Visual analysis on the study status and trends of acupuncture and moxibustion for Alzheimer's disease. / é’ˆç¸æ²»ç–—é˜¿å°”èŒ¨æµ·é»˜ç— ç ”ç©¶çŠ¶å†µåŠè¶‹åŠ¿çš„å¯è§†åŒ–åˆ†æž.

The research history, hot spots and frontier trends of acupuncture and moxibustion for Alzheimer's disease (AD) were explored using knowledge graph technology. The articles on acupuncture and moxibustion for AD were searched from 6 databases, i.e. CNKI, VIP, Wanfang, SinoMed, Pubmed and Web of Science, from January 1st, 1993 to January 1st, 2023. Using CiteSpace6.2.R2 Advance and VOSviewer V1.6.19 softwares, the knowledge map was graphed and the visual analysis was performed. A total of 1 228 Chinese and 309 English articles were included. The high-frequency keywords were generally divided into the keywords of clinical diseases (AD, dementia), those of therapeutic methods (electroacupuncture, acupuncture-moxibustion and acupuncture) and those of mechanism study (ß-amyloid, mice). Thirteen keyword clusters were formed among the articles of Chinese version, e.g. acupuncture-moxibustion, dementia, acupuncture and electroacupuncture; and 8 clusters were obtained among English articles, e.g. electroacupuncture, drug therapy and hippocampus. The high-frequency keywords of acupoints included Baihui (GV 20), Dazhui (GV 14), Yintang (GV 24+), Zusanli (ST 36), Fenglong (ST 40), etc. Six clusters of "acupuncture techniques → acupoints" were obtained for the treatment of AD with acupuncture and moxibustion. The therapeutic methods and modes of AD with acupuncture and moxibustion are constantly progressed, the development of clinical research tends to the evaluation of novel therapeutic mode and clinical effect, and the mechanism of acupuncture and moxibustion for the effect on AD are more deeply explored. Among the various therapeutic methods, acupuncture-moxibustion, acupuncture and electroacupuncture have been early predominant; while, many novel methods are gradually displayed later, such as music electroacupuncture and hydro-acupuncture. In recent 30 years, among Chinese and English articles for the studies of AD treated with acupuncture and moxibustion, the theme of them focuses on the two aspects, the observation of clinical effect and the mechanism research. It is found that the clinical therapeutic methods have been gradually improved and the mechanism exploration been deepened.

Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. METHODS: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. RESULTS: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. CONCLUSIONS: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. TRIAL REGISTRATION: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.

Based on functional and histopathological correlations: is diffusion kurtosis imaging valuable for noninvasive assessment of renal damage in early-stage of chronic kidney disease?

PURPOSE: To evaluate the potential of 3 T magnetic resonance diffusion kurtosis imaging (DKI) in assessing the renal damage in early-stage of chronic kidney disease (CKD) patients with normal or slightly changed functional index, using histopathology as reference standard. METHODS: 49 CKD patients and 18 healthy volunteers were recruited in this study. CKD patients were divided into two groups based on estimated glomerular filtration rate (eGFR): Study group I (eGFR ≥ 90 ml/min/1.73 m2 [n = 20]) and Study group II (eGFR < 90 ml/min/1.73 m2 [n = 29]). DKI was performed in all participants. The DKI parameters (mean kurtosis [MK], mean diffusivity [MD], fractional anisotropy [FA]) of renal cortex and medulla were measured. The differences of parenchymal MD, MK and FA values among the different groups were compared. The correlations between DKI parameters and clinicopathological characteristics were assessed. Diagnostic performance of DKI to assess renal damage in early-stage of CKD was analyzed. RESULTS: The cortex MD and MK showed significant difference among three groups (P < 0.05): trend of cortex MD: Study group II < Study group I < control group; trend of cortex MK: control group < Study group I < Study group II. The cortex MD and MK and medulla FA were correlated with eGFR and Interstitial fibrosis/Tubular atrophy score (0.3 < r < 0.5). Cortex MD and MK yielded an AUC of 0.752 for differentiating healthy volunteers from CKD patients with eGFR ≥ 90 ml/min/1.73 m2. CONCLUSION: DKI shows potential in non-invasive and multi-parameter quantitative assessment of renal damage in early-stage of CKD patients and provide additional information for changes in renal function and histopathology.

Plasma D-dimer levels are associated with disease progression in diabetic nephropathy: a two-center cohort study.

