1.Ten-year real-world data analysis of clinical characteristics in treatment-naive patients with highly suspected prostate cancer and PSA level ≥20 ng/mL
Baolong PENG ; Mingzhe CHEN ; Junxin WANG ; Ranlu LIU ; Baojie MA ; Shanqi GUO ; Xingkang JIANG
Journal of Modern Urology 2025;30(1):13-21
[Objective] To analyze the clinicopathological characteristics of treatment-naive patients with highly suspected prostate cancer (PCa) with prostate-specific antigen (PSA) level ≥20 ng/mL, to provide reference for promoting early screening of PCa. [Methods] A retrospective analysis was conducted on the clinical data of treatment-naive patients with PSA level ≥20 ng/mL, undergoing prostate biopsy for highly suspected PCa at the Department of Urology, Tianjin Medical University Second Hospital during Jan.2013 and Jun.2023. The correlation between patients' age, body mass index (BMI), PSA, prostate volume (PV), prostate cancer-specific antigen density (PSAD), prostate imaging reporting and data system (PI-RADS) score, and International Society of Urological Pathology (ISUP) grade with highly suspected PCa metastasis and PSA stratification were analyzed. [Results] A total of 1778 suspected patients were enrolled. Pathological findings confirmed PCa in 1465 cases (82.4%), with 487(33.2%) diagnosed as metastatic PCa. Over the past decade, the number of patients undergoing prostate biopsy for highly suspected PCa and being confirmed has been increasing annually, with the proportion of metastatic cases remaining at around 30%. Compared with those with PSA level being 20-50 ng/mL, patients with PSA level >50 ng/mL had older age, lower BMI, higher PSAD, higher PI-RADS, higher ISUP, more diverse pathological types, and a higher incidence of metastasis (P<0.05) with lower proportion of urban residents. Additionally, analysis of metastatic PCa cases showed that 46.8%(228/487) had oligometastasis (≤5 metastatic lesions), including 99.0% bone metastasis, 4.1% extraregional lymph node metastasis, and 4.3% other organ metastasis. [Conclusion] Over the past 10 years, there has been a continuous increase in the number of treatment-naive biopsied cases and newly diagnosed cases of highly suspicious PCa with PSA level ≥20 ng/mL, while the proportion of metastatic cases remains high. Therefore, proactive efforts should be made to promote early screening of high-risk suspected cases.
2.Efficacy of flexible ureteroscope lithotripsy with flexible vacuum-assisted urethral access sheath for 1-2 cm lower renal calyceal stones
Dujian WANG ; Qinglai TANG ; Fade LIU ; Xingzhu ZHOU ; Rongzhen TAO
Journal of Modern Urology 2025;30(1):29-33
[Objective] To compare the clinical efficacy and safety of flexible ureteroscope lithotripsy (FURL) combined with flexible vacuum-assisted urethral access sheath (FV-UAS) and traditional UAS in the treatment of 1-2 cm lower renal calyceal stones, so as to provide reference for clinical practice. [Methods] Clinical data of 157 patients with 1-2 cm lower renal calyceal stones treated with FURL during Mar.2021 and Oct.2023 were retrospectively analyzed, including 80 treated with traditional UAS, and 77 with FV-UAS.General and clinical information of the two groups were compared. [Results] The immediate stone-free rate (SFR) (84.4% vs.67.5%, P=0.013) and final SFR (88.3% vs. 75.0%, P=0.032) of the FV-UAS group were significantly higher than those of the traditional UAS group, with significant difference.The incidence of postoperative complications such as fever, renal colic, and perirenal hematoma was significantly higher in the traditional UAS group than in the FV-UAS group (15.0% vs.5.2%, P=0.042). After treatment with anti-infective and analgesic drugs, both groups were improved, and no severe sepsis or septic shock occurred after surgery.The hospitalization expenses of the FV-UAS group were significantly lower than those of the traditional UAS group [ (18 341±1519)yuan vs.(19 152±1826)yuan, P=0.003]. [Conclusion] Compared to the traditional UAS, the combination of FURL and FV-UAS for the 1-2 cm lower renal calyceal stones has a high SFR and low incidence of complications.Patients experience less pain, recover faster and spend less.It's a new treatment option for inferior calyceal calculi.
