1.Exploration on the Protective Effects and Mechanisms of Modified Shenqi Dihuang Decoction on Podocytes in db/db Mice Based on ROS/NLRP3/GSDMD Signaling Pathway
Guiyan SUN ; Mingzhe LI ; Yan SHI ; Xiaoyan ZHUANG ; Xiaonan DUAN ; Moyan ZHANG ; Zhihan LEI ; Chunhui ZHANG ; Guanqi YANG ; Yufeng YANG ; Jing LYU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(11):123-132
Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.
2.Exploration on the Protective Effects and Mechanisms of Modified Shenqi Dihuang Decoction on Podocytes in db/db Mice Based on ROS/NLRP3/GSDMD Signaling Pathway
Guiyan SUN ; Mingzhe LI ; Yan SHI ; Xiaoyan ZHUANG ; Xiaonan DUAN ; Moyan ZHANG ; Zhihan LEI ; Chunhui ZHANG ; Guanqi YANG ; Yufeng YANG ; Jing LYU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(11):123-132
Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.
3.Modified Wenshen Yixin Formula (温肾益心方加减) for Coronary Heart Disease Complicated with Hypothyroidism of Spleen-kidney Yang Deficiency:A Prospective Real-world Study of 51 Cases
Aolin LI ; Zhipeng YAN ; Lu LIAN ; Qianqian ZHANG ; Chi ZHANG ; Boyu ZHU ; Lei WEI ; Zhihan YANG ; Junping ZHANG
Journal of Traditional Chinese Medicine 2024;65(20):2116-2125
ObjectiveTo observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula (温肾益心方加减, MWYF) as an auxiliary treatment of coronary heart disease (CHD) complicated with hypothyroidism of spleen-kidney yang deficiency. MethodsA total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group (67 cases) and experimental group (68 cases) according to the patients' wishes of herbal medicine administration. The control group was given conventional western medicine, while the treatment group was additionally given MWYF, 1 dose per day; both groups were treated for 8 weeks. The traditional Chinese medicine (TCM) syndrome scores, angina scores, SF-36 scores, thyroid function indicators including thyroid stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3), as well as serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), monocyte chemoattractant ligand 2 (CCL2), and tumor necrosis factor-related activator protein (CD40L) levels before and after treatment were compared between the two groups. The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups. The effectiveness regarding TCM syndrome and angina pectoris was evaluated, and the safety was assessed. ResultsBias was adjusted by matching on propensity score, and 102 cases were finally included in the statistical analysis, with 51 cases in each group. The total effective rate regarding TCM syndrome [94.12% (48/51) versus 64.71% (33/51)], the total effective rate regarding angina pectoris [80.39% (41/51) versus 62.75% (32/51)], and the reduction and discontinuation rate of thyroid hormone preparation [39.21% (20/51) versus 5.88% (3/51)] were significantly higher in the experimental group than those in the control group (P<0.05 or P<0.01). After treatment, the total TCM syndrome score, individual scores of major symptoms , the major symptoms score, the secondary symptoms score, angina pectoris score, and TSH level were significantly reduced (P<0.01), while all dimensions of SF-36 scores, T4, T3, and cAMP levels significantly increased in both groups (P<0.05 or P<0.01). The dosage of thyroid hormone preparations and the levels of cGMP, CCL2, and CD40L in the experimental group significantly decreased after treatment (P<0.01). When compared between the two groups after treatment, the total TCM syndrome score, the major symptoms score, the scores of individual major symptom (chest tightness, chest pain, fear of cold, cold limbs, waist and kness soreness and weakness), the secondary symptoms score, angina pectoris score, TSH, cGMP, CCL2, and CD40L levels of the experimental group were significantly lower than those of the control group (P<0.05 or P<0.01), while all dimension scores of SF-36, T4, T3, and cAMP levels were significantly higher (P<0.01). A total of three adverse events occurred during treatment, none of which were judged to be related to the interventions of this study. ConclusionMWYF can significantly ameliorate the TCM syndrome, angina pectoris, quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency, and can promote the reduction and disconti-nuation of thyroid hormone preparations. The mechanism may be related to the regulation of cAMP/cGMP balance, the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.
