1.Xiaozheng Zhitong Paste Alleviates Bone Cancer Pain by Regulating PD-1/PD-L1-induced Osteoclast Formation
Lu SHANG ; Juanxia REN ; Guangda ZHENG ; Linghan MENG ; Lingyun WANG ; Changlin LI ; Dongtao LI ; Yaohua CHEN ; Guiping YANG ; Yanju BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):72-79
ObjectiveThis study aims to investigate the action mechanism by which Xiaozheng Zhitong paste (XZP) alleviates bone cancer pain (BCP) by regulating programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway-induced osteoclast formation. MethodsThirty female C57BL/6 mice were randomly allocated into the following groups (n=6 per group): normal control group, model group, low‑dose XZP group (31.5 g·kg-1), high‑dose XZP group (63 g·kg-1), and PD‑1 inhibitor (Niv) group. A bone cancer pain (BCP) model was established by injecting Lewis lung carcinoma cells. Mice in the normal control and model groups received topical application of a blank paste matrix at the wound site. Mice in the low‑ and high‑dose XZP groups were treated with XZP applied topically twice daily. Mice in the Niv group were topically administered the blank paste matrix and additionally received Niv via tail‑vein injection every two days. All interventions were continued for 21 days. During this period, behavioral tests were performed to assess mechanical, motor, and thermal nociceptive sensitivities. After 21 days, all mice were euthanized, and bone tissue from the operated side was collected for sectioning and preservation. Tartrate‑resistant acid phosphatase (TRAP) staining was used to evaluate osteoclast expression in the lesioned bone tissue. Immunohistochemistry was performed to detect the expression of Runt‑related transcription factor 2 (Runx2) in the lesioned bone tissue. Immunofluorescence was employed to assess the expression of PD‑1 and PD‑L1 in the lesioned bone tissue. ResultsCompared with the normal group, the model group showed significantly decreased limb mechanical withdrawal threshold, spontaneous paw flinching, and thermal withdrawal latency (P<0.01), increased number of osteoclasts in the lesioned bone tissue (P<0.01), and reduced expression of Runx2 (P<0.01). Compared with the model group, the BCP mice in the XZP low-dose group, XZP high-dose group, and Niv group exhibited increased limb mechanical withdrawal threshold, movement scores, and thermal withdrawal latency (P<0.01). The XZP low-dose group showed no significant changes in osteoclast number or Runx2 expression, while the XZP high-dose group and Niv group demonstrated significantly reduced osteoclast numbers (P<0.01) and significantly increased Runx2 expression (P<0.01). In the lesioned bone tissue of BCP mice, the XZP low-dose group showed no significant decrease in the percentage of PD-1 expression, but a decrease in the percentage of PD-L1 expression (P<0.05). In contrast, both the XZP high-dose group and the Niv group exhibited significant reductions in the percentages of PD-1 and PD-L1 expression (P<0.01). ConclusionXZP alleviates the pain of mice with BCP by blocking the PD-1/PD-L1 pathway to inhibit osteoclastogenesis.
2.Xiaozheng Zhitong Paste Relieves Bone Cancer Pain in Mice by Alleviating Activation of Microglia in Spinal Cord and Damage to Neurons via Blocking PAR2/NF-κB/NLRP3 Pathway
Guangda ZHENG ; Linghan MENG ; Lu SHANG ; Juanxia REN ; Dongtao LI ; Haixiao LIU ; Lingyun WANG ; Changlin LI ; Yaohua CHEN ; Guiping YANG ; Yanju BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):91-100
ObjectiveTo investigate the effects and underlying mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain (BCP). MethodsThirty female BALB/c mice were randomly divided into five groups: a Sham group, a BCP group, a BCP+low-dose XZP group, a BCP+high-dose XZP group, and a BCP+high-dose XZP + protease-activated receptor 2 (PAR2) agonist GB-110 group. BCP mice model was constructed by injecting Lewis lung carcinoma cells into the femoral cavity of the right leg, which was followed by being treated with XZP for 21 d. After 21 d, the mice were sacrificed. Nissl staining was used to evaluate the survival of spinal cord neurons. Immunofluorescence staining was conducted to localize ionized calcium-binding adapter molecule 1 (Iba1) and neuronal nuclear antigen (NeuN) in spinal cord tissue, thereby assessing microglial activation and neuronal survival. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in spinal cord tissue. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels associated with M1/M2 polarization of microglia. Western blot analysis was performed to examine the expression of proteins related to microglial polarization as well as those involved in the PAR2/nuclear factor kappa B (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway in the spinal cord. ResultsCompared with the Sham group, the spinal cord neurons were damaged, the number of Nissl-positive spinal cord neurons in the spinal cord tissue was significantly reduced (P<0.01), and the rate of NeuN-positive cells was significantly decreased (P<0.01). The spinal cord microglia were activated, the inflammatory level of the spinal cord tissue was enhanced, and Iba1 staining was significantly enhanced (P<0.01). The levels of IL-1β, TNF-α, IL-6, TGF-β, IL-4 and IL-10 were significantly increased (P<0.01). The mRNA expressions of IL-1β, TNF-α and inducible nitric oxide synthase (iNOS) were significantly increased (P<0.01), and the expression of PAR2, NLRP3, ASC and NF-κB p65 proteins in the spinal cord tissue of the BCP mice was significantly enhanced (P<0.01). Compared with the BCP group, high-dose XZP treatment significantly increased the number of Nissl-positive spinal cord neurons in the BCP mice (P<0.01), significantly enhanced the rate of NeuN-positive cells in the spinal cord tissue, and significantly weakened Iba1 staining (P<0.01). In addition, the levels of IL-1β, TNF-α, and IL-6 were significantly decreased, while the levels of TGF-β, IL-4, and IL-10 were significantly increased (P<0.05, P<0.01). The mRNA expression levels of IL-1β, TNF-α, and iNOS were decreased, whereas those of cluster of differentiation 206 (CD206), arginase-1 (Arg-1), and YM1/2 were significantly increased (P<0.05, P<0.01). Low-dose and high-dose XZP treatment significantly decreased the expression of PAR2, NLRP3, ASC, and NF-κB p65 proteins in the spinal cord tissue (P<0.05, P<0.01). These effects could all be significantly eliminated by the PAR2 agonist GB-110. ConclusionXZP can mitigate BCP in mice, which may be achieved through blocking the activated PAR2/NF-κB/NLRP3 pathway.
3.Xiaozheng Zhitong Paste Alleviates Bone Cancer Pain of Mice by Reducing Ferroptosis in Spinal Cord Tissue and Neuronal Damage via Regulating Nrf2/HO-1/GPX4/SLC7A11 Signaling Pathway
Juanxia REN ; Lu SHANG ; Guangda ZHENG ; Linghan MENG ; Lingyun WANG ; Changlin LI ; Dongtao LI ; Yaohua CHEN ; Guiping YANG ; Yanju BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):101-113
ObjectiveThe paper aims to investigate the action mechanism by which the Xiaozheng Zhitong paste (XZP) relieves bone cancer pain (BCP). MethodsA model of mice with BCP was established by using Lewis tumor cells. The therapeutic effects of XZP, the ferroptosis inhibitor Ferrostatin-1 (Fer-1), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor Brusatol (Bru) on BCP were examined. Mice were randomly divided into the Sham operation group, BCP group, BCP+XZP-L group, BCP+XZP-H group, BCP+Fer-1 group, and BCP+XZP-H+Bru group, with six mice in each group. Pain behavior tests were conducted on the mice to assess pain levels. Colorimetric assays were employed to measure ferroptosis-related factors in serum and spinal cord tissue including Fe, malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). Immunofluorescence staining was used to assess ROS production in spinal cord tissue. Transmission electron microscopy was used to observe the ultrastructure of mitochondria in lumbar spinal cord tissue. Quantitative real-time polymerase chain reaction (Real-time PCR) was employed to detect mRNA expression of Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) in spinal cord neuron tissue. The protein expression of Nrf2, HO-1, GPX4, and SLC7A11 in spinal cord neurons was measured by Western blot. ResultsCompared with the Sham group, mice in the BCP group exhibited significantly reduced limb usage scores, mechanical foot withdrawal thresholds, and thermal foot withdrawal thresholds (P<0.01). Serum and lumbar spinal cord tissue levels of Fe, MDA, and reactive oxygen species (ROS) were significantly elevated (P<0.05), while superoxide dismutase (SOD) levels were significantly decreased (P<0.05). Lumbar spinal cord mitochondrial structural damage was observed, and mRNA and protein expression of Nrf2, HO-1, GPX4, and SLC7A11 were significantly downregulated (P<0.01). Compared with the BCP group, both low- and high-dose XZP groups improved the aforementioned pain behavioral indicators (P<0.05,P<0.01), reduced ferroptosis-related biomarkers including Fe, MDA, and ROS levels (P<0.05), increased SOD levels (P<0.05,P<0.01), alleviated mitochondrial damage, and upregulated Nrf2, HO-1, GPX4, SLC7A11 mRNA and protein expression (P<0.05,P<0.01). The high-dose XZP group exhibited comparable efficacy to Fer-1 in alleviating pain and inhibiting ferroptosis. Following Bru administration, XZP's effects on pain behavioral indicators, regulation of ferroptosis-related markers, mitochondrial structural protection, and activation of the Nrf2/HO-1/GPX4/SLC7A11 pathway were significantly reversed (P<0.05,P<0.01). ConclusionExternal application of XZP alleviates pain symptoms in BCP mice by activating the Nrf2/HO-1/GPX4/SLC7A11 pathway, thereby inhibiting ferroptosis and neuronal damage in spinal cord neurons.
