1.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
2.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
3.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
4.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
5.Effects of saphenous nerve combined with posterior capsular block of knee joint on stress response,analgesic effect and joint function recovery after total knee arthroplasty
Teng-Chen FENG ; Jia-Yi WANG ; Jie YAO ; Ji-Bo ZHAO ; Xiao-Jia SUN ; Fu-Long LI
Journal of Regional Anatomy and Operative Surgery 2024;33(6):509-513
Objective To investigate the effects of saphenous nerve combined with posterior capsular block of knee joint on stress response,analgesic effect and joint function recovery of patients after total knee arthroplasty.Methods A total of 98 patients who received total knee arthroplasty in our hospital from January 2021 to January 2022 were selected and divided into the observation group(received saphenous nerve combined with posterior capsular block of knee joint)and the control group(received saphenous nerve block)by random number table,with 49 patients in each group.The visual analogue scale(VAS)score of resting and dynamic pain 6 hours,12 hours and 24 hours after surgery of patients in the two groups were compared.The range of knee joint motion before surgery,3 days,5 days and 7 days after surgery of patients in the two groups were compared.The stress indexes[cortisol(Cor),adrenocorticotropic hormone(ACTH)],and pain mediator indexs[calcitonin gene-related peptide(CGRP),beta-endorphins(β-EP),6-keto prostaglandin E1α(6-Keto-pGE1α),substance P(SP)]before surgery,4 hours,12 hours,24 hours,and 48 hours after surgery of patients in the two groups were compared.The occurrence of adverse reactions during treatment of patients in the two groups were recorded.Results There were statistically significant differences in the resting and dynamic VAS scores at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the range of knee joint motion at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the Cor and ACTH contents at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the contents of β-EP,SP,CGRP and 6-keto-PGE1α at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Saphenous nerve combined with posterior capsular block of knee joint for total knee arthroplasty can reduce patients' stress response,enhance postoperative analgesic effect,and improve the early motor function,with high safety.
6.Diagnosis and treatment of small-cell carcinoma of the prostate:A report of 2 cases
Long-Wei LU ; Xiu-Quan SHI ; Song XU ; Ding WU ; Lei WANG ; Dian FU ; Zhen-Yu XU
National Journal of Andrology 2024;30(1):40-43
Objective:To explore the clinical manifestations,diagnosis,pathological features and treatment of small-cell carci-noma of the prostate(SCCP).Methods:We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018,and reviewed relevant literature.Results:Both the patients had the symptoms of frequent,urgent and difficult urination,with an elevated level of PSA and grades Ⅱ-Ⅲ enlargement of the prostate at palpation.One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor.Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases.One of them was treated by eto-poside-platinum(EP)chemotherapy and died of systemic multiple organ failure 20 months after diagnosis,while the other underwent endocrine therapy and has lived with tumor up to the present day.Conclusion:The incidence rate of SCCP is low,its malignancy is high,and its prognosis is poor.The average survival of the patient is about 7 to 10 months after diagnosis.Currently there is no effec-tive management of the dissease,except by relying on the experience of the treatment of small-cell lung cancer,with chemotherapy as the main option.
7.Performance test of high-flow nasal cannula oxygen therapy device at different altitudes
Chun-Wei HE ; Ya-Ting WANG ; Yi-Long ZHOU ; Hui WANG ; Zi-Yu FU ; De-Dong MA
Chinese Medical Equipment Journal 2024;45(6):49-58
Objective To investigate the performance of brands and types of high-flow nasal cnnula oxygen therapy(HFNC)devices at different altitudes.Methods Four different models of HFNC devices,including R-80S bi-level non-invasive ventilator integrated with HFNC device,HF-60A HFNC device,HFT-300 HFNC device and H-80A HFNC device,were connected with the gas flow meter,simularted head and QuickLung and then put into a low-pressure chamber.The flow rates of the HFNC devices were set to 10,15,20,25,30,35,40,45,50,55 and 60 L/min,and the simulated altitudes of the low-pressure chamber were set to 6 000,5 000,4 000,3 000,2 000,1 000 and 0 m.The actual output airway flow rates,airway pressure changes and trends of the four HFNC devices were recorded at different setting altitudes and flow rates.SPSS 25.0 software was used for statistical analysis.Results The actual output airway flow rates of the four HFNC devices showed an increasing trend as the altitude rose with the simulated altitude of 6 000 m and the setting flow rate kept constant,which increased slowly and even went to decrease when the altitude and flow rate exceeded some limits.The degree of changes in the flow rate with the increasing altitude varied,and there was no uniform pattern.With the rising of altitude,the actual output airway pressure of the four HFNC devices with the flow rate raning from 10 to 35 L/min also increased gradually,which showed a decreasing trend(turning point)after going up to some certain value when the flow rate exceeded 35 L/min,and the altitude where the turning point appeared was lowered as the flow rate increased.Conclusion The actual output airway flow rates and airway pressure during HFNC rise at a high-altitude environment,and generally considerations have to be taken on required airway pressure,patient comfort and the altitude of the patient's usual place of residence when setting the flow rates of the HFNC device.[Chinese Medical Equipment Journal,2024,45(6):49-58]
8.The correlation analysis of coronary artery plaque AI quantitative parameter with FFR-CT in coronary CT angiography
Qingdong YAO ; Chengbing ZHANG ; Jun FU ; Peng WANG ; Bin LONG ; Haifeng LIU
