Association between dietary patterns and chronic kidney disease combined with hyperuricemia.

Background and aims: Chronic kidney disease (CKD) combined with hyperuricemia is a concerning health issue, but the association between this condition and dietary patterns remains poorly understood. The aim of this study was to assess the associations between dietary patterns and CKD combined with hyperuricemia. Methods: This cross-sectional study was conducted involving 12 318 participants aged 18-79 years during 2018-2020. Dietary intake information was collected using a validated 110-item food frequency questionnaire. Factor analysis was used to identify major dietary patterns. CKD was defined as the presence of albuminuria or an estimated glomerular filtration rate <60 mL min-1 1.73 m-2. Hyperuricemia was defined as serum uric acid levels >420 µmol L-1 both in men and women. Logistic regression models were applied to assess the association between dietary patterns and the risk of CKD combined with hyperuricemia. Results: Five major dietary patterns were identified: 'healthy pattern', 'traditional pattern', 'animal foods pattern', 'sweet foods pattern', and 'tea-alcohol pattern', which together explained 38.93% of the variance in the diet. After adjusting for potential confounders, participants in the highest quartile of the traditional pattern had a lower risk of CKD combined with hyperuricemia (OR = 0.49, 95% CI: 0.32-0.74, Pfor trend < 0.01). Conversely, participants in the highest quartile of the sweet foods pattern had a higher risk compared to those in the lowest quartile (OR = 1.69, 95% CI: 1.18-2.42, Pfor trend < 0.01). However, no significant association was observed between the healthy pattern, animal foods pattern and tea-alcohol pattern and the risk of CKD combined with hyperuricemia. Conclusions: Our results suggest that the traditional pattern is associated with a reduced risk of CKD combined with hyperuricemia, whereas the sweet foods pattern is associated with an increased risk.

Mechanism of Chinese Medicine Against Diabetic Gastroparesis： A Review / 中国实验方剂学杂志

Diabetic gastroparesis （DGP） is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically， it often manifests as abdominal distension， nausea and vomiting， early satiety， dyspepsia， etc. The pathogenesis of DGP is multifactorial， closely related to many factors， such as chronic hyperglycemia， neuropathy， autonomic nervous system disorders， inflammation， and oxidative stress. These factors can interact with each other， leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine （TCM） has significant advantages in the prevention and treatment of DGP， including a long history， remarkable efficacy， individualized treatment， diverse therapeutic formulations， and improvement in the quality of life. Additionally， TCM is known for its low adverse reactions， good tolerance， and multi-targeted effects， making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones， inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and modulation of related signaling pathways such as stem cell factor （SCF）/cellular growth factor receptor （c-Kit）， adenosine monophosphate-activated protein kinase （AMPK）， Ras homologous genome member A （RhoA）/Rho-associated coiled-coil forming kinase （ROCK）. This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and regulation of related signaling pathways， aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.

Therapeutic effect of acupoint pressing acupuncture combined with moxibustion at Baihui acupoint on infantile cold and nasal obstruction caused by exogenous wind and cold / 中国基层医药

