OBJECTIVE To comprehensively evaluate the quality of Sanzi powder from different batches based on 12 components quantitative analysis combined with chemical pattern recognition and entropy weight-TOPSIS method. METHODS The contents of 12 components in 15 batches of Sanzi powder （No. S1-S15） were determined by HPLC-MS/MS， such as ethyl gallate， gallic acid， ferulic acid， corilagin， genipin-1-O-β-D-gentiobioside， toosendanin， geniposide， caffeic acid， methyl deacetylated coumarinate， tannic acid， rutin， quercetin. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted on the assay results. Using variable importance projection （VIP） value＞1 and P＜0.05 as the evaluation criteria， the quality differential markers in Sanzi powder were screened. The entropy weight method was used to calculate the weight value， and TOPSIS method was used to rank the quality of 15 batches of Sanzi powder from superior to inferior. RESULTS The contents of the 12 components were 13.494-24.292， 2 069.608-3 188.100， 1.410-3.616， 1 065.030-2 630.584， 1 404.704-1 838.078， 101.640-354.268， 9 193.720-14 777.854， 1.240-5.060， 148.028-5 541.990， 4 261.422-5 607.438， 107.560- 195.512， 2.226-4.192 μg/g， respectively. The results of CA， PCA and OPLS-DA indicated that 15 batches of Sanzi powder could be clustered into two groups. Specifically， batches S3， S7， S10 and S15 were grouped into one category， and remaining batches were grouped into one category. VIP values of geniposide， quercetin， caffeic acid， and methyl deacetylated coumarinate were all greater than 1， with corresponding P-values less than 0.05. The results of the entropy weight-TOPSIS analysis revealed that methyl deacetylate exhibited the smallest information entropy and the highest weight. The relative closeness degrees of samples S3， S7， S10 and S15 ranged from 0.789 to 0.973， while the remaining samples ranged from 0.054 to 0.172. CONCLUSIONS The contents of 12 components in Sanzi powder could be determined accurately by using HPLC-MS/MS technology. Methyl deacetylated coumarinate， geniposide， quercetin and caffeic acid were identified as the quality differential markers. It was found that the overall quality of samples S3， S7， S10 and S15 were superior to that of other batches. Notably， the quality of Gardeniae Fructus decoction pieces emerges as a critical factor in ensuring the consistency of the preparation’s quality.

OBJECTIVE: To observe the effect of "Zhibian" (BL54)-toward-"Shuidao" (ST28) needling technique on the relative protein expression of the signaling pathway of nucleotide-binding oligomerization domain-containing protein 1 (NOD1)/ receptor-interacting protein 2 (RIP2)/nuclear factor kappa-B (NF-κB) and the expression of proinflammatory cytokines in the rats with primary dysmenorrhea (PD), so as to explore the underlying mechanism of this acupuncture technique for pain alleviation in PD. METHODS: Thirty female SD rats of SPF grade with normal estrous cycle were randomized into a blank group, a model group and an acupuncture group, 10 rats in each one. Using the intraperitoneal injection with estradiol benzoate combined with oxytocin, PD model was prepared in the model group and the acupuncture group. In the acupuncture group, during model preparation, the intervention with "Zhibian" (BL54)-toward-"Shuidao" (ST28) needling technique was delivered simultaneously, 20 min each time, once daily for consecutive 10 days. On day 11, within 30 min after the intraperitoneal injection with oxytocin, the writhing reaction (latency, frequency and score) was recorded; the morphology of uterine tissue was observed with HE staining, the contents of prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α), interleukin (IL)-1β, IL-18, cyclooxygenase-2 (COX-2), and tumor necrosis factor-α(TNF-α) in the serum were detected using ELISA method; the relative protein expression of NOD1, RIP2, NF-κB p65, phosphorylation-NF-κB p65 (p-NF-κB p65) was detected in the uterine tissue using Western blot method; and the mRNA expression of NOD1, RIP2 and NF-κB p65 was detected with the quantitative real-time PCR employed. RESULTS: Compared with the blank group, in the model group, the writhing latency was prolonged (P<0.01), the writhing frequency and score increased (P<0.01) in the rats; the endometrial epithelial cells showed massive degeneration and necrosis, with severe endometrial edema and widespread shedding, combined with neutrophil infiltration; the serum PGE₂ content was dropped (P<0.01), while those of PGF_2α, IL-1β, IL-18, COX-2, and TNF-α elevated (P<0.01); the protein expression of NOD1, RIP2, NF-κB p65 and p-NF-κB p65, and the mRNA expression of NOD1, RIP2 and NF-κB p65 in uterine tissue increased (P<0.01). In comparison with the model group, in the acupuncture group, the writhing latency was prolonged (P<0.01), the writhing frequency and score were reduced (P<0.01) in the rats; there was less degeneration and necrosis of endometrial epithelial cells, with mild endometrial edema and very little neutrophil infiltration; the serum PGE₂ content increased (P<0.01), while those of PGF_2α, IL-1β, IL-18, COX-2, and TNF-α decreased (P<0.01); the protein expression of NOD1, RIP2, NF-κB p65 and p-NF-κB p65 and the mRNA expression of NOD1, RIP2 and NF-κB p65 in uterine tissue were dropped (P<0.05, P<0.01). CONCLUSION "Zhibian" (BL54)-toward-"Shuidao" (ST28) needling technique can alleviate the pain symptom of PD rats, and its action mechanism may be related to inhibiting the active expression of NOD1/RIP2/NF-κB signaling pathway in the uterine tissue, thereby reducing the inflammatory response.
Animals ; Female ; Rats, Sprague-Dawley ; Rats ; Signal Transduction ; Dysmenorrhea/metabolism* ; NF-kappa B/metabolism* ; Acupuncture Points ; Humans ; Acupuncture Analgesia ; Nod1 Signaling Adaptor Protein/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinase 2/metabolism* ; Acupuncture Therapy

