The influence of adjunctive traditional Chinese medicine therapy on survival in primary liver cancer: a real-world study based on electronic medical records.

Background: Traditional Chinese medicine (TCM) effectively improves the survival rate and quality of life of primary liver cancer patients, but high-level evidence is lacking. Patients and methods: Patients were selected from 5 tertiary hospitals in Henan Province, China. Two thousand sixty-seven patients with primary liver cancer were included in the study. The electronic medical records (EMRs) of the patients were collected. Patients who received adjunctive TCM treatment and underwent treatment cumulative time for more than 1 month were classified as the TCM intervention cohort. Patients who did not receive adjunctive TCM treatment or underwent treatment cumulative time for less than 1 month were classified as the non-TCM intervention cohort. The main outcome indicators were the survival rate and overall survival time. The propensity score inverse probability weighting method was used to balance the differences between the groups. Results: The primary cohort comprised 2,067 patients, including 462 patients who received adjunctive TCM treatment and 1,605 patients who did not receive adjunctive TCM treatment. The results of the Kaplan‒Meier survival curve indicated that the survival rate and median survival time of the exposure group before and after propensity score weighting were greater than those of the control group (p < 0.0001). Univariate Cox regression analysis after propensity score weighting showed that adjunctive TCM treatment was an independent protective factor for survival [regression coefficient = -0.215, hazard ratio (HR) = 0.8066, 95% confidence interval (CI) (0.6609-0.9844)]. Conclusion: Adjuvant treatment with TCM has a protective effect on the prognosis of patients with primary liver cancer; it can reduce the mortality and prolong the survival time.

A comparative metabolomics study between grain-sized moxibustion and suspended moxibustion on rats with gastric ulcers.

Grain-sized moxibustion (GS-Moxi) and suspended moxibustion (S-Moxi) represent the two typical local heat therapies in Traditional Chinese Medicine (TCM) and have been extensively used in treating gastric ulcers (GU) in China. However, the difference in biological response between the two moxibustion therapies in treating GU remains unclear. Here we investigated the therapeutic effect and potential mechanistic difference underlying the two moxibustion methods. Ethanol-induced GU model was established and was treated with GS-Moxi or S-Moxi at ST36 and ST21 for 5 days separately. And then, gastric histopathological examination, immunohistochemical staining for repair factors (EGFR, VEGF, Ki67), and 1H NMR-based metabolomics analysis of plasma and stomach of rats were conducted. We found GS-Moxi and S-Moxi effectively alleviated gastric damage and significantly increased the expression of related repair factors. However, S-Moxi corrected aberrant energy metabolism and lipids metabolism in GU rats but had little effect on neurotransmitter-related metabolism, while GS-Moxi regulated energy metabolism and neurotransmitter-related metabolism in GU rats but had no effect on lipids metabolism. We further proposed that the main target of S-Moxi may be liver and vasculature, whereas GS-Moxi specially targeted the stomach via regulating nervous system. This study strongly verified the outstanding gastroprotective effects of moxibustion and enriched our understanding of the varied biological responses triggered by different moxibustion methods.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

