Multi-feature, Chinese-Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP.

BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

The effects of Danzhi Jiangtang capsule on clinical indices and vascular endothelial function in patients with impaired glucose tolerance of Qi-Yin deficiency type.

OBJECTIVE: To observe the effect of Danzhi Jiangtang capsule (DJC) on the clinical indexes and vascular endothelial function indexes in patients with impaired glucose tolerance (IGT). METHODS: A total of 106 patients were enrolled and randomly assigned to the treatment group and control group following a four-week washout period. The patients in the control group received a general lifestyle intervention, while those in the treatment group received DJC (2.0 g 3× a day) in conjunction with the intervention given to the control group patients. The physiological and biochemical levels, vascular endothelial function indices, and traditional Chinese medicine (TCM) syndrome ratings of the patients in the two groups were compared after 12 weeks of therapy. RESULTS: In the control group, the diastolic blood pressure (DBP) was significantly improved compared with those before treatment (83.31 ± 6.47 vs. 79.21 ± 6.17, p < .01) (CI: 1.45, 6.73; Cohen's d: 10.51), as was the case with the nitric oxide (NO) levels and TCM syndrome points (35.71 ± 4.58 vs. 43.96 ± 5.17, 9.57 ± 2.63 vs. 5.38 ± 1.79, p < .001) (CI: -10.28, -6.24; 3.12, 5.18; Cohen's d: 0.90). In the treatment group, the levels of fasting blood glucose, endothelin and vascular endothelial growth factor were significantly improved compared with control group (4.92 ± 0.21 vs. 5.59 ± 0.31, 59.37 ± 13.25 vs. 72.13 ± 12.37, 19.25 ± 2.80 vs. 26.76 ± 1.88, p < .001) (CI: 0.55, 0.78; 7.40, 18.13; 6.52, 8.50; Cohen's d: 4.94, 0.41, 1.32), as was the case with 2-h post-load plasma glucose and total cholesterol (TC) (8.33 ± 0.62 vs. 8.89 ± 1.55, 4.61 ± 1.05 vs. 5.22 ± 1.12, p < .05) (CI: 0.07, 1.07; 0.15, 1.06; Cohen's d: 0.40, 0.51). CONCLUSIONS: Treatment with DJC could significantly improve the physiological and biochemical indicators, vascular endothelial function, and TCM syndrome points of IGT patients, indicating that DJC could be a potential drug to treat patients with IGT of Qi-Yin deficiency type.

The Effect of Yiqi Huoxue Tongluo Decoction on Spinal Cord Microglia Activation and ASK1-MKK3-p38 Signal Pathway in Rats with Diabetic Neuropathic Pain.

Diabetic neuropathic pain (DNP) is one of the most common chronic peripheral neuropathies in diabetes mellitus (DM). Objective. To observe the underlying mechanism of the effects of Yiqi Huoxue Tongluo Decoction (YQHX) on DNP rats. Methods. SD rats were intraperitoneally injected with 35 mg/kg streptozotocin (STZ) to prepare DNP models and were treated with YQHX for 8 weeks. Results. Studies have shown that the drug restores some levels of MWT, TWL, and MNCV, downregulates the levels of inflammatory factors IL-6, IL-1ß, and TNF-α, downregulates the levels of ASK1-MKK3-p38, and weakens the level of OX42 activation. Conclusion. Yiqi Huoxue Tongluo Decoction can relieve DNP by affecting the activity of spinal cord microglia and the ASK1-MKK3-p38 signaling pathway, thereby reducing the central sensitization caused by the inflammatory response of DNP rats.

The Protective Effects of a Modified Xiaohua Funing Decoction against Acute Liver Failure in Mice Induced by D-Gal and LPS.

OBJECTIVE: The aim of this study was to evaluate the effects of a modified Xiaohua Funing decoction (Xfd) on acute liver failure (ALF) and determine whether the protective mechanisms are related to alterations in the gut microbiota. METHODS: An animal model of ALF was induced by intraperitoneal injection of D-galactosamine (D-Gal, 0.5 g/kg) and lipopolysaccharide (LPS, 100 µg/kg). Male BALB/c mice were randomly divided into the following 4 groups: the control group (saline, Con), model group (D-Gal/LPS, Mod), silymarin pretreatment group (200 mg/kg, Sil), and modified Xfd pretreatment group (650 mg/kg, Xfd). The Sil and Xfd groups received the respective intervention orally for 14 days and 2 h before D-Gal/LPS treatment. The liver injury markers included alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver histology. 16S rRNA gene sequencing was performed to assess the effects on the caecum content. RESULTS: D-Gal/LPS treatment caused severe ALF, illustrating that the ALF model was successfully established. The administration of Sil and Xfd greatly reduced the serum ALT and AST levels and improved the pathological signs of liver injury. However, no significant difference was found between the two groups. In contrast to the Mod group, the Sil and Xfd groups showed a shift toward the Con group in terms of the gut microbiota structure. The abundances of Firmicutes and Bacteroidetes and the Bacteroidetes/Firmicutes ratio in the Mod group significantly differed from those in the Con group. The Sil and Xfd groups showed restoration of the disordered microbiota. Significantly increased relative abundances of Lachnospiraceae_NK4A136_group and Candidatus_Saccharimonas and a markedly decreased Muribaculaceae abundance were found in the Sil and Xfd mice compared with those in the Mod mice (P < 0.01, P < 0.05). Interestingly, a negative correlation was observed between the abundances of the gut microbiota constituents, specifically Clostridia_UCG-014, and ALT and AST levels. CONCLUSION: In summary, our results indicate that Xfd may protect the liver and modify the gut microbiota in ALF mice.