The expert consensus on the clinical treatment of herpes zoster with fire needling was developed, and the commonly used fire needling treatment scheme verified by clinical research was selected to form a standardized diagnosis and treatment scheme for acute herpes zoster and postherpetic neuralgia (PHN), so as to answer the core problems in clinical application. The consensus focuses on patients with herpes zoster, and forms recommendations for 9 key clinical issues, covering simple fire needling and TCM comprehensive therapy based on fire needling, including fire needling combined with cupping, fire needling combined with Chinese herb, fire needling combined with cupping and Chinese herb, fire needling combined with filiform needling, fire needling combined with moxibustion, and provides specific recommendations and operational guidelines for various therapies.
Humans ; Herpes Zoster/therapy* ; Acupuncture Therapy/instrumentation* ; Consensus ; Clinical Protocols

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.
Humans ; Adenosine Deaminase/deficiency* ; Monocytes/cytology* ; Cell Differentiation ; Intercellular Signaling Peptides and Proteins/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Biomarkers/metabolism* ; Macrophages/metabolism* ; Pneumonia/metabolism*

The study aims to explore the methods for preparing nanocomplexes of Prussian blue nanoparticles (PBNPs) with UNO peptide (UNO-PBNPs) and the functions of the nanocomplexes targeting M2-type macrophages in vitro. PBNPs were prepared by the hydrothermal synthesis method. Subsequently, the peptide UNO (CSPGAKVRC) targeting the mannose receptor was modified on their surface by a heterobifunctional coupling approach. The morphological characteristics of nanoparticles were observed by scanning and transmission electron microscopy. Additionally, their particle size, Zeta potential, and dispersion stability were assessed. The structural characteristics of nanoparticles were analyzed by X-ray diffraction and other techniques. The biological safety of the nanoparticles was evaluated by the CCK-8 assay and hemolysis experiments. Moreover, the targeting performance of UNO-PBNPs towards M2-type macrophages was assessed in vitro. The results showed that the synthesized UNO-PBNPs exhibited uniform cubic morphology, with an average particle size of (202.00±4.21) nm. They were negative charged, well dispersed, and stable. At concentrations ≤ 200 μg/mL, the synthesized UNO-PBNPs led to the hemolysis rate below 5%, demonstrating excellent biocompatibility. The laser confocal imaging results showed that after co-incubation with M2-type macrophages, the FITC-labeled UNO-PBNPs were effectively accumulated in the cells, presenting a distinct fluorescence signal. Quantitative analysis by flow cytometry showed that the intracellular mean fluorescence intensity (6 019.00±346.04) of UNO-PBNPs was higher than that (4 054.00±379.14) of unmodified PBNPs (P < 0.001). In summary, the UNO-PBNPs prepared in this study exhibited a targeting effect on M2-type macrophages, providing a potential method for targeted delivery of PBNPs in the tumor microenvironment and laying a foundation for the remodeling of the tumor immunosuppressive microenvironment.
Ferrocyanides/chemistry* ; Nanoparticles/chemistry* ; Macrophages/drug effects* ; Peptides/chemistry* ; Particle Size ; Animals ; Mannose Receptor ; Mice ; Lectins, C-Type ; Mannose-Binding Lectins ; Receptors, Cell Surface

