Collision of herbal medicine and nanotechnology: a bibliometric analysis of herbal nanoparticles from 2004 to 2023.

BACKGROUND: Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. RESULTS: In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal "International Journal of Nanomedicine" has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. "Traditional Chinese medicine," "drug delivery," and "green synthesis" are the main research focal points. Themes such as "green synthesis," "curcumin," "wound healing," "drug delivery," and "carbon dots" may represent emerging research areas. CONCLUSIONS: Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine.

Research progress on miR-124-3p in the field of kidney disease.

MicroRNAs (miRNAs) are 18-25 nucleotides long, single-stranded, non-coding RNA molecules that regulate gene expression. They play a crucial role in maintaining normal cellular functions and homeostasis in organisms. Studies have shown that miR-124-3p is highly expressed in brain tissue and plays a significant role in nervous system development. It is also described as a tumor suppressor, regulating biological processes like cancer cell proliferation, apoptosis, migration, and invasion by controlling multiple downstream target genes. miR-124-3p has been found to be involved in the progression of various kidney diseases, including diabetic kidney disease, calcium oxalate kidney stones, acute kidney injury, lupus nephritis, and renal interstitial fibrosis. It mediates these processes through mechanisms like oxidative stress, inflammation, autophagy, and ferroptosis. To lay the foundation for future therapeutic strategies, this research group reviewed recent studies on the functional roles of miR-124-3p in renal diseases and the regulation of its downstream target genes. Additionally, the feasibility, limitations, and potential application of miR-124-3p as a diagnostic biomarker and therapeutic target were thoroughly investigated.

Association of systemic immune-inflammation index (SII) and aggregate index of systemic inflammation (AISI) with thyroid nodules in patients with type 2 diabetes mellitus: a retrospective study.

OBJECTIVE: This retrospective study aimed to investigate the association between TNs and the systemic immune-inflammation index (SII) and the aggregate index of systemic inflammation (AISI) in patients with T2DM. METHODS: A total of 370 T2DM patients, who were admitted to Dongzhimen Hospital between January 2020 and March 2023, were included in this retrospective study. Binary logistic regression models with multivariable adjustment were employed to assess the relationship between SII, AISI quartiles, and TNs. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of SII and AISI in identifying T2DM patients with TNs. RESULTS: Age, diabetes duration, diabetic nephropathy (DN), SII, and AISI demonstrated significant positive associations with TNs. Compared to the first quartile of SII, the second, third, and fourth quartiles showed increased risks of TNs with hazard ratios (HRs) of 1.578 (0.883-2.820), 2.279 (1.257-4.131), and 3.626 (1.931-6.810), respectively (P < 0.001). Similar results were observed for AISI and TNs. ROC curve analysis revealed that SII and AISI exhibited a high discriminatory capability for identifying TNs in the overall and male participant group, whereas the significance among females was not discernible. CONCLUSIONS: This study provides evidence that SII and AISI are independent risk factors for TNs, suggesting that elevated SII and AISI levels may contribute to the development of TNs in patients with T2DM particularly among male individuals.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy.

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. OBJECTIVE: To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. MATERIALS AND METHODS: Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 µg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. RESULTS: Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. DISCUSSION AND CONCLUSION: M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

[Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3/caspase-1/GSDMD pyroptosis pathway].

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1ß(IL-1ß) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.

