A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.

Subtalar arthrodesis in the treatment of sinus tarsi syndrome with peroneal spasm / 中华骨科杂志

Objective:To explore the long-term clinical efficacy of subtalar arthrodesis for treating sinus tarsi syndrome (STS) with peroneal spasm.Methods:Clinical informationof 32 patients with sinus tarsi syndrome complicated with peroneal spasm who were treated by subtalar arthrodesis from January 2006 to December 2016 was retrospectively analysed. There were 19 males and 13 females, aged 29.3±10.9 y (range: 13-56 y), and course of disease is 2.1±1.7 y (range: 1-10 y). All patients suffered from tarsal sinus pain and intractable peroneal spasm. The aetiology was foot or ankle inversion sprainin 25 patients, lower limb nerve injury in four patients, and ambiguous causes in three patients.The patients were divided into three groups according to their initial symptoms. Group A: Patients with simple peroneal spasm underwent tarsal sinus debridement firstly and subtalar joint fusion after symptom recurrence. Group B: Patients with peroneal spasm combined with other symptomsunderwent sinus tarsal cleansing and other symptomatic operations, and received subtalar joint fusion after symptoms recurred. Group C: Patients with peroneal spastic flat foot were treated withsubtalar joint fusion directly.Preoperative and postoperative American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, visual analogue scale (VAS) scores for pain during daily activities, and 36-item short form health survey (SF-36) scoreswere investigated.Results:32 cases were successfully completed operation, following-up 87 (40, 133) months. Group A(14 cases): The patients were treated withsinus tarsi debridement first. But their symptoms recurred in an average of 7.7 months after surgery. Later they received subtalar joint fusion. Group B (15 cases): In addition to tarsal sinus debridement, 3 cases were undergone tarsal coalitions resection, 3 cases were got denervation of tarsal sinus, 6 cases were received subtalar joint stabilization, and 3 cases were released their peroneal tendons. Their symptoms recurred in an average of 6.4 months after surgery, and they eventually were undergone subtalar arthrodesis. Group C (3 cases): Their initial symptoms were severe, manifested as rigid flat feet caused by peroneal tendons spasm, so they directly underwent subtalar joint fusion. The average AOFAS ankle and hindfoot scores for all patients increased from 27.86±10.79 points before treatment to 86.34±7.17 points at the last follow-up after operation ( t=23.505, P<0.05). The VAS scores decreased from 8.00±1.57 points before treatment to 1.91±1.06 points at the last follow-up after operation ( t=18.407, P<0.05). The SF-36 scores increased from 35.84±12.12 points before treatment to 86.20±10.32 points at the last follow-up after operation ( t=24.203, P<0.05). Conclusion:Sinus tarsi syndrome with peroneal spasm due to its complicated etiology and pathogenesis can give priority to sinus tarsal debridement or other symptomatic surgeries. If the symptoms recur, subtalar arthrodesis can be an alternative choice to achieve the long-term effects.

Clinical value of ankle arthroscopy in type Danis-Weber B ankle fracture with the distal tibiofibular syndesmosis injury / 中华骨科杂志

