Efficacy and Postoperative Complication Rates of Different Surgical Approaches for Calcaneal Fractures: A Network Meta-analysis.

Context: Calcaneal fractures (CFs) are the most common kind of tarsal fracture. The choice of surgical approach is a key element in the management of CFs, but the best method remains in dispute. Also, no single approach is appropriate for all kinds of CFs. Objective: The study intended to evaluate the relationship between six surgical approaches for clinical treatment of CFs and prevention of postoperative complications, to provide an evidence-based approach for treatment. Design: The research team performed a meta-analysis using the data from a previously published review and updating that data through a new narrative review. The team performed a systematic search in PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Internet (CNKI) from inception until January 2022, with no language restrictions. The search used the following keywords for the search: calcaneus, heel bone, surgical wounds, surgical incisions, prospective trials, prospective trials, and randomized controlled trials. Outcome Measures: The research team compared the complication rates, American Orthopedic Foot and Ankle Society (AOFAS) scores, and Bohler's angles for the six surgical approaches, which were: (1) the extensive lateral approach (ELA), (2) the sinus tarsi approach (STA), (3) the horizontal arc approach (HAA), (4) the longitudinal approach (LA), (5) the oblique lateral incision (OLI), and (6) the modified incision (MI)). The team summarized the results using a random effects model. Results: The research team analyzed the data from 19 RCTs with 1521 participants. They all were randomized controlled trials (RCTs). The complication rates were available for 18 studies, which included 1474 participants. The rates were significantly lower: (1) for HAA compared to ELA, [OR=-2.03; 95% CrI: [-3.63, -0.43)]; (2) for LA compared to ELA (OR=-1.83; 95% CrI: [-2.83, -0.84]); and (3) for STA compared to ELA (OR=- 1.22; 95% CrI: [-1.67, -0.78]). Of the 19 studies, 11 RCTs, with 942 participants, used the AOFAS scale. The probabilities for the surface under the cumulative ranking curve (SUCRA) indicated that OLI (0.694 ) >LA (0.596) >HAA (0.51) >STA (0.477) >ELA (0.224). In addition, ELA had the worst SUCRA (0.224). Of the 19 studies, 15 RCTs, with 1376 participants, used the Bohler angle as an outcome measure. The probability of SUCRA for the surgical approaches indicated that LA (0.723) >ELA (0.667) >STA (0.468) >HAA (0.373) >MI (0.27). Conclusions: The meta-analysis provides an evidence-based approach to the clinical treatment of CFs for six surgical approaches. HAA had the best outcomes, and ELA had the worst.

Causal effects of tea intake on multiple types of fractures: A two-sample Mendelian randomization study.

Fracture is a global public health disease. Bone health and fracture risk have become the focus of public and scientific attention. Observational studies have reported that tea consumption is associated with fracture risk, but the results are inconsistent. The present study used 2-sample Mendelian randomization (MR) analysis. The inverse variance weighted method, employing genetic data from UK Biobank (447,485 cases) of tea intake and UK Biobank (Genome-wide association study Round 2) project (361,194 cases) of fractures, was performed to estimate the causal relationship between tea intake and multiple types of fractures. The inverse variance weighted indicated no causal effects of tea consumption on fractures of the skull and face, shoulder and upper arm, hand and wrist, femur, calf, and ankle (odds ratio = 1.000, 1.000, 1.002, 0.997, 0.998; P = .881, 0.857, 0.339, 0.054, 0.569, respectively). Consistent results were also found in MR-Egger, weighted median, and weighted mode. Our research provided evidence that tea consumption is unlikely to affect the incidence of fractures.