BACKGROUND: This study aimed to investigate the relationship between plasma D-dimer levels, clinicopathological features, and clinical outcomes in patients with biopsy-proven diabetic nephropathy (DN). METHODS: A total of 137 patients with biopsy-proven DN were enrolled in this two-center cohort study. Patients were stratified into tertiles based on plasma D-dimer levels. We investigated the relationship between plasma D-dimer levels and clinical outcomes, including a composite of death, a 40% decline in estimated glomerular filtration rate (e-GFR) from baseline, or end-stage renal disease (ESRD) (defined as e-GFR < 15 mL/min/1.73 m2 or need for renal replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), assessed using Cox regression models with adjustment for confounders. RESULTS: At baseline, the mean age was 52.61 ± 11.63 years, and the mean e-GFR was 58.02 ± 28.77 mL/min/1.73 m2. During a median 26-month follow-up period, 65 (47% of patients) achieved clinical outcomes. Compared with the low plasma D-dimer level group, those with higher plasma D-dimer levels were more likely to have higher 24-h proteinuria (p = .002), lower e-GFR (p = .001), lower hemoglobin (p = .001), a higher glomerular lesion class (p = .03), and higher interstitial fibrosis and tubular atrophy (IFTA) scores (p = .002). After adjustment for demographic, DN-specific covariates, and treatments, it was observed that a higher tertile of plasma D-dimer was nonlinearly associated with an increased risk of the clinical outcomes (Hazard Ratio (HR) for tertile 2 vs. 1, 1.7; 95% Confidence Interval (CI), 0.80-3.75; HR for tertile 3 vs. 1, 2.2; 95% CI, 0.93-5.27; p for trend = .001) in the Cox proportional hazards models. CONCLUSION: In this study, DN patients with higher levels of plasma D-dimer had higher 24-h proteinuria, lower e-GFR, a higher glomerular lesion class, and higher IFTA scores. Furthermore, a high level of plasma D-dimer was nonlinearly associated with DN progression.

Current situation and trend of translational research of acupuncture-moxibustion in treatment of aphasia based on knowledge graph analysis. / åŸºäºŽçŸ¥è¯†å›¾è°±æŠ€æœ¯åˆ†æžé’ˆç¸æ²»ç–—å¤±è¯­ç—‡è½¬åŒ–ç ”ç©¶çš„çŽ°çŠ¶ä¸Žè¶‹åŠ¿.

OBJECTIVES: To investigate the hot topics in acupuncture-moxibustion research for treatment of aphasia and explore the current situation and trend of technology transformation in this field through analyzing the relevant Chinese literatures in recent 30 years by means of knowledge graph technology. METHODS: CiteSpace 6.1.R 2 and VOSviewer V1.6.16 software were used to collate the data, draw knowledge graphs and conduct visual analysis of the literatures related to acupuncture-moxibustion treatment of aphasia, searched from CNKI, WanFang and VIP databases.The time line view and strongest bursts of keywords were formed in the field of acupuncture-moxibustion treatment for aphasia. The treatment-based keyword networks were visualized. RESULTS: A total of 773 Chinese articles were included. Through visual analysis of the co-occurrence networks, the top 10 high-frequency overall keywords and the top 10 clusters of overall keywords were listed. The top 5 high-frequency aphasia categories were Broca aphasia, hysterical aphasia, transcortical motor aphasia, nominal aphasia and sensory aphasia. Regarding the keywords of the techniques of acupuncture-moxibustion, the occurrence frequencies of scalp acupuncture, tongue acupuncture, body acupuncture and electroacupuncture were ≥ 10 times.The occurrence frequencies of 16 acupoints were ≥25 times. After collation and cluster analysis of acupoints and techniques of acupuncture-moxibustion, 7 keyword clusters of "acupuncture techniques-acupoints" were obtained. The time line view showed that the strongest burst of keywords were transcranial magnatic stimulation, language rehabilitation training, acupuncture-medicine therapy and stroke, etc. in the recent 5 years. CONCLUSIONS: Acupuncture-moxibustion displays its unique advantage in treatment of aphasia. With the deepening of modern research, the hot topics for aphasia treated with acupuncture-moxibustion are present and the achievements enriched. In future, these therapeutic methods should be further investigated to explore a model of translational medicine for aphasia in line with the characteristics of acupuncture-moxibustion.

[Study on the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng].

To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.

