1.23-Hydroxybetulinic Acid Inhibits NNK and LPS-induced Lung Inflammation-related Carcinogenesis by Regulating Immune Cells in Mice
Penghaobang LIU ; Wenbin DUAN ; Yajuan CHEN ; Lanying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):98-106
ObjectiveTo investigate the suppressive effect of 23-hydroxybetulinic acid (23-HBA), a key constituent of Pulsatillae Radix, on the pulmonary inflammation-related carcinogenesis induced by the combined exposure of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and lipopolysaccharide (LPS) in mice, alongside exploring its influence on immune cells and delving into the underlying mechanisms. MethodsA murine model of pulmonary inflammation-related carcinogenesis induced by NNK combined with LPS was established. Mice were randomly assigned into blank control, model, aspirin (10 mg·kg-1), and low-, medium-, and high-dose (3.75, 7.5, 15 mg·kg-1, respectively) 23-HBA groups. The treatment lasted for 26 weeks, after which the spleen, lung, and peripheral blood samples were collected. Lung and spleen indices were calculated. Histopathological changes in the lung tissue were observed by hematoxylin-eosin staining. Immunohistochemistry was employed to assess the expression levels of thyroid transcription factor-1 (TTF-1), neuron-specific enolase (NSE), and proliferating cell nuclear antigen (Ki-67) in the lung tissue. High-throughput protein microarray was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the mouse serum. Flow cytometry was employed to evaluate the expression of macrophages, myeloid-derived suppressor cells (MDSCs), and exhausted T lymphocytes in the lung and spleen tissue. Molecular docking was performed to predict the binding affinity of 23-HBA to Janus kinase 2 (JAK2), Src homology 2 domain-containing phosphatase 2 (SHP2), and suppressor of cytokine signaling 3 (SOCS3). Western blot was performed to assess the protein levels of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), p53, and SHP2 in the M1-activated macrophages and A549 lung adenocarcinoma cells treated with 23-HBA. ResultsCompared with the normal group, the lung and spleen indexes of the model group were increased to varying degrees (P<0.05, P<0.01), the expression of TTF-1, NSE and Ki-67 protein was significantly increased (P<0.05, P<0.01), and the serum levels of TNF-α, IL-1β and IL-6 were significantly increased (P<0.01). The number of macrophages in the model group was significantly decreased (P<0.01), and the number of exhausted T cells and MDSCs was significantly increased (P<0.05, P<0.01). Compared with the model group, the spleen and thymus index of mice in each dose group of 23-HBA decreased significantly (P<0.05), and the lung index of mice in the middle dose group of 23-HBA decreased significantly (P<0.05). The high and middle dose groups of 23-HBA could improve the occurrence of inflammatory infiltration and malignant lesions in the lungs of mice induced by NNK combined with LPS in the model group. The expression of TTF-1 in the middle and high dose groups of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The expression of NSE and Ki-67 protein in each dose group of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The contents of IL-1β in the low and high dose groups of 23-HBA were significantly decreased (P<0.05), and the contents of IL-6 and TNF-α in each dose of 23-HBA were significantly decreased (P<0.05, P<0.01). The number of macrophages in the lung of the middle dose group of 23-HBA was significantly increased (P<0.05), and the number of exhausted T cells and MDSCs expressing PD-1 in the lung was significantly decreased (P<0.05, P<0.01). In addition, 23-HBA had strong molecular docking ability to SHP2, SOCS3 and JAK2 (≥7 kcal·mol-1), and significantly down-regulated the protein levels of p-STAT3, SHP2 and p53 in M1 macrophages and A549 lung adenocarcinoma (P<0.01). Conclusion23-HBA holds promise as a potential therapeutic agent for mitigating pulmonary inflammation and inhibiting malignant transformation induced by the combination of LPS and NNK. It may exert effects by regulating immune cell responses, improving the tumor immune microenvironment, and regulating key signaling pathways.
2.Impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province
Chinese Journal of School Health 2025;46(10):1401-1405
Objective:
To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies.
Methods:
In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach.
Results:
The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05).
Conclusions
Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.
3.Expert consensus on the rational use of psychotropic drugs related to intensive care medicine
Shenglin SHE ; Zhen SONG ; Tongwen SUN ; Jingguo ZHAI ; Yan YU ; Ningbo YANG ; Maosheng FANG ; Wenbin GUO ; Man WANG ; Guanglei XUN ; Lulu ZHANG ; Xijia XU ; Xiaoli WU ; Qinling WEI ; Fang LIU ; Huiping LI ; Xingrong SONG ; Youping WANG ; Yingjun ZHENG ; Xueqin SONG
Chinese Journal of Nervous and Mental Diseases 2024;50(9):513-524
Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.
