1.Effect of Modified Duhuo Jisheng Mixture Regulating PI3K/Akt/mTOR Signaling Pathway on Synoviocyte Pyroptosis in Rabbit Models of Knee Osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Xuyi TAN ; Liang OU ; Gaoyan KUANG ; Min LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):170-179
ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture (JDJM) in treating synovial lesions in knee osteoarthritis (KOA). MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group (n=8) and a model group (n=35). The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage, with a modeling period of 6 weeks, resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group, celecoxib group, JDJM group and JDJM+740Y-P group, each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg-1, while the JDJM was administered a single dose of 6.8 mL·kg-1 (4.515 2 g·kg-1) of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway activator + JDJM group received 4.515 2 g·kg-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg-1 740Y-P. For a period of 6 weeks, the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period, the knee joint pain threshold and circumference were measured, and hematoxylin-eosin (HE) staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay (ELISA) measured the levels of interleukin-1β (IL-1β), interleukin-6 (IL-18) and tumor necrosis factor-α (TNF-α) in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, NOD-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1) and gasdermin D (GSDMD) in the synovial tissues. Immunohistochemical (IHC) assay was performed to assess the protein expression of NLRP3, Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD. ResultsCompared to the blank group, the model group showed a significant increase in knee joint circumference and decrease in pain threshold, the synovial tissue pathology score was higher (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid significantly increased (P<0.01). PI3K, Akt, mTOR phosphorylation as well as mRNA and protein expression increased (P<0.01), while the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD also significantly increased (P<0.01). Compared to the model group, the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold, the synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid decreased (P<0.01). The mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, NLRP3, Caspase-1 and GSDMD were reduced (P<0.01). Compared to the JDJM group, the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions, an increase in knee joint circumference, and a decrease in pain threshold. The synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid were higher (P<0.01). The mRNA and protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD increased (P<0.01). ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues, inhibiting pyroptosis, reducing inflammatory factor release, and protecting bony structures.
2.Study on the effect and mechanism of modified Yanghe decoction on bone destruction in rats with breast cancer bone metastasis
Shun LU ; Ang CAI ; Tingting FAN ; Weihua HE
China Pharmacy 2026;37(4):431-437
OBJECTIVE To explore the improvement effect and potential mechanism of modified Yanghe decoction on bone destruction in rats with breast cancer bone metastasis based on the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3 pathway. METHODS The rat model of breast cancer bone metastasis was established by injecting a suspension of breast cancer cells into the bone marrow cavity. The rats with successful modeling were randomly divided into a model group (intragastric administration of equal volume of normal saline), modified Yanghe decoction low-, medium-, and high-dose groups (intragastric administration of corresponding decoction at 1.30, 2.60 and 5.20 g/kg, calculated by the dosage of crude drug), high-dose modified Yanghe decoction+si-RIPK1 group (intragastric administration of corresponding decoction at 5.20 g/kg, calculated by the dosage of crude drug; simultaneous injection of small interfering RNA for RIPK1 via the tail vein), and high-dose modified Yanghe decoction+si-NC group (intragastric administration of corresponding decoction at 5.20 g/kg, calculated by the dosage of crude drug; simultaneous injection of small interfering RNA for negative control via the tail vein), with 12 rats in each group. Another 12 healthy rats were selected as the control group and were given the same volume of normal saline intragastrically, once a day, for 14 consecutive days. Body weight was measured before administration and at the end of the last administration. The mechanical pain threshold and thermal pain threshold were measured, and the bone destruction, pathological changes and osteoclast formation of the tibia were observed. The positive expression of receptor activator of nuclear factor-κB (RANK) and receptor activator of nuclear factor-κB ligand (RANKL) in the tibial tissue, as well as the phosphorylation levels of RIPK1, RIPK3 and mixed lineage kinase domain-like protein (MLKL) were detected. RESULTS Compared with the control group, the tumor cells of tibia tissues in rats of the model group showed significant proliferation and diffuse infiltration into the bone marrow cavity. Extensive areas of tumor necrosis of cells, severe bone destruction, thinning of the bone cortex, and damage to the bone trabeculae were observed. The body weight (before administration and at the end of the last administration), mechanical pain threshold, thermal pain threshold, and the phosphorylation levels of RIPK1, RIPK3 and MLKL were decreased significantly; the tumor volume, the proportion of bone destruction area, the number of osteoclasts, and the positive expressions of RANK and RANKL were increased/up-regulated significantly (P<0.05). Compared with the model group, the above pathological changes in the tibial tissues of rats in modified Yanghe decoction low-, medium- and high-dose groups were all alleviated, and all quantitative indicators showed dose-dependent improvement (P<0.05). After silencing RIPK1, the aforementioned beneficial effects of high-dose modified Yanghe decoction were significantly weakened (P<0.05).CONCLUSIONSModified Yanghe decoction can alleviate bone destruction in rats with breast cancer bone metastasis. The above effect is related to the activation of the RIPK1/RIPK3 pathway.
