[The new target of Rapamycin: lysosomal calcium channel TRPML1].

Rapamycin (Rap) is an immunosuppressant, which is mainly used in the anti-rejection of organ transplantation. Meanwhile, it also shows great potential in the fields of anticancer, neuroprotection and anti-aging. Rap can inhibit the activity of mammalian target of Rap (mTOR). It activates the transcription factor EB (TFEB) to up-regulate lysosomal function and eliminates the inhibitory effect of mTOR on ULK1 (unc-51 like autophagy activating kinase 1) to promote autophagy. Recent research showed that Rap can directly activate the lysosomal cation channel TRPML1 in an mTOR-independent manner. TRPML1 activation releases lysosomal calcium. Calcineurin functions as the sensor of the lysosomal calcium signal and activates TFEB, thus promoting lysosome function and autophagy. This finding has greatly broadened and deepened our understanding of the pharmacological roles of Rap. In this review, we briefly introduce the canonical Rap-mTOR-ULK1/TFEB signaling pathway, and then discuss the discovery of TRPML1 as a new target of Rap and the pharmacological potential of this novel Rap-TRPML1-Calcineurin-TFEB pathway.

Osteogenic differentiation characteristics of hip joint capsule fibroblasts obtained from patients with ankylosing spondylitis.

BACKGROUND: Autoimmune disease are fairly common and one that has an excessive degree of disability is Ankylosing spondylitis (AS). As the main cells in connective tissues, fibroblasts may play important roles in AS ossification. The conducted research aims to establish the osteogenic disparity characteristics of fibroblasts cultured in vitro, obtained via AS patients hip joint capsule, as well as investigating the pathological osteogenic molecular workings of AS. METHODS: AS patients hip joint capsules were acquired and fracture patients as the control with the finite fibroblast line were established by using tissue culture method. AS fibroblast proliferation, cycle and apoptosis, expression of osteogenic marker genes, osteogenic phenotypes, and the activation degree of the bone morphogenetic protein (BMP)/Smads signalling pathway were detected by flow cytometry, western blotting and real-time fluorescent quantitative polymerase chain reaction. RESULTS: Proliferative activity in AS fibroblasts were abnormally high, and the apoptotic rate decreased. Compared with normal fibroblasts, the mRNA expression of osteogenic marker genes, expression of osteogenic phenotypes, protein expression of core-binding factor a1 (Cbfa1), Smad1, Smad4, Smad5, phosphorylated (p) Smad1, and pSmad5 in AS fibroblasts were higher; however, the expression of Smad6 was lower. Moreover, recombinant human bone morphogenetic protein-2(rhBMP-2) stimulated Cbfa1 expression by normal and AS fibroblasts through the BMP/Smads signalling pathway. CONCLUSIONS: The fibroblasts of hip joint capsules in patients with AS cultured in vitro have biologic characteristics of osteogenic differentiation and may be important target cells of AS ossification. The Activated BMP/Smads signalling pathway could potentially be a mechanism relating to fibroblasts differentiating into osteoblasts and an ossification mechanism for AS.

[Spatial and temporal responses of habitat quality to urbanization: A case study of Changchun City, Jilin Province, China]. / 生境质量对城镇化的时空响应­­ä»¥é•¿æ˜¥å¸‚为例.

