[Influence of wind, cold and dampness on clinical manifestation of knee osteoarthritis patients based on the stratifications of traditional Chinese medicine constitution].

OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m-2 with an average of (23.80±2.86) kg·m-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m-2 with an average of(23.42±2.97) kg·m-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m-2 with an average of (24.15±2.33) kg·m-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m-2 with an average of (23.79±2.49) kg·m-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION: The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.

Molecular mechanisms of the Guizhi decoction on osteoarthritis based on an integrated network pharmacology and RNA sequencing approach with experimental validation.

Background: Our aim was to determine the potential pharmacological mechanisms of the Guizhi decoction (GZD) in the treatment of osteoarthritis (OA) through an integrated approach of network pharmacological analyses, RNA sequencing (RNA-seq), and experimental validation. Methods: The quality control and identification of bioactive compounds of the GZD were carried out by using ultra-performance liquid chromatography (UPLC), and their OA-related genes were identified through overlapping traditional Chinese medicine systems pharmacology database (TCMSP), DrugBank and SEA Search Server databases, and GeneCards. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were implemented after constructing the component-target network. RNA-seq was used to screen differentially expressed genes (DEGs) under intervention conditions with and without the GZD in vitro. The crossover signaling pathways between RNA-seq and network pharmacology were then analyzed. Accordingly, protein-protein interaction (PPI) networks, GO, and KEGG analysis were performed using the Cytoscape, STRING, or DAVID database. The OA rat model was established to further verify the pharmacological effects in vivo. Hematoxylin-eosin (H&E) and safranin O/fast green (S-O) staining were used to grade the histopathological features of the cartilage. We verified the mRNA and protein expressions of the key targets related to the TNF signaling pathways in vivo and in vitro by qPCR, Western blotting (WB), and immunofluorescence assay. In addition, we also detected inflammatory cytokines in the rat serum by Luminex liquid suspension chip, which included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Results: Eighteen compounds and 373 targets of the GZD were identified. A total of 2,356 OA-related genes were obtained from the GeneCards database. A total of three hub active ingredients of quercetin, kaempferol, and beta-sitosterol were determined, while 166 target genes associated with OA were finally overlapped. The RNA-seq analysis revealed 1,426 DEGs. In the KEGG intersection between network pharmacology and RNA-seq analysis, the closest screening relevant to GZD treatment was the TNF signaling pathway, of which TNF, IL-6, and IL-1ß were classified as hub genes. In consistent, H&E and S-O staining of the rat model showed that GZD could attenuate cartilage degradation. When compared with the OA group in vivo and in vitro, the mRNA levels of TNF-α, IL-1ß, IL-6, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) were all downregulated in the GZD group (all p < 0.05). The expression levels of anabolic proteins (Col2α1 and SOX9) were all higher in the GZD group than in the OA group (p < 0.05), while the expression levels of the catabolic proteins (MMP9 and COX-2) and TNF-α in the GZD group were significantly lower than those in the OA group (p < 0.05). In addition, the expression levels of TNF, IL-6, and IL-1ß were upregulated in the OA group, while the GZD group prevented such aberrations (p < 0.01). Conclusion: The present study reveals that the mechanism of the GZD against OA may be related to the regulation of the TNF signaling pathway and inhibition of inflammatory response.

Self-powered photoelectrochemical aptasensor for sensitive detection of Microcystin-RR by integrating TiO2/S-doped Ti3C2 MXene photoanode and MoS2/S-doped Ti3C2 MXene photocathode.