Probiotics, prebiotics, and synbiotics for the improvement of metabolic profiles in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to quantify the effects of probiotic, prebiotic, and synbiotic supplementation on biomarkers of inflammation and oxidative stress, as well as lipid profiles among patients with chronic kidney disease (CKD). Electronic databases, including PubMed, the Cochrane Database, and the Web of Science were searched from January 1, 2000, to May 15, 2019. All RCTs that investigated the effect of prebiotics, probiotics, and synbiotics on a circulating (serum and plasma) inflammatory marker (C-reactive protein [CRP]), oxidative stress indicators (malondialdehyde [MDA], glutathione [GSH], and total anti-oxidant capacity [TAC]); and lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-c], and high-density lipoprotein cholesterol [HDL-c]) among patients with CKD were included. Data were pooled and expressed as a standardized mean difference (SMD) with a 95% confidence interval (CI). The protocol for this meta-analysis is registered with PROSPERO; No. CRD42019139090. Thirteen trials that included 671 patients were identified for analysis. The methodological quality varied across studies. Meta-analysis indicated that microbial therapies significantly reduced CRP (SMD, -0.75; 95% CI, -1.03 to -0.47; p = 0.000), MDA (SMD, -1.06; 95% CI, -1.59 to -0.52; p = 0.000), TC (SMD, -0.33; 95% CI, -0.52 to -0.13; p = 0.000), and LDL-c (SMD, -0.44; 95% CI, -0.86 to -0.02; p = 0.000) levels; they also increased the GSH (SMD, 0.44; 95% CI, 0.25 to 0.65; p = 0.000), TAC (SMD, 0.61; 95% CI, 0.07 to 1.15; p = 0.000), and HDL-c (SMD, 0.45; 95% CI, 0.03 to 0.87; p = 0.000) levels in CKD patients, as compared to the placebo groups; however, there was no statistically significant TG concentration among patients with CKD. Subgroup analyses showed that other key factors, such as the duration of intervention, participants' baseline body mass index (BMI), type of intervention, and age, had an effect of microbial therapies on outcomes. This meta-analysis supports the potential use of probiotic, prebiotic, and synbiotic supplements in the improvement of established biomarkers of inflammation and oxidative stress, as well as lipid profiles among patients with CKD, which are well-known cardiovascular risk factors. Further research into these interventions should consider the limitations of our study to explore the effect of long-term administration of these supplements in the CKD population.

Lysosomal dysfunction-induced autophagic stress in diabetic kidney disease.

The catabolic process that delivers cytoplasmic constituents to the lysosome for degradation, known as autophagy, is thought to act as a cytoprotective mechanism in response to stress or as a pathogenic process contributing towards cell death. Animal and human studies have shown that autophagy is substantially dysregulated in renal cells in diabetes, suggesting that activating autophagy could be a therapeutic intervention. However, under prolonged hyperglycaemia with impaired lysosome function, increased autophagy induction that exceeds the degradative capacity in cells could contribute toward autophagic stress or even the stagnation of autophagy, leading to renal cytotoxicity. Since lysosomal function is likely key to linking the dual cytoprotective and cytotoxic actions of autophagy, it is important to develop novel pharmacological agents that improve lysosomal function and restore autophagic flux. In this review, we first provide an overview of the autophagic-lysosomal pathway, particularly focusing on stages of lysosomal degradation during autophagy. Then, we discuss the role of adaptive autophagy and autophagic stress based on lysosomal function. More importantly, we focus on the role of autophagic stress induced by lysosomal dysfunction according to the pathogenic factors (including high glucose, advanced glycation end products (AGEs), urinary protein, excessive reactive oxygen species (ROS) and lipid overload) in diabetic kidney disease (DKD), respectively. Finally, therapeutic possibilities aimed at lysosomal restoration in DKD are introduced.

Identification of lysine acetylome in cervical cancer by label-free quantitative proteomics.

BACKGROUND: Lysine acetylation is a post-translational modification that regulates a diversity of biological processes, including cancer development. METHODS: Here, we performed the quantitative acetylproteomic analysis of three primary cervical cancer tissues and corresponding adjacent normal tissues by using the label-free proteomics approach. RESULTS: We identified a total of 928 lysine acetylation sites from 1547 proteins, in which 495 lysine acetylation sites corresponding to 296 proteins were quantified. Further, 41 differentially expressed lysine acetylation sites corresponding to 30 proteins were obtained in cervical cancer tissues compared with adjacent normal tissues (Fold change > 2 and P < 0.05), of which 1 was downregulated, 40 were upregulated. Moreover, 75 lysine acetylation sites corresponding to 58 proteins were specifically detected in cancer tissues or normal adjacent tissues. Motif-X analysis showed that kxxxkxxxk, GkL, AxxEk, kLxE, and kkxxxk are the most enriched motifs with over four-fold increases when compared with the background matches. KEGG analysis showed that proteins identified from differently and specifically expressed peptides may influence key pathways, such as Notch signaling pathway, viral carcinogenesis, RNA transport, and Jak-STAT, which play an important role in tumor progression. Furthermore, the acetylated levels of CREBBP and S100A9 in cervical cancer tissues were confirmed by immunoprecipitation (IP) and Western blot analysis. CONCLUSIONS: Taken together, our data provide novel insights into the role of protein lysine acetylation in cervical carcinogenesis.

