Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Four types of RNA modification writers predict the prognosis of prostate cancer.

RNA modification is an important part of epigenetic regulation. However, the relationship between RNA modification writers and prostate cancer (PCa) remains unclear. We obtained transcriptome data from The Cancer Genome Atlas; the expression of writers for four RNA modifications (N6-methyladenosine, N1-methyladenosine, alternative polyadenylation and adenosine-to-inosine RNA editing) was altered in PCa tissue when compared with normal tissue. RNA modification writers affect the expression of immune checkpoints. Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the RNA modification was related to the cell cycle. Hub genes were screened using machine learning, and a risk score model was established using multivariate Cox analysis. Univariate and multivariate Cox analyses showed that a risk score model based on RNA modification writers could be an independent prognostic factor for PCa. In conclusion, our study showed that RNA modification writers are differentially expressed in PCa and might influence the development of PCa by regulating immune checkpoints and the cell cycle. The risk score model of RNA modification writers is predicted to be an independent prognostic factor for PCa. Thus, RNA modification writers might be used as potential indicators for the clinical diagnosis of PCa.

Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/ß-catenin signaling pathway in ovariectomized rats.

Fructus Ligustri Lucidi (FLL) has been preclinically and clinically used to treat musculoskeletal diseases. However, whether and how FLL affect the canonical Wnt/ß-catenin signaling in the management of osteoporosis remains largely unknown. To this end, ovariectomized (OVX) rats and primary osteoblasts were administrated with FLL aqueous extract and medicated serum, respectively. Supplement of FLL to OVX rats maintains bone quality by attenuating the reduction in bone mineral density, strength and microstructure. The maintenance may be associated with upregulating the expression of insulin-like growth factor-1, osteoprotegerin, phospho (p)-low-density lipoprotein receptor-related protein 6, p-glycogen synthase kinase 3 beta (GSK3ß), ß-catenin, Runx2 and c-Myc, and downregulating the expressions of sclerostin (SOST), dickkopf-related protein 1 (DKK1), GSK3ß and p-ß-catenin in rat femurs and tibias. In addition, the medicated serum promotes osteoblastic bone formation through activation of Wnt/ß-catenin signaling via inhibition of DKK1 and SOST overexpression. Salidroside may be one of the active ingredients in FLL that are beneficial for bone homeostasis. In summary, our results suggest that FLL may preserve bone quality through induction of canonical Wnt/ß-catenin signaling via inhibition of DKK1 and SOST overexpression. And FLL may offer a new source of the DKK1 or SOST inhibitors in protection against osteoporosis.

[Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice].

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

A risk scoring system for the decreased glomerular filtration rate in Chinese general population.

OBJECTIVE: The aim of this study was to establish a risk scoring system for the decreased glomerular filtration rate (GFR) in Chinese general population. METHODS: Totally 781 participants who underwent a health checkup in The First Affiliated Hospital of Nanjing Medical University from January to September 2017 were involved in the study. Significant variables chosen by multivariable logistic regression analysis were allocated the integral scores in proportion to its odds ratio (OR), and then the risk of decreased GFR was assessed based on the scores. RESULTS: The people with abnormal homocysteine (Hcy) level (OR: 1.534, 95% confidential interval [CI]: 1.075-2.190, P = .018), males (OR: 2.054, 95%CI: 1.365-3.092, P < .001), and those at the age of 46-52 years (OR: 2.943, 95%CI: 1.546-5.605, P = .001), 52-59 years (OR: 3.664, 95%CI: 1.937-6.931, P < .001) and ≥59 years (OR: 13.452, 95%CI: 7.339-24.657, P < .001) were subjected to GFR reduction. These three variables were allocated the integral scores in proportion to its OR, and four risk categories were divided according to the scores. The prevalence of the decreased GFR in people with low (score 0-4, n = 8), below the average (score 4-6, n = 37), above the average (score 6-13, n = 47), and high risks (score ≥ 13, n = 103) was 5.26%, 16.89%, 22.93% and 50.24%, respectively, and this prevalence raised with the increase of scores (P < .001). CONCLUSIONS: A risk scoring system is developed in this study, which may offer a specific risk stratification for GFR reduction in Chinese general population.