Screening sufficient Fermi level differentiation of photoeletrodes is significantly meaningful for developing high-performance self-powered photoelectrochemical (PEC) sensors. In this work, a dual-photoelectrode self-powered system was fabricated for sensitive detection of Microcystin-RR (MC-RR) by integration of the TiO2/S-doped Ti3C2 photoanode and MoS2/S-doped Ti3C2 photocathode. The introduction of S-doped Ti3C2 nanosheets synergistically integrated with semiconductors (TiO2 and MoS2) could generate the unique Schottky junctions, which could adjust the Fermi energy levels, facilitate the separation of electron-hole pairs and broaden light absorption, leading to high photoelectric conversion efficiency. The electric output of self-powered sensing systems was increased by the substantial inherent bias between the Fermi energy levels of various photoelectrodes and the complementary functions of Schottky junctions, which provided a necessary foundation for the development of sensitive sensors. After the immobilization of the MC-RR aptamer, a novel signal-off dual-photoelectrode self-powered sensor was constructed for sensitive detection of MC-RR based on steric hindrance effect. Moreover, the as-fabricated sensor exhibited prominent analytical performance including wide detection range (10-16 M to 10-9 M), low detection limit (3.4 × 10-17 M), good selectivity, stability and reproducibility, so as to be successfully applied to real sample analysis. The designing ideas of the proposed S-doped Ti3C2 MXene-based Schottky junctions can provide a foothold for the innovative construction of dual-photoelectrode internal-driven self-powered sensing platforms with satisfactory performance.

Medium & long-chain acylcarnitine's relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study.

BACKGROUND: Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. METHODS: In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. RESULTS: Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. CONCLUSIONS: The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.

Curcumin Conjugated Gold Nanoclusters as Perspective Therapeutics for Diabetic Cardiomyopathy.

Accumulation of lipids in the myocardium contributes to the development of cardiac dysfunctions and various chronic diseases, such as diabetic cardiomyopathy (DCM). Curcumin (Cur) can relieve lipid accumulation problems, but its efficiency is limited by poor water solubility and biocompatibility. Herein, gold nanoclusters (AuNCs) were used to improve the efficiency of Cur, and the conjugates Curcumin-AuNCs (AuCur) were developed. In the treatment of high-fat-induced myocardial cell damage, we found that AuCur could effectively reduce intracellular lipid accumulation, the increase of reactive oxygen species (ROS), the increase of mitochondrial division, and the increase of apoptosis compared with Cur. AuCur decreased the expression of the peroxisome proliferator-activated receptors-α subtype (PPARα), and the therapeutic effect of AuCur was canceled when the expression of PPARα was enhanced. For the above reasons, AuCur treated the toxic effect of high lipid on cardiomyocytes by regulating PPARα, providing a new idea and method for the treatment of DCM.

Observation on effect characteristics of electroacupuncture for different types of functional constipation / 中国针灸

<p><b>OBJECTIVE</b>To explore the differences of electroacupuncture (EA) on onset time and symptom improvement for treatment of different types of functional constipation.</p><p><b>METHODS</b>Thirty-eight cases of constipation were selected, including 9 cases of constipation-predominant irritable bowel syndrome (IBS-C), 10 cases of slow transit constipation (STC), 10 cases of pelvic floor dyssynergia (PFD) and 9 cases of inadequate defecatory propulsion (IDP). The electroacupuncture was applied at Tianshu (ST 25), Fujie (SP 14), Shenshu (BL 23), Dachangshu (BL 25) and so on in abdominal and lumbosacral area, 5 times per week, 10 times as a treatment course. The onset time, score of clinical symptoms of constipation and improvement of every symptom in each group were compared.</p><p><b>RESULTS</b>(1) The onset time was (1.78 +/- 0.83) days in IBS-C type, (3.11 +/- 1.90) days in IDP type, (4.10 +/- 1.85) days in STC type and (4.30 +/- 2.00) days in PFD type, indicating statistical differences between IBS-C type and STC type, IBS-C type and PFD type (both P < 0.05). (2) Compared before the treatment, the total scores of symptoms on the onset day in each group were all improved (P < 0.05, P < 0.01), and score of IBS-C type was superior to the rest 3 types (P < 0.05, P < 0.01). (3) EA improved desire to defecate or frequency of defecation in each type (P < 0.05, P < 0.01), in which both were improved in STC type and PFD type, and the improvement of defecation frequency was more significant in STC type (P < 0.01). EA relieved unsmooth defecation or pendant-expansion feeling in each type (all P < 0.05), in which both were improved in IBS-C type (both P < 0.05). EA relieved abdominal distension and pain in IBS-C type, STC type and PFD type (all P < 0.05), while its effects were not obvious on defecation difficulty, defecation time and defecation texture (all P > 0.05).</p><p><b>CONCLUSION</b>The electroacupuncture for treatment of 4 types of constipation is characterized by rapid onset; the improved symptoms are not identical in the electroacupuncture treatment plan for each type of defecation; the main improvement of symptoms are lied on desire to defecate and frequency of defecation, unsmooth defecation or pendant-expansion feeling and abdominal distension and pain. Meanwhile the improvements of defecation texture, defecation difficulty and defecation time were not signi-ficant.</p>

