Wenyang-Tianjing-Jieyu Decoction Improves Depression Rats of Kidney Yang Deficiency Pattern by Regulating T Cell Homeostasis and Inflammation Level.

Purpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms. Materials and Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB. Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression. Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats.

Pharmacodynamics and Mechanism of Astragali Radix and Anemarrhenae Rhizoma in Treating Chronic Heart Failure by Inhibiting Complement Activation.

Astragali radix (AR) and anemarrhenae rhizoma (AAR) are used clinically in Chinese medicine for the treatment of chronic heart failure (CHF), but the exact therapeutic mechanism is unclear. In this study, a total of 60 male C57BL/6 mice were divided into 5 groups, namely sham, model, AR, AAR, and AR-AAR. In the sham group, the chest was opened without ligation. In the other groups, the chest was opened and the transverse aorta was ligated to construct the transverse aortic constriction model. After 8 weeks of feeding, mice were given medicines by gavage for 4 weeks. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected by echocardiography. Heart weight index (HWI) and wheat germ agglutinin staining were used to evaluate cardiac hypertrophy. Hematoxylin-eosin staining was used to observe the pathological morphology of myocardial tissue. Masson staining was used to evaluate myocardial fibrosis. The content of serum brain natriuretic peptide (BNP) was detected by enzyme-linked immunosorbent assay kit. The content of serum immunoglobulin G (IgG) was detected by immunoturbidimetry. The mechanism of AR-AAR in the treatment of CHF was explored by proteomics. Western blot was used to detect the protein expressions of complement component 1s (C1s), complement component 9 (C9), and terminal complement complex 5b-9 (C5b-9). The results show that AR-AAR inhibits the expression of complement proteins C1s, C9, and C5b-9 by inhibiting the production of IgG antibodies from B cell activation, which further inhibits the complement activation, attenuates myocardial fibrosis, reduces HWI and cardiomyocyte cross-sectional area, improves cardiomyocyte injury, reduces serum BNP release, elevates LVEF and LVFS, improves cardiac function, and exerts myocardial protection.

Juan-tong-yin potentially impacts endometriosis pathophysiology by enhancing autophagy of endometrial stromal cells via unfolded protein reaction-triggered endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain largely unknown. AIM OF THE STUDY: To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. MATERIALS AND METHODS: The major components of JTY were detected using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). RESULTS: In total, 241 compounds were analyzed and identified from JTY using UPLC-MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157-a highly selective PERK inhibitor-reversed these changes. CONCLUSION: JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs.

Donepezil combined with traditional Chinese medicine has promising efficacy on mild cognitive impairment: a systematic review and meta-analysis.

Objective: Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI. Methods: We conducted a comprehensive search of various databases, including Medline (via PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA. Results: Our meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: -0.02 to 2.96). Conclusion: The combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution.

A systematic review and meta-analysis of acupuncture in Parkinson's disease with dysphagia.

