Research progress in the treatment of Alzheimer's disease by regulating brain-gut-microbiome axis with "Sanjiao" acupuncture method / 中华老年医学杂志

Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.

Bioinformatics analysis and identification to immune-related markers of osteoporosis / 细胞与分子免疫学杂志

Objective To identify immune-related dysregulation mechanisms and potential diagnostic predictive biomarkers in osteoporosis. Methods Gene expression data for both osteoporosis and control populations were retrieved from the GSE35958 and GSE56815 datasets. Immune-related differentially expressed genes (DEGs) were obtained by screening DEGs and were compared with the immunology database and analysis portal (ImmPort) database. Enrichment analysis of these immune-related DEGs was conducted using the Clusterprofiler software package. A protein-protein interaction network was built with the STRING database, which is a search tool for finding interacting genes/proteins, and the top 10 genes with the highest network connectivity were identified as candidate genes. Subsequently, the diagnostic predictive effect of candidate genes was evaluated using receiver operating characteristic (ROC) curves, logistic regression, and column plots. Finally, PCR and Western blot analysis were applied to detect the differential expression of these genes in bone marrow tissue of patients with osteoporosis. Results A total of 138 immune-related DEGs were obtained through intersection analysis. The results of the enrichment analysis indicated that these genes were involved in biological functions such as immune inflammation and signaling pathways including T cell receptors, mitogen activated protein kinase (MAPK), rat sarcoma virus oncogene homologs (Ras), osteoclast differentiation, and B cell receptors. In addition, among the candidate genes, upregulated vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR) and downregulated AKT1, SRC, and JUN in osteoporosis showed the highest connectivity. Among them, VEGFA, EGFR, JUN, and AKT1 demonstrated the best diagnostic predictive value. Conclusion The screening of immune-related DEGs will enhance the understanding of osteoporosis and facilitate the development of immunotherapy targets.

ß-hydroxybutyrate inhibits ferroptosis-mediated pancreatic damage in acute liver failure through the increase of H3K9bhb.

Acute pancreatitis and hyperamylasemia are often seen in patients with acute liver failure (ALF). However, the underlying mechanisms remain elusive. This study describes pancreatic tissue damage and exocrine dysfunction in a mouse model of major-liver-resection-induced ALF. The analysis of 1,264 clinical cases of liver failure (LF) showed that the incidence of hyperamylasemia and hyperlipasemia in patients with LF is 5.5% and 20%, respectively. Metabolomic studies indicate that glutathione (GSH)-deficiency-caused ferroptosis contributes to pancreatic damage in mouse ALF. ß-hydroxybutyrate (ß-HB) is the only metabolite downregulated in the liver, serum, and pancreas. Our data suggest that ß-HB protects pancreatic cells and tissues from GSH-deficiency-caused ferroptosis. ß-HB administration in ALF mice restores the expression of ferroptosis-suppressor genes through histone H3 lysine 9 ß-hydroxybutyrylation (H3K9bhb)-mediated chromatin opening. Our findings highlight ß-HB as an endogenous metabolite regulating ferroptosis in the pancreas and extend our understanding of the pathophysiology of ALF-induced pancreatitis.

Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osgin1-Mediated Restoration of Efficient Autophagy.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

Targeted therapy of atherosclerosis by pH-sensitive hyaluronic acid nanoparticles co-delivering all-trans retinal and rapamycin.

Atherosclerosis, the leading cause of death in the elderly worldwide, is typically characterized by elevated reactive oxygen species (ROS) levels and a chronic inflammatory state at the arterial plaques. Herein, pH-sensitive nanoparticles (HRRAP NPs) co-delivering all-trans retinal (ATR), an antioxidant linked to hyaluronic acid (HA) through a pH-sensitive hydrazone bond, and rapamycin (RAP), an anti-atherosclerotic drug loaded into the nanoparticle core, are developed for targeted combination therapy of atherosclerosis. In this way, HRRAP NPs might simultaneously reduce ROS levels via ATR antioxidant activity and reduce inflammation via the anti-inflammatory effect of RAP. In response to mildly acidic conditions mimicking the lesional inflammation in vitro, HRRAP NPs dissociated and both ATR and RAP were effectively released. The developed HRRAP NPs effectively inhibited pro-inflammatory macrophage proliferation, and displayed dose- and time-dependent specific internalization by different cellular models of atherosclerosis. Also, HRRAP NP combination therapy showed an efficient synergetic anti-atherosclerotic effect in vitro by effectively inhibiting the inflammatory response and oxidative stress in inflammatory cells. More importantly, HR NPs specifically accumulated in the atherosclerotic plaques of apolipoprotein E-deficient (ApoE-/-) mice, by active interaction with HA receptors overexpressed by different cells of the plaque. The treatment with HRRAP NPs remarkably inhibited the progression of atherosclerosis in ApoE-/- mice which resulted in stable plaques with considerably smaller necrotic cores, lower matrix metalloproteinase-9, and decreased proliferation of macrophages and smooth muscle cells (SMCs). Furthermore, HRRAP NPs attenuated RAP adverse effects and exhibited a good safety profile after long-term treatment in mice. Consequently, the developed pH-sensitive HRRAP NP represent a promising nanoplatform for atherosclerosis combination therapy.