Antitumor activity of arsenite in combination with tetrandrine against human breast cancer cell line MDA-MB-231 in vitro and in vivo.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat due to its aggressive, metastatic behavior, and a lack of a targeted therapy. Trivalent arsenic derivatives (arsenite, AsIII) with remarkable clinical efficacy in acute promyelocytic leukemia has been demonstrated to exhibit inhibitory effect against breast cancer cells. To provide novel insight into the development of new therapeutic strategies, antitumor activity of AsIII and tetrandrine (Tetra), a Chinese plant-derived alkaloid, against the TNBC cell line MDA-MB-231 in vitro and in vivo was investigated. METHODS: Cytotoxicity was evaluated using cell viability, lactate dehydrogenase leakage and cell cycle assay. Alterations of genes related to cell proliferation and death were analyzed using western blotting. In vivo antitumor activity of AsIII alone or in combination with Tetra was studied using MDA-MB-231 xenografts in nude mice. RESULTS: Synergistic cytotoxic effects of two drugs were observed in the cells. In vivo study also showed that co-administration of AsIII and Tetra significantly reduced tumor volume and weight, directly supporting its in vitro antitumor activity. No deaths and reduction of body-weight were observed after a long-term co-administration, indicating its good tolerability. S-phase arrest associated with the upregulation of FOXO3a, p27 along with decreased Cyclin D1 expression was observed in the cells treated with the combined regimen. A substantial upregulated p21 expression and downregulated phospho-FOXO3a and Cyclin D1 expression was observed in the tumor tissues of mice co-administered with AsIII and Tetra. Autophagy induction was observed in the combination treatment in vitro and in vivo. The addition of wortmannin, a potent autophagy inhibitor, significantly rescued MDA-MB-231 cells from their cytotoxicity of AsIII and Tetra. CONCLUSIONS: S-phase arrest, autophagic and necrotic cell death contribute to the cytocidal effects of the combined regimen of AsIII and Tetra. Considering our previous study showing synergistic cytotoxic effects of the combined regimen in estrogen receptor-positive breast cancer cell line MCF-7, these results suggest that development of the combination regimen of AsIII plus Tetra may offer many benefits to patients with different types of breast cancer.

Estimating glomerular filtration rate by serum creatinine or/and cystatin C equations: An analysis of multi-centre Chinese subjects.

AIM: Various equations based on serum creatinine or/and cystatin C, required further validation in a Chinese population. We compared the performance of six Chinese equations (Mascr, Peiscr, Macys, Fengcys, Mascr-cys and Fengscr-cys) with the CKD-EPI equations in multi-centre Chinese subjects and evaluated their applicability in clinical practice. METHODS: A total of 1522 adult patients from four different hospitals of China were enrolled in the study. (99m) Tc-DTPA renal dynamic imaging was used as the reference GFR (rGFR), and serum creatinine and cystatin C were measured by standardized assays. An optimal score system was implemented in the study. RESULTS: The average rGFR of recruited subjects was 67.30±28.89 mL/min per 1.73m(2) . All estimated GFR (eGFR) correlated well with rGFR. In accordance with Bland-Altman analysis, the Fengscr-cys equations achieved optimal overall performance (score 14 vs 0-6), with least bias (median difference, -0.57 mL/min per 1.73m(2) ; median absolute difference, 8.83 mL/min per 1.73m(2) ), best precision (17.99 mL/min per 1.73m(2) ), highest accuracy (percentage of eGFR within 15%, 30% and 50% of the rGFR (P15 , P30 and P50 ; 49.7%, 78.7% and 91.8%, respectively); root-mean-square-error (RMSE, 16.28)). The Fengcys equation, a typical cystatin C based equation, was another well-behaved formula with an impressive performance. The Ma equations performed much poorer than the CKD-EPI equations. Consistent results can be observed in the GFR- /age- and sex-specific subgroups, while none equation yielded ideal accuracy in GFR<60 mL/min per 1.73 m(2) subgroup. CONCLUSION: The Fengscr-cys equation appeared to achieve the best performance for GFR estimation in overall Chinese adult patients. However, further research is warranted to improve the accuracy of available equations in GFR less than 60 mL/min per 1.73 m(2) individuals.

Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem worldwide with dramatically increasing incidence and prevalence. Serum cystatin C (sCysC) has been clarified by many studies as a relatively accurate marker to evaluate renal function. STUDY DESIGN: Meta-analysis of diagnostic test studies. SETTING AND POPULATION: Various clinical settings of CKD, including adult patients with diabetes, renal transplant patients, and so on. SELECTION CRITERIA: A computerized search of PubMed, Cochrane clinical trial database, and Current Contents (from inception until June 16, 2014) was performed to identify potentially relevant articles. INDEX TESTS: Increased sCysC concentration. REFERENCE TESTS: The measured glomerular filtration rate measured by nuclear medicine techniques such as 99Tc-diethylene triamine pentacaetic acid (99Tc-DTPA) or 51Cr-ethylenediamine tetra-acetic acid (51Cr-EDTA), or calculated by Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula or 24 hours creatinine clearance rate. RESULTS: In total 19 studies were included in this study. Across all settings, the diagnostic odds ratio (DOR) of sCysC in predicting CKD was 40 (95% CI, 26 - 61) when sensitivity and specificity was 0.85 (95% CI, 0.81 - 0.89) and 0.87 (95% CI, 0.84 - 0.90), respectively. The area under the curve for the receiver-operating characteristic (AUROC) of sCysC to predict CKD was 0.92 (95% CI, 0.90 - 0.94). For the diagnostic value of sCysC in diabetics with CKD, the DOR was 51 (95% CI, 22 - 122), with sensitivity and specificity of 0.89 and 0.87, respectively. Subgroup analysis showed that sCysC was of better diagnostic value in the West than in Asia, and the diagnostic value of sCysC assayed by particle-enhanced nephelometric immunoassay (PENIA) was higher than sCysC assayed by particle-enhanced turbidimetric immunoassay (PETIA). CONCLUSION: SCysC appears to be a good biomarker in the definition of CKD. However, its performance is different in subgroups restricted by clinical settings, race, and sCysC assay.

Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing.

AIMS: Micro-vesicles (MVs) from bone mesenchymal stem cells (MSCs) have been shown to contribute to the recovery of damaged kidney. The aims of the present study are to investigate the biological effects and repair mechanisms of MVs. METHODS: Micro-vesicles were obtained from MSC supernatants. In vitro, the proximal tubular epithelial cells (HK-2) were treated with transforming growth factor (TGF-ß1). The expressions of E-cadherin and α-smooth muscle actin (α-SMA) were evaluated. In vitro, the mice were divided into: control, unilateral ureteral obstruction (UUO), UUO+MSC, and UUO+MV group. MVs and MSCs were injected after surgery. The mice were killed 7/14 days after surgery and handled for further tests. The micro-RNA expressions were labeled using the miRCURY Hy3/Hy5 Power labeling kit and hybridized on the miRCURY LNA Array. RESULTS: In vitro, MV reversed transforming growth factor-ß1 (TGF-ß1)-induced morphological changes, and firmed the expression of E-cadherin and reduced the secretion of α-SMA in HK2 cells. In vivo, the level of blood urea nitrogen (BUN) in the MV and MSC group was lower than the UUO (P < 0.01). The Scr level decreased after 7 days of MV treatment (P < 0.05). Administration of MSC and MV reduced Scr level at day 14 (P < 0.05). The level of serum UA decreased with MV administration (day 7,14, P < 0.01). Herein, a total of 503 expressed miRNAs were detected, of which, 266 were in MSC, including 237 in MVs. CONCLUSION: Micro-vesicles (MVs) protect kidneys both in vivo and vitro, and MVs are superior to MSCs in some respects. MVs can be a potential therapy in treatment of kidney diseases.

