ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Research on frequency of application with modern Chinese herbal medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the relationship between 500 kinds of commonly used Chinese herbal medicine and the classification of their efficacies in Chinese Materia Medica in relation to the common diseases listed in Internal Medicine.</p><p><b>METHODS</b>Database retrieval frequency of the quantitative statistical method was adopted. First, the 8 980 kinds of Chinese herbal medicine recorded in Chinese Materia Medica were used as the original search objects, and 4 493 kinds which were cited in more than five articles were picked out and then rechecked for further title citations. Second, as judged based on the Criterion, the numbers of articles which included the medicines in the line of standards were examined. As a result, 500 species of Chinese herbal medicine were singled out based on their retrieval frequency and were then used for compilation of the classification statistics according to their efficacy and the common diseases in Internal Medicine.</p><p><b>RESULTS</b>From the classification of Chinese medicines, herbs with wide efficiency and a meek nature had higher frequencies, but those which were not appropriate as decoctions had relatively lower frequencies. However, according to the average frequency, the Chinese herbal medicine for nourishing qi and tonifying blood, at 36,346 times and 34,544 times, respectively, were the most commonly used. Analyzed from the frequency of application of the Chinese medicine in the treatment of common diseases, most of the top 10 kinds of Chinese herbal medicine with the highest frequencies generally coincided with the 500 selected medicines. In addition, the Chinese medicines with clear pharmacological efficiency were easily isolated and purified to be made into injections, although other forms are more commonly used.</p><p><b>CONCLUSION</b>The results of the research objectively reflected the current applications of Chinese herbal medicine, and could be used as references in teaching, research, clinical applications, and in compiling and increasing the drugs in textbooks and Pharmacopoeia.</p>

Study on acupuncture treatment of diabetic neurogenic bladder / 中国针灸

<p><b>OBJECTIVE</b>To probe into a better therapy for diabetic neurogenic bladder.</p><p><b>METHODS</b>The patients were randomly divided into a treatment group and a control group, 35 cases in each group. The control group were treated with intramuscular injection of Methycobal 250 microg, once every other day; the treatment group were treated with intramuscular injection of Methycobal 250 microg, once every other day, and acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Ciliao (BL 32), Huiyang (BL 35), once every day. The residual urine were compared before and after treatment in the two groups; the effective rate for improvement of symptoms were compared between the two groups. The mental and healthy nursing were conducted for the patients.</p><p><b>RESULTS</b>After treatment, the improving rate for the urgency of urination, frequency of micturition, dribbling urination, urinary incontinence and dysuria in the treatment group was significantly better than that in the control group, but with no significant difference between the two groups in prolongation of urination time. After treatment, the residual urine in the bladder significantly improved in the two groups with more significantly improved in the treatment group than in the control group.</p><p><b>CONCLUSION</b>Methycobal plus acupuncture has a better result than the simple Methyeobal for treatment of diabetic neurogenic bladder, and strengthening nursing care in the treatment can significantly enhance life quality of the patient.</p>