Objective To screen the quality evaluation indicators of Bushen Huoxue Prescription(BHP)in the treatment of diabetic retinopathy(DR)by network pharmacology and molecular docking technology,and to establish content determination of active components in BHP by ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry(UHPLC-QqQ-MS/MS).Methods Network pharmacology was used to screen the disease-related targets and key components,followed by molecular docking to further verify the interaction between them and confirm the active ingredients in BHP as the quality evaluation indicators.A UHPLC-QqQ-MS/MS method for the content determination of the active ingredients in BHP was established.A ZORBAX SB-C18 column(2.1 mm×50 mm,1.8 μm)was used,and methanol(A)-0.1％formic acid solution(B)was used as mobile phase.Gradient elution was performed in multiple reaction monitor mode.The flow rate was 0.3 mL·min-1 and the injection volume was 1 μL.Results Network pharmacology and molecular docking revealed five core targets and 12 BHP-related components(verbascoside,echinacoside,isoacteoside,tanshinone ⅡA,cryptotanshinone,dihydrotanshinone I,ginsenoside Re,Rd and Rb1,puerarin,daidzin,biochanin A)for the treatment of DR.There was a strong binding affinity between them(binding energy≤-5.0 kcal·mol-1).The established quantitative method demonstrated each component presented a good linearity within the specified range(r>0.999 5).The average recovery was in the range of 97.57％～101.48％.The contents of 12 components in eight batches of BHP samples were 0.027 9％～0.050 6％,0.006 4％～0.022 0％,0.017 1％～0.041 5％,0.009 2％～0.015 4％,0.012 6％～0.020 5％,0.004 4％～0.007 6％,0.334％～0.643％,0.238％～0.530％,0.353％～0.693％,3.411％～6.048％,1.023％～1.352％,0.000 8％～0.001 8％,respectively.Conclusion Based on network pharmacology,molecular docking and UHPLC-QqQ-MS/MS,a method for rapid screening and determination of 12 active components of BHP in the prevention and treatment of DR was established.This study provided a reference for comprehensive assessment of the quality and effectiveness of BHP.

Objective:To investigate the predictive value of inflammatory and nutritional indices for postoperative survival of elderly patients with esophageal squamous carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 130 elderly patients with esophageal squamous carcinoma who were admitted to Sichuan Cancer Hospital from January 2019 to April 2020 were collected. There were 102 males and 28 females, aged (70±4)years. Mea-surement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test. Receiver opera-ting characteristic (ROC) curves were plotted. The area under the curve (AUC) and optimal cut-off values were calculated. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for survival analysis. The COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Postoperative survival of elderly patients with esophageal squamous carcinoma predicted by inflammatory and multitional indices. Results of ROC curves analysis showed that the best cut-off values of preoperative systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI) for predicting postoperative survival of elderly patients with esophageal squamous carcinoma were 470.71×10 9/L, 1.11, 2.07, 136.24, and 46.28, respectively. (2) Risk factors analysis of postoperative survival of elderly patients with esophageal squamous carcinoma. Results of multivariate analysis showed that preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI<46.28, score of preoperative patient-generated subjective global assessment (PG-SGA) ≥4, postoperative pathological stage Ⅳ and post-operative complications were independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma ( hazard ratio=3.30, 2.50, 0.36, 4.86, 1.57, 1.97, 95% confidence interval as 1.10?9.88, 1.07?5.88, 0.16?0.81, 1.13?20.87, 1.20?2.06, 1.02?3.82, P<0.05). (3) Follow-up. All the 130 patients were followed up for 39(range, 1?60)months. Of the 130 patients, 81 cases survived, 49 cases died, and the median overall survival time was not reached. The 1- and 3-year survival rates of the 130 patients were 83.85% and 54.62%, respectively. ① The median overall survival time was 25(0,43)months for patients with SII ≥470.71×10 9/L, and unreached for patients with SII <470.71×10 9/L, showing a significant difference between them ( χ2=60.59, P<0.05). ② The median overall survival time was 26(0,44)months for patients with SIRI ≥1.11, and unreached for patients with SIRI <1.11, showing a significant difference between them ( χ2=45.57, P<0.05). ③ The median overall survival time was unreached for patients with PNI ≥46.28, and 38(0,47)months for patients with PNI <46.28, showing a significant difference between them ( χ2=12.53, P<0.05). ④ The median overall survival time was unreached for patients with PG-SGA <4 and ≥4, showing a signifi-cant difference between them ( χ2=14.41, P<0.05). ⑤ The median overall survival time was 25(1,47)months for patients in pathological stage Ⅲ, 12(1,32)months for patients in stage Ⅳ, and unreached for patients in stage 0, Ⅰ, Ⅱ, respectively, showing a significant difference among them ( χ2=58.75, P<0.05). ⑥ The median overall survival time was 33(1,47)months for patients with postoperative complication, and unreached for patients without postoperative complication, showing a significant difference between them ( χ2=14.27, P<0.05). Conclusions:Preoperative SII, SIRI and PNI have good predictive value for postoperative survival in elderly patients with esophageal squamous carcinoma. Preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI <46.28, score of preoperative PG-SGA ≥4, postoperative pathological stage Ⅳ, and postoperative complications are independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma. Patients with preoperative SII <470.71×10 9/L, preoperative SIRI <1.11, preoperative PNI >46.28, score of preoperative PG-SGA <4, postoperative pathological stage 0, Ⅰ, Ⅱ, and non post-operative complications have better survival.

