Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis.

BACKGROUND: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. METHOD: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. RESULT: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 (I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 (I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks. CONCLUSION: This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.

Integration of untargeted and pseudotargeted metabolomics reveals specific markers for authentication and adulteration detection of Fritillariae Bulbus using tandem mass spectrometry and chemometrics.

Authentication and adulteration detection of closely related herbal medicines is a thorny issue in the quality control and market standardization of traditional Chinese medicine. Taking Fritillariae Bulbus (FB) as a case study, we herein proposed a three-step strategy that integrates mass spectrometry-based metabolomics and multivariate statistical analysis to identify specific markers, thereby accurately identifying FBs and determining the adulteration level. First, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based untargeted metabolomics method was employed to profile steroid alkaloids in five sorts of FB and screen potential differential markers. Then, the reliability of the screened markers was further verified by the distribution in different FB groups acquired from ultra-high performance liquid chromatography triple quadrupole mass spectrometry-based pseudotargeted metabolomics analysis. As a result, a total of 16 compounds were screened out to be the specific markers, which were successfully applied to distinguish five FBs by using discriminant analysis model. Besides, partial least squares regression models based on specific markers allowed accurate prediction of three sets of adulterated FBs. All the models afforded good linearity and good predictive ability with regression coefficient of prediction (R2p) > 0.9 and root mean square error of prediction (RMSEP) < 0.1. The reliable results of discriminant and quantitative analysis revealed that this proposed strategy could be potentially used to identify specific markers, which contributes to rapid chemical discrimination and adulteration detection of herbal medicines with close genetic relationship.

Dosage impact of submerged plants extracts on Microcystis aeruginosa growth: From hormesis to inhibition.

Allelopathy has been demonstrated to be an environmentally friendly way to control harmful algal blooms. Allelochemicals of submerged plants have attracted extensive research due to their bioavailability. The dose-response of submerged plant extracts on algae growth is worth further study to improve the efficiency of bioremediation. In this study, the ultrasonic-enzymatic assistance method was utilized to extract allelochemicals from Ceratophyllum, Myriophyllum spicatum, and Vallisneria. The effects of low-dosage and high-dosage extracts on the growth of Microcystis aeruginosa were compared based on cell biomass and morphology, photosynthetic parameters, reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. The results showed that the three submerged plant extracts exhibited hormetic effects at low dosages and inhibitory effects at high dosages on algal growth. Within 48 h of cultivation, the enzymatic activities of Microcystis aeruginosa fluctuated, suggesting that the extracts of the three submerged plants induced different oxidative reactions. After 120 h of cultivation with high-dosage extracts, the physiological and biochemical reactions of Microcystis aeruginosa significantly decreased, indicating the effectiveness of the allelopathy of Ceratophyllum, Myriophyllum spicatum, and Vallisneria extracts in controlling algal blooms. The phenomenon of hormesis and inhibition effect confirmed a significant dose-response relationship between the allelochemicals of submerged plant extracts and Microcystis aeruginosa, which could be attributed to the composition and content of allelochemicals. These findings highlight the importance of the relative concentration of the biological algaecide and will benefit other researchers in determining the safe dosage of plant allelochemicals when used in water.

Huangqi Guizhi Wuwu decoction alleviates oxaliplatin-induced peripheral neuropathy via the gut-peripheral nerve axis.

BACKGROUND: Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora. METHODS: In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis. RESULTS: HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis. CONCLUSIONS: HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.

Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway.

OBJECTIVE: This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats. METHODS: The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA. RESULTS: APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05). CONCLUSION: EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.

Does music intervention relieve depression or anxiety in people living with dementia? A systematic review and meta-analysis.

BACKGROUND: This study aimed to summarize the available evidence on music intervention alleviating depression or anxiety in dementia. METHODS: A comprehensive literature search was performed to analyze the effects of music intervention on depression or anxiety. Subgroups were created to explore the effect of intervention period, duration, and frequency on efficacy. The effect size was reported as a mean standardized difference (SMD) with 95% confidence interval (CI). RESULTS: The analysis included 19 articles involving 614 samples. Thirteen studies for relieving depression revealed that, with an increase in intervention period, the efficacy decreased and then increased, whereas with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Seven studies verifying the impact on anxiety relief revealed that the effect of intervention within 12 wk is significant; with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Collaborative analysis showed that long low-frequency interventions are more efficient than short high-frequency interventions. CONCLUSIONS: Music intervention can relieve depression or anxiety in people living with dementia. Weekly short interventions of more than 45 min are effective for emotional regulation. Future research should concentrate on severe dementia and follow-up impact.