Habitat quality is an important index to evaluate regional ecological security. Revealing its spatial and temporal responses to urbanization is conducive to the in-depth implementation of new urbanization. Based on land use data, we analyzed the spatio-temporal characteristics of Changchun's landscape pattern, habitat quality and its sample zone from the grid scale with comprehensive utilization of spatial analysis and ecological model analysis. We further discussed the responses of habitat quality during urbanization. The results showed that the low values of patch density (PD), edge density (ED) and Shannon diversity index (SHDI) were distributed in the western plains, while the high aggregation index (AI) showed a patchy distribution in eastern and southern of the city. During 2000-2015, the habitat quality of Changchun showed a trend of degradation and significant spatial heterogeneity, showing a distribution of "high in the east, and low in the west". The expansion of construction land and the transportation infrastructure played a leading role in the degradation of regional habitat quality. The changes of habitat quality differed significantly in different zones. The overall variation of water belt was relatively small, while the variation frequency and amplitude of mountain, urban expansion, and traffic belt were relatively high. Natural factors including slope and elevation basically shaped the overall distribution pattern of habitat quality in Changchun, while urbanization factors including population density, GDP and night light index showed significant negative correlation with habitat quality. To alleviate the ecological pressure of urbanization and promote habitat quality, we proposed differentiated development strategies, such as preventing deforestation in the Dahei Mountains, using ecological strategies to restore habitat degradation areas, improving land use efficiency in built-up urban areas, promoting "smart growth" in urban areas, setting red line of farmland in hilly areas, and strengthening ecological infrastructure construction.

Bushen Qiangji Granule () medicated serum inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by inhibiting the BMP/Smads signal pathway in vitro.

OBJECTIVE: To explore the mechanism of Bushen Qiangji Granule (, BSQJ) in restraining the osteogenic differentiation of ankylosing spondylitis (AS) fifibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement and healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery as a control. Finite fifibroblast lines were established from these tissue samples to observe the effect of BSQJ on suppressing osteogenic differentiation of fifibroblasts. The expression of osteogenic marker gene corebinding factor a1 (Cbfa1) and Smad family proteins were examined by Western blot and real-time quantitative polymerase chain reaction (qPCR). RESULTS: The mRNA expression level of Cbfa1 was significantly higher in AS fibroblasts than that in normal fibroblasts and the expression of pSmad1, pSmad5, Smad4 and Cbfa1 in AS fibroblasts was also higher, demonstrating the activation of the BMP/Smads signal pathway in AS fifibroblasts. BSQJ-medicated serum not only restrained the mRNA and protein expression levels of Cbfa1 and inhibited protein expression level of Smad4 but also decreased the expression quantities of pSmad1 and pSmad5. CONCLUSIONS: BSQJ can inhibit osteogenic differentiation of AS fifibroblasts in vitro by suppressing the activation of the BMP/Smads signal pathway. This may be the important molecular mechanism of BSQJ in regulating AS ossifification.

Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis (RA), but its clinical efficacy and safety remain largely undefined in comparison with conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). METHODS: PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang Databases. Endpoints were ACR 20, 50, and 70, and the number of withdrawals due to adverse events. Initially, traditional pairwise meta-analysis was performed by using a random-effects model. Then, we performed network meta-analysis to compare different therapies by using frequentist approach. RESULTS: A total of 22 trials (5255 participants) were identified. By direct comparison, TwHF was superior to sulphasalazine according to ACR 20, 50 and 70. TwHF was superior to placebo according to ACR 20 and 50. By indirect comparisons, TwHF was superior to methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline and placebo according to ACR 20. Ranking by the Surface under the Cumulative Ranking curve (SUCRA) values showed that TwHF had the greatest probability for being the best treatment option according to ACR 20 (92.0 %) and ACR 50 (81.3 %), and the highest probability to be in the second (57.8 %) ranking position after leflunomide (69.6 %) according to ACR 70. By both direct and indirect comparisons, TwHF caused no more significant withdrawals than the placebo. The SUCRA values showed that TwHF had the highest probability to rank sixth (26.7 %) after the placebo (45.6 %) in causing withdrawals. CONCLUSIONS: Our data suggest that TwHF is effective and safe in the treatment of RA and has better clinical efficacy in terms of ACR 20 and 50 than existing conventional synthetic DMARDs. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.

Elemene, the essential oil of Curcuma wenyujin, inhibits osteogenic differentiation in ankylosing spondylitis.

OBJECTIVE: To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). RESULTS: The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene. CONCLUSIONS: Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

[Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation].

