Clinical Comparative Study of Two Kind Doses of Bortezomib Combinated with Bisphosphonates for Treating Patients with Multiple Myeloma Ostespathy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy and safety of conventional dose and reduction dose of bortezomib in combination with bisphosphonates for treating patients with multiple myeloma ostespathy.</p><p><b>METHODS</b>A total of 150 patients with multiple myeloma ostespathy were chosen in the period from March 2011 to July 2015 and randomly were divided into 2 groups: A group (75 cases) and B group (75 cases). The patients in A and B groups were treated with conventional dose of bortezomib and reduction dose of bortezomib on the basis of bisphosphonates respectively and the clinical efficacy, the improvement rate of life quality, NRS score, levels of IL-6 and CRP before and after treatment, and the adverse effects of 2 groups were compared.</p><p><b>RESULTS</b>There was no significant difference in the clinical efficacy between 2 groups (P<0.05). The improvement rate of patients life quality in B group was significantly better than that in A group (P>0.05). There was no significant difference in the NRS score, levels of IL-6 and CRP after treatment between 2 groups (P>0.05). There was no significant difference in the incidence of neutrophil reduction and thrombocytopenia between 2 groups (P<0.05). The incidence of BiPN, nausea and vomiting, herpes zoster and fatigue of B group was significantly lower than that in A group (P<0.05).</p><p><b>CONCLUSION</b>Conventional dose and reduction dose of bortezomib in combination with bisphosphonates for treating patients with multiple myeloma ostespathy possess the same effects, including pain relief and disease progression control; but the reduction dose of bortezomib application can efficiently improve the life quality of patients and reduce the risk of adverse reactions.</p>

Effect of G Protein-coupled Receptor Kinase 6 on Proliferation and Apoptosis of Multiple Myeloma Cells and Its Mechanisms / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the effect of G protein-coupled receptor kinase 6(GRK6) on proliferation and apoptosis of multiple myeloma(MM) cells and its mechanisms.</p><p><b>METHODS</b>The samples were collected from MM patients and healthy people for study in vivo. The plasma cells isolated from multiple myeloma patients, as well as U266 and NCI H929 myeloma cell lines were used for study in vitro. Western blot and quantitative real-time PCR were used to evaluate the protein and mRNA of expression of GRK6 in multiple myeloma, cell proliferation and apoptosis were tested by BrdU and Annexin V-FITC/PI assays.</p><p><b>RESULTS</b>The protein and mRNA expression of GRK6 in multiple myeloma was higher than those in control group, and the expression level of GRK6 in stage I of MM was higher than that in control group, while the expression level of GRK6 in stage II was higher than that in stage I, but lower than that in stage III (P<0.05). U266 and MM cells showed high-sensitivity to CX-4945, except NCI H929. GRK6 expression level in U266, NCI H929 and MM cells treated with siRNA and CX-4945, significantly decreased as compared with those cells treated by CX-4945 alone. Cell proliferations of U266, NCI H92 and MM groups treated with CX-4945 were (58.25±18.24)%, (64.32±20.03)% and (45.42±25.01)% respectively, moreover, their apoptotic rates were (62.82±53.21)%, (43.25±47.05)% and (85.67±40.32)% respectively.</p><p><b>CONCLUSION</b>The expression level of GRK6 in multiple myeloma increases, and GRK6 inhibitor CX-4945 inhibits proliferation and promotes apoptosis of myeloma cells; GRK6 regulates Rac1 and involves in the proliferation and apoptosis pathway of multiple myeloma cells.</p>

JNK in spinal cord facilitates bone cancer pain in rats through modulation of CXCL1 / 华中科技大学学报（医学）（英德文版）

In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP.

JNK in spinal cord facilitates bone cancer pain in rats through modulation of CXCL1 / 华中科技大学学报（医学）（英德文版）

In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP.

Soft tissue reconstruction for secondary deformity after correction of Wassel type IV-D thumb duplication / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate an effective therapeutic method for the secondary deformity after the correction of the Wassel type IV thumb duplication.</p><p><b>METHODS</b>9 cases of Wassel W-D Complex thumb deformities in children with postoperative secondary deformity, including 6 males and 3 female, were treated. The age ranged from 2.0 to 14 years old with an average of 5.3 years old. During the operation, the anatomical structure was dissected to observe the structure and alignment of the flexor tendon as well as anatomical structure of the joint. In the meantime, the flexor pollicis longus tendon was shifted, A2 pulley was reconstructed, joint capsule was released and contracted, the end point of thenar was shifted. Kirschner wires fixation were used for about 4-5 weeks, the brace fixation for about 3 months.</p><p><b>RESULTS</b>All the patients had radial side skin contracture of the interphalangeal joint, radial deviation of the thumb tip, radial side contracture and ulnar relaxation of the joint capsule. Flexor hallucis longus tendon was located in front of the radial side of the proximal phalanx, with no wrapped sheath or A2 pulley. Flexor hallucis longus tendon was attached to the thumb tip substrate, of which 1/3 was located in the center and 2/3 in the radial side. The thumb tip rotated about 10 degrees-15 degrees to the radial side. The patients were followed up for 6-38 months, with an average of 24 months. We adopted Tada standard to evaluate the follow-up results as excellent in 7 cases, good in 1 case, poor in 1 case.</p><p><b>CONCLUSIONS</b>Soft tissue reconstruction for the secondary deformity after the correction of the Wassel type IV-D thumb duplication is an effective method. Application of the brace after removal of Kirschner wires has an important role in preventing the secondary deformity.</p>