Electroacupuncture Alleviates CFA-Induced Inflammatory Pain via PD-L1/PD-1-SHP-1 Pathway.

Inflammatory pain is difficult to treat clinically, but electroacupuncture (EA) has been demonstrated to be effective in alleviating inflammatory pain. Programmed cell death ligand-1 (PD-L1) and its downstream signal, Src homology region two domain-containing phosphatase-1 (SHP-1) have a critical role in relieving inflammatory pain. However, whether the PD-L1/PD-1-SHP-1 pathway mediates the analgesic and anti-inflammatory effects of EA in inflammatory pain remains unclear. Here, we observed that EA reversed the complete Freund's adjuvant (CFA)-induced hyperalgesia. EA reduced the expression of IL-6, iNOS, and NF-κB pathway in dorsal root ganglia (DRG) on day 7 after CFA injection but had no effect on the expression of IL-6, iNOS, and NF-κB PP65 on day 21 after CFA injection. Moreover, EA upregulated the protein levels of the PD-L1/PD-1-SHP-1 pathway on day 7 and day 21 after CFA injection. Furthermore, EA upregulated PD-L1 expression in calcitonin gene-related peptide (CGRP)+ but not in isohaemagglutinin B4 (IB4)+ and NF200+ neurons on day 7 and day 21 after CFA injection. Intrathecal injection of the PD-L1/PD-1 inhibitor BMS-1 (50 or 100 µg) blocked the EA-induced analgesic effect, significantly increased IL-6 and iNOS levels, and reduced the levels of PD-L1/PD-1-SHP-1. BMS-1 (50 or 100 µg) significantly reduced the expression of PD-L1 in IB4+, CGRP+, and NF200+ neurons. Our results show that EA's anti-inflammatory and analgesic effects are associated with activating the PD-L1/PD-1-SHP-1 pathway and suppressing its regulated neuroinflammation. This study provides a new potential therapeutic target for treating inflammatory pain.

Phytochemical gallic acid alleviates nonalcoholic fatty liver disease via AMPK-ACC-PPARa axis through dual regulation of lipid metabolism and mitochondrial function.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) usually includes NAFL called simple hepatosteatosis and nonalcoholic steatohepatitis (NASH) called more steatohepatitis. The latter is a leading pathogenic promotor of hepatocellular carcinoma (HCC). Phytochemical gallic acid (GA) has been proved to exert positive efficacy in HCC in our work, but it remains unclear whether its hepatoprotective effect attributes to the controlled transition from simple steatosis to steatohepatitis. PURPOSE: This work aims to provide mechanistic evidence that the therapeutic application of GA in NAFLD is indispensable for GA-meliorated NASH progression. METHODS: The high-fat diet (HFD)-fed mice and palmitic acid (PA) and oleic acid (OA)-treated hepatocytes were used collectively in this study. Bioinformatic analysis, clinical subjects, RNA-Seq, molecular docking, and confirmatory experiments were performed comprehensively to uncover the pathological link between the AMPK-ACC-PPARα axis and the treatment of NAFLD. RESULTS: By analyzing the clinical subjects and GEO database, we find a close link between the activation of AMPK-ACC-PPARα axis and the progression of NAFLD in human fatty liver. Subsequent assays show that GA exhibits pharmacological activation of AMPK, reprogramming lipid metabolism, and reversing mitochondrial function in cellular and murine fatty liver models. AMPK activation conferred substantial protection against murine NASH and fibrosis in the context of HFD-induced NAFLD. In contrast, silencing AMPK badly aggravates lipid deposition in hepatocytes, boosting NASH and NAFLD-associated HCC progression. The in silico docking, in vitro surface plasmon resonance and in vivo cellular thermal shift assay collectively reveal that GA directly interacts with AMPKα, which inactivates the ACC-PPARα axis signaling. Notably, GA repairs the liver damage, lipotoxicity, and mitochondrial respiratory capacity caused by excessive mtROS, while showing minimal effects in other major organs in mice. CONCLUSION: Our work identifies GA as an important suppressor of NAFLD-HCC progression, and underscores the AMPK-ACC-PPARα signal axis as a potential therapeutic target for NAFLD treatment.