Objective:To investigate the clinical efficacy of acupoint pressing acupuncture combined with moxibustion at Baihui acupoint on infantile cold and nasal obstruction caused by exogenous wind and cold. Methods:This study included a total of 120 children with exogenous wind and cold-induced infantile cold and nasal obstruction who were treated at the Jinhua Maternal & Child Health Care Hospital from February 2021 to May 2022. They were divided into three groups using a random number table method, namely the acupoint pressing acupuncture group, the moxibustion group, and the combined therapy group, each containing 40 children. Based on routine treatment, children in the acupoint pressing acupuncture group received acupoint ( Yintang, Shuangyingxiang, Shuangbitong) pressing acupuncture treatment, while those in the moxibustion group underwent mild moxibustion at Baihui acupoint, and those in the combined therapy group underwent acupoint ( Yintang, Shuangyingxiang, Shuangbitong) pressing acupuncture Baihui combined with mild moxibustion at Baihui acupoint. The clinical efficacy of each group was evaluated. At 2, 24, 48, and 72 hours after treatment, differences in nasal congestion symptom scores were compared among the three groups. Sleep quality was also compared among the three groups before and after treatment. Results:The response rate in the combined therapy group was 92.5% (37/40), which was significantly higher than 75% (30/40) in the acupoint pressing acupuncture group and 65% (26/40) in the moxibustion group ( χ2 = 4.50, 9.04, both P < 0.05). At 2, 24, 48, and 72 hours after treatment, the nasal congestion symptom score in the combined therapy group was (2.05 ± 0.55) points, (1.80 ± 0.64) points, (1.33 ± 0.59) points, and (0.90 ± 0.18) points, respectively, while it was (2.43 ± 0.59) points, (2.15 ± 0.57) points, (1.73 ± 0.84) points, and (1.18 ± 0.80) points, respectively, in the acupoint pressing acupuncture group, and (2.50 ± 0.59) points, (2.13 ± 0.78) points, (1.88 ± 0.81) points, and (1.45 ± 0.81) points, respectively, in the moxibustion group. At the above-mentioned time points, the nasal congestion symptom score was statistically significant among the three groups ( F = 3.15, 9.27, 16.17, 20.22, all P < 0.05). After treatment, daytime sleep duration and nocturnal sleep duration in the combined therapy group were (3.41 ± 0.31) hours and (12.36 ± 1.17) hours, respectively, which were significantly longer than (2.95 ± 1.07) hours and (11.33 ± 1.38) hours in the acupoint pressing acupuncture group and (2.93 ± 0.98) hours and (11.21 ± 1.93) hours in the moxibustion group ( F = 6.37, 12.31, both P < 0.05). Nocturnal wake time, the number of night wakings, and sleep onset time in the combined therapy group were (18.74 ± 2.21) minutes, (1.64 ± 0.18) times, and (15.43 ± 2.03) minutes, respectively, which were significantly shorter or less than (21.13 ± 3.78) minutes, (2.15 ± 0.66) times, and (17.63 ± 5.24) minutes in the acupoint pressing acupuncture group, and (20.53 ± 2.90) minutes, (2.11 ± 0.32) times, and (17.22 ± 2.88) minutes in the moxibustion group ( F = 15.93, 15.36, 10.11, all P < 0.05). There was a significant difference in sleep quality score among the three groups ( F = 23.45, P < 0.05). Conclusion:The combination of acupoint pressing acupuncture and moxibustion at Baihui acupoint is highly effective against infantile cold and nasal obstruction caused by exogenous wind and cold. The combined therapy can alleviate the symptoms of nasal congestion in children and improve sleep quality.

First Report of Broad Bean Wilt Virus 2 Infecting Balsam (Impatiens balsamina) in China.

