Clinical effects of multi-oil versus pure soybean oil-based lipid emulsions for preterm infants: An observational study.

BACKGROUND AND OBJECTIVES: Conventional soybean oil-based intravenous lipid emulsions (SO-ILEs) have high polyunsaturated fatty acid (PUFA) contents and phytosterols that may have adverse effects in preterm infants. Recently, the multi-oil-based intravenous lipid emulsion (MO-ILE), SMOFlipid, has been widely utilized in the neonatal intensive care unit (NICU), but significant benefits over SO-ILEs in low gestational age neonates have yet to be demonstrated. This study was performed to compare the effects of the SO-ILE, Intralipid, and the MO-ILE, SMOFlipid, on neonatal health outcomes in preterm infants. METHODS AND STUDY DESIGN: We performed a retrospective review of preterm infants born at gestational week (GW) <32 receiving parenteral nutrition for longer durations (≥14 d) in the NICU between 2016 and 2021. The primary aim of this study was to investigate differences in morbidity between preterm infants receiving SMOFlipid and Intralipid. RESULTS: A total of 262 preterm infants were included in the analysis, with 126 receiving SMOFlipid and 136 receiving Intralipid. The SMOFlipid group had lower rates of ROP (23.8% vs 37.5%, respectively; p=0.017), although the rate of ROP was not different in multivariate regression analysis. The length of hospi-tal stay was significantly shorter in the SMOFlipid than SO-ILE group (median [IQR]=64.8 [37] vs 72.5 [49] days; p<0.001). CONCLUSIONS: The use of SMOFlipid as the lipid emulsion was associated with higher clinical efficacy than SO-ILE in preterm infants.

Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate delays aging phenotypes in mice.

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period.

Metabolic Engineering of Saccharomyces cerevisiae for High-Level Friedelin via Genetic Manipulation.

Friedelin, the most rearranged pentacyclic triterpene, also exhibits remarkable pharmacological and anti-insect activities. In particular, celastrol with friedelin as the skeleton, which is derived from the medicinal plant Tripterygium wilfordii, is a promising drug due to its anticancer and antiobesity activities. Although a previous study achieved friedelin production using engineered Saccharomyces cerevisiae, strains capable of producing high-level friedelin have not been stably engineered. In this study, a combined strategy was employed with integration of endogenous pathway genes into the genome and knockout of inhibiting genes by CRISPR/Cas9 technology, which successfully engineered multiple strains. After introducing an efficient TwOSC1T502E, all strains with genetic integration (tHMG1, ERG1, ERG20, ERG9, POS5, or UPC2.1) showed a 3.0∼6.8-fold increase in friedelin production compared with strain BY4741. Through further double knockout of inhibiting genes, only strains GD1 and GD3 produced higher yields. Moreover, strains GQ1 and GQ3 with quadruple mutants (bts1; rox1; ypl062w; yjl064w) displayed similar increases. Finally, the dominant strain GQ1 with TwOSC1T502E was cultured in an optimized medium in shake flasks, and the final yield of friedelin reached 63.91 ± 2.45 mg/L, which was approximately 65-fold higher than that of the wild-type strain BY4741 and 229% higher than that in ordinary SD-His-Ura medium. It was the highest titer for friedelin production to date. Our work provides a good example for triterpenoid production in microbial cell factories and lays a solid foundation for the mining, pathway analysis, and efficient production of valuable triterpenoids with friedelin as the skeleton.

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells.

Evidence from epidemiological and laboratory studies, as well as randomized placebo-controlled trials, suggests supplementation with n-3 polyunsaturated fatty acids (PUFAs) may be efficacious for treatment of major depressive disorder (MDD). The mechanisms underlying n-3 PUFAs potential therapeutic properties remain unknown. There are suggestions in the literature that glial hypofunction is associated with depressive symptoms and that antidepressants may normalize glial function. In this study, induced pluripotent stem cells (iPSC)-derived neuronal stem cell lines were generated from individuals with MDD. Astrocytes differentiated from patient-derived neuronal stem cells (iNSCs) were verified by GFAP. Cells were treated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or stearic acid (SA). During astrocyte differentiation, we found that n-3 PUFAs increased GFAP expression and GFAP positive cell formation. BDNF and GDNF production were increased in the astrocytes derived from patients subsequent to n-3 PUFA treatment. Stearic Acid (SA) treatment did not have this effect. CREB activity (phosphorylated CREB) was also increased by DHA and EPA but not by SA. Furthermore, when these astrocytes were treated with n-3 PUFAs, the cAMP antagonist, RP-cAMPs did not block n-3 PUFA CREB activation. However, the CREB specific inhibitor (666-15) diminished BDNF and GDNF production induced by n-3 PUFA, suggesting CREB dependence. Together, these results suggested that n-3 PUFAs facilitate astrocyte differentiation, and may mimic effects of some antidepressants by increasing production of neurotrophic factors. The CREB-dependence and cAMP independence of this process suggests a manner in which n-3 PUFA could augment antidepressant effects. These data also suggest a role for astrocytes in both MDD and antidepressant action.