4.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
5.Clinical observation on Jiu-Wei-Yong-An granule combined with cetirizine in the treatment of eczema with damp-heat accumulation of skin syndrome
Yuanyuan MENG ; Yunyang WU ; Tingru CHEN ; Qinwufeng GU ; Yanlong YANG
Journal of Pharmaceutical Practice and Service 2025;43(6):298-302
Objective To observe the clinical effect of Jiu-Wei-Yong-An granule combined with cetirizine in the treatment of damp-heat accumulation syndrome of eczema. Methods 108 eczema patients with syndrome of damp-heat accumulated in the skin, treated in the Department of Traditional Chinese Surgery in the First Affiliated Hospital of Naval Medical University from December 2021 to March 2023, were selected. They were randomly divided into an observation group and a control group, 54 cases in each. Both groups took cetirizine tablets orally for basic treatment. The observation group was given Jiu-Wei-Yong-An granules, and the control group was given placebos of the same. The clinical efficacy before and after treatment in the two groups was observed and compared, including TCM syndrome scores, eczema area and severity index (EASI), visual analogue scale (VAS), and adverse reactions. Results After treatment, the total effective rate of the observation group (88.9%) was higher than that of the control group (77.8%), and the difference was statistically significant (P<0.05). After treatment, the TCM syndrome score, EASI and VAS in the observation group were significantly lower than those in the control group (P<0.05), and the difference was statistically significant. There was no significant difference in the total rate of adverse reactions between the two groups (P>0.05). Conclusion The combination of Jiu-Wei-Yong-An granules and cetirizine tablets in the treatment of damp-heat eczema showed significantly better clinical outcomes in the observation group compared to the control. It effectively improved patient conditions, reduced skin lesion areas, and alleviated itching, with both safety and efficacy that merit clinical promotion.
6.Effect of Exercise Intervention on Bone Mineral Density in Postmenopausal Osteoporosis Woman——a Network Meta-analysis
Ying HAO ; Ning-Ning YANG ; Meng-Ying SUN ; Xiao-Bin ZHOU ; Zhuo CHEN
Progress in Biochemistry and Biophysics 2025;52(6):1544-1559
Postmenopausal osteoporosis (PMOP) is a chronic metabolic bone disease caused by a decrease in estrogen levels. With the acceleration of population aging process, the public health burden caused by it is becoming increasingly severe. The prevalence rate of osteoporosis in people over 65 years old in China is as high as 32%, which is especially prominent after menopause, which is about 5 times that of elderly men. About 40% of postmenopausal women are at risk of osteoporotic fractures, with a disability rate of up to 50% and a fatality rate of about 20%. The prevention and treatment of osteoporosis has become a major public health issue of global concern, and it is particularly urgent to develop reasonable and effective prevention and treatment programs and explore their scientific basis. Exercise is an important non-drug means for the prevention and treatment of PMOP, it can improve estrogen levels and the expression of bone formation transcription factors, and inhibit the levels of proinflammatory factors and bone resorption markers, macroscopically manifested by the improvement of bone microstructure and bone density. However, the effectiveness of exercise in improving bone mineral density (BMD) remains controversial. Some studies revealed significant changes of bone to mechanical stimulation, while others showed no significant effect of mechanical training, this heterogeneity in bone adapt to mechanical stimulation is particularly evident in postmenopausal women. Although the evidence that a wide range of exercise programs can improve osteoporosis, the optimal solution to address bone mineral loss remains unclear. The most effective exercise type, dosage and personalized adaptation are still being determined. This study will fully consider the differences in gender and hormone levels, searching and screening randomized controlled trials of PubMed, CNKI and other databases regarding exercise improving bone mineral density in women with PMOP. Strictly following the PRISMA guidelines to reviewed and compared the effects of different types of exercise modalities on BMD at different sites in women with PMOP by network Meta-analysis, to provide theoretical guidance to maintain or improve BMD in women with PMOP.