Effect of hyperoside on cervical cancer cells and transcriptome analysis of differentially expressed genes.

BACKGROUND: Hyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types. The objective of the current study was to explore Hy effects on cervical cancer cell proliferation, and to perform a transcriptome analysis of differentially expressed genes. METHODS: Cervical cancer HeLa and C-33A cells were cultured and the effect of Hy treatment was determined using the Cell Counting Kit-8 (CCK-8) assay. After calculating the IC50 of Hy in HeLa and C-33A cells, the more sensitive to Hy treatment cell type was selected for RNA-Seq. Differentially expressed genes (DEGs) were identified by comparing gene expression between the Hy and control groups. Candidate genes were determined through DEG analysis, protein interaction network (PPI) construction, PPI module analysis, transcription factor (TF) prediction, TF-target network construction, and survival analysis. Finally, the key candidate genes were verified by RT-qPCR and western blot. RESULTS: Hy inhibited HeLa and C33A cell proliferation in a dose- and time-dependent manner, as determined by the CCK-8 assay. Treatment of C-33A cells with 2 mM Hy was selected for the subsequent experiments. Compared with the control group, 754 upregulated and 509 downregulated genes were identified after RNA-Seq. After functional enrichment, 74 gene ontology biological processes and 43 Kyoto Encyclopedia of Genes and Genomes pathways were obtained. According to the protein interaction network (PPI), PPI module analysis, TF-target network construction, and survival analysis, the key genes MYC, CNKN1A, PAX2, TFRC, ACOX2, UNC5B, APBA1, PRKACA, PEAR1, COL12A1, CACNA1G, PEAR1, and CCNA2 were detected. RT-qPCR was performed on the key genes, and Western blot was used to verify C-MYC and TFRC. C-MYC and TFRC expressions were lower and higher than the corresponding values in the control group, respectively, in accordance with the results from the RNA-Seq analysis. CONCLUSION: Hy inhibited HeLa and C-33A cell proliferation through C-MYC gene expression reduction in C-33A cells and TFRC regulation. The results of the current study provide a theoretical basis for Hy treatment of cervical cancer.

The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials.

The role of gut microbiota in the management of diabetes has been shown. Several current trials are investigating the effect of probiotics and prebiotics, which are widely used to modulate intestinal microbiota, on inflammatory factors and biomarkers of oxidative stress in diabetic patients; however, their findings are controversial. The aim of the current meta-analysis was to evaluate the effects of probiotic and synbiotic supplementation on levels of serum high-sensitivity C-reactive protein (hs-CRP) and biomarkers of oxidative stress in diabetic patients. We searched the PubMed, Web of Science, and The Cochrane Library databases from the inception to October 31, 2018. Randomized controlled trials (RCTs) which reported the effect of probiotics or synbiotics on circulating (serum and plasma) inflammatory marker (hs-CRP) and oxidative stress indicators (malondialdehyde [MDA], glutathione [GSH], nitric oxide [NO], and total antioxidant capacity [TAC]) among patients with diabetes were included. Eligible studies were assessed for risk of bias and subjected to qualitative and quantitative synthesis using either fixed- or random-effects models accounting for clinical heterogeneity. Our meta-analysis identified 16 eligible RCTs (n = 1060). The methodological quality varied across these trials. Pooled data from these trials demonstrated that probiotic and synbiotic consumption significantly decreased hs-CRP level (standardized mean difference [SMD]=-0.38; 95% confidence interval [CI]:-0.51,-0.24; P = 0.000) and MDA (SMD=-0.61; 95% CI: -0.89, -0.32; P = 0.000) in diabetic patients compared to those in subjects receiving placebos. In addition, probiotic and symbiotic supplementation was found to increase TAC (SMD = 0.31; 95% CI: 0.09, 0.52; P = 0.006), NO (SMD, 0.62; 95% CI, 0.25 to 0.99; P = 0.001) and GSH (SMD = 0.41; 95% CI: 0.26, 0.55, P = 0.000) levels. The results of this systematic review and meta-analysis suggest that probiotic and synbiotic supplementation may help to improve biomarkers of inflammation and oxidative stress in diabetic patients. Further studies are needed to develop clinical practice guidelines for the management of inflammation and oxidative stress in these patients.