Clinical Features and Rules of Chinese Herbal Medicine in Diabetic Peripheral Neuropathy Patients.

OBJECTIVE: To analyse the clinical features of diabetic peripheral neuropathy (DPN) and employ data mining technology to explore the rules of Chinese herbal medicine (CHM) therapy. METHODS: The clinical data of 216 patients with DPN and qi-yin deficiency syndrome were obtained, and the clinical features of the patients were assessed by cluster analysis. Relevant information was entered into the clinical diagnosis and treatment collection system, and data mining techniques were used to analyse the drug frequency, core CHM, CHM pair, and so on. RESULTS: In this study, glycated haemoglobin (HbA1c) and homocysteine (HCY) were closely related to the pathogenesis of DPN. Overall, 162 patients had typical DPN syndrome characteristics, and we analysed 216 prescriptions, including 182 CHM. The frequencies of prescription of Astragalus membranaceus, Ligusticum wallichii, Poria cocos, and Radix Rehmanniae were greater than 45%. A Bayesian network analysis diagram showed that the 9 most common core CHM included Astragalus membranaceus, Ligusticum wallichii, Poria cocos, atractylodes rhizome, and Salvia miltiorrhiza Bge. According to the association rules of CHM, Radix Ophiopogon is used for Codonopsis pilosula; Astragalus membranaceus and atractylodes rhizome for Rehmannia are also frequently used. Astragalus membranaceus and Cinnamomi Ramulus or Ligusticum wallichii and Moutan bark were highly related to a decreased Michigan Diabetic Neuropathy Score. CONCLUSION: HbA1c and HCY are related risk factors for DPN. Numbness is a typical syndrome characteristic. Astragalus membranaceus is a monarch CHM and is used most frequently.

The Chinese Herbal Formula Shenzhu Tiaopi Granule Results in Metabolic Improvement in Type 2 Diabetic Rats by Modulating the Gut Microbiota.

OBJECTIVE: The aim of this study is to investigate the implication of the Chinese herbal formula (CHF) Shenzhu tiaopi Granule (STG) in type 2 diabetes mellitus (T2DM) and discuss the mechanisms by which STG regulates the gut microbiota. METHOD: Goto-Kakizaki (GK) rats and age-matched Wistar (W) rats were acclimatized for 1 week. The GK rats were randomly divided into 3 groups and orally gavaged with saline (model group, M), acarbose (acarbose group, A), and STG (granule of CHF group, G; the component of this formula includes Codonopsis pilosula, Rhizoma Atractylodis, Pinellia, Poria cocos, Pericarpium Citri Reticulatae, Coptis chinensis Franch, and Pueraria). The W rats were orally gavaged with saline (control group, C). The observation time was 8 weeks. The weight, fasting blood glucose (FBG) level, and blood lipid levels were tested. The 16S rRNA genes in the V3-V4 region were sequenced, and the structure of the gut microbiota was analysed. RESULTS: Compared to C, M displayed significant differences in blood glucose, gut microbiota, etc. (P<0.05; P<0.01). Compared to M, A and G showed a similar reduction in the FBG gain and a shift in the structure of the gut microbiota (P<0.05; P<0.01). Compared with A, G exhibited a significant decrease in weight, FBG level, and total cholesterol (P<0.05). The gut microbiota, Bacteroidetes, the Firmicutes/Bacteroidetes ratio, Allobaculum, and Desulfovibrionaceae were significantly decreased in response to the STG treatment, while Lactobacillus was significantly enriched (P<0.05; P<0.01). The community composition also differed at the phylum and genus levels based on the linear discriminant analysis effect size and heat map. CONCLUSION: Our findings suggest that the composition of the gut microbiota was significantly changed in the diabetic GK rats compared with that in the normal W rats. STG treatment can improve glucose and lipid levels and modulate the gut microbiota in T2DM rats.

Danzhi Jiangtang Capsule ameliorates kidney injury via inhibition of the JAK-STAT signaling pathway and increased antioxidant capacity in STZ-induced diabetic nephropathy rats.