The anti-tumor effects of Celastrus orbiculatus Thunb. and its monomer composition: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb. has been included in "The Plant List" (http://www. theplantlist.org) and is the most widely researched species in its genus. It is called Nanshe Teng in China. Celastrus orbiculatus Thunb. is a plant of Euonymus and it's medicinal part is the vine and stem. It is also called Alias Dragon grass, Yellow Yine, etc. It has good anti-tumor, anti-inflammatory and other effects. More and more studies have shown that Celastrus orbiculatus Thunb. has a significant therapeutic effect on a variety of malignant tumors. The research on Celastrus orbiculatus Thunb. has a good application prospect for the development of anti-tumor drugs. However, no systematic reports on Celastrus orbiculatus Thunb. have been published before. AIM OF THE REVIEW: This paper summarizes the metabolic products for anti-tumor and the mechanism for anti-tumor of Celastrus orbiculatus Thunb. to provide reference for further development and research. MATERIALS AND METHODS: The relevant information on Celastrus orbiculatus Thunb. was collected from the scientific databases including PubMed, CNKI, ScienceDirect, Wiley, Springer, Web of Science, Google Scholar, Baidu Scholar, Pharmacopoeia of the People's Republic of China and Flora Republicae Popularis Sinicae, etc. RESULTS: At present, more than 200 compounds have been identified from Celastrus orbiculatus Thunb., including terpenoids, flavonoids, phenylpropanoids, polyketides and benzene derivatives, etc. Pharmacological studies have shown that Celastrus orbiculatus Thunb. has a variety effects of inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cells invasion, metastasis and angiogenesis, reversing multi-drug resistance, and also collaborativing Micro RNA to inhibit tumor growth, etc. It has a significant effect on gastric cancer, liver cancer, lung cancer, etc. The extracts of Celastrus orbiculatus Thunb. have been widely used in experiments, and the toxic and side effects are small. CONCLUSIONS: Celastrus orbiculatus Thunb. is rich in chemical constituents, diverse in pharmacological activities and abundant in resources, which is widely used in clinics from traditional to modern. However, there is no systematic report on the chemical compounds and anti-tumor effects of Celastrus orbiculatus Thunb. We organize and summarize it to provide reference for further development and research.

Magnetic/Zeolitic Imidazolate Framework-67 Nanocomposite for Magnetic Solid-Phase Extraction of Five Flavonoid Components from Chinese Herb Dicranopteris pedata.

A magnetically functionalized Fe3O4@ZIF-67 metal-organic framework (MOF) was prepared by electrostatic self-assembly using magnetic Fe3O4 nanoparticles as the core and ZIF-67 as the shell. The composite was characterized by electron microscopy, X-ray diffraction, Fourier- transform infrared spectroscopy, and Brunauer-Emmett-Teller measurements. Magnetic solid-phase extraction (MSPE) was performed on five flavonoids from Dicranopteris pedata using Fe3O4@ZIF-67 as an adsorbent. The developed MSPE method was combined with high-performance liquid chromatography-ultraviolet detection to preconcentrate and separate five flavonoids (rutin, quercitrin, kaempferol-3-O-α-L-rhamnoside, quercetin, and kaempferol) from Dicranopteris pedata. The factors affecting the extraction, such as the amount of Fe3O4@ZIF-67 adsorbent, salt ion concentration in the sample solution, vortex time, type and amount of desorbing solvent, concentration of formic acid to acidify the desorbing solvent, and acetonitrile ratio, were optimized. The developed method showed good linearity over the concentration range of 1.09-70.0 µg∙mL-1 for the five flavonoids, with R2 values between 0.9901 and 0.9945. The limits of detection and average recoveries for the five flavonoids were in the ranges of 39.5-56.2 ng∙mL-1 and 92.2-100.7%, respectively. The method presented herein is simple, efficient, and sensitive; it can be used for enrichment analysis of the five flavonoids in Dicranopteris pedata.

Transcatheter Arterial Embolization Combined with Anti-vascular Agent Combretastatin A4 Phosphate Inhibits Growth and Vascularization of Liver Tumor in an Animal Model.