Balsam (Impatiens balsamina L.) is an ornamental plant cultivated extensively in China and elsewhere, but it has also been used as a medicinal plant for thousands of years (Qian et al., 2023). In 2022, an examination of 10 garden-grown I. balsamina plants in Chaoyang, Beijing, China revealed eight plants with blotches, mosaic symptoms, and deformed leaves (Fig. S1A). Total RNA was extracted from the symptomatic leaf tissue of these eight plants using the TRIzol reagent (Invitrogen, USA). Four RNA preparations (high quality and quantity) were combined for the small RNA sequencing analysis (TIANGEN Biotech Co., China). A total of 16,509,586 clean reads (18-30 nt) were obtained and assembled into larger contigs using Velvet 1.0.5. A search of the National Center for Biotechnology Information non-redundant database using BLASTX indicated 72, 24, and 19 contigs were homologous to broad bean wilt virus 2 (BBWV2), cucumber mosaic virus (CMV), and impatiens cryptic virus 1 (ICV1) sequences (Zheng et al., 2022), respectively. To verify the next-generation sequencing data, the following three sets of primer pairs were designed according to the contig sequences of these three viruses: CMV-F:5'-ATGGACAAATCTGAATCAACCAGTGC-3'/CMV-R: 5'-CCGTAAGCTGGATGGACAACC-3'; BBWV2-F:5'-CAATTTGGACAACTACAATTTGCC-3'/ BBWV2-R: 5'-GCTGAGTCTAAATCCCATCTATC-3'; and ICV1-F: 5'-CGCACAACT CTACAAT GACATGGTC-3'/ICV1-R: 5'-AGTTCCATCGTCCAGTAGGCG-3'. The primers were used to amplify CMV, BBWV2, and ICV1 sequences by reverse transcription-polymerase chain reaction (RT-PCR), with individual RNA preparations serving as the template. The CMV, BBWV2, and ICV1 target sequences were amplified from eight, four, and four samples, respectively (Fig. S1B). To evaluate virus infectivity, Nicotiana benthamiana seedlings were inoculated using a leaf tissue extract prepared from an infected I. balsamina plant. At 7 days post-inoculation, disease symptoms were detected on N. benthamiana systemic leaves (e.g., deformation and apical necrosis) (Fig. S1C). Confirmation tests involving RT-PCR indicated the N. benthamiana plants were infected with BBWV2 and CMV, but not with ICV1 (Fig. S1D). To obtain the complete BBWV2 genome sequence (RNA1 and RNA2), virus-specific PCR primers (Table S1) were designed to produce the terminal sequences via 5' and 3' rapid amplification of cDNA ends (RACE), which was completed using the SMARTer RACE 5'/3' Kit (Clontech, China). The RNA1 and RNA2 sequences comprised 5,957 nt (GenBank: OQ857921) and 3,614 nt (GenBank: OQ857922), respectively. The BLAST analyses revealed RNA1 and RNA2 were similar to sequences in other BBWV2 isolates (sequence identities of 78.88% to 95.15% and 80.83% to 91.51%, respectively). Using the neighbor-joining method and MEGA 7.0, the phylogenetic relationships between the BBWV2 isolated in this study and other isolates were determined on the basis of the full-length RNA1 and RNA2 sequences (Kumar et al., 2016). According to the RNA1 and RNA2 sequences, the BBWV2 isolated in this study was most closely related to the BBWV2 isolate from Gynura procumbens (GenBank: KX686589) and the BBWV2 isolate from Nicotiana tabacum (GenBank: KX650868), respectively (Fig. S1E). To the best of our knowledge, this is the first report of I. balsamina naturally infected with BBWV2 in China. The study findings may be useful for detecting BBWV2 in I. balsamina and for diagnosing and managing the associated disease. The authors declare no conflict of interest. Yanhong Qiu and Haijun Zhang contributed equally to this paper. Funding: This research was supported by the Beijing Academy of Agriculture and Forestry Foundation, China (KYCX202305, QNJJ202131, and KJCX20230214). References: Qian H.Q., et al. 2023. J Ethnopharmacol. 303. Zheng Y., et al. 2022. Arch Virol. 167: 2099-2102. Kumar et al. 2016. Mol Biol Evol. 33: 1870-1874.

Therapeutic effect of tempo in Mozart's "Sonata for two pianos" (K. 448) in patients with epilepsy: An electroencephalographic study.

BACKGROUND: Mozart's "Sonata for two pianos" (Köchel listing 448) has proven effective as music therapy for patients with epilepsy, but little is understood about the mechanism of which feature in it impacted therapeutic effect. This study explored whether tempo in that piece is important for its therapeutic effect. METHODS: We measured the effects of tempo in Mozart's sonata on clinical and electroencephalographic parameters of 147 patients with epilepsy who listened to the music at slow, original, or accelerated speed. As a control, patients listened to Haydn's Symphony no. 94 at original speed. RESULTS: Listening to Mozart's piece at original speed significantly reduced the number of interictal epileptic discharges. It decreased beta power in the frontal, parietal, and occipital regions, suggesting increased auditory attention and reduced visual attention. It also decreased functional connectivity among frontal, parietal, temporal, and occipital brain regions, also suggesting increased auditory attention and reduced visual attention. No such effects were observed after patients listened to the slow or fast version of Mozart's piece, or to Haydn's symphony at normal speed. CONCLUSIONS: These results suggest that Mozart's "Sonata for two pianos" may exert therapeutic effects by regulating attention when played at its original tempo, but not slower or faster. These findings may help guide the design and optimization of music therapy against epilepsy.