3.Effects of oral non-peptidic thrombopoietin receptor agonists on hepatic enzyme in adult patients with immune thrombocytopenia:a meta-analysis
Tiantian LU ; Nan SHEN ; Suyue ZHU ; Jingjing YAN
China Pharmacy 2026;37(4):510-515
OBJECTIVE To systematically evaluate the effects of oral non-peptidic thrombopoietin receptor agonists (TPO-RAs) on hepatic enzyme in adult patients with immune thrombocytopenia. METHODS A comprehensive literature search was conducted in PubMed, Web of Science, CNKI, Wanfang database and the Chinese Medical Association Journal Full-Text Database to collect randomized controlled trials (RCTs) comparing oral non-peptidic TPO-RAs (intervention group) with placebo or conventional therapy (control group). All databases were searched from their inception to June 2025. After literature screening, data extraction and quality assessment of the included studies, meta-analysis was conducted using RevMan 5.4.1 software. RESULTS Twelve RCTs comprising 1 388 patients were included, with 971 in the intervention group and 417 in the control group. Meta-analysis results showed that there were no significant differences between the two groups in terms of the incidence of hepatic enzyme elevation[OR=1.24, 95%CI (0.77, 1.99), P =0.37 ] , the incidence of hepatic enzyme elevation in patients treated for ≥6 weeks[OR=1.21, 95%CI (0.73, 1.99), P =0.46 ] , and the incidence of severe hepatic enzyme elevation[OR=1.39, 95%CI(0.46, 4.20), P =0.55 ] . Subgroup analysis showed that there were no significant differences in the incidence of hepatic enzyme elevation between the intervention group and control group among patients using eltrombopag[OR=1.57,95%CI(0.85,2.87), P =0.15 ] , avatrombopag[OR=0.88,95%CI (0.09,8.46), P =0.91 ] , and hetrombopag[OR=1.04,95%CI(0.30,3.65), P =0.95 ] , respectively. CONCLUSIONS Oral non-peptidic TPO-RAs do not significantly increase the risk of hepatic enzyme elevation in adult patients with immune thrombocytopenia, and show an overall favorable hepatic safety profile.
4.Analysis on the practical challenges and paths of “clown doctors” practice from the perspective of narrative medicine
Hui WANG ; Yutong PAN ; Liqun LU ; Can ZHANG
Chinese Medical Ethics 2026;39(2):215-222
Narrative medicine focuses on empathy, relevance, and emotion, precisely aligning with the elements of “clown doctor” such as compassion, interaction, and pain relief. From the perspective of narrative medicine, the practice of “clown doctors” not only focuses on the emotional changes of patients but also enhances their sense of belonging by recreating their experiences. The key element for the success of “clown doctors” lies in establishing a multi-dimensional trust relationship among medical workers, patients, colleagues, and society, while ensuring their practice adheres to medical ethics norms. “Clown doctors” should concentrate on dimensions such as concept dissemination, clinical application, social recognition, and ethical practice of narrative medicine. They should also constantly optimize narrative techniques, deepen the understanding of patients’ stories, and intervene in the medical process in a more delicate and comprehensive way, thereby fostering in-depth communication and understanding between doctors and patients.
