Effect of acupuncture treatment on nonketotic hyperglycemic hemichorea-hemiballismus: a case report.

Nonketotic hyperglycemic hemichorea-hemiballismus is a rare syndrome in the clinic, and treatment is often delayed. Hypoglycemic therapy is the most widely used and effective treatment, but some patients experience a slower improvement. Other symptomatic treatment medicines have some degree of side effects. Acupuncture treatment is beneficial for hemichorea-hemiballismus. A male patient, aged 59 years, first visited our hospital outpatient department due to motor agitation with involuntary movements of the right limb. He had a history of type 2 diabetes mellitus and poor blood glucose control. His serum glucose was 26.5 mmol/L (normal: 4.4-6.1 mmol/L), and magnetic resonance imaging demonstrated an irregular area of high signal intensity in T1-weighted imaging, low signal intensity on T2-weighted imaging, and high signal intensity in the left corpus striatum in T2-FLAIR imaging. Hospitalization was recommended for the patient. After ruling out other possibilities, he was eventually diagnosed with nonketotic hyperglycemic hemichorea-hemiballismus. Intensive glycemic control was immediately started with subcutaneous injection and acupuncture treatment at "governor vessel 13 acupoints", and the involuntary movements completely disappeared on the ninth day of hospitalization. The pathophysiology of nonketotic hyperglycemic hemichorea-hemiballismus is unclear. Different patient histories lead to different brain tissue conditions, and relapses and uncontrolled blood glucose add difficulties to treatment. According to Traditional Chinese Medicine theory, insufficient kidney essence leads to brain dystrophy and causes the symptoms of hemichorea-hemiballismus. Research evidence has shown that acupuncture at "governor vessel 13 acupoints" has a beneficial treatment effect on nonketotic hyperglycemic hemichorea-hemiballismus.

Immediate effect of small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation in improving the treatment of braces for adolescent idiopathic scoliosis / 针灸推拿医学（英文版）

Objective: To observe the immediate effect of small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation in improving the correction of braces for adolescent idiopathic scoliosis. Methods: A total of 50 cases of adolescent idiopathic scoliosis were selected and given brace correction first. The whole spine anteroposterior and lateral radiographs were taken, the Cobb angle was measured, and the visual analog scale (VAS) score of pain caused by brace wearing was recorded. After removal of the brace, small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation was performed once. After treatment, the same brace was put on again to take a whole spine anteroposterior radiograph, the Cobb angle was measured, and the VAS score was recorded. The changes in Cobb angle and VAS score after manipulation were compared, and the immediate efficacy was evaluated. Results: After the manipulation, the Cobb angle was significantly smaller than that before treatment (P<0.01) and the VAS score was significantly lower than that before treatment (P<0.01). Conclusion: Small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation can improve the immediate efficacy of brace in treating adolescent idiopathic scoliosis and relieve the pain caused by brace wearing at the same time.

Construction and validation of a Nomogram-based prediction model for the risk of gout in men / 中华内分泌代谢杂志

Objective:To investigate the risk factors of gout and establish a columnar graph model to predict the risk of gout development.Methods:A total of 1 032 Han Chinese men attending the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, People′s Hospital of Xinjiang Uygur Autonomous Region, and the First Affiliated Hospital of Xinjiang Medical University from 2018 to 2020 were selected as study subjects and divided into training set(722 cases)and validation set(310 cases)by simple random sampling method in the ratio of 7∶3. General information and biochemical indices of the subjects were collected. The collected information was used to assess the risk of gout prevalence. LASSO regression analysis of R Studio software was used to screen the best predictors, and was introduced to construct a column line graph model for predicting gout risk using receiver operating characteristic(ROC)curves, and the Hosmer-Lemeshow test was used to assess the discrimination and calibration of the column line graph model. Finally, decision curve analysis(DCA)was performed using the rmda program package to assess the clinical utility of the model in validation data.Results:Age, uric acid, body mass index, total cholesterol, and waist-to-hip ratio were risk factors for gout( P<0.05). The column line graph prediction model based on the above five independent risk factors had good discrimination(AUC value: 0.923 for training set validation and 0.922 for validation set validation)and accuracy(Hosmer-Lemeshow test: P>0.05 for validation set validation); decision curve analysis showed that the prediction model curve had clinical practical value. Conclusion:The nomogram model established by combining age, uric acid, body mass index, total cholesterol, and waist-to-hip ratio indicators can predict the risk of gout more accurately.