Managing Severe Evaporative Dry Eye with Intense Pulsed Light Therapy.

INTRODUCTION: This study assessed the efficacy and safety of intense pulsed light (IPL) therapy in participants with severe evaporative dry eye disease (DED). METHODS: This randomized, controlled, single-center study included 49 adult participants (≥ 18 years) with severe evaporative DED who received either IPL therapy (n = 56 eyes) or sham therapy (n = 42 eyes) three times. The primary efficacy parameters were ocular surface disease index (OSDI) score, non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctivocorneal staining score (CS), MG Score, meibomian gland (MG) quality, and MG expression score. RESULTS: The mean ages for the IPL group and the control group were 28.05 ± 3.41 years (57.1% female) and 28.14 ± 3.53 years (52.4% female), respectively. Comparison between the IPL group and the control group found significant differences in the mean OSDI score (22.16 ± 6.08 vs. 42.38 ± 6.60; P < 00.01), NITBUT (6.27 ± 0.84 vs. 3.86 ± 0.68; P < 0.001), TFLL (2.14 ± 0.44 vs. 3.45 ± 0.50; P < 0.001), MG Score (1.34 ± 0.55 vs. 1.88 ± 0.33; P < 0.001), MG quality (1.59 ± 0.07 vs. 2.67 ± 0.08), and MG expression (1.54 ± 0.57 vs. 2.45 ± 0.55) at 12 weeks follow-up; however, there was no significant difference in CS (3.32 ± 1.11 vs. 3.74 ± 1.04; P = 0.063). CONCLUSION: The findings suggest that IPL therapy is clinically beneficial in ameliorating the signs and symptoms of severe evaporative dry eye disease.

Association between blood selenium levels and gestational diabetes mellitus: A systematic review and meta-analysis.

Introduction: The association between blood (serum or plasma) selenium concentrations and gestational diabetes mellitus (GDM) has been evaluated in some studies. However, the reported findings are debatable, and only case-control and cross-sectional studies were included. Objective: This research aimed to assess the association between blood selenium levels and GDM by analyzing existing literature. To provide a reference for the prevention and treatment of GDM, we included prospective studies which are not included in previous studies to collate more high-quality evidence and better test the etiological hypothesis between blood Se concentrations and GDM. Methods: The PubMed, EMBASE, and Web of Science databases were retrieved for literature up to September 2022, and relevant references were manually searched. Raw data from relevant studies were extracted, and a random effect model was adopted for meta-analysis. The total effects were reported as weighted mean differences. All data were analyzed using Stata 16.0 software. Results: Fourteen studies involving 890 pregnant women with GDM and 1618 healthy pregnant women were incorporated in the meta-analysis. Pregnancies with GDM had significantly lower blood selenium levels than those with normal glucose tolerance (weighted mean difference = -8.11; 95% confidence interval: -12.68 to -3.54, P = 0.001). Subgroup analyses showed that the association between blood selenium levels and GDM was consistent in the residents of Asia and Africa, but not in European. This trend was significant in the second and third trimester subgroups, but not in the first trimester subgroup. Articles published in 2006-2015 also showed this trend, but those published before 2005 and 2016-2019 did not show significant results. This difference was evident in non-prospective studies, but not significant in prospective studies. Studies using the Carpenter and Coustan diagnostic criteria were consistent with this trend, whereas studies using other diagnostic criteria found no differences. In addition, in terms of blood selenium measurement methods, atomic absorption spectrometry showed more significant differences than other methods. In the subgroup analysis based on the sample size of included studies and the quality of the studies, each subgroup showed statistical differences. Conclusion: Lower blood selenium concentrations are associated with GDM as shown in our study. Therefore, supplementing an appropriate amount of selenium may be helpful for GDM prevention and treatment.

[Research progress on antitumor effect and molecular mechanism of capsaicin].