[Effect of electroacupuncture on the expression of Iba-1 in spinal dorsal horn and hippocampus of chronic pain rats with knee osteoarthritis].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on pain-ralated behaviors, morphology of hippocampus, concentrations of inflammatory cytokines and expression of ionized calcium binding adapter molecule 1(Iba-1) in dorsal horn of the spinal cord and the hippocampus, and brain-derived neurotrophic factor (BDNF) in hippocampus of rats with knee osteoarthritis (KOA), so as to explore the mechanism of EA in improving chronic pain of KOA. METHODS: Forty SD rats were randomly divided into blank group, saline group, model group and EA group, with 10 rats in each group. Monosodium iodoacetate(MIA, 80 mg/mL, 50 µL) was injected into the left knee joint cavity of rats in the model group and EA group to establish the chronic pain model of KOA, while the same volume of normal saline was injected into the left knee joint cavity of rats in the saline group. Rats in the EA group received EA stimulation(2 Hz/100 Hz, 1-2 mA) at left "Yanglingquan"(GB34) and "Neixiyan"(EX-LE4) for 15 min, 14 d after MIA injection. The treatment was given once daily, 5 d as 1 session and 2 sessions of treatment were required. Methanical withdrawl threshold(MWT) and weight-bearing capacity tests on left hind limbs were carried out 1 d before, 7 d，14 d, 20 d and 26 d after MIA injection. At the 27th day, rats were sacrificed and HE staining was used to observe the morphology of hippocampal CA1 area. Concentrations of interleukin(IL)-1ß and tumor necrosis factor(TNF)-α in the left L3-L5 spinal dorsal horn and hippocampal CA1 area were detected by ELISA, the expressions of Iba-1 in the spinal dorsal horn and hippo-campal CA1 area were detected by immunofluorescence, and the expression of BDNF in left hippocampal CA1 area was detected by Western blot. RESULTS: The HE staining results of the hippocampal CA1 area showed reduced number of neurons, unclear cell contour and boundary between nucleus and cytoplasm, and nuclear pyknosis in the model group, which was relatively milder in the EA group. Compared with the blank group, MWT and weight-bearing capacity of rats' left hind limbs, and expression of BDNF protein in hippocampal CA1 area were significantly decreased (P<0.01), while the contents of IL-1ß and TNF-α, the expression of Iba-1 in spinal dorsal horn and hippocampal CA1 area were significantly increased (P<0.01) in the model group. In comparison with the model group, MWT and weight-bearing capacity of rats' left hind limbs, and protein expression of BDNF in hippocampal CA1 area were significantly increased (P<0.01), while the contents of IL-1ß and TNF-α, and the expression of Iba-1 protein in spinal dorsal horn and hippocampal CA1 area were significantly decreased after EA intervention(P<0.01). CONCLUSION: EA at GB34 and EX-LE4 can alleviate the pain-related behaviors of KOA rats. The mechanism might be related to the inhibition of inflammatory reaction mediated by microglia in spinal dorsal horn and hippocampus, and the up-regulation of BDNF expression in hippocampus.