Acupuncture for glaucoma-induced optic atrophy: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy.@*METHODS@#A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups.@*RESULTS@#Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05).@*CONCLUSION@#On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics / 药学学报

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Establishment of Anti-inflammatory Activity Evaluation Method of Qingjin Huatantang Based on Phosphodiesterase Inhibitory Activity / 中国实验方剂学杂志

ObjectiveBased on the inhibitory activity of phosphodiesterase （PDE）， a method for determining the anti-inflammatory activity of Qingjin Huatantang was established to supplement and improve the quality control system of this famous classical formula. MethodHigh performance liquid chromatography （HPLC） was used to determine the activity of PDE， and the dose-effect relationship of inhibiting PDE activity of Qingjin Huatantang was investigated. The mobile phase consisted of methanol-0.5% acetic acid aqueous solution （5∶95）， and the detection wavelength was 254 nm. By measuring the PDE inhibition rate of multiple batches of Qingjin Huatantang water extract lyophilized powder， biological activity was marked with the activity of the neutralizing enzyme in the international unit U. ResultWhen the concentration of reaction substrate （cyclic adenosine monophosphate） was 50 μmol·L-1 and the reaction time was 60 min， the enzymatic reaction was stable with 4 U·mL-1 of PDE. In this reaction system， when the concentration of Qingjin Huatantang water extract lyophilized powder was 0.11-3.0 g·L-1， the inhibitory effect of PDE showed a concentration-dependent relationship. It was determined that the concentration of Qingjin Huatantang water extract lyophilized powder to be tested was 1 g·L-1， which showed a significant and stable inhibitory effect on PDE， and the inhibitory rate was >45%， that is， 1 mg of Qingjin Huatantang water extract lyophilized powder could neutralize the activity of 1.8 U PDE at least. ConclusionThis study establishes a biological activity evaluation method of Qingjin Huatantang based on the inhibitory activity of PDE， and the anti-inflammatory activity of Qingjin Huatantang is characterized by international unit U of PDE activity， which can provide a new method for the determination of biological activity of traditional Chinese medicine compounds.

Q-marker prediction analysis of Gentiana rigescens Franch. based on HPLC and network pharmacology / 药学学报

Aa a characteristic medicinal plant in China, Gentiana rigescens Franch. has the function of protecting the liver and invigorating the spleen. At present, there are a few studies on the content determination method of characteristic components of G. rigescens, so it is necessary to establish a scientific and effective quality control method; In this study, The high performance liquid chromatography (HPLC) fingerprint of G. rigescens was established, based on literature reviewed and characteristic spectrum identified, the source range of G. rigescens quality marker (Q-marker) was screened. The effectiveness of the ingredients and the corresponding targets and pathways was analyzed through network pharmacology, and drew the diagram of ''component-target-pathway''. Qualitative and quantitative analysis of G. rigescens was performed by HPLC, and screen the main marker components leading to the differences between groups which were determined the Q-marker of G. rigescens; The literature and HPLC had determined that five iridoids were the main source of G. rigescens Q-marker. The network pharmacology (effectiveness) and qualitative and quantitative (detectability) analysis of G. rigescens from different producing areas confirmed that gentiopicroside, swertiamarin, and sweroside can be used as the main landmark components, and there were significant differences in their contents among different producing areas; The analysis of G. rigescens from different producing areas was carried out by network pharmacology and chemical fingerprints, it is confirmed can be used as potential Q-marker to provide sufficient theoretical basis for the quality control of G. rigescens in the later period.

Effect and Safety of Acupuncture for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of 21 Randomised Controlled Trials / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM).@*METHODS@#PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.@*RESULTS@#Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild.@*CONCLUSIONS@#The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).

