1.Antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center
Jiayu TIAN ; Tianyi YANG ; Jingen XIE ; Linlin CHEN ; Qian RAO ; Xiong XIAO ; Yongchun HOU ; Wenhong LI
China Pharmacy 2026;37(7):870-876
OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group, model group, dexamethasone group (positive control), and Ephedrae Herba-Armeniacae Semen Amarum 2∶1, 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g (crude drug)/kg], dexamethasone suspension (0.5 mg/kg), or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration, medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration, the nucleus tractus solitarius (NTS) was located using a stereotaxic apparatus. Histamine phosphate (1 μL) was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats; the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor (NGF), substance P (SP), norepinephrine (NA), 5-hydroxytryptamine (5-HT) and acetylcholine (Ach)] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor (NK-1R), p38 mitogen-activated protein kinase (MAPK), and c-fos in the medulla oblongata, as well as the protein expressions of NK-1R, p38 MAPK, and c-fos in the NTS region, were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine, pseudoephedrine, and methylephedrine. Compared with blank group, the contents of NGF, SP, NA, 5-HT and Ach, and the relative expression levels of NK-1R, p38 MAPK, and c-fos mRNA and protein were significantly increased in the model group ( P <0.01). Compared with model group, Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R, p38 MAPK, and c-fos mRNA and protein ( P <0.01), with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.
2.SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.
Tongzhu JIN ; Huiying GAO ; Yuquan WANG ; Zhiwei NING ; Danyang BING ; Yan WANG ; Yi CHEN ; Xiaomu TIAN ; Qiudi LIU ; Zhihui NIU ; Jiayu GUO ; Jian SUN ; Ruoxuan YANG ; Qianqian WANG ; Shifen LI ; Tianyu LI ; Yuhong ZHOU ; Wenxin HE ; Yanjie LU ; Yunyan GU ; Haihai LIANG
Acta Pharmaceutica Sinica B 2025;15(6):3041-3058
Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.
3.Mechanism of Modified Guishenwan in Regulating AMPK/Akt/Nrf2 Pathway to Improve Glucose and Lipid Metabolism and Oxidative Stress in Polycystic Ovary Syndrome Rats
Jiayu TIAN ; Wenyi QIN ; Juan YANG ; Xiaofeng RONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):1-8
ObjectiveBased on the adenosine 5'-monophosphate (AMP)-activated protein kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (AMPK/Akt/Nrf2) pathway, this study aims to explore the mechanism by which modified Guishenwan improves glucose and lipid metabolism and oxidative stress in polycystic ovary syndrome (PCOS) rats. MethodsA PCOS rat model was established by continuous oral administration of letrozole (1 mg·kg-1·d-1) for 21 days. Successfully modeled rats were randomly divided into a model group, a metformin group (0.25 g·kg-1), and low-, medium-, and high-dose modified Guishenwan groups (4.01, 8.02, and 16.04 g·kg-1·d-1), with 8 rats in each group. Ten normal rats were assigned to the normal group. The drug groups were given their respective doses, while the normal and model groups were given an equal volume of normal saline. Intervention lasted for 4 weeks. Testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio was calculated. Fasting blood glucose (FPG), fasting insulin (FINS), triglyceride (TG), and total cholesterol (TC) levels were measured using an automatic biochemical analyzer, and the insulin resistance index (HOMA-IR) and insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. Malondialdehyde (MDA), advanced glycation end products (AGEs), and superoxide dismutase (SOD) levels in serum and ovarian tissue were measured using a chemical fluorescence method. Hematoxylin-eosin (HE) staining was used to assess ovarian tissue pathology. Real-time quantitative fluorescent polymerase chain reaction (Real-time PCR) and Western blot were used to measure the expression of AMPK/Akt/Nrf2 pathway-related genes and proteins in ovarian tissue. ResultsCompared with the normal group, the model group