Chinese herbal medicine for subacute thyroiditis: a systematic review of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbal medicine (CHM) in the treatment of subacute thyroiditis. METHODS: Randomized controlled trials found in PubMed, Cochrane Library, and three Chinese databases were selected. RevMan 5.2 software was used to analyze the data with relative risk or mean difference, expressed with 95% of confidence interval. The quality of trials was assessed and graded the quality of evidence with GRADE profiler software. RESULTS: Twenty one studies were included. CHM was superior to Western Medicine (include prednisone and NSAIDs) in abating fever, relieving thyroid pain, recovering blood sedimentation, improving thyroid function, and preventing hypothyroidism (P < 0.05), while no statistical differences were found in eliminating goiter and reducing relapse rate. CHM plus Western Medicine were superior to Western Medicine in abating fever, relieving thyroid pain, eliminating goiter, and reducing relapse rate, while no statistical differences (P > 0.05) were found in recovering blood sedimentation and improving thyroid function. The incidence of adverse reactions in treatment group was lower than that in control group (relative risk was 0.12 and 95% confidence interval was 0.03-0.51). The methodological quality of trials is generally poor with a high risk of bias. CONCLUSION: CHM (particularly CHM combined with Western Medicine) used to treat subacute thyroiditis may improve clinical symptoms and signs, reduce relapse rate, and alleviate the side effects of hormones. Due to poor methodological quality of included trials, further more high-quality studies are warranted to confirm the effectiveness and safety of CHM.

The global landscape and research trend of lymphangiogenesis in breast cancer: a bibliometric analysis and visualization.

Background: Breast cancer persists as a major public health issue on a global scale. Lymphangiogenesis is an indispensable element in the promotion of breast cancer metastasis. Inhibiting the metastasis of breast cancer can be accomplished through targeting lymphangiogenesis. The purpose of this study was to examine research trends, major topics, and development directions of lymphangiogenesis in breast cancer through a bibliometric analysis, which may serve as a reference for future research and clinical practice. Methods: English publications with article type article or review about lymphangiogenesis in breast cancer from inception to September 30, 2023, retrieved from the Web of Science Core Collection Database (WOSCC), and VOSviewer, CiteSpace, and Microsoft Excel were applied for bibliometric study. Results: In this paper, a total of 369 articles and reviews were included. The 369 papers were written by 2120 authors from 553 organizations across 42 countries, published in 199 journals, and cited 12458 references from 1801 journals up to September 30, 2023. Moreover, the annual publications had a rising trajectory between 2004 to 2014 but declined from 2015. The US was the leading nation in publications and citations. Meanwhile, academics Mousumi Majumder and Peeyush Lala had the highest cumulative number of publications. Based on the number of publications/citations, Cancer Research was the most influential journal. The most cited paper was "Lymphangiogenesis: Molecular Mechanisms and Future Promise" by Tuomas Tammela, published in the Journal of Cell. Additionally, keywords frequency analysis demonstrated that "lymphangiogenesis," "breast cancer," "VEGF-C," "angiogenesis," and "metastasis" were the most frequent keywords, and the newly emergent topics could be represented by "tumor microenvironment," "metastasis," "stem-cell," "triple-negative breast cancer," and "blood vessels." Conclusions: Currently, there is a strong research basis for lymphangiogenesis in breast cancer. The core research team was primarily situated in the US. Investigating the mechanism of lymphangiogenesis in breast cancer will always remain a highly discussed topic. In particular, it was essential to emphasize the relationship between lymphangiogenesis and tumor microenvironment, stem cells, triple-negative breast cancer, and metastasis, which could be the frontiers.