OBJECTIVE: This study aimed to investigate the effect of combretastatin A4 phosphate (CA4P) on proliferation, migration, and capillary tube formation of human umbilical vein endothelial cells (HUVECs) and the efficacy of transcatheter arterial embolization combined with CA4P in the treatment of rabbit VX2 liver tumor. METHODS: The effects of different concentrations of CA4P on proliferation, migration and capillary tube formation of HUVECs were investigated by cell proliferation assay, wound healing assay and capillary tube formation assay, respectively. Thirty-two rabbits implanted with liver VX2 tumors were randomly divided into 4 groups. After catheterization of the left hepatic artery, the infusion was performed using normal saline (group A), CA4P aqueous solution (group B), lipiodol and polyvinyl alcohol particles (group C), and CA4P lipiodol emulsion and polyvinyl alcohol particles (group D), respectively. Half of the animals in each group were euthanized for immunohistochemical analysis to evaluate microvessel density (MVD) at 3 days post-treatment. The other half were examined by MRI and histology to evaluate tumor growth and necrosis at 7 days post-treatment. RESULTS: CA4P could inhibit the proliferation, migration, and tube formation of HUVECs in cell experiments. After interventional treatment, the level of MVD in group D was lower than that in group C (P<0.01). The tumor volume in group C or D was lower than that in group A or B (P<0.01). The tumor necrosis rate was higher in group D than in the other groups. CONCLUSION: The study suggests that CA4P could inhibit the proliferation, migration, and capillary tube formation of HUVECs, and transcatheter arterial embolization combined with CA4P could inhibit the growth of VX2 tumor and obviously induce tumor necrosis.

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells.

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

Investigating Acupoint Selection and Combinations of Acupuncture for Tic Disorders: An Association Rule Mining and Network Analysis Study.

Objective: Tic disorders (TDs) are common mental disorders in children and adolescents, and the clinical application of acupuncture for treating TDs is becoming increasingly widespread. However, the criteria for selecting acupoint prescriptions and combinations have not been summarized. Therefore, data mining was used herein to determine the treatment principles and the most effective acupoint selection and compatibility criteria for the treatment of TDs. Methods: Clinical studies and observations of the efficacy of acupuncture treatment for TDs were obtained from the PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Chinese Biomedical (CBM) databases. The data on the acupoint prescriptions applied in these studies were collected, and network and association analyses were used to reveal the relationships between acupoints and to identify acupoint combinations. Additionally, the principles of acupuncture for TDs were determined through cluster analysis. Subgroup analysis of acupuncture prescriptions based on specific categorical diagnoses was performed to further assess the selection of acupoints. Results: Eighty-six trials were identified, and 257 groups of effective prescriptions involving 121 acupoints were extracted. Bai-hui (DU20), Feng-chi (GB20), Tai-chong (LR3), He-gu (LI4), and San-yin-jiao (SP6) were the most regularly used acupoints for treating TDs. The Governor Vessel, gallbladder, and large intestine meridians were more commonly used than other meridians. Moreover, most acupoint sites focused on the head and neck. Network analysis revealed potentially effective acupoint prescriptions for their commonly used acupoints, namely, Bai-hui (DU20), Si-shen-cong (EX-HN1), Feng-chi (GB20), Nei-guan (PC6), Shen-men (HT7), He-gu (LI4), Zu-san-li (ST36), San-yin-jiao (SP6) and Tai-chong (LR3). Association rule mining indicated that potential point combinations that should be prioritized in TD treatment are Bai-hui (DU20), Neiguan (PC6) and Sanyinjiao (SP6). Cluster analysis revealed the treatment principle of "coordinating yin and yang, tonifying qi and blood, dispelling pathogenic wind and eliminating phlegm". The core acupoint prescription of TS treatment comprised He-gu (LI4), Feng-chi (GB20), Tai-chong (LR3), Bai-hui (DU20), Yin-tang (EX-HN3), Si-shen-cong (EX-HN1), San-yin-jiao (SP6), and Nei-guan (PC6). The core group included He-gu (LI4) and Feng-chi (GB20). Proximal points were usually used in TS as an additional method of point selection. Conclusion: Using data mining analysis of published studies, this study provides valuable information regarding the selection of the most effective acupoints and point combinations for clinical acupuncture practice for treating TDs.

Myristica fragrans Extract Regulates Gut Microbes and Metabolites to Attenuate Hepatic Inflammation and Lipid Metabolism Disorders via the AhR-FAS and NF-κB Signaling Pathways in Mice with Non-Alcoholic Fatty Liver Disease.

Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is closely related to the gut microbiome. Myristica fragrans is widely used as a traditional seasoning and has a therapeutic effect on gastrointestinal diseases. Although previous studies have shown that M. fragrans extracts have anti-obesity and anti-diabetes effects in mice fed a high-fat diet, few studies have determined the active components or the corresponding mechanism in vivo. In this study, for the first time, an M. fragrans extract (MFE) was shown to be a prebiotic that regulates gut microbes and metabolites in mice fed a high-fat diet. Bioinformatics, network pharmacology, microbiome, and metabolomics analyses were used to analyze the nutrient-target pathway interactions in mice with NAFLD. The National Center for Biotechnology Information Gene Expression Omnibus database was used to analyze NAFLD-related clinical data sets to predict potential targets. The drug database and disease database were then integrated to perform microbiome and metabolomics analyses to predict the target pathways. The concentrations of inflammatory factors in the serum and liver, such as interleukin-6 and tumor necrosis factor-α, were downregulated by MFE. We also found that the hepatic concentrations of low-density lipoprotein cholesterol, total cholesterol, and triglycerides were decreased after MFE treatment. Inhibition of the nuclear factor kappa B (NF-κB) pathway and downregulation of the fatty acid synthase (FAS)-sterol regulatory element-binding protein 1c pathway resulted in the regulation of inflammation and lipid metabolism by activating tryptophan metabolite-mediated aryl hydrocarbon receptors (AhR). In summary, MFE effectively attenuated inflammation and lipid metabolism disorders in mice with NAFLD through the NF-κB and AhR-FAS pathways.

Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification.

AIMS: Tetrahydrobiopterin (BH4) is a critical determinant of the biological function of endothelial nitric oxide synthase. The present study was to investigate the role of valvular endothelial cell (VEC)-derived BH4 in aortic valve calcification. METHODS AND RESULTS: Plasma and aortic valve BH4 concentrations and the BH4:BH2 ratio were significantly lower in calcific aortic valve disease patients than in controls. There was a significant decrease of the two key enzymes of BH4 biosynthesis, guanosine 5'-triphosphate cyclohydrolase I (GCH1) and dihydrofolate reductase (DHFR), in calcified aortic valves compared with the normal ones. Endothelial cell-specific deficiency of Gch1 in Apoe-/- (Apoe-/-Gch1fl/flTie2Cre) mice showed a marked increase in transvalvular peak jet velocity, calcium deposition, runt-related transcription factor 2 (Runx2), dihydroethidium (DHE), and 3-nitrotyrosine (3-NT) levels in aortic valve leaflets compared with Apoe-/-Gch1fl/fl mice after a 24-week western diet (WD) challenge. Oxidized LDL (ox-LDL) induced osteoblastic differentiation of valvular interstitial cells (VICs) co-cultured with either si-GCH1- or si-DHFR-transfected VECs, while the effects could be abolished by BH4 supplementation. Deficiency of BH4 in VECs caused peroxynitrite formation increase and 3-NT protein increase under ox-LDL stimulation in VICs. SIN-1, the peroxynitrite generator, significantly up-regulated alkaline phosphatase (ALP) and Runx2 expression in VICs via tyrosine nitration of dynamin-related protein 1 (DRP1) at Y628. Finally, folic acid (FA) significantly attenuated aortic valve calcification in WD-fed Apoe-/- mice through increasing DHFR and salvaging BH4 biosynthesis. CONCLUSION: The reduction in endothelial-dependent BH4 levels promoted peroxynitrite formation, which subsequently resulted in DRP1 tyrosine nitration and osteoblastic differentiation of VICs, thereby leading to aortic valve calcification. Supplementation of FA in diet attenuated hypercholesterolaemia-induced aortic valve calcification by salvaging BH4 bioavailability.

Determining three isoflavones from Pueraria lobata using magnetic ZIF-8 nanoparticle-based solid-phase extraction and pressurized capillary electrochromatography.