exhibited significantly increased levels of T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly decreased (P<0.05, P<0.01). MDA and AGEs levels were significantly higher in both serum and ovarian tissue, and SOD levels were significantly reduced (P<0.05). AMPK, Akt, and Nrf2 mRNA and protein expression in ovarian tissue was also significantly reduced (P<0.05). The OGTT and ITT results showed significantly higher blood glucose levels at each time point (P<0.05, P<0.01), with impaired glucose and insulin tolerance. Ovarian follicles showed polycystic changes, reduced corpus luteum, and sparse granulosa cell layers. Compared with the model group, the metformin group and the high-dose modified Guishenwan group showed significant decreases in T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly increased (P<0.05, P<0.01). In the high-dose modified Guishenwan group, MDA and AGEs levels in serum and ovarian tissue were significantly reduced, and SOD levels were significantly increased (P<0.05). The mRNA and protein expression of AMPK, Akt, and Nrf2 in ovarian tissue was significantly increased (P<0.05). OGTT and ITT results showed that blood glucose levels in rats decreased significantly at each time point (P<0.05, P<0.01). No obvious abnormalities were observed in ovarian tissue. Compared with the low-dose modified Guishenwan group, the high-dose group showed significant decreases in T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly increased (P<0.05). OGTT and ITT results indicated that the high-dose modified Guishenwan group significantly improved glucose and insulin tolerance in rats. No significant abnormalities were observed in ovarian tissue. ConclusionModified Guishenwan effectively improves glucose and lipid metabolism abnormalities and inhibits oxidative stress in PCOS rats, potentially through regulation of the AMPK/Akt/Nrf2 pathway.
4.Modified Guishenwan Alleviates Inflammation in Rat Model of Polycystic Ovary Syndrome by Inhibiting MAPK/NF-κB Pathway
Jiayu TIAN ; Wenyi QIN ; Juan YANG ; Xiaofeng RONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):86-94
ObjectiveTo explore the mechanism by which modified Guishenwan alleviates inflammation in the rat model of polycystic ovary syndrome (PCOS) by regulating the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. MethodsAccording to the random number table method, 60 SPF female SD rats were randomized into a normal group (n=10) and a modeling group (n=50). The normal group received routine feeding, while the modeling group was administrated with letrozole (1 mg·kg-1·d-1) by gavage for 21 days for the modeling of PCOS. The successfully modeled rats were randomized into model, diane-35 (0.2 g·kg-1·d-1), high- (16.04 g·kg-1·d-1), medium- (8.02 g·kg-1·d-1), low- (4.01 g·kg-1·d-1) dose modified Guishenwan groups. The drug intervention groups were administrated with modified Guishenwan at corresponding doses by gavage, and the normal group and model group were given equal volumes of normal saline. All the groups were continuously treated for 28 days. After treatment, Gram staining of vaginal smears was employed to observe the estrous cycle in each group. Enzyme-linked immunosorbent assay was employed to determine the levels of follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), testosterone (T), and progesterone (PROG) in the plasma, as well as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in the plasma and ovarian tissue. The LH/FSH ratio was calculated. The morphological changes in the ovarian tissue were observed by hematoxylin-eosin (HE) staining. Western blot was employed to determine the protein levels of extracellular-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38 MAPK, NF-κB p65, IκBα, p-JNK, p-ERK, p-p38 MAPK, p-NF-κB p65, and p-IκBα in the ovarian tissue. Real-time quantitative polymerase chain reaction was used to determine the mRNA levels of ERK, JNK, p38 MAPK, NF-κB p65, and IκBα in the ovarian tissue. ResultsCompared with the normal group, the model group was in the estrus phase, with an increase in the number of ovarian vesicles