Qingchang Wenzhong Decoction Prevents the Occurrence of Intestinal Tumors by Regulating Intestinal Microbiota and Gasdermin E.

Background: Intestinal tumors are the third most common malignant tumors worldwide, accounting for approximately 10% of all new cancer cases worldwide. Cancer prevention is a promising way to limit the intestinal tumor incidence rate; however, challenges remain. Qingchang Wenzhong decoction (QCWZD) can clinically treat mild to moderate ulcerative colitis symptoms. Moreover, the mechanism by which it prevents intestinal tumors has not been clarified. In this study, we explored the mechanism by which QCWZD prevents the occurrence of intestinal tumors. Methods: To study the preventive mechanism of QCWZD on intestinal tumors, we used two model mice with azoxymethane/dextran sodium sulfate (AOM/DSS)- and Apcmin/+-induced intestinal tumor formation. The two models exhibited colitis-associated cancer and familial adenomatous polyposis, respectively. Colon and small intestine tissues were collected and analyzed based on histopathology and immunohistochemistry analyses. Fecal samples were collected, and 16S rRNA sequencing was used to analyze the correlation between intestinal microbiota and the prevention of intestinal tumors. Results: In the AOM/DSS mice, the QCWZD reduced the number and size of tumors, as well as tumor load. Similarly, in the Apcmin/+ mice, QCWZD can also reduce the number of tumors and the tumor load. The results of 16S rRNA sequencing confirmed that QCWZD altered the composition of intestinal microbiota in mice, a phenomenon that may prevent the occurrence of intestinal tumors by aiding the increase in the abundance of beneficial bacteria, such as Ralstonia and Butyricicoccus, and reducing that of pathogenic bacteria, such as Desulfobacterota and Bacteroides, in the intestine. Further, immunohistochemistry reveald that QCWZD can improve the expression of intestinal barrier-related proteins and inhibit pyroptosis-related proteins. Conclusions: QCWZD has the potential to prevent the occurrence of intestinal tumors. The anti-tumor activity may be achieved by regulating the intestinal microbiota, improving the function of the intestinal barrier, and inhibiting GSDME mediated pyroptosis.

Allelopathic inhibitory effect on the growth of microcystis aeruginosa by improved ultrasonic-cellulase extract of Vallisneria.

The unique and efficient characteristics of allelopathy in submerged plants make it an environmentally friendly method to control harmful algal blooms. Increased research focus has been placed on the improved allelochemical extraction methods of submerged plants because of their cost-utility relationships. In this study, the growth inhibition effect of Vallisneria extract on Microcystis aeruginosa (M. aeruginosa) cells through the combination of enzyme and ultrasonic-assisted extraction method was analyzed. By establishing a co-cultivation experiment, the growth indicators, photosynthetic system, and oxidative stress system of M. aeruginosa were determined. The reactive oxygen species (ROS) and superoxide dismutase (SOD) activity, as well as the catalase (CAT) and Malondialdehyde (MDA) levels of algal cells were found to have increased significantly after co-cultivation, which indicated that the Vallisneria ultrasonic-cellulase extract could induce oxidative stress in Microcystis aeruginosa cells. The Vallisneria extract could promote at low concentrations and inhibit at high concentrations on the growth of Microcystis aeruginosa. The effective suppression of growth of algae cells with the extract was observed at 5 g/L (fresh weight). The results showed that the Vallisneria ultrasonic-cellulase extract had a significant inhibitory effect on M. aeruginosa, making the effective ingredients a useful reference for algae inhibitors.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma.

BACKGROUND: The relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk. METHODS: This case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model. RESULTS: When comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21-0.51), PUFA (OR: 0.32, 95% CI: 0.20-0.51), and TFA (OR: 0.44, 95% CI: 0.28-0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19-0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC. CONCLUSIONS: This study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs.

Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk.

