The anti-inflammatory effect of simplified Zhiqin Decoction was observed by using lipopolysaccharide (LPS)-induced inflammation mouse model. The main chemical constituents and the main mechanism of action of simplified Zhiqin Decoction were predicted by network pharmacology. Animal experiments verified the anti-inflammatory mechanism of simplified Zhiqin Decoction (this experiment was approved by the Animal Experiment Ethics Committee of Southwest University, approval number: IACUC-20210825-02). Simplifying Zhiqin Decoction has a significant anti-inflammatory effect on inflammatory mice, can significantly improve the overall macro shape of mice, reduce body temperature, water intake, increase the number of autonomous activities; alleviate liver, lung, spleen, thymus inflammation and pathological damage; decrease tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, nitric oxide (NO), prostaglandin E₂ (PGE₂) content in serum and urine. The contents of serum immune factors IgG, IgA and IgM were increased. Network pharmacology predicted 66 potential anti-inflammatory active components of simplified Zhiqin Decoction involving 132 inflammatory targets, and the key anti-inflammatory signaling pathway involved PI3K/AKT, TNF, JAK-STAT, etc. Animal experiments show that simplified Zhiqin Decoction can significantly reduce the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway related proteins in lung tissue of inflammatory mice. The results of this study showed that simplified Zhiqin Decoction had significant anti-inflammatory effects, and its main anti-inflammatory components were quercetin, β-sitosterol, kaempferol, wogonin, stigmasterol, luteolin, neobaicalein, etc. The main mechanism of its anti-inflammatory action is that it significantly inhibits the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway protein.

Objective: Develop a nutrition health educational guidance outline for primary and secondary school students which is adapted to the characteristics of Shanghai and meets the cognitive level of students at different levels, so as to provide a reference for planning the content and target of nutrition health education among students of different school stages. Methods: Through literature search and qualitative interviews, the framework of nutrition health education for primary and secondary school students in Shanghai was developed, and 21 experts in the fields of nutrition, school health and health education were invitied to conduct a Delphi consultation, and determined the content of nutrition and health education for students in each school section based on the consultation results. Results: The recall rate for both rounds of consultation was 100%, the degree of expert authority was 0.74 and 0.89 , and the coordination coefficients were 0.31 and 0.33( P <0.01), suggesting high credibility of expert opinion. The resulting guidance outline included 2 first level entries, 6 second level entries, 60 third level entries and corresponding entry explanations. The 2 first level entries were rational nutrition and food safety; the 6 second level entries were food and nutrients, balanced diet, good eating habits, nutritional practices, good hygiene habits and food borne diseases; the 60 third level entries needed to be studied in Level 1 were 24, Level 2 were 41, Level 3 were 55, and Level 4 were 59. Conclusion The nutrition health educational guidance outline for primary and secondary school students in Shanghai developed in this study focuses on key nutrition knowledge, rational dietary behaviors and nutrition practice skills, which can provide a reference and basis for the phased implementation of nutrition health education in primary and secondary schools.

The manufacturing process of traditional Chinese medicine is subject to material fluctuation and other uncertain factors which usually cause non-optimal state and inconsistent product quality. Therefore, it is necessary to design and collect the quality-rela-ted physical parameters, process parameters, and equipment parameters in the whole manufacturing process of traditional Chinese medicine for digitization and modeling of the process. In this paper, a method for non-optimal state identification and self-recovering regulation was developed for active quality control in the manufacturing process of traditional Chinese medicine. Moreover, taking vacuum belt drying process as an example, a DQN algorithm-based intelligent decision model was established and verified and the implementation process was also discussed and studied. Thus, the process parameters-based self-optimization strategy discovery and path planning of optimal process control were rea-lized in this study. The results showed that the deep reinforcement learning-based artificial intelligence technology was helpful to improve the product quality consistency, reduce production cost, and increase benefit.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Artificial Intelligence ; Quality Control ; Algorithms