Analysis of Chemical Composition in Essential Oil of Zanthoxyli Pericarpium from Different Producing Areas and Investigation of Antifungal Effect of Zanthoxyli Pericarpium Essential Oil Solid Preparation / 中国实验方剂学杂志

Objective:To extract essential oil of Zanthoxyli Pericarpium， to prepare Zanthoxyli Pericarpium essential oil solid preparation and investigate its anti-fungal effect， in order to provide safe， green and efficient fungicide for the storage of Chinese herbal medicine and food. Method:The essential oil of Zanthoxyli Pericarpium was extracted by steam distillation method， gas chromatography-mass spectrometry （GC-MS） was adopted to analyze the chemical compositions and their relative contents in essential oil of Zanthoxyli Pericarpium from different producing areas， Agilent HP-5 capillary column was used for separation at programmed temperature （the initial temperature was 60 ℃， kept for 2 min， then increased to 280 ℃ by 10 ℃·min^-1， kept for 5 min）， the scanning range was <italic>m</italic>/<italic>z</italic> 35-590. Zanthoxyli Pericarpium essential oil solid preparation was prepared by nanomolecular sieve adsorption method， and its inhibitory effect on <italic>Aspergillus flavus</italic> and its conidia was investigated. Ultra-high performance liquid chromatography-fluorescence detector （UPLC-FLD） was used to analyze the inhibitory effect of Zanthoxyli Pericarpium essential oil solid preparation on aflatoxin under the conditions of excitation wavelength of 360 nm and emission wavelength of 440 nm. Result:The average extraction rate of essential oil in Zanthoxyli Pericarpium from four producing areas was 5.2%. （+）-Limonene， linalool and linalyl acetate were the main components of Zanthoxyli Pericarpium<italic> </italic>essential oil<italic> </italic>from different producing areas. When the volume fraction of essential oil in the solid preparation was 0.1%， the inhibition rate of the solid preparation on the conidia of <italic>A</italic>. <italic>flavus</italic> was （16.41±8.89）%. When the volume fraction of essential oil in the solid preparation was 0.2%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus</italic> was （8.11±2.70）%. When the volume fraction of essential oil in the solid preparation was 0.5%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus </italic>was （21.62±5.41）%， the inhibition rate for <italic>A</italic>. <italic>flavus</italic> conidia was （45.43±5.67）%， and the inhibition effect for the aflatoxin could reach （90.47±12.77）%. Conclusion:There are some differences in the chemical composition of essential oil of Zanthoxyli Pericarpium from different producing areas. Zanthoxyli Pericarpium<italic> </italic>essential oil has a certain inhibitory effect on the formation of <italic>A. flavus</italic> conidia and the production of aflatoxin B₁. It shows that Zanthoxyli Pericarpium essential oil can be developed into bacteriostatic preparation and used in the storage of Chinese medicinal materials and food.

Effect of Qigesan on Proliferation， Apoptosis and miR-133a/Akt/mTOR Signaling Pathway of Esophageal Cancer EC9706 Cells / 中国实验方剂学杂志

