The prognosis and treatment of newly diagnosed bone metastasis of head and neck squamous cell cancer: an analysis of racial disparity / El pronóstico y el tratamiento de las metástasis óseas recién diagnosticadas de cáncer de células escamosas de cabeza y cuello: un análisis de la disparidad racial

Objective: There is a lack of research investigating racial disparity in newly diagnosed head and neck squamous cell carcinoma with isolated bone metastases (HNSCC-BM). This study aims to investigate the clinical characteristics and prognostic factors in HNSCC-BM patients from different racial backgrounds to aid clinical decision making and management. Methods: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for 345 cases of HNSCC-BM that were diagnosed between 2010 and 2017. Survival was compared using univariate and multivariate Cox proportional hazards models, Kaplan–Meier analysis, and log-rank tests. We also used propensity score matching to adjust for confounders. Results: In white patients, those who were over 40 years of age had a significantly shorter survival (HR, 4.49; 95% CI 1.03–19.56; P < 0.05). Female black patients were found to survive longer compared to male patients (HR, 0.34; 95% CI 0.15–0.76; P < 0.01). Single (never married) Asians had shorter survival than married Asians (HR, 4.68; 95% CI 1.34–16.41; P < 0.05). In all three racial groups, patients who received radiotherapy in addition to chemotherapy did not survive longer than those receiving chemotherapy (P > 0.05). In Asian patients, those who underwent surgery at the primary site combined with chemoradiotherapy had significantly better survival outcomes than those who received chemoradiotherapy (HR: 0.10, 95% CI 0.01–0.88; P = 0.01). Conclusion: Prognostic factors differ between HNSCC-BM patients from different racial backgrounds.(AU)

Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury.

Electroacupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of EA in neurologic repair after SCI. First, we investigated the role of EA in the neurologic repair of the SCI rat model. The expression levels of human antigen R (HuR) and Krüppel-like factor 9 (KLF9) in spinal cord tissues were quantified after treatment. Second, we conducted bioinformatics analysis, RNA pull-down assays, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Last, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurologic repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA significantly diminished the SCI-mediated upregulation of HuR, and HuR could bind to the 3' untranslated region of KLF9 mRNA to protect its decay. In addition, a series of in vivo experiments confirmed that CMLD-2 administration increased EA-mediated pain thresholds and motor function in SCI rats. Collectively, the present study showed that EA improved pain thresholds and motor function in SCI rats via impairment of HuR-mediated KLF9 mRNA stabilization, thus providing a better understanding of the regulatory mechanisms regarding EA-mediated neurologic repair after SCI.

[Effect of elongated-needle by Hui-puncture method on piriformis syndrome].

OBJECTIVE: To observe the clinical effect of elongated needle by Hui-puncture method in the treatment of piriformis syndrome. METHODS: A total of 100 piriformis syndrome patients were randomly divided into routine acupuncture group (n＝50) and elongated needle by Hui-puncture method (Hui-puncture) group (n＝50). For patients of the routine acupuncture group, Huantiao (GB30), Juliao (GB29), Zhibian (BL54), Weizhong (BL40), Yanglingquan (GB34), Juegu (GB39) and Ashi-point on the affected side of the body were punctured with filiform needles for 30 min. And for those of the Hui-puncture group, elongated needles were respectively inserted into GB30 and Ashi-point. The treatment was conducted once every other day for 10 times. The visual analog scale (VAS) pain score and the severity scores of symptoms (hip pain, lower limb pain, walking ability, straight leg elevation test, piriformis muscle tension test, piriformis muscle tenderness, 0-15 points) were measured before and after the treatment. The therapeutic effect was assessed by Criteria for Diagnosis and Assessment of Therapeutic Effect of Syndromes or Illnesses of Traditional Chinese Medicine (1994). RESULTS: After the treatment, the scores of symptoms and VAS scores of both routine acupuncture and Hui-puncture groups were significantly decreased in comparison with their own pre-treatment (P<0.05), and the scores of the two indexes of the Hui-puncture group were evidently lower than those of the routine acupuncture group (P<0.05). Of the two 50 cases in the routine acupuncture and Hui-puncture groups, 39 and 47 were effective, with the effective rate being 78.00% and 94.00%, respectively. The comprehensive therapeutic effect of the Hui-puncture group was significantly superior to that of the routine acupuncture group (P<0.05). CONCLUSION: Elongated-needle by Hui-puncture method has significant effect in treating piriformis syndrome patients and is worthy of promotion.