3.Preliminary application of sacral neuromodulation in patients with benign prostatic hyperplasia complicated with underactive bladder after transurethral resection of the prostate
Ning LIU ; Yan ZHANG ; Tao LI ; Qiang HU ; Kai LU ; Lei ZHANG ; Jianping WU ; Shuqiu CHEN ; Bin XU ; Ming CHEN
Journal of Modern Urology 2025;30(1):39-42
[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.
4.Mechanism of Modified Danggui Shaoyaosan in Improving Inflammation and Apoptosis in Acne via Regulating JNK/p38 MAPK Pathway
Gongzhen CHEN ; Yuqi YANG ; Xin LIU ; Ting TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):31-40
ObjectiveTo explore the therapeutic effects and mechanisms of modified Danggui Shaoyaosan on acne based on the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway. MethodsA rat ear acne model was established in SD rats, and the rats were divided into a blank group, a model group, and low-, medium-, and high-dose groups of modified Danggui Shaoyaosan (7.15, 14.30, 28.60 g·kg·d-1), with six rats in each group. After the administration for 14 consecutive days, morphological changes in the rats' auricles were observed, and hematoxylin-eosin (HE) staining was used to examine the pathological changes in the acne-affected ear tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the ear tissue. Quantitative reverse transcription polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression levels of Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), JNK, and p38 MAPK in the ear tissue. Additionally, Western blot analysis was conducted to assess the protein levels of Caspase-3, Bcl-2, Bax, JNK, and p38 MAPK in the ear tissue. The active components and key targets of modified Danggui Shaoyaosan in the treatment of acne were identified through network pharmacology analysis. Molecular docking was then employed to evaluate the interactions between the main active components and the key targets. ResultsThe results of the animal experiment demonstrated that compared with those in the blank group, rats in the model group exhibited redness, swelling, thickening, hardening, dryness, and roughness of the auricle. The surface showed sebaceous scales and desquamation, accompanied by acne-like lesions such as papule-like elevations or cysts. Histopathological changes included keratinization, epidermal thickening, dermal collagen fiber degeneration and necrosis, subcutaneous muscle degeneration and necrosis, inflammatory cell infiltration, and fibrous tissue proliferation. The mRNA and protein expression levels of IL-1β, TNF-α, Caspase-3, Bax, JNK, and p38 MAPK were significantly increased (P<0.01), while those of Bcl-2 were significantly decreased (P<0.01). In comparison to the model group, the modified Danggui Shaoyaosan groups showed marked improvement in acne-like lesions of the auricle, with varying degrees of histopathological damage reduction. Additionally, the mRNA and protein expression levels of IL-1β, TNF-α, Caspase-3, Bax, JNK, and p38 MAPK in the tissue were significantly decreased (P<0.05, P<0.01), while those of Bcl-2 were significantly increased (P<0.05, P<0.01). Network pharmacology analysis indicated that the key compounds in modified Danggui Shaoyaosan responsible for its effects in treating acne may include acacetin, kaempferol, luteolin, quercetin, wogonin, and baicalein. These compounds exerted their effects by modulating core targets such as TNF, IL-1β, Caspase-3, and Bcl-2, thereby alleviating inflammation and apoptosis and ultimately improving acne symptoms. ConclusionModified Danggui Shaoyaosan may exert its therapeutic effects on acne by inhibiting the activation of the JNK/p38 MAPK pathway, thereby alleviating inflammation and apoptosis.