and decreases in granulosa cells and corpus luteum formation (P<0.05), and lowered levels of FSH and E2 and elevated levels of LH, T, and LH/FSH in the plasma (P<0.05). Compared with the model group, high-, medium-, and low-dose modified Guishenwan recovered the estrous cycle, increased the generation of granulosa cells and corpus luteum, reduced the number of vesicles, elevated the levels of FSH and E2, and lowered the levels LH, T, and LH/FSH (P<0.05, P<0.01) in a dose-dependent manner. High-dose modified Guishenwan demonstrated the best therapeutic effect. Therefore, subsequent experiments for exploring the treatment mechanism were conducted in the normal group, model group, and high-dose modified Guishenwan group. The results showed that compared with the model group, high-dose modified Guishenwan lowered the levels of IL-1β, TNF-α, and IL-10 and elevated the level of IL-10 in the plasma and ovarian tissue (P<0.05, P<0.01), down-regulated the protein levels of p-ERK, p-JNK, p-p38 MAPK, p-NF-κB p65, and p-IκBα, while up-regulating the protein level of IκBα (P<0.01). At the same time, the mRNA levels of ERK, JNK, p38 MAPK, and NF-κB p65 in the high-dose modified Guishenwan group were down-regulated (P<0.05, P<0.01). ConclusionModified Guishenwan can improve the ovarian function in rat model of PCOS induced by letrozole and has anti-inflammatory effects, which may be related to inhibition of the MAPK/NF-κB pathway.
5.Effects of intravenous lidocaine infusion on the quality of intraoperative neurophysiologic monitoring in patients with thyroid tumor
Chenyuan ZHANG ; Zixin ZHAO ; Mengge LI ; Xuesen SU ; Jiayu ZHU ; Xin YUAN ; Shouyuan TIAN
Cancer Research and Clinic 2025;37(1):39-44
Objective:To investigate the effects of intravenous lidocaine infusion (IVLI) on the quality of intraoperative neurophysiologic monitoring (IONM) in patients with thyroid tumor.Methods:A prospective randomized controlled study was conducted. A total of 60 patients with thyroid tumor undergoing thyroidectomy in the First Clinical Medical College of Shanxi Medical University between September 2022 and May 2023 were selected. According to the random number table method, all patients were divided into the lidocaine group and the control group, 30 cases in each group. The patients in the lidocaine group were continually given IVLI during the operation and the patients in the control group were continually given the equal 0.9% NaCl solution infusion during the operation. All patients in the 2 groups were induced by the same way of total intravenous anesthesia, and no muscle relaxants were added during anesthesia except the induction dose, and enhanced nerve monitoring tracheal catheter was inserted in the 2 groups. According to the standardized procedure of IONM, the electrode impedance values were measured at the time of eliciting the V1 and V2 signals from the vagus nerve, respectively, and the difference value was defined as the drop in the aggregate impedance level (DAIL). DAIL, perioperative hemodynamic parameters and postoperative recovery quality were compared between the 2 groups.Results:There were no statistically significant differences in the baseline data, operation time, intraoperative dosage of propofol and remifentanil between the 2 groups (all P > 0.05). Compared with the control group, the lidocaine group had a higher proportion of patients with DAIL<50% [80.0% (24/30) vs. 40.0% (12/30), χ2 = 10.00, P = 0.002], a lower hemodynamic fluctuation during extubation [mean arterial pressure: (95±6) mmHg (1 mmHg = 0.133 kPa) vs. (104±7) mmHg, t = 31.00, P < 0.001; heart rate: (73±5) times/min vs. (92±6) times/min, t = 172.58, P < 0.001], a lower visual analog score 24 h after surgery [(2.0±0.7) scores vs. (3.7±0.8) scores, t = -8.86, P < 0.001], a higher score of quality of recovery-15 scale [(127±11) points vs. (118±13) points, t = 2.92, P = 0.005]. Conclusions:IVIL can improve the quality of IONM in patients with thyroid tumor during surgery, reduce perioperative hemodynamic fluctuation and improve postoperative recovery quality of patients.
