1.Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
Yuzhuo WEI ; Li LIU ; Shu BU ; Yongqi WANG ; Zhiwei MIAO ; Yi XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):40-50
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos (DH) in the treatment of ulcerative colitis (UC) using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium (DSS). The experimental groups were the normal group, the model group, the salazosulfapyridine group (100 mg·kg-1), and the low, medium, and high dose groups of DH (1.2, 2.4, and 4.8 g·kg-1). The efficacy of the treatment was assessed through the general condition of the mice, histopathological examination, and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA (mRNA) detection of colonic angiogenesis-related mediators, vascular endothelial growth factor (VEGF) immunohistochemistry, microvessel density (MVD) detection, and transmission electron microscopy. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH, of which the core targets were tumor protein 53 (TP53), JUN, interleukin (IL)-6, Akt1, and tumor necrosis factor (TNF). Compared with the normal group, mice in the model group showed significant weight loss, colon shortening, and high DAI score, increased expression of inflammatory factors IL-6, IL-1β, and TNF-α, as well as increased mRNA expression levels of angiogenesis-related mediators VEGF, vascular cell adhesion molecule 1 (VCAM1), angiotensin 1 (Ang1), matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased, and the protein expression of the PI3K/Akt pathway was increased (P<0.05). The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group, mice in the DH groups had significantly reduced weight loss and colon shortening, lower DAI scores, and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition, there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway (P<0.05). ConclusionNetwork pharmacology, molecular docking, and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC, and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
2.Inhibition of Angiogenesis by Sanguisorbae Radix and Sophorae Flos in Ulcerative Colitis Mice by Regulating PI3K/Akt Signaling Pathway
Yuzhuo WEI ; Li LIU ; Shu BU ; Yongqi WANG ; Zhiwei MIAO ; Yi XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):40-50
ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos (DH) in the treatment of ulcerative colitis (UC) using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium (DSS). The experimental groups were the normal group, the model group, the salazosulfapyridine group (100 mg·kg-1), and the low, medium, and high dose groups of DH (1.2, 2.4, and 4.8 g·kg-1). The efficacy of the treatment was assessed through the general condition of the mice, histopathological examination, and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA (mRNA) detection of colonic angiogenesis-related mediators, vascular endothelial growth factor (VEGF) immunohistochemistry, microvessel density (MVD) detection, and transmission electron microscopy. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH, of which the core targets were tumor protein 53 (TP53), JUN, interleukin (IL)-6, Akt1, and tumor necrosis factor (TNF). Compared with the normal group, mice in the model group showed significant weight loss, colon shortening, and high DAI score, increased expression of inflammatory factors IL-6, IL-1β, and TNF-α, as well as increased mRNA expression levels of angiogenesis-related mediators VEGF, vascular cell adhesion molecule 1 (VCAM1), angiotensin 1 (Ang1), matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased, and the protein expression of the PI3K/Akt pathway was increased (P<0.05). The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group, mice in the DH groups had significantly reduced weight loss and colon shortening, lower DAI scores, and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition, there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway (P<0.05). ConclusionNetwork pharmacology, molecular docking, and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC, and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.
3.Ca2+ Release From The Endoplasmic Reticulum Mediates Electric Field Guided Cell Migration of Dictyostelium discoideum
Yi-Fan WANG ; Shu-Qin YUAN ; Run-Chi GAO ; San-Jun ZHAO
Progress in Biochemistry and Biophysics 2025;52(5):1252-1263
ObjectiveAs a second messenger in intracellular signal transduction, Ca2+ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca2+ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca2+ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca2+ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca2+ chelator EGTA, Ca2+-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca2+ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca2+ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca2+ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca2+ influx and intracellular Ca2+ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca2+ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca2+ release mediated by caffeine restored the electrotaxis of the Gα2-, Gβ -, and Erk2- mutant cells partially or completely, but did not restore electrotaxis in the Gγ- mutant cells. ConclusionCa2+ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.
4.The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice
Yu-hao ZHANG ; Yi-ning LI ; Xin-hai JIANG ; Wei-zhi WANG ; Shun-wang LI ; Ren SHENG ; Li-juan LEI ; Yu-yan ZHANG ; Jing-rui WANG ; Xin-wei WEI ; Yan-ni XU ; Yan LIN ; Lin TANG ; Shu-yi SI
Acta Pharmaceutica Sinica 2025;60(1):141-149
Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg-1) and a high dose (15 mg·kg-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D303)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.