Recovery of spinal cord injury following electroacupuncture in rats through enhancement of Wnt/ß-catenin signaling.

Electroacupuncture (EA) has been demonstrated to promote the functional recovery of neurons following spinal cord injury (SCI); however, the mechanisms underlying its effects have yet to be elucidated. The Wnt/ß-catenin signaling pathway has been implicated in the regulation of the balance between growth, proliferation and differentiation of neural precursor cells. The present study aimed to investigate the effects of EA therapy on Wnt/ß­catenin­regulated gene expression and neuronal recovery in rats with SCI. The Allen method was used to establish SCI in rats, and alterations in Wnt1 and Nestin mRNA and protein expression levels in response to SCI were determined on days 1, 3, 7 and 14 post­injury using reverse transcription­quantitative polymerase chain reaction and western blot analysis. To evaluate the effects of EA treatment on SCI, the following four treatment groups were employed: SCI, SCI + EA, SCI + lithium chloride (LiCl) and SCI + LiCl + EA. The protein expression levels of Wnt1, Nestin and nuclear ß­catenin were evaluated on day 3 post­treatment, and neuronal nuclear antigen (NeuN) protein expression levels were evaluated on day 21 post­treatment using western blot analysis. The Basso, Beattie and Bresnahan scoring method was used to evaluate spinal cord recovery on day 28 post­treatment across the four treatment groups. EA therapy at the Dazhui and Mingmen acupuncture points significantly increased the expression levels of Wnt1, Nestin, ß­catenin and NeuN, thus suggesting that EA therapy may promote spinal cord recovery following injury. The underlying mechanism was demonstrated to involve enhanced Wnt/ß­catenin signaling, which may promote the proliferation and differentiation of neural stem cells. However, further studies are required to elucidate the detailed effects and underlying molecular mechanisms of EA therapy on SCI.

[Correlation study on effects of electroacupuncture on the muscle condition and MNCV in rabbits with lumbar nerve root compression].

OBJECTIVE: To observe the effects of electroacupuncture on the muscle condition and electrophysiology of the muscle in rabbits with lumbar nerve root compression and to explore potential mechanisms. METHODS: Twenty-four New Zealand white rabbits were randomly divided into a normal group, a model group, a medication group and an electroacupuncture group. The rabbit model with lumbar nerve root compression was established in the model group, the medication group and the electroacupuncture group. The model and the treatment were not produced in the normal group. The medication group was treated with oral administration of Loxoprofen tablets at a dose of 30 mg each day for 14 days. The electroacupuncture group was treated with electroacupuncture at "Jiaji" (EX-B 2) of L5 and L6 for 14 days. The hibateral muscle condition before and after making model and after treatment was detected and the electromyogram and the nerve conduction velocity (NCV) were observed. RESULTS: The spontaneous potential and the insertion potential were increased in the model group, the medication group and the electroacupuncture group after making model. The value of the activation and the relaxed condition of the strength-creep (ARCSC) in the right muscle was significantly decreased. The motor nerve conduction velocity (MNCV) and the wave amplitude of evoked potential (WAEP) were significantly decreased in the model group, the medication group and the electroacupuncture group after treatment, but the value of MNCV and WAEP in the electroacupuncture group, and ARCSC in the right muscle in the electroacupuncture group and the medicine group were closed to those level in the normal group, among them, the relaxed condition in the electroacupuncture group was more close to the level in the normal group. CONCLUSION: Electroacupuncture can improve the strength-creep condition of the muscle that damage nerve place controls and the electrophysiology of the muscle can recover the MNCV and the wave amplitude of evoked potential in the compression nerve root.

Commentary--the proteomics: a new tool for Chinese medicine research.