5.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
6.Effect of Berberine-Baicalin Combination on Fecal Microbiota Transplantation-induced Type 2 Diabetes Mellitus Due to Internal Accumulation of Dampness-heat in Mice from Perspectives of Gut Microbiota and Metabolomics
Mengjie CHEN ; Yimin LIU ; Yun ZHOU ; Keming YU ; Min XIA ; Hongning LIU ; Yanhua JI ; Zhijun ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):52-64
ObjectiveTo investigate the mechanisms by which the combination of berberine (BBR) and baicalin (BAI) ameliorates type 2 diabetes mellitus (T2DM) due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group (n=10) and a T2DM (syndrome of internal accumulation of dampness-heat) fecal microbiota transplantation group (n=20). The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage, respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group (n=8) and a BBR-BAI group (n=11). BBR was administrated at a dose of 200 mg·kg-1, and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin (INS), triglycerides (TG), total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1, zonula occludens-1 (ZO-1), and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction(Real-time PCR) was employed to assess the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS), respectively. ResultsThe BBR-BAI combination lowered the FBG, HbA1c, and INS levels (P<0.05, P<0.01) and alleviated insulin resistance (P<0.01) in T2DM mice. Additionally, BBR-BAI elevated the levels of ZO-1, occludin, and claudin-1 (P<0.05, P<0.01) and down-regulated the expression levels of TNF-α, IL-1β, and IL-6 in the colon (P<0.05, P<0.01). The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus, Phascolarctobacterium, and Akkermansia (P<0.05), while significantly decreasing the relative abundance of Alistipes, Odoribacter, and Colidextribacter (P<0.05). UPLC-Q-TOF-MS identified 28 differential metabolites, which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.
7.Effect of Modified Chunzetang on Bladder Fibrosis and Detrusor Function in Rats with Neurogenic Bladder Urinary Retention Induced by Spinal Cord Injury via Regulating NF-κB/TGF-β1 Signaling Pathway
Zhenhua XU ; Yanjie LI ; Yafeng REN ; Haoyuan LIU ; Bochao ZHU ; Juan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):95-103
ObjectiveTo investigate the therapeutic effect and mechanism of modified Chunzetang on bladder fibrosis and detrusor function in rats with neurogenic bladder urinary retention induced by spinal cord injury. MethodsIn this study, an improved Hassan Shaker spinal cord transection method was used to establish a model of neurogenic bladder urinary retention induced by spinal cord injury, and rats with a spinal cord injury behavior score of 0 were selected for follow-up experiments. The selected rats were randomly divided into a model group (normal saline gavage), low-dose traditional Chinese medicine (TCM) group (gavage of 14.4 g·kg-1 modified Chunzetang), high-dose TCM group (gavage of 28.8 g·kg-1 modified Chunzetang), positive drug group [intraperitoneal injection of 0.05 g·kg-1 nuclear transcription factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)], and combination group (intraperitoneal injection of 0.05 g·kg-1 PDTC + gavage of 28.8 g·kg-1 modified Chunzetang). The rats in these groups were administrated with corresponding drugs once a day for four weeks. The BL-420s biofunction acquisition system was used in the experiment to calculate the urodynamic indexes, and the isolated bladder was quickly weighed. The detrusor traction experiment was used to record the minimum bladder contraction tension and frequency in each group. The pathological morphology and tissue fibrosis of detrusor in each group observed by Hematoxycin-eosin (HE) staining and Masson staining were compared. The expression level of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Western blot was used to detect the protein expression of NF-κB p65, nuclear transcription factor-κB suppressor protein α (IκBα), transforming growth factor-β1 (TGF-β1), type Ⅰ collagen (ColⅠ), and type Ⅲ collagen (ColⅢ) in bladder tissue of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in serum levels of IL-6, IL-1β, and TNF-α. ResultsCompared with that in the sham operation group, the pressure at the urinary leakage point in the model group decreased (P<0.01), and the bladder mass, bladder contractile tension, maximum bladder capacity, and bladder compliance increased (P<0.05,P<0.01). HE staining showed that the arrangement of bladder epithelial cells was disordered, and the pathological manifestations