5.The Influence of Social Context on Perceptual Decision Making and Its Computational Neural Mechanisms
Yu-Pei LIU ; Yu-Shu WANG ; Bin ZHAN ; Rui WANG ; Yi JIANG
Progress in Biochemistry and Biophysics 2025;52(10):2568-2584
Perceptual decision making refers to the process by which individuals make choices and judgments based on sensory information, serving as a fundamental ability for human adaptation to complex environments. While traditional research has focused on perceptual decision making in isolated contexts, growing evidence highlights the profound influence of social contexts prevalent in real-world scenarios. As a crucial factor supporting individual survival and development, social context not only provides rich information sources but also shapes perceptual decision making through top-down processing mechanisms, prompting researchers to recognize the inherently social nature of human decisions. Empirical studies have demonstrated that social information, such as others’ choices or group norms, can systematically bias individuals’ perceptual decisions, often manifesting as conformity behaviors. Social influence can also facilitate performance under certain conditions, particularly when individuals can accurately identify and adopt high-quality social information. The impact of social context on perceptual decisions is modulated by a variety of external and internal factors, including group characteristics(e.g., group size, response consistency), attributes of peers (e.g., familiarity, social status, distinctions between human and artificial agents), as well as individual differences such as confidence, personality traits, and developmental stage. The motivations driving social influence encompass three primary mechanisms: improving decision accuracy through informational influence, gaining social acceptance through normative influence, and maintaining positive self-concept. Recent computational approaches have employed diverse theoretical frameworks to provide valuable insights into the cognitive mechanisms underlying social influence in perceptual decision making. Reinforcement learning models demonstrate how social feedback shapes future choices through reward-based updating. Bayesian inference frameworks describe how individuals integrate personal beliefs with social information based on their respective reliabilities, dynamically updating beliefs to optimize decisions under uncertainty. Drift diffusion models offer powerful tools to decompose social influence into distinct cognitive components, allowing researchers to differentiate between changes in perceptual processing and shifts in decision criteria. Collectively, these models establish a comprehensive methodological foundation for disentangling the multiple pathways by which social context shapes perceptual decisions. Neuroimaging and electrophysiological studies provide converging evidence that social context influences perceptual decision making through multi-level neural mechanisms. At early perceptual processing stages, social influence modulates sensory evidence accumulation in parietal cortex and directly alters primary visual cortex activity, while guiding selective attention to stimulus features consistent with social norms through attentional alignment mechanisms. At higher cognitive levels, the reward system (ventral striatum, ventromedial prefrontal cortex) is activated during group-consistent decisions; emotion-processing networks (anterior cingulate cortex, insula, amygdala) regulate experiences of social acceptance and rejection; and mentalizing-related brain regions (dorsomedial prefrontal cortex, temporoparietal junction) support inference of others’ mental states and social information integration. These neural circuits work synergistically to achieve top-down multi-level modulation of perceptual decision making. Understanding the mechanisms by which social context shapes perceptual decision making has broad theoretical and practical implications. These insights inform the optimization of collective decision-making, the design of socially adaptive human-computer interaction systems, and interventions for cognitive disorders such as autism spectrum disorder and anorexia nervosa. Future studies should combine computational modeling and neuroimaging approaches to systematically investigate the multi-level and dynamic nature of social influences on perceptual decision making.
6.The protective effect of Jujing formula on tretina of mice with dry age-related macular degeneration
Cheng-Cheng QI ; Ruo-Ying FAN ; Xue-Sen WANG ; Shu-Lan SU ; Yue ZHU ; Sheng GUO ; Hong-Jie KANG ; Xue-Yi ZHOU ; Jin-Ao DUAN
Chinese Pharmacological Bulletin 2024;40(7):1358-1367
Aim To investigate the protective effect of Jujing formula on retina of mice with dry age-related macular degeneration(AMD).Methods The mouse model of dry AMD was induced by intraperitoneal in-jection of sodium iodate,and the prognosis was given to the Jujing formula.Retinal thickness was detected by optical coherence tomography(OCT),the retinal morphological changes were observed by hematoxylin-eosin(HE)staining,and the apoptosis of retinal cells was detected by in situ terminal transferase labeling(TUNEL)staining.Combination of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1 β)in eyeballs and serum,superoxide dis-mutase(SOD),glutathione(GSH)and malondialde-hyde(MDA)were evaluated to assess the protective effects of Jujing formula on retinal injury in mice with dry AMD.Results The results of OCT,HE and TUNEL staining showed that Jujing formula significant-ly improved the retinal injury induced by sodium iodate in mice with dry AMD,increased the retinal thickness(P<0.05),reduced the apoptosis of retinal cells(P<0.01),and increased the levels of GSH,IL-6 and SOD activity in eyeballs and serum(P<0.01).The levels of TNF-α,IL-6,IL-1β and MDA were reduced(P<0.01).Conclusions Jujing formula has certain therapeutic effects on retinal injury in dry AMD,which may be related to inhibiting inflammatory response and enhancing antioxidant capacity.
