This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Esculetin, a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini, has demonstrated significant pharmacological activities, including anticancer properties. Ferroptosis, an iron-dependent form of regulated cell death, has garnered considerable attention due to its lethal effect on tumor cells. However, the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma (HCC) effects remains poorly understood. This study investigated the impact of esculetin on HCC cells both in vitro and in vivo. The findings indicate that esculetin effectively inhibited the growth of HCC cells. Importantly, esculetin promoted the accumulation of intracellular Fe²⁺, leading to an increase in ROS production through the Fenton reaction. This event subsequently induced lipid peroxidation (LPO) and triggered ferroptosis within the HCC cells. The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde (MDA) levels, the depletion of glutathione peroxidase (GSH-Px) activity, and the disruption of mitochondrial morphology. Notably, the inhibitor of ferroptosis, ferrostatin-1 (Fer-1), attenuated the anti-tumor effect of esculetin in HCC cells. Furthermore, the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells. Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4, consequently alleviating esculetin-induced ferroptosis. In conclusion, this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis, thereby triggering ferroptosis in HCC cells. These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
Umbelliferones/administration & dosage* ; Ferroptosis/drug effects* ; Carcinoma, Hepatocellular/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Humans ; Liver Neoplasms/physiopathology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Animals ; Cell Line, Tumor ; Mice ; Amino Acid Transport System y+/genetics* ; Mice, Inbred BALB C ; Male ; Signal Transduction/drug effects* ; Lipid Peroxidation/drug effects* ; Reactive Oxygen Species/metabolism* ; Mice, Nude

ObjectiveTo investigate the different effects of Yunvjian with or without Achyranthis Bidentatae Radix on glucose and lipid metabolism and inflammatory response in diabetic rats with the syndrome of Yin deficiency and internal heat. MethodThe rat model of diabetes due to Yin deficiency and internal heat was established by feeding with a high-sugar and high-fat diet and injection of thyroxine and streptozotocin. The successfully modeled rats were randomized into model control， Yunvjian without Achyranthis Bidentatae Radix （11.8 g·kg^-1）， Yunvjian with Achyranthis Bidentatae Radix （12.8 g·kg^-1）， and Achyranthis Bidentatae Radix （1.0 g·kg^-1） groups （n=10）， and another 10 rats were taken as the normal control group. Each group was administrated with corresponding drugs or saline by gavage for 28 days. The fasting blood glucose （FBG）， fasting insulin （FINS）， total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in rats were measured. Enzyme-linked immunosorbent assay was employed to determine the levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， triiodothyronine （T₃）， thyroxine （T₄）， interleukin （IL）-1β， IL-6， tumor necrosis factor （TNF）-α， and C-reactive protein （CRP） in the serum. The histopathological changes of the liver were observed. The expression of lipoxygenase-2 （COX-2） was detected by immunofluorescence. The mRNA levels of nuclear transcription factors-κB （NF-κB）， monocyte chemotactic protein-1 （MCP-1）， and intercellular adhesion molecule-1 （ICAM-1） were determined by real-time polymerase chain reaction （Real-time PCR）.Western blot was employed to determine the protein levels of NF-κB in hibitory protein（IκB） kinase β （IKKβ）， IκBα， and phosphorylated IκBα （p-IκBα） in the liver and the protein levels of NF-κB in the cytoplasm and nucleus. ResultCompared with the normal group， the model group showed elevated levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T₃， T₄， IL-1β， IL-6， TNF-α， and CRP， up-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and up-regulated protein levels of COX-2， p-IκBα， and nuclear NF-κB （P<0.01）. Compared with the model group， Yunvjian without Achyranthis Bidentatae Radix lowered the levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T₃， T₄， IL-1β， IL-6， TNF-α， and CRP， down-regulated the mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated the protein levels of COX-2， p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. Compared with the Yunvjian without Achyranthis Bidentatae Radix， Yunvjian with Achyranthis Bidentatae Radix showed lowered levels of FBG， FINS， insulin resistance index， and inflammatory cytokines， down-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated protein levels of p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. ConclusionAchyranthis Bidentatae Radix can enhance the performance of Yunvjian in reducing blood glucose and inhibiting inflammation in diabetic rats with the syndrome of yin deficiency and internal heat by down-regulating the IKK/IκB/NF-κB signaling pathway.