Multiple and large simple renal cysts are associated with glomerular filtration rate decline: a cross-sectional study of Chinese population.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

A case of chronic kidney disease patient with rapid deterioration of renal function, hair loss, and spontaneous resolution of facial warts after COVID-19 infection.

Background: Individuals with pre-existing chronic kidney disease (CKD) are at an increased risk of experiencing severe symptoms if infected with COVID-19. This report presents the case of a patient with CKD who contracted COVID-19 and subsequently experienced rapid deterioration of kidney function, hair loss, and spontaneous remission of facial warts. Case presentation: A 60-year-old Chinese man with a decade-long history of abnormal serum creatinine (Scr) levels and recently heightened fatigue sought treatment. The disease was previously managed and deemed resolved in 2020. However, when he contracted the novel coronavirus on December 20, 2022, he experienced persistent fatigue without other symptoms. In early January 2023, Scr levels was examined as more than 300 µmol/L. This was followed by hair loss, including eyebrows and lashes, and the spontaneous resolution of a longstanding facial wart. During this period, although the patient received kidney-protecting drugs and a lifestyle optimization, Scr increased continuously and the disease eventually progressed to the uremic stage. As the patient still had relatively abundant urine volume, the patient chose peritoneal dialysis treatment. At a two-month follow-up, he had adhered to the CAPD protocol without complications and his hair had begun to regrow. After eight months, his hair had mostly regrown, and his Scr levels kept stable. Conclusion: This case may represent the inaugural instance of CKD patients experiencing rapid deterioration of renal function, hair loss, and spontaneous remission of common warts. The underlying mechanisms of this unique phenomenon warrant further researches and debate.

BRD4 plays an antiaging role in the senescence of renal tubular epithelial cells.

Background: Age-related kidney failure is often induced by a decrease in the bioavailability of tubular epithelial cells in elderly chronic kidney disease (CKD) patients. BRD4, an epigenetic regulator and a member of the bromodomain and extraterminal (BET) protein family, acts as a super-enhancer (SE) organizing and regulating genes expression during embryogenesis and cancer development. But the physiological function of BRD4 in normal cells has been less studied. This study aimed to research certain biological roles of BRD4 in the process of normal cell aging and discuss the potential mechanisms. Methods: In this study, we investigated the biological functions of BRD4 proteins in the aging of renal tubular cells. At first, we used a D-galactose (D-gal) and BRD4 inhibitor (Abbv-075) to replicate kidney senescence in vivo. D-gal and Abbv-075 were then used to measure the aging-related changes, such as changes in cell cycle, ß-galactosidase activity, cell migration, and p16 protein expression in vitro. At last, we knocked down and over-expressed BRD4 to investigate the aging-related physiological phenomena in renal tubular cells. Results: In vitro, D-gal treatment induced noticeable aging-related changes such as inducing cell apoptosis and cell cycle arrest, increasing ß-galactosidase activity as well as up-regulating p16 protein expression in primary human tubular epithelial cells. In the aging mice model, D-gal significantly induced renal function impairment and attenuated BRD4 protein expression. At the same time, the BRD4 inhibitor (Abbv-075) was able to mimic D-gal-induced cell senescence. In vivo, Abbv-075 also decreased kidney function and up-regulated p21 protein expression. When we knocked down the expression of BRD4, the senescence-associated ß-galactosidase (SA-ß-gal) activity increased dramatically, cell migration was inhibited, and the proportion of cells in the G0/G1 phase increased. Additionally, the knockdown also promoted the expression of the senescence-related proteins p16. When the renal tubular cells were overexpressed with BRD4, cell aging-related indicators were reversed in the D-gal-induced cell aging model. Conclusions: BRD4 appears to have an active role in the aging of renal tubular cells in vivo and in vitro. The findings also suggest that BRD4 inhibitors have potential nephrotoxic effects for oncology treatment. BRD4 may be a potential therapeutic biomarker and drug target for aging-related kidney diseases, which warrants additional studies.

Systematic review and meta-analysis of mesenchymal stem/stromal cells therapy for impaired renal function in small animal models.