Objective: The systematic review and meta-analysis aimed to comprehensively evaluate acupuncture's efficacy and safety in treating dysphagia in Parkinson's disease (PD). Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, China Knowledge Infrastructure (CNKI), China Science Journal Database (VIP), Wan-fang Database, and the China Biomedical Literature Service System (CBM) for randomized controlled trials (RCTs) comparing the efficacy of acupuncture alone or in combination with control treatment in improving dysphagia by October 2022. The degree of dysphagia was the primary outcome indicator, with secondary outcomes including serum albumin (ALB) and hemoglobin (Hb) levels, the incidence of pneumonia, and adverse events. Two investigators independently extracted information according to the inclusion and exclusion criteria. Data synthesis was calculated by RevMan (V.5.4.1) software. Results: This study included ten randomized controlled trials with 724 patients. Most RCTs have a high or uncertain risk of bias due to the lack of a blinded design. Meta-analysis showed that acupuncture combined with control treatment was superior to control treatment alone in improving Videofluoroscopic Swallowing Study (VFSS) scores (MD: 1.48; 95% CI: 1.16, 1.81; P < 0.00001) and reducing Standardized Swallowing Assessment (SSA) scores (MD: -3.08; 95% CI: -4.01, -2.15; P < 0.00001). Acupuncture combined with control therapy has a more significant benefit in improving the clinical efficiency of dysphagia in PD (RR: 1.40; 95%CI: 1.25, 1.58; P < 0.00001). Compared to the control group without acupuncture, acupuncture improved the nutritional status of patients and increased their serum ALB (MD: 3.38, 95%CI: 1.83, 4.92, P < 0.00001) and Hb levels (MD: 7.66; 95%CI: 5.57, 9.75; P < 0.00001). Three RCTs reported that the rate of pulmonary infections in the acupuncture group was lower than without acupuncture intervention (RR: 0.29, 95% CI: 0.14, 0.63; P = 0.001). Conclusion: Acupuncture could be recommended as an adjunctive treatment for dysphagia in PD. However, due to the high risk of bias in the included studies, more high-quality evidence is needed to confirm the efficacy and safety of acupuncture for dysphagia in PD. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370221.

Saponin of Aralia taibaiensis promotes angiogenesis through VEGF/VEGFR2 signaling pathway in cerebral ischemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia taibaiensis is known for its ability to promote blood circulation and dispel blood stasis, activate meridians and remove arthralgia. The saponins of Aralia taibaiensis (sAT) are the main active components that are often used to treat cardiovascular and cerebrovascular diseases. However, it has not been reported whether sAT can improve ischemic stroke (IS) by promoting angiogenesis. AIM OF THE STUDY: In this study, we investigated the potential of sAT to promote post-ischemic angiogenesis in mice and determined the underlying mechanism through in vitro experiments. METHODS: To establish the middle cerebral artery occlusion (MCAO) mice model in vivo. First of all, we examined the neurological function, brain infarct volume, and degree of brain swelling in MCAO mice. We also observed pathological changes in brain tissue, ultrastructural changes in blood vessels and neurons, and the degree of vascular neovascularization. Additionally, we established the oxygen-glucose deprivation/reoxygenation (OGD/R) -human umbilical vein endothelial cells (HUVECs) model in vitro to detect the survival, proliferation, migration and tube formation of OGD/R HUVECs. Finally, we verified the regulatory mechanism of Src and PLCγ1 siRNA on sAT promoting angiogenesis by cell transfection technique. RESULTS: In the cerebral ischemia-reperfusion mice, sAT distinctly improved the cerebral infarct volume, brain swelling degree, neurological dysfunction, and brain histopathological morphology due to cerebral ischemia/reperfusion injury. It also increased the double positive expression of BrdU and CD31 in brain tissue, promoted the release of VEGF and NO and decreased the release of NSE and LDH. In the OGD/R HUVECs, sAT significantly improved cell survival, proliferation, migration and tube formation, promoted the release of VEGF and NO, and increased the expression of VEGF, VEGFR2, PLCγ1, ERK1/2, Src and eNOS. Surprisingly, the effect of sAT on angiogenesis was inhibited by Src siRNA and PLCγ1 siRNA in OGD/R HUVECs. CONCLUSION: The results proved that sAT promotes angiogenesis in cerebral ischemia-reperfusion mice and its mechanism is to regulate VEGF/VEGFR2 and then regulate Src/eNOS and PLCγ1/ERK1/2.

Mitochondrial dysfunction in a rat model and the related risk of metabolic disorders.