OBJECTIVE: To evaluate the curative effect and safety of Bushen Qiangji Decoction (BQD) and Qingre Qiangji Decoction (QQD) in treating ankylosing spondylitis (AS) patients, and to verify the clinical utility of AS syndrome differentiation and treatment scheme [Shen-deficiency induced stasis obstruction syndrome (SDISOS) and dampness-heat obstruction syndrome (DHOS) being two basic syndrome types, Shen invigorating blood activating method (SIBAM) and heat clearing dampness resolving method (HCDRM) being two basic treatment methods]. METHODS: Totally 354 AS patients of SDISOS and DHOS were randomly assigned to the treatment group and the control group using a multi-center randomized, positive drug parallel-controlled clinical trail. Patients in treatment group were treated by BQD or QQD according to syndrome typing, while those in the control group took Sulfasalazine enteric-coated tablet (SECT), 24 weeks as one therapeutic course. After treatment, the clinical efficacy was evaluated by using ASAS20 standard (set by Asessment in Ankylosing Spondylitis working group), Chinese medical efficacy evaluation standards, and BASDAI, BASFI, BASMI, night-pain index, spinal pain index, PGA, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: After 24 weeks of treatment by BQD or QQD, ASAS20 standard rate was 86.75% in the treatment group, and the total effective rate of Chinese medical syndrome was 85.47%. They could significantly reduce patients' integrals of Chinese medical syndrome, BASDAI, BASFI, BASMI, night-pain index, spinal pain index, and PGA (all P < 0.01). CONCLUSIONS: QQD and BQD got confirmable clinical effects in treating AS, providing strong evidence of evidence-based medicine for syndrome differentiation and treatment of AS.

Surgical treatment of a giant neurofibroma.

Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.

[Three-dimensional analysis of facial structure for unilateral cleft lip patients repaired by Millard's method].

OBJECTIVE: To evaluate the aesthetic effect of Millard' s method in patients with unilateral cleft lip by three dimensional sensing system. METHODS: 19 patients with unilateral cleft lip (class II: 7 cases, class III: 12 cases) were randomly selected. The pre- and postoperative 3-D facial profiles were recorded using a 3 DSS scanner. Then 3D geometric models were established by Geomagic Studio 10.0. In the software, columella length, nostril floor width, alar base-subnasale distance, alar length, upper lip height, lateral upper lip height and lip length were measured before and after lip repair respectively. Paired-samples T test and one-sample T test were used for statistical analysis with SPSS 12. 0 software package. RESULTS: There were significant differences in the nostril floor width, alar base-subnasale distance, alar length and lip length before and after operation (P < 0.05, P < 0.01). The ratio of asymmetry in normal people was no more than 0.1. There was significant difference in the asymmetry ratio of columella length and lateral upper lip height between postoperative class II patients and normal people (P < 0.05). There was significant difference in the asymmetry ratio of columella length, nostril floor width, alar base-suhnasale distance, lateral upper lip height and lip length between postoperative class III patients and normal people (P < 0.05 or P < 0.01). CONCLUSIONS: Millard's technique is useful for repairing unilateral cleft lip in rebuilding nasal floor, the Cupid' bow and in correction of the columella deviation, except for a relatively insufficient lip height and columella length at the operated side. Besides, the nostril floor width at the operated side in class III patients is still wider than that at the opposite side.

[Constructing tissue engineered trachea-like cartilage graft in vitro by using bone marrow stromal cells sheet and PLGA internal support: experimental study in bioreactor].