5.Two cases of acute radiation-induced skin injury caused by external exposure to 192Ir
Li LI ; Wei SHANG ; Yan LING ; Mi WANG ; Huisheng ZHANG ; Chiqiao LU ; Xiaohu ZHONG ; Shenglong XU ; Juan GUO ; Chang LIU ; Yulong LIU
Chinese Journal of Radiological Health 2026;35(1):56-61
Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.
6.Investigation of radon activity concentration and dose assessment in subways of Nanning City, China
Xiufang LU ; Yilong MA ; Rongzheng HUANG ; Ziyue LI ; Jiajie LEI ; Lanying FENG ; Zhangfan CHEN ; Xinchun ZHAO
Chinese Journal of Radiological Health 2026;35(1):67-73
Objective To investigate the radon activity concentrations in subways of Nanning City and assess the average annual effective doses for subway staff and passengers due to radon exposure. Methods Sixty-three stations across the subway lines 2, 3, and 5 were selected as study sites. Radon activity concentrations were measured using the scintillation counting method with scintillation vials. Results The radon activity concentrations in subway lines 2, 3, and 5 were 7.9-24.4, 12.0-26.2, and 12.6-18.2 Bq/m3, respectively. The average radon activity concentrations for these three lines were (17.4 ± 4.6), (19.1 ± 4.1), and (14.6 ± 1.7) Bq/m3, respectively. Statistical analysis using SPSS 26.0 software revealed a significant difference in radon activity concentrations among these stations (P<0.01). Considering the data in previous research, the average radon activity concentration across all stations in the subway lines of Nanning City was determined to be 17.4 Bq/m3. The estimated average annual effective dose due to radon exposure was 0.131 mSv for subway staff and 0.033 mSv for passengers. Conclusion The radon activity concentrations in the subway lines of Nanning City were significantly lower than the national standard limit (400 Bq/m3). The annual effective doses from radon exposure for both subway staff and passengers were below the limits specified in the Basic Standards for Protection Against Ionizing Radiation and for the Safety of Radiation Sources (GB18871—2002). The health impact of radon and its progeny on subway staff and passengers in the subway lines of Nanning City was extremely low and can be considered negligible.
7.Research on the current situation and development suggestions of centralized (cloud) prescription review center of the close-knit county-level medical consortium in a city
Lu HE ; Mingyang ZHU ; Xiaolei HU ; Yan QIAN
China Pharmacy 2026;37(5):578-583
OBJECTIVE To investigate the actual construction and operation status of established and under-construction centralized (cloud) prescription review centers (shortened for “prescription review center”) of close-knit county-level medical consortium in a certain city, so as to provide reference for improving the construction quality of the prescription review center. METHODS An online questionnaire survey was conducted to collect the data from 51 established and under-construction prescription review center in the city, covering basic information, funding sources, talent management, system construction, review rule maintenance, prescription review practices, prescription evaluation, data utilization, and current challenges. The collected data were summarized and analyzed. RESULTS A total of 51 valid questionnaires were retrieved, covering 32 established and 19 under-construction prescription review center. Among the 32 established prescription review centers, the main funding sources for their construction came from government financial allocations, accounting for 56.25%. Only 25.00% of prescription review center had review pharmacists who fully met national qualification requirements, and just 55.00% updated more than 10 review rule entries per month on average. Outpatient prescription verification realized full coverage, but 37.50% of prescription review centers only supported rationality verification of single prescriptions, and 50.00% could not retrieve laboratory and examination results to assist in prescription review. Additionally, 40.62% of prescription review center had not regularly conducted prescription evaluations for primary care institutions. The data from prescription review center was mainly used to support medication monitoring. Among the 19 prescription review centers currently in the planning stage, 63.16% had no identified funding sources. CONCLUSIONS The operation and construction of prescription review center in the city face challenges, such as funding shortages, absence of collaborative incentive mechanisms, and insufficient manpower.It is suggested that the state should issue a unified standard for the construction of the prescription review center as soon as possible, and local health administrative departments should formulate supporting policies and clarify assessment indicators in combination with the actual situation of the region.