such as mucosa and myometria neutrophil infiltration were obvious. The lamina propria structure was destroyed, and the muscle fiber arrangement was disordered. The interstitial widening and tissue edema were obvious. Masson staining showed that the bladder wall of the model group had more collagen fiber deposition, and the degree of detrusor fibrosis was more severe. The content of detrusor in the visual field was reduced. At the same time, the protein expressions of NF-κB p65, TGF-β1, IκBα, ColⅠ, and ColⅢ in bladder tissue of rats in the model group were significantly increased (P<0.01), and the serum levels of IL-6, IL-1β, and TNF-α were significantly increased (P<0.05). Compared with that in the model group, the pressure at the urinary leakage point in the modified Chunzetang and positive drug groups was increased (P<0.05), and the wet bladder weight, minimum bladder contractile tension, maximum bladder capacity, and bladder compliance were restored (P<0.05, P<0.01). HE and Masson showed that the bladder epithelial cells were relatively neatly arranged, and the structure of the bladder lamina propria was relatively stable. The detrusor bundles were arranged in an orderly manner, and the interstitium was narrow. The degree of tissue edema was relatively low, and the degree of bladder detrusor fibrosis in the modified Chunzetang and positive drug groups was reduced, while the degree of bladder detrusor fibrosis in the positive drug group and combination groups was not obvious. The results of Western blot showed that the expression of NF-κB p65, IκBα, TGF-β1, ColⅠ, and ColⅢ in bladder tissue, as well as the serum levels of IL-6, IL-1β, and TNF-α in modified Chunzetang and positive drug groups were significantly lower, and the expression of bladder tissue-related proteins and the serum levels of IL-6, IL-1β, and TNF-α in the TCM groups decreased significantly with the increase in dose (P<0.05). The results of immunohistochemistry suggested that modified Chunzetang could fully affect the expression of α-SMA in bladder tissue. ConclusionModified Chunzetang can inhibit collagen deposition in bladder tissue of rats with urinary retention induced by spinal cord injury, delay the occurrence and development of bladder fibrosis, and protect the normal contractile function of bladder detrusor, and its mechanism may be related to inhibiting the NF-κB/TGF-β1 signaling pathway, reducing the production of NF-κB p65, IκBα, TGF-β1, ColⅠ, ColⅢ, and other related proteins, and protecting the muscle strength of detrusor.
8.Meta-analysis and Grade Evidence Evaluation of Qi-reinforcing and Blood-activating/ Stasis-expelling Chinese Patent Medicines in Treatment of Coronary Microvascular Disease
Jiaping CHEN ; Juju SHANG ; Hongxu LIU ; Xiang LI ; Xiaolei LAI ; Huiwen ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):157-166
ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease (CMD). MethodsPubMed, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for the randomized controlled trials (RCTs) on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31, 2023. The primary outcome indicators included the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and corrected TIMI flow frame count (cTFC). The secondary outcome indicators included symptomatic efficacy, left ventricular ejection fraction (LVEF), hypersensitive C-reactive protein (hs-CRP), nitric oxide (NO), and adverse events. Cochrane risk-of-bias assessment tool 2.0 (RoB 2.0) and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study, involving 3 029 patients. Compared with conventional Western medicine alone, the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR [mean difference (MD)=-5.93, 95% confidence interval (95%CI) [-8.73,-3.14], n=382, P<0.01], cTFC (MD=-9.35, 95%CI [-13.94,-4.76], n=618, P<0.01), and hs-CRP [standard mean difference (SMD)=-1.50, 95%CI [-1.90,-1.11], n=1 483, P<0.01], improved the CFR (SMD=1.14, 95%CI [0.08,2.19], n=304, P=0.03), symptomatic efficacy [relative risk (RR)=1.36, 95%CI [1.21,1.53], n=756, P<0.01], LVEF (MD=4.39, 95%CI [2.31,6.47], n=533, P<0.01), and NO (SMD=3.16, 95%CI [2.07,4.25], n=946, P<0.01) of CMD patients. In terms of safety, the combined therapy reduced the occurrence of adverse events in CMD patients (RR=0.49, 95%CI [0.29,0.82], n=591, P=0.01). GRADE showed moderate quality evidence for adverse events, low quality evidence for cTFC, symptomatic efficacy, LVEF, and NO, and very low quality evidence for IMR, CFR, and hs-CRP. ConclusionBased on microcirculatory function indicators, the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.