Analysis on Evolution of Ancient Documents of Xiehuangsan / 中国实验方剂学杂志

Xiehuangsan， derived from QIAN Yi's Key to Therapeutics of Children's Diseases， consists of 5 medicines， namely Gypsum Fibrosum，Gardeniae Fructus，Saposhnikoviae Radix，Pogostemonis Herba and Glycyrrhizae Radix et Rhizoma. It is used to treat children with spleen heat and tongue scratching. With the clinical use of later generations of physicians，the scope of diseases and syndromes of this prescription was gradually expanded，including aphthous bad breath，dry lips，yellow eyes，and sweet mouth. Modern doctors used this prescription to treat children with anorexia，constipation，allergic purpura，tic disorder， and other diseases. At present，more and more attention has been paid to the research of classical famous prescriptions. At the same time，the application of classical famous prescriptions of traditional Chinese medicine（TCM） must be researched and verified in ancient literature. Therefore，it has become important contents in the study of classic prescriptions that researching the source of prescriptions from the ancient books，combing and analyzing literature，and studying the evolution rules of indications，preparations，methods of administration and taboos.The author searched a variety of ancient Chinese medicine databases and collected the relevant documents related to Xiehuangsan in ancient medical books. A total of 242 pieces of relevant ancient document data were obtained，involving 131 types of ancient Chinese medicine books. Through combing the relevant records of historical documents，this paper analyzes and researches the historical evolution of Xiehuangsan，the source and composition of the prescriptions，the indications，the dosage，the textual research of Chinese herbal medicine and the determination of the basis，and the method of prescription preparation and administration，etc. The historical changes of Xiehuangsan and its internal relations are expected to provide literature references and theoretical basis for the modern development and research of Xiehuangsan.

Huaier Extractum Promotes Dendritic Cells Maturation and Favors them to Induce Th1 Immune Response: One of the Mechanisms Underlying Its Anti-Tumor Activity.

Huaier, a sandy beige mushroom with anti-tumor effects, has been applied into Traditional Chinese Medicine for more than 1600 years. Previous studies showed that Huaier exerted its anti-tumor effects not only by direct action on tumor cells, but also indirectly by modulation of immune function. In the present study, we found that Huaier treatment significantly repressed tumor growth in mice with 4T1 breast cancer and resulted in significant accumulation of CD4+ T cells and mature dendritic cells (DCs) in the tumor microenvironment. In vitro experiments demonstrated that Huaier treatment promoted both DC2.4 and bone marrow derived DCs (BMDCs) to express costimulatory molecules, enhance production of IL-1ß and IL-12p70, while it inhibited their phagocytic activities, suggesting that Huaier treatment promotes maturation of DCs. Furthermore, we found Huaier-treated DCs profoundly stimulated proliferation of alloreactive CD4+ T cells and drove them to differentiate into Th1 subset. Expression of PI3K, Akt, p-Akt, JNK, and p-JNK was up-regulated, while p-p38 MAPK was down-regulated in Huaier-treated BMDCs, suggesting that Huaier promotes maturation of DCs with potent ability to activate Th1 immune response via modulation of MAPK and PI3K/Akt signaling pathways. Our findings provide further evidence for the mechanisms underlying the anti-tumor activity of Huaier.

Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.

A novel UPLC/MS/MS method for rapid determination of murrayone in rat plasma and its pharmacokinetics.

