1.Action Mechanism of Resolving Dampness and Phlegm of Pinelliae Rhizoma Praeparatum Based on Interconnection Between Lung and Large Intestine
Xingbao TAO ; Chentao ZHAO ; Xiaofu ZHU ; Hao WU ; Jun HE ; Weiguo CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):122-131
ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum (PRP) on lung tissue, gut microbiota, and short-chain fatty acid (SCFA) metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group, model group, positive control group (Xiaoqinglong granules, 6.5 g·kg-1), and high-dose and low-dose PRP decoction groups (3.0, 1.5 g·kg-1), with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin (OVA) sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E (IgE), interferon-γ (IFN-γ), interleukin-4 (IL-4), and BALF levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were quantified by enzyme-linked immunosorbent assay (ELISA). Lung histopathology was assessed using hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC) was employed to detect mucin 5AC (MUC5AC) and aquaporin 5 (AQP5) protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis, and fecal SCFA levels were measured by gas chromatography-mass spectrometry (GC-MS). ResultsCompared with the normal group, the model group exhibited significantly increased airway resistance value (RI) (P<0.05), elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF (P<0.05), increased serum IgE and IL-4 levels (P<0.05), with reduced IFN-γ levels (P<0.05). It also showed thickened bronchial walls, widened alveolar septa, narrowed lumens, and mucus plugs in lung tissue, upregulated MUC5AC protein expression and downregulated AQP5 protein expression (P<0.05), decreased relative abundance of beneficial gut microbiota (Firmicutes, Clostridia, Clostridiales, Lactobacillaceae, and Lactobacillus), and increased abundance of harmful microbiota (Bacteroidetes, Bacteroidia, Bacteroidales, Muribaculaceae, and Muribaculum). In addition, the model group presented reduced fecal SCFA levels (acetate, propionate, and butyrate) (P<0.05). After the intervention of PRP decoction, compared to the model group, all drug administration groups showed decreased RI (P<0.05), increased phenol red excretion, declined eosinophil and neutrophil counts and IL-6, IL-8, IgE, and IL-4 levels (P<0.05), and improved IFN-γ levels (P<0.05) and lung pathology improved. The MUC5AC protein expression decreased (P<0.05), and the AQP5 protein expression increased (P<0.05). The disorder of gut microbiota was improved, and the diversity of gut microbiota was restored, with a significantly increased relative abundance ratio of beneficial microbiota (P<0.05) and a significantly reduced relative abundance ratio of harmful microbiota (P<0.05). The SCFA levels (acetate, propionate, and butyrate) increased (P<0.05). The efficacy indicators of serum inflammatory factors (IgE, IL-4, and IFN-γ), phlegm-resolving effect, airway resistance, total pathological score, and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis, promoting beneficial gut microbiota, enhancing SCFA production, restoring the balance of gut microbiota, and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.
2.Action Mechanism of Resolving Dampness and Phlegm of Pinelliae Rhizoma Praeparatum Based on Interconnection Between Lung and Large Intestine
Xingbao TAO ; Chentao ZHAO ; Xiaofu ZHU ; Hao WU ; Jun HE ; Weiguo CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):122-131
ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum (PRP) on lung tissue, gut microbiota, and short-chain fatty acid (SCFA) metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group, model group, positive control group (Xiaoqinglong granules, 6.5 g·kg-1), and high-dose and low-dose PRP decoction groups (3.0, 1.5 g·kg-1), with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin (OVA) sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E (IgE), interferon-γ (IFN-γ), interleukin-4 (IL-4), and BALF levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were quantified by enzyme-linked immunosorbent assay (ELISA). Lung histopathology was assessed using hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC) was employed to detect mucin 5AC (MUC5AC) and aquaporin 5 (AQP5) protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis, and fecal SCFA levels were measured by gas chromatography-mass spectrometry (GC-MS). ResultsCompared with the normal group, the model group exhibited significantly increased airway resistance value (RI) (P<0.05), elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF (P<0.05), increased serum IgE and IL-4 levels (P<0.05), with reduced IFN-γ levels (P<0.05). It also showed thickened bronchial walls, widened alveolar septa, narrowed lumens, and mucus plugs in lung tissue, upregulated MUC5AC protein expression and downregulated AQP5 protein expression (P<0.05), decreased relative abundance of beneficial gut microbiota (Firmicutes, Clostridia, Clostridiales, Lactobacillaceae, and Lactobacillus), and increased abundance of harmful microbiota (Bacteroidetes, Bacteroidia, Bacteroidales, Muribaculaceae, and Muribaculum). In addition, the model group presented reduced fecal SCFA levels (acetate, propionate, and butyrate) (P<0.05). After the intervention of PRP decoction, compared to the model group, all drug administration groups showed decreased RI (P<0.05), increased phenol red excretion, declined eosinophil and neutrophil counts and IL-6, IL-8, IgE, and IL-4 levels (P<0.05), and improved IFN-γ levels (P<0.05) and lung pathology improved. The MUC5AC protein expression decreased (P<0.05), and the AQP5 protein expression increased (P<0.05). The disorder of gut microbiota was improved, and the diversity of gut microbiota was restored, with a significantly increased relative abundance ratio of beneficial microbiota (P<0.05) and a significantly reduced relative abundance ratio of harmful microbiota (P<0.05). The SCFA levels (acetate, propionate, and butyrate) increased (P<0.05). The efficacy indicators of serum inflammatory factors (IgE, IL-4, and IFN-γ), phlegm-resolving effect, airway resistance, total pathological score, and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis, promoting beneficial gut microbiota, enhancing SCFA production, restoring the balance of gut microbiota, and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.