OBJECTIVE: To explore whether kidney deficiency (KYD) is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic tissues. METHODS: A rat model of KYD was used, which was established using Sprague Dawley rat dams with warm preference subjected to herbal treatment that can improve kidney . The human relevance was confirmed by reduced serum corticosterone levels, and increased preference for warm location. RESULTS: KYD Rats were underdeveloped. Adenosine-triphosphate (ATP) production was reduced in the brown fat, but increased in the muscle. However, oxidative phosphorylated complexes to generate ATP and mitochondrial biogenesis marker were reduced in both tissues. When the second insult of high-fat diet (HFD) was introduced, KYD rats gained less weight yet developed more severe lipid and glucose metabolic disorders. This may be driven by disregulated liver gluconeogenesis marker forkhead box protein O1 and lipid metabolic regulator cholesterol 7 alpha-hydroxylase. CONCLUSION: KYD rats exhibited reduced mito-chondrial function in the brown fat, but were partially compensated by skeletal muscle, associated with the phenotype of warm preference and metabolic disorder, which was further exacerbated by additional HFD consumption. Future studies can focus on treatment targetting mitochondria function to reverse this phenotype.

Mechanisms and network pharmacological analysis of Yangyin Fuzheng Jiedu prescription in the treatment of hepatocellular carcinoma.

OBJECTIVE: To identify the key drugs of Yangyin Fuzheng Jiedu prescription (YFJP) and investigate their therapeutic effects against hepatocellular carcinoma (HCC) and the potential mechanism using network pharmacology. METHODS: The H22 tumor-bearing mouse model was established. Thirty male BALB/c mice were divided randomly into five groups. The mice were orally treated with either disassembled prescriptions of YFJP or saline solution continuously for 14 days. The mice were weighed every 2 days during treatment and the appearance of tumors was observed by photographing. The tumor inhibition rate and the spleen and thymus indexes were calculated. Hematoxylin and eosin and immunohistochemical staining were performed to observe the histological changes and tumor-infiltrating lymphocytes. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. The proportion of CD8+ T cells and the expression of programmed cell death protein 1 (PD-1), T cell immunoglobulin domain and mucin domain-3 (Tim-3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were analyzed using flow cytometry. The production of serum cytokines was detected using the Milliplex® MAP mouse high sensitivity T cell panel kit. The active components of the key drugs and HCC-related target proteins were obtained from the corresponding databases. The putative targets for HCC treatment were screened by target mapping, and potential active components were screened by constructing a component-target network. The interactive targets of putative targets were obtained from the STRING database to construct the protein-protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed based on potential targets. The gene-gene inner and component-target-pathway networks were constructed and analyzed to screen the key targets. Western blotting was used to evaluate the protein expression of the key targets in the tumor-bearing mouse model. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: Among the three disassembled prescriptions of YFJP, the Fuzheng prescription (FZP) showed significant antitumor effects and inhibited weight loss during the treatment of H22 tumor-bearing mice. FZP increased the immune organ index and the levels of CD8+ and CD3+ T cells in the spleen and peripheral blood of H22 tumor-bearing mice. FZP also reduced the expression of PD-1, TIGIT, and TIM3 in CD8+ T cells and the production of IL-10, IL-4, IL-6, and IL-1ß. Network pharmacology and experimental validation showed that the key targets of FZP in the treatment of HCC were PIK3CA, TP53, MAPK1, MAPK3, and EGFR. The therapeutic effect on HCC was evaluated based on HCC-related signaling pathways, including the PIK3-Akt signaling pathway, PD-L1 expression, and PD-1 checkpoint pathway in cancer. GO enrichment analysis indicated that FZP positively regulated the molecular functions of transferases and kinases on the cell surface through membrane raft, membrane microarea, and other cell components to inhibit cell death and programmed cell death. CONCLUSION: FZP was found to be the key disassembled prescription of YFJP that exerted antitumor and immunoregulatory effects against HCC. FZP alleviated T cell exhaustion and improved the immunosuppressive microenvironment via HCC-related targets, pathways, and biological processes.

Efficacy and safety of zuranolone in the treatment of major depressive disorder: a meta-analysis.

Objective: This study aimed to systematically review zuranolone's efficacy and safety in treating major depressive disorder (MDD). Methods: We conducted electronic searches in databases like PubMed, Embase, Cochrane, and Web of Science to identify randomized controlled trials using zuranolone for severe depression from study inception to September 15, 2023. Two independent reviewers screened studies, extracted data, and assessed study quality. Our meta-analysis included four studies with 1,454 patients. The findings showed significant improvements with zuranolone across various measures: Hamilton Depression Rating Scale (HAM-D) scores indicated notable alleviation in depressive symptoms (WMD: -2.03; 95% CI: -2.42 to -1.65); the treatment group's HAM-D score response rate was significantly higher than the control group's at day 15 (OR: 1.46, 95% CI: 1.11 to 1.92, P = 0.01). The meta-analysis also revealed higher remission rates for the treatment group compared to the control group at day 15 (OR: 1.68, 95% CI: 1.18 to 2.39, P = 0.03). Additionally, HAM-A scores on day 15 and MADRS scores on day 15 showed improvement, and HAM-D scores for 30 mg zuranolone on different treatment days exhibited improvement (WMD, -2.55; 95% CI, -3.24 to -1.58; P = 0.05). However, analyzing HAM-D scores on day 15 for various zuranolone doses revealed no significant differences. Importantly, zuranolone use was associated with an increased incidence of adverse reactions. Results: Our meta-analysis included four studies with 1454 patients, showing significant improvements with zuranolone across various measures, including HAM-D scores, HAM-A scores, MADRS scores, and specific HAM-D scores for 30 mg zuranolone on different treatment days. However, no significant differences were found in HAM-D scores on day 15 for various doses of zuranolone. Conclusions: Our findings suggest that zuranolone is a promising, simple, and convenient treatment for patients with major depressive disorder, offering potential guidance for clinical practice.

Function of Rice High-Affinity Potassium Transporters in Pollen Development and Fertility.

Plant High-affinity K+ transporters/K+ uptake permeases/K+ transporters (HAK/KUP/KT) transporters have been predicted as membrane H+-K+ symporters in facilitating K+ uptake and distribution, while their role in seed production remains to be elucidated. In this study, we report that OsHAK26 is preferentially expressed in anthers and seed husks and located in the Golgi apparatus. Knockout of either OsHAK26 or plasma membrane located H+-K+ symporter gene OsHAK1 or OsHAK5 in both Nipponbare and Dongjin cultivars caused distorted anthers, reduced number and germination rate of pollen grains. Seed-setting rate assay by reciprocal cross-pollination between the mutants of oshak26, oshak1, oshak5 and their wild types confirmed that each HAK transporter is foremost for pollen viability, seed-setting and grain yield. Intriguingly, the pollens of oshak26 showed much thinner wall and were more vulnerable to desiccation than those of oshak1 or oshak5. In vitro assay revealed that the pollen germination rate of oshak5 was dramatically affected by external K+ concentration. The results suggest that the role of OsHAK26 in maintaining pollen development and fertility may relate to its proper cargo sorting for construction of pollen walls, while the role of OsHAK1 and OsHAK5 in maintaining seed production likely relates to their transcellular K+ transport activity.

Research on Data Analysis Network of TCM Tongue Diagnosis Based on Deep Learning Technology.

The aim of the study is to build a tongue image intelligent analysis "end-to-end" deep learning network based on a tongue diagnosis image of traditional Chinese medicine. The tongue target region in the original image was segmented by the UNet tongue segmentation model at the front end of the network. After segmentation, the feature vector of the tongue target region was extracted by the ResNet network, and then the blood pressure on the day of shooting was fused with the feature vector extracted by the ResNet network through the convolution operation method to complete the extraction of two groups of data of tongue feature and fusion feature. Based on analyzing the data of blood pressure, tongue image, and their fusion at the end of the network, four regression analysis methods were used to predict the stage mean value. After training, the model is tested with the test set data, and the test results are evaluated with mean absolute error (MAE). The prediction error of the model based on the fusion data of tongue image and blood pressure on the day of shooting was lower than that of the other two data modes. The UNet tongue segmentation model combined with the ResNet network can realize the automatic extraction of tongue image features. The extracted features combined with machine learning modeling can be used to explore the complex hierarchical mathematical association between tongue image and clinical data. The experimental results show that the multimodal data fusion method is an important way to mine the clinical value of the TCM tongue image.