Tongdu Tiaoshen acupuncture combined with Bobath rehabilitation training for upper limb spasm after stroke: a randomized controlled trial. / 通督调神法针刺联合Bobathåº·å¤è®­ç»ƒæ²»ç–—å’ä¸­åŽä¸Šè‚¢ç—‰æŒ›ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe clinical effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) acupuncture combined with Bobath rehabilitation training in the treatment of upper limb spasm after stroke. METHODS: A total of 66 patients with upper limb spasm after stroke were randomly divided into an observation group (33 cases, 1 case dropped out) and a control group (33 cases, 2 cases dropped out). The control group received Bobath rehabilitation training. On the basis of the control group, the patients in the observation group received Tongdu Tiaoshen acupuncture at Baihui (GV 20), Fengfu (GV 16), Mingmen (GV 4), Yaoyangguan (GV 3) and bilateral C4-T1 Jiaji points (EX-B 2), etc. Both groups were treated once a day, with 6 days of continuous treatment followed by 1 day of rest, and totally 4 weeks were required. The modified Ashworth scale ( MAS ) grade, Fugl-Meyer assessment of upper extremity ( FMA-UE ) score, modified Barthel index ( MBI ) score, serum level of neurotransmitter (glutamic acid [Glu] and γ-aminobutyric acid [GABA]) were compared between the two groups before and after treatment, and the clinical effect was evaluated. RESULTS: After treatment, MAS grade and serum level of Glu in the two groups were lower than those before treatment (P<0.05), and FMA-UE, MBI scores and serum level of GABA were higher than those before treatment (P<0.05). The MAS grade and serum level of Glu in the observation group were lower than those in the control group (P<0.05), and the FMA-UE, MBI scores and serum level of GABA were higher than those in the control group (P<0.05). The total effective rate of the observation group was 87.5% (28/32), which was better than 45.2% (14/31) of the control group (P<0.05). CONCLUSIONS: The combination of Tongdu Tiaoshen acupuncture and Bobath rehabilitation training can effectively reduce the upper limb muscle tension level of patients with upper limb spasm after stroke, improve upper limb motor function, enhance self-care ability, and regulate serum level of neurotransmitter.

Effects on Autophagy of Moxibustion at Governor Vessel Acupoints in APP/PS1double-Transgenic Alzheimer's Disease Mice through the lncRNA Six3os1/miR-511-3p/AKT3 Molecular Axis.

Objective: To explore the effect and mechanism of moxibustion at acupoints of the governor vessel on lncRNA Six3os1 in amyloid precursor protein/presenilin1 (APP/PS1) double-transgenic Alzheimer's disease (AD) mice. Methods: Twenty-four specific pathogen-free and APP/PS1 double-transgenic male mice were randomly allocated into the AD model and moxibustion groups, with 12 cases in each group. Twelve syngeneic C57BL/6J mice were selected as the control group. Mice in the moxibustion group received aconite cake-separated moxibustion at the Baihui acupoint. Suspension moxibustion was applied at Fengfu and Dazhui for 15 minutes each day. All treatments were conducted over two weeks. Control and AD model mice were routinely fed without any intervention. Behavioral observation tests were conducted before and after the intervention. The autophagosome in the hippocampus was observed using transmission electron microscopy. Immunohistochemistry was performed to detect Aß1-42 expression. LC3B and P62 expressions were evaluated by immunofluorescence. The expression levels of the lncRNAs Six3os1, miR-511-3p, and AKT3 were detected by qRT-PCR. The differential expression of PI-3K, AKT3, mTOR, LC3B-II/I, and P62 proteins in the hippocampus was detected by western blot. The dual-luciferase assay was undertaken to examine the targeting relationships of the lncRNAs Six3os1, miR-511-3p, and AKT3. Results: Compared with the control group, the AD model showed higher escape latency in the Morris Water Maze and reduced autophagic vacuoles in the cytoplasm of hippocampal neurons (both p < 0.01). Compared with the control group, the AD model showed higher expression of Aß1-42, the lncRNAs Six3os1, PI-3K, mTOR, P62, and AKT3 protein (all p < 0.01); but lower mir-511-3p and LC3B (both p < 0.01). Compared with the AD model group, the moxibustion group had a shorter escape latency, more autophagic bubbles in the hippocampus, and lower expression of positive Aß1-42, the lncRNAs Six3os1, PI-3K, mTOR, P62, and AKT3 protein (all p < 0.01). In contrast, the levels of miR-511-3p and LC3B proteins were considerably increased in the moxibustion group compared to the AD model group (both p < 0.01). Based on the dual-luciferase assay, there was a targeting link among the lncRNAs Six3os1, miR-511-3p, and AKT3. Conclusion: Moxibustion at acupoints of the governor vessel can suppress the lncRNA Six3os1 expression, promote cell autophagy, accelerate Aß1-42 clearance and alleviate cognitive dysfunction of AD mediated by the PI3K/AKT/mTOR signaling pathway through the lncRNA Six3os1/miR-511-3p/AKT3 axis.