7.Influencing factors, clinical manifestations and preventive strategies of hypercoagulable state after kidney transplantation
Rentian CHEN ; Zehua YUAN ; Hongtao JIANG ; Tao LI ; Meng YANG ; Liang XU ; Yi WANG
Organ Transplantation 2025;16(4):640-647
Hypercoagulable state (HCS) after kidney transplantation is one of the common and serious complications in kidney transplant recipients, which has attracted increasing attention in recent years. HCS refers to the abnormal and excessive activation of blood coagulation function, leading to the increased risk of thrombosis. After kidney transplantation, the combined effects of hemodynamic changes, surgical trauma and severe rejection increase the incidence of HCS, not only raising the risk of thrombosis but also potentially causing graft failure and affecting the postoperative survival rate of patients. This article reviews the influencing factors, clinical manifestations, diagnostic methods and preventive strategies of HCS after kidney transplantation, aiming to provide a theoretical basis for optimizing perioperative management and improving the prognosis of patients.
8.Meta-analysis of external treatment by Traditional Chinese Medicine for skin pruritus induced by eczema
Tingru CHEN ; Qinwufeng GU ; Yunyang WU ; Yuanyuan MENG ; Yanlong YANG ; Ruimin LI
Journal of Pharmaceutical Practice and Service 2025;43(8):383-389
Objective To evaluate the clinical efficacy of Traditional Chinese Medicine (TCM)external treatment methods in alleviating skin pruritus caused by eczema through a Meta-analysis. Methods Randomized clinical trials investigating the use of TCM external treatment methods for skin pruritus caused by eczema were searched in databases including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, Sinomed, PubMed, Embase, LILACS, and Cochrane, up to December 2024. Two reviewers independently screened and entered the statistical data, conducted bias risk assessment by the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0, and performed Meta-analysis using RevMan 5.4.1. Results Ultimately, 14 studies involving 1 788 patients were included. Compared to the control group, TCM external treatment methods (treatment group)showed better improvement in pruritus scores (Z=11.88, P<0.000 01), better improvement in Eczema Area and Severity Index (EASI) scores (Z=23.15, P<0.000 01), higher overall clinical efficacy rate (Z=6.21, P<0.000 01), better improvement in TCM symptoms (Z=5.49, P<0.000 01), and lower clinical recurrence rate (Z=2.88, P=0.004). Three of the included studies mentioned adverse reactions, with the treatment group showing lower adverse reactions than the control group. Conclusion The external treatment of TCM was more effective in treating skin pruritus caused by eczema compared to the control group. Given the biases and heterogeneity in the included literature, this conclusion needs to be further substantiated by more large-scale, multi-center, randomized, controlled, and double-blind studies.
9.Self-reported chronic disease prevalence among HIV/AIDS patients aged 50 years and above receiving antiretroviral therapy in Wuxi City
LI Qian ; YANG Bolin ; CHEN Jibiao ; YIN Hanlu ; XU Zhuping ; MENG Xiaojun
Journal of Preventive Medicine 2025;37(4):390-394
Objective:
To investigate the prevalence of hypertension, diabetes and hyperlipidemia among HIV/AIDS patients aged 50 years and above receiving antiretroviral therapy (ART) in Wuxi City, Jiangsu Province, so as to provide insights into the prevention and intervention of chronic diseases for these populations.
Methods:
The HIV/AIDS patients aged 50 years and above receiving ART were recruited at designated HIV/AIDS medical institutions in Wuxi City using the convenient sampling method from March to June 2024. Demographic information, treatment status and self-reported prevalence of hypertension, diabetes and hyperlipidemia were collected through questionnaire surveys. Factors affecting the prevalence of chronic diseases were analyzed using a multivariable logistic regression model.