A systematic review and meta-analysis of the clinical efficacy and safety of Chinese patent medicines in treating subacute thyroiditis.

BACKGROUND: This meta-analysis was performed to evaluate the clinical efficacy and safety of Chinese patent medicines in the treatment of subacute thyroiditis (SAT). METHODS: Chinese databases were searched using a combination of "patent Chinese medicine", "traditional Chinese medicine", "traditional Chinese and western medicine", "sub-thyroiditis", and "subacute thyroiditis". Studies that set Chinese patent medicine treatment of SAT as the experimental group were selected. Then, meta-analysis was performed by RevMan 5.3. RESULTS: A total of 12 studies were included, and most of them had a high risk of bias (low quality). The heterogeneity test results of clinical efficacy showed that Chi2=6.21, df=7, P=0.52>0.1, and I2=0%<50%. Then, the fixed effects model (FEM) was used, with OR =2.80; 95% confidence interval (CI): 1.89-4.13. The heterogeneity test of recurrence rate showed that Chi2=10.69, df=9, P=0.30>0.1, and I2=16%<50%. The heterogeneity test of erythrocyte sedimentation rate showed that I2=97%, P<0.00001, MD =-10.02; 95% CI: -12.88 to -7.16, and P<0.00001. The heterogeneity test of free triiodothyronine showed that Chi2=500.75, I2=99%>50%, P<0.00001, MD =-2.88; 95% CI: -3.85 to -1.91; Z=5.83, and P<0.00001. The heterogeneity test of free thyroid hormone showed that Chi2=25.15, I2=72%>50%, P=0.0007, MD =-2.48; 95% CI: -3.69 to -1.26; Z=3.99, and P<0.0001. The heterogeneity test of the occurrence of adverse reactions showed that Chi2=11.28, df=11, P=0.42>0.1, and I2=3%<50%, and the combined effect size was Z=6.49 and P<0.00001, with OR =0.21; 95% CI: 0.13-0.34. DISCUSSION: The meta-analysis of this study confirms that Chinese patent medicines have considerable clinical effects in the treatment of SAT. They can reduce the recurrence rate, adjust the levels of free triiodothyronine and free thyroid hormone, and have good safety.

A Nonlinear Association between Tongue Fur Thickness and Tumor Marker Abnormality: A Cross-Sectional Study.

BACKGROUND: Many associations between tongue fur and different physiological and biochemical indexes have been revealed. However, the relationship between tongue fur and tumor markers remains unexplored. METHODS: We collected the medical examination reports of 1625 participants. Participants were residents of Chengdu, China, undergoing routine health checkups at the health management center of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. The participants' tongue fur thickness was measured using the DAOSH four-diagnostic instrument. Tumor marker levels, including t-PSA, AFP, CEA, CA125, and CA199, were measured in the clinical laboratory. Curve-fitting and multivariable logistic regression were used to analyze the association between tongue fur thickness and tumor marker abnormality. RESULTS: Curve-fitting showed that the relationship between tongue fur thickness and abnormal tumor marker rate was nonlinear, similar to a U shape. As the tongue fur thickness value increased, the abnormal tumor marker probability initially decreased and then increased. Logistic regression showed that, in the crude model, compared with the thin tongue fur group, the odds ratios (ORs) and 95% confidence intervals (CIs) of the less or peeling tongue fur group and thick tongue fur group for tumor marker abnormality were 1.79 (1.02-3.17) and 1.70 (1.13-2.54), respectively. After adjusting gender, age, body mass index (BMI), smoking history, drinking history, tongue color, the form of the tongue, and fur color, the ORs and 95% CIs of the less or peeling tongue fur group and thick tongue fur group were 1.93 (1.04-3.57) and 1.82 (1.17-2.81), respectively. CONCLUSIONS: Excessive or very little tongue fur is associated with tumor marker abnormality. Further cross-sectional studies are needed to evaluate the clinical value of tongue fur for cancer diagnosis and screening.