Murraya paniculata (L.) is a traditional Chinese medicine (TCM) wildly grown in southeast China, and used for abortion in folk. Murrayone, a coumarin-containing compound extracted from M. paniculata, is the most bioactive substance in this species and is being developed as a novel cancer metastasis chemopreventive agent based on its unique pharmacological properties. In the present study, a novel rapid and sensitive method for quantitative analysis of murrayone in rat plasma and for determining its pharmacokinetics in rats was developed and validated using UPLC/MS/MS. Plasma samples were subjected to protein precipitation and then directly analyzed by UPLC/MS/MS. Both murrayone and coumarin as an internal standard (I.S.) were carried on a C18 column with a gradient mobile phase consisting of acetonitrile and water at a flow rate of 0.3 mL/min. Several gradient elution procedures were evaluated to achieve effective chromatography resolution and a sensitive response to murrayone and the I.S.. Mass spectrometry was carried out using a triple-quadrupole system via positive electrospray ionization and multiple reaction monitoring (MRM). Good linearity (r 2 = 0.9987) was achieved over a linear range of 4.0-1600 ng/mL with a lower limit of quantitation (LLOQ) of 4.0 ng/mL for murrayone. The inter- and intraday accuracy and precision ranged from 90.0 to 99.7% and 1.1 to 12.3% at four quality control concentrations, respectively. The average absolute recoveries of murrayone and the I.S. were determined to be 85.9-92.4% and 86.5-90.7%, respectively, at 10.0, 80.0, and 800 ng/mL. Murrayone was stable under a variety of storage and processing conditions that may be routinely encountered in laboratories based on all the stability tests. This newly developed method was successfully applied to the pharmacokinetic study of murrayone in rats for the first time, and the current assay methodology could provide important insights into potential therapeutics and facilitate further pharmacodynamic explorations of murrayone.

Trametes robiniophila Murr: a traditional Chinese medicine with potent anti-tumor effects.

Trametes robiniophila Murr also known as Huaier, one of the traditional Chinese medicines, has been shown an effective adjuvant of cancer therapy. Accumulating evidence suggests that the anti-cancer effects of Huaier can be briefly divided into two aspects: the direct effects on tumor cells and the indirect effects on immune cells. In vitro and in vivo experiment showed Huaier directly inhibited tumor cell proliferation, induced tumor cell death, prevented metastasis and interfered with angiogenesis via various signaling pathways. The immunomodulatory effect of Huaier is associated with enhancement of the number and function of CD4+ T cells and NK cells, regulation of the polarization and function of macrophages, and elevated secretion of immune stimulatory cytokines. In this review, the anti-cancer effects and combined treatments of Huaier with other anti-cancer therapies, and the underlying mechanisms are summarized and discussed.

Sustained substrate cycles between hexose phosphates and free sugars in phosphate-deficient potato (Solanum tuberosum) cell cultures.

MAIN CONCLUSION: Futile cycling between free sugars and hexose phosphates occurring under phosphate deficiency could be involved in the maintenance of a threshold level of free cellular phosphate to preserve respiratory metabolism. We studied the metabolic response of potato cell cultures growing in Pi sufficient (2.5 mM, +Pi) or deficient (125 µM, -Pi) conditions. Under Pi deficiency, cellular growth was severely affected, however -Pi cells were able to maintain a low but steady level of free Pi. We surveyed the activities of 33 primary metabolic enzymes during the course of a 12 days Pi deficiency period. Our results show that many of these enzymes had higher specific activity in -Pi cells. Among these, we found typical markers of Pi deficiency such as phosphoenolpyruvate phosphatase and phosphoenolpyruvate carboxylase as well as enzymes involved in the biosynthesis of organic acids. Intriguingly, several ATP-consuming enzymes such as hexokinase (HK) and phosphofructokinase also displayed increased activity in -Pi condition. For HK, this was associated with an increase in the steady state of a specific HK polypeptide. Quantification of glycolytic intermediates showed a pronounced decrease in phosphate esters under Pi deficiency. Adenylate levels also decreased in -Pi cells, but the Adenylate Energy Charge was not affected by the treatment. To investigate the significance of HK induction under low Pi, [U-14C]-glucose tracer studies were conducted. We found in vivo evidence of futile cycling between pools of hexose phosphates and free sugars under Pi deficiency. Our study suggests that the futile cycling between hexose phosphates and free sugars which is active under +Pi conditions is sustained under Pi deficiency. The possibility that this process represents a metabolic adaptation to Pi deficiency is discussed with respect to Pi homeostasis in Pi-deficient conditions.