OBJECTIVE: To explore the feasibility of constructing tissue engineered trachea-like cartilage graft in vitro by using bone marrow stromal cells (BMSCs) sheet and PLGA internal support. METHODS: Rabbit BMSCs were expanded and induced by transforming growth factor-1 to improve chondrocyte phenotype of BMSCs. BMSCs sheets were obtained by continuous culture and wrapped the PGLA scaffold in the shape of cylinder. The constructs were incubated in spinner flask for 8 weeks and cartilage formation was investigated by gross inspection, histology, glycosaminoglycan and mechanical strength content. RESULTS: After in vitro culture, cartilage like tissue in cylindrical shape had been regenerated successfully. Stiff, shiny, pearly opalescence tissues were observed. Histological analysis showed engineered trachea cartilage consisted of evenly spaced lacunae embedded in matrix, cells stationed in the lacunae could be noticed clearly. Safranin-O staining on the sections showed homogenous and positive red staining, which demonstrated that the engineered tissue was rich in proteoglycans. CONCLUSIONS: Based on the cell sheet and internal support strategy, trachea-like cartilage in cylindrical shape could be successfully fabricated which provided a highly effective cartilage graft substitute and could be useful in many situations of trachea-cartilage loss encountered in clinical practice.

[Correction of progressive hemifacial atrophy using dermis-fat graft and Medpor implant shaped by reverse engineering technique].

OBJECTIVE: To evaluate the therapeutic effect of dermis-fat graft combined with Medpor implant shaped by reverse engineering technique in the correction of the progressive hemifacial atrophy. METHODS: A skull model was made by rapid prototyping and the bony deficiency model was acquired with reverse engineering technique. The Medpor implant was shaped precisely based on the deficiency model and implanted with dermis-fat graft at the same stage. RESULTS: 11 cases were treated successfully without infection, necrosis and rejection. The patients were followed up for six months to one year with satisfactory cosmetic improvement. The dermis-fat graft survived without obvious absorption. CONCLUSION: The technique can correct both the bony and soft tissue deficiency for progressive hemifacial atrophy. It is very practical and easily performed with reliant results and less morbidity.

Hyper-excitability in low threshold mechanical A fibers is potentially involved in scorpion BmK sting pain.

In the present study, using the single fiber recording technique, we found that BmK I, the main toxic component in scorpion Buthus martensi Karsch (BmK) venom, induced dramatic increase in excitability of rapidly adapting (RA) and type I slowly adapting (SAI) low threshold mechanical A fibers of rat. Five micrograms BmK I (691 nmol, in 10 microl saline) administrated to the receptive fields induced spontaneous activity in 80% of RA and SAI fibers, increased the response to 10 g-10 s stimulation at about 20 times and altered the firing pattern to burst mode with maximal NS (number of spikes in burst) averaging from all fibers studied as many as 59. The increase in the excitability of RA and SAI fibers did not recover completely in 2h. Our finding suggests that the gigantic abnormal activity in low threshold mechanical A fibers is involved in BmK scorpion sting pain, and the experimental model of BmK scorpion sting pain can be used to study A-fiber related central pathway which is important for relief of refractory neuropathic pain likewise.

Electrophysiological characterization of BmK I, an alpha-like scorpion toxin, on rNav1.5 expressed in HEK293t cells.

A recent study described the pharmacological properties of BmK I, an alpha-like toxin from the Chinese scorpion Buthus martensi Karsch, on the cardiac sodium channel (hH1) expressed in Xenopus oocytes. Considering that alpha-like toxins are unique in their inability to bind to rat synaptosomes despite a high toxicity by intravenous injection, the present study investigated the pharmacological properties of BmK I on rNav1.5 expressed in a mammalian HEK293t cell line. The results include: (1) BmK I slowed and partially inhibited the inactivation of rNav1.5, produced a substantial persistent current and increased peak current (the EC(50) for increasing peak current by BmK I was 99.4+/-20.1 nM); (2) BmK I delayed the recovery of the sodium channel from inactivation; (3) after exposure to 300nM BmK I, the steady-state activation curve of rNav1.5 was negatively shifted by about 19 mV; and (4) the association of BmK I and rNav1.5 was faster than their dissociation. The results show that BmK I displayed the pharmacological characteristics of an alpha-like toxin on rNav1.5 channels expressed in HEK293t cells, and suggested that the host expression system should be taken into consideration when characterizing the pharmacological properties of toxins.