Efficacy of the acupressure wrist-ankle strap in mild insomnia patients with anxiety disorders: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is very common in current society, and patients are often accompanied by a certain degree of anxiety, depression, etc. Recent studies have found that the hypothalamic-pituitary-adrenal (HPA) axis excitement-inhibition state is an important indicator of sleep quality. Wrist-ankle acupuncture (WAA) is safe and effective for insomnia. Based on WAA theory, the acupressure wrist-ankle straps are portable WAA point compression straps that can treat diseases by automatically applying pressure to the treatment location and being operated by patients themselves. We design this trial to evaluate the clinical effect of the acupressure wrist-ankle strap in the treatment of mild insomnia patients with anxiety disorders. METHODS/DESIGN: This trial is a parallel-design, patients-assessor blinded, randomized, sham-controlled. In total, 114 patients diagnosed with mild insomnia and anxiety disorders will be randomly assigned into two groups, the acupressure wrist-ankle strap group or the non-acupressure wrist-ankle strap group; they will receive treatments for eight weeks with five sessions each week. Rating scales, sleep monitors, and laboratory tests will be used to observe the clinical effect. From the perspective of the circadian secretion of peripheral blood-related hormones in the hypothalamic-pituitary-adrenal (HPA) axis, the possible mechanism of acupressure wrist-ankle straps for treating insomnia is studied. DISCUSSION: The results of this study will confirm the efficacy of acupressure wrist-ankle strap in treating mild insomnia patients with anxiety disorder and whether its mechanism is related to the HPA axis. The acupressure wrist-ankle strap may become a pure physical, no side effect treatment of mild insomnia. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039352 . Registered on 24 October 2020.

The Efficacy and Safety of Acupuncture for Treating Osteoporotic Vertebral Compression Fracture- (OVCF-) Induced Pain: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) are common health issues in the elderly that cause chronic pain in over one-third of patients. This study was sought to evaluate the efficacy and safety of acupuncture for alleviating pain caused by OVCFs. METHODS: We performed a search of 8 electronic databases for publications from the inception to 30th March 2021. Eligible studies were randomized clinical trials (RCTs) that evaluated the effect of acupuncture for the treatment of OVCFs. Two investigators evaluated literature quality and extracted data independently. RevMan V.5.4.1 was used for data analyses, with pooled risk estimates presented as mean difference (MD) or relative risk (RR) along with corresponding 95% confidence intervals (CIs), as appropriate. RESULTS: Fourteen RCTs involving 1,130 patients were included in this meta-analysis. Compared with the control group, acupuncture showed a greater benefit on pain reduction caused by OVCFs (1 week: MD = -1.26, 95% CI: (-1.82,-0.70); 1 month: MD = -1.63, 95% CI: (-1.82,-1.43); 6 months: MD = -1.13, 95% CI: (-1.55, -0.70)). Acupuncture treatment was also associated with fewer adverse events, lower ODI index, and higher bone density than the control group (safety: (RR: 0.30, 95% CI: 0.12-0.75); ODI: MD = -3.19, 95% CI: (-5.20, -1.19); bone density: MD = 0.15, 95% CI: (0.05, 0.26)). The GRADE quality of these results was assessed as low or very low. CONCLUSIONS: Compared with the control treatment, acupuncture was more effective and safer in relieving the pain caused by OVCF and made a greater improvement on patient's ODI score and bone density. Given the low level of our study evidence, future high-quality studies are needed to verify our study findings.

[Discussion on relationship between autophagy and endometriosis based on pathogenesis of "dampness and stasis"].