Role of the lung in the progression of multiple organ dysfunction syndrome in ageing rat model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multiple organ dysfunction syndrome in the elderly (MODSE) is a problem with high mortality in the critical care of elderly patients. The pathogenesis of MODSE remains elusive. This study aimed to establish rat models of MODSE and to investigate the pathogenetic mechanism responsible for the development of MODSE in the rat models.</p><p><b>METHODS</b>Twenty-four-month old rats (elderly) received intravenous injection of lipopolysaccharide (LPS) to induce rat model of MODSE. In the model, we observed the physical responses, biochemical indices changes, histopathological features of vital organs, including lung, liver, heart, and kidney. We also investigated the sequence of individual organ dysfunction and changes of proinflammatory factors. Three-month-old rats, serving as young rat controls, received parallel procedures. Besides, normal saline injection was also performed on elderly and young control rats.</p><p><b>RESULTS</b>All rats displayed different degree of physical response after LPS injection, preceded by deterioration of respiratory status. At 6 hours, lung injury was observed, which started earlier than other organ injury that was observed in about 24 hours. Furthermore, all vital organ injury was more severe in elderly rats than in young rats at the same time points. After LPS injection, pulmonary alveolar macrophages apoptosis rate increased obviously, and was more significant in elderly rats ((43.4 ± 8.4)%) than in young rats ((24.2 ± 3.0)%). LPS injection also enhanced tumor necrosis factor a (TNF-a) concentration significantly in these organs. Its peak concentration appeared at 6 hours in lung tissue and at 24 hours in other organs after LPS injection. TNF-a level was higher in elderly rats than in young rats at the same time points. The increase was most significant in lung tissue. After intravenous administration of LPS, toll-like receptor 4 (TLR4) expression in lung tissue was upregulated markedly, and peaked at 6 hours. In contrast, upregulation of TLR4 expression in liver peaked at 24 hours, lagging behind that in the lung.</p><p><b>CONCLUSION</b>Lung is the first and most seriously injured organ in rat model of MODSE and it may play an "initiating" role in the development of MODSE.</p>

The prevention of denhong injection on contrast-induced renal impairment after percutaneous coronary intervention / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the prevention of Danhong Injection (DHI) on contrast-induced renal impairment after percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>Eighty patients receiving PCI were randomly assigned to the control group and the treatment group, 40 in each. All patients used loperamide injection as the contrast media, and received routine medicines such as enteric coated aspirin and Betaloc, as well as routine rehydration therapy. As for patients in the treatment group, 20 mL DHI was intravenously dripped by adding in 250 mL 0.9% sodium chloride injection from 2 -3 days before PCI to 3 days after PCI, once daily. The levels of serum creatinine (SCr), cystatin C (CysC), urine micro-albumin (mAlb), and beta2-microglobulin (beta2-MG) were measured before PCI, and 24, 48, 72 h after PCI. The occurrence of radio contrast-induced nephropathy (RCIN) of the two groups was observed.</p><p><b>RESULTS</b>The serum SCr and CysC levels of the two groups reached the peak 24 h after PCI (P < 0.05, P < 0.01). But they respectively restored to the pre-PCI levels at 48 and 72 h after PCI in the treatment group. In the control group the serum SCr level basically restored to the pre-PCI level at 72 h after PCI. The urinary mAlb and beta2-MG levels of the two groups reached the peak at 24 and 48 h after PCI (P < 0.05, P < 0.01), and basically restored to the pre-PCI level at 72 h after PCI. But they did not restore in the control group (P < 0.05). Seven patients suffered from RCIN in the two groups, of them 5 (12.5%) in the control group and 2 (5.0%) in the treatment group, with no statistical difference (P > 0.05).</p><p><b>CONCLUSIONS</b>DHI could effectively prevent contrast-induced renal impairment and shorten the recovery time of renal impairment. It was worth further studies.</p>

Effect of Xin'anning Nasal Drop in treating coronary heart disease with unstable angina pectoris / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Xin'anning Nasal Drop (XAND) in treating coronary heart disease with unstable angina pectoris (CHD-UAP).</p><p><b>METHODS</b>Sixty patients with CHD-UAP were assigned, according to the randomizing number table, to two groups, the control group treated with conventional Western medicine, and the treated group treated with conventional Western medicine plus XAND. The clinical efficacy and the changes of S-T segment in resting EKG and total ischemia burden (TIB) in 24-h dynamic EKG were observed.</p><p><b>RESULTS</b>The clinical efficacy, including the effect of angina alleviation, its initiation, and the effect of TCM syndrome score reduction, were significantly superior in the treated group to those in the control group ( P<0.05 or P<0.01). The degree and extent of myocardial ischemia were significantly improved in both groups ( P<0.01), but the improvement in the treated group was better than that in the control group ( P<0.05). Moreover, it was worth mentioning that the immediate effect in the treated group was better than that in the control group, and the reduction of TIB, the improvement in heart rate and myocardial oxygen consumption (immediately after the first administration or by the end of the therapeutic course), and systolic blood pressure after treatment in the former were all superior to those in the latter, showing significant difference (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>XAND has a quick effect in alleviating angina in patients with CHD-UAP, and it is worthy of further studies and spreading in clinical practice. unstable angina pectoris, Xin'anning Nasal Drop, clinical study</p>