[Effect of moxibustion on autophagy in mice with Alzheimer's disease based on mTOR/p70S6K signaling pathway].

OBJECTIVE: To investigate the effect of moxibustion on autophagy and amyloid ß-peptide1-42 (Aß1-42) protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD). METHODS: After 2-month adaptive feeding, fifty-six 6-month-old APP/PS1 double transgenic AD mice were randomly divided into a model group, a moxibustion group, a rapamycin group and an inhibitor group, 14 mice in each group. Another 14 C57BL/6J mice with the same age were used as a normal group. The mice in the moxibustion group were treated with monkshood cake-separated moxibustion at "Baihui"(GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) for 20 min; the mice in the rapamycin group were intraperitoneally injected with rapamycin (2 mg/kg); the mice in the inhibitor group were treated with moxibustion and injection of 1.5 mg/kg 3-methyladenine (3-MA). All the treatments were given once a day for consecutive 2 weeks. The morphology of hippocampal tissue was observed by HE staining; the ultrastructure of hippocampal tissue was observed by transmission electron microscopy; the expression of Aß1-42 protein in frontal cortex and hippocampal tissue was detected by immunohistochemistry; the expressions of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), p70 ribosomal protein S6 kinase (p70S6K) and phosphorylated p70S6K (p-p70S6K) protein in hippocampus were detected by Western blot method. RESULTS: Compared with the normal group, the number of neuron cells was decreased, cells were necrotic and deformed, and autophagy vesicle and lysosome were decreased in the model group. Compared with the model group, the number of neuron cells was increased, cell necrosis was decreased, and autophagy vesicle and lysosome were increased in the moxibustion group and the rapamycin group. Compared with the normal group, the protein expressions of Aß1-42, mTOR, p-mTOR, p70S6K and p-p70S6K in the model group were increased (P<0.05); compared with the model group, the protein expressions of Aß1-42, mTOR, p-mTOR, p70S6K and p-p70S6K in the moxibustion group, rapamycin group and inhibitor group were decreased (P<0.05); compared with the inhibitor group, the protein expressions of Aß1-42, mTOR, p-mTOR, p70S6K and p-p70S6K in the moxibustion group and rapamycin group were decreased (P<0.05); compared with the rapamycin group, the protein expressions of mTOR, p-mTOR, p70S6K and p-p70S6K in the moxibustion group were decreased (P<0.05). CONCLUSION: Moxibustion could enhance autophagy in hippocampal tissue of APP/PS1 double transgenic AD mice and reduce abnormal Aß aggregation in brain tissue, the mechanism may be related to the inhibition of mTOR/p70S6K signaling pathway.

Acupuncture relieves the visceral pain of diarrhea-predominant irritable bowel syndrome rats by regulating P2X4 expression.

OBJECTIVES: We researched the effect and mechanism of acupuncture treatment for visceral pain in rats with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: We set up a rat model of IBS-D with chemical and chronic- and acute-pressure stimulations. Then, the IBS-D rats were treated with acupuncture or 5-BDBD, and the therapeutic efficacy of acupuncture in IBS-D rats was assessed by means of the Bristol scale, diarrhea index, abdominal withdrawal reflex (AWR) score, mast cell count and histologic staining. RESULTS: Acupuncture significantly decreased clinical symptoms in IBS-D rats after a 14 day-treatment. Furthermore, significant down-regulation of P2X4, OX42, BDNF (brain-derived neurotrophic factor) and IRF-5 (interferon regulatory factor 5) expressions were observed in the IBS-D rats, along with the decreased inflammatory factors [interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6)], chemokines [monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), and C-X-C motif chemokine ligand 1 (CXCL1)], and neurotransmitters [substance P (SP), 5-hydroxytryptamine (5-HT), and calcitonin gene-related peptide (CGRP)]. 5-BDBD treatment had a similar effect on IBS-D rats. CONCLUSIONS: Acupuncture can effectively alleviate abdominal pain by decreasing visceral hypersensitivity and controlling the expression of P2X4 and spinal microglial inflammation in IBS rats.