Objective To investigate clinical value of ankle arthroscopy in diagnosis of type Danis-Weber B ankle fracture with the distal tibiofibular syndesmosis injury.Methods From August 2014 to January 2018,a total of 52 cases of type Danis-Weber B ankle fractures with an average age of 35.37± 11.19 years,including 31 males and 21 females were treated.Each patient underwent preoperative assessment,according to the patient's clinical manifestations and imaging examination before operation.The Cotton test and the external rotation test were conducted in the C arm X-ray to evaluate whether there is the distal tibiofibular syndesmosis injury.All fractures were treated with open reduction and internal fixation.Repair was conducted with 3.5 mm wire anchor and nail for triangular ligament injury.The Cotton test and external rotation test were performed under ankle arthroscopy.The injury of the lower tibiofibular syndesmosis was observed and evaluated by cotton test and external rotation test in patients who were found to be associated with lower tibiofibular joint injury.After internal fixation of fracture and repair of tibiofibular syndesmosis injury with TightRope,the repair effects of tibiofibular syndesmosis injury was observed under direct vision of ankle arthroscopy.The VAS score,AOFAS score and Baird-Jackson score was used as an index to observe the pain and ankle function before and after operation for 12 months follow-up.Results Preoperative X-ray showed 19 cases of lower tibiofibular joint injury.Preoperative CT showed 28 cases of lower tibiofibular joint injury.Preoperative MRI showed 39 cases of lower tibiofibular joint injury.A total of 36 cases of joint injury of lower tibiofibular syndesmosis were confirmed under arthroscopy of ankle.After repair of tibiofibular syndesmosis injury with TightRope,complete reduction and stability of inferior tibiofibular syndesmosis were confirmed under ankle arthroscopy.At 12 months after operation,the VAS score decreased from 8.13 ± 1.32 points preoperation to 0.75±0.73 points after operation.The AOFAS and Baird-Jackson scores increased from 26.59±3.35 points,16.44±3.63 points preoperation to 94.36±3.03 points,90.29±6.45 points after operation,respectively.There was significant difference before and after operation (P＜0.05).The postoperative VAS score,AOFAS score and Baird-Jackson score of 16 patients without lower tibiofibular ligament injury were confirmed in the ankle arthroscopy group,namely 0.58±0.67 points,95.27±4.67 points,91.98±9.23 points.Conclusion Ankle arthroscopy can be used to observe the injury of tibiofibular syndesmosis under direct vision.The positive rate of diagnosis of inferior tibiofibular syndesmosis injury was 69.2％ (36/52).It can provide reliable evidence for correct diagnosis and treatment of type Danis-Weber B ankle fracture with lower tibiofibular joint injury with significant meaning in selecting operative methods and in evaluating the effect of lower tibiofibular ligament repair.

Clinical value of ankle arthroscopy in type Danis-Weber B ankle fracture with the distal tibiofibular syndesmosis injury / 中华骨科杂志

Objective@#To investigate clinical value of ankle arthroscopy in diagnosis of type Danis-Weber B ankle fracture with the distal tibiofibular syndesmosis injury.@*Methods@#From August 2014 to January 2018, a total of 52 cases of type Danis-Weber B ankle fractures with an average age of 35.37±11.19 years, including 31 males and 21 females were treated. Each patient underwent preoperative assessment, according to the patient's clinical manifestations and imaging examination before operation. The Cotton test and the external rotation test were conducted in the C arm X-ray to evaluate whether there is the distal tibiofibular syndesmosis injury. All fractures were treated with open reduction and internal fixation. Repair was conducted with 3.5 mm wire anchor and nail for triangular ligament injury. The Cotton test and external rotation test were performed under ankle arthroscopy. The injury of the lower tibiofibular syndesmosis was observed and evaluated by cotton test and external rotation test in patients who were found to be associated with lower tibiofibular joint injury. After internal fixation of fracture and repair of tibiofibular syndesmosis injury with TightRope, the repair effects of tibiofibular syndesmosis injury was observed under direct vision of ankle arthroscopy. The VAS score, AOFAS score and Baird-Jackson score was used as an index to observe the pain and ankle function before and after operation for 12 months follow-up.@*Results@#Preoperative X-ray showed 19 cases of lower tibiofibular joint injury. Preoperative CT showed 28 cases of lower tibiofibular joint injury. Preoperative MRI showed 39 cases of lower tibiofibular joint injury. A total of 36 cases of joint injury of lower tibiofibular syndesmosis were confirmed under arthroscopy of ankle. After repair of tibiofibular syndesmosis injury with TightRope, complete reduction and stability of inferior tibiofibular syndesmosis were confirmed under ankle arthroscopy. At 12 months after operation, the VAS score decreased from 8.13±1.32 points preoperation to 0.75±0.73 points after operation. The AOFAS and Baird-Jackson scores increased from 26.59±3.35 points, 16.44±3.63 points preoperation to 94.36±3.03 points, 90.29±6.45 points after operation, respectively. There was significant difference before and after operation (P<0.05). The postoperative VAS score, AOFAS score and Baird-Jackson score of 16 patients without lower tibiofibular ligament injury were confirmed in the ankle arthroscopy group, namely 0.58±0.67 points, 95.27±4.67 points, 91.98±9.23 points.@*Conclusion@#Ankle arthroscopy can be used to observe the injury of tibiofibular syndesmosis under direct vision. The positive rate of diagnosis of inferior tibiofibular syndesmosis injury was 69.2% (36/52). It can provide reliable evidence for correct diagnosis and treatment of type Danis-Weber B ankle fracture with lower tibiofibular joint injury with significant meaning in selecting operative methods and in evaluating the effect of lower tibiofibular ligament repair.

