Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9％NaCl),model group(intraperitoneal injection of 0.9％NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P＜0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P＜0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P＜0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H₂O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min^-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS² data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

OBJECTIVE: To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation. METHODS: Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups. RESULTS: Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05). CONCLUSION The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.
Humans ; Pharynx ; Deglutition Disorders/therapy* ; Acupuncture Therapy ; Stroke/complications* ; Water ; Electric Stimulation

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 μg·g~(-1)) was higher than that in GFA(0.03-10.41 μg·g~(-1)) and GS(0.04-13.66 μg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.
Flavonoids/analysis* ; Alkaloids ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry ; Drugs, Chinese Herbal

This study was designed to comprehensively characterize and identify the chemical components in traditional Chinese medicine Psoraleae Fructus by establishing an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) method in combination with in-house library. The chromatographic separation conditions(stationary phase, column temperature, mobile phase, and elution gradient) and key MS monitoring parameters(capillary voltage, nozzle voltage, and fragmentor) were sequentially optimized via single-factor experiments. A BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was finally adopted, with the mobile phase consisting of 0.1% formic acid in water(A) and acetonitrile(B) at the flow rate of 0.4 mL·min~(-1) and column temperature of 30 ℃. Auto MS/MS was utilized for data acquisition in both positive and negative ion modes. By comparison with reference compounds, analysis of the MS~2 fragments, in-house library retrieval and literature research, 83 compounds were identified or tentatively characterized from Psoraleae Fructus, including 58 flavonoids, 11 coumarins, 4 terpenoid phenols, and 10 others. Sixteen of them were identified by comparison with reference compounds, and ten compounds may have not been reported from Psoraleae Fructus. This study achieved a rapid qualitative analysis on the chemical components in Psoraleae Fructus, which provided useful reference for elucidating its material basis and promoting the quality control.
Chromatography, High Pressure Liquid ; Medicine, Chinese Traditional ; Tandem Mass Spectrometry ; Cell Cycle ; Coumarins

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness