Research progress of Paris polyphylla in the treatment of digestive tract cancers.

Cancer has become one of the most important causes of human death. In particular, the 5 year survival rate of patients with digestive tract cancer is low. Although chemotherapy drugs have a certain efficacy, they are highly toxic and prone to chemotherapy resistance. With the advancement of antitumor research, many natural drugs have gradually entered basic clinical research. They have low toxicity, few adverse reactions, and play an important synergistic role in the combined targeted therapy of radiotherapy and chemotherapy. A large number of studies have shown that the active components of Paris polyphylla (PPA), a common natural medicinal plant, can play an antitumor role in a variety of digestive tract cancers. In this paper, the main components of PPA such as polyphyllin, C21 steroids, sterols, and flavonoids, amongst others, are introduced, and the mechanisms of action and research progress of PPA and its active components in the treatment of various digestive tract cancers are reviewed and summarized. The main components of PPA have been thoroughly explored to provide more detailed references and innovative ideas for the further development and utilization of similar natural antitumor drugs.

Phytochelatin-Mediated Cultivar-Dependent Cd Accumulations of Lactuca sativa and Implication for Cd Pollution-Safe Cultivars Screening.

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.

Myofascial acupuncture versus routine acupuncture for mechanical neck pain: a protocol for a multicentre randomised controlled trial.

INTRODUCTION: Mechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP. METHODS AND ANALYSIS: The study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the 'Sancai-Tianbu' myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2200061453.

Hesperidin Reversed Long-Term N-methyl-N-nitro-N-Nitroguanidine Exposure Induced EMT and Cell Proliferation by Activating Autophagy in Gastric Tissues of Rats.

Gastric cancer is a common malignant tumor worldwide. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the most important inducing factors of gastric cancer. Autophagy can affect the occurrence and development of gastric cancer, but the mechanism is not clear. Chemoprevention has been shown to be a rational and very promising approach to the prevention of gastric cancer. Hesperidin is a citrus flavone, an abundant polyphenol in citrus fruits and traditional Chinese medicine. It has an excellent phytochemistry that plays an intervention role in gastric cancer. However, it is unclear whether long-term exposure to MNNG will affect the occurrence of gastric cancer by regulating autophagy and whether hesperidin can play an intervention role in this process. In the present study, we demonstrated that long-term MNNG exposure inhibits autophagy in stomach tissues of rats, promotes the epithelial-mesenchymal transition (EMT) process and cell proliferation and suppresses the activity of the PI3K/AKT pathway. We further found that after rapamycin-activated autophagy, long-term MNNG exposure promoted cell proliferation and EMT were inhibited. In addition, hesperidin promotes autophagy and the activity of the PI3K/AKT pathway, as well as the suppression of proliferation and EMT in the stomach tissues of rats. Our findings indicate that hesperidin reverses MNNG-induced gastric cancer by activating autophagy and the PI3K/AKT pathway, which may provide a new basis for the early prevention and treatment of MNNG-induced gastric cancer.

[Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism].

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.

Effect of electroacupuncture on cyclic adenosine monophosphate-protein kinase A-vanillic acid receptor subtype 1 of the transient receptor potential/PLK-protein kinase C-vanillic acid receptor subtype 1 of the transient receptor potential pathway based on RNA-seq analysis in prostate tissue in rats with chronic prostatitis/chronic pelvic pain syndrome.

Objective: To investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: Thirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 µL of complete Freund's adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR. Results: The RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01). Conclusion: The analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.

Neuroanatomical subtypes of schizophrenia and relationship with illness duration and deficit status.

BACKGROUND: The heterogeneity of schizophrenia (SCZ) regarding psychopathology, illness trajectory and their inter-relationships with underlying neural substrates remain incompletely understood. In a bid to reduce illness heterogeneity using neural substrates, our study aimed to replicate the findings of an earlier study by Chand et al. (2020). We employed brain structural measures for subtyping SCZ patients, and evaluate each subtype's relationship with clinical features such as illness duration, psychotic psychopathology, and additionally deficit status. METHODS: Overall, 240 subjects (160 SCZ patients, 80 healthy controls) were recruited for this study. The participants underwent brain structural magnetic resonance imaging scans and clinical rating using the Positive and Negative Syndrome Scale. Neuroanatomical subtypes of SCZ were identified using "Heterogeneity through discriminative analysis" (HYDRA), a clustering technique which accounted for relevant covariates and the inter-group normalized percentage changes in brain volume were also calculated. RESULTS: As replicated, two neuroanatomical subtypes (SG-1 and SG-2) were found amongst our patients with SCZ. The subtype SG-1 was associated with enlargements in the third and lateral ventricles, volume increase in the basal ganglia (putamen, caudate, pallidum), longer illness duration, and deficit status. The subtype SG-2 was associated with reductions of cortical and subcortical structures (hippocampus, thalamus, basal ganglia). CONCLUSIONS: These replicated findings have clinical implications in the early intervention, response monitoring, and prognostication of SCZ. Future studies may adopt a multi-modal neuroimaging approach to enhance insights into the neurobiological composition of relevant subtypes.

Expression Profiling of L5-S2 Spinal Cord Dorsal Horn in a Rat Model of Chronic Pelvic Pain Syndrome Uncovers Potential Mechanism of Electroacupuncture Mediated Inflammation and Pain Responses.

Purpose: We aim to explore expression profiles of genes in SCDH of CPPS model rat relevant to pain and inflammation by RNA-Seq and to investigate the mechanism of anti-inflammatory and analgesic of EA. Methods: Thirty-six SD male rats were randomly divided into three groups (n = 12): sham operation, model, and EA. The rat CPPS model was established by injecting CFA into the ventral lobes of the prostate. The rats in EA group were treated at Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) for a total of 20 times, with a frequency of 2/100Hz. Mechanical allodynia, H&E staining and ELISA were used to detect the changes of pain threshold and tissue inflammation; RNA-Seq technique was used for profiling gene changes in SCDH and qRT-PCR was used for further validation. Results: Persistent mechanical allodynia and severe tissue inflammatory reaction both occurred in CPPS rats. After EA therapy, the pain sensitivity and inflammatory response of CPPS rats decreased significantly. RNA-Seq identified that a total of 46 DEGs were significantly up-regulated and 65 DEGs down-regulated after EA. GO enrichment showed that EA was mainly reflected in the regulation of the immune system by participating in the regulation of leukocyte, neutrophil cellular processes and cytokine metabolism. KEGG enrichment demonstrated that signal transduction and immune system were the most significant pathways. We further identified that the expressions of Pik3r2, Akt1, and Casp9 were significantly up-regulated and Jak2 and Stat3 down-regulated in the PI3K-AKT/JAK-STAT signal pathway. Conclusion: Our study revealed that immune and inflammatory responses are the main biological events that induce chronic pelvic pain in rats, and EA can exert anti-inflammatory and analgesic effects by regulating the expression of related genes on PI3K-AKT/JAK-STAT signal pathway in SCDH. This study provided putative novel targets of EA, which may have anti-inflammatory and analgesic effects of CPPS.

[Application of teaching method for the interpretation of acupoint names in the course of Science of Meridians and Acupoints].

The paper summarizes the valuable experience of the famous teachers of all generations in the teaching & research room of meridians and acupoints of Beijing University of CM. The shortcomings are presented when the acupoints are explained in accordance with the flowing route of meridians in classroom teaching of Science of Meridians and Acupoints. Hence, it is proposed that the acupoint names should be interpreted specially for the acupoints distributed on the same meridians or adjacent ones. It is suggested to emphasize the correlation of each acupoint with its adjacent ones from the perspective of the cultural connotation of acupoint names, and then, the differences and similarities in their clinical indications can be analyzed. Eventually, a new approach to the classroom teaching of Science of Meridians and Acupoints may be provided to guide the excavation of traditional cultural connotation and establish the cultural self-confidence and professional identity.

[Effect of moxibustion combined with acupoint catgut embedding on IL-6/JAK/STAT3 signaling pathway in colonic mucosa of ulcerative colitis rats].

OBJECTIVE: To observe the effect of moxibustion combined with acupoint catgut embedding on the content of interleukin 6 (IL-6), and the expressions of janus activated kinase (JAK), signal transducer and activator of transcription 3 (STAT3) in colonic mucosa of rats with ulcerative colitis (UC), so as to explore its mechanism underlying improvement of UC. METHODS: Thirty SD rats were randomly divided into normal, model, acupoint catgut embedding (ACE), moxibustion and acupoint catgut embedding combined with moxibustion (combination) groups (n=6 rats in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral "Tianshu" (ST25), "Dachangshu" (BL25) and "Shangjuxu" (ST37) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed by H.E. staining, the level of IL-6 in colonic mucosa was assayed by ELISA, and the expressions of JAK and STAT3 in colonic mucosa were detected by immunohistochemistry and Western blot. RESULTS: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and combination groups. After modeling, the content of colonic IL-6, and the expression levels of JAK and STAT3 were obviously increased (P<0.01) in the model group relevant to the normal group. Following the intervention, the increase of IL-6 contents, and JAK and STAT3 expressions were reversed (P<0.05, P<0.01) in moxibustion, ACE and combination groups. The therapeutic effects of moxibustion combined with ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of JAK and STAT3 expression (P<0.01). CONCLUSION: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effect in suppressing the activation of IL-6/JAK/STAT3 signaling pathway.

[Effect of electroacupuncture on pain threshold and expression of pain-related factors cyclooxygenase-2, prostaglandin E2 and ß-endorphin in rats with chronic pelvic pain syndrome].

OBJECTIVE: To explore the possible mechanism of electroacupuncture (EA) underlying improvement of chronic pelvic pain syndrome (CPPS). METHODS: Fifty SD rats were randomly divided into control, model, sham operation, EA and sham EA groups (n=10 rats in each group). The CPPS model was established by injecting complete Freund's adjuvant (CFA, 50 µL) into the ventral lobes of the prostate. EA (2 Hz/100 Hz) was applied to "Guanyuan"(CV4), "Zhongji"(CV3), "Sanyinjiao" (SP6) and "Huiyang"(BL35) once daily for 40 min, 5 days a week for 4 weeks, while rats in the sham EA group were treated with the same acupoints but without electrical stimulation. Mechanical pain threshold (MPT) and heat pain threshold (HPT) were measured before and after intervention. The body weight and prostate weight were measured and prostate index was calculated. Histopathological changes of prostate tissue were observed by HE staining. The levels of cycloxygenase-2 (COX-2), prostaglandin E2 (PGE2) and ß-endorphin (ß-EP) in prostate tissue were detected by ELISA. RESULTS: Compared with the control and sham operation groups, the MPT and HPT were significantly lower (P<0.01), and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly increased (P<0.01), while the content of ß-EP was significantly decreased (P<0.01) in the model group. Compared with the model group, the MPT and HPT were significantly increased (P<0.01) after 3 and 4 courses of treatment, and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly decreased (P<0.01), while the content of ß-EP was significantly increased (P<0.01) in the EA group, rather than in the sham EA group (P>0.05). CONCLUSION: EA can effectively relieve pain in CPPS rats, which may be related to its functions in down-regulating COX-2 and PGE2, and up-regulating ß-EP.

[Analysis of CiteSpace knowledge map for traditional Chinese medicine prevention and treatment of cerebral small vessel diseases].

This study aims to analyze the research on the prevention and treatment of cerebral small vessel diseases(CSVDs) with traditional Chinese medicine(TCM) based on knowledge map, and to preliminarily explore the research hotspots and trends. To be specific, articles on TCM treatment of CSVDs in CNKI, Wanfang, and VIP(from establishment to November 2021) were retrieved, followed by bibliometric analysis. Then CiteSpace 5.7 R4 and Gephi were employed for generation of maps on annual number of articles, author cooperation, institution cooperation, keyword co-occurrence, keyword clustering, and keyword emergence. A total of 106 eligible articles were screened out, and the annual number of articles presented a steady upward trend. A total of 277 authors were included in the author cooperation network, among whom CHEN Zhigang published the most articles. A total of 87 institutions were included in the institution cooperation network, among which Dongfang Hospital of Beijing University of Chinese Medicine showed the most frequent cooperation with other institutions. Keyword clustering showed that research on the TCM treatment of CSVDs mainly focused on five aspects: related disease research, neurological function deficits, disease nature and location in TCM, TCM treatment methods, and formulas. The prevention and treatment of CSVDs with TCM in China has been developing steadily in the past ten years, and TCM has unique advantages in the prevention and treatment of this disease. The knowledge maps vividly demonstrated the development and research hotspots and trends in this field. The result is expected to provide a reference for further research in this field.

Potent Inhibition of Human Cytochrome P450 3A4 by Biflavone Components from Ginkgo Biloba and Selaginella Tamariscina.