[Clinical and fundamental research Yinhua Miyanling Tablets in treating urinary tract infection].

As the famous Chinese patent medicine, Yinhua Miyanling Tablets, which was derived from ancient prescription denominated Bazhengsan, has not only the effects in clearing away heat and purging pathogenic fire, removing dampness and relieving stranguria, but also have the functions of detoxifying and tonifying. A great number of scientific studies have demonstrated that Yinhua Mi-yanling Tablets played significant roles in destroying harmful microbes and resisting inflammatory and diuresis. Compared with antibiotics, traditional antibacterial Chinese patent medicine Yinhua Miyanling Tablets has the advantage in bacterial resistance in long-term use. Fundamental studies about the content of pharmaceutical ingredients and the modern pharmacology of Yinhua Miyanling Tablets were collected and summarized, which conduces to indicating the active ingredients of Yinhua Miyanling Tablets with the medicinal efficacy from the molecular level and the internal mechanism of Yinhua Miyanling Tablets in the treatment of urinary tract infection(UTI) from the scientific perspective. In the field of clinical research, literatures associated with Yinhua Miyanling Tablets for the treatment of UTI were summarized and analyzed in terms of treatment type, administration mode, dosage, frequency of medication, course, efficiency, side effects and whether combined with healthy lifestyle. These literatures confirmed the medicinal values and the application prospect of Yinhua Miyanling Tablets in treating UTI, especially acute UTI, which provides a scientific theoretical foundation and a correct direction for the clinical application of Yinhua Miyanling Tablets. In conclusion, this article contributes to the standardization of Yinhua Miyanling Tablets in the treatment of UTI, in the expectation of giving the scientific guidance for clinical practice.

[Technical specification of expert consensus statement in developing clinical practice guidelines of traditional Chinese medicine].

The formation of expert consensus statement is an indispensable part in the process of developing clinical practice guidelines. The Guidelines International Network believes that experts make group decisions for different stages and issues,and the process of gathering expert opinions is the process of reaching the consensus. GRADE system also requires that recommendations should be formed based on expert consensus in consideration of the risk and bias,patients' preferences and values,resources and other factors. At present,the main method for reaching consensus is the formal consensus method. According to the published clinical guidelines,most of them failed to report the specific methods and process of reaching expert consensus. Therefore,it is impossible to obtain an objective evaluation. This phenomenon is more common in the field of clinical practice guidelines of traditional Chinese medicine( TCM). There are two main reasons for this phenomenon. For one thing,the developers of the guidelines neglect the importance of transparency and objectivity in the implementation of expert consensus. For another,they know little about the methods and technical specifications for the formation of expert consensus. To solve them,based on the internationally recognized consensus-building methods,as well as the specific stages in the process of developing clinical practice guidelines of traditional Chinese medicine,it is of great significance to put forward the technical norms for TCM researchers to develop the expert consensus. This guide will provide detailed guidance for forming the expert consensus for TCM clinical practice guideline. This guideline has been approved and published by the Chinese Association of Traditional Chinese Medicine( No. T/CACM 1049-2017).