Results:
A total of 830 HIV/AIDS patients receiving ART were surveyed, including 656 males (79.04%) and 375 patients aged 50 to <60 years (45.18%). Among them, 366 patients reported having at least one type of chronic disease, including hypertension, diabetes and hyperlipidemia, with a self-reported prevalence rate of 44.10%. Specifically, 280, 114 and 61 patients reported having hypertension, diabetes and hyperlipidemia, with the self-reported prevalence rates of 33.73%, 13.73% and 7.35%, respectively. Multivariable logistic regression analysis showed that male patients (OR=1.725, 95%CI: 1.187-2.507), those with monthly income less than 3 000 yuan (OR=1.521, 95%CI: 1.122-2.063), those with body mass index of 24 kg/m2 and above (OR=1.577, 95%CI: 1.168-2.130), those who initiated ART at ages of 50 years and above (50 to <60 years, OR=1.535, 95%CI: 1.052-2.238; ≥60 years, OR=3.322, 95%CI: 2.191-5.038), those with ART duration of 10 years and above (OR=2.069, 95%CI: 1.419-3.017), and those who received non-first-line regimens (OR=1.776, 95%CI: 1.304-2.418) had higher risks of developing at least one type of chronic disease, including hypertension, diabetes and hyperlipidemia.
Conclusions
The self-reported prevalence of at least one type of chronic disease, including hypertension, diabetes and hyperlipidemia among HIV/AIDS patients aged 50 years and above receiving ART in Wuxi City was 44.10%. Gender, monthly income, body mass index and ART status are the main influencing factors for the risk of chronic diseases.
10.Knowledge, attitude, practice regarding hypertension and home blood pressure monitoring among hypertension patients in rural areas of Shanghai Municipality
MENG Yang ; WAN Jinbao ; WU Cui ; CHEN Qiuyan ; YAN Qinghua ; CHENG Minna
Journal of Preventive Medicine 2025;37(7):737-742
Objective:
To investigate the knowledge, attitudes, practices (KAP) and the situation of home blood pressure monitoring (HBPM) among hypertension patients in rural areas of Shanghai Municipality, so as to provide a basis for enhancing blood pressure management in this population.
Methods:
From June to October 2021, hypertension patients under management in Luodian Town and Luojing Town of rural areas of Shanghai Municipality were selected as survey subjects using a multistage random sampling method. Demographic information, KAP related to hypertension, and HBPM status were collected through questionnaire surveys. Patients were categorized into short disease duration (≤5 years), medium disease duration (6-10 years), and long disease duration (≥11 years) groups. KAP and HBPM status across different disease duration groups were analyzed statistically.
Results:
A total of 2 894 hypertensive patients were surveyed, including 1 317 (45.51%) males and 1 577 (54.49%) females. The median age was 69.00 (interquartile range, 10.00) years. There were 610 cases with short disease duration, accounting for 21.08%; 629 cases with medium duration, accounting for 21.73%; and 1 655 cases with long duration, accounting for 57.19%. The awareness of "hypertension control measures" was relatively high (97.89%), while awareness of "hypertension complications" was relatively low (71.70%). The adherence rate of "not perceiving difficulty in remembering to take medication on time and in correct doses" was relatively low (78.89%), and the proportion of participants who "walked ≥10 minutes per session at least once in the past 7 days" was relatively high (80.48%). A total of 1 209 cases (41.78%) engaged in HBPM, including 233 cases with short disease duration (19.27%), 252 cases with medium disease duration (20.84%), and 724 cases with long disease duration (59.88%). Compared with long disease duration hypertension patients, those with short disease duration had a alower awareness of "principles of pharmacological treatment for hypertension", a lower adherence rate of "medication should not be stopped after blood pressure control", and a lower proportion of providing their blood pressure measurement results to doctors (all P<0.017). However, they had higher proportions of alcohol consumption and daily salt intake >6 g/d (both P<0.017).
Conclusions
Short disease duration hypertension patients exhibit poorer performance in hypertension-related KAP and HBPM compared to long disease duration patients in rural areas of Shanghai Municipality. It is recommended to implement tailored health education based on disease duration, promote HBPM, and enhance blood pressure control rate.


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