Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

Ductal carcinoma in situ of the breast (DCIS) most commonly manifests as asymptomatic calcifications at mammography. The most common manifestation of MRI is nonmass enhancement. The ultrasound mainly presents as a hypoechoic irregular hypervascular mass without posterior features. Core-needle biopsy is a commonly used method for preoperative diagnosis of DCIS. Due to differences in needle type and sample size, there is a certain degree of pathological upgrading of the lesion. In recent years, there has been controversy over the diagnosis and treatment of DCIS. With the development of breast disease diagnostic technology, advances in digital breast tomography, artificial intelligence, and radiomics are expected to help DCIS management and address issues such as overdiagnosis.

Objective The characteristics of supramolecular"imprinting template"of volatile oil of Curcuma kwangsiensis and Curcuma phaeocaulis were analyzed and studied based on the supramolecular"qixi"theory of Chinese materia medica combined with chemometrics.Methods The volatile oil of C.kwangsiensis and C.phaeocaulis were extracted by steam distillation,and the fingerprint and composition information of each batch were obtained by GC-MS.Total statistical moment method was used to compare the imprinting characteristics of the"imprinting template"of C.kwangsiensis and C.phaeocaulis.The core index(CI)of each batch of essential oil of C.kwangsiensis and C.phaeocaulis was calculated,and the topological characteristics of types of"imprinting template"of C.kwangsiensis and C.phaeocaulis were compared by chemometrics.Results There was no significant difference in the extraction rate of volatile oil between C.kwangsiensis and C.phaeocaulis.The average values of total zero order moment(AUCT)were(1.907±0.177)×108,(1.979±0.413)×108 μV·s,respectively,showing that there was no significant difference in the total content of volatile oil between the two groups.The mean values of the total first order moment(MCRTT)were(30.969±0.962)and(33.198±0.409)min.The average value of total second order moment(VCRTT)was(56.176±11.368)and(43.891±4.113)min2,respectively,indicating that there were significant differences in the content ratio and species of volatile oils between the two groups.The similarity of total statistical moments of C.kwangsiensis and C.phaeocaulis was mostly lower than the defined value,indicating that the chemical composition and composition ratio of the volatile oil were different.Principal component analysis and orthogonal partial least squares discriminant analysis could obviously divide C.kwangsiensis and C.phaeocaulis into two categories.Through the analysis of P value and VIP value,the CI values of Xvp 4th order,Xvpc 5th order,Xvpc 6th order,Xvpc 7th order,Xvc 3rd order,Xvpc 4th order were the main difference values of C.kwangsiensis and C.phaeocaulis.Conclusion Through the characterization of"imprinting property"and"topological characteristics"of the supramolecular"imprinting template"and combining with chemometric analysis,it is possible to successfully distinguish C.kwangsiensis and C.phaeocaulis,and find the different CI values between two"imprinting templates".

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Tumor Suppressor Protein p53 ; Network Pharmacology ; ErbB Receptors ; Protein Serine-Threonine Kinases ; Serine ; Adenosine Triphosphate ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology*

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-β(TGF-β), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1β in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-β, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-β/Smad4 signaling pathway.
Mice ; Male ; Animals ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Olive Oil/therapeutic use* ; Carbon Tetrachloride/metabolism* ; Liver Cirrhosis/metabolism* ; Liver ; Superoxide Dismutase/metabolism* ; Transforming Growth Factor beta/metabolism*