[Predictive role of diagnostic information in treatment efficacy of rheumatoid arthritis based on neural network model analysis].

OBJECTIVE: To analyze the indications of the therapies for rheumatoid arthritis (RA) with neural network model analysis. METHODS: Three hundred and ninety-seven patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine (WM) treated group, 194 cases; and traditional Chinese herbal medicine (CM) treated group, 203 cases. A complete physical examination and 18 common clinical manifestations were prepared before the randomization and after the treatment. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The CM therapy included Glucosidorum Tripterygii Totorum Tablet and syndrome differentiation treatment. The American College of Rheumatology 20 (ACR20) was taken as efficacy evaluation. All data were analyzed on SAS 8.2 statistical package. The relationships between each variable and efficacy were analyzed, and the variables with P<0.2 were included for the data mining analysis with neural network model. All data were classified into training set (75%) and verification set (25%) for further verification on the data-mining model. RESULTS: Eighteen variables in CM and 24 variables in WM were included in the data-mining model. In CM, morning stiffness, swollen joint number, peripheral immunoglobulin M (IgM) level, tenderness joint number, tenderness, rheumatoid factor (RF), C-reactive protein (CRP) and joint pain were positively related to the efficacy, and disease duration and more urination at night negatively related to the efficacy. In WM, erythrocyte sedimentation rate (ESR), weak waist, white fur in tongue, joint pain, joint stiffness and swollen joint were positively related to the efficacy, and yellow fur in tongue, red tongue, white blood negatively related to the efficacy. In the analysis with the neural network model in the patients of verification set, the predictive response rates of 20% patients would be 100% and 90% in the treatment with CM and WM, respectively. CONCLUSION: Neural network model analysis, based on the full clinical trial data with collection of both traditional Chinese medicine and modern medicine diagnostic information, shows a good predictive role for the information in the efficacy in rheumatoid arthritis.

[Clinical study on effect and safety of bushen qiangji granule in treating ankylosing spondylitis patients].

OBJECTIVE: To evaluate the efficacy and safety of Bushen Qiangji Granule (BQG) in treating ankylosing spondylitis (AS) patients with Shen-deficiency and blood-stasis syndrome. METHODS: A randomized controlled and single-blinded prospective clinical trial was carried out on 68 patients, who were randomly assigned into the BQG group treated with BQG alone and the combined treated (CT) group treated with BQG and sulfasalazine, six-month medication was successively applied to both groups. The therapeutic effects were evaluated before treatment and at the end of the 1st, 3rd and 6th month of the treatment. RESULTS: The total effective rate was 81.82% in the BQG group and 86.82% in the CT group after 6 months of treatment, showing no significant difference between the two groups, but that after 1 months of treatment in the BQG group was lower than that in the combined group (15.15% vs. 27.59%, P < 0.01). Bath AS disease activity index (BASDAI), Bath AS function index (BASFI), and clinical symptoms such as ache and morning stiffness, as well as indexes of Schober test, activity of thoracic cage, finger-ground distance, erythrocyte sedimentation rate (ESR) and Creactive protein (CRP) in both groups were improved remarkably. BQG showed a time-dependant' effect, the therapeutic effect intensified as the time went by (P < 0.05 or P < 0.01). Moreover, the effect initiating time was earlier in the CT group than that in the BQG group. CONCLUSION: BQG has satisfactory efficacy, good safety and compliance, and is convenient for administering, therefore, it has broad applying prospect with high exploiting value.

The anti-nociceptive effect of BmK AS, a scorpion active polypeptide, and the possible mechanism on specifically modulating voltage-gated Na+ currents in primary afferent neurons.