OBJECTIVE: To investigate the effect of miR-125b on T cell activation in patients with aplastic anemia (AA) and its molecular mechanism. METHODS: A total of 30 AA patients were enrolled in department of hematology, Binzhou Medical University Hospital from January 2018 to October 2021, as well as 15 healthy individuals as healthy control (HC) group. Peripheral blood mononuclear cells (PBMCs) were isolated, in which the levels of miR-125b and B7-H4 mRNA were detected by RT-qPCR. Immunomagnetic beads were used to separate naive T cells and non-naive T cells from AA patients and healthy people to detect the levels of miR-125b and B7-H4 mRNA. Lentivirus LV-NC inhibitor and LV-miR-125b inhibitor were transfected into cells, and T cell activation was detected by flow cytometry. The dual-luciferase reporter gene assay was used to detect the targetting relationship between miR-125b and B7-H4. RT-qPCR and Western blot were used to detect the levels of miR-125b, CD40L, ICOS, IL-10 mRNA and B7-H4 protein. RESULTS: Compared with HC group, the expression of miR-125b was up-regulated but B7-H4 mRNA was down-regulated in PBMCs of AA patients (P <0.05), and the proportions of CD4⁺CD69⁺ T cells and CD8⁺CD69⁺ T cells in PBMCs of AA patients were higher (P <0.05). The expression of miR-125b was significantly up-regulated but B7-H4 mRNA was down-regulated in both naive T cells and non-naive T cells of AA patients (P <0.05), and non-naive T cells was more significant than naive T cells (P <0.05). Compared with NC inhibitor group, the expression of miR-125b was significantly decreased, the expression level of CD69 on CD4⁺ and CD8⁺ T cells in PBMCs was also significantly decreased, while the luciferase activity was significantly increased after co-transfection of miR-125b inhibitor and B7-H4-3'UTR-WT in the miR-125b inhibitor group (P <0.05). Compared with NC inhibitor group, the mRNA and protein levels of B7-H4 were significantly increased in the miR-125b inhibitor group (P <0.05). Compared with miR-125b inhibitor+shRNA group, the expression levels of CD69 on CD4⁺ and CD8⁺ T cells were significantly increased, and the levels of CD40L, ICOS and IL-10 mRNA were also significantly increased in the miR-125b inhibitor+sh-B7-H4 group (P <0.05). CONCLUSION MiR-125b may promote T cell activation by targetting B7-H4 in AA patients.
Humans ; Anemia, Aplastic/genetics* ; CD40 Ligand/metabolism* ; Interleukin-10 ; Leukocytes, Mononuclear/metabolism* ; Luciferases ; MicroRNAs/genetics* ; RNA, Messenger/metabolism* ; Lymphocyte Activation ; T-Lymphocytes/metabolism*

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

Renal outer medullary potassium (ROMK) channel is an important K⁺ excretion channel in the body, and K⁺ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K⁺ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na⁺-Cl^- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
Potassium Channels, Inwardly Rectifying/metabolism* ; Kidney Tubules, Distal/metabolism* ; Potassium/metabolism* ; Epithelial Sodium Channels/metabolism* ; Diet

OBJECTIVE: To compare the clinical therapeutic effect and the impacts on recurrence rate on chronic spontaneous urticaria (CSU) between the combined treatment of bloodletting therapy and auricular point sticking on the base of xuanfu theory and the oral solution of levocetirizine hydrochloride. METHODS: A total of 86 patients with CSU were randomized into an observation group (43 cases, 1 case dropped off) and a control group (43 cases, 3 cases dropped off). In the observation group, bloodletting therapy at Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17) and Pishu (BL 20) was combined with auricular point sticking at lung (CO₁₄), kidney (CO₁₀), shenmen (TF₄) and heart (CO₁₅), etc. This combined treatment was given once every two days. In the control group, the oral solution of levocetirizine hydrochloride was prescribed, 10 mL each time, once daily. The treatment lasted for 4 weeks in the two groups. Before and after treatment, urticaria activity score 7 (UAS7), the score of dermatology life quality index (DLQI) and the levels of serum immune globulin E (IgE), interleukin 4 (IL-4) and interferon γ (IFN-γ) were compared in the patients between the two groups. The clinical therapeutic effect was evaluated in patients of the two groups and the recurrence rate was followed up 4, 8 and 12 weeks after treatment separately. RESULTS: After treatment, the scores of UAS7 and DLQI, as well as the levels of serum IgE and IL-4 were all reduced as compared with those before treatment in the two groups (P<0.05), and the level of serum IFN-γ was increased (P<0.05). The total effective rate was 83.3% (35/42) in the observation group and was 85.0% (34/40) in the control group. There was no statistical significance for the difference in the clinical therapeutic effect between the two groups (P>0.05). Eight and 12 weeks after treatment, the recurrence rates were 21.1% (4/19) and 26.3% (5/19) in the observation group, lower than 55.0% (11/20) and 65.0% (13/20) in the control group, respectively (P<0.05). CONCLUSION The combined therapy of bloodletting and auricular point sticking on the base of xuanfu theory relieves the clinical symptoms, regulates the levels of serum IgE, IL-4 and IFN-γ and improves the quality of life in the patients with CSU. The clinical therapeutic effect of this combined treatment is similar to the oral solution of levocetirizine hydrochloride. But, the recurrence rate of the combined treatment of bloodletting and auricular point sticking is lower and its long-term curative effect is better.
Acupuncture Points ; Acupuncture Therapy ; Acupuncture, Ear ; Bloodletting ; Chronic Urticaria ; Humans ; Quality of Life ; Treatment Outcome

Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.
Animals ; Colitis/drug therapy* ; Colitis-Associated Neoplasms/drug therapy* ; Humans ; Macrophages ; Mice ; Panax notoginseng ; Saponins/therapeutic use* ; Tumor Microenvironment

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.
Andrographis ; Taste ; Aspartame ; Excipients ; Molecular Docking Simulation

Despite the distinctive characteristics and remarkable efficacy, animal medicine is stenchy, which decreases the comp-liance of patients. At the moment, the research on the method for deodorizing animal medicines lags behind. To be specific, the components related to the odor and the basic properties transformation of the components are unclear and there is a lack of specific deodorizing method. This study aims to clarify the main components related to the stench of animal medicine, such as aldehydes, amines, trimethylamines and sulfur compounds, and their basic properties, and to explore their metabolism and transformation in vivo and in vitro, which is expected to serve as a reference for the research on deodorization of animal medicine and development of new techniques.
Animals ; Odorants ; Aldehydes