Kangxianling formula attenuates renal fibrosis by regulating gut microbiota.

BACKGROUND: Renal fibrosis (RF) produced adverse effect on kidney function. Recently, intestinal dysbiosis is a key regulator that promotes the formation of renal fibrosis. This study will focus on exploring the protective mechanism of Kangxianling Formula (KXL) on renal fibrosis from the perspective of intestinal flora. METHODS: Unilateral Ureteral Obstruction (UUO) was used to construct rats' model with RF, and receive KXL formula intervention for 1 week. The renal function indicators were measured. Hematoxylin-eosin (HE), Masson and Sirus red staining were employed to detect the pathological changes of renal tissue in each group. The expression of α-SMA, Col-III, TGF-ß, FN, ZO-1, and Occuludin was detected by immunofluorescence and immunohistochemistry. Rat feces samples were collected and analyzed for species' diversity using high-throughput sequencing 16S rRNA. RESULTS: Rats in UUO groups displayed poor renal function as well as severe RF. The pro-fibrotic protein expression in renal tissues including α-SMA, Col-III, TGF-ß and FN was increased in UUO rats, while ZO-1 and Occuludin -1 expression was downregulated in colon tissues. The above changes were attenuated by KXL treatment. 16S rRNA sequencing results revealed that compared with the sham group, the increased abundance of pathogenic bacteria including Acinetobacter, Enterobacter and Proteobacteria and the decreased abundance of beneficial bacteria including Actinobacteriota, Bifidobacteriales, Prevotellaceae, and Lactobacillus were found in UUO group. After the administration of KXL, the growth of potential pathogenic bacteria was reduced and the abundance of beneficial bacteria was enhanced. CONCLUSION: KXL displays a therapeutical potential in protecting renal function and inhibiting RF, and its mechanism of action may be associated with regulating intestinal microbiota.

Reabsorption of intervertebral disc prolapse after conservative treatment with traditional Chinese medicine: A case report.

BACKGROUND: Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation (LIDH) within a few weeks. CASE SUMMARY: Computed tomography and magnetic resonance imaging (MRI) of the lumbar region of a 25-year-old male diagnosed with LIDH showed prolapse of the L5/S2 disc. The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge. The patient elected a conservative treatment regimen that included traditional Chinese medicine (TCM), acupuncture, and massage. During a follow-up period of more than 12 mo, good improvement in pain was reported without complications. MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation. CONCLUSION: A conservative treatment regimen of TCM, acupuncture, and massage promoted reabsorption of a prolapsed disc.

Network Pharmacology and Molecular Docking-Based Investigation of Potential Targets of Astragalus membranaceus and Angelica sinensis Compound Acting on Spinal Cord Injury.

Background: Astragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach. Methods: AM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above. Result: The overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets. Conclusions: Altogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis.

Serum Irisin as a Potential Biomarker for Cognitive Decline in Vascular Dementia.

Background: Irisin, a new exercise-related myokine, has been shown to be associated with a variety of diseases including serious neurological disorders. However, whether irisin is involved in the pathogenesis of vascular dementia (VD) has not yet been reported. Our aim is to determine the serum irisin level in patients with VD and investigate its relationship with cognitive function. Methods: The subjects of the study were VD patients and controls with normal cognitive function who were hospitalized in the Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University from July 2018 to June 2020. Upon admission, a cognitive function assessment was performed. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of irisin in serum. Results: During the study period, 187 subjects (82 controls and 105 VD patients) were included in the analysis. The serum irisin level of VD patients was significantly lower than that of the control group (p < 0.001). Spearman analysis showed that irisin was positively correlated with HLD-C and MoCA, and negatively correlated with all clinical characteristics except for HCY. Logistic regression analysis showed that after adjusting for all clinical characteristics, the serum irisin of VD patients still had a significant correlation with MoCA (ß = 0.304, p = 0.029). According to receiver operating characteristic (ROC) curve analysis, the diagnostic accuracy for serum irisin levels on VD was 76% with the sensitivity and 71% with specificity respectively. Conclusions: These data indicate that a decrease in serum irisin levels is a powerful biological marker for cognitive decline in patients with VD, even after adjustment for risk factors. Further multi-center studies need to confirm this connection, which may pave the way for new treatment options.

Mechanism of Radix Astragali and Radix Salviae Miltiorrhizae Ameliorates Hypertensive Renal Damage.