Endometriosis(EMs) is a stubborn gynecological disease caused by persistent immune-inflammatory effects, and is known as "benign tumor" because of its similar characteristics to malignant tumors. National physician master Professor BAN Xiu-wen believes that the spread of damp-evil is the pathologic foundation for inflammatory response of ectopic endometrium; accumulation of blood stasis is the pathological product of continuous inflammatory attacks, and the combination of dampness and stasis is the main pathogenesis for refractory EMs. Modern researches have shown that immune-inflammatory effect is the key mechanism for development of EMs, and is closely related to cell autophagy, all of which have made it become the hot spots in research of the pathogenesis, diagnosis and treatment of EMs. Therefore, with immune-inflammatory effect as the breakthrough point in this research, and with reference to the related research of autophagy, the correlation between "combination of dampness and stasis" and abnormal autophagy-induced immune inflammatory response in ectopic endometrium was discussed, to provide guidance for the clinical application of traditional Chinese medicine and modern research.

Yangyin Fuzheng Jiedu Prescription exerts anti-tumor immunity in hepatocellular carcinoma by alleviating exhausted T cells.

BACKGROUND: Yangyin Fuzheng Jiedu Prescription (YFJP), a formulated Chinese herbal medicine, has been used for several decades in the treatment of hepatocellular carcinoma (HCC). Previous studies have demonstrated its anti-tumor efficacy, but the mechanism of action remains uncharacterized. This study aims to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice. PURPOSE: This study aimed to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice. METHODS: A total of 50 male H22 tumor-bearing mice were randomly divided into 6 groups and continuous administered either different doses of YFJP or cyclophosphamide (CTX) or normal saline. for 2 weeks. The tumor appearance was observed by taking photos, and the tumor volume, weight, spleen and thymus index were calculated. Morphology of tumor infiltrating lymphocytes and the CD8+ T lymphocytes were detected through HE staining immunohistochemistry respectively. The frequency of CD3+, CD8+ T cell subsets and co-inhibitory receptors PD-1, TIGIT, Tim-3 on CD8+ T cell in spleen, peripheral blood and tumor tissue was performed by flow cytometry. Meanwhile, the killing and apoptotic functions of CD8+ T cells in tumor tissues were also detected by the same method. The levels of cytokines in peripheral blood were detected by Milliplex map mouse highs sensitivity T Cell kit. The expression of T cell transcription factor T-bet and Eomes in tumor tissues were observed by Western blot. RESULTS: We found that YFJP could effectively inhibit the solid tumor growth and spleen indexes, but showed little effect on the body weight in the established mouse model of HCC. Furthermore, we investigated the effect of YFJP on the phenotypic and functional changes of T cells. The results showed that YFJP could maintain the high ratio of CD3+ and CD8+ T cells in the peripheral blood, spleen, and tumor tissues while decreasing the expression of programmed cell death-1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin domain and mucin domain-3 (Tim-3) in CD8+ T cells, respectively. Surprisingly, PD-1/Tim-3 double-positive T cells in the peripheral blood and tumor tissues were significantly decreased. Additionally, YFJP restored the cytotoxicity of tumor-infiltrating T cells and delayed their apoptosis in H22 tumor-bearing mice. In addition, treatment with YFJP significantly decreased the expression of inflammatory and immunosuppressive cytokines (including IL-1ß, IL-6, and IL-10) in the serum and tumor tissues whereas enhancing that of effector cytokines TNF-α, and IFN-γ. Moreover, T cell transcription factors T-bet increased and Eomes degraded in the tumor tissues upon YFJP treatment. CONCLUSION: In conclusion, these results demonstrated that YFJP could simultaneously exert anti-tumor immune response in H22 tumor-bearing mice by alleviating T cell exhaustion and immunosuppression.

Network differentiation: A computational method of pathogenesis diagnosis in traditional Chinese medicine based on systems science.