AIM: The meta-analysis of recent small animal experiments of mesenchymal stem/stromal cells (MSC) therapy for impaired kidney could provide significant clues to design large animal experiments as well as human clinical trials. METHOD: A total of 21 studies was analyzed. These, were indexed from PubMed and Embase databases. All data were analyzed by RevMan 5.1 and SPSS 17.0. Pooled analysis and multivariable meta-regression were calculated by random effects models. Heterogeneity and publication bias across the studies were also explored. RESULTS: Pooled analysis showed elevated serum creatinine (Scr) reduction in the animal models of renal failure following MSC therapy. By exploratory multivariable meta-regression, significant influence factors of Scr reduction were the time point of Scr measurement (early measurement showed greater reduction than the late (P = 0.005)) and the route of MSC delivery (arterial delivery of MSCs caused greater reduction in elevated Scr, when compared with the intra-renal delivery and intravenous injection (P = 0.040)). Subgroup analysis showed there tended to be greater reduction in Scr with higher MSC number (>10(6)), the renal ischemia-reperfusion injury (IRI) model, and late administration (>1 day) after injury. CONCLUSION: The present meta-analysis confirmed that MSC therapy could improve impaired renal function. MSCs might get obvious effect in the early stage of renal injuries after arterial delivery. Further, this meta-analysis may provide important clues for animal experiments even for human clinical trials in MSC studies.

Effectiveness of external Sanjierupi Gao on mastalgia caused by mammary gland hyperplasia: a placebo controlled trial.

OBJECTIVE: To evaluate the curative effect of external application of the Chinese drug, Sanjierupi Gao, on mastalgia caused by mammary gland hyperplasia. METHODS: This randomized, double-blinded, and placebo controlled study enrolled 260 patients with mammary gland hyperplasia from five hospitals. Patients were randomly and equally divided into a Sanjierupi Gao treatment group and a placebo control group. An adhesive plaster was applied to the most painful area on either breast for 7 h a day. Treatment lasted for two menstrual cycles without application during menstruation. Mastalgia was used as the main index of curative effect. The change before and after treatment in days of mastalgia, the time to alleviate pain, pain extent, and severe pain scores were observed. RESULTS: Compared to the control group, the treatment group had significantly fewer days of mastalgia (P < 0.01), a significantly lower severe pain score (P < 0.01), and significantly less subjective pain and tenderness (P < 0.05 and P < 0.01, respectively). Three days before the follow-up visit, the pain score in the treatment group was significantly lower than that in the control group (P < 0.05). A non-parametric test was used to compare the time to alleviate mastalgia between the two groups and found no statistical difference (Z = -0.313, P = 0.754). CONCLUSION: Application of Sanjierupi Gao can decrease mastalgia duration in patients with mammary gland hyperplasia during menstruation and alleviate the extent of mastalgia. The time to alleviate pain is psychologically influenced.

[Research of the glomerular filtration rate estimation model].

The glomerular filtration rate (GFR) is an important index of renal function with advantages of accurate, sensitive, stable, repetitive and accurate measurement of renal functions. The GFR is mainly determined in the clear rate of radioisotope markers (99m)Tc-DTPA, the process of which is complicated, long time-taking, high cost, and radioactively injuring. Recently, the methods using other renal function parameters measured easily to create the mathematic models and to estimate GFR are being investigated in the world. In this paper, for the renal function data of the Chinese, the efficiency in the three existing GFR formulas has been optimized with multi-function optimization techniques and the accuracy of the computation has been improved. Then the BP neural network technology is used for establishing a new GFR formula, which is a simpler form and obtains higher precision result than the formulas existed. The rmse and P30 of the new formula are better than those of the old ones.

Mechanisms of single herbs and herbal pairs in the treatment of mammary gland hyperplasia: An integrated review.