Capsaicin is a lipid-soluble vanillin alkaloid extracted from Capsicum plants in the Solanaceae family, which is the main active ingredient in capsicum, with multiple functions such as anti-inflammation, analgesia, cardiovascular expansion, and gastric mucosa protection. Recently, capsaicin has been confirmed as a potential antitumor compound. It can induce cell cycle arrest, inhibit cancer cell proliferation, metastasis, invasion, and angiogenesis, and promote apoptosis or autophagy in malignancy cell models and animal models of lung cancer, breast cancer, gastric cancer, and liver cancer. Meanwhile, capsaicin shows a synergistic antitumor effect when combined with other antitumor drugs such as sorafenib. Based on the recent literature on the antitumor effect of capsaicin, the present study analyzed the molecular mechanism of capsaicin in resisting tumors by inducing apoptosis and reviewed the effects of capsaicin in inducing tumor cell cycle arrest, inhibiting tumor cell proliferation, metastasis, and angiogenesis, and combating tumors with other drugs, thereby providing a theoretical basis for further research of capsaicin and its rational development and utilization.

Polymeric photothermal nanoplatform with the inhibition of aquaporin 3 for anti-metastasis therapy of breast cancer.

Metastasis, as one of major challenges in the cancer treatment, is responsible for the high mortality of breast cancer. It has been reported that breast cancer cell invasion and metastasis are related to aquaporin 3 (AQP3), which is the transmembrane transport channel for H2O2 molecules. Moreover, there is agreement that preventing the metastasis of breast tumor cells in combination with inhibiting the tumor growth is a promising strategy for cancer chemotherapy. Herein, we constructed a flexible photothermal crosslinked polymeric nanovehicle for the delivery of the AQP3 inhibitor, [AuCl2(phen)]+Cl- (Auphen). The polymeric nanovehicle (pOMPC-Dex) is comprised of three modules: 1) pOEGMA-co-pMEO2MA serves as the temperature-responsive segment; 2) pCyanineMA acts as the near-infrared (NIR) optical absorbing motif for photothermal therapy and is conjugated with pOEGMA-co-pMEO2MA to obtain NIR light stimuli-responsive drug release; and 3) pPBAMA-Dex functions as an acidic tumor microenvironment-responsive unit. Auphen was encapsulated into a nanovehicle (Auphen@pOMPC-Dex) through electrostatic interactions. The designed nanoplatform showed a pH- and NIR light stimuli-responsive drug release profile and exhibited the strong inhibition of intracellular H2O2 uptake by breast cancer cells, which led to the inhibition of breast cancer cell migration and invasion in vitro. In a breast cancer mouse model, Auphen@pOMPC-Dex markedly reduced the number of lung metastases in tumor-bearing mice due to the combined suppression of tumor growth and metastasis. Consequently, the fabricated Auphen@pOMPC-Dex may provide a new strategy for the development of comprehensive oncotherapies. STATEMENT OF SIGNIFICANCE: High mortality due to metastasis-induced breast cancer has been a key issue that needs to be addressed. It has been reported that aquaporin 3 (AQP3), a transmembrane transport channel for H2O2 molecules was found to have an accelerated effect on breast cancer cell migration. Hence, a flexible crosslinked polymeric nanoplatform with the inhibition of AQP3 was designed to inhibit metastasis of breast cancer cells. At the same time, we combined suppression of tumor growth with photothermal therapy to enhance the anticancer therapy effect.

Discovery and Characterization of the Key Constituents in Ginkgo biloba Leaf Extract With Potent Inhibitory Effects on Human UDP-Glucuronosyltransferase 1A1.

Human UDP-glucuronosyltransferase 1A1 (hUGT1A1) is one of the most essential phase II enzymes in humans. Dysfunction or strong inhibition of hUGT1A1 may result in hyperbilirubinaemia and clinically relevant drug/herb-drug interactions (DDIs/HDIs). Recently, a high-throughput fluorescence-based assay was constructed by us to find the compounds/herbal extracts with strong inhibition against intracellular hUGT1A1. Following screening of over one hundred of herbal products, the extract of Ginkgo biloba leaves (GBL) displayed the most potent hUGT1A1 inhibition in HeLa-UGT1A1 cells (Hela cells overexpressed hUGT1A1). Further investigations demonstrated that four biflavones including bilobetin, isoginkgetin, sciadopitysin and ginkgetin, are key constituents responsible for hUGT1A1 inhibition in living cells. These biflavones potently inhibit hUGT1A1 in both human liver microsomes (HLM) and living cells, with the IC50 values ranging from 0.075 to 0.41 µM in living cells. Inhibition kinetic analyses and docking simulations suggested that four tested biflavones potently inhibit hUGT1A1-catalyzed NHPN-O-glucuronidation in HLM via a mixed inhibition manner, showing the K i values ranging from 0.07 to 0.74 µM. Collectively, our findings uncover the key constituents in GBL responsible for hUGT1A1 inhibition and decipher their inhibitory mechanisms against hUGT1A1, which will be very helpful for guiding the rational use of GBL-related herbal products in clinical settings.