The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells.

BACKGROUND: Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a hydroxycinnamic acid derived from a rich polyphenolic compound. This study aimed to investigate the effect of ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA) on cell proliferation, invasion, apoptosis, and autophagy in Hela and Caski cervical carcinoma cell lines. METHODS: The cell proliferation of FA in Hela and Caski cells were detected by MTT assay. The cell invasion of FA in Hela and Caski cells were detected by Transwell assay. Subsequently, MMP-9 mRNA expression for cell invasion was detected by RT-PCR. Additionally, cell cycle and apoptosis were assayed using flow cytometry. Expression levels of 7 proteins for both cell cycle and autophagy were measured by Western blot analysis. RESULTS: After treated with FA (2.0 mM) for 48 h, the inhibition rates of FA in Hela and Caski cells were 88.3 and 85.4%, respectively. In addition, FA inhibited cell invasion through reducing MMP-9 mRNA expression. FA induced arrest in G0/G1 phase of the cell cycle in Hela and Caski cells with dose dependent (P < 0.05). Meanwhile, FA induced the cell cycle-related proteins expression such as p53 and p21, and reduced Cyclin D1 and Cyclin E levels. Moreover, FA decreased the autophagy-related proteins such as LC3-II, Beclin1 and Atg12-Atg5 in a dose-dependent manner. CONCLUSION: FA can significantly inhibit cell proliferation and invasion in Hela and Caski cells. It might be acted as an anti-cancer drug through inhibiting the autophagy and inducing cell cycle arrest in human cervical carcinoma cells.

[Technical specification for re-evaluation of post-marketing clinical effectiveness of traditional Chinese medicine (first draft)].

The post-marketing re-evaluation of traditional Chinese medicine (TCM) is a crucial stage for drug evaluation. Due to the particularity of TCM, it is necessary to re-evaluate the effectiveness of certain Chinese medicines by studying and collecting the studies on safety of long-term/extensive populations under actual clinical application, in order to verify the effectiveness of post-marketing TCM. However, there is an absence in technical specifications for relevant clinical trials on re-evaluation of effectiveness at present. As a consequence, the preliminary technical specifications were drafted in this article, focusing on several perspectives related to the re-evaluation of post-marketing clinical effectiveness of TCM, including ethical protection, research plan formulation, real-world research methods, randomized controlled trial methods, research methods of clinical pharmacological mechanism, sublimation method of TCM theory and so on. The objective of writing this article is to provide general methodological guidance for the re-evaluation of TCM post-marketing effectiveness, so that the process and results of post-marketing re-evaluation of TCM can be more scientific and reasonable.

[Clinical application evaluation of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection].

A questionnaire survey of 1 000 clinicians having experience in treating uncomplicated lower urinary tract infections from different levels of hospitals was conducted to mainly evaluate the applicability and effectiveness of clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection(hereinafter referred to as Guideline). The research was conducted with the three-level quality control strictly throughout the process, and the data was real and reliable. The survey's results showed that: most clinicians considered that the Guideline had good clinical applicability. The availability and price of the recommended medicine were moderate. Traditional Chinese medicine had obvious features and advantages in treating lower urinary tract infection for it could reduce the usage of antibiotics and shorten the course of antibiotic application. In the recommendation section, clinicians proposed increasing medication guidance, updating the Guideline timely, as well as increasing treating methods and techniques, strengthen propaganda and promotion, and improve the use of evidence-based methods. In the evaluation of effectiveness, the majority of clinicians agreed that the definition in both traditional Chinese medicine (TCM) and Western medicine and differential diagnosis in the Guideline were accurately described and the basic principle of treatment as well as the treating method of TCM were recommended appropriately. The TCM formulas and Chinese patent medicine had good effect. Some clinicians suggested refining the syndrome differentiation of stranguria. Some clinicians considered that the formulas and herbs recommended in Guideline didn't have obvious effect and some had doubts about the manipulation of fumigation and washing in the part of other methods recommended in Guideline. Moreover, specification and procedure of manipulation of fumigation and washing using herbs and the acupuncture included in characteristic TCM therapy treating uncomplicated lower urinary tract infection remained to be developed.