Background: The pathogenesis of hyperplasia of mammary glands (HMG) is a complex process, involving multiple links and systems within the body. Current clinical research indicates that traditional Chinese medicine (TCM) demonstrates a significant therapeutic effect in treating HMG. Single herbs or herbal pairs (two herbs) are the basic units of preventing and treating HMG. It is of great significance to explore the mechanism of single herbs or herbal pairs in treating HMG for clarifying the mechanism of preventing HMG with TCM. Purpose: This study aimed to review the literature, summarize the known mechanisms of single herbs and herbal pair therapy for treating hyperplasia of mammary glands (HMG), and elucidate the relevant substances involved within and outside the body during these treatments. Study design: In this study, the action mechanism of single herbs or herbal pairs in treating HMG was selected as the research object. English articles were mainly selected and Chinese articles were supplemented. We conducted a literature search in PubMed, CNKI, WanFang Database, etc，including full-text studies published between January 1992 and December 31, 2022. The primary literature was carefully screened, and the mechanism of action was explored by logical analysis. Methods: We conducted a literature review focusing on basic studies that explored the mechanisms underlying the effects of herbal treatments for mammary gland hyperplasia. The literature search was performed in PubMed, CNKI, and WanFang Database, covering full-text articles published from January 1992 to 31 December 2022, using various keywords (e.g., hyperplasia of mammary glands, single herb, herbal pair, effect, mechanism, inclusion criteria). Exclusion criteria were also set. We employed methods such as literature measurement, literature research, and content analysis to logically analyze, induce, and deduce the findings of the collected literature. Results: This review reveals that several distinct mechanisms contribute to the beneficial effects of single herbs or herbal pairs on the recovery of mammary gland hyperplasia. Regarding hormone levels, Chinese herbs can decrease hormones such as Estradiol(E2) and Prolactin(PRL), increase Progesterone(P) levels, balance the E2/P ratio, reduce the expression of sex hormone receptors, and lessen the self-sensitivity of breast tissue under the influence of E2. Histologically, Chinese herbs can inhibit breast neovascularization and alleviate blood viscosity. At the cellular level, Chinese herbs can modulate the expression of apoptosis genes and proteins, decrease cell proliferation activity, and ultimately inhibit or even reverse breast hyperplasia. From a pharmacological perspective, Chinese herbs exhibit analgesic, anti-inflammatory, antioxidant, and immune-regulating properties. Conclusion: The evidence in this review demonstrates the effectiveness of single herbs or herbal pairs in preventing and treating mammary gland hyperplasia, with precise underlying mechanisms.

Treatment of gastric paralysis after gastric schwannoma by electroacupuncture: A case report and literature review.

OBJECTIVE: We identified the potential role of electroacupuncture (EA) as an alternative therapy to traditional Chinese medicine (TCM) in a rare case of postoperative gastroparesis after gastric schwannoma (GS). CLINICAL PRESENTATION: A 31-year-old woman presented with impaired gastric emptying after gastrectomy for GS and was diagnosed with postoperative gastroparesis syndrome (PGS). The symptoms were slightly relieved after routine placement of the jejunal tube; however, symptoms such as dietary intolerance and impaired gastric emptying persisted. After the consultation, the patient agreed to undergo EA therapy. INTERVENTION AND RESULTS: The patient was able to tolerate oral intake after seven days of EA treatment, and the frequency and amount of food intake increased. The jejunal tube was removed at the outpatient follow-up two weeks after discharge, and the patient resumed a semi-liquid diet and was able to eat small amounts of rice. Reexamination of the upper digestive tract angiography showed that part of the contrast agent passed through the pyloric sinus, which showed improvement. CONCLUSION: EA stimulation increased tolerance to transoral feeding in patients with postoperative gastroparesis and facilitated the passage of contrast agents through the pyloric sinus. No adverse effects were observed during treatment, and the treatment was well accepted and tolerated by patients. A review article noted the benefits of acupuncture for gastrointestinal disorders but lacked high-quality evidence to support this.1 Therefore, the therapeutic role of EA needs to be further elucidated to provide high-quality evidence-based medical evidence for its clinical use.