Study on the measurement and locating of Baliao points (eight sacral foramina) / 中国针灸

<p><b>OBJECTIVE</b>To seek the problems of position, measuring and locating methods of Baliao points (posterior sacral foramina) in modern researches.</p><p><b>METHODS</b>Using Baliao (eight sacral foramina), Shangliao(BL 31), Ciliao(BL 32), Zhongliao(BL 33), Xialiao(BL 34), Dihoukong (posterior sacral foramina), Dikong (sacral foramina) and Digu(sacrum) as the key words, literature in the database of the CNKI from 1957 to 2012 were re trieved and analyzed.</p><p><b>RESULTS</b>Problems were found in the past researches including limited numbers of relative literature, disunity of the measurement targets, complicated terms of indices, disunity of the starting and ending point of measurement, unclear weight of indices, deviation of results, lacking of combination with clinical practice and variety of locating methods.</p><p><b>CONCLUSION</b>Position of Baliao points (eight sacral foramina) are clear. However, the locating methods are blurred and vary a lot. Study on living body has more significance for measurement and researches. Factors of gender, body weight, height and childbearing should also be taken into consideration. Therefore, it is necessary to find a more accurate and easier way of locating.</p>

Influence of microsatellite instability on survival of patients with sporadic colorectal cancer in China / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the role of microsatellite instability(MSI) in Chinese sporadic coloretal cancer.</p><p><b>METHODS</b>A total of 146 patients with colorectal cancer were treated surgically from August 2004 to September 2006 in the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Data were collected prospectively. Univariate and multivariable analyses were performed for parameters such as age, gender, tumor location, differentiation, MSI, tumor type, lymph node metastasis, TNM stage, and survival.</p><p><b>RESULTS</b>Follow-up was available in 134 patients including telephone call and office visit. MSI(P=0.029), tumor type(P=0.000), TNM stage(P=0.000) were independently associated with survival on Cox regression model. There were 26 patients with MSI, and the 1-, 3-, and 5-year survival rates were 100%, 92.3%, and 92.3%, respectively. The remaining 108 patients had microsatellite stable tumor, and the 1-, 3-, and 5-year survival rates were 96.3%, 72.2%, and 63.5%, respectively. The difference was statistically significant(P=0.016).</p><p><b>CONCLUSION</b>Microsatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.</p>

Clinical study on acupuncture for treatment of chronic functional constipation / 中国针灸

<p><b>OBJECTIVE</b>To discuss the effect of acupuncture for treatment of chronic functional constipation (CFC).</p><p><b>METHODS</b>Ninety cases were treated with acupuncture. The following two groups of acupoints were used alternatively once every other day. The acupoints in the first group were Tianshu (ST 25), Qihai (CV 6), Shangjuxu (ST 37) etc., and Zhongliao (BL 33), Xialiao (BL 34), Dachangshu (BL 25) etc. in the second group, electroacupuncture was used at Zhongliao (BL 33), Xialiao (BL 34), Tianshu (ST 25) and Shangjuxu (ST 37), once a day, 10 times constituting one course. The defecation frequency, difficulty degree of defecation, defecation time, endless sensation of defecation, stool quality and awareness of defecation were observed and the Patient Assessment of Constipation Quality of Life (PAC-QOL) was evaluated by constipation patients' diaries.</p><p><b>RESULTS</b>The scores of defecation frequency, difficulty degree of defecation, defecation time, endless sensation of defecation, stool quality, awareness of defecation and PAC-QOL were obviously improved after treatment (all P < 0.01). The total effective rate was 67.7% (61/90). The effect of acupuncture for chronic functional constipation in different dynamic mechanism was different. The effect of slow transit constipation (STC) was better than that of spastic pelvic floor syndrome (SPFS) (P < 0.05), and the effect of constipation caused by irritable bowel syndrome (IBS-C) was better than that of SPFS and relaxant pelvic floor syndrome (RPFS) (both P < 0.05). Fifty-two cases were effectively followed up. Three cases were cured, 6 cases were remarkably effective, 23 cases were effective and 20 cases were ineffective after 1 month of treatment. Three cases were cured, 5 cases were remarkably effective, 16 cases were effective and 28 cases were ineffective after 3 months.</p><p><b>CONCLUSION</b>The effect of acupuncture for CFC with exact etiology, disease location and classification diagnosis is definite, but different dynamic mechanism has different effect. The treatment programs for SPFS and RPFS need to be optimized to improve the therapeutic effect.</p>