Danzhi Jiangtang Capsule (DJC), a traditional Chinese medicinal formula, has been used clinically in treating diabetes and diabetic nephropathy (DN). We previously demonstrated that DJC is capable of improving renal function in patients and rats with DN, but the mechanisms underlying these therapeutic benefits of DJC are not quite clear yet. In this study, STZ-induced diabetic rats were orally administered DJC for 8 weeks. Fasting blood glucose, renal function indicators in the serum, renal index, and the expression of proteins related to JAK-STAT signaling pathway were evaluated at the end of the experiment. The kidneys were sliced for pathological histology. Antioxidant status was assessed by measuring SOD, LPO and MDA in serum. The expression levels of COX2, iNOS, SOCS and the phosphorylation status of JAK2, STAT1, and STAT3 in renal tissues were evaluated by Western blot analyses. IL-6, TNF-α, and MCP-1 expression levels in renal tissues were determined using double-antibody sandwich ELISA. Diabetic renal dysfunction and its associated pathologies were ameliorated by DJC treatment. DJC significantly reversed the high expression of COX2 and iNOS in renal tissues. Furthermore, DJC inhibited the JAK2-STAT1/STAT3-SOCS3 signaling pathway, resulting in decreased concentrations of IL-6, TNF-α, and MCP-1. Moreover, the oxidant status in the kidney was substantially ameliorated by DJC treatment. In conclusion, the ability of DJC to ameliorate diabetic renal dysfunction and the associated pathologies of this disease might be due to its antioxidant capacity and suppression of the JAK2-STAT1/STAT3 cascade.

Effect of vitamin D on ventricular remodelling in heart failure: a meta-analysis of randomised controlled trials.

OBJECTIVES: The level of vitamin D is considered to be associated with the development and progression of heart failure (HF). However, it is still unclear whether supplementation of vitamin D could improve ventricular remodelling in patients with HF. This study aimed to systematically evaluate the influence and safety of additional vitamin D supplementation on ventricular remodelling in patients with HF. DESIGN: This study is a meta-analysis of randomised controlled trials (RCTs). SETTING: The PubMed, EMBASE, CNKI, Cochrane library, Web of Science databases and grey literature were searched for RCTs regarding the effect of vitamin D on ventricular remodelling in patients with HF (from database creation to October 2017). RevMan V.5.3 software was employed for data analysis. PARTICIPANTS: Seven RCTs with a total of 465 patients, including 235 cases in the vitamin D group and 230 cases in the control group, were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF) and the incidence of adverse reactions. RESULTS: Compared with the control group, a decrease in the LVEDD (mean difference (MD)=-2.31 mm, 95% CI -4.15 to -0.47, p=0.01) and an increase in the LVEF (MD=4.18%, 95% CI 0.36 to 7.99, p=0.03) were observed in the vitamin D group. Subgroup analysis also revealed a reduced LVEDD in adults (>18 years) and adolescents (<18 years) of the vitamin D group relative to that in those of the control group. High-dose vitamin D (>4000 IU/day) was more effective at reducing the LVEDD than low-dose vitamin D (<4000 IU/day). Moreover, vitamin D supplementation was more effective at reducing the LVEDD and increasing the LVEF in patients with reduced ejection fraction than in patients without reduced ejection fraction. CONCLUSION: Vitamin D supplementation inhibits ventricular remodelling and improves cardiac function in patients with HF. TRIAL REGISTRATION NUMBER: CRD42017073893.

DJC Suppresses Advanced Glycation End Products-Induced JAK-STAT Signaling and ROS in Mesangial Cells.

The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC. TNF-α, IL-6, and MCP-1 were determined using double-antibody sandwich ELISA. ROS and NADPH oxidase activity were measured by DCFH-DA assay and lucigenin-enhanced chemiluminescence, respectively. DJC significantly reversed the AGEs-induced expression of COX2 and iNOS. Moreover, DJC inhibited the AGEs-induced JAK2-STAT1/STAT3 activation, resulting in the inhibition of inflammatory cytokines such as IL-6, MCP-1, and TNF-α in a concentration-dependent manner. The ability of DJC to suppress STAT activation was also verified by the observation that DJC significantly increased the SOCS3 protein level. DJC reversed the AGEs-induced accumulation of ROS and NADPH oxidase activity, thus confirming that DJC possesses antioxidant activity. The results suggest that the anti-inflammatory effects of DJC in GMCs may be due to its ability to suppress the JAK2-STAT1/STAT3 cascades and reduce ROS production.

Xiyanping injection therapy for children with mild hand foot and mouth disease: a randomized controlled trial.

