Objective To compare the effects of heat-sensitive moxibustion and ginger-partition moxibustion on refractory peripheral facial paralysis. Methods Fifty-five patients with refractory peripheral facial paralysis were randomized into heat-sensitive moxibustion group (N=28) and ginger-partition moxibustion group (N=27). For two cases dropped out during the treatment, a total of 25 cases were finally enrolled into the ginger-partition moxibustion group. Two groups received oral use of mecobalamin tablets and conventional acupuncture, and heat-sensitive moxibustion group was given heat-sensitive moxibustion and ginger-partition moxibustion group was given ginger-partition moxibustion additionally. The moxibustion was performed once a day and ten times constituted one course, the treatment covered 6 courses. The clinical effect of the two groups was evaluated by 40-score method, House-Brackmann facial neurological function evaluation standard, blink reflex ( BR) , electromyogram and electroneurography. Results ( 1) Symptoms integral was increased in both groups after treatment ( P<0.01) , and the scores of heat-sensitive moxibustion group were higher than those of ginger-partition moxibustion group ( P<0.01). ( 2) The markedly effective rate of heat-sensitive moxibustion group was 75.00% and that of ginger-partition moxibustion group was 44.00%, and there was statistically significant difference between them ( P<0.05). ( 3) The results of electrophysiological examination showed that the difference values of ipsilateral and contralateral BR R1, R2, R2’ in both groups after treatment were less than those before treatment ( P<0.01) , and the abnormal rate of electromyography for heat-sensitive moxibustion group was improved obviously after treatment ( P<0.01) . The amplitude of compound muscle action potentials ( CMAP) of orbicularis oculi/orbicularis oris at the affected side of both groups showed a decreasing trend, but the differences were insignificant between the two groups after treatment ( P>0.05). Conclusion The curative effect of heat-sensitive moxibustion for the treatment of refractory peripheral facial paralysis is better than that of ginger-partition moxibustion.

ObjectiveForskolin （FSK） analogs，isoforskolin （isoF），deacetylforskolin（deaF），and 1-acetylforskolin（1-aF），extracted from Coleus forskohlii native to Yunnan，were assayed for their adenylate cyclase stimulating activities in vitro and for effects of two analogs on ocular hypertension （OHT） in water-loaded rabbits．MethodsAdenylate cyclase stimulation was determined by protein-binding method of radioimmunoassay，and intraocular pressure was monitored by pneumatonometer．ResultsIt showed that isoforskolin and forskolin stimulated adenylate cyclase in vitro with almost equal activity，deacetylforskolin with milder activity，and 1-acetylforskolin with little activity in vitro．1％ deaF and 1-aF suppressed rabbit OHT induced by water-loading for at least 3h，with the maximal inhibitory rates of 6.0，10.9% respectively．ConclusionThis study suggests that two foskolin analogs （isoforskolin，deacetylforskolin） possess adenylate cyclase stimulation activities in vitro；deacetylforskolin and 1-acetylforskolin suppress OHT induced by water-loading in rabbits．

Objective: To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) . Methods: Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis. Results: Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (HR=2.656, 95%CI 1.204-5.858, P= 0.016) and the level of serum ferritin before tansplantation (HR=3.170, 95%CI 1.400-7.180, P=0.006) were significant risk factors for PGF. Conclusion Unrelated donor transplantation and the high level of serum ferritin before transplantation are risk factors for PGF.

OBJECTIVE: To observe the therapeutic effect of tetramethylpyrazine on immune-mediated bone marrow failure (BMF) induced by different doses of X-ray exposure in C57 mice. METHODS: C57BL6 mice were randomized into 4 groups, including a blank control group and 3 X-ray exposure groups with X-ray exposure at low (5.0 Gy), moderate (5.75 Gy), and high (6.5 Gy) doses. After total body irradiation with 0.98 Gy/min X-ray. The mice as recipient received injections of 4×10 lymphocytes from DBA/2 mice via the tail vein within 4 h. The survival rate of the recipient mice, peripheral blood cell counts, bone marrow nucleated cell count, and bone marrow pathology were examined at 14 days after the exposure. In the subsequent experiment, C57 mice were exposed to 5.0 Gy X-ray and treated with intraperitoneal injection of tetramethylpyrazine at the low (5 mg/mL), moderate (10 mg/mL), or high (20 mg/mL) doses (12 mice in each group) for 14 consecutive days, and the changes in BMF were observed. RESULTS: X-ray exposure, especially at the high dose, resulted in significantly lowered survival rate in the mouse models of BMF at 14 days. As the X-ray dose increased, the mice showed significantly reduced peripheral blood counts of red blood cells, white blood cells, platelets and lowered bone marrow nucleated cell counts with obvious bone marrow congestion and reduction of nucleated cells ( < 0.05 or 0.001). In the mice exposed to 5.0 Gy X-ray, tetramethylpyrazine at the high dose most obviously increased bone marrow nucleated cells ( < 0.01) and red blood cells ( < 0.001), and even at the low dose, tetramethylpyrazine significantly increased the counts of white blood cells ( < 0.05) and platelets ( < 0.01) following the exposure. Tetramethylpyrazine dose-dependently alleviated bone marrow hyperemia, increased bone marrow nucleated cell counts, and lowered Fas protein expression in the bone marrow. CONCLUSIONS X-ray irradiation at 5.0 Gy is suitable for establish mouse models of immune-mediated BMF. Tetramethylpyrazine promotes bone marrow repair by regulating Fas cell apoptosis signals, which further expands the traditional Chinese medicine theory of "removing blood stasis to create new."
Animals ; Bone Marrow ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Pyrazines ; Whole-Body Irradiation

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
Animals ; Mice ; Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Actins/metabolism* ; Neoplasm Recurrence, Local ; TOR Serine-Threonine Kinases/metabolism* ; Urinary Bladder Neoplasms ; Glycolysis ; Cell Line, Tumor ; Cell Proliferation ; Mammals/metabolism* ; Tripartite Motif Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Integrin beta Chains