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Osteoarthritis (OA) is one of the most common diseases leading to physical disability, with age being the main risk factor, and degeneration of articular cartilage is the main focus for the pathogenesis of OA. Autophagy is a crucial intracellular homeostasis system recycling flawed macromolecules and cellular organelles to sustain the metabolism of cells. Growing evidences have revealed that autophagy is chondroprotective by regulating apoptosis and repairing the function of damaged chondrocytes. Then, OA is related to autophagy depending on different stages and models. In this review, we discuss the character of autophagy in OA and the process of the autophagy pathway, which can be modulated by some drugs, key molecules and non-coding RNAs (microRNAs, long non-coding RNAs and circular RNAs). More in-depth investigations of autophagy are needed to find therapeutic targets or diagnostic biomarkers through in vitro and in vivo situations, making autophagy a more effective way for OA treatment in the future. The aim of this review is to introduce the concept of autophagy and make readers realize its impact on OA. The database we searched in is PubMed and we used the keywords listed below to find appropriate article resources.

ZFP36L1, a CCCH-type zinc finger protein, is an RNA-binding protein that participates in controlling cellular mRNA abundance and turnover by posttranscriptional regulation. Here, we demonstrated that ZFP36L1 has an important role in host defense against influenza A virus (IAV) infection. Overexpression of ZFP36L1 reduced IAV replication via translational repression of HA, M and NS RNA segment transcripts. IAV infection upregulated cellular ZFP36L1 expression, and endogenous ZFP36L1 knockdown significantly enhanced IAV replication. ZFP36L1 directly binds to IAV NS1 mRNA in the cytoplasm and blocks the expression and function of NS1 protein. Mutation of CCCH-type zinc finger domains of ZFP36L1 lost its antiviral potential and NS1 mRNA binding. Thus, ZFP36L1 can act as a host innate defense by targeting HA, M and NS mRNA transcripts to suppress viral protein translation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 2019 (COVID-19). However, the long-term health consequences of COVID-19 are not fully understood. We aimed to determine the long-term lung pathology and blood chemistry changes in Syrian hamsters infected with SARS-CoV-2. Syrian hamsters (Mesocricetus auratus) were inoculated with 10

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.

Backgrounds While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM. Materials and methods We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay. Results The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Department of Health and Welfare of Taiwan) had EC50 of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells – with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir. Conclusions Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19., Graphical abstract Image 1

This study has two purposes: (1) to compare the clinical results between the Titanium Elastic Nail (TEN) and plate fixation of the displaced midshaft clavicle fracture; and (2) to demonstrate the relationship between length shortening and functional outcome after TEN fixation, especially in the comminuted fracture pattern. A retrospective, case-controlled study was conducted and 55 patients were included in our study: 25 in the TEN fixation group (TEN group) and 30 in the plate fixation group (plate group). All patients were classified into four subgroups: simple fracture in the TEN group (ST; n = 13), simple fracture in the plate group (SP; n = 15), comminuted fracture in the TEN group (CT; n = 12), and comminuted fracture in the plate group (CP; n = 15). Wound size was significantly smaller in the TEN group (p

Irreducible metatarsophalangeal joint dislocation of the lesser toes is a rare injury. We present a 37-year-old man who was injured in a motorcycle accident and dislocated the first to third metatarsophalangeal joints and fractured the fourth metatarsal head. The left first metatarsophalangeal joint was reduced successfully through the closed method, but multiple attempts at closed reduction under local anesthesia failed to reduce the dislocated second and third metatarsophalangeal joints. We performed a dorsal incision between the second and third metatarsals, and the metatarsal heads were found to be entrapped under the plantar plate. Dislocation reduction was performed without damage to the plantar plate, and one Kirschner wire was used to fix the fourth metatarsal head fracture. The pin was removed 8 weeks after surgery, and the patient regained normal gait and returned to work and his previous physical activity level without recurrent dislocation. (J Am Podiatr Med Assoc 103(3): 236–240, 2013)

Open reduction and internal fixation has been the gold standard for displaced fracture involving weightbearing dome and fractures with intra-articular fragments. However, extensile exposure can lead to complications. Fracture with minimal displacement can be fixed by a minimally invasive method. Percutaneous screwing for an anterior column fracture of acetabulum under conventional 2D fluoroscopy is a demanding technique. With fluoroscopic-based computerized navigation, we can determine the position of a screw real time intra-operatively with less exposure to radiation. We proposed that a fluoroscopy-based computerized navigational system would simplify operation procedures. The purpose of this study is to test the application of the fluoroscopy-based computerized navigational system for anterior column fracture of acetabulum.A prospective cohort study was conducted. Three patients with mildly displaced or non-displaced anterior column fracture of acetabulum were treated with a retrograde lag screw under a fluoroscopy-based computer navigation system. There were two males and one female with a mean age of 39 years and all patients were followed up for more than 1 year. Patients were allowed to perform joint movement exercises and to walk with partial weightbearing on the first day post-operatively.The mean operation time was 40 min (range 30-45 min) from the use of fluoroscopy to wound closure and the mean total fluoroscopy time was 38 s (range 35-45 s). Total blood loss was less than 10 ml. The patients were pain free 1 week after the operation and had good functional recovery thereafter. No complication was noted postoperatively.Though the indication for this procedure is limited, we think that there should be potential to apply the screw with less radiation by fluoroscopic-based computerized navigation. Once anatomic reduction can be achieved by the close method in the anterior column fracture of the acetabulum, percutaneous screw fixation under fluoroscopic-based computerized navigation could be a reliable method; however; validating the position of the guide pin and screw by fluoroscopy is suggested.