3.Establishment and evaluation of a rapid PCR-colloidal gold test strip method for the detection of Fritillaria ussuriensis
Yu-he MA ; Cong-hui SHANG ; Qiu-he MA ; Tao LI ; Yue LIU ; Bei-zhen PAN ; Li-jun GAO ; Ming-cheng LI ; Wei XIA ; Yong-mei QU
Acta Pharmaceutica Sinica 2024;59(6):1773-1778
This study design of specific identification primers for the ITS2 sequence of
4.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.
5.Dosimetric study of two-arc and dual-arc techniques in VMAT program for lower mid-thoracic esophageal cancer
Yong-Fu FENG ; Yu-Song LONG ; Jun-Wen TAN ; Xian-Tao HE ; Gang LI ; Zhan-Yu WANG
Chinese Medical Equipment Journal 2024;45(1):62-66
Objective To compare the effects of two arc(TA)and dual arc(DA)techniques on the dose distribution to the planning target volume(PTV)and organs at risk(OAR)in volumetric modulated arc therapy(VMAT)for lower mid-thoracic esophageal cancer.Methods Ten patients with lower mid-thoracic esophageal cancer who received radiation therapy at some hospital from July 2020 to June 2022 were selected retrospectively.A TA radiation therapy plan and a DA radiation therapy plan were developed for each patient using the Ray Arc module of RayStation 4.7.5.4 planning system,and the two kinds of radiation plans were compared in terms of dosimetric parameters including D2,D5,D50,D95,D98,homogeneity index(HI),conformity index(CI),beam-on time and total monitor unit for PTV and lung V5,V10,V20,V30 and Dmean and heartV30,V40 and Dmean and spine cord Dmax for OAR.SPSS 22.0 was used for statistical analysis.Results TA and DA radiation therapy plans had no significant differences in PTV CI,HI,D2,D5,D50,D95 and beam-on time(P>0.05),and DA plan had D98 and total monitor unit higher obviously than those of TA plan(P<0.05).In terms of OARs protection,DA plan had heart V30,V40 and Dmean slightly lower than those of TA plan with non-significantly differences(P>0.05),while lung V5,V30 and Dmean and spine cordDmax significantly lower(P<0.05).Conclusion DA technique gains advantages over TA technique in PTV dose distribution and dose to OAR,and the involvement of DA technique in preparing the VMAT plan for esophageal cancer contributes to enhancing the treatment efficacy.[Chinese Medical Equipment Journal,2024,45(1):62-66]
6.MRI-based habitat radiomics analysis for identifying molecular subtypes of endometrial cancer:a feasible study from two institutions
Wen-Tao JIN ; Tian-Ping WANG ; Xiao-Jun CHEN ; Guo-Fu ZHANG ; Hai-Ming LI ; He ZHANG
Fudan University Journal of Medical Sciences 2024;51(6):890-899
Objective To develop an MRI-based habitat radiomics model for the preoperative prediction of endometrial cancer(EC)molecular subtypes.Methods Patients with pathologically proven EC from two hospitals were included in the training(n=270)and testing(n=70)cohorts.All patients had preoperative MRI and histological and molecular diagnoses.First,the tumor was divided into habitat subregions based on diffusion-weighted imaging(DWI)and contrast-enhanced(CE)images.Subsequently,habitat radiomic features were extracted from different subregions of T1-weighted imaging(T1WI),T2-weighted imaging(T2WI),DWI,and CE images.Three machine learning classifiers,including logistic regression,support vector machines,and random forests,were applied to develop predictive models for p53-abnormal endometrial cancer,with model performance validated.The model demonstrating the best overall predictive performance was selected as the habitat radiomics model.Using the same procedure,a whole-region radiomics model based on T1WI,T2WI,DWI,and CE sequences and a clinical model were constructed.The performance of the models was evaluated using receiver operating characteristic curves,and DeLong's test was employed to compare differences between the models.Decision curve analysis was used to assess the clinical benefits of the models'application.Results After feature selection,eight habitat radiomic features were retained to construct the habitat radiomics model,ten features for the whole-region radiomics model,and three clinical features for