Objective:To observe the effect of Qigesan on the proliferation and apoptosis of the human esophageal cancer cell EC9706， and the effect on miR-133a/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway. Method:The effective constituent of Qigesan was extracted by ethyl acetate. Thiazolyl blue tetrazolium bromide（MTT） colorimetric assay was used to determine the dosage of Qigesan on cells and to detect the effect of Qigesan on the proliferation of EC9706 cells. The effect of Qigesan on apoptosis of EC9706 cells was detected by flow cytometry. The effect of Qigesan on miR-133a and insulin-like growth factor 1 receptor（IGF-1R） mRNA expression was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） . The protein expression of Akt and mTOR in EC9706 cells was detected by Western blot. Result:Qigesan can inhibit the proliferation of EC9706 cells in a dose-dependent manner（<italic>P</italic><0.01）. Inhibitory concentrations 30% inhibition concentration（IC₃₀） 40 mg·L^-1 and median inhibition concentration（IC₅₀） 80 mg·L^-1 were selected for follow-up experiments. Compared with the blank group， both the inhibitor group and the combination drug group can inhibit the proliferation of EC9706 cells （<italic>P</italic><0.01）. The inhibitor at 0.25 μmol·L^-1 was selected for subsequent experiments. Compared with the blank group， Qigesan 80 mg·L^-1 dose group could significantly promote the late apoptosis rate and total apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， and the 40 mg·L^-1 dose group could significantly promote the late apoptosis rate of EC9706 cells（<italic>P</italic><0.05）， which shows synergistic effect after concomitant use with Akt/mTOR inhibitor（<italic>P</italic><0.05）. Compared with the blank control group， each group can effectively increase expression of miR-133a（<italic>P</italic><0.05）. The combination of inhibitor and traditional Chinese medicine（TCM） has obvious promotion effect. Compared with blank control group， the expressions of Akt and mTOR were significantly decreased in each group（<italic>P</italic><0.05）. Compared with single medication， the expressions of Akt and mTOR were decreased in combination of inhibitor and TCM group. Conclusion:Qigesan can inhibit the growth of EC9706 cells and promote apoptosis， and its inhibitory mechanism may be related to the Akt/mTOR signaling pathway by regulating the expression of miR-133a.

Revealing the mechanisms underlying the therapeutic effects of acupuncture on migraine using neuroimaging: a narrative review / 生理学报

Migraine is a neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Acupuncture, as a commonly used non-pharmacological therapy, has the advantage of obvious therapeutic effect and few side effects in the prevention and treatment of migraine. But the underlying mechanism of acupuncture on migraine remains unclear. Recently, advances in neuroimaging technology have helped to objectively assess the effect of acupuncture on treating migraine and offered new opportunities to explore the central mechanism of acupuncture on treating migraine. In order to better understand the current status of neuroimaging studies on the therapeutic mechanism of acupuncture on migraine and shed light on future research, this review aims to overview the neuroimaging studies in recent 10 years from two aspects: (1) Central mechanism of acupuncture on treating acute migraine attack; (2) Central mechanism of acupuncture on preventing migraine attack.

Analysis of the results of international demand survey on / 中国针灸

The survey is conducted prior to the development of international standard,

Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology / 中国天然药物

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.

Research progress on Polygalae Radix / 中国中药杂志

Polygalae Radix has long been used in China for calming the mind, promoting intelligence, communicating the heart and kidney, eliminating phlegm, and reducing swelling. At present, it is used to treat amnesia, insomnia, and malaise. Modern research has revealed that Polygalae Radix mainly contains triterpenoid saponins, xanthone, oligosaccharide esters, etc., with the activities of improving memory, resisting dementia, protecting the brain, relieving cough, and removing phlegm, as well as sedation and hypnosis. The present study reviews the research progress on chemical composition, pharmacological action, quality control, and metabolism of Polygalae Radix in the past 30 years, to provide a theoretical basis for further research and development.

[Molecular regulatory mechanisms of hypoxia-inducible factor and interventional effect of Chinese herbal medicine].

Hypoxia-inducible factors(HIFs)are the key transcription factors that sense and regulate cellular oxygen concentration in vivo. HIF-1 is composed of 2 subunits,α and ß,in which,the molecular regulatory mechanism of HIF-1α involves the main processes of its degradation and activation. The degradation of HIF-1α is regulated by oxygen-dependent pathways,including "von hippel-lindau protein(pVHL)-dependent pathway" and "pVHL-independent pathway". The activation of HIF-1α is regulated by oxygen-independent pathways,including mammalian target of rapamycin(mTOR)/eukaryotic initiation factor 4 E-binding protein 1(4 EBP1)/HIF-1α pathway,phosphatidylinositol 3-kinase(PI3 K)/proteirrserinc-threonine kinases(Akt)/HIF-1α pathway and silent information regulator1(Sirt1)/HIF-1α pathway. In recent years,based on the molecular regulatory mechanism of HIFs,Roxadustat,a new drug for the treatment of renal anemia has been developed. Besides, some macromolecular substances with similar pharmacological effect to HIFs have been found in the extracts from Chinese herbal medicine(CHM),such as emodin,notoginseng triterpenes,honokiol and clematichinenoside. These natural macromolecular substances play the regulatory roles in inflammatory response,epigenetic modification and auto-phagy. It is worth noting that,for common hypoxic-related diseases including diabetic kidney disease,HIFs-mediated "pyroptosis" may be a new target of CHMs for clearing dampness and heat and its representative classical prescriptions(Ermiao Pills)in treating inflammatory injury in cells and tissues.