Proteomics technology is based on the vast analytical power for protein/peptide identification and quantification offered by modern mass spectrometry coupled with hyphenated separation techniques such as two-dimensional gel electrophoresis (2DE) and micro- or nano-scale multidimensional liquid chromatography. The rapid growth of proteomics field provides an array of new tools for the integration of traditional Chinese medicine (TCM) with modern technology and systems biology, and is potentially advancing the progress of modernization and internationalization of TCM. Cho, in this issue of the American Journal of Chinese Medicine, highlights the recent application of 2DE-based and bottom-up proteomics in Chinese medicine research, including the exploration of pharmacological mechanisms of the actions of TCM, the facilitation of herb authentication and identification, and the profiling of protein expression following acupuncture treatment in animal models. Recent development in proteomics has provided further refinement on the analysis of proteins posttranslational modifications as well as quantitative comparison of different proteomes, and enabled the study of proteomes of specific diseases or biological processes under clinically relevant conditions. It is conceivable that the application of technologies developed in proteomics, genomics and metabonomics in the clinical practice and basic research of Chinese medicine will eventually lead to the reconciliation and integration of TCM and contemporary medicine. Chinese medicine is fundamentally a highly personalized medicine; perhaps it is time to embrace the arrival of TCM OMICS era in Chinese medicine research.

(+)-Myristinins A and D from Knema elegans, which inhibit DNA polymerase beta and cleave DNA.

A survey of crude plant extracts for DNA polymerase beta inhibitors resulted in the identification of a methyl ethyl ketone extract prepared from Knema elegans that strongly inhibited the enzyme. Subsequent bioassay-guided fractionation of the extract, using an assay to monitor the activity of DNA polymerase beta, led to the isolation of two potent inhibitors, (+)-myristinins A (1) and D (2), which are known flavans having unusual structures. (+)-Myristinins A and D exhibited IC50 values of 12 and 4.3 microM, respectively, as inhibitors of DNA polymerase beta in the presence of bovine serum albumin (BSA), and 2.7 and 1.2 microM in the absence of BSA. As such, they are the most potent DNA polymerase beta inhibitors reported to date. Compounds 1 and 2 potentiated the cytotoxicity of bleomycin toward cultured P388D1 cells, reducing the number of viable cells by at least 30% when employed at 9 microM concentration for 6 h in the presence of an otherwise nontoxic concentration of bleomycin (75 nM). Principles 1 and 2 also induced strong Cu2+-dependent DNA strand scission in a DNA cleavage assay. Accordingly, 1 and 2 exhibit two activities, namely, DNA polymerase beta inhibition and DNA damage.

DNA polymerase beta lyase inhibitors from Maytenus putterlickoides.

During a survey of plant secondary metabolites for DNA polymerase beta lyase inhibitors, we found that a crude methyl ethyl ketone extract prepared from Maytenus putterlickoides showed strong inhibition of the lyase activity of DNA polymerase beta in an in vitro assay. Bioassay-guided fractionation of the extract, using an in vitro assay, resulted in the discovery of a new active principle, 30-(4'-hydroxybenzoyloxy)-11alpha-hydroxylupane-20(29)-en-3-one (1), as well as a known compound, (-)-epicatechin (2). Compounds 1 and 2 exhibited DNA polymerase beta lyase inhibitory activity with IC50 values of 62.8 and 18.5 microM, respectively. Compound 2 was capable of potentiating the action of the monofunctional methylating agent methyl methanesulfonate in cultured human cancer cells, consistent with the possible utility of inhibitors of this type in vivo.

Plant sterols as selective DNA polymerase beta lyase inhibitors and potentiators of bleomycin cytotoxicity.

In a survey of crude plant extracts for DNA polymerase beta lyase inhibitors, the hexanes extracts of Cladogynus orientalis, Hymenache donacifolia, and Heteropsis integerrima, and the methyl ethyl ketone extract of Acacia pilispina were found to exhibit good inhibition of the dRP lyase activity of DNA polymerase beta. Bioassay-guided fractionation of these extracts led to the isolation of three DNA polymerase beta lyase inhibitory phytosterols, namely stigmasterol (1) and beta-sitosterol (2), isolated from the hexanes extracts, and beta-sitosterol-beta-d-glucoside (3), isolated from the methyl ethyl ketone extract. Compounds 1-3 inhibited the DNA polymerase beta lyase activity with IC(50) values of 43.6, 43.3, and 72.4 microM, respectively. Compounds 1 and 2 were found capable of potentiating the action of bleomycin in cultured human tumor cells, consistent with the possibility that lyase inhibitors may find utility in vivo.