PURPOSE: This study was to evaluate the associations of dietary intake of total and specific phytosterols and risk of esophageal squamous cell carcinoma (ESCC) and to explore their joint effects with PLCE1 rs2274223 polymorphisms. METHODS: A population-based case-control study was conducted in a Chinese rural population and 856 eligible incident ESCC cases and 856 controls were included. A validated food frequency questionnaire was used to collect dietary consumption and PLCE1 rs2274223 polymorphisms were genotyped. Unadjusted and adjusted odds ratios (ORs) with 95% confidence interval (CI) were assessed via logistic regression model. RESULTS: When comparing the highest with lowest intake quartiles, ß-sitosterol, campesterol, stigmasterol, ß-sitostanol, campestanol, and total phytosterols were all associated with a decreased risk of ESCC, with adjusted ORs being 0.32 (95% CI 0.20-0.48), 0.18 (95% CI 0.11-0.27), 0.45 (95% CI 0.29-0.70), 0.13 (95% CI 0.08-0.20), 0.14 (95% CI 0.09-0.22) and 0.28 (95% CI 0.18-0.43), respectively. An exposure-response relationship was also observed for both total and five specific phytosterols (all P for trend < 0.001). In comparison to rs2274223 AA genotype, both GA genotype (OR: 1.47, 95% CI 1.16-1.85) and GG genotype (OR: 2.13, 95% CI 1.20-3.84) were associated with an increased risk of ESCC. However, no interaction was observed between total/specific phytosterols intake and rs2274223 polymorphisms. CONCLUSION: Higher dietary intake of total and five specific phytosterols was associated with a lower risk of ESCC, and the risk of ESCC increased with the increment of rs2274223 G allele. The negative association between phytosterols and ESCC risk was not modified by rs2274223 polymorphisms. Foods or supplements rich in phytosterols are a promising source for chemoprevention of ESCC, and still, clinical trials will be required in any specific case.

Dietary flavonoid intake and risk of esophageal squamous cell carcinoma: A population-based case-control study.

OBJECTIVES: The aim of this population-based case-control study was to investigate the association between dietary consumption of the total flavonoids, subclasses, and specific flavonoids and the risk of esophageal squamous cell carcinoma (ESCC) among adults in a high-risk area of China. METHODS: We recruited 820 ESCC participants and 863 control participants from Yanting County. Dietary flavonoids were assessed using a validated 76-item food frequency questionnaire. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression after considering potential confounders. RESULTS: Comparing the highest and lowest intake quartiles, we observed a negative association of ESCC risk with consumption of isoflavones (OR = 0.34, 95% CI = 0.23-0.50, P for trend < 0.001), daidzein (OR = 0.31, 95% CI = 0.21-0.45, P for trend < 0.001), genistein (OR = 0.34, 95% CI = 0.23-0.50, P for trend < 0.001), and glycitein (OR = 0.32, 95% CI = 0.22-0.48, P for trend < 0.001) after adjustment for potential confounders. A more pronounced negative association was observed when comparing the third quartile, rather than the fourth, with the lowest quartile for consumption of anthocyanidins (OR = 0.58, 95% CI = 0.42-0.80, P for trend = 0.004), delphinidin (OR = 0.57, 95% CI = 0.41-0.78, P for trend = 0.004), and cyanidin (OR = 0.48, 95% CI = 0.35-0.66, P for trend = 0.003) after considering potential confounders. Consumption of total flavonoids, flavones, flavonols, and six other specific flavonoids (quercetin, myricetin, kaempferol, luteolin, apigenin, and peonidin) was not associated with ESCC risk. CONCLUSIONS: The results suggest that increased dietary intake of isoflavones and moderate consumption of anthocyanidins were associated with a decreased risk of ESCC. Future nutritional guidelines may emphasize foods or supplements rich in specific isoflavones and anthocyanidins for ESCC chemoprevention.

Effect of acupotomy in knee osteoarthritis patients: study protocol for a randomized controlled trial.