4.Cardiac Pacemaker Implantation Under Transthoracic Ultrasound Guidance
Daoliang ZHANG ; Jun LIU ; Yong JIANG ; Wenbin OUYANG ; Guangzhi ZHAO ; Xiangbin PAN
Chinese Circulation Journal 2024;39(10):1025-1027
This report describes a case of an elderly patient whose cardiac pacemaker lead had dislocated and whose battery had depleted.After evaluation,the patient required implantation of a leadless pacemaker.The procedure was successfully completed using solely transthoracic ultrasound guidance,marking the first leadless pacemaker implantation done with only ultrasound guidance,and achieved favorable clinical outcomes.
5.Research progress in radiopharmaceuticals targeting tumor immune microenvironment
Kai ZHU ; Caiyun LIU ; Wenbin XIN ; Tingting LIU ; Xu WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(9):559-563
Immunotherapy has made breakthrough in the field of tumor treatment. How to accurately predict the response of tumor patients to immunotherapy in the early stage is currently a clinical challenge. Nuclear medicine molecular imaging provides a new technological means for early accurate diagnosis, treatment monitoring, early warning of recurrence and metastasis, and guidance for personalized treatment of diseases. Therefore, it plays an irreplaceable role in precise diagnosis and treatment of tumors and patient stratification. This article reviews the progress of molecular imaging research on immune cells and related targets within the tumor microenvironment.
6.Hearing loss and microvascular complications in diabetes
Mingyu LIU ; Jia LI ; Wenbin TAN ; Yongxin LU ; Pengxin ZHANG ; Huang CHEN ; Hongmei LI ; Shuwen LI ; Kaixuan ZHU ; Liu YANG ; Xuesong JIANG ; Jiaqi XI
Chinese Journal of Endocrinology and Metabolism 2024;40(8):654-659
Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.
7.Combined liver-kidney transplantation for giant polycystic liver and polycystic kidney involving iliac fossa: one case report
Longshan LIU ; Wenbin ZHANG ; Weiqiang JU ; Maogen CHEN ; Yongcheng WEI ; Yingzhen HE ; Jun LI ; Changxi WANG ; Xiaoshun HE
Chinese Journal of Organ Transplantation 2024;45(10):728-729
This report described one patient of giant polycystic liver and polycystic kidney involving iliac fossa. Preoperative computed tomography (CT) revealed a large polycystic kidney occupying partially iliac fossa space. A decompression of lower pole of original kidney was planned for placing transplanted kidney. During total liver resection plus orthotopic liver transplantation, right polycystic kidney could move up on its own and iliac fossa space was released for placing transplanted kidney smoothly. Polycystic kidney shrunk markedly post-operation. It provided references for surgical planning of combined liver-kidney transplantation for this type of disease.
8.Application of multiple frequency bioelectrical impedance analysis in evaluation of the effect of staged surgery on breast cancer-related lymphedema
Xin LIU ; Wenbin SHEN ; Song XIA ; Yuguang SUN ; Kun CHANG ; Jianfeng XIN ; Ran AN ; Zhong LIU
Chinese Journal of Microsurgery 2024;47(4):368-374
Objective:To explore the significance of multiple frequency bioelectrical impedance analysis (MFBIA) in the combined surgical treatment of breast cancer-related lymphedema (BCRL).Methods:A retrospective analysis was conducted on the clinical data of 30 patients with unilateral postoperative BCRL. The patients recieved staged liposuction and lymphaticovenular anastomosis (LVA) from April to October 2021 at the Department of Lymphatic Surgery in Beijing Shijitan Hospital, Capital Medical University. After LVA surgery, patients were followed-up by telephone and other means, and asked to come to the hospital at 1 year and 2 years, respectively. The circumference of each part of the upper limbs, the length of forearm and arm were measured, and the limb volume was calculated. MFBIA were also performed to record limb bioelectrical impedance, extracellular water(ECW), and extracellular water ratios (ECW/TBW). SPSS 21.0 was used for statistical analysis. Clinical data of the patients were analysed by One-way Repeated Measurement Anova to examine the changes in volume of the affected arms before and after surgery and the changes in values collected by MFBIA. Subsequently, differences in the volumes and values of MFBIA of the affected arms before and after surgery, and the ratios of the above were analysed by paired t-test to compare each pair, then followed by Pearson correlation test. P<0.05 was considered statistically significant. Results:After liposuction, the volume differences of affected and healthy arms were reduced from 1 147 ml ± 484 ml before surgery to 261 ml ± 304 ml after