In the present study, we investigated the anti-nociceptive effect and the underlying mechanism of BmK AS, an active peptide purified from scorpion Buthus martensi Karsch. The results showed that BmK AS can significantly relieve formalin-induced two-phase spontaneous flinching response and carrageenan-induced mechanical hyperalgesia. Using the whole-cell patch-clamp recording, exposure of acutely isolated sensory neurons to 500 nM BmK AS produced a one-fold decrease in the number of action potentials (APs) evoked by a ramp of depolarizing current. To investigate the mechanism of action of BmK AS, isolated membrane current and Ca2+ influx on rat primary sensory neurons were examined. BmK AS produced insignificant effect on voltage-dependent I(K) and KCl or caffeine-induced Ca2+ influx, but caused remarkable suppressive effect on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) I(Na). Further experiments showed that BmK AS reduced the peak TTX-R and TTX-S Na+ conductance in a dose-dependent manner, prompted the voltage-dependent activation, and caused a negative shift of the steady-state inactivation of TTX-R and TTX-S I(Na). Thus, the present results indicate the anti-nociceptive response of BmK AS may be ascribed to its specific modulation of voltage-gated Na+ channels of sensory neurons.

[Correlations of clinical symptoms and treatment efficacy in patients with rheumatoid arthritis treated with Chinese herbal drugs or Western medicine].

OBJECTIVE: To evaluate the correlations between clinical symptoms and treatment efficacy in patients with rheumatoid arthritis (RA). METHODS: Four hundred and thirteen patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine-treated group with 204 cases and Chinese herbal drug-treated group with 209 cases. Eighteen clinical symptoms were evaluated before and after treatment. The Western medicine therapy included voltaren extended release tablets, methotrexate and sulfasalazine. The Chinese herbal drug therapy included glucosidorum Tripterygii totorum tablets and Yishen Juanbi Tablets combined with treatment based on syndrome differentiation. The American College of Rheumatology 20 (ACR20) was used as efficacy evaluation criteria. RESULTS: In the Chinese herbal drug-treated group, clinical symptoms such as arthralgia and tenderness of joints were positively correlated with the efficacy after 12-week treatment, while frequent urination at night was negatively correlated. In the same group, tenderness of joints and fever were positively correlated with the efficacy after 24-week treatment, while deep-colored and turbid urine was negatively correlated. In the Western medicine-treated group, tenderness of joints and thirst were positively correlated with the efficacy after 12-week treatment, while vertigo was negatively correlated. And in the same group, tenderness of joints was positively correlated with the efficacy after 24-week treatment, while heaviness of limbs was negatively correlated to the efficacy. The statistical results showed that the treatment efficacy was improved when the correlated symptoms were included in the indications. CONCLUSION: The treatment efficacy of RA is correlated with some symptoms, so further studies should proceed on these correlations in order to achieve better treatment outcome.

The modulation effects of BmK I, an alpha-like scorpion neurotoxin, on voltage-gated Na(+) currents in rat dorsal root ganglion neurons.

The present study investigated the effects of BmK I, a Na(+) channel receptor site 3 modulator purified from the Buthus martensi Karsch (BmK) venom, on the voltage-gated sodium currents in dorsal root ganglion (DRG) neurons. Whole-cell patch-clamping was used to record the tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) components of voltage-gated Na(+) currents in small DRG neurons. It was found that the inhibitory effect of BmK I on open-state inactivation of TTX-S Na(+) currents was stronger than that of TTX-R Na(+) currents. In addition, BmK I exhibited a selective enhancing effect on voltage-dependent activation of TTX-S currents, and an opposite effect on time-dependent activation of TTX-S and TTX-R Na(+) currents. The results suggested that the inhibitory effect of BmK I on open-state inactivation might contribute to the increase of peak TTX-S and TTX-R currents, and the enhancing effect of BmK I on time-dependent activation might also contribute to the increase of peak TTX-S currents. It was further suggested that a combined effect of BmK I including inhibiting the inactivation of TTX-S and TTX-R channels, accelerating activation and decreasing the activation threshold of TTX-S channels, might produce a hyperexcitability of small DRG neurons, and thus contribute to the BmK I-induced hyperalgesia.