[Effect of moxibustion on autophagy lysosome function mediated by mTOR/TFEB pathway and lncRNA H19 expression in APP/PS1 double transgenic mice].

OBJECTIVE: To observe the effect of moxibustion (Moxi) at acupoints of Governor Vessel on autophagy lysosomal function and lncRNA H19 in amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic Alzheimer's disease (AD) mice, so as to explore its underlying mechanisms in relieving AD. METHODS: Fifty two male APP/PS1 double transgenic AD mice were randomly divided into model, Moxi, Moxi+inhibitor and medication (rapamycin) groups, with 13 mice in each group. Other 13 male C57BL/6J mice of the same age were selected as the control group. The mice of the Moxi group received aconite cake-separated Moxi stimulation at "Baihui" (GV20), "Dazhui"(GV14) and "Fengfu" (GV16), for 15 min, those of the Moxi+inhibitor group received intraperitoneal injection of 3-methyladenine (an inhibitor of PI3K for suppressing autophagy) 1.5 mg· kg-1 · d-1 on the basis of Moxi, and those of the medication group received intraperitoneal injection of rapamycin 2 mg· kg-1 · d-1. The treatment was conducted once daily for 2 weeks. The mouse's learning-memory ability was detected by Morris water maze tests. The hippocampus tissue was sampled for observing the formation of autophagy by using transmission electron microscope, detecting the expression of Aß_(1-42) protein with immunohistochemical staining, and for detecting the expression levels of long noncoding RNA H19 (lncRNA H19), mammalian target of rapamycin kinase (mTOR), nuclear transcription factor EB (TFEB), Cathepsin D and lysosome associated membrane protein-1 (LAMP1) genes and proteins as well as microtubule associated protein 1 light chain 3B (LC3B)-Ⅱ/LC3B-Ⅰand autophagy protein p62 protein by quantitative real-time PCR and Western blot, respectively. RESULTS: In contrast to the control group, the model group had an evident increase in the escape latency of Morris water maze test, and in the expression levels of Aß_(1-42) protein, lncRNA H19 mRNA, mTOR mRNA and protein, and p62 protein (P<0.05), and a significant decrease in the expression levels of TFEB, Cathepsin D, LAMP1 mRNAs and proteins and LC3B-Ⅱ/LC3B-Ⅰ (P<0.05). After the treatment and relevant to the model and Moxi+inhibitor groups, both the Moxi and medication groups had an obvious down-regulation in the levels of latency of Morris water maze, expression levels of Aß_(1-42) protein, lncRNA H19 mRNA, mTOR mRNA and protein, and p62 protein (P<0.05), and a significant up-regulation in the levels of TFEB, Cathepsin D, LAMP1 mRNAs and proteins and LC3B-Ⅱ/LC3B-Ⅰ (P<0.05). CONCLUSION: Moxi at acupoints of Governor Vessel can improve cognitive function of AD mice, which may be associated with its functions in inhibiting mTOR/TFEB pathway by down-regulating the expression of lncRNA H19, improving autophagy lysosomal function, promoting autophagy and clearing away Aß1-42 in the hippocampus.

Network Pharmacology and In Vivo Experimental Validation to Uncover the Renoprotective Mechanisms of Fangji Huangqi Decoction on Nephrotic Syndrome.

Background: Fangji Huangqi decoction (FHD) is a traditional Chinese medicine formula that has the potential efficacy for nephrotic syndrome (NS) treatment. This study aims to explore the effects and underlying mechanisms of FHD against NS via network pharmacology and in vivo experiments. Methods: The bioactive compounds and targets of FHD were retrieved from the TCMSP database. NS-related targets were collected from GeneCards and DisGeNET databases. The compound-target and protein-protein interaction networks were constructed by Cytoscape 3.8 and BisoGenet, respectively. GO and KEGG analyses were performed by the DAVID online tool. The interactions between active compounds and hub genes were revealed by molecular docking. An NS rat model was established to validate the renoprotective effects and molecular mechanisms of FHD against NS in vivo. Results: A total of 32 hub genes were predicted to play essential roles in FHD treating NS. Eight main bioactive compounds of FHD had the good affinity with 9 hub targets (CCL2, IL-10, PTGS2, TNF, MAPK1, IL-6, CXCL8, TP53, and VEGFA). The therapeutic effect of FHD on NS was closely involved in the regulation of inflammation and PI3K-Akt pathway. In vivo experiments confirmed the renoprotective effect of FHD on NS, evidenced by reducing the levels of proteinuria, serum creatinine, blood urea nitrogen, and inflammatory factors in NS rats. The PI3K activator 740Y-P weakened the effects of FHD against NS. Furthermore, FHD downregulated the levels of PTGS2, MAPK1, IL-6, and p-Akt in NS rats. Conclusions: FHD alleviates kidney injury and inflammation in NS by targeting PTGS2, MAPK1, IL-6, and PI3K-Akt pathway.

Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study.

INTRODUCTION: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. METHODS: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0-25%], moderate [26-50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. RESULTS: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m2] of 1.34 [95% CI: -2.56 to 5.23], 3.50 [95% CI: -0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10-3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52-5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. CONCLUSION: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

Job burnout is associated with slow improvement of quality of life in the employees after a first episode of acute coronary syndrome: A hospital-based longitudinal study in China.

OBJECTIVE: This study investigated the association between job burnout and quality of life (QoL) after acute coronary syndrome (ACS) in a Chinese sample. METHODS: This was a one-year longitudinal study. Participants included patients with a first episode of ACS who were still employed. The Copenhagen Burnout Inventory (CBI) assessed job burnout before discharge, and QoL was assessed using the Medical Outcome Study 8-Items Short Form Health Survey (SF-8) and the Seattle Angina Questionnaire (SAQ) before discharge (baseline), at one month, six months and 12 months after discharge. Generalized estimating equations determined the association between job burnout and longitudinal changes of QoL. RESULTS: All participants were assigned to either a "low job burnout" group (n = 70) or a "high job burnout" group (n = 50), based on the upper quartile of job burnout scores. Longitudinally over 1-year follow-up period, the scores of the SF-8 and SAQ among patients with a high level of burnout were lower than those in the low job burnout group. Job burnout was significantly associated with lower physical and mental health (SF-8), as well as greater physical limitation and lower treatment satisfaction (SAQ) over time. CONCLUSION: Job burnout at baseline predicted slow improvement of QoL after ACS in a Chinese working sample.

Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade.

BACKGROUND: Podocytes have become a crucial target for interventions in proteinuric kidney diseases. Many studies have reported that overexpression of transient receptor potential cation channel protein 6 (TRPC6) in podocyte injury upregulates intracellular Ca2+ influx and stimulates Ca2+-dependent protease calpain-1 signaling. The traditional Chinese drug, tetrandrine, a nonselective Ca2+ channel blocker, has long been used to treat chronic kidney disease. This research aimed to explore the possible mechanisms underlying the anti-proteinuric properties of tetrandrine. METHODS: We investigated the involvement of tetrandrine in Ca2+ dependent calpain-1 signaling in mouse podocytes and adriamycin-induced nephropathy rats. Cyclosporine A (CsA) and U73122 were used as positive controls. Cell viability, cytotoxicity, Ca2+ concentration, calpain activity, and mRNA and protein expression levels of calpain-1 signaling pathways were examined. The clinical and pathological changes were measured. RESULTS: Tetrandrine decreased intracellular Ca2+ influx in cultured TRPC6-overexpressing podocytes. In both in vitro and in vivo studies, the administration of tetrandrine downregulated calpain activity and the expression of calpain-1 and restored the expression of downstream Talin-1 and nephrin. Compared to CsA, tetrandrine treatment exhibited superior inhibitory effects on calpain activity and calpain-1 expression. CONCLUSIONS: Tetrandrine has therapeutic potential in podocyte damage by blocking Ca2+-dependent activation of the calpain-1 signaling pathway. Tetrandrine reduced proteinuria, improved renal function, and alleviate renal pathological damage.

[Effect of moxibustion on cognitive function and proteins related with apoptosis of hippocampal neurons in rats with vascular dementia].