Application of Traditional Chinese Medicine in medical practice: a survey of community residents in Beijing, China.

OBJECTIVE: To investigate how community residents in Beijing understood and used Traditional Chinese Medicine (TCM) in their medical practice. METHODS: This was a cross-sectional study conducted on 3410 community residents from four large communities of Tongzhou district in Beijng, China. A validated, self-administered questionnaire comprised of three sections was used to gather the data. A systematic sampling procedure was applied to recruit the community residents. RESULTS: A total of 3410 participants completed the questionnaire survey. It showed that in highly educated residents, 33.4% (170) knew of the names of 3-10 Chinese herbals, 35.8% (182) knew of names of 3-10 traditional Chinese patent drug. Among all the respondent residents, 80.7% (2753) believed that TCM herbal therapy and TCM non-drug treatments were effective in disease treatment, health enhancement, 85.7% (2923) had taken traditional Chinese patent drug in their life, 56.8% (1937) of residents had used herbal decoction, 40.0% (1365) had received non-drug treatment of TCM, such as acupuncture, massage, cupping, auricular acupuncture. Among the elderly residents, 11.4% (98) often used Chinese patent drug and 9.8% (85) often used herbal decoction. In addition, 70.8% (2415) of residents were willing to accept knowledge and information on TCM for health enhancement and disease prevention, such as medicated diet, medicinal tea, Tai Chi and Qi Gong, although 82.8% (2825) of residents had never used them. CONCLUSION: Chinese patent drug and herbal decoction are widely used in the communities in Beijing, and there existed a possible close correlation between high educational level and better understanding of TCM. Age and occupation also correlated with the attitude to TCM therapies. The characteristics of the residents should be considered seriously in the course of promoting the understanding and application of TCM.

[Review on advantages and evidence of treating and preventing urinary tract infection in traditional Chinese medicine].

Urinary tract infection (UTI) in traditional Chinese medicine (TCM) belongs to the category of stranguria. This article describes the unsatisfactory situations in clinical practice such as antibiotics abuse, increasing of drug-resistant bacteria, high recurrence rate, etc. According to evidence-based medicine, literatures as evidence are collected for summarizing and analyzing and the result shows the advantages of TCM of relieving symptoms, reducing the dosage of antibiotics, less side effects, lower recurrence rate, etc. In the field of fundamental research, literatures associated with UTI are also summarized and analysed from several perspectives, such as causes, pathogenesis, syndrome differentiation, pharmacological effects of Chinese herbal medicine, working mechanism of non-drug therapy, etc and the result presents that integrated treatment of TCM in UTI has significant advangtages and its own characteristic.

DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer.

Delta-like ligand 4 (DLL4), one of the five Notch signaling ligands in mammals, has an important function in proliferation, invasion, metastasis, progression, and angiogenesis of malignancies. This study aimed to investigate DLL4 expression level in early-stage cervical carcinoma and to evaluate its clinical significance. We used fresh frozen and paraffin-embedded cervical cancer tissues to analyze DLL4 expression and its clinical significance. DLL4 expression at both mRNA and protein levels in cervical cancer tissues was significantly higher than that in normal cervical tissues. High DLL4 protein level was clearly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), lymphovascular space involvement (LVSI) (P = 0.015), pelvic lymph node metastasis (PLNM) (P = 0.001), and recurrence (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated that DLL4 overexpression was strongly associated with lymph node metastasis (odds ratio, 2.790; 95 % CI, 1.344-5.791; P = 0.006). Moreover, survival analysis revealed that DLL4 expression was an independent factor of unfavorable overall survival (hazard ratio, 2.130; 95 % CI, 1.108-4.097; P = 0.023) and disease-free survival (hazard ratio, 1.965; 95 % CI, 1.085-3.560; P = 0.026) in patients with cervical cancer. Overall, our data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer. Therefore, DLL4 may be a potential clinical diagnostic marker for patients with early-stage cervical cancer.