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

Mechanism of PI3K/Akt Signaling Pathway in Affecting Growth of Esophageal Cancer Cell and Research Progress of Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Esophageal cancer is one of the malignant tumors with a high morbidity and mortality in China. According to China's latest cancer report released by the National Cancer Center in 2019, the number of people suffering from esophageal cancer reached 246 000 in 2015, and the death toll reached 188 000. How to effectively treat esophageal cancer and improve the survival rate of patients is one of the most urgent problems in the field of medicine. Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most important signaling pathway for regulating cell survival, differentiation and apoptosis in the body. It also plays an important role in the occurrence and mechanism of various cancers. Recent studies have shown that the activation of PI3K/Akt signaling pathway is an important factor in regulating proliferation, apoptosis, cycle arrest, migration and invasion of esophageal cancer cells. The long-term clinical observation found that traditional Chinese medicine has a stable effect in the treatment of esophageal cancer and little side effects, especially in improving the quality of life of cancer patients and prolonging the survival period of patients. At present, it is a research hotspot to intervene this signal pathway with traditional Chinese medicine in the treatment of esophageal cancer, so as to explore its mechanism of action on esophageal cancer. This paper focused on literatures in CNKI and PubMed databases from 2009 to 2019, with PI3K/Akt signaling pathway, esophageal cancer and miRNA as the key words. A total of 226 literatures were retrieved, and 61 literatures relating to traditional Chinese medicine, esophageal cancer, miRNA and PI3K/Akt signaling pathway were sorted out and summarized. This paper reviewed the mechanism of PI3K/Akt signaling pathway in esophageal cancer, the relationship between miRNA and PI3K/Akt signaling pathway and esophageal cancer, and how traditional Chinese medicine can regulate the expressions of relevant proteins in PI3K/Akt signaling pathway to inhibit cell proliferation, affect cell growth cycle, induce cell apoptosis, inducing cell autophagy, inhibit tumor invasion and metastasis, inhibit angiogenesis. Finally, it can improve esophageal cancer to provide theoretical basis and scientific basis for the treatment of esophageal cancer with traditional Chinese medicine.