Erythrocyte transglutaminase-2 combats hypoxia and chronic kidney disease by promoting oxygen delivery and carnitine homeostasis.

Due to lack of nuclei and de novo protein synthesis, post-translational modification (PTM) is imperative for erythrocytes to regulate oxygen (O2) delivery and combat tissue hypoxia. Here, we report that erythrocyte transglutminase-2 (eTG2)-mediated PTM is essential to trigger O2 delivery by promoting bisphosphoglycerate mutase proteostasis and the Rapoport-Luebering glycolytic shunt for adaptation to hypoxia, in healthy humans ascending to high altitude and in two distinct murine models of hypoxia. In a pathological hypoxia model with chronic kidney disease (CKD), eTG2 is critical to combat renal hypoxia-induced reduction of Slc22a5 transcription and OCNT2 protein levels via HIF-1α-PPARα signaling to maintain carnitine homeostasis. Carnitine supplementation is an effective and safe therapeutic approach to counteract hypertension and progression of CKD by enhancing erythrocyte O2 delivery. Altogether, we reveal eTG2 as an erythrocyte protein stabilizer orchestrating O2 delivery and tissue adaptive metabolic reprogramming and identify carnitine-based therapy to mitigate hypoxia and CKD progression.

A Network Pharmacology Approach to Explore the Mechanisms of Artemisiae scopariae Herba for the Treatment of Chronic Hepatitis B.

BACKGROUND: As a traditional Chinese medicine, Artemisiae scopariae Herba (ASH) is used to treat various liver diseases. The purpose of this study was to explore the mechanisms of ASH for treating chronic hepatitis B (CHB) using a network pharmacological method. METHODS: Bioactive ingredients and related targets of ASH were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Gene names of targets were extracted from UniProt database. Differentially expressed genes (DEGs) of CHB were obtained from microarray dataset GSE83148. The intersect genes between DEGs and target genes were annotated using clusterProfiler package. The STRING database was used to obtain a network of protein-protein interactions. Cytoscape 3.7.2 was used to construct the "ingredient-gene-pathway" (IGP) network. Molecular docking studies were performed using Autodock vina. RESULTS: A total of 13 active components were extracted from TCMSP database. Fifteen intersect genes were obtained between 183 target genes and 403 DEGs of GSE83148. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that ASH against CHB mainly involved in toll-like receptor signaling pathway, cellular senescence, hepatitis B, and chemokine signaling pathway. We screened one hub compound, five core targets, and four key pathways from constructed networks. The docking results indicated the strong binding activity between quercetin and AKT1. CONCLUSIONS: This study provides potential molecular mechanisms of ASH against CHB based on exploration of network pharmacology.

Discovery and characterization of naturally occurring potent inhibitors of catechol-O-methyltransferase from herbal medicines.