Hypertensive-induced renal damage (HRD) is an important public health and socioeconomic problem worldwide. The herb pair Radix Astragali- (RA-) Radix Salviae Miltiorrhizae (RS) is a common prescribed herbal formula for the treatment of HRD. However, the underlying mechanisms are unclear. The purpose of our study is to explore the mechanism of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) ameliorating HRD by regulation of the renal sympathetic nerve. Thirty 24-week-old spontaneously hypertensive rats (SHRs) as the experimental group were randomly divided into the RA group, the RS group, the RA+RS group, the valsartan group, and the SHR group and six age-matched Wistar Kyoto rats (WKY) as the control group. After 4 weeks of corresponding drug administration, venipuncture was done to collect blood and prepare serum for analysis. A color Doppler ultrasound diagnostic instrument was used to observe renal hemodynamics. Enzyme-linked immunosorbent assay was used to detect norepinephrine (NE), epinephrine (E), angiotensin II (Ang II), and B-type brain natriuretic peptide (BNP). Simultaneously, the kidneys were removed immediately and observed under a transmission electron microscope to observe the ultrastructural changes. And the concentration of transforming growth factor-ß1 (TGF-ß1), angiotensin type 1 receptor (AT1), and nitric oxide (NO) was detected by immunohistochemistry. Our results showed that renal ultrasonography of rats showed no significant difference in renal size among groups. The RA+RS group had obviously decreased vascular resistance index. The levels of NE, E, BNP, Ang II, AT1, and TGF-ß1 were decreased (P < 0.05), and the density of NO was increased. Pathological damage of the kidney was alleviated. In conclusion, the results of the present study suggested sympathetic overexpression in the pathogenesis of HRD. The combination of RA and RS may inhibit the hyperexcitability of sympathetic nerves and maintain the normal physiological structure and function of kidney tissue and has a protective effect on the cardiovascular system.

Clinical Efficacy and Safety of "Three-Dimensional Balanced Manipulation" in the Treatment of Cervical Spondylotic Radiculopathy by Finite Element Analysis.

Cervical spondylotic radiculopathy (CSR) is the most commonly encountered cervical spine disorder. Cervical manipulation has been demonstrated as an effective therapy for patients. However, the mechanisms of manipulations have not been elucidated. A total of 120 cervical spondylotic radiculopathy patients were divided into the "three-dimensional balanced manipulation" treatment group (TBM group) and control group randomly. The control group was treated with traditional massage; the TBM treatment group was treated with "three-dimensional balanced manipulation" based on traditional massage. The symptoms and clinical efficacy of the patients were compared before and after treatment for one month. A three-dimensional finite element model was established. The mechanical parameters were imported to simulate TBM, and finite element analysis was performed. The results showed that the total effective rate was significantly higher in the TBM group compared with the control group. The biomechanical analysis showed the vertebral body stress was mainly distributed in the C3/4 spinous processes; the deformation mainly concentrated in the anterior processes of the C3 vertebral body. The intervertebral disc stress in the C3~C7 segment was mainly distributed in the anterior part of the C3/4 intervertebral disc, and the deformation extends to the posterior part of the C3/4 nucleus pulposus. In summary, these data are suggesting that TBM was effective in CSR treatment. The results of the finite element model and biomechanical analysis provide an important foundation for effectively avoiding iatrogenic injuries and improving the effect of TBM in the treatment of CSR patients.

Serum IL-37 Level Is Associated with Rheumatoid Arthritis and Disease Activity: A Meta-Analysis.

Interleukin-37 (IL-37) inhibits the pathogenesis of rheumatoid arthritis (RA) via downregulating proinflammatory cytokines. Accordingly, we performed an analysis to accurately assess the relationship between serum IL-37 cytokine levels and disease activity of RA. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Correlation coefficient (r) was utilized to evaluate the relationship between IL-37 and disease activity of RA patients. Ten studies were included into the research. Functional analysis revealed elevated serum IL-37 concentrations in RA patients (SMD = 1.61, P < 0.00001). The relationship between serum IL-37 levels and disease activity was statistically significant (C-reactive protein: r = 1.47, P = 0.0002; erythrocyte sedimentation rate: r = 1.55, P < 0.00001; rheumatoid factor: r = 1.40, P = 0.004; tumor necrosis factor⁃α: r = 1.64, P = 0.0003; Disease Activity Score for 28 joints: r = 1.63, P < 0.00001; tender joint count: r = 1.48, P < 0.00001; and swollen joint count: r = 1.52, P = 0.0003), but anti-CCP was not significant (anti-CCP: r = 0.98, P = 0.72). In summary, these data are suggesting that the elevated serum level of IL-37 in RA is positively correlated with the disease activity of RA, suggesting a role for IL-37in the pathogenesis of RA.

Association between Serum IL-37 and Spinal Cord Injury: A Prospective Observational Study.

OBJECTIVE: Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI. METHODS: All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination. RESULTS: A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant (p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant (p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly (p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score (r = -0.327, p < 0.05). CONCLUSION: The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI.

Serum CCL21 as a Potential Biomarker for Cognitive Impairment in Spinal Cord Injury.

OBJECTIVE: Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI. METHODS: In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population. RESULTS: A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups (p > 0.05). Compared with the NC group, the SCI group had a higher serum CCL21 level (p < 0.001) and a lower MoCA score (p < 0.001). Serum CCL21 level in SCI was negatively correlated with MoCA score (p = 0.023). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI. CONCLUSIONS: MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI.

Risk prediction of in-hospital mortality among patients with type 2 diabetes mellitus and concomitant community-acquired pneumonia.

BACKGROUND: The aim of the present study was to investigate the risk factors for in-hospital mortality among patients with type 2 diabetes mellitus (T2DM) and concomitant community-acquired pneumonia (CAP) and establish a risk prediction score. METHODS: Data from 1,360 adult patients with T2DM and concomitant CAP hospitalized in two grade 3A hospitals between 2009 and 2019 were collected through electronic medical records. Data obtained included the status of diabetes mellitus, comorbidities, laboratory and imaging findings, and treatment outcomes. Statistical analysis was conducted to investigate the risk factors affecting prognosis, and a clinical risk prediction score was designed. RESULTS: Based on the patients' treatment outcomes (deceased, improved and cured), the cohort was divided into two groups: deceased and improved; 16 parameters were significant after segmentation. However, the following nine parameters were independent predictors of mortality: neutrophil-lymphocyte ratio (NLR) ≥4, pulse rate ≥125 bpm, change in state of consciousness, arterial blood pH ≤7.35, age ≥65 years, serum sodium ≤130 mmol/L, initial fasting blood glucose ≥9 mmol/L, multilobar involvement, and diabetic nephropathy. Based on these findings, a risk prediction score was established, and bootstrap validation was performed. The risk prediction score was significantly superior to CURB-65 [confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic <90 mmHg or diastolic <60 mmHg), age >65 years] and slightly superior than the pneumonia severity index (PSI). CONCLUSIONS: The influencing factors for in-hospital mortality among patients with T2DM and concomitant CAP included advanced age, change in state of consciousness, increased pulse rate, acidosis, high NLR, high platelet-lymphocyte ratio, hyponatremia, hyperglycemia, and diabetic nephropathy. These parameters should be recognized in clinical practice, with active interventions to improve the treatment success rate. The risk prediction score effectively differentiated the mortality risk of inpatients, thereby providing guidance on clinical decision-making.

Protective Effects of Combination of Radix Astragali and Radix Salviae Miltiorrhizae on Kidney of Spontaneously Hypertensive Rats and Renal Intrinsic Cells.

OBJECTIVE: To evaluate the effects of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) on kidney of spontaneously hypertensive rats (SHRs) and renal intrinsic cells. METHODS: SHRs were intragastrically administrated with RA (5.09 g/kg) and RS (2.55 g/kg) either alone or with combination for 4 weeks; valsartan (13.35 mg/kg) was used as a positive control. Blood pressure and renal ultrasonography were monitored periodically. The biomarkers [microalbumin (mALB), cystatin ^C, angiotensin II (Ang II), interleukin-1 beta (IL-1ß), and ß2-microglobulin (ß2-Mg), etc.] in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions [phosphorylated adenosine 5'-monophosphate-activated protein kinase-α1 (p-AMPKα1), sestrin-ß, calcium/calmodulin-dependent protein kinase kinase-ß (CaMKK-ß), phosphoinositide 3-kinases (PI3K), serine-threonine protein kinase 1 (AKT1), and vascular endothelial growth factor receptor 2 (VEGFR2)] in renal cortex were determined by Western blot. In vitro, the hypertensive cellular model was established by applying 2×10-6 mol/L Ang ^II. The primary human podocytes, human glomerular endothelial cells (HRGECs), and human proximal tubular epithelial cells (HK-2s) were pre-incubated with sulfotanshinone sodium (Tan, 10 µg/mL) and/or calycosin-7-O-ß-D-glucoside (Cal, 5 µg/mL). The cellular viability and apoptosis were assayed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Annexin V/PI staining, respectively. The level of endothelial nitric oxide synthase (eNOS) in culture supernatant was determined by ELISA. RESULTS: RA+RS signifificantly decreased the diastolic blood pressure, renal vascular resistance index, and parenchymal thickness, increased 24 h urinary volume as well as lowered the levels of urine mALB and serum cystatin ^C, IL-1ß and ß2-Mg of SHRs (P <0.05 vs. SHRs). The decreased protein levels of p-AMPKα1, sestrinß and CaMKK-ß and the increased protein levels of PI3K, AKT1 and VEGFR2 in renal cortex of SHRs were normalized after RA+RS treatment (P <0.05). In vitro, Tan and Cal attenuated the Ang II-induced abnormal proliferation and increased the apoptosis of HRGECs and HK-2s and improved the level of eNOS in culture supernatant. Whereas, neither of them showed powerful effect on podocyte. CONCLUSION: The combination of RA and RS had potential effects on alleviating the renal damages of SHRs and the renoprotection was independent of blood pressure level.