The new target of Rapamycin: lysosomal calcium channel TRPML1 / 生理学报

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.

Bushen Qiangji Granule () medicated serum inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by inhibiting the BMP/Smads signal pathway in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of Bushen Qiangji Granule (, BSQJ) in restraining the osteogenic differentiation of ankylosing spondylitis (AS) fifibroblasts.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>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].</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>QQD and BQD got confirmable clinical effects in treating AS, providing strong evidence of evidence-based medicine for syndrome differentiation and treatment of AS.</p>

Three-dimensional analysis of facial structure for unilateral cleft lip patients repaired by Millard's method / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate the aesthetic effect of Millard' s method in patients with unilateral cleft lip by three dimensional sensing system.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Correction of progressive hemifacial atrophy using dermis-fat graft and Medpor implant shaped by reverse engineering technique / 中华整形外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Constructing tissue engineered trachea-like cartilage graft in vitro by using bone marrow stromal cells sheet and PLGA internal support: experimental study in bioreactor / 中华整形外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Clinical study on effect and safety of bushen qiangji granule in treating ankylosing spondylitis patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Bushen Qiangji Granule (BQG) in treating ankylosing spondylitis (AS) patients with Shen-deficiency and blood-stasis syndrome.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>BQG has satisfactory efficacy, good safety and compliance, and is convenient for administering, therefore, it has broad applying prospect with high exploiting value.</p>

Surgical orthodontic technique for the treatment of maxillofacial deformities and dysfunction of occlusion after maxillofacial fractures / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate a new technique to treat severe maxillofacial deformity and dysfunction of occlusion after the maxillofacial fractures.</p><p><b>METHODS</b>Thirty-four consecutive patients, with delayed maxillofacial deformities and dysfunction of occlusion after the maxillofacial fractures, were treated by the use of x-ray cephalometric analysis, model surgery, open reduction and rigid internal fixation.</p><p><b>RESULTS</b>Thirty-three patients were successfully corrected the maxillofacial deformities, facilitated normal occlusal relationship. Only one patient with severe damage of the brain was presented a mild occlusion dysfunction one year after the operation.</p><p><b>CONCLUSIONS</b>The above-mentioned technique may be a viable and effective option for the management of the deformities of the face and dentition after the maxillofacial fractures.</p>