OBJECTIVE: To evaluate the clinical effects of Xiyanping injection intervention in pediatric patients with mild hand foot and mouth disease (HFMD). METHODS: A total of 329 patients were stratified and block-randomized for symptomatic treatment of HFMD and assigned to one of the following groups: Western Medicine (group A, n = 103), Xiyanping injection (group B, n = 109), or Xiyanping injection and symptomatic treatment using Western Medicine (group C, n = 117). During the trial, fever, rash, ulcers of the mouth were observed among participants in each group before and after treatment, and conversion rates from mild to severe HFMD were measured. RESULTS: After 3-7 days' treatment, no significant differences in the conversion rates from mild to severe HFMD were observed among the three groups (P > 0.05). There was a significantly low number of patients with the onset time of antifebrile effect, vanished time of hand and foot rashes and cumulative time for the ulcers in the mouth vanished, among the three groups (P < 0.05, P < 0.01). The onset time of antifebrile effect of patients in groups B and C were markedly shorter compared with those in group A (P < 0.05, P < 0.01); there was no statically significant difference observed between groups B and C (P > 0.05). No significant differences were observed in the time for body temperature recovery among the three groups (P > 0.05). There were no significant differences in adverse effects among the three groups (P > 0.05). CONCLUSION: Xiyanping injection together with use of Western Medicine is most effective for symptomatic treatment of mild HFMD. No severe adverse reactions were observed.

[Research advances on astragaloside-IV in treatment of diabetes mellitus and its complications pharmacological effects].

Diabetes has become a global public health problem that seriously threatens human health. Traditional Chinese medicine, the characteristics of the role of multiple targets, has a unique advantage in the prevention and treatment of diabetes mellitus and its complications. Astragaloside-Ⅳ (AS-Ⅳ), one of the main activities of Astragalus membranaceus, has a series of pharmacological effects including improvement in the function of endothelial cells and neovascularization, anti-inflammatory, antioxidant, regulating energy metabolism, protectionnervous, anti-cancer and so on. In this paper, AS-Ⅳ to prevent and treat diabetes and its complications has been reviewed, which has effect on lowering blood sugar, lowering blood pressure, improving insulin resistance, inhibiting inflammatory reaction and oxidative stress. Additionally, it also can improve the diabetic animal and cell model of diabetic vascular disease, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy, diabetic cardiomyopathy and other pathological damages. AS-Ⅳ may be a potential active substance for the treatment of diabetes and its complications.

Proteogenomic analysis and global discovery of posttranslational modifications in prokaryotes.

We describe an integrated workflow for proteogenomic analysis and global profiling of posttranslational modifications (PTMs) in prokaryotes and use the model cyanobacterium Synechococcus sp. PCC 7002 (hereafter Synechococcus 7002) as a test case. We found more than 20 different kinds of PTMs, and a holistic view of PTM events in this organism grown under different conditions was obtained without specific enrichment strategies. Among 3,186 predicted protein-coding genes, 2,938 gene products (>92%) were identified. We also identified 118 previously unidentified proteins and corrected 38 predicted gene-coding regions in the Synechococcus 7002 genome. This systematic analysis not only provides comprehensive information on protein profiles and the diversity of PTMs in Synechococcus 7002 but also provides some insights into photosynthetic pathways in cyanobacteria. The entire proteogenomics pipeline is applicable to any sequenced prokaryotic organism, and we suggest that it should become a standard part of genome annotation projects.

Shenzhu Tiaopi granule combined with lifestyle intervention therapy for impaired glucose tolerance: a randomized controlled trial.

OBJECTIVE: The purpose of the study was to evaluate the clinical effects of the Shenzhu Tiaopi granule (SZTP) combined with a lifestyle intervention in patients with impaired glucose tolerance (IGT), who also had a spleen deficiency and damp overabundance syndrome (SDDOS). METHODS: After a one-month washout period, a total of 514 patients were randomly assigned to the control (lifestyle intervention) and experimental (SZTP plus lifestyle intervention) groups, with 257 patients in each group. Patients in the control group received the lifestyle intervention (diet and exercise) for 12 months, while the patients in the experimental group were treated with SZTP plus the lifestyle intervention for 12 months. The Traditional Chinese Medicinal (TCM) symptom scores were observed in each group before and after treatment; the conversion rates from IGT to diabetes mellitus (DM) were also measured. RESULTS: Following 12 months of treatment, the conversion rate from IGT to DM in the experimental group was significantly lower than in the control group (8.52% vs. 15.28%, P<0.05). A significantly higher number of patients with IGT reverted to normal blood glucose levels in the experimental group than in the control group (42.15% vs. 32.87%, P<0.05). In addition, after following the treatment for 12 months, the TCM symptoms of patients in the experimental group were markedly alleviated, as compared to the control group (P<0.01). CONCLUSION: The combination of SZTP and lifestyle intervention showed a reduction in the conversion from IGT to DM, and an increase in the conversion from IGT to normal blood glucose levels.