6.Research progress on assessment tools for health behavior motivation in patients with cardiovascular diseases
Zhifeng ZHANG ; Lei LIU ; Yikang XU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Kaiwen ZHAN ; Siqi SUN ; Manman LI
Journal of Shenyang Medical College 2025;27(2):198-201
Health behavior motivation significantly affects the quality of life of patients with cardiovascular diseases.Assessing the level of health behavior motivation can measure the health behavior of individuals,help to promote the participation rate of cardiac rehabilitation,reduce the readmission rate of patients,and promote patients'healthy lifestyles.This article reviews the content,characteristics and application of assessment tools for health behavior motivation of patients with cardiovascular diseases at home and abroad,with the aim of providing references for the development and application of such tools in China,and offering a basis for scientifically assessing their health behavior motivation level and formulating effective strategies to promote health behavior motivation.
7.Research progress on assessment tools for the treatment burden of patients with chronic diseases
Kaiwen ZHAN ; Lei LIU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Manman LI ; Siqi SUN ; Zhifeng ZHANG
Journal of Shenyang Medical College 2025;27(1):74-78
The number of patients with chronic diseases in China has been increasing year by year,followed by the increase of treatment burden.It is particularly important to effectively evaluate the treatment burden of patients with chronic diseases.This paper reviews the main contents,application scope,advantages and disadvantages of the assessment tools for the treatment burden of patients with chronic diseases at home and abroad,so as to provide references and basis for medical staff to reasonably select assessment tools and conduct relevant clinical research.
8.Construction and performance evaluation of polycaprolactone/nanodiamond-phospholipid composite materials
Jiayu TIAN ; Duohua LI ; Feng ZHANG ; Hu FENG ; Wei SUN
Chinese Journal of Tissue Engineering Research 2025;29(16):3380-3387
BACKGROUND:Polycaprolactone has been widely used in bone tissue engineering due to its excellent processing and degradation performance,but its poor hydrophilicity and mechanical strength cannot provide a good growth environment for osteoblasts.OBJECTIVE:To prepare polycaprolactone/nanodiamond-phospholipid composite materials,evaluate its biocompatibility and in vitro ability to promote bone differentiation.METHODS:Nanodiamond was modified using phospholipids,and polycaprolactone was used as the raw material.Polycaprolactone/nanodiamond-phospholipid composite materials with different mass ratios(0%,2.5%,7.5%,and 10%)were prepared by solution casting method.Polycaprolactone/nanodiamonds were used for comparison.The surface morphology,elemental composition,mechanical properties,and water contact angle of each group of materials were observed to select composite materials with better physical and chemical properties.MC3T3-E1 cells were inoculated onto pure polycaprolactone membrane,polycaprolactone/7.5%nanodiamond-phospholipid membrane,and polycaprolactone/7.5%polycaprolactone/nanodiamond membrane,respectively,to detect cell proliferation,adhesion,and osteogenic differentiation ability.RESULTS AND CONCLUSION:(1)The successful preparation of the polycaprolactone/nanodiamond-phospholipid composite material was confirmed by scanning electron microscopy and surface element composition.Compared with pure polycaprolactone membrane,the tensile strength of the polycaprolactone/7.5%nanodiamond-phospholipids membrane increased by 86.06%,the elastic modulus increased by 54.76%,and the water contact angle decreased to 70.0°,showing good physical and chemical properties.(2)The CCK-8 assay results showed that compared with pure polycaprolactone membrane and polycaprolactone/7.5%nanodiamond membrane,polycaprolactone/7.5%nanodiamond-phospholipid membrane could promote the proliferation of MC3T3-E1 cells.Phalloidine staining exhibited that compared with the polycaprolactone/7.5%nanodiamond membrane,the MC3T3-E1 cells on pure polycaprolactone and polycaprolactone/7.5%nanodiamond-phospholipid membrane were mostly rhomboid or spindle-shaped fibers,and the cells were more closely connected.Alkaline phosphatase staining showed that MC3T3-E1 cells on polycaprolactone/7.5%nanodiamond-phospholipid membrane exhibited stronger osteogenic differentiation ability compared with pure polycaprolactone membrane and polycaprolactone/7.5%nanodiamond membrane.(3)The results indicate that the polycaprolactone/nanodiamond-phospholipid composite material has good mechanical properties,hydrophilicity,biocompatibility,and the ability to promote osteogenic differentiation in vitro.
