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Objective To investigate the effect of hsa-Let-7a-5p on the fibrosis process of localized scleroderma fibroblasts (LSFs) and its correlation with transforming growth factor-β receptor (TGF-βR) and TGF-β/Smad signaling pathway. Methods LSFs were infected with lentiviral vectors carrying hsa-Let-7a-5p and shTGF-βR1 and blank lentiviral vectors. The proliferation and migration of LSFs in each group were detected by CCK-8 method and scratch test. Real-time quantitative PCR (RT-qPCR), immunofluorescence and Western blot were used to detect the transfection efficiency, and the mRNA and protein levels of collagen type Ⅰ & Ⅲ, α-SMA, TGF-βR1, TGF-β, p-Smad2/3 in LSFs in each group. Results After virus infection of LSFs, the expression of TGF-βR1 in the shTGF-βR1 group was significantly lower than that in the control groups (P＜0.05); the cell proliferation rate and migration of shTGF-βR1 group were inhibited(P＜0.05); The mRNA and protein expression of collagen type Ⅰ & Ⅲ, α-SMA, TGF-β, p-Smad2/3 were significantly lower than those of the control groups(P＜0.05). Bioinformatics analysis showed that hsa-Let-7a-5p can be matched with the target region of TGF-βR1 3′-UTR, and the expression of hsa-Let-7a-5p in the lentivirus transfection group was significantly increased compared with the control groups(P＜0.05), the expression of TGF-βR1 was significantly decreased(P＜0.05). The cell proliferation rate and migration ability of the hsa-Let-7a-5p group were decreased; the mRNA and protein expression of collagen type Ⅰ & Ⅲ, α-SMA, TGF-β, p-Smad2/3 in the hsa-Let-7a-5p group were significantly lower than those of the control groups(P＜0.05). Conclusions hsa-Let-7a-5p regulates TGF-β/Smad pathway by targeting at TGF-βR1,inhibits proliferation and migration of LSFs, decreases fibrotic markers in LSFs thereby inhibiting fibrosis in localized scleroderma.

Lipoedema is an uncommon disease disorder characterized by bilateral enlargement of the legs due to abnormal depositions of subcutaneous fat and essentially affects females. The disease has been reported with genetic tendency and can also be affected by hormone level of the host. Lipoedema has characteristic clinical manifestations, like pain, easy bruising and “cuff sign”. In clinical, main diseases considered for differential diagnosis are lymphedema, obesity, Dercum's disease and chronic venous disease. Management of lipoedema includes psychological health education, weight loss, conservative treatment and operative treatment. There are increasing reports supporting liposuction using super tumescent local anesthesia and vibrating cannulas as the preferred surgical option.

The geographical location of the Lhasa terrane in the Permian remains a subject of debate. The recognition of the Permian basalts in the Tethyan Himalaya and the Permian volcanic rocks in the Lhasa terrane in southern Tibet together with the geochemistry of these rocks offer some new insights. The Permian basalts in the Tethyan Himalaya show a geochemical affinity with tholeiitic continental flood basalts, and are interpreted to have formed in an extensional setting. The new geochemical data and the geographical distribution of these basalts indicate that they probably represent the easternmost extent of the Panjal continental flood basalt province. All of the Permian basalts in the Lhasa terrane show a calc-alkaline, high-alumina basalt affinity, with significant negative Nb-Ta-Ti anomalies. These geochemical features, combined with the recent documentation of the Permian Songdo eclogite and sedimentological observations, indicate the existence of a subduction system beneath the central Lhasa subterrane in the Permian. The presence of both extension- and arc-type magmatism of Permian age in present-day southern Tibet is inconsistent with the general view that the Lhasa terrane did not rift away from the northern margin of the Greater India until the Late Permian or Triassic. Instead, we suggest that the central Lhasa subterrane may have been a microcontinent isolated in the Paleo-Tethyan Ocean basin, at least during the Carboniferous-Middle Permian time. doi: 10.1130/B30062.1