OBJECTIVE: To observe the effect of moxibustion on proteins related with apoptosis of hippocampal neurons in rats with vascular dementia (VD), and to explore the possible mechanism of moxibustion on improving VD. METHODS: Thirty SD rats were selected from 100 rats (3 rats were excluded) and randomly divided into a normal group and a sham operation group, 15 rats in each group. The remaining 67 rats were treated with ischemia-reperfusion method at bilateral common carotid artery to establish VD model. The 45 rats with successful VD model were randomly divided into a model group, a moxibustion group and a medication group, 15 rats in each group. On the 7th day after successful modeling, the rats in the moxibustion group were treated with suspended moxibustion at "Guanyuan" (CV 4), "Mingmen" (GV 4) and "Dazhui" (GV 14), 15 min per acupoint, once a day; there was 1 d of rest after 6 d of moxibustion, and the treatment was given for 4 weeks. The rats in the medication group was treated with nimodipine tablets by gavage, 2 mg/kg per day, 3 times a day for 4 weeks. Before and after intervention, the Morris water maze test was used to detect the escape latency of rats in each group; after the intervention, the TUNEL method was used to detect the apoptosis rate of neurons in hippocampal CA1 area; the immunofluorescence double labeling method was used to detect the number of co-expression positive cells of B-cell lymphoma-2 (Bcl-2)/neuronal nuclear antigen (NeuN) and Bcl-2-associated X protein (Bax)/NeuN in hippocampal CA1 area; the immunofluorescence single labeling method was used to detect cytochrome C (cytC) and outer mitochondrial membrane receptor Tom20 (Tom20) in hippocampal CA1 area; the Western blot method was used to detect the p53 upregulated modulator of apoptosis (PUMA) in hippocampus. RESULTS: Before intervention, compared with the normal group and the sham operation group, the escape latency in the model group, the moxibustion group and the medication group was prolonged (P<0.01). After intervention, the escape latency in the moxibustion group and the medication group was shorter than that before intervention (P<0.01). Compared with the model group, the escape latency in the moxibustion group and the medication group was shortened (P<0.05); compared with the medication group, the escape latency in the moxibustion group was shortened (P<0.05). Compared with the normal group and the sham operation group, the apoptosis rate of neurons in hippocampal CA1 area was increased, the number of Bcl-2/NeuN co-expression positive cells was decreased, and the number of Bax/NeuN co-expression positive cells was increased in the model group (P<0.01); compared with the model group, the apoptosis rates of hippocampal CA1 neurons were decreased, the number of Bcl-2/NeuN co-expression positive cells was increased, and the number of Bax/NeuN co-expression positive cells was decreased in the moxibustion group and the medication group (P<0.01); compared with the medication group, the apoptosis rate of neurons in hippocampal CA1 area was decreased, the number of Bcl-2/NeuN co-expression positive cells was increased, and the number of Bax/NeuN co-expression positive cells was decreased in the moxibustion group (P<0.01, P<0.05). Compared with the normal group and the sham operation group, the expressions of cytC, Tom20 protein in hippocampal CA1 area and PUMA protein in hippocampal tissue in the model group were increased (P<0.01); compared with the model group, the expressions of cytC, Tom20 protein in hippocampal CA1 area and PUMA protein in hippocampal tissue in the moxibustion group and the medication group were decreased (P<0.01); compared with the medication group, the expressions of cytC, Tom20 protein in hippocampal CA1 area and PUMA protein in hippocampal tissue in the moxibustion group were decreased (P<0.05, P<0.01). CONCLUSION: Moxibustion could improve the cognitive function of VD rats, which may be related to reducing the expression of Bax, cytC, Tom20 and PUMA protein in hippocampal CA1 area, promoting the release of Bcl-2 and inhibiting the apoptosis of hippocampal neurons.

Comparing learners' knowledge, behaviors, and attitudes between two instructional modes of computer programming in secondary education.

BACKGROUND: Unplugged programming is proved to be an effective means to foster the learner-centered programming learning. In addition to the final tests, learners' programming knowledge, skills, and capacities are primarily demonstrated throughout the programming process, particularly in the situation when they encounter challenges and problems. However, few studies examine how learners engage in the programming processes and to what extent unplugged programming fosters learning. This research used a quasi-experimental design to investigate two instructional modes in China's secondary education, namely, the instructor-directed lecturing and the learner-centered unplugged programming. Based on an analytical framework, this research used mixed methods to compare learners' knowledge, behaviors, and attitudes under these two instructional modes. RESULTS: The research results revealed discrepancies between two instructional modes. First, learners in the unplugged programming class achieved significantly higher scores on the programming knowledge assessment, compared to learners in the traditional lecturing class. Second, compared to the traditional lecturing class, learners in the unplugged programming class had higher test scores of the computational thinking skills, particularly on the cooperativity dimension. Next, discrepancies of in-class behaviors showed that learners in the unplugged programming class had frequent behaviors of listening to the instructor's instructions and discussing with peers, while learners in the instructor-directed class had frequent behaviors of listening to instructor, taking notes, and irrelevant activities. Learners' self-reported attitudes in the unplugged programming indicated a higher level of confidence than learners in the traditional lecturing class. Overall, this research revealed that the learner-centered unplugged programming had potential to improve learners' programming knowledge, behaviors, and attitudes compared to the traditional instructor-directed lecturing of programming. CONCLUSIONS: As a feasible and easy-to-use instructional activity in computer science education, unplugged programming is encouraged to be integrated in formal education to increase learners' programming interests, motivations, and qualities. This quasi-experimental research compared learners' programming knowledge, behaviors, and attitudes under two instructional modes. The results revealed critical discrepancies between two instructional modes on learners' knowledge gains, in-class behaviors, and changes of attitudes towards programming. Pedagogical and analytical implications were provided for future instructional design and learning analytics of computer programming education. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40594-021-00311-1.