Ankle arthroscopy for diagnosis and treatment of Danis-Weber type B ankle fracture associated with injury to the distal tibiofibular syndesmosis / 中华创伤骨科杂志

Objective To evaluate the clinical value of ankle arthroscopy in diagnosis and treatment of Danis-Weber type B ankle fracture associated with injury to the distal tibiofibular syndesmosis.Methods A retrospective study was conducted of the 35 patients who had been treated at Department of Orthopaedics,Ruijin Hospital North for Danis-Weber type B ankle fracture from February 2014 to December 2016.They were 23 males and 12 females,with an average age of 43.1 years (from 18 to 65 years).Each of them underwent 4 examinations to detect whether injury to the distal tibiofibular syndesmosis was complicated or not:preoperative CT and MRI,C-ann roentgenography and ankle arthroscopy before and after internal fixation of the ankle.The diagnostic rates of the complicated injury by the 4 examinations were compared.The patients complicated with injury to the distal tibiofibular syndesmosis received surgical repair of the injury using TightRope in addition to internal fixation of the ankle,and injury to the deltoid ligament was repaired simultaneously using 3.5 mm anchor nails in case the injury was concomitant.The repair and stability of the distal tibiofibular syndesmosis were observed using ankle arthroscopy again.Results The Cotton and external rotation tests under C-arm roentgenography before surgery and after internal fixation of the ankle demonstrated that 13 cases were complicated with injury to the distal tibiofibular syndesmosis.Of the other 22 patients who had not been diagnosed with the injury by C-arm roentgenography,6,13 and 11 were diagnosed with the injury respectively by CT,MRI and ankle arthroscopy.The diagnostic rates of Danis-Weber type B ankle fracture associated with injury to the distal tibiofibular syndesmosis were 37.1％ (13/35),54.3％ (19/35),74.3％ (26/35) and 68.6％ (24/35) respectively by C-arm roentgenography,CT,MRI and ankle arthroscopy.In the sensitivity to the injury,MRI ＞ ankle arthroscopy ＞ CT ＞ C-arm roentgenography,with significant differences between them (P ＜ 0.05).The ankle arthroscopy confirmed the repair efficacy in the 24 patients complicated with injury to the distal tibiofibular syndesmosis and negative results of Cotton and external rotation tests in them.Additionally,ankle arthroscopy revealed 16 cases of injury to the deltoid ligament at the medial ankle.Conclusions Ankle arthroscopy can provide evidence for correct diagnosis and treatment of Type B ankle fracture complicated with injury to the distal tibiofibular syndesmosis,because it allows direct observation of the medial deltoid ligament of the ankle and the distal tibiofibular syndesmosis.It can be also used to assess the stability of the tibiofibular syndesmosis after repair of the injury.

C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death

Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A-D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.

Evaluation of midfoot function after subtalar arthrodesis / 中华骨科杂志

Objective To evaluate the influence of simple subtalar arthrodesis to the motion and degeneration of midfoot.Methods Data of 37 patients (27 males,10 females) with an average age of 42.6 years who had undergone subtalar joint fusion from January 1996 to August 2011 were retrospectively analyzed.The MOS item short form health survey (SF-36),American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score were used.Midfoot sagittal and coronal motion were measured on ankle radiographs of maximum plantar flexion and dorsiflexion.On sagittal plane,the Meary angle was measured and the bilateral tarsometatarsal joints mobility was compared.On coronal plane,tibio-plantar angles (TPA) on 30 degrees varus slope and 30 degrees valgus slope were respectively measured on the anterio-posterior ankle X-ray films to observe the changes of midfoot activities.Besides,single photon emission computed tomography/computed tomography (SPECT/CT) of bilateral foot and ankle was taken to estimate the degeneration of midfoot joint.Results All the 37 patients were followed-up,with mean follow-up period of 9.2 years.The average SF-36 scores was increased from 34.26± 11.02 points preoperatively to 77.59± 12.57 points postoperatively.The average AOFAS midfoot scores were 86.14± 16.79 points preoperatively and 86.43± 16.70 points postoperatively without any statistical significant difference.On sagittal plane,medial tarsometatarsal joints mobility was limited by 20％.According to coronal plane of varus slope,the average TPA of healthy side and operated side were 61.32° and 64.91°,respectively,so the varus mobility of operated side was limited by 12.5％.While standing on the valgus slope,the average TPA of both sides were 76.54° and 82.28°,which indicated that valgus mobility of operated side was reduced by 42.6％.35.1％ patients of talonavicular joint,56.8％ patients of calcaneocuboid joint,and 27.0％ patients of metatarsal cuboid joint were found mild joint degeneration on SPECT/CT images without any clinical symptoms.Conclusion Subtalar arthrodesis can affect midfoot with less limit of sagittal mobility and more limit of coronal movement.And the lateral joints degeneration is more likely to happen for their compensatory activity.