Mechanism of protective effect of xuan-bai-cheng-qi decoction on LPS-induced acute lung injury based on an integrated network pharmacology and RNA-sequencing approach.

Xuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein-protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Verification experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were down-regulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.

Whole exome sequencing and trio analysis to broaden the variant spectrum of genes in idiopathic hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

Correction to: Emodin alleviated pulmonary inflammation in rats with LPS-induced acute lung injury through inhibiting the mTOR/HIF-1α/VEGF signaling pathway.

In the original publication of the article.

Emodin alleviated pulmonary inflammation in rats with LPS-induced acute lung injury through inhibiting the mTOR/HIF-1α/VEGF signaling pathway.

OBJECTIVE AND DESIGN: This study aimed to investigate the anti-pulmonary inflammation effect of emodin on Wistar rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI) and RAW264.7 cells through the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. SUBJECTS: Wistar rats and RAW264.7 cells were studied. TREATMENT: LPS was used to induce inflammation in rats or RAW264.7 cells and emodin was given once a day before LPS stimulation and continued for a certain number of days. METHODS: Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for the in vivo experiment, while cells and supernatant were collected for the in vitro experiment. Pathological changes in the lung tissues were assessed by hematoxylin and eosin staining. The levels of inflammatory factors, including TNF-α, IL-1ß, and IL-6, were determined by enzyme-linked immunosorbent assay. The expression levels of p-mTOR, HIF-1α, and VEGF proteins were measured by Western blot analysis and immunohistochemistry. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E were measured by quantitative polymerase chain reaction. RESULTS: Emodin ameliorated pathological changes and infiltrated inflammatory cells in LPS-induced ALI. It also significantly reduced the expression of inflammatory factors, including TNF-α, IL-1ß, and IL-6, in BALF and downregulated the expression of p-mTOR, HIF-1α, and VEGF proteins in the lung tissues. Similar anti-inflammatory effects and the downregulation of the mTOR/HIF-1α/VEGF signaling pathway were found in RAW264.7 cells. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E also decreased in the macrophages. CONCLUSION: Emodin alleviated LPS-induced pulmonary inflammation in rat lung tissues and RAW264.7 cells through inhibiting the mTOR/HIF-1α/VEGF signaling pathway, which accounted for the therapeutic effects of emodin on ALI.

Graphene oxide enhanced polyacrylamide-alginate aerogels catalysts.

Biomass aerogel is a promising catalyst and has attracted extensive attention. However, most of the biomass aerogels are fragile, which limits their practical application. Herein, we significantly enhance the mechanical property of biomass aerogel catalysts by 30 times through incorporating graphene oxide into polyacrylamide and Cu-cross-linked alginate formed supper-strong double network aerogels. In addition to enhance the mechanical property, the graphene oxide also significantly increases the catalytic activity. Graphene oxide enhancement for biomass aerogel catalyst provides a new method to develop next generation supper catalysts.

True chylothorax induced by infection-caused lymphadenopathy: A case report and literature review / 吉林大学学报(医学版)

Objective: To explore the etiology of chylothorax by analyzing the clinical data of one patient with chylothorax and combining with the review of relative literatures, and to improve the ability of clinicians for understanding the rare etiology of chylothorax. Methods: A young female with cough, chest pain and dyspnea as the first symptom was admitted to the hospital. Left lymph node enlargement in the neck of the patient was found in examination and bilateral pleural effusion was found in chest CT scanning. After puncture drainage and testing, the pleural effusion was confirmed the chylothorax. Since the examinations for common causes of chylothorax produced negative results, the patient was eventually diagnosed as infectious chylothorax. The patient received anti-infective therapy for 5 d. Results: After treatment, the symptoms of the patients were improved obviously; the pleural effusion disappeared, and the lymph nodes in the neck were shrink detected with chest color ultrasound. One month after follow-up, all the symptoms, enlarged lymph nodes and pleural effusion were recovered. There was no abnormity in chest CT. Conclusion: The possibility of infection should be considered in clinic for the patients with atypical chylothorax and anti-infective treatment should be performed in order to avoid the failed diagnosis and misdiagnosis.