surgery, which achieved a significant reduction with statistical significance ( P<0.05). However, there were no significant changes in ECW or bioelectrical impedance at various frequencies (1-1 000 K) ( P>0.05). After LVA, the differences in volume of the affected and healthy arms further decreased to 17 ml±264 ml with statistical significance compared to that before surgery ( P<0.05), ECW decreased from 1.115 L ± 0.207 L to 0.937 L ± 0.164 L with statistical significance ( P<0.05), ECW/TBW decreased from 0.412 ± 0.008 to 0.405 ± 0.007 with statistical significance ( P<0.05), and the bioelectrical impedance at various frequencies was significantly increased with statistical significance ( P<0.05). After LVA, the difference in arm volume was positively correlated with the difference in ECW (correlation coefficient 0.602, P<0.05), positively correlated with the difference in Rate of ECW (correlation coefficient 0.560, P<0.05), and negatively correlated with the ratios of impedance at various frequencies (correlation coefficients 0.529-0.545, P<0.05). Conclusion:In the staged surgical treatment of BCRL, with the application of MFBIA, it is found that lymphatic liposuction removes the pathological adipose tissue of an arm, hence significantly reduces the volume of the affected arm. However, lymphatic stasis remains unrelieved, therefore without a significant reduction in arm oedema. After the second-stage LVA, the improvement of lymphatic return leads to the relief of arm oedema, and the volume of the affected arm approaches to that of the healthy side. MFBIA can be used for assessment of arm oedema.
9.Microsurgical treatment of primary lymphedema with interstitial lung disease: a report of 13 cases
Chen LIANG ; Song XIA ; Kun CHANG ; Zhong LIU ; Xin LIU ; Ran AN ; Jianfeng XIN ; Yuguang SUN ; Wenbin SHEN
Chinese Journal of Microsurgery 2024;47(4):375-381
Objective:To investigate the characteristics and diagnostic methods for the patients with primary lymphedema and interstitial lung disease, as well as the efficacy of thoracic duct or right lymphatic duct plasty.Methods:A retrospective study was performed on 13 patients who were treated for primary lymphedema in the Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University, from January 2018 to December 2022. All patients were confirmed with interstitial lung disease by high-resolution CT (HRCT) and then underwent thoracic duct or right lymphatic duct plasty surgery. The 13 patients in this study were 7 males and 6 females aged 7.3 (0.7-30.0) years old. Primary lymphedema was the first manifestation in all patients, with an average morbidity age at 1.0 (0-11.0) years old. The average time from the onset of lymphedema to the confirmed interstitial lung disease was 6.3 (0.3-19.0) years. All patients underwent thoracic duct or right lymphatic duct plasty for improvement of the lymphatic flow. In addition, 9 cases (69.2%) received a direct lymphangiography (DLG). In which, 4 cases (44.4%) received further treatment of ligation of the reflux branches, and 1 (11.1%) had the treatment plans changed, because a chylous reflux into the lung through a bronchomediastinal trunk was found from DLG, therefore a ligation of the abnormal reflux branches was performed and a life-long strict low-fat diet was required. Postoperative follow-ups for evaluation of the improvements of lymphedema and pulmonary lymphatic flow were carried out by visit of outpatient clinic or via telephone interviews.Results:All patients recovered well after surgery with an average follow-up time of 47.5 (19.0-68.0) months. Lymphedema was stable in 2 cases (15.4%) and relieved in 11 cases (84.6%). Ten cases (76.9%) had completed the postoperative HRCT reviews and 9 (90.0%) were found with significant improvement in the interstitial lung disease.Conclusion:The interstitial lung disease found during the examination of patients with primary lymphedema can be explained with a lymphatic flow disorder. DLG can identify the cause and make to guide the treatment. Thoracic duct or right lymphatic duct plasty can effectively improve both of the symptom of lymphedema and interstitial lung disease.
10.Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns
Qimin MA ; Wenbin TANG ; Xiaojian LI ; Fei CHANG ; Xi YIN ; Zhaohong CHEN ; Guohua WU ; Chengde XIA ; Xiaoliang LI ; Deyun WANG ; Zhigang CHU ; Yi ZHANG ; Lei WANG ; Choulang WU ; Yalin TONG ; Pei CUI ; Guanghua GUO ; Zhihao ZHU ; Shengyu HUANG ; Liu CHANG ; Rui LIU ; Yongji LIU ; Yusong WANG ; Xiaobin LIU ; Tuo SHEN ; Feng ZHU
Chinese Journal of Burns 2024;40(3):249-257
Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.


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