Study on thirty patients with slow-transmission constipation treated by acupuncture and moxibustion / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the therapeutic effects and acting specialty of acupuncture and moxibustion for treatment of slow-transmission constipation (STC).</p><p><b>METHODS</b>A clinical pathway was created and Patient-Reported Outcomes (PROs) method was taken for efficacy evaluation dominantly. Acupuncture and moxibustion were applied to 30 STC patients on two groups of acupoints in alternation, with acupoints of Tianshu (ST25), Daheng (SP15), Fujie (SP14), Qihai (RN6), Guanyuan (RN4), Zusanli (ST36), and Shangjuxu (ST37) as group 1; Dachangshu (BL25), Shenshu (BL23), Baliao (BL31, BL32, BL33, BL34), and Sishencong (Ex-HN1) as group 2. Deep needling was applied on acupoints of abdominal and back region and moxibustion was put on Sishencong, 20 times as one course. The therapeutic effect was assessed based on the Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) method by comparing the Bristol scoring on quality of stool, awareness and frequency of defecation, degree of abdominal fullness sensation, and patients' quality of life (QOL) at different time points, i.e., pre-treatment, after 1, 2 and 3 weeks of treatment.</p><p><b>RESULTS</b>Compared with the condition of pre-treatment, after 1, 2 and 3 weeks of treatment, cases using irritant laxative or glycerin enema reduced, with quality of stool normalized, scores for awareness and frequency of defecation increased, and abdominal fullness sensation lessened (all P < 0.01); both the total score and scores on the 4 domains of QOL (malaise, psychosocial complaint, anxiety and interest related to constipation, and satisfaction) were obviously reduced. No adverse event occurred during the treatment course. Therapeutic effectiveness assessment at the end of treatment showed that 13 patients were cured, 9 improved and 8 treated in vain; the corresponding cases assessed at 1 month after treatment were 10, 7, 13; and those at 3 months after were 7, 8, 15, respectively.</p><p><b>CONCLUSION</b>Establishing a clinical pathway is helpful to patients in their continuous diagnosis and treatment. Using PROs method to evaluate the therapeutic effect could clearly reveal the superiority of acupuncture and moxibustion in improving symptoms and QOL in patients of STC.</p>

Diagnosis and surgical management of adult Hirschsprung disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and surgical treatment of adult Hirschsprung disease (AHD).</p><p><b>METHODS</b>Clinical data of 10 patients with AHD undergoing operation from May 1985 to May 2005 were analyzed retrospectively.</p><p><b>RESULTS</b>There were 7 males and 3 females with an age ranged from 14 to 40 years. All the cases had constipation, and were diagnosed by barium enema. Aganglionosis was located in distal sigmoid and rectum in 2 cases, in rectum in 7 cases, unknown in one case. Colostomy was performed in one, Ikeda s operation in 6, Rehbein operation in two,modified Swenson operation in one. After radical operation,7 patients had excellent continence function, one had good function, one had poor function.</p><p><b>CONCLUSIONS</b>The diagnosis of adult HD mainly depends on the history of constipation, barium enema and manometry examination. The pull-through procedures are effective surgical treatments for adult HD. The operation type should be selected individually.</p>