BACKGROUND: Symptomatic knee osteoarthritis (KOA) is common in China. Pharmacological therapy is not the first recommendation because of its safety issues. Nonpharmacological therapy, such as lifestyle adjustments, weight loss, muscle strengthening, and aerobic exercise programs, is strongly recommended for KOA. However, these approaches may fail due to poor patient compliance. There is a lack of high-quality randomized controlled trials of acupotomy, an effective treatment for KOA. This study was designed to investigate the efficacy of acupotomy in patients with KOA. METHODS: A total of 136 patients will be enrolled at the First Affiliated Hospital of Guangzhou University of Chinese Medicine and assigned to the acupotomy group or sham acupotomy group according to the block randomization scheme. Patients in the acupotomy group will receive 2 sessions of acupotomy for 2 weeks (once a week). Patients in the sham group will receive 2 sessions of sham stimulation for 2 weeks (once a week). All patients will use indomethacin cream externally. The primary outcome will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the secondary outcomes will be the visual analog scale (VAS) score, plantar pressure distribution test result, X-ray examination findings, musculoskeletal ultrasound findings, maximum knee circumference, joint mobility, and quality of life. Measurements will be taken at baseline, 1 week after the end of treatment, and at the 3- and 6-month follow-ups. DISCUSSION: To the best of our knowledge, this will be the first single-blind, sham-controlled study of acupotomy. The outcome assessors will also be blinded. The aim of this work is to demonstrate the efficacy of acupotomy in treating KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033047 . Registered on 18 May 2020.

Association of mineral metabolism biomarkers with chronic kidney disease in Chinese adults.

BACKGROUND: We aimed to examine the association of three mineral metabolism markers, including serum calcium, inorganic phosphorus, and intact parathyroid hormone with the risk of chronic kidney disease (CKD) at all stages. METHODS: This retrospective cohort study involved 3563 participants, including 3274 CKD patients and 289 healthy controls. CKD is diagnosed according to clinical guidelines from the 2012 KDIGO. Effect sizes are expressed odds ratio (OR) and 95 confidence interval (CI). RESULTS: After propensity score matching, per 0.5 mg/dL increment of inorganic phosphorus was significantly associated with 1.33-, 1.61-, and 2.85-fold increased risk of CKD at stages 1-2, 4, and 5, respectively. Regarding per 8 pg/mL increment of intact parathyroid hormone, significance was only noted for stage 5. In subsidiary analyses, the risk prediction of mineral metabolism markers under study was more evident in males and hypertensive subjects. A nomogram prediction model was constructed based on age, sex, and three mineral metabolism markers for CKD, with decent accuracy. CONCLUSIONS: Our findings indicate that serum calcium was associated with all-stage CKD risk, whereas the association for inorganic phosphorus and intact parathyroid hormone was significant at advanced stages.

Effect of Tang-Shen-Ning decoction on podocyte epithelial-esenchymal transformation via inhibiting Wnt/ß-catenin pathway in diabetic mice.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Podocyte epithelial-esenchymal transformation (EMT) induced by the activated Wnt/ß-catenin pathway plays a key role in DN. Tang-Shen-Ning (TSN), a Chinese herbal formula, has been shown to decrease proteinuria and protect the renal function in DN. However, the effect of TSN on the Wnt/ß-catenin pathway and podocyte EMT is unclear. METHODS: TSN was orally administrated in KK-Ay mice for 4 weeks, at a daily dose of 20 g/kg body weight in our in vivo study. Rat serum containing TSN was added in podocyte cultured in high glucose for 24 h. The levels of 24 h urine protein, serum creatinine and blood urea nitrogen were detected by ELISA. Nephrin, Synaptopodin, P-cadherin, desmin, FSP-1, and collagen I protein and mRNA expressions were detected by western blot, immunohistochemistry, immunofluorescence, and RT-PCR. Snail, ß-catenin, and TCF/LEF were detected by Western blot, RT-PCR and luciferase. RESULTS: TSN significantly decreased 24-h urine protein, serum creatinine, and blood urea nitrogen in DN mice. Further, TSN also significantly increased the expression of nephrin, synaptopodin, and P-cadherin, while the expression of desmin, fibroblast-specific protein 1 (FSP-1), and collagen I of podocytes was significantly decreased. Moreover, TSN significantly inhibited the activation of the Wnt/ß-catenin pathway in podocytes cultured under high glucose (HG). Notably, the effect of TSN on podocyte EMT was reversed by activation of the Wnt/ß-catenin pathway. CONCLUSIONS: TSN could protect podocytes from injury in DN, partly via inhibiting the activation of the Wnt/ß-catenin pathway and ameliorating podocyte EMT.