Tetrandrine may treat membranous glomerulopathy via P13K/Akt signaling pathway regulation: therapeutic mechanism validation using Heymann nephritis rat model.

Membranous glomerulopathy (MGN) is an autoimmune kidney disease that is the primary cause of nephrotic syndrome (NS) in adults. Tetrandrine, a bisbenzylisoquinoline alkaloid, is known to have numerous pharmacological effects. In this study, network pharmacology analysis and experimental validation were conducted to analyze the mechanisms by which tetrandrine functions as a therapeutic intervention for MGN. A systematic network pharmacology method was applied to identify potential targets and determine the therapeutic mechanism of tetrandrine in MGN treatment. A Heymann nephritis (HN) rat model was developed to assess the therapeutic effects of tetrandrine on NS and validate the predicted molecular mechanisms. We obtained 86 potential targets of tetrandrine for the treatment of NS. In vivo experiments showed that tetrandrine could reduce the 24-h urine protein content, decrease glomerular basement membrane proliferation, and significantly decrease thylakoid stroma and cell proliferation in the HN rat kidney tissue. Moreover, tetrandrine suppressed kidney cell apoptosis and upregulated the expression of nephrin and podocin in HN model rats. qRT-PCR results revealed that tetrandrine inhibited IL-1ß, TNFα, and MCP-1 levels in HN model rats. Western blot results indicated that tetrandrine can protect against MGN via the PI3K/Akt signaling pathway. Thus, by using a combination of network and experimental pharmacology methods, we demonstrate that tetrandrine can treat MGN via the PI3K/Akt signaling pathway and provide novel insights into the mechanisms underlying tetrandrine-mediated management of MGN.

High Job Burnout Predicts Low Heart Rate Variability in the Working Population after a First Episode of Acute Coronary Syndrome.

(1) Background: Job burnout may affect the prognosis of patients with acute coronary syndrome (ACS) through mechanisms involving heart rate variability (HRV). However, no study has yet examined those potential associations. Hence, we conducted the present study to investigate this issue. (2) Method: Participants included patients who presented with a first episode of ACS and who were employed. The Copenhagen Burnout Inventory (CBI) was used to assess job burnout. Twenty-four-hour ambulatory electrocardiography recorded HRV on four occasions, i.e., during the hospitalization and follow-ups at one, six, and 12 months, respectively. (3) Results: A total of 120 participants who at least completed three Holter examinations throughout the study were enrolled in the final analysis. Job burnout scores at baseline were inversely associated with LnSDNN, LnTP, LnHF, LnLF, LnULF, and LnVLF during the consequent one-year follow-up. Each 1 SD increase in job burnout scores predicted a decline ranging from 0.10 to 0.47 in the parameters described above (all p < 0.05), and all relationships were independent of numerous confounders, including anxiety and depression. (4) Conclusion: High job burnout predicted reduced HRV parameters during the one-year period post-ACS in the working population.

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases.

AIM: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). METHODS: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m2, and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83-2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68-2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15-3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84-2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68-2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09-3.07) in the fully adjusted model. Then, hemoglobin levels were transformed to a binary variable for fitting the model according to the criteria for anemia of 110 g/L in the women and 120 g/L in men in China. The participants in the anemia group had an increased risk of developing outcomes compared with the nonanemia group in both genders (primary outcome: male: HR, 1.64; 95% CI, 1.01-2.68; female: HR, 1.68; 95% CI, 1.02-2.76; kidney failure: male: HR, 1.60; 95% CI, 0.97-2.64; female: HR, 1.58; 95% CI, 0.95-2.61) in the fully adjusted model. CONCLUSIONS: A low level of hemoglobin was nonlinearly associated with IgAN progression. The anemic IgAN patients presented a higher risk of developing poor outcomes compared with the nonanemic patients.