Human catechol-O-methyltransferase (hCOMT) is considered a therapeutic target due to its crucial roles in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs. There are nevertheless few safe and effective COMT inhibitors and there lacks a diversity in structure. To discover novel safe and effective hCOMT inhibitors from herbal products, in this study, 53 herbal products were collected and their inhibitory effects against hCOMT were investigated. Among them, Scutellariae radix (SR) displayed the most potent inhibitory effect on hCOMT with an IC50 value of 0.75 µg mL-1. To further determine specific chemicals as COMT inhibitors, an affinity ultrafiltration coupled with liquid chromatography-mass spectrometry method was developed and successfully applied to identify COMT inhibitors from SR extract. The results demonstrated that scutellarein 2, baicalein 9 and oroxylin A 12 were potent COMT inhibitors, showing a high binding index (>3) and very low IC50 values (32.9 ± 3.43 nM, 37.3 ± 4.32 nM and 18.3 ± 2.96 nM). The results of inhibition kinetics assays and docking simulations showed that compounds 2, 9 and 12 were potent competitive inhibitors against COMT-mediated 3-BTD methylation, and they could stably bind to the active site of COMT. These findings suggested that affinity ultrafiltration allows a rapid identification of natural COMT inhibitors from a complex plant extract matrix. Furthermore, scutellarein 2, baicalein 9 and oroxylin A 12 are potent inhibitors of hCOMT in SR, which could be used as promising lead compounds to develop more efficacious non-nitrocatechol COMT inhibitors for biomedical applications.

Electroacupuncture ameliorates mechanical hypersensitivity by down-regulating spinal Janus kinase 2/signal transducer and activation of transcription 3 and interleukin 6 in rats with spared nerve injury.

BACKGROUND: Evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway participates in the pathogenesis of neuropathic pain. Our previous study revealed that electroacupuncture (EA) attenuated neuropathic pain via activation of alpha-7 nicotinic acetylcholine receptor (α7nAChR) in the spinal cord. However, whether 2 Hz EA alleviates neuropathic pain by regulating the downstream molecules JAK2/STAT3 has not been fully clarified. METHODS: Paw withdrawal threshold (PWT) was used as a marker of mechanical allodynia in rats with spared nerve injury (SNI). After applying 2 Hz EA on day 3, 7, 14 and 21 post-surgery, spinal expression of JAK2, STAT3 and pro-inflammatory cytokine interleukin (IL)-6 was examined using quantitative reverse transcription and real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Intrathecal injection of the α7nAChR antagonist alpha-bungarotoxin (α-Bgtx) was used to further explore the mechanism underlying the effects of 2 Hz EA on expression of JAK2/STAT3 in SNI rats. RESULTS: It was found that levels of spinal STAT3 and IL-6 mRNA, as well as levels of phosphorylated (p)-JAK2, p-STAT3 and IL-6 protein, were markedly increased in SNI rats. 2 Hz EA attenuated the SNI-induced up-regulation of p-JAK2, p-STAT3 and IL-6 expression in the spinal cord. Furthermore, intrathecal injection of α-Bgtx (1.0 µg/kg) not only inhibited the effect of 2 Hz EA on mechanical hypersensitivity but also ameliorated the down-regulation of p-JAK2, p-STAT3 and IL-6 expression induced by 2 Hz EA. CONCLUSION: This study revealed that 2 Hz EA attenuated SNI-induced mechanical hypersensitivity and the concomitant up-regulation of spinal JAK2, STAT3 and IL-6 in SNI rats, suggesting that suppression of the JAK2/STAT3 signaling pathway might be the mechanism underlying the therapeutic effect of 2 Hz EA on neuropathic pain.

Blood donor exposome and impact of common drugs on red blood cell metabolism.

Computational models based on recent maps of the RBC proteome suggest that mature erythrocytes may harbor targets for common drugs. This prediction is relevant to RBC storage in the blood bank, in which the impact of small molecule drugs or other xenometabolites deriving from dietary, iatrogenic, or environmental exposures ("exposome") may alter erythrocyte energy and redox metabolism and, in so doing, affect red cell storage quality and posttransfusion efficacy. To test this prediction, here we provide a comprehensive characterization of the blood donor exposome, including the detection of common prescription and over-the-counter drugs in blood units donated by 250 healthy volunteers in the Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell-Omics (REDS-III RBC-Omics) Study. Based on high-throughput drug screenings of 1366 FDA-approved drugs, we report that approximately 65% of the tested drugs had an impact on erythrocyte metabolism. Machine learning models built using metabolites as predictors were able to accurately predict drugs for several drug classes/targets (bisphosphonates, anticholinergics, calcium channel blockers, adrenergics, proton pump inhibitors, antimetabolites, selective serotonin reuptake inhibitors, and mTOR), suggesting that these drugs have a direct, conserved, and substantial impact on erythrocyte metabolism. As a proof of principle, here we show that the antacid ranitidine - though rarely detected in the blood donor population - has a strong effect on RBC markers of storage quality in vitro. We thus show that supplementation of blood units stored in bags with ranitidine could - through mechanisms involving sphingosine 1-phosphate-dependent modulation of erythrocyte glycolysis and/or direct binding to hemoglobin - improve erythrocyte metabolism and storage quality.

Effects of Acupuncture on Motor and Corticospinal Tract Impairment after Cerebral Infarction: Using Diffusion Tensor Imaging and Tractography / 中国康复理论与实践

Objective:To explore the effects of Tiaoren Tongdu Acupuncture on motor function and corticospinal tract (CST) remodeling after cerebral infarction. Methods:From February, 2017 to December, 2020, 54 patients with cerebral infarction were randomly divided into control group (n = 27) and acupuncture group (n = 27), each group was divided into subgroups 1, 2 and 3 according to the impairment of corticospinal tract, with nine cases for each subgroup. All the patients received routine medicine, while the acupuncture group received Tiaoren Tongdu Acupuncture, for four weeks. They were assessed with Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI) before and after treatment, and scanned with diffusion tensor imaging and diffusion tensor tractography, to obtain the fractional anisotropy (FA) and the bilateral FA ratio (rFA). Results:The scores of FMA and MBI, and FA and rFA increased in both groups (t > 2.841, P < 0.05) after treatment, and increased more in the acupuncture group than in the control group (t > 2.140, P < 0.05). Conclusion:Tiaoren Tongdu Acupuncture can promote the recovery of CST to improve motor function for patients with cerebral infarction.

Chinese Medicine Prevention and Treatment of Tumor Based on Ferroptosis： A Review / 中国实验方剂学杂志

Ferroptosis is a new type of cell death caused by abnormal accumulation of iron-dependent reactive oxygen species （ROS） and imbalance of redox with the participation of iron ions. In recent years， studies have found that ferroptosis is associated with various diseases and can especially regulate the development of tumors. Chinese medicine has unique advantages in tumor prevention and treatment. How to use ferroptosis theory to guide the prevention and treatment of cancer and other tumor diseases by Chinese medicine is a new research hotspot. This paper summarizes the proposal， action mechanism， and signaling pathway of ferroptosis， its application in tumor therapy， and the research on the activity of Chinese medicine based on ferroptosis. Results found that the occurrence of ferroptosis is related to iron metabolism， lipid ROS metabolism， and other signaling pathways and gene expressions. Ferroptosis can regulate tumor initiation and development， treatment， and tumor immunity， which provides strategies for tumor treatment and anti-tumor drug development. By analyzing the biological activity of Chinese medicine against ferroptosis， we found that Chinese medicines （Scutellariae Radix， Puerariae Lobatae Radix， Astragali Radix， Ginkgo， Epimedii Folium， Artemisiae Annuae Herba， and Salviae Miltiorrhizae Radix et Rhizoma）， Chinese herbal compounds （ Naotaifang， Si Junzitang， and Shenmai injection）， and Chinese medicine effective components （baicalein， dihydroartemisinin， puerarin， piperlongumine， luteolin， and quercetin） can exert antitumor and other biological activities by regulating ferroptosis. Therefore， Chinese medicine has great potential in preventing and controlling tumors and other diseases by regulating ferroptosis. This paper provides theoretical basis and research ideas for the in-depth study of ferroptosis theory and guides the prevention and treatment of tumor diseases by Chinese medicine.

Review of chemical constituents,pharmacological effects and clinical applications of Danggui Buxue Decoction and prediction and analysis of its Q-markers / 中国中药杂志

Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-β-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.

Study on effect of gypenosides on insulin sensitivity of rats with diabetes mellitus via regulating NF-κB signaling pathway / 中国中药杂志

This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg~(-1)) and metformin group(100 mg·kg~(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase β(p-IKKβ), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1β and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKβ, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKβ, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.

Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

Neuropathic pain is more complex and severely affects the quality of patients' life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.