4.Clinical application of adaptive minute ventilation + IntelliCycle ventilation mode in patients with mild-to-moderate acute respiratory distress syndrome
Zhihan LIU ; Xingwei DI ; Lei ZHONG ; Zichen SU ; Bo XU ; Xiaoyu ZHANG ; Zhuang LIANG ; Guangming ZHAO ; Zhansheng HU
Chinese Critical Care Medicine 2020;32(1):20-25
Objective:To verify the clinical safety and efficacy of new intelligent ventilation mode adaptive minute ventilation (AMV)+IntelliCycle ventilation in patients with mild-to-moderate acute respiratory distress syndrome (ARDS).Methods:The patients with mild-to-moderate ARDS, admitted to intensive care unit (ICU) of the First Affiliated Hospital of Jinzhou Medical University from February 2018 to February 2019, were enrolled in the study. The patients were divided into synchronous intermittent mandatory ventilation+pressure support ventilation (SIMV+PSV) group and AMV+IntelliCycle group according to the random number table method. All patients were given mechanical ventilation, anti-infection, analgesia and sedation, nutritional support and symptomatic treatment of primary disease after admission. SV800 ventilator was used for mechanical ventilation. In the AMV+IntelliCycle group, after setting the minute ventilation volume (VE), inhaled oxygen concentration (FiO 2) and positive end expiratory pressure (PEEP), the ventilator was turned on the full-automatic mode, and the preset value of VE percentage was 120%. In the SIMV+PSV group, the ventilator parameters were set as follows: the ventilation frequency was 12-20 times/min, the inspiratory expiratory ratio was 1∶1-2, the peak inspiratory pressure (PIP) limit level was 35-45 cmH 2O (1 cmH 2O = 0.098 kPa), and the setting of FiO 2 and PEEP was as the same as that of AMV+IntelliCycle group, the triggering flow was set to 2 L/min. All of the clinical parameters between the two groups were compared. The main outcomes were duration of mechanical ventilation, ventilator alarm times, manual operation times, and the mechanical power; the secondary outcomes were respiratory rate (RR), VE, tidal volume (VT), PIP, mouth occlusion pressure (P0.1), static compliance (Cst), work of breathing (WOB), and time constant at 0, 6, 12, 24, 48, 72, and 120 hours; and the blood gas analysis parameters of patients before and after ventilation were recorded. Results:A total of 92 patients with mild-to-moderate ARDS were admitted during the study period, excluding those who quit the study due to death, abandonment of treatment, accidental extubation of tracheal intubation and so on. Eighty patients were finally enrolled in the analysis, with 40 patients in SIMV+PSV group and AMV+IntelliCycle group respectively. ① Results of main outcomes: compared with the SIMV+PSV mode, AMV+IntelliCycle ventilation mode could shorten the duration of mechanical ventilation (hours: 106.35±55.03 vs. 136.50±73.78), reduce ventilator alarm times (times: 10.35±5.87 vs. 13.93±6.87) and the manual operations times (times: 4.25±2.01 vs. 6.83±3.75), and decrease the mechanical power (J/min: 12.88±4.67 vs. 16.35±5.04, all P < 0.05). But the arterial partial pressure of carbon dioxide (PaCO 2) of AMV+IntelliCycle group was significantly higher than that of SIMV+PSV group [mmHg (1 mmHg = 0.133 kPa): 41.58±6.81 vs. 38.45±5.77, P < 0.05]. ② Results of secondary outcomes: the RR of both groups was improved significantly with the prolongation of ventilation time which showed a time effect ( F = 4.131, P = 0.005). Moreover, compared with SIMV+PSV mode, AMV+IntelliCycle mode could maintain a better level of RR, with intervention effect ( F = 5.008, P = 0.031), but no interaction effect was found ( F = 2.489, P = 0.055). There was no significant difference in VE, PIP, P0.1 or Cst between the two groups, without intervention effect ( F values were 3.343, 2.047, 0.496, 1.456, respectively, all P > 0.05), but they were significantly improved with the prolongation of ventilation time in both groups, with time effect ( F values were 2.923, 12.870, 23.120, 7.851, respectively, all P < 0.05), but no interaction effect was found ( F values were 1.571, 1.291, 0.300, 0.354, respectively, all P > 0.05). The VT, WOB or time constant in both groups showed no significant changes with the prolongation of ventilation time, and no significant difference was found between the two groups, there was neither time effect ( F values were 0.613, 1.049, 2.087, respectively, all P > 0.05) nor intervention effect ( F values were 1.459, 0.514, 0.923, respectively, all P > 0.05). Conclusion:AMV+IntelliCycle ventilation mode can shorten the ventilation time of patients with mild-to-moderate ARDS, reduce mechanical power, and reduce the workload of medical care, but PaCO 2 in the patients with AMV+IntelliCycle mode is higher than that in the patients with SIMV+PSV mode.
5.Role of dynamic magnetic resonance imaging in the diagnosis of female stress urinary incontinence
Zhikang YU ; Zhihan YAN ; Lei HUANG ; Chuanwan MAO ; Yunxin ZHOU ; Jiayu LIN
Chinese Journal of Urology 2008;29(8):560-563
Objective To evaluate the application of dynamic magnetic resonance imaging in the diagnosis of female stress urinary incontinence(SUI). Methods Dynamic magnetic resonance imaging(DMRI)were performed on 30 healthy female volunteers and 35 female SUI patients.DMRI of the pelvic floor at rest and OR maximal strain were performed by using sagittal T2-weighted fast gradient sequences.The distance of Urethra-vesical junction to the pubococcygeal line,the posterior vesicourethral angle and angle of inclination of the urethral axis were measured at rest and on maximal strain position.The t-value exact test were used to analyze the data. Results At rest the Urethravesical junction laid above pubococcygeal line on both control and SUI groups.Mean distance from the Urethra-vesical junction to pubococcygeal line at rest had no difference between the two groups.On straining,the mean Urethra-vesical junction descent distance in the SUI group(-0.9±1.1cm)was significantly higher than in control group(-0.14±0.3 cm),(P<0.001).On straining,the mean angle of urethral inclination in the SUI group(65±37°)was significantly bigger than in control groups (17±21°),(P<0.05).The posterior vesicourethral angle in the SUI groups(156±36°)was significantly bigger than in control groups(113±28°),(P<0.05). Conclusion Dynamic magnetic resonance imaging is a non-invasive.easily applied method in the diagnosis of SUI.

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