Guanxining injection alleviates fibrosis in heart failure mice and regulates SLC7A11/GPX4 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort., Apiaceae, Chuanxiong in Chinese) both are important traditional Chinese medicine (TCM) for activating blood and eliminating stasis. Danshen-chuanxiong herb pair has been used for more than 600 years in China. Guanxinning injection (GXN) is a Chinese clinical prescription refined from aqueous extract of Danshen and Chuanxiong at the ratio of 1:1 (w/w). GXN has been mainly used in the clinical therapy of angina, heart failure (HF) and chronic kidney disease in China for almost twenty years. AIM OF THE STUDY: This study aimed to explore the role of GXN on renal fibrosis in heart failure mice and the regulation of GXN on SLC7A11/GPX4 axis. MATARIALS AND METHODS: The transverse aortic constriction model was used to mimic HF accompanied by kidney fibrosis model. GXN was administrated by tail vein injection in dose of 12.0, 6.0, 3.0 mL/kg, respectively. Telmisartan (6.1 mg/kg, gavage) was used as a positive control drug. Cardiac ultrasound indexes of ejection fraction (EF), cardiac output (CO), left ventricle volume (LV Vol), HF biomarker of pro-B type natriuretic peptide (Pro-BNP), kidney function index of serum creatinine (Scr), kidney fibrosis index of collagen volume fraction (CVF) and connective tissue growth factor (CTGF) were evaluated and contrasted. Metabolomic method was employed to analyze the endogenous metabolites changes in kidneys. Besides, contents of catalase (CAT), xanthine oxidase (XOD), nitricoxidesynthase (NOS), glutathione peroxidase 4 (GPX4), the x(c)(-) cysteine/glutamate antiporter (SLC7A11) and ferritin heavy chain (FTH1) in kidney were quantitatively analyzed. In addition, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical composition of GXN and network pharmacology was used to predict possible mechanisms and the active ingredients of GXN. RESULTS: The cardiac function indexes of EF, CO and LV Vol, kidney functional indicators of Scr, the degree of kidney fibrosis indicators CVF and CTGF were all relieved to different extent for the model mice treated with GXN. 21 differential metabolites involved in redox regulation, energy metabolism, organic acid metabolism, nucleotide metabolism, etc were identified. Aspartic acid, homocysteine, glycine, and serine, methionine, purine, phenylalanine and tyrosine metabolism were found to be the core redox metabolic pathways regulated by GXN. Furthermore, GXN were found to increase CAT content, upregulate GPX4, SLC7A11 and FTH1 expression in kidney significantly. Not only that, GXN also showed good effect in down-regulating XOD and NOS contents in kidney. Besides, 35 chemical constituents were initially identified in GXN. Active ingredients of GXN-targets-related enzymes/transporters-metabolites network was established to find out that GPX4 was a core protein for GXN and the top 10 active ingredients with the most relevant to renal protective effects of GXN were rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A. CONCLUSION: GXN could significantly maintain cardiac function and alleviate the progression of fibrosis in the kidney for HF mice, and the mechanisms of action were related to regulating redox metabolism of aspartate, glycine, serine, and cystine metabolism and SLC7A11/GPX4 axis in kidney. The cardio-renal protective effect of GXN may be attributed to multi-components like rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A et al.

Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis.

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1ß, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.

Research progress on metabolomics in the quality evaluation and clinical study of Panax ginseng.

Panax ginseng, an essential component of traditional medicine and often referred to as the king of herbs, has played a pivotal role in medicine globally for several millennia. Previously, traditional phytochemical methods were mainly used for quality evaluation and pharmacological mechanism studies of ginseng, resulting in the lack of systematicness and innovation and hindering the development and utilization of ginseng resources. Since the beginning of the new century, systems biology technology represented by metabolomics has shown unique advantages in the modernization and internationalization of herbal medicine, establishing a bridge for communication between traditional medicine and modern medicine. P. ginseng, a special herb used in medicine and food, is one of the main research objects for qualitative and quantitative analysis of metabolomics and has gradually become the focus of researchers globally. Here, we conducted a comprehensive summary and analysis of numerous studies published in ginseng metabolomics. This review aims to provide more novel ideas for the quality evaluation, development, and clinical application of ginseng in the future and offer more useful technical references for the modernization and internationalization of herbal medicine based on metabolomics.

Therapeutic potential of plant iridoids in depression: a review.

CONTEXT: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. OBJECTIVE: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. METHODS: The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression. RESULTS: Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. DISCUSSION AND CONCLUSIONS: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.

Quality analysis of hawthorn leaves (the leaves of Crataegus pinnatifida Bge. var major N.E.Br) in different harvest time.