9.Effect of Different Degrees of Blood Stasis on Cognitive Function and Plasma Differential Metabolites in Patients with Coronary Heart Disease
Shihan XU ; Yanfei LIU ; Fenglan LIU ; Qing WANG ; Fengqin XU ; Yue LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):167-176
ObjectiveTo explore the correlation between the blood stasis score of coronary heart disease(CAD) and mild cognitive impairment(MCI), as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI(CADMCI) through a cross-sectional study, and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients. MethodsAccording to the diagnostic criteria of CAD and CAD blood stasis, patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included. According to the Montreal Cognitive Assessment(MoCA) scale score, the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group. The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model. The receiver operating characteristic(ROC) curve was drawn, and the area under the curve(AUC) was calculated to evaluate the sensitivity and specificity of the model. According to the blood stasis score, the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detect plasma metabolites in each group of patients. The differential metabolites were screened according to variable importance in the projection(VIP) value≥1, fold change(FC)<0.67 or >1.5, and P<0.05. ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples. ResultsA total of 266 CAD patients were included in this study. Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI[odds ratio(OR)=1.619, 95% confidence interval(CI) 1.223-2.142, P<0.001, ROC curve AUC was 0.615(95% CI 0.547-0.683, P=0.001)], indicating that the CAD blood stasis score has a certain predictive value for MCI. Plasma non-targeted metabolomics analysis showed that the main differential metabolites between CAD blood stasis and CADMCI blood stasis were lipid metabolites, among which phosphatidylcholine[20∶4(5Z, 8Z, 11Z, 14Z)/P-18∶1(11Z)] had the best discriminatory efficiency(ROC curve AUC=0.867, 95% CI 0.754-0.942). Further analysis of the differential metabolites between mild and severe blood stasis showed that lipid metabolites were also the main differential metabolites between mild and severe blood stasis. Among them, 1α,25-dihydroxy-2β-(2-hydroxyethoxy) vitamin D3 had the best efficacy in distinguishing mild and severe CAD blood stasis(AUC=0.813, 95% CI 0.649-0.951), and phosphatidylcholine 34∶2 had the best efficacy in distinguishing mild and severe CADMCI blood stasis(AUC=0.819, 95% CI 0.640-0.941). ConclusionThere is a significant correlation between CAD blood stasis score and MCI. Phosphatidylcholine metabolites play an important role in the pathogenesis of CADMCI blood stasis and severe blood stasis. The CAD blood stasis score combined with the detection of phosphatidylcholine metabolites can provide a reference for the development of early and efficient identification strategies for CADMCI.
10.Material Basis and Its Distribution in vivo of Qili Qiangxin Capsules Analyzed by UPLC-Q-Orbitrap-MS
Jianwei ZHANG ; Jiekai HUA ; Rongsheng LI ; Qin WANG ; Xinnan CHANG ; Wei LIU ; Jie SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):185-193
ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), the chemical constituents of Qili Qiangxin capsules was identified, and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules, as well as the serum, brain, heart, lung, spleen, liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software, the compound information database was constructed, and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time, accurate relative molecular mass and fragments, the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds, including 70 terpenoids, 60 flavonoids, 23 organic acids, 17 alkaloids, 20 steroids, 7 coumarins and 36 others, were identified or predicted from Qili Qiangxin capsules, 73 of which were identified matching with standard substances. Tissue distribution results showed that 71, 17, 38, 33, 32, 58 and 43 migrating components were detected in blood, brain, heart, lung, spleen, liver and kidney, respectively. Thirty-seven components were absorbed into the blood and heart, including quinic acid, benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues, including calycosin, methylnissolin, formononetin, alisol B, alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them, astragaloside Ⅳ, salvianolic acid B, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rd, ginsenoside Rg3, calycosin-7-glucoside, and sinapine may be the important components for the treatment of heart failure, which can provide useful reference for its quality control and research on pharmacodynamic material basis.

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