Objective:To systematically evaluate the prevalence of malnutrition in elderly patients with diabetes.Methods:A total of eight databases, namely PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and VIP Database, were systematically searched for cross-sectional studies on malnutrition in elderly diabetic patients published from the inception of the databases to September 13, 2023. Two researchers independently conducted literature screening, data extraction, and quality assessment. Data analysis was performed using Stata 16.0 software.Results:A total of 22 studies were included, involving 6 349 elderly diabetic patients. Results of the meta-analysis showed that the overall prevalence of malnutrition in elderly patients with diabetes was 32.3% (95% CI: 0.21 to 0.43), and the prevalence of at-risk of malnutrition was 49.0% (95% CI: 0.31 to 0.67). Subgroup analysis showed that the prevalence of malnutrition in elderly diabetic patients with chronic complications (56.8%) was significantly higher than those without chronic complications (21.9%). Inpatients also showed a higher prevalence compared with outpatients and community (44.4%, 29.0%, and 18.5%, respectively). The prevalence of malnutrition as per mini-nutritional assessment scale was higher than that as per mini-nutritional assessment short-form scale (35.8% vs. 23.3%, P<0.05). There was no significant difference in the prevalence of malnutrition in elderly diabetic patients of different genders ( P>0.05). Conclusions:The prevalence of malnutrition and at-risk of malnutrition in elderly diabetic patients is high. In clinical practice, we should not only strengthen the early diagnosis of malnutrition in patients, but also emphasize the screening of malnutrition risk, implement timely corresponding interventions, and promote patient education on nutrition and health, to improve the prognosis and quality of life in elderly diabetes patients.

Objective To understand the status and influencing factors of kinesiophobia in patients with diabetic peripheral neuropathic pain(DPNP).Methods From February to June 2023,192 patients with DPNP in a tertiary general hospital in Nanchang City,Jiangxi Province were selected by convenience sampling method.The patients were investigated by the demographic information questionnaire,Tampa Scale for Kinesiophobia,Numerical Rating Scale,Medical Coping Modes Questionnaire,Diabetes Distress Scale,and Summary of Diabetes Self-care Activities.Multiple linear regression were used to analyze the influencing factors of kinesiophobia in patients with DPNP.Results The score of kinesiophobia in patients with DPNP was(36.68±3.88),and the incidence of kinesiophobia was 38.5％.Multiple linear regression analysis showed that marital status,pain level,coping style,diabetic distress and self-management behavior were influential factors for kinesiophobia in patients with DPNP(all P＜0.05).Conclusion Patients with DPNP have a moderate level of kinesiophobia.Nursing staff should pay attention to the early assessment of patients'kinesiophobia,promptly identify and take effective measures to reduce the level of patients'kinesiophobia,increase their motivation to exercise,and improve their prognosis and quality of life.