OBJECTIVE To investigate the regulatory effects of couplet medicinals of Atractylodes macrocephala-Aucklandia lappa on gut microbiota and short-chain fatty acids （SCFAs） in the diarrhea-type irritable bowel syndrome （IBS-D） rats with spleen deficiency. METHODS The IBS-D rat model with spleen deficiency was induced by intragastric administration of Senna alexandrina combined with restraint stimulation. The model rats were divided into model group， positive control group （pinaverium bromide 1.5 mg/kg）， A. macrocephala-A. lappa low-dose， medium-dose and high-dose groups （0.7， 1.4， 2.8 g/kg）， with 6 rats in each group. Another 6 healthy rats were taken as the blank control group. The blank control group and the model group were given normal saline intragastrically， and other groups were given relevant drug liquid intragastrically， once a day， for consecutive 14 days. The general characteristics of rats and fecal water content were observed， and intestinal sensitivity [evaluating by abdominal wall withdrawal reflex （AWR） threshold] and the intestinal propulsion rate were determined. The serum levels of 5- hydroxytryptamine（5-HT）and SP were detected， and the pathological changes of colon tissue were observed； the protein expressions of 5-HT-3 receptor（5-HT3R）， 5-HT4R and 5-HT transporter（SERT） in colon tissue of rats were detected. 16S rRNA sequencing was performed for the feces of rats in blank control group， model group and A. macrocephala-A. lappa high-dose group； the contents of acetic acid， propionic acid and butyric acid in the feces of the rats were determined. RESULTS Compared with the model group， the body weight after 7 and 14 days of medication， fecal water content， AWR threshold， and the protein expressions of 5-HT4R and SERT in colon tissue were increased significantly in the A. macrocephala-A. lappa medium-dose and high-dose groups （P＜0.05 or P＜0.01）； serum contents of 5-HT and SP， intestinal propulsion rate （except for A. macrocephala-A. lappa medium-dose group）， the protein expression of 5-HT3R in colon tissue were decreased significantly （P＜0.01）； diarrhea relief， mental state recovery， and partially recovery of the structure of colon tissue were all found； moreover， the diversity and species number of gut microbiota were reduced in A. macrocephala-A. lappa high-dose group and the content of butyric acid in fecal samples was significantly reduced （P＜0.05）. CONCLUSIONS The compatibility of A. macrocephala and A. lappa can improve intestinal motility and sensitivity of IBS-D model rats with spleen deficiency， and alleviate diarrhea. This may be related to improving changes in intestinal microbiota structure， reducing 5-HT expression and butyric acid content， and increasing 5-HT4R and SERT expression.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

BACKGROUND:Studies have shown that both Panax notoginseng saponins and concentrated growth factor can promote fracture healing,but there are few studies addressing their combined effects on fracture healing.Panax notoginseng saponins may accelerate fracture healing by promoting the release of concentrated growth factor-related factors over a certain period of time. OBJECTIVE:To study the effect of Panax notoginseng saponins on concentrated growth factor release and fracture healing in rats. METHODS:Eighteen 8-week-old Sprague-Dawley rats were numbered and randomly divided into three groups:Panax notoginseng saponins group,model control group and blank group.Panax notoginseng saponins group was fed with Panax notoginseng saponins for 2 weeks.Model control group was given 2 mL of normal saline for 2 weeks and blank group was fed normally.Concentrated growth factor was obtained by the centrifugation method both from the Panax notoginseng saponins group and model control group.After 1 week of normal feeding,all animals underwent modeling for femoral fracture.The Panax notoginseng saponins group and the model control group were implanted with autologous concentrated growth factor,and then the release concentration of growth factors at different time points(1 hour,1,3,5,7,9 and 11 days)were measured by ELISA.Fracture healing was assessed based on postoperative X-ray and hematoxylin-eosin staining of bone tissues. RESULTS AND CONCLUSION:Compared with the model control group,the Panax notoginseng saponins group had higher release concentrations of vascular endothelial growth factor A and transforming growth factor β at 7,9,and 11 days,Platelet-derived growth factor BB at 5,9,and 11 days,and basic fibroblast growth factor at 1-11 days(P<0.01).X-ray examinations indicated that fracture healing in the Panax notoginseng saponins group was better than that in the model control group,and fracture healing in these two groups was better than that in the blank group at 2 months after surgery.Hematoxylin-eosin staining results found that the constituent osteocyte density in the Panax notoginseng saponins group was greater than that in the model control group,and the constituent osteocyte density in these two groups was better than that in the blank group.These findings indicate that Panax notoginseng saponins can increase the concentration of concentrated growth factor-related factors.After intervention with Panax notoginseng saponins,concentrated growth factors are more advantageous in promoting fracture healing in rats.