Bu-Shen-Yi-Sui Capsule, an Herbal Medicine Formula, Promotes Remyelination by Modulating the Molecular Signals via Exosomes in Mice with Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a common inflammatory demyelinating disorder of the central nervous system. Bu-shen-yi-sui capsule (BSYSC) could significantly reduce the relapse rate, prevent the progression of MS, and enhance remyelination following neurological injury in experimental autoimmune encephalomyelitis (EAE), an established model of MS; however, the mechanism underlying the effect of BSYSC on remyelination has not been well elucidated. This study showed that exosomes carrying biological information are involved in the pathological process of MS and that modified exosomes can promote remyelination by modulating related proteins and microRNAs (miRs). Here, the mechanism by which BSYSC promoted remyelination via exosome-mediated molecular signals was investigated in EAE mice and oligodendrocyte progenitor cells (OPCs) in vitro. The results showed that BSYSC treatment significantly improved the body weight and clinical scores of EAE mice, alleviated inflammatory infiltration and nerve fiber injury, protected the ultrastructural integrity of the myelin sheath, and significantly increased the expression of myelin basic protein (MBP) in EAE mice. In an in vitro OPC study, BSYSC-containing serum, especially 20% BSYSC, promoted the proliferation and migration of OPCs and induced OPCs to differentiate into mature oligodendrocytes that expressed MBP. Furthermore, BSYSC treatment regulated the expression of neuropilin- (NRP-) 1 and GTX, downregulated the expression of miR-16, let-7, miR-15, miR-98, miR-486, and miR-182, and upregulated the level of miR-146 in serum exosomes of EAE mice. In conclusion, these results suggested that BSYSC has a neuroprotective effect and facilitates remyelination and that the mechanism underlying the effect of BSYSC on remyelination probably involves regulation of the NRP-1 and GTX proteins and miRs in serum exosomes, which drive promyelination.

Effects of Selenium on Differentiation and Antioxidant Activity of Sclerotium of Penicillium thomii Q1 Strain.

Selenium is an essential trace element, which has certain antioxidant properties. Na2SeO3 is toxic, and its use is limited. SeMet, as an organic selenium, is less toxic than Na2SeO3. In this experiment, different concentrations of Na2SeO3 and SeMet were added to MEA and PDA media to observe the effect of selenium on the sclerotium differentiation of Q1 strain, and the contents of carotenoids, ascorbic acid, and total phenol and their reducing power, DPPH free radical scavenging ability, ferrous ion chelating ability, and superoxide anion scavenging ability were determined. Meanwhile, the orthogonal design was used to optimize the selenium enrichment culture conditions of Q1. The results showed that the addition of selenium in the PDA medium was not conducive to the differentiation of Q1 strain. The addition of inorganic and organic selenium in the MEA medium at different concentrations resulted in the accumulation of carotenoids, ascorbic acid, phenols, and selenium in the sclerotia of Q1 strain, and the contents of carotenoids, ascorbic acids, and selenium in the sclerotia of Q1 strain were increased to different degrees, but it cannot increase the content of total phenol. In addition, when the concentration of Na2SeO3 and SeMet in the medium was 10 µg/mL, the reducing power of the extract was improved. The experimental results can provide a new research idea for the utilization and development of Penicillium sclerotium and selenium.

[Permeation mechanism of phenolic acid components from traditional Chinese medicine on PES membrane separation process].

To explore the permeation mechanism of micro-molecule medicinal ingredients of water extract of tradition Chinese medicine(TCM) in membrane separation process. With phenolic acid components as the model solute, five phenolic acids with similar molecular weight and structure, namely gallic acid, protocatechuate acid, 4-hydroxybenzoic acid, 3-hydroxybenzoic acid and salicylic acid, were selected in the PES membrane separation experiments. With the relative flux and the transmission rate as indexes, the scanning electron microscopy(SEM) and the electrochemical impedance spectroscopy(EIS) were used to analyze the permeation mechanism of different phenolic acid components. The results showed phenolic acids with similar molecular weight had different permeation behaviors, with decreased relative flux and increased solute permeation with the increase of solute concentration. According to the permeation behavior analyzed by the molecular structure of solute, the transmission rate of phenolic acids increased with the increase of the number of hydroxyl, and the order of substituent positions of phenolic acids based on the permeation rate as follows: para-substituted > meta-substitution > ortho-substitution. Electrochemical impedance spectroscopy reflected the role of charge repulsion in the membrane process; that is to say, the greater the resistance is, the less the solute permeation is. Therefore, the permeation phenomenon of the phenolic acid components in the PES membrane is not only the result of simple sieving mechanisms, but also has the effects of steric hindrance and charge repulsion during the membrane process.