INTRODUCTION: Harvest time plays an important role on the quality of medicinal plants. The leaves of Crataegus pinnatifida Bge. var major N.E.Br (hawthorn leaves) could be harvested in summer and autumn according to the Pharmacopoeia of the People's Republic of China (Pharmacopoeia). However, little is known about the difference of the chemical constituents in hawthorn leaves with the harvest seasonal variations. OBJECTIVE: The chemical constituents of hawthorn leaves in different months were comprehensively analysed to determine the best harvest time. METHODS: Initially, the chemical information of the hawthorn leaves were obtained by ultra-high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Subsequently, principal component analysis (PCA) was applied to compare the chemical compositions of hawthorn leaves harvested in different months. Then, an absolute quantitation method was established using high-performance liquid chromatography-charged aerosol detector (HPLC-CAD) to determine the contents of five compounds and clarify the changes of these components with the harvest seasonal variations. Meanwhile, a semi-quantitative method by integrating HPLC-CAD with inverse gradient compensation was also established and verified. RESULTS: Fifty-eight compounds were identified through UHPLC-Q-TOF-MS. PCA revealed that the harvest season of hawthorn leaves had a significant effect on the chemical compositions. The contents of five components were relatively high in autumn. Other four main components without reference standards were further analysed through the semi-quantitative method, which also showed a high content in autumn. CONCLUSIONS: This work emphasised the effect of harvest time on the chemical constituents of hawthorn leaves and autumn is recommended to ensure the quality.

Ilex rotunda Thunb Protects Against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Restoring the Intestinal Mucosal Barrier and Modulating the Oncostatin M/Oncostatin M Receptor Pathway.

Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

A chalcone-syringaldehyde hybrid inhibits triple-negative breast cancer cell proliferation and migration by inhibiting CKAP2-mediated FAK and STAT3 phosphorylation.

BACKGROUND: Although triple-negative breast cancer (TNBC) accounts for only 15% of breast cancer cases, it is associated with a high relapse rate and poor outcome after standard treatment. Currently, the effective drugs and treatment strategies for TNBC remain limited, and thus, developing effective treatments for TNBC is pressing. Several studies have demonstrated that both chalcone and syringaldehyde have anticancer effect, but their potential anti-TNBC bioactivity are still unknown. PURPOSE: The present study aimed to synthesize a chalcone-syringaldehyde hybrid (CSH1) and explore its potential anti-TNBC effects and the underlying molecular mechanism. METHODS: Cell cytotoxicity was determined by 3-(4,5-dimethythiazol)-2,5-diphenyltetrazolium bromide (MTT). The activity of cell proliferation was measured by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Cell cycle distribution and cell apoptosis were determined by fluorescence-activated cell sorter (FACS). The situation of DNA damage was observed using fluorescence microscopy. The ability of cell-matrix adhesion, migration and invasion was detected using cell adhesion assay and transwell assay. Transcriptome sequencing was performed to find out the changed genes. Levels of various signaling proteins were assessed by western blotting. RESULTS: CSH1 treatment triggered DNA damage and inhibited DNA replication, cell cycle arrest, and cell apoptosis via suppressing signal transducer and activator of transcription 3 (STAT3) phosphorylation. Whole genome RNA-seq analysis suggested that 4% of changed genes were correlated to DNA damage and repair, and nearly 18% of changed genes were functionally related to cell adhesion and migration. Experimental evidence indicated that CSH1 treatment significantly affected the distribution of focal adhesion kinase (FAK) and its phosphorylation, resulting in cell-matrix-adhesion reduction and migration inhibition of TNBC cells. Further mechanistic studies indicated that CSH1 inhibited TNBC cell proliferation, adhesion, and migration by inhibiting cytoskeleton-associated protein 2 (CKAP2)-mediated FAK and STAT3 phosphorylation signaling. CONCLUSION: These results suggest that CKAP2-mediated FAK and STAT3 phosphorylation signaling is a valuable target for TNBC treatment, and these findings also reveal the potential of CSH1 as a prospective TNBC drug.

Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats.

Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (α-asaronol), a major compound isolated from the Chinese medicinal herb Acorus gramineus by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of α-asaronol on myelination in a rat model of PWMI induced by HI. Notably, α-asaronol promoted OPC differentiation and myelination in the corpus callosum of PWMI rats. Meanwhile, the concentration of glutamate was significantly decreased, and the levels of PPARγ and glutamate transporter 1 (GLT-1) were increased by α-asaronol treatment. In vitro, it was also confirmed that α-asaronol increased GLT-1 expression and recruitment of the PPARγ coactivator PCG-1a in astrocytes under oxygen and glucose deprivation (OGD) conditions. The PPARγ inhibitor GW9662 significantly reversed the effect of α-asaronol on GLT-1 expression and PCG-1a recruitment. Interestingly, the conditioned medium from α-asaronol-treated astrocytes decreased the number of OPCs and increased the number of mature oligodendrocytes. These results suggest that α-asaronol can promote OPC differentiation and relieve dysmyelination by regulating glutamate levels via astrocyte PPARγ-GLT-1 signaling. Although whether α-asaronol binds to PPARγ directly or indirectly is not investigated here, this study still indicates that α-asaronol may be a promising small molecular drug for the treatment of myelin-related diseases.

Revealing the Antiepileptic Effect of α-Asaronol on Pentylenetetrazole-Induced Seizure Rats Using NMR-Based Metabolomics.

α-Asaronol from Acorus tatarinowii (known as "Shichangpu" in Traditional Chinese medicine) has been proved to possess more efficient antiepileptic activity and lower toxicity than α-asarone (namely "Xixinnaojiaonang" as an antiepileptic drug in China) in our previous study. However, the molecular mechanism of α-asaronol against epilepsy needs to be known if to become a novel antiepileptic medicine. Nuclear magnetic resonance (NMR)-based metabolomics was applied to investigate the metabolic patterns of plasma and the brain tissue extract from pentylenetetrazole (PTZ)-induced seizure rats when treated with α-asaronol or α-asarone. The results showed that α-asaronol can regulate the metabolomic level of epileptic rats to normal to some extent, and four metabolic pathways were associated with the antiepileptic effect of α-asaronol, including alanine, aspartate, and glutamate metabolism; synthesis and degradation of ketone bodies; glutamine and glutamate metabolism; and glycine, serine, and threonine metabolism. It was concluded that α-asaronol plays a vital role in enhancing energy metabolism, regulating the balance of excitatory and inhibitory neurotransmitters, and inhibiting cell membrane damage to prevent the occurrence of epilepsy. These findings are of great significance in developing α-asaronol into a promising antiepileptic drug derived from Traditional Chinese medicine.

Advances in Anti-Osteoporosis Polysaccharides Derived from Medicinal Herbs and Other Edible Substances.

Osteoporosis is a common metabolic bone disease, and treatment is required for the prevention of low bone mass, deterioration of microstructural bone tissue, and fragility fractures. Osteoporosis therapy includes calcium, vitamin D, and drugs with antiresorptive or anabolic action on the bone. Therapy for osteoporosis does not include taking non-steroidal anti-inflammatory drugs (NSAID), but pain associated with osteoporotic fractures can be treated by taking non-steroidal anti-inflammatory drugs (NSAID). Recently, polysaccharides extracted from medicinal herbs and edible substances (PsMHES) have attracted attention on account of their safety and promising anti-osteoporosis effects, whereas a systematic review about their potential in anti-osteoporosis is vacant to date. Herein, we reviewed the recent progress of PsMHES with anti-osteoporosis activities, looking to introduce the advances in the various pharmacological mechanisms and targets involved in the anti-osteoporosis effects, extraction methods, main mechanism involved in Wnt/[Formula: see text]-catenin pathways and RANKL (Receptor Activator for NF[Formula: see text]B ligand or TNFSF25) pathways, and Structure-Activity Relationships (SAR) analysis of PsMHES. Typical herbs likeAchyranthes bidentate and Morinda officinalis used for the treatment of osteoporosis are introduced; their traditional uses in traditional Chinese medicine (TCM) are discussed in this paper as well. This review will help to the recognition of the value of PsMHES in anti-osteoporosis and provide guidance for the research and development of new anti-osteoporosis agents in clinic.