True chylothorax induced by infection-caused lymphadenopathy:A case report and literature review / 吉林大学学报(医学版)

Objective:To explore the etiology of chylothorax by analyzing the clinical data of one patient with chylothorax and combining with the review of relative literatures,and to improve the ability of clinicians for understanding the rare etiology of chylothorax.Methods:A young female with cough,chest pain and dyspnea as the first symptom was admitted to the hospital.Left lymph node enlargement in the neck of the patient was found in examination and bilateral pleural effusion was found in chest CT scanning.After puncture drainage and testing,the pleural effusion was confirmed the chylothorax.Since the examinations for common causes of chylothorax produced negative results,the patient was eventually diagnosed as infectious chylothorax.The patient received anti-infective therapy for 5 d.Results:After treatment,the symptoms of the patients were improved obviously;the pleural effusion disappeared,and the lymph nodes in the neck were shrink detected with chest color ultrasound.One month after follow-up,all the symptoms,enlarged lymph nodes and pleural effusion were recovered.There was no abnormity in chest CT.Conclusion:The possibility of infection should be considered in clinic for the patients with atypical chylothorax and anti-infective treatment should be performed in order to avoid the failed diagnosis and misdiagnosis.

Clinical analysis of bronchofibroscope-guided bronchoalveolar lavage and topical antibiotics in the treatment of pediatric patients with severe pneumonia / 中国医师杂志

Objective To investigate the clinical effect,safety,and value of bronchofibroscopeguided bronchoalveolar lavage and topical antibiotics in the treatment of pediatric patients with severe pneumonia.Methods A total of 60 patients with severe pneumonia was randomly divided into two groups with 30 cases in each group.Patients in the control group were treated with conventional anti-infection therapy,while patients in the treatment group were treated with bronchofibroscope-guided bronchoalveolar lavage and topical antibiotics on the basis of conventional therapy.The sputum positive rate,clinical effect,hospital stays,treatment costs,and adverse reactions were compared to analyze its value.Results The total effective rate of treatment group was 93.3％,which was significantly higher than that (60.0％) in the control group (P ＜0.01).The sputum positive rate of treatment group was 80.0％,which was significantly higher than that (43.3％) in the control group (P ＜0.01).The hospital stays and the treatment costs of the treatment group were both significantly less than those in control group (P ＜0.01 orP ＜0.05).No serious complications were found in patients of the treatment group.Conclusions Bronchofibroscope-guided bronchoalveolar lavage and topical antibiotics in the treatment of pediatric patients with severe pneumonia show exactly clinical effects and significant improvement in dyspnea,which shortens the hospital stays,reduces the treatment costs,and has no seriously adverse reactions.Therefore,it is worthy of clinical promotion and application.

Isolation and culture of human amniotic mesenchymal stem cells:proper digestion time and concentrations of trypsin and collagenase / 中国组织工程研究

BACKGROUND:Extraction methods of human amniotic mesenchymal stem cells are inconsistent in the number of cells. OBJECTIVE:To explore the optimal method to in vitro isolate and culture human amniotic mesenchymal stem cells. METHODS:Under sterile conditions, ful-term cesarean fetal amniotic membrane was cut into pieces, then to isolate human amniotic mesenchymal stem cells by seven methods in four experiments. In experiment 1, human amniotic mesenchymal stem cells were isolated by the fol owing three methods:(1) 0.05 g/L trypsin digestion for 10 minutes fol owed by 0.75 g/L col agenase digestion for 60 minutes;(2) 0.75 g/L col agenase I for 120 minutes;(3) co-digestion with 0.05 g/L trypsin and 0.75 g/L col agenase for 60 minutes. In experiment 2, the samples were digested with 0.05 g/L trypsin digestion for 30 minutes fol owed by 0.75 g/L col agenase digestion for 30 minutes. In experiment 3, the samples were digested by two methods:(1) 0.05 g/L trypsin digestion for 30 minutes×2, fol owed by 0.75 g/L col agenase digestion for 60 minutes;(2) 0.05 g/L trypsin digestion for 40 minutes×2, fol owed by 0.75 g/L col agenase digestion for 60 minutes. In experiment 4, the samples were digested with 0.05 g/L trypsin digestion for 30 minutes×2, fol owed by 1 g/L col agenase digestion for 60 minutes. Fol owing morphology observation under a microscope, we studied the most suitable method for isolating human amniotic mesenchymal stem cells. RESULTS AND CONCLUSION:Digestion with 0.05 g/L trypsin for 30 minutes twice fol owed by 1 g/L of col agenase digestion of 60 minutes was the most suitable isolation and culture condition in vitro. cells became elongated fusiform or star-shaped with rich cytoplasm, and nuclei were round with 1-3 nuts. We can harvest the most number of human amniotic mesenchymal stem cells using the method described in experiment 4.