Acupoint Catgut Embedding Alleviates Insomnia in Different Chinese Medicine Syndrome Types: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To investigate the effects and safety of catgut embedding on alleviating insomnia.@*METHODS@#Totally 510 patients with insomnia were divided into 5 Chinese medicine (CM) syndrome types: Xin (Heart) and Pi (Spleen) deficiency, yin deficiency with excess fire, Xin and gut qi deficiency, Wei (Stomach) disorder, and qi and blood deficiency, respectively. These 5 types of patients were randomly assigned to a catgut embedding group, an acupuncture group or a medication group (30 cases in Xin and Pi deficiency type, Wei disorder type, Xin and gut qi deficiency type, respectively; 40 cases in yin deficiency with excess fire type and qi and blood deficiency type, respectively). In the catgut embedding group, patients were treated by implanting catgut into acupoints once every 10 days for a total of 30 days. In the acupuncture group, patients were treated with acupuncture once per day over 30 days (excluding weekends); and patients in the medication group took 1 mg Eurodin Tablet orally every night for 30 days. Pittsburgh Sleep Quality Index (PSQI) was evaluated before treatment, on 30 and 60 days after the first treatment, respectively. The International Unified Sleep Efficiency Value (IUSEV) was measured at 30 and 60 days. The safety was evaluated after treatment and adverse events were analyzed.@*RESULTS@#The objective PSQI scores including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, and total scores at 30 days were significantly improved compared with pre-treatment in the catgut embedding and acupuncture groups (P<0.01 or P<0.05). At 30 days, the PSQI scores in catgut embedding group were superior to the medication group in the patients with each type of insomnia, with the exception of sleep duration (P<0.01 or P<0.05). At 60 days, significant differences were found between the catgut embedding group and the medication group (P<0.01 for all indices). The IUSEV scores in the catgut embedding group were significantly higher than the acupuncture group at 60 days, and the scores in acupuncture group were higher than the medication group at 30 days (P<0.05 for all types). No severe adverse events were found in this study.@*CONCLUSIONS@#Acupoint catgut embedding and acupuncture were more effective than medication in alleviating insomnia syndrome in different Chinese medicine syndrome type. However, the sustained effects of acupoint catgut embedding were superior to acupuncture.

Squamous cell carcinoma of the spleen: A case report.

Tumor incidence in the spleen is relatively low compared with that in other organs. The majority of primary splenic tumors are benign, and the majority of malignant tumors are lymphoma or fibrosarcoma. While the occurrence of single squamous cell carcinoma in the spleen is rare, the present study reports a case of single splenic squamous cell carcinoma in which the patient received surgery, chemotherapy and Chinese herbal treatment, and died 14 months after diagnosis. As to the best of our knowledge this case type has not been previously reported; the present study provides insight into the response for standard treatment and the prognosis of the splenic squamous cell carcinoma for a single case.

A Flavonoid Glycoside Compound from Murraya paniculata (L.) Interrupts Metastatic Characteristics of A549 Cells by Regulating STAT3/NF-κB/COX-2 and EGFR Signaling Pathways.

Metastasis remains the leading cause of death from lung carcinoma. It is urgent to find safe and efficient pre-metastasis preventive agents for cancer survivors. We isolated a flavonoid glycoside, hexamethoxy flavanone-o-[rhamnopyranosyl-(1 â†’ 4)-rhamnopyranoside (HMFRR), from the traditional Chinese medicine (TCM) Murraya paniculata (L.) that can effectively inhibit the adhesion, migration, and invasion of lung adenocarcinoma A549 cells in vitro. Molecular and cellular studies demonstrated that HMFRR significantly downregulated the expressions of cell adhesion-related and invasion-related molecules such as integrin ß1, EGFR, COX-2, MMP-2, and MMP-9 proteins. Additionally, HMFRR effectively downregulated the expressions of epithelial-mesenchymal transition (EMT) markers (N-cadherin and vimentin) and upregulated that of E-cadherin. Moreover, these inhibitions were mediated by interrupting STAT3/NF-κB/COX-2 and EGFR/PI3K/AKT signaling pathways. Furthermore, HMFRR counteracted the expressions of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin) stimulated by interleukin-1ß in human pulmonary microvascular endothelial cells (HPMECs). As a result, HMFRR interrupted the adhesion of A549 cells to HPMECs. Collectively, these results indicate that HMFRR may become a good candidate for cancer metastatic chemopreventive agents by interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways.

Small molecule inhibitor TW-37 is tolerable and synergistic with chemotherapy in nasopharyngeal carcinoma.