In this study, magnetic functionalized ZIF-8 nanoparticles were prepared by electrostatic self-assembly using magnetic Fe3O4 nanoparticles as cores and ZIF-8 as shells. ZIF-8 was used as the adsorbent to efficiently extract and sensitively analyze isoflavones due to its positive charge and strong adsorption capacity. Prepared samples were investigated by SEM and TEM, BET and ζ-potential analyses, FT-IR spectroscopy, powder XRD, and vibrating sample magnetism (VSM) experiments. The synthesized ZIF-8 has a dodecahedral structure that adsorbs well. Magnetic functionalized ZIF-8/Fe3O4 @SiO2 nanoparticles were prepared as a new SPE adsorbent, and a magnetic ZIF-8-pressurized capillary electrochromatography (pCEC) method was developed to separate and detect puerarin, daidzin, and daidzein (isoflavones) from Pueraria lobata by optimizing the extraction conditions, including adsorbent dosage, salt concentration, extraction time, desorption conditions, and other parameters. The developed method exhibited good linearities in the 50-2000 µg/mL concentration range for the three isoflavones, with coefficients of determination of 0.9934-0.9962. The limits of detection (LODs) for puerarin, daidzin, and daidzein were determined to be 0.02, 0.03, and 0.03 µg/mL, respectively. All analytes showed average recoveries in the 98.5-100.3% range, with relative standard deviations (RSDs, n = 6) of less than 4.0%. The developed method is convenient, enriches effectively, and shows good applications prospects for separating and analyzing components in Chinese herbal medicines.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Traditional Chinese medicine shenhuang granule in patients with severe/critical COVID-19: A randomized controlled multicenter trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still a pandemic, with a high mortality rate in severe/critical cases. Therapies based on the Shenghuang Granule have proved helpful in viral infection and septic shock. HYPOTHESIS/PURPOSE: The objective of the current study was to compare the efficacy and safety of the traditional Chinese medicine, Shenhuang Granule, with standard care in hospitalized patients with severe/critical COVID-19. STUDY DESIGN AND METHODS: This was an open-label, multicenter, randomized, controlled clinical trial. At 4 medical centers, a total of 111 severe/critical patients were randomly assigned to receive Shenhuang Granule (SHG group) twice a day for 14 days, in addition to standard care, or to receive standard care alone (Control group). The maximal follow up time was 75 days. The clinical endpoint was clinical improvement and mortality. RESULTS: 54 patients were assigned to the control group and 57 to the SHG group. The overall mortality was 75.9% (41/54) in the control group, and 38.6% (22/57) in the SHG group (p < 0.01 vs. control). The post hoc analysis showed that in the severe category, the mortality of the control group vs. the SHG group was 58.8% (10/17) vs. 5.3% (1/19) (p < 0.01); while in the critical category, it was 83.8% (31/37) vs. 55.3% (21/38) (p < 0.05). In the severe category, the mortality of patients who eventually received an invasive ventilator in the control vs. the SHG group was 58.8% (10/17) vs. 0 (0/19) (p < 0.01). Administration of SHG was associated with increased lymphocytes and decreased adverse events. CONCLUSION: Shenhuang Granule is a promising integrative therapy for severe and critical COVID-19.

Pulmonary arterial hypertension and flavonoids: A role in treatment.

Pulmonary arterial hypertension (PAH) is a high mortality progressive pulmonary vascular disease that can lead to right heart failure. The use of clinical drugs for the treatment of PAH is limited to a great extent because of its single target and high price. Flavonoids are widely distributed in nature, and have been found in fruits, vegetables, and traditional Chinese medicine. They have diverse biological activities and various pharmacological effects such as antitumor, antioxidation, and anti-inflammatory. This review summarizes the progress in pharmacodynamics and mechanism of flavonoids in the treatment of PAH in recent years, in order to provide some theoretical references for relevant researchers.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

A rare case of ectopic ACTH syndrome with rhabdomyolysis.