Effect and Mechanism of Four Kinds of Traditional Chinese Medicine Moisturizers Based on Shaoyao Gancaotang on Atopic Dermatitis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect and possible mechanism of four types of Chinese herbal moisturizers made in laboratory for atopic dermatitis induced by 2，4-dinitrofluorobenzene （DNFB） in mice. Method:According to the body weight， BALA/c mice were randomly divided into normal group， model group， blank cream group （moisturizer A）， Shaoyao Gancaotang group （moisturizer B）， Shaoyao Gancaotang with Portulacae Herba，Ginseng Radix et Rhizoma and Honeysuckle Stem group （moisturizer C）， and Shaoyao Gancaotang with Ginseng Radix et Rhizoma and Honeysuckle Stem group （moisturizer D） ， with the dose of 25 g·kg-1 per day， as well as tacrolimus ointment group of 3 g·kg-1 per day， with 10 to 12 mice in each group. Except the normal group， the mice in the other groups were treated with 0.5% DNFB in the hair removal skin of back， 100 μL each for 7 days. Starting from the 7th day， each group was given the appropriate skin cream for external use intervention， once per day， for 15 consecutive days， except for the normal and the model groups. The animal body mass was measured once a week， and the animal back skin was graded three times a week， and the skin lesion score was recorded. After the mice were killed， the left and right ears were taken， the weight of both ears was punched and the degree of swelling was calculated. The back skin was fixed and stained with hematoxylin-eosin（HE） method， and then pathologic examination was conducted to observe and score the pathological changes of mouse back skin. Blood was obtained after the last dose and enzyme-linked immunosorbent assay （ELISA） was used to determine the immunoglobulin（Ig）E content in serum. Western blot was used to measure the expression of signal transduction and activator of transcription 3 （STAT3）， phosphorylation （p）-STAT3 in the skin tissue. Result:Compared with the normal group， the body mass decreased continuously， a series of inflammatory changes such as erythema， edema， dryness， desquamation and callus exfoliation and so on occurred in the modeling area， and the skin lesion score increased significantly in the model group. Additionally， the cuticle of ear skin was thickened and the degree of ear swelling was obviously increased in the model group. Microscopically， the occurred changes in the model mice included the local necrosis of the epidermis， epidermal thickening， epidermal hyperplasia， and the hyperkeratosis and hypokeratosis in the cuticle， as well as the subcutaneous inflammatory cell infiltration and so on. Furthermore， the content of serum IgE andthe expression of p-STAT3 in skin tissues increased significantly in the model group. Compared with the model group， the body mass of mice in group C and D was significantly increased （P<0.01）， and the skin lesion status score was decreased （P<0.05，P<0.01）.The degree of auricle swelling was significantly reduced in group B， C and D compared with that in the model group （P<0.01）.The degree of skin necrosis and defect and epidermal hyperplasia of mice in moisturizer C group was significantly reduced compared with that in model group （P<0.05，P<0.01）. Serum IgE levels of mice in group C and D were significantly lower than those in the model group （P<0.05，P<0.01）. The expression of p-STAT3 protein in skin tissues of mice in moisturizer C group was significantly lower than that in model group （P<0.05）. Conclusion:The moisturizers B， C and D all have certain therapeutic effect on atopic dermatitis， among which moisturizers C has the most obvious therapeutic effect. The possible mechanism may be that it reduces the level of inflammatory cytokines by inhibiting the increase of serum IgE content and the phosphorylation of STAT3.

Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways / 中国中药杂志

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Multi-targeted therapeutic effects of Huangkui Capsules on insulin resistance and urine microalbumin in early diabetic kidney disease patients / 中国中药杂志

To observe the multi-targeted therapeutic effects of Huangkui Capsules(HKC)on insulin resistance(IR)and urine microalbumin in the early diabetic kidney disease(DKD)patients. The case data from the 83 DKD patients at G2 and A2 stage were collected respectively and analyzed retrospectively. According to the different treatment,all patients were divided into the control(A)group(40 cases)and the treated(B)group(43 cases). Among them,the A group patients were received "routine basic treatment";the B group patients were received "routine basic treatment+HKC". For the 2 group patients,firstly,the baseline parameters before receiving the treatment were compared respectively,and then,the changes of the total scores of traditional Chinese medicine(TCM) syndromes and the indicators of IR,urine protein,renal function,blood lipids and safety after receiving the treatment for 8 weeks were compared,respectively. Furthermore,for the all patients,the correlation analysis between IR and urine protein or IR and the total scores of TCM syndromes was carried out,respectively. The results showed that,for the B group patients received "routine basic treatment",their total scores of TCM syndromes,urine protein indicators including urine microalbumin(micro-UAlb) and urine microalbumin/urinary creatinine(UACR),IR indicators including fasting serum insulin(FIN)and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly improved,respectively. For the all DKD patients,before and after the treatment,the main IR indicators(FIN and HOMA-IR)were positively correlated with urine protein indicators(micro-UAlb and UACR). The main IR indicators(FIN and HOMA-IR) were also positively correlated with the total scores of TCM syndromes. In addition,2 treatments had no significant effects on renal function,blood lipids and safety indicators in the all DKD patients. Overall, "routine basic treatment+HKC" can ameliorate IR and reduce urine microalbumin in the early DKD patients. Its therapeutic targets may be not only proteinuria,but also IR,which is the upstream risk factor of proteinuria.