Chemotherapy is a crucial adjuvant therapy of advanced nasopharyngeal carcinoma (NPC). However, enhancing sensitivity and tolerance of chemotherapeutics in NPC treatment have been challenging. Both Bcl-2 and Mcl-1, 2 pro-survival proteins of Bcl-2 family, play essential roles on the chemotherapy tolerance of numerous cancers. In the present study, we explored the influences of TW-37, a small molecule inhibitor of Bcl-2 and Mcl-1, on the efficiency of chemotherapy for NPC. Oncomine cancer database shows that NPC tissues have higher expression of Bcl-2 and Mcl-1 than those of normal nasopharyngeal epithelial (NPE) tissues. And our results reveal that chemotherapeutics, Cisplatin (CDDP) and 5-Fluoracil (5-FU), result in the greater decrease of protein level of Bcl-2 and Mcl-1 in NPC cells than those in NPE cells. TW-37 does not have significant impact on the chemotherapeutics-treated NPE cell viability at a dosage that efficiently reduces chemotherapeutics-treated NPC cell viability. Moreover, impacts of TW-37 on the cell viability of chemotherapeutics-treated NPC cells are dependent on the expression of Bcl-2 and Mcl-1 in NPC cells. Further explorations suggest that TW-37 prominently promotes apoptosis in NPC cells under chemotherapeutics treatments but not in NPE cells. Meanwhile, TW-37 also remarkably reduces colony formation ability of chemotherapeutics-treated NPC cells. Importantly, in vivo models, TW-37 observably increases chemosensitivity of NPC tumors but has not markedly influence on the normal tissues in mice. In conclusion, our results point to TW-37 as a promising ancillary drug for the chemotherapy of NPC.

The traditional Chinese medicine Achyranthes bidentata and our de novo conception of its metastatic chemoprevention: from phytochemistry to pharmacology.

Our recent biosystems analysis revealed similarities between embryonic implantation and cancer cell adhesion, which suggests that abortifacients may be good for safe and effective metastatic chemoprevention targeting circulating tumor cells (CTC). Here we test the hypothesis by using the well-known abortion herb Achyranthes bidentata Blume (A. bidentata). Five compounds were separated from the herb root. Among them, ginsenoside Ro was the most potent in inhibiting embryonic implantation within non-cytotoxic concentrations. It specifically inhibited the metastatic dissemination capability of colon cancer cells HT29, including the migration and invasion ability, and their adhesion to human endothelium through inhibiting integrin αvß6, MMP-2, MMP-9, and ERK phosphorylation by HT29. Pretreatment of nude mice with oral ginsenoside Ro followed by HT29 intravenous inoculation and 40-day oral ginsenoside Ro significantly prevented lung metastasis with downregulation of integrin αvß6 and no toxicity. The present study firstly introduces the new conception of utilizing safe and effective abortion botanic medicines for CTC-based metastatic chemoprevention.

[Clinical effects of rehabilitation exercise in the treatment of knee osteoarthritis based on the theory of "treating muscle for bone"].

OBJECTIVE: To study the efficacy and safety of voluntary rehabilitation exercise in the treatment of knee osteoarthritis, based on the traditional Chinese medicine theory of "treating muscle for bone". METHODS: Ninety participants with early knee osteoarthritis were randomly divided into experimental group (n=45) and control group (n=45). Patients in experimental group were treated with voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris. Patients in control group were treated with apparatus training combined with isometric extension of quadriceps femoris. The treatment course lasted for two weeks. Visual analogue scale (VAS), Lysholm score and total therapeutic effect were evaluated before and after treatments. RESULTS: After two weeks of treatment, cure-remarkable-effective rate in experimental group (86.67%) was higher than that in control group (71.11%). The VAS scores and Lysholm scores were significantly improved in both two groups (P<0.05). The results were significantly better in experimental group those in control group (P<0.05). There were no serious adverse events. CONCLUSIONS: Voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris was effective and safe in the treatment of early knee osteoarthritis.

Promising Compounds From Murraya exotica for Cancer Metastasis Chemoprevention.