Hesperidin inhibits HeLa cell proliferation through apoptosis mediated by endoplasmic reticulum stress pathways and cell cycle arrest.

BACKGROUND: Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavanone that is found mainly in citrus fruits and has been shown to have some anti-neoplastic effects. The aim of the present study was to investigate the effect of hesperidin on apoptosis in human cervical cancer HeLa cells and to identify the mechanism involved. METHODS: Cells were treated with hesperidin (0, 20, 40, 60, 80, and 100 µM) for 24, 48, or 72 h and relative cell viability was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Hesperidin inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Hesperidin-induced apoptosis in HeLa cells was characterized by increased nuclear condensation and DNA fragmentation. Furthermore, increased levels of GADD153/CHOP and GRP78 indicated hesperidin-induced apoptosis in HeLa cells involved a caspase-dependent pathway, presumably downstream of the endoplasmic reticulum stress pathway. Both of these proteins are hallmarks of endoplasmic reticulum stress. Hesperidin also promoted the formation of reactive oxygen species, mobilization of intracellular Ca(2+), loss of mitochondrial membrane potential (ΔΨm), increased release of cytochrome c and apoptosis-inducing factor from mitochondria, and promoted capase-3 activation. It also arrested HeLa cells in the G0/G1 phase in the cell cycle by downregulating the expression of cyclinD1, cyclinE1, and cyclin-dependent kinase 2 at the protein level. The effect of hesperidin was also verified on the human colon cancer cell HT-29 cells. CONCLUSION: We concluded that hesperidin inhibited HeLa cell proliferation through apoptosis involving endoplasmic reticulum stress pathways and cell cycle arrest.

Thonningianin A ameliorated renal interstitial fibrosis in diabetic nephropathy mice by modulating gut microbiota dysbiosis and repressing inflammation.

Objectives: This study was conducted to examine the potential health benefits of thonningianin A (TA) on renal injury and interstitial fibrosis in diabetic nephropathy (DN) mice. Methods: In this study, a DN mice model was established using male C57BL/6 mice injected with streptozotocin (STZ, 50 mg/kg) intraperitoneally and treated with TA for 12 weeks. Firstly, the therapeutic and anti-fibrotic effects of TA on DN were evaluated. Secondly, the effect of TA on renal inflammation was evaluated and Western blot was used to detect the changes of NLRP3/ASC/Caspase-1 pathway-related protein expressions in kidney. Furthermore, the effect of TA on impairments in the intestinal mucosa barrier was evaluated and the changes of lipopolysaccharide (LPS) levels in feces and serum were detected by ELISA. Finally, 16S rRNA sequencing was used to detect alteration of gut microbiota diversity and abundance in mice after TA treatment. Results: The results showed that TA markedly mitigated blood glucose (Glu), decreased 24-h urinary total protein (24hUTP), improved renal dysfunction and kidney index (KI) in DN mice. Furthermore, TA significantly alleviated renal injury and interstitial fibrosis, repressing renal inflammation. Western blot results showed that the NLRP3/ASC/Caspase-1 signaling pathway-related proteins decreased after TA treatment. In addition, TA also ameliorated impairments in the intestinal mucosa barrier and restored the expressions of intestinal tight junction proteins (Claudin-1, Occludin and ZO-1). Subsequently, it reduced LPS levels of DN mice in fecal and serum. Furthermore, 16S rRNA high-throughput sequencing showed that TA modulated gut microbiota dysbiosis and decreased the abundance of Gram-negative bacteria (Proteobacteria and Escherichia-Shigella). Conclusion: This study suggested that TA might exert a beneficial effect on renal interstitial fibrosis in DN mice by modulating gut microbiota dysbiosis, ameliorating impairments in the intestinal mucosa barrier, reducing the production and release of LPS, inhibiting the activation of NLRP3/ASC/Caspase-1 signaling pathway, and repressing renal inflammatory.