Hyperbaric Oxygen Therapy: An Effective Auxiliary Treatment Method for Large Jaw Cysts.

Background: To evaluate hyperbaric oxygen therapy (HBOT) on infection rates and repair rates during the treatment of large jaw cysts. Methods: A prospective randomized, non-blinded, controlled clinical trial included 90 patients with jaw cysts, randomly divided into three groups. Patients were treated with enucleations and bone substitute was used in the experimental and control groups. The experimental group received HBOT. The primary predictor variable was HBOT. The infection rate, repair rate, preoperative volume of the jaw cysts, age, and sex were statistically analyzed. The Fisher exact test was used to compare the infection rate and postoperative complications. The repair rate of the bone defects was analyzed using the repeated-measures analysis of variance and the least significant difference tests. The Kendall's coefficient of concordance and Kappa statistics were calculated to evaluate the consistency between the two investigators. Results: The infection rate was 3.4% in the experimental group, 14.3% in the blank group, and 32.1% in the control group (P<0.05). The repair rate in the experimental group was significantly higher than in the control and blank groups at 1, 3 and 6 months after surgery (P<0.05). Conclusion: The results showed that HBOT reduced the postoperative infection rate following the enucleation of large jaw cysts with bone substitute filling, and it also improved the bone repair rate.

[Applications of chromatography in giant complex drug-organism system].

Chromatography is an important branch of analytical chemistry that focuses on the separation and analysis of complex structures. Following more than 100 years of development and improvement, chromatography theory and technology have gradually become sophisticated. It has become a coalition of science, technology, and art. Recently, chromatography has been successfully used in combination with mass spectrometry, nuclear magnetic resonance spectroscopy, and atomic emission spectroscopy. Chromatography and the combination with other techniques has significantly improved the analysis of complex systems, such as the environment, food, petrochemicals, biological specimens, and medicine. As one of the oldest healing systems, Traditional Chinese Medicine (TCM) has served to maintain the health of people in China and worldwide for thousands of years. Therefore, it has become a core representative of traditional Chinese culture. In the past two years, TCM has been widely used to treat COVID-19, especially in patients with mild symptoms. Recently, Chinese government emphasized the inheritance and innovation of TCM and stepped up efforts to promote its modernization. TCM includes herbal medicine, acupuncture, moxibustion, massage, food therapy, and physical exercise, such as Tai Chi. In most cases, the patients are administered a mixture of TCM formulas containing more than two herbal medicines, resulting in a highly complicated compound mixture. There is no doubt that long-term clinical practices have demonstrated the safety and therapeutic effect of TCM. However, the compound mixture must be simplified to identify the active compounds. This is mainly because of the existence of carcinogenic compounds, pesticides, and heavy metal residues introduced through plantation and production processes. Moreover, enzymes within the human system generate further new compounds in response to the entry of the TCM containing thousands of components. Consequently, the complex TCM and organism systems interact with each other, constituting a giant complex drug-organism system. The analysis of this giant complex system is acknowledged as a key aspect in the modernization process of TCM. In the last 20 years, many studies have been conducted to screen and identify effective compounds in TCM. These effective compounds can be either the original compounds or new metabolic components generated in vivo. All these efforts are aimed at simplifying the components of TCM and elucidating the therapeutic mechanism. It is well known that chromatography can provide technical support for complex systems owing to its unique advantage of outstanding separation and analysis capabilities. Therefore, chromatography and its combination with other technologies have become mainstream technologies for promoting the compilation of molecular structure, information, digitalization, and modernization of TCM. This paper reviews the research and application of chromatography and combination technologies in a giant complex TCM formula-organism system. Furthermore, the authors briefly introduce and summarize the understanding, research ideas, and activities of the authors' team on the modernization of TCM. "Liang Guanxi" and "He strategy" are proposed as novel strategies for studying the giant complex drug-organism system. A distinguished technology integrated with mathematical model of causal relation, combined receptor chromatography, identification of chemical molecular structure and evaluating of pharmacological activities was established. It was successfully employed to determine the core effector-response substances of "Liang Guanxi" herb pairs in a giant complex drug-organism system. Subsequently, utilizing the proposed technology of Combination of Traditional Chinese Medicine Molecular Chemistry, the author's team designed and developed four series of innovative drugs. Inspired by the hundred years of chromatography history and thousands of years of TCM culture, the future development of chromatographic technology is expected. Furthermore, the mechanisms of TCM in medical healthcare, prevention, and treatment of diseases are likely be explained through chromatography, leading to a new strategy to realize the molecularization and digitalization of TCM, which is beneficial to the development of original new drugs.