Objective: To compare the treatment effect of distraction osteogenesis (DO) and maxillomandibular advancement (MMA) for severe obstructive sleep apnea hypopnea syndrome (OSAHS) patients and to guide clinical decisions about treatment of OSAHS. Methods: Thirty-seven OSAHS patients which accepted maxillomandibular advancement (MMA) or distraction osteogenesis (DO) in Stomatological Hospital of the Department of Maxillofacial Trauma and Orthognathic Surgery, School of Stomatology, The Forth Military Medical University from June 2017 to June 2019 were collected. Their preoperative and postoperative data of cephalometry, polysomnography (PSG), Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale (ESS) scores were collected and analyzed. With propensity score matching method, the treatment effect of MMA and DO was analyzed and compared. Results: According to the statistics of MMA group, only AHI was correlated with operative successful rate and cure rate. With the increase of AHI, the treatment effect of MMA on OSAHS patients gradually decreased. The cut-off point of AHI as a predictor of MMA treatment failure was 78.2 n/h. All the matched cases were severe OSAHS patients. Statistical analysis showed that the mandibular elongation of DO patients[(24.00±4.39) mm] was significantly more than that of MMA group [(11.20±1.37) mm] (t=-6.11, P<0.001), the improvement of PSG index [including lowest oxygen saturation (LSpO₂), longest apnea (LA) and longest hypopnea (LH)] in DO group [LSpO₂=(93.40±1.82)%; LA=(18.28±8.32) s; LH=(61.84±32.94) s] was significantly higher than that in the MMA group [LSpO₂=(86.00±4.06)%, LA=(64.08±21.78) s, LH=(172.40±30.70) s](t=-3.72, P=0.005; t=4.39, P=0.003; t=5.49, P=0.004). The PSQI and the ESS scores of DO group (PSQI=4.20±0.83; ESS=3.40±1.52) were also significantly better than that of MMA group (PSQI=8.80±2.39, ESS=9.40±2.88)(t=4.07, P=0.001; t=4.12, P=0.002). Conclusions: For severe OSAHS patients, the objective and subjective indicators of DO treatment group showed a better therapeutic effect than that of MMA.
Humans ; Mandibular Advancement ; Osteogenesis, Distraction ; Retrospective Studies ; Sleep Apnea, Obstructive/surgery* ; Treatment Outcome

Cardiovascular diseases， with high incidence and high mortality， belong to the category of "chest impediment and heart pain" in traditional Chinese medicine （TCM）. Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills， one of the National Essential Drugs， is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease （Qi deficiency and blood stasis syndrome）. This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi， activate blood， and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow， regulating immune functions， alleviating inflammation， detoxifying， and tranquilizing mind. Clinically， it is suitable for patients with angina pectoris caused by the lack of heart Yang， chest tightness， shortness of breath， palpitation， fear of cold for limbs and so on， especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports， this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets， location and links. Furthermore， we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research， aiming to provide data support and evidence for the clinical application of this medicine.

ObjectiveTo investigate the compatibility rule of traditional Chinese patent medicines （TCPMs） against liver diseases through network analysis. MethodWith “liver” as the search term， TCPMs against liver diseases were retrieved from volume Ⅰ of Chinese Pharmacopoeia （2020 edition）， and the basic information of them was collected. TCPMs with same Chinese medicinal materials （CMMs）， usage， and indications， but different dosage forms， were unified as one formula. Mutual information entropy （MIE） of CMM couples was calculated to quantify the relationship between them， and the top 25% CMM pairs in MIE were used to construct the compatibility network， with CMM as node and the relationship between CMM pairs as the edge. Key CMM and frequently used CMM combinations were identified based on node centrality and cluster analysis， respectively. The indications of TCPMs related to the CMMs in clusters were recorded. Cytoscape 3.6.1 was employed for visualization and topology analysis of the compatibility network. ResultA total of 179 TCPMs， involving 428 CMMs， were retrieved. Angelicae Sinensis Radix， Paeoniae Radix Alba， and Glycyrrhizae Radix et Rhizoma were identified as key CMMs with high frequency， and Cuscutae Semen-Lycii Fructus， Citri Reticulatae Pericarpium-Cyperi Rhizoma， and Ecliptae Herba-Ligustri Lucidi Fructus combinations had high MIE. Furthermore， the CMMs were clustered into ten groups corresponding to different diseases which， however， all belonged to digestive diseases. ConclusionThis study unveils potential CMM pairs and common CMM combinations against liver diseases， which can serve as a reference for revealing compatibility rules of CMMs and research and development of Chinese medicine.

This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.
Animals ; Disease Models, Animal ; Gastrointestinal Microbiome ; Liver ; Male ; Medicine, Tibetan Traditional ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy*

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
Acetaminophen/toxicity* ; Animals ; Antioxidants/pharmacology* ; Glutamate-Cysteine Ligase/pharmacology* ; Glutathione ; Interleukin-6/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Medicine, Tibetan Traditional ; Mice ; NF-E2-Related Factor 2/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*