the clinical model.The habitat radiomics model achieved the highest area under the curve(AUC),with 0.855(0.788-0.922)in the training cohort and 0.769(0.631-0.907)in the testing cohort.DeLong's test showed that the habitat radiomics model outperformed the whole-region radiomics model in the training cohort(P=0.001),but there was no significant difference in the testing cohort(P=0.543).In both cohorts,the habitat radiomics model outperformed the clinical model(P=0.007,training cohort;P=0.038,testing cohort).Decision curve analysis(DCA)demonstrated that this model provided clinical benefit for diagnosis within a threshold probability range of approximately 0.2-0.8.Conclusion The MRI-based habitat radiomics model can accurately predict p53-abnormal EC,outperforming both the whole-region radiomics model and the clinical model,and is useful for the non-invasive molecular subtyping of endometrial cancer before surgery.
7.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
8.Mortality, morbidity, and care practices for 1750 very low birth weight infants, 2016-2021
Yang HE ; Meng ZHANG ; Jun TANG ; Wanxiu LIU ; Yong HU ; Jing SHI ; Hua WANG ; Tao XIONG ; Li ZHANG ; Junjie YING ; Dezhi MU
Chinese Medical Journal 2024;137(20):2452-2460
Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.
9.Internal iliac artery ligation as a damage control method in hemodynamically unstable pelvic fractures: A systematic review of the literature
Hui LI ; Tao AI ; Guang-Bin HUANG ; Jun YANG ; Gong-Bin WEI ; Jin-Mou GAO ; Ping HE ; Xue-Mei CAO ; Ding-Yuan DU
Chinese Journal of Traumatology 2024;27(5):288-294
Purpose::Internal iliac artery ligation (IIAL) has been used as a damage control procedure to treat hemodynamically unstable pelvic fracture for many years. However, there is ongoing debate regarding the effectiveness and safety of this hemostatic method. Therefore, we performed a systematic literature review to assess the efficacy and safety of IIAL for pelvic fracture hemostasis.Methods::Three major databases, PubMed, Embase, and Google Scholar, were searched to screen eligible original studies published in English journals. Two reviewers independently read the titles, abstracts, and full texts of all literature. Articles were included if they reported the use and effects of IIAL.Results::A total of 171 articles were initially identified, with 22 fully meeting the inclusion criteria. Among the analyzed cases, up to 66.7% of patients had associated abdominal and pelvic organ injuries, with the urethra being the most frequently injured organ, followed by the bowel. The outcomes of IIAL for achieving hemostasis in pelvic fractures were found to be satisfactory, with an effective rate of 80%. Hemorrhagic shock was the leading cause of death, followed by craniocerebral injury. Notably, no reports of ischemic complications involving the pelvic organs due to IIAL were found.Conclusion::IIAL has a good effect in treating hemodynamically unstable pelvic fracture without the risk of pelvic organ ischemia. This procedure should be considered a priority for hemodynamically unstable pelvic fracture patients with abdominal organ injuries.
10.Diagnostic concordance and influencing factors of quantitative flow fraction and fractional flow reserve
Rui-Tao ZHANG ; Peng-Xin XIE ; Zhen-Yu TIAN ; Lin MI ; Ji-Sheng ZHOU ; Ben-Zhen WU ; Li-Yun HE ; Li-Jun GUO
Chinese Journal of Interventional Cardiology 2024;32(9):481-488
Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and>0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8%were male.All patients had 30%-70%coronary stenosis.The consistency rate of QFR and FFR was 78.0%(n=184),and the Person correlation coefficient was 0.557(P<0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P<0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P<0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95%CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95%CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P<0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.

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