[Terpenoids from leaves of Chinese hawthorn].

Fifteen compounds were isolated from the 70% EtOH extract of leaves of Chinese hawthorn(Crataegus pinnatifida var. major) by various purification steps, and their structures were determined as 2α,3α,12ß,19α,-tetrahydroxyursan-13ß,28-olide(1),euscaphic acid(2), tormentic acid(3), ursolic acid(4), pomolic acid(5), corosolic acid(6), maslinic acid(7), linalyl rutinoside(8),(Z)-3-hexenyl ß-D-glucoside(9),(3S, 6S)-cis-linalool-3,7-oxide-ß-D-glucopyranoside(10), pisumionoside(11), icariside B6(12), byzantionoside B(13),(6R,7E,9R)-9-Hydroxy-4,7-megastigmadien-3-one 9-O-ß-D-glucopyranoside(14) and(6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-ß-D-glucopyranoside(15) mainly based on the mass spectrum(MS) and nuclear magnetic resonance(NMR) spectroscopic techniques, of which compound 1 was a new pentacyclic triterpene, and compounds 2, 5, 6, 8, 10, 13 and 15 were isolated form this plant for the first time.

Feiyangchangweiyan capsule protects against ulcerative colitis in mice by modulating the OSM/OSMR pathway and improving gut microbiota.

BACKGROUND: Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE: To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS: Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS: FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1ß, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION: FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.

Effect of co-administration of Acori Tatarinowii Rhizoma volatile oil on pharmacokinetic fate of xanthotoxol, oxypeucedanin hydrate, and byakangelicin from Angelicae Dahuricae Radix in rat.

A combination of Angelicae Dahuricae Radix and Acori Tatarinowii Rhizoma has been widely used as the herb pair in traditional Chinese medicine to treat stroke, migraine, and epilepsy. However, the underlying synergistic mechanism of the herb pair remains unknown. This study was aimed at investigating the effects of Acori Tatarinowii Rhizoma volatile oil on the pharmacokinetic parameters of xanthotoxol, oxypeucedanin hydrate, and byakangelicin from Angelicae Dahuricae Radix in rat, and in vitro absorption behavior of the three compounds using rat everted gut sac, in situ single-pass intestinal perfusion, and Caco-2 cell monolayer models. The pharmacokinetic study exhibited clear changes in the key pharmacokinetic parameters of the three main coumarins through co-administering with Acori Tatarinowii Rhizoma volatile oil (50 mg/kg), the area under curve and the maximum plasma concentration of xanthotoxol increased 1.36 and 1.31 times; the area under curve, the maximum plasma concentration, mean residence time, half-life of elimination, and the time to reach peak concentration of oxypeucedanin hydrate increased by 1.35, 1.18, 1.24, 1.19 and 1.49 times, respectively; the area under curve, mean residence time, half-life of elimination, and time to reach peak concentration of byakangelicin climbed 1.29, 1.27, 1.37, and 1.28 times, respectively. The three coumarin components were absorbed well in the jejunum and ileum in the intestinal perfusion model, when co-administered with Acori Tatarinowii Rhizoma volatile oil (100 µg/mL). The in vivo and in vitro experiments showed good relevance and consistency. The results demonstrated that the three coumarin compounds from Angelicae Dahuricae Radix were absorbed through the active transportation, and Acori Tatarinowii Rhizoma volatile oil could promote the intestinal absorption and transport of these compounds by inhibiting P-glycoprotein (P-gp)-mediated efflux.