BACKGROUND: Manifestations of hypokalaemia in ectopic adrenocorticotropic hormonesyndrome(EAS) vary from mild muscle weakness to life-threatening arrhythmia. Herein, we present a rare case of EAS with concomitant rhabdomyolysis(RM) as a result of intractable hypokalaemia. CASE PRESENTATION: A 64-year-old man was admitted for limb weakness and facial hyperpigmentation for 2 weeks. Lab tests revealed intractable hypokalaemia (lowest at 1.8 mmol/L) and metabolic alkalosis. The diagnosis of RM was based on a creatine kinase(CK)level of 5 times the upper limit. The elevated CK and myohemoglobin (Mb) levels returned to within the normal range after the alleviation of hypokalaemia. The patient was diagnosed with ACTH-dependent Cushing's syndrome (CS) based on unsuppressed serum cortisol after a low-dose dexamethasone suppression test(LDDST) and remarkably elevated ACTH levels. The diagnosis of EAS was made based on the results of a high-dose dexamethasone suppression test(HDDST) and bilateral inferior petrosal sinus sampling(BIPSS). Multiple lymph nodes in the left supraclavicular fossa, right root of neck, mediastinum and bilateral hili of the lung were found with abnormal uptake of 68Ga-DOTA-NOC. Mediastinoscopic lymph node biopsy was performed. The pathological diagnosis was small-cell and large-cell neuroendocrine carcinoma with positive ACTH staining. The patient was prescribed mifepristone and received one cycle of chemotherapy. The patient could not tolerate subsequent chemotherapy and died of dyscrasia. CONCLUSIONS: RM is a rare complication of EAS with insidious onset and atypical clinical manifestations. Serum potassium levels should be vigilantly monitored to avoid RM in EAS.

Cysteiniphilum marinum sp. nov., isolated from coastal seawater.

Six aerobic Gram-negative bacteria were isolated from seawater in Guangdong Province, P.R. China. Cells were observed to be Gram-negative, aerobic, non-motile and non-spore forming. Growth of the designated type strain 19X3-30T occurred at a temperature range of 14-37 °C (optimum, 28 °C), a pH range of 6.0-8.0 (optimum, pH 7) and up to 7.5% NaCl (optimum, 1.5%; w/v), and was enhanced by CO2 and L-cysteine supplementation. The major polar lipids identified in strain 19X3-30T were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The principal cellular fatty acids profile showed the presence of anteiso-C15:0, anteiso-C17:0 and C18:0 (> 8% of total fatty acids), and the respiratory quinone was ubiquinone 8 (UQ-8). According to the analysis of 16S rRNA gene sequences, these strains represented a novel species within the family Fastidiosibacteraceae, sharing maximum similarities with Cysteiniphilum litorale DSM 101832T (96.6%) and Cysteiniphilum halobium DSM 103992T (95.3%). Phylogenetic dendrograms based on 16S rRNA gene and protein marker genes from the genomic sequences both indicated that the strains formed a monophyletic lineage closely linked to the genus Cysteiniphilum, which was also supported by the UPGMA dendrogram based on the MALDI-TOF MS profile. The genomic DNA G + C contents of six strains ranged from 38.0% to 38.1%. Based on different taxonomic genomic metrics, phylogeny and phenotypic features, we propose that the strains warrant the assignment to a novel species, for which the name Cysteiniphilum marinum sp. nov. is proposed. The type strain is 19X3-30T (= KCTC 82154T = CGMCC 1.18585T).

Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis.

Clinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development. To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use is of great interest. Systematic structure activity relationship study and multi-parameter optimization led to the discovery of a novel RORγ antagonist (SHR168442) with desired properties for a topical drug. It suppressed the transcription of IL-17 gene, leading to reduction of IL-17 cytokine secretion. It showed high exposure in skin, but low in plasma. Topical application of SHR168442 in Vaseline exhibited excellent efficacy in the imiquimod-induced and IL-23-induced psoriasis-like skin inflammation mouse models and correlated with the reduction of Th17 pathway cytokines, IL-6, TNFα and IL-17A. This work demonstrated restricted skin exposure of RORγ antagonist may provide a new topical treatment option as targeted therapeutics for mild to moderate psoriasis patients and may be suitable for the treatment of any other inflammatory disorders that are accessible locally.