included: 3 clinical decision articles, 3 guidelines, 1 evidence summary, 5 expert consensuses, 1 systematic review, and 1 randomized controlled trial. A total of 27 best evidence items were extracted, covering seven aspects: principles of fluid therapy, preoperative fluid management, intraoperative fluid management, postoperative fluid management, fluid type selection, assessment and monitoring, and training and education.Conclusions:This study summarizes the best evidence on perioperative fluid management for hepatectomy in liver cancer patients and provides an evidence-based reference for clinical nursing practice. Healthcare professionals should apply the evidence in a personalized manner based on the actual clinical context to promote scientific fluid management in the perioperative period.

Objective:To design and develop a cone-beam CT imaging system for small animals with continuously adjustable spatial resolution.Methods:The imaging system used an X-ray source with a focal spot size of 30 μm and a flat panel detector with a pixel size of 100 μm. On this premise, a " stepping-focusing-rotating" image acquisition mode was proposed, in which the " focusing" and " stepping" systems were sequentially embedded in the " rotating" system. In this acquisition mode, the X-ray source and flat panel detector were relatively stationary to form the " focusing" system. When the " stepping" system accurately transported the object to the scanning position, the " focusing" system could achieve adjustable spatial resolution by making linear motion around the object to be scanned according to different experimental requirements. Finally the " rotating" system achieve high-quality imaging.Results:The variable spatial resolution of small animal CBCT ranges from 35.7 μm to 71.4 μm, and the FOV ranges from 39.6 mm to 108.0 mm. The conversion time for the limit spatial resolution is 19.125 s, which allowed accurate 3D reconstruction of normal mice at different resolutions with high reproducibility.Conclusions:A cone-beam CT suitable for small animals has been developed, whose spatial resolution and FOV can be adjusted arbitrarily within a certain range, which can meet the different imaging requirements in rodent experiments.

Systemic sclerosis is an autoimmune rheumatic disease that often leads to multisystem diseases,frequently resulting in pulmonary interstitial fibrosis.According to the theory of sanjiao(triple energizers)membranous channels,sanjiao connects the five zang-organs and six fu-viscera internally and the skin,muscles,and bones externally.It serves as a four-way membranous channel that connects internal organs and external structures,linking with the micromembranes of organs and blood vessels.The pathogenesis of pulmonary interstitial fibrosis secondary to systemic sclerosis involves external cold obstructing the skin and interstitial layers,impairing the defense qi and defense yang,which originate in the essence of the kidney.This leads to weak defensive qi and kidney deficiency,causing stagnation in sanjiao's energy flow and disruption of water and gasification and loss of fluid,resulting in accumulation of dampness,phlegm,and blood stasis.These obstructive factors spread along sanjiao's membranous channels,leading to multiorgan micromembrane involvement and systemic damage.The lungs,which are in direct contact with the external environment,are particularly susceptible to invasion by external pathogens.When combined with stagnation of dampness,phlegm,and blood in the lungs,this leads to secondary pulmonary fibrosis,resulting in lung dysfunction.Continuous stagnation of sanjiao exacerbates the overall condition of the patient,leading to a mixed cold-heat imbalance.Treatment focuses on"unblocking,transforming,and regulating"to restore sanjiao function,promote qi and fluid circulation,invigorate blood,and adjust the cold-heat imbalance,ultimately restoring the overall condition of the patient.