Preparation of water-soluble chitosan/poly-gama-glutamic acid-tanshinone IIA encapsulation composite and its in vitro/in vivo drug release properties.

Some diseases could be treated by Tanshinone IIA (TA), which is an isolated component from the Chinese medicinal herb Tanshen (Salvia miltiorrhiza). However, the poor water solubility and low oral bioavailability of TA limited its clinical application. In this paper, TA was encapsulated by water - soluble chitosan/poly - γ - glutamic acid (WCS-γ-PGA) to improve its dissolution and oral bioavailability. The in vitro dissolution and in vivo metabolism of the encapsulated composite in rats were employed to evaluate the efficiency of the improvement. FTIR spectroscopy was applied to confirm the validity of encapsulation for TA by WCS-γ-PGA. The study's results showed that the optimal ratio of TA to drug carrier (WCS + Î³-PGA) was 1:5.5 in weight with a reaction time of 1 h at room temperature for the encapsulation. The proper concentrations for WCS and TA in preparing the encapsulated composite using γ-PGA 0.125 mg ml-1 were 6 mg ml-1 and 1 mg ml-1, respectively; The encapsulation efficiency and drug loading efficiency of WCS-γ-PGA-TA composite were (93.99 ± 2.20)% and (10.73 ± 0.75)%, respectively. The cumulative release of TA from the WCS-γ-PGA-TA encapsulated composite reached to 81% within 60 min, which was 5.56 times of that of the original TA in vitro dissolution. The peak concentration Cmax of TA from the encapsulated composite in rat blood as measured by an ultracentrifugation test of an intra - gastric administration was 4.43 times that of the original TA concentration, and the area under the drug-time curve AUC (0-t) and AUC (0-∞) (p<0.01) of the WCS-γ-PGA-TA encapsulated composite were 4.56 and 4.20 times that of the original TA, respectively. It indicated that the encapsulation of TA with WCS-γ-PGA improved its solubility and bioavailability significantly.

Pharmacokinetics of 13 active components in a rat model of middle cerebral artery occlusion after intravenous injection of Radix Salviae miltiorrhizae-Lignum dalbergiae odoriferae prescription.

As a representative formulation of Radix Salviae miltiorrhizae (Danshen)-Lignum Dalbergiae odoriferae (Jiangxiang), Xiangdan injection is widely prescribed for cardio- and cerebrovascular diseases in practice. This necessitates a pharmacokinetic investigation of this formulation to make it safer and more broadly applicable. We developed and validated a sensitive, selective, and reliable high-performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of 11 phenolic compounds including danshensu plus two diterpenoid quinones like cryptotanshinone and tanshinone IIA in rat. We applied this method for the pharmacokinetic studies of the 13 compounds in a rat model of middle cerebral artery occlusion after intravenous injection of Xiangdan injection or Danshen injection. In sham-operated rats, the animals taking Xiangdan injection exhibited significant growth of the area under the curve for danshensu, protocatechuic aldehyde, and tanshinone IIA compared with the changes seen in the data of those administrated with Danshen injection. Such a pattern was also observed in middle cerebral artery occlusion rats, whereas increased the area under the curve values were observed for danshensu, protocatechuic aldehyde, caffeic acid, rosmarinic acid, and tanshinone IIA. These results demonstrated that synergistic interactions occurred between the components of Danshen and the active compounds of Jiangxiang both in sham-operated and middle cerebral artery occlusion rats, increasing the bioavailability of Danshen. The results presented herein can be used to determine a reference dose for the clinical application of Xiangdan injection, and to elucidate the synergistic mechanism of Danshen and Jiangxiang.