Most of the present anticancer drugs are highly cytotoxic and focus mainly on killing tumor cells rather than slowing the progress of cancer metastasis. Evidence has been reported that bridges the mechanisms of inflammation and tumor invasion. Therefore, we evaluated the potency in cancer metastasis chemoprevention of compounds and a coumarin extracted from Murraya exotica, which is known for its anti-inflammation bioactivity. By carrying out experiments in vitro, we found the root extracts more efficient than the leaf extracts in restraining cell migration of MDA-MB-231 cells, while leaf extracts presented slightly stronger inhibition of tumor cell adhesion at low concentrations. In addition, compared to root extracts, a novel coumarin identified previously from root extracts showed equal inhibition on cancer cell adhesion and less inhibition on cell migration. All extracts used in this study presented low cytotoxicity in vitro. Through comparison of the contents of leaf and root extracts from M exotica, several compounds are considered promising against cancer metastasis. This study evaluates the worth of further development of M exotica to find its effect on cancer metastasis chemoprevention.

Clinical effects of rehabilitation exercise in the treatment of knee osteoarthritis based on the theory of "treating muscle for bone" / 中国骨伤

<p><b>OBJECTIVE</b>To study the efficacy and safety of voluntary rehabilitation exercise in the treatment of knee osteoarthritis, based on the traditional Chinese medicine theory of "treating muscle for bone".</p><p><b>METHODS</b>Ninety participants with early knee osteoarthritis were randomly divided into experimental group (=45) and control group (=45). Patients in experimental group were treated with voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris. Patients in control group were treated with apparatus training combined with isometric extension of quadriceps femoris. The treatment course lasted for two weeks. Visual analogue scale (VAS), Lysholm score and total therapeutic effect were evaluated before and after treatments.</p><p><b>RESULTS</b>After two weeks of treatment, cure-remarkable-effective rate in experimental group (86.67%) was higher than that in control group (71.11%). The VAS scores and Lysholm scores were significantly improved in both two groups (<0.05). The results were significantly better in experimental group those in control group (<0.05). There were no serious adverse events.</p><p><b>CONCLUSIONS</b>Voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris was effective and safe in the treatment of early knee osteoarthritis.</p>

The paradigm-shifting idea and its practice: from traditional abortion Chinese medicine Murraya paniculata to safe and effective cancer metastatic chemopreventives.

Recent large epidemiological studies demonstrated benefit of oral contraceptives in reducing cancer risk, and our analysis also showed molecular and cellular similarities between embryo implantation and CTCs adhesion-invasion to endothelium. We here hypothesize that abortion traditional Chinese medicine (TCM) may serve well for pre-metastatic chemoprevention. To test the hypothesis, we selected the safe and well-known abortifacient TCM Murraya paniculata and identified a most-promising extracted fraction G (containing flavonoids and coumarins) from its many raw ethanol/dichloromethane extracts by using the bioactivity-guided fast screen assay. G showed free radical scavenging effect, and specifically inhibited both embryo implantation to human endometrial bed and cancer HT29 cells to human endothelium in a concentration-dependent manner (1-30 µg/mL) without significant cytotoxicity demonstrated by its high adhesion inhibition ratio. The inhibition may result from its down-regulation on expression of integrin ß1 and α6, and CD44 on HT29 cells, as well as E-selectin on endothelial cells. Furthermore, G inhibited invasion and migration of HT29 cells. Pretreatment followed by one-month oral administration of G to the immunocompetent mice inoculated with mouse melanoma cells produced significant inhibition on lung metastasis without marked side effects. Collectively, this paradigm-shifting study provides, for the first time, a new strategy to discover safe and effective pre-metastatic chemopreventives from abortion TCM.

Bioactivity-guided fast screen and identification of cancer metastasis chemopreventive components from raw extracts of Murraya exotica.

Murraya exotica is a traditional Chinese medicine (TCM) widely grown in southeast China. We herein proposed a fast strategy for separation and identification of active components of cancer metastatic chemopreventives from the root, leaf, twig and stem bark extracts that were obtained by reflux in 80% acidic ethanol and then liquid-liquid extraction. High performance liquid chromatography (HPLC) analysis showed that the extract mixtures from leaf, bark and twig were similar, while the root extract contained a characteristic component (CM1). Bioactivity assays revealed that the root extract contained some active components that significantly inhibited cancer cell viability and migration. Ultra performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (UPLC-DAD-ESI-MS) analysis indicated the existence of coumarins in the root and leaf extracts. Semi-preparative chromatographic separation and physicochemical characterization indicated that CM1 was a novel coumarin derivative that warrants further chemopreventive studies on cancer metastasis. The present phytochemical and phytopharmacological studies exemplify a fast strategy for screening and identifying active component(s) from raw extracts of phytomedicines.