The Journal of Practical Medicine 2024;40(17):2489-2494
Objective To investigate the relationship between coronary artery plaque AI quantitative parameter and FFR-CT in coronary computed tomography angiography.Methods A total of 84 patients suspected of having CAD[52 males and 32 females,aged 27 to 81 years with a mean age of(58.1±11.9)years]were enrolled in this study.All patients underwent coronary computed tomography angiography.The CCTA data was processed using shukun(SK)software for labeling and analysis of the coronary arteries,as well as obtaining quantitative parameters of coronary artery plaque AI and corresponding FFR-CT values.The quantitative parameters included plaque length,total volume,minimum lumen area(MLA),minimal lumen degree(MLD),lipid composition volume and proportion,fibrous-lipid composition volume and proportion,fibrous composition volume and proportion,calcified composition volume and proportion.Coronary artery hemodynamic abnormality or myocardial ischemia was defined as an FFR-CT value≤0.8.Correlational analysis was performed to evaluate the association between AI plaque quantitative param-eters and FFR-CT values.Univariate and multivariate binary logistic regression analyses were conducted to identify independent risk factors for predicting FFR-CT≤0.8.The predictive performance of the model based on AI plaque quantitative parameters was assessed using receiver operating characteristic(ROC)curve analysis and calculation of the area under the curve(AUC).Sensitivities,specificities,diagnostic test accuracy rates were also calculated.Results The predominant symptoms observed in the cohort of 84 patients were chest pain(n=39,46.4%)and distress(n=27,32.1%).Spearman analysis results revealed a weak positive correlation between FFR-CT and MLA(r=0.49,P<0.0001),while weak negative correlations were found for plaque length,total volume,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume(r=-0.44,-0.56,-0.40,-0.36,-0.42,-0.40;all P<0.05).Additionally,MLD exhibited a moderate negative correlation with FFR-CT(r=-0.60,P<0.0001).In the univariate binary logistic regression analysis,several variables including plaque length,total volume,MLA,MLD,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume were found to be independently associated with FFR-CT≤0.8(All P<0.05).The adjusted multivariate binary logistic regression analysis model revealed that MLD was the sole independent predictor(OR=1.082,95%CI:1.034~1.133,P=0.001).The logistics re-gression model expression was logit(P)=0.079X1-4.052,where X1 represents the value of MLD and achieved a predictive accuracy of 85.2%.The ROC AUC of plaque length,total volume,MLA,MLD,lipid composition vol-ume,fibrous-lipid composition volume,fibrous composition volume and calcified composition volume were 0.796,0.886,0.711,0.754 and 0.698 respectively,and the coresponding sensitivities and specificities were 47.83%,73.91%,73.90%,52.17%,60.87%and 92.11%,73.68%,60.53%,84.21%,89.47%.The five in-dexes combined diagnostic model possessed the largest AUC of 0.906,and 73.91%,71.05%of sensitivity and specificity.Conclusion The AI quantitative parameters of coronary artery plaque exhibited varying degrees of correlation with FFR-CT,while MLD emerged as the sole independent predictor of FFR-CT≤0.8,demonstrating high diagnostic efficiency.
9.Antimicrobial resistance of Escherichia spp.:surveillance report from Hunan Province Antimicrobial Resistance Surveillance System,2012-2021
Fang-Wei LONG ; Li-Hua CHEN ; Chen-Chao FU ; Chen LI ; Yan-Ming LI ; Xing-Wang NING ; Jun LIU ; Guo-Min SHI ; Jing-Min WU ; Hong-Xia YUAN ; Ming ZHENG ; An-Hua WU ; Xun HUANG ; Huai-De YANG ; Nan REN
Chinese Journal of Infection Control 2024;23(8):975-983
Objective To understand the antimicrobial resistance of Escherichia spp.from member units of Hu-nan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),data about Escherichia spp.and the anti-microbial susceptibility testing results reported from member units of Hunan Province Antimicrobial Resistance Sur-veillance System were analyzed by WHONET 5.6 software.Results From 2012 to 2021,a total of 476 351 clini-cally isolated Escherichia spp.were collected,475 520 of which were Escherichia coli,accounting for 99.8%;92.6%were isolated from inpatients;39.3%were isolated from urine specimens.Over the past 10 years,the proportion of Escherichia spp.in total detected pathogens remained relatively stable,ranging 20%-23%,the lowest rate was 18.7%in 2012,and the highest rate was 22.9%in 2015.In the past 10 years,the resistance rates of Escherichia spp.to ampicillin,ceftriaxone,cefotaxime and ampicillin/sulbactam were>80%,>47%,>45%,and>39%,respectively;resistance rates to piperacillin/tazobactam,cefoperazone/sulbactam,and nitrofurantoin were all<8%,to tigecycline,amikacin,imipenem,and meropenem(except in 2012)were all<5%.Resistance of Escherichia spp.to 22 commonly clinically used antimicrobial agents fluctuated,but overall trend decreased year by year.The resistance rates of Escherichia spp.from patients in the intensive care unit(ICU),non-ICU patients,outpatients,and emergency patients to 22 clinically commonly used antimicrobial agents were compared among different depart-ments,and the differences were statistically significant(all P<0.05).The resistance rates of Escherichia spp.iso-lated from ICU and non-ICU patients were compared,and except for tigecycline,the resistance rates to the other 21 antimicrobial agents were statistically different(all P<0.05).The resistance rates of Escherichia spp.isolated from patients to commonly clinically used antimicrobial agents were statistically different among patients of different age groups(all P<0.05).Conclusion Escherichia spp.isolated from patients in different years,departments,specimens,and ages have different resistance to commonly used antimicrobial agents.It is necessary to continue to strengthen the surveillance on bacterial resistance,so as to guide the rational choice of antimicrobial agents.
10.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Result Analysis
Print
Save
E-mail