CYP3A4-mediated Phase I biotransformation is the rate-limiting step of elimination for many commonly used clinically agents. The modulatory effects of herbal medicines on CYP3A4 activity are one of the risk factors affecting the safe use of drug and herbal medicine. In the present study, the inhibitory effects of nearly hundred kinds of herbal medicines against CYP3A4 were evaluated based on a visual high-throughput screening method. Furthermore, biflavone components including bilobetin (7-demethylginkgetin, DGK), ginkgetin (GK), isoginkgetin (IGK), and amentoflavone (AMF) were identified as the main inhibitory components of Ginkgo biloba L. (GB) and Selaginella tamariscina (P. Beauv.) Spring (ST), which displayed very strong inhibitory effects toward CYP3A4. The inhibitory effects of these biflavones on clinical drugs that mainly undergo CYP3A4-dependent metabolism were evaluated. The IC 50 of GK toward tamoxifen, gefitinib and ticagrelor were found to be of 0.478 ± 0.003, 0.869 ± 0.001, and 1.61 ± 0.039 µM, respectively. These results suggest the potential pharmacokinetic interactions between the identified biflavones and clinical drugs undergoing CYP3A4-mediated biotransformation. The obtained information is important for guiding the rational use of herbal medicine in combination with synthetic pharmaceuticals.

[Effect of Astragali Radix-Curcumae Rhizoma compatibility combined with 5-fluorouracil on Th17/Treg balance and tumor-related mRNA and protein expression in orthotopic xenograft model mice of CT26.WT colorectal carcinoma].

Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-ß(TGF-ß), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-ß, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-ß, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice.

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice / 神经科学通报·英文版

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

Application of teaching method for the interpretation of acupoint names in the course of Science of Meridians and Acupoints / 中国针灸

The paper summarizes the valuable experience of the famous teachers of all generations in the teaching & research room of meridians and acupoints of Beijing University of CM. The shortcomings are presented when the acupoints are explained in accordance with the flowing route of meridians in classroom teaching of Science of Meridians and Acupoints. Hence, it is proposed that the acupoint names should be interpreted specially for the acupoints distributed on the same meridians or adjacent ones. It is suggested to emphasize the correlation of each acupoint with its adjacent ones from the perspective of the cultural connotation of acupoint names, and then, the differences and similarities in their clinical indications can be analyzed. Eventually, a new approach to the classroom teaching of Science of Meridians and Acupoints may be provided to guide the excavation of traditional cultural connotation and establish the cultural self-confidence and professional identity.

Effect of Astragali Radix-Curcumae Rhizoma compatibility combined with 5-fluorouracil on Th17/Treg balance and tumor-related mRNA and protein expression in orthotopic xenograft model mice of CT26.WT colorectal carcinoma / 中国中药杂志

Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

Analysis of CiteSpace knowledge map for traditional Chinese medicine prevention and treatment of cerebral small vessel diseases / 中国中药杂志

This study aims to analyze the research on the prevention and treatment of cerebral small vessel diseases(CSVDs) with traditional Chinese medicine(TCM) based on knowledge map, and to preliminarily explore the research hotspots and trends. To be specific, articles on TCM treatment of CSVDs in CNKI, Wanfang, and VIP(from establishment to November 2021) were retrieved, followed by bibliometric analysis. Then CiteSpace 5.7 R4 and Gephi were employed for generation of maps on annual number of articles, author cooperation, institution cooperation, keyword co-occurrence, keyword clustering, and keyword emergence. A total of 106 eligible articles were screened out, and the annual number of articles presented a steady upward trend. A total of 277 authors were included in the author cooperation network, among whom CHEN Zhigang published the most articles. A total of 87 institutions were included in the institution cooperation network, among which Dongfang Hospital of Beijing University of Chinese Medicine showed the most frequent cooperation with other institutions. Keyword clustering showed that research on the TCM treatment of CSVDs mainly focused on five aspects: related disease research, neurological function deficits, disease nature and location in TCM, TCM treatment methods, and formulas. The prevention and treatment of CSVDs with TCM in China has been developing steadily in the past ten years, and TCM has unique advantages in the prevention and treatment of this disease. The knowledge maps vividly demonstrated the development and research hotspots and trends in this field. The result is expected to provide a reference for further research in this field.