8.Effects and mechanism of short-acting exenatide on improving diabetic cognitive dysfunction
Xin LING ; Deming WANG ; Qi LU ; Jinyue HUANG ; Xian ZHENG ; Xiaona ZHU
China Pharmacy 2026;37(5):589-594
OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group (normal saline) and exenatide group (50 μg/kg), with db / m mice as the normal control group (normal saline), with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) ] , cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group (25 mmol/L glucose), high glucose group (125 mmol/L glucose), high glucose+exenatide group (125 mmol/L glucose+20 nmol/L exenatide), high glucose+exenatide+H89 (PKA inhibitor) group (125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89), and high glucose+H89 group (125 mmol/L glucose+10 μmol/L H89). After 48 h of intervention with corresponding solutions/culture medium, the levels of oxidative stress indicators, cAMP and PKA, the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ, and the phosphorylation level of dynamin-related protein 1 (Drp1) were measured. RESULTS Animal experiments showed that compared with the normal control group, the model group exhibited significantly increased body weight, fasting blood glucose and MDA level in the hippocampus ( P <0.05), as well as significantly prolonged escape latency ( P <0.05); swimming speed significantly slowed down, the time spent in the target quadrant, the number of platform crossings, and the levels of SOD, GSH, cAMP and PKA in the hippocampus were significantly decreased ( P <0.05). Compared with model group, all the above indicators (except for swimming speed) in the exenatide group were significantly reversed ( P <0.05). Cell experiments showed that compared with high glucose group, the high glucose+exenatide group had significantly decreased MDA level ( P <0.05), and significantly increased levels of SOD, GSH, cAMP and PKA, the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ, and phosphorylation level of Drp1 ( P <0.05). Compared with high glucose+exenatide group, the above indicators in the high glucose+exenatide+H89 group were significantly reversed ( P <0.05). CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway, promote Drp1 phosphorylation, and increase the activities of mitochondrial respiratory enzymes, thereby maintaining mitochondrial stability, reducing oxidative stress injury, and ultimately improving diabetic cognitive dysfunction.
9.Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma
Guiping MA ; Yuanjie ZHANG ; Yichi ZHOU ; Jinzhen LYU ; Conghui WANG ; Fenping LU ; Bowen LIU ; Yun RAN ; Shiping HU
China Pharmacy 2026;37(5):620-625
OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules (CQYG) improving hepatocellular carcinoma (HCC). METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group (normal saline), sorafenib group (positive control, 50 mg/kg), and CQYG low-, medium- and high-dose groups (24.83, 49.66, 99.32 g/kg), with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically, once a day, for 14 consecutive days. After last administration, pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition (EMT) [N-cadherin, E-cadherin, Vimentin, matrix metalloproteinase 7 (MMP7)] and the mitogen-activated protein kinase (MAPK) signaling pathway [p38 MAPK, phosphorylated p38 MAPK, c-Jun N-terminal kinase (JNK), phosphorylated JNK, extracellular regulated protein kinase 1/2 (ERK1/2), phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways, pathways in cancer, and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments, the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group, CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover, the expression levels of Ki-67, N-cadherin, MMP7 and Vimentin proteins, along with the phosphorylation levels of ERK1/2 and JNK proteins, were all significantly reduced ( P <0.05). The expression level of E-cadherin protein was significantly increased ( P <0.05), the phosphorylation level of p38 MAPK protein was increased, the difference was not statistically significant ( P >0.05). CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway, thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.
10.Advances in the JAK2/STAT3 signaling pathway and its inhibitors in diffuse large B cell lymphoma
Chuanyang LU ; Qiuni CHEN ; Yuye SHI ; Yuan DENG ; Tingting JI ; Zhengyuan LIU ; Chunling WANG ; Liang YU
China Pharmacy 2026;37(5):682-688
Abnormal activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). In recent years, inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors (e.g., ruxolitinib) and STAT3 inhibitors (direct small-molecule inhibitors, the antisense oligonucleotide, and proteolysis targeting chimeras, etc.) in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile, the development of novel drug delivery systems has significantly enhanced the stability, bioavailability, and targeting ability of the compounds. Furthermore, JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies (such as combinations with B-cell receptor signaling pathway inhibitors, immunomodulators, or other targeted drugs). However, current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL, and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

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