Objective To evaluate the effectiveness of different nursing techniques of traditional Chinese medicine (TCM) on post-stroke sleep disorders (PSSD). Methods A systematic search for RCTs(randomized controlled trial) on effects of TCM-based nursing techniques was conducted online through the databases of CNKI,WanFang Data,VIP Data,CBM,PubMed,The Cochrane Library and EMBASE from the inception of the databases to December 2022. Two reviewers independently screened the retrieved literature,assessed the risk of bias in the included studies,and extracted relevant data. A network meta-analysis was then performed using Stata 17.0 software to analyse the data. Results A total of 11 RCTs involving 962 stroke patients cared with 8 TCM-based nursing techniques were included. The 8 techniques comprised acupoint massage,Guasha+auricular acupoint pressing,acupoint plaster therapy,moxibustion,Tuina,five elements music+auricular acupoint pressing,auricular acupoint pressing,and routine nursing care. The regular meta-analysis demonstrated that the therapeutic effects of the 7 nursing techniques relieved PSSD of the patients[OR=3.18,95％CI (2.15,4.70),P<0.001]. The best probability ranking of the therapeutic effects showed by network meta-analysis was:acupoint massage>Guasha+auricular acupoint pressing>acupoint plaster therapy>moxibustion>Tuina>five elements music+auricular acupoint pressing>auricular acupoint pressing>routine care. Conclusion Acupoint massage is recommend as a priority option to alleviate the symptoms of PSSD. Further high-quality studies are necessary to verify this conclusion due to the limitations on quality and quantity of the included RCTs.

Objective To investigate the effect of Ba Bao Dan(BBD)on cardiac injury induced by doxorubicin in zebrafish.Methods We induced a zebrafish myocardial injury model using the chemotherapeutic drug,doxorubicin.We then examined the effects of different concentrations of BBD on pericardial edema and heart rate under an in vivo microscope.We also examined the inhibitory effects of BBD on neutrophil infiltration in the heart in Tg(mpx:EGFP)transgenic zebrafish.The impacts of BBD on superoxide dismutase,catalase,and malondialdehyde were observed.mRNA expression levels of ferroptosis-related factors,including glutathione peroxidase 4a(gpx4a),prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),and acyl-CoA synthetase long-chain family member 4(acsl4)were determined by Real-time quantitative polymerase chain reaction.The accumulation of ferrous ions in zebrafish heart was assessed using a fluorescent probe for ferrous ions.Results BBD alleviated doxorubicin-induced pericardial edema and bradycardia in zebrafish,reduced neutrophil infiltration in the heart(P＜0.05),decreased malondialdehyde concentration(P＜0.05),and enhanced the activities of superoxide dismutase and catalase(P＜0.05).BBD also significantly inhibited ferroptosis,reduced the accumulation of ferrous ions in the zebrafish heart,suppressed the expression of ptgs2,alox5a,and acsl4(P＜0.05),and promoted the expression of gpx4a(P＜0.05).Conclusions BBD can attenuate doxorubicin-induced zebrafish myocardial injury and improve cardiac function by inhibiting lipid peroxidation and regulating ferroptosis.