Analysis on early results of using osteochondral autografts harvested from medial femoral condyle of the ipsilateral knee for the treatment of osteochondral lesion of the talus / 中华骨科杂志

Objective To evaluate the curative effect and related factors of the treatment for the osteochondral lesion of talus (OLT) by the osteochondral autografts harvested from medial femoral condyle of the ipsilateral knee.Methods The data of 15 OLT patients was retrospectively analyzed who received the operation during July 2009 to November 2012.There were 8 males,and 7 females,with an average age of 49.6±17.2 years (range,19-73 years).International Knee Documentation Committee (IKDC) and Lysholm score were used to evaluate the knee function preoperatively and postoperatively respectively.The ankle functions and pain were assessed according to American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hind-foot score and visual analogue scale (VAS) preoperatively and postoperatively respectively.Correlations between age or follow-up duration and all the score increments were further analyzed by Spearman rank correlation test.Results Twelve patients complete the follow up,with an average duration of 21.8±10.4 months.The average IKDC,Lysholm,AOFAS,and VAS were 90.91±6.44,95.33±8.00,63.58±18.50,and 7.25±1.54 respectively before operation,and 85.63±11.89,90.75±11.83,90.33±4.98,2.17±1.19 respectively after operation.Correlation coefficients of age between AOFAS,Lysholm,and IKDC score increments were -0.74,-0.63,and-0.76,respectively.There were 4 cases which received excellent effect (33％),5 cases (42％) good and 3 (25％) fair.Conclusion The ankle joint function of patients with OLT recovered well by treated with osteochondral autografts harvested from medial femoral condyle of the ipsilateral knee operation.A correlation was found between patients' age and postoperative functional recovery of ankle and knee joint.

Periarticular osteotomy in the treatment of ankle arthritis / 中华骨科杂志

ObjectiveTo evaluate effect of periarticular osteotomy in the treatment of asymmetrical ankle arthritis.MethodsSixty-five patients with asymmetrical ankle arthritis were treated with periarticular osteotomy between February 2005 and May 2011,including 43 females and 22 males,aged from 35 to 74 years (mean,55.5 years).According to the Takakura classification of ankle arthritis,there were 29 patients in grade 2,32 in grade 3 and 4 in grade 4.Supramalleolar tibial osteotomy were performed in 20 patients,supramalleolar tibial and fibular osteotomy in 12,supramalleolar osteotomy combined with calcaneal osteotomy in 30 patients,and supramalleolar tibial and fibular osteotomy combined with calcaneal osteotomy in 3patients.Forty three patients underwent ligament reconstruction procedures.Based on radiographs,the tibial anterior surface angle (TAS) and tibial lateral surface angle (TLS) were compared before and after operation.AOFAS-AH score was used to evaluate the function of the ankle.ResultsFifty-nine patients were followed up for an average of 35.7 months (range,7 to 94 months).Bone healing was observed in all patients,and the average healing time was 7 to 8 weeks.The average AOFAS-AH score was improved from 49.7 points preoperatively to 78.6 points 12 months postoperatively.Tbe average TAS and TLS was improved from 86.1° and 70.0° preoperatively to 93.9° and 81.5° 6 months postoperatively,respectively.Delayed wound healing occurred in 5 patients,which was resovled after nursing care.Forty-two patients felt excellent about results,15 felt good and 2 fell fair.ConclusionPerarticular osteotomy is a sound method in the treatment of asymmetrical ankle arthritis,based on chosing proper patients.The procedure can decrease the contact pressures on the degenerated cartilage and prolong the life span of the ankle.