9.Therapeutic effect and mechanism of sanguinarine in rats with postherpetic neuralgia by regulating CXCL12/CXCR4 signaling pathway
Jiayu TIAN ; Dan FENG ; Han HU ; Shuli ZHANG ; Shengxiong TONG ; Shaojun LI
Chinese Journal of Immunology 2025;41(1):57-62
Objective:To investigate therapeutic effect and mechanism of sanguinarine on postherpetic neuralgia(PHN)rats by modulating C-X-C chemokine ligand 12(CXCL12)/C-X-C chemokine receptor 4(CXCR4)signaling pathway.Methods:SD rats were randomly grouped into control group,model group,low-dose(50 mg/kg)sanguinarine group,high-dose(100 mg/kg)sanguina-rine group,NUCC-390(CXCL12/CXCR4 signal activator,2.2 mg/kg)group,high-dose(100 mg/kg)sanguinarine+NUCC-390(2.2 mg/kg)group,with 10 rats in each group.Rats in model group and drug-treated groups were injected with resin toxin(RTX)by intraperitoneal injection to induce PHN model,rats in control group were intraperitoneally injected with an equal dose of normal saline containing 10%Tween 80 and 10%ethanol.After treatment of sanguinarine and NUCC-390,symptoms of long-term spontaneous pain,mechanical hyperalgesia and thermal hyperalgesia were detected,number of spontaneous paw withdrawal reflexes,paw with-drawal threshold to mechanical stimulation(PWMT),and response latency to thermal stimulation(PWTL)were compared;spinal cord nerve cell apoptosis was detected by TUNEL staining;ELISA was used to detect levels of inflammatory factors TNF-α,IL-1β,cyclooxygenase-2(COX-2)in rat spinal cord tissue and serum;Western blot was used to detect expressions of CXCL12/CXCR4 path-way-related proteins in spinal cord tissues of rats in each group.Results:Compared with control group,PWMT of model group was obviously decreased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were obviously increased(P<0.05).Compared with model group,PWMT of rats in low-dose sanguinarine group and high-dose sanguinarine group was increased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were all decreased(P<0.05);PWMT of rats in NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Compared with high-dose sanguinarine group,PWMT of rats in high-dose sanguinarine+NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Conclusion:Sanguinarine can reduce expression of inflammatory factors by down-regulating CXCL12/CXCR4 signaling pathway,thereby preventing occurrence of inflammatory response in PHN rats,inhibiting apoptosis of spinal nerve cells,and finally reducing long-term spontaneous pain,mechanical allodynia and thermal hypoalgesia in rats.
10.Research progress on assessment tools for health behavior motivation in patients with cardiovascular diseases
Zhifeng ZHANG ; Lei LIU ; Yikang XU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Kaiwen ZHAN ; Siqi SUN ; Manman LI
Journal of Shenyang Medical College 2025;27(2):198-201
Health behavior motivation significantly affects the quality of life of patients with cardiovascular diseases.Assessing the level of health behavior motivation can measure the health behavior of individuals,help to promote the participation rate of cardiac rehabilitation,reduce the readmission rate of patients,and promote patients'healthy lifestyles.This article reviews the content,characteristics and application of assessment tools for health behavior motivation of patients with cardiovascular diseases at home and abroad,with the aim of providing references for the development and application of such tools in China,and offering a basis for scientifically assessing their health behavior motivation level and formulating effective strategies to promote health behavior motivation.

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