Studies on the purification of water-soluble holothurian glycosides from Apostichopus japonicus and their tumor suppressing activity / 药学学报

To obtain water-soluble holothurian glycosides with high tumor suppressing activities from Apostichopus japonicus, macroporous resin, silica gel and gel-filtration column chromatograghy were used to purify the water-soluble holothurian glycosides, and their tumor suppressing activity and inducing apoptosis of tumor cells were examined in this study. The 70% ethanol fraction of macroporous resin column, the pSC-2 and pSC-3 fractions from silica gel column showed very strong tumor suppressing activity towards HeLa cells, A-549 lung cancer cells, SGC-7901 stomach cancer cells and Bel-7402 liver cancer cells. SC-2 and SC-3 fraction purified from Sephadex LH-20 gel-filtration column chromatography, with a purity above 99.6%, all had the properties of triterpenoid glycosides. Purified SC-2 fraction had remarkable tumor suppressing activity on HeLa cells in a dose- and time-dependent manner, and had prominent tumor suppressing activity to mouse S180 solid tumors in a dose-dependent manner. Besides, the SC-2 fraction also had remarkable ability in elevating mouse thymus index and spleen index. The purified SC-2 fraction could induce apoptosis of HeLa cells in a dose-dependent manner, and DNA fragmentation of HeLa cells occurred after treated 12 h with 10 mg x L(-1) and 50 mg x L(-1) of SC-2 fractions. From the results, it can be concluded that the purified SC-2 fraction of water-soluble holothurian glycosides has extremely strong tumor suppressing activity, and the suppression is realized by inducing tumor cells to undergo apoptosis. This study lays solid foundation for development of highly effective new natural anticancer agents from sea cucumbers.

Clinical observation on treatment of Tourette syndrome by integrative medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the clinical efficacy of integrative Chinese and Western medicine in treating Tourette syndrome (TS).</p><p><b>METHODS</b>Ninety children with TS were randomized into two groups by randomizing: digital table method: the 60 patients in the treated group were treated by Ningdong Granule (NDG) plus haloperidol, and the 30 in the control group treated by haloperidol alone. The course for both groups was 6 months. Conditions of the patients were estimated before and after treatment with Yale Global Tic Severity Scale (YGTSS), the short-term efficacy, adverse reaction of treatment were assessed at the end of treatment, and the long-term efficacy as well as the recurrent rate were evaluated half a year after the treatment was ended.</p><p><b>RESULTS</b>Of the 60 patients in the treated group, the treatment on 36 was evaluated as remarkably effective, 21 as effective, and 3 as ineffective, the total effective rate being 95.0% (57/60), while of the 30 patients in the control group, the corresponding data were 9, 13, 8 and 73.3% (22/30), respectively, differences between groups in markedly effective rate and total effective rate were statistically significant (chi(2)=7.20, and chi(2)=6.85, P<0.01). The improvement on the condition of illness, motor tic and vocal tic, as well as the long-term efficacy of treatment were all better in the treated group than in the control group (P<0.05 or P<0.01). The incidence of adverse reaction and the recurrent rate in the treated group were 13.3% (8/60) and 8.3% (5/60) respectively, all were lower than those in the control group, 36.7% (11/30) and 43.3 (13/30), showing statistical significances (P<0.05 and P<0.01).</p><p><b>CONCLUSION</b>Integrative medical treatment on TS was markedly effective in clinical practice with less adverse reaction and lower recurrent rate.</p>

Characteristics of TCM Syndromes in 126 Children with Tourette Syndrome / 中医杂志

Objective To investigate the characteristics of TCM syndromes of Tourette syndrome (TS) to find out the basis for its TCM treatment. Methods Based on the preliminary studies,the TCM syndrome scale of TS is designed to investigate the general data,main symptoms and syndromes of 126 cases of TS children to find out the frequency of each syndrome. Results Of the 126 TS cases,97 were males,accounting for 77%; the average age was 8.31 years; and 32 had a positive family history,accountting for 25.4%. In the tic behavior,the facial twitching and limb twitching occupied 91.6% of the muscular stereotyped tic. In the vocal behavior,the throat and nasal sound occupied 42.1%. In the accompanied symptoms,the inattention occupied 69.8%. In the personality offset,the willfulness occupied 49.2%,irritable hyperactivity occupied 78.6%,and silence occupied 7.1%. More than 50% of the patients had red or dark red tongue with thick or sticky coating. Nearly 70% of them had string-taut or rolling pulse. As for the syndromes,heart-liver deficiency with deficiency wind stirred up,and liver-kidney yin deficiency with yang hyperactivity stirring up wind were common,being 41.3% and 34.1% respectively. Conclusion TS takes the heart-liver deficiency with deficiency wind stirred up and liver-kidney yin deficiency with yang hyperactivity stirring up wind as the common syndromes. The basic treating principle is enriching yin and reducing yang,and smoothing the liver to stop wind. At the same time,reinforcing the spleen and nourishing the heart,and dissolving phlegm and enlightening the brain should be applied for treatment.