7.Curative effect analysis of anterior cervical discectomy and fusion in patients with cervical spondylosis of vertebral artery type
Yi-Xiang AI ; Jian-Tao LIU ; Ding-Jun HAO ; Xi GONG ; Yi-Han ZHU ; Xing-Yuan LI ; Xi-Wei ZHANG ; Kao WANG ; Jia-Jun SUN ; Shu-Yuan ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(7):670-675
Objective To investigate the clinical effect of anterior cervical discectomy and fusion(ACDF)in the treatment of cervical spondylosis of vertebral artery type(CSA).Methods The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed.There were 25 males and 17 females,aged from 30 to 74 years old with an average of(53.9±11.0)years old.There were 18 cases with single-segment lesions,17 cases with two-segment lesions,and 7 cases with three-segment lesions.The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score(CHE),the Neck Disability Index(NDI)and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months.Results All 42 ACDF patients were followed up for 6 to 30 months with an average of(14.0±5.2)months.The operative time ranged from 95 to 220 min with an average of(160.38±36.77)min,the intraoperative blood loss ranged from 30 to 85 ml with an average of(53.60±18.98)ml.Tow patients had mild postoperative dysphagia,which improved with symptomatic treatment such as nebulized inhalation.CHE score decreased from(4.05±0.96)preoperatively to(2.40±0.70)at 6 months postoperatively(t=12.97,P<0.05).The number of improved vertigo at 6 months postoperatively was 38,with an im-provement rate of 90.5%.NDI score was reduced from(34.43±8.04)preoperatively to(20.76±3.91)at 6 months postopera-tively(t=1 1.83,P<0.05).The cervical curvature Cobb angle improved from(8.04±6.70)° preoperatively to(12.42±5.23)° at 6 months postoperatively(t=-15.96,P<0.05).Conclusion The ACDF procedure has outstanding clinical efficacy in treating CSA.The operation can rapidly relieve patients'episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature.However,it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in pa-tients,and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.
8.Early gait analysis after total knee arthroplasty based on artificial intelligence dynamic image recognition
Ming ZHANG ; Ya-Nan SUI ; Cheng WANG ; Hao-Chong ZHANG ; Zhi-Wei CAI ; Quan-Lei ZHANG ; Yu ZHANG ; Tian-Tian XIA ; Xiao-Ran ZU ; Yi-Jian HUANG ; Cong-Shu HUANG ; Xiang LI
China Journal of Orthopaedics and Traumatology 2024;37(9):855-861
Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P<0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P<0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P<0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P<0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.
9.Comparison of Blood Oxygen Saturation Detection Methods in Patients with Hyperleukocytic Acute Leukemia
Hui-Xia GUO ; Shu-Ya CAO ; Yi-Juan CHEN ; Qian LI ; Yue WU ; Yu-Xi SHANG ; Li-Ru WANG
Journal of Experimental Hematology 2024;32(4):1026-1031
Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P<0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.
10.Pediatric appendicovesical fistula: a case report and literature review
Zheng FANG ; Xiangming YAN ; Ting ZHANG ; Xu CAO ; Tianyi WANG ; Hongchao WANG ; Jun LIU ; Ting FENG ; Yi SUN ; Shu DAI
Chinese Journal of Urology 2024;45(8):619-623
Objective:This study aims to discuss the diagnosis and treatment of pediatric appendicovesical fistula (AVF).Methods:A retrospective analysis was conducted on the clinical data of a pediatric patient with AVF admitted to our hospital in March 2023. The patient was a 6-year and 11-month old male who was hospitalized on March 21, 2023, due to difficulty urinating accompanied by diarrhea for two weeks. Computed tomography (CT) revealed bladder stones. The preoperative diagnosis was bladder stones. Transurethral cystoscopic lithotripsy with laser was performed under general anesthesia. Two weeks postoperatively, the child presented with recurrent symptoms of frequent urination, urinary pain, and diarrhea. Urine routine examination indicated a urinary tract infection. Over a month of antibiotic treatment was ineffective, and symptoms such as pneumaturia and fecaluria emerged, with exacerbation of diarrhea, suggesting the possibility of a fistulous tract between the child's intestine and bladder. Further bladder ultrasonography with contrast showed microbubbles of contrast medium leaking from the right posterior bladder wall into the intestinal tract. Enhanced magnetic resonance imaging (MRI) demonstrated a small, sharp tube-like shadow at the upper edge of the right posterior bladder, with a strip-like, significantly enhanced shadow within the lumen. The preoperative diagnosis was revised to appendicovesical fistula. During cystoscopic examination, a papillary-like protrusion was identified on the right lateral wall of the bladder, with no evident orificium fistulae or foreign body discharge noted at the protrusion site. Consequently, robot-assisted laparoscopic partial cystectomy, appendectomy, and lysis of adhesions were performed.Results:The patient was administered antibiotic for a 10-day course of anti-infection and a urinary catheter was maintained for 13 days. The patient recovered entirely and had been discharged after the removal of the urinary catheter. At an 11-month follow-up, there were no reported specific discomforts.Conclusions:Pediatric AVF is rare, and bladder contrast-enhanced ultrasonography and MRI are preferred for initial diagnostic evaluation. The diagnosis can be confirmed by specific clinical presentations such as intermittent pneumaturia and fecaluria, diarrhea with bladder stones. Laparoscopic surgery or robot-assisted laparoscopic surgery could be a feasible treatment option.

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