Resembling the role of disease diagnosis in Western medicine, pathogenesis (also called Bing Ji) diagnosis is one of the utmost important tasks in traditional Chinese medicine (TCM). In TCM theory, pathogenesis is a complex system composed of a group of interrelated factors, which is highly consistent with the character of systems science (SS). In this paper, we introduce a heuristic definition called pathogenesis network (PN) to represent pathogenesis in the form of the directed graph. Accordingly, a computational method of pathogenesis diagnosis, called network differentiation (ND), is proposed by integrating the holism principle in SS. ND consists of three stages. The first stage is to generate all possible diagnoses by Cartesian Product operated on specified prior knowledge corresponding to the input symptoms. The second stage is to screen the validated diagnoses by holism principle. The third stage is to pick out the clinical diagnosis by physician-computer interaction. Some theorems are stated and proved for the further optimization of ND in this paper. We conducted simulation experiments on 100 clinical cases. The experimental results show that our proposed method has an excellent capability to fit the holistic thinking in the process of physician inference.

The RIG-I Signal Pathway Mediated Panax notoginseng Saponin Anti-Inflammatory Effect in Ischemia Stroke.

Panax notoginseng saponins (PNS), the main bioactive constituents of a traditional Chinese herb Panax notoginseng, were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia. The oxygen-glucose-deprived (OGD) model of rat brain microvascular endothelial cells (BMECs) was used in this study. The alteration of gene expression in rat BMECs after PNS treatment was measured by microarray and indicated that there were 38 signaling pathways regulated by PNS. Among them, RIG-I receptor and related signaling molecules TNF receptor-associated factor 2 (Traf2) and nuclear factor-kappa B (NF-κB) were significantly suppressed by PNS, which was verified again in OGD-induced BMECs measured by FQ-PCR and western blotting and in middle cerebral artery occlusion (MCAO) rats measured by immunohistochemistry. The levels of TNF-α, IL-8, and the downstream cytokines regulated by RIG-I receptor pathway were also decreased by PNS. Meanwhile, the neurological evaluation, hematoxylin and eosin (HE) staining, and Evans blue staining were conducted to evaluate the effect of PNS in MCAO rats. Results showed PNS significantly improved functional outcome and cerebral vascular leakage. Flow cytometry showed the number of the inflammatory cells infiltrated in brain tissue was decreased in PNS treatment. Our results identified that RIG-I signaling pathway mediated anti-inflammatory properties of PNS in cerebral ischemia, which provided the novel insights of PNS application in clinics.

Cinnamon as Dietary Supplement Caused Hyperlipidemia in Healthy Rats.

OBJECTIVE: Cinnamon is a cooking spice and a medicinal herb. It is increasingly used as a health supplement due to its perceived benefit to prevent and or manage type 2 diabetes and metabolic disorders. However, it is unclear if regular consumption of this medicinal plant will interfere with normal physiological functions. Therefore, this study investigated the impact of daily cinnamon supplements on glucose and lipid metabolic profiles in healthy rats. METHODS: Male rats (Sprague Dawley, 8 weeks) were supplied with cinnamon in their diet (equivalent to ∼1 g/day in humans) for two weeks. Blood glucose and lipid levels, as well as metabolic markers in both liver and abdominal white adipose tissue, were measured. RESULTS: Cinnamon significantly increased fat mass and blood cholesterol and low-density lipoprotein (LDL) levels, but reduced fasting blood glucose level by 12%. Liver functional enzymes were normal in rats consuming cinnamon. However, several lipid metabolic markers were impaired which may contribute to dyslipidemia, including two main switches for energy metabolism (sirtuin 1 and peroxisome proliferator-activated receptor-gamma coactivator-1α) and the LDL receptor. However, de novo lipid synthesis enzymes and inflammatory markers were also reduced in the liver by cinnamon treatment, which may potentially prevent the development of steatosis. Markers for lipid oxidation were downregulated in fat tissue in cinnamon-treated rats, contributing to increased fat accumulation. CONCLUSION: Daily low-dose cinnamon supplementation seems to promote abdominal adipose tissue accumulation and disturb lipid homeostasis in healthy rats, raising the concerns regarding daily use in healthy people.