The prognosis of type II floating knee injuries was not as good as that of type I. Our purpose is to clarify the factors affecting the outcome of type II floating knee injuries. Thirty-five patients (36 limbs) with type II floating knee injury were studied with a mean follow-up of 52 months (26-96). Blake and McBryde had classified these injuries into type I for pure diaphyseal (true type) fracture and type II if the intra-articular involvements are one or more including hip, knee and ankle joints (variant type). According to this classification, we divided these patients into two groups depending on whether their knees were involved or not. Those cases with intra-articular knee involvement were classified as type IIA, while those without intra-articular knee involvement were classified as type IIB. Of the 36 cases, 21 were classified as type IIA and 15 were type IIB. The functional outcomes of these injuries were evaluated by using the criteria of Karlström and Olerud and analyzed with multivariate analysis. After multivariate analysis with logistic regression, we show the following results: first, the poor functional outcome of type II floating knee is contributed by type IIA. Second, the type IIA group has severer femoral open fracture grading (P = 0.027) and poorer functional outcome (P = 0.009) than type IIB. Third, the significant contributing factors to final outcome are the group (P = 0.013) and the fixation time after injury in femur (P = 0.015). Intra-articular knee involvement is the most important factor contributing to poor outcome of type II floating knee. The treatment of floating knee injuries with intra-articular knee involvement is still difficult. Further efforts to search better methods of treatment are required for these complex injuries in the future.

Clavicular fractures account for 2.6% of all fractures, and more than 80% involve the middle third of the clavicle. Plate fixation has been the most common method of fixation reported but has been associated with complications such as infection, wound breakdown, nonunion, implant failures, poor cosmetic outcome, and local skin numbness. We report on a series of cases receiving minimally invasive insertion of titanium elastic nails (TEN) to fix the displaced midclavicular fractures.Prospective, clinical study.Regional referral center.From November 2006 to October 2007, we operated on 23 patients (16 men) with displaced (no cortical contact between the proximal and distal fragments radiographically and/or greater than 2 cm of shortening) midclavicular fractures fixed with TEN. The mean age of the patients was 41.57 years.All patients with displaced midclavicular fractures were treated with TEN. The nails were inserted from the medial entry point on the sternal end and passed through the fracture site under fluoroscopy monitoring.Complications, clavicular shortening after TEN fixation, Constant shoulder score, and Disability of the Arm, Shoulder, and Hand score for functional outcome measurement.Closed reduction was successful in 16 patients, and seven patients needed open reduction. There was no nonunion, infection, nail breakage, or refracture after nail removal in our series. The mean operative wound length was 2.2 cm, and mean clavicular length shortening was 0.32 cm. Iatrogenic perforation of the lateral cortex occurred in two patients, and nail misplacement occurred in one patient requiring revision. All patients followed up greater than 12 months. The mean Disability of the Arm, Shoulder, and Hand score was 6 (range, 0-35; standard deviation, 10.47) and mean Constant score was 96 (range, 78-100; standard deviation, 6.34).Minimally invasive fixation with TEN is a safe method and can be performed with minor complications. This method of fixation of displaced midclaviclular fractures should result in a good cosmetic appearance and satisfactory stabilization of displaced midclavicular fractures without comminution.

Fractures of the posteromedial tibial plateau are rare and their treatment is not well established. Between January 2004 and December 2008, eight patients with fractures of the posteromedial tibia plateau were identified. All patients were treated with fracture reduction using an anterior approach. After a mean follow-up of 21 months, the average range of knee motion was 0-123 degrees of flexion. Seven patients had been injured in motor-scooter accidents, in which the protective front plate of the scooter had hit the knee while it was in the 90 degrees -flexion position. At the final follow-up, 87.5% (7/8) patients had satisfactory reductions of the articular surface, and all patients had acceptable alignments. There were no neural or vascular injuries following surgery, and no superficial or deep infections. The average Hospital for Special Surgery Knee Score was 89. In conclusion, fracture reduction using the anterior approach is associated with fewer complications than the posterior approach, and good functional recovery can be expected.

Knee ligament injuries associated with tibia shaft fractures are usually neglected and treatment is delayed. To our knowledge, no case presentation discusses the clinical result of closed tibial shaft fracture with concomitant ipsilateral isolated PCL injury. In this literature, we report the clinical result of two cases that sustained closed tibial shaft fracture with concomitant PCL injury and discuss the treatment options.We report the clinical result of two cases that sustained closed tibial shaft fracture with concomitant posterior cruciate ligament (PCL) injury. Case 1 received open reduction with plate fixation for the tibial shaft fracture, and he also received arthroscopic reconstruction of PCL with bone-patellar tendon-bone graft due to neglecting PCL injury 5 months later after fracture fixation. Case 2 sustained left tibial-fibular shaft fracture with isolated PCL injury confirmed by magnetic resonance image on the first day of injury. She received tibia fixation with intramedullary nail and conservative treatment with bracing and rehabilitation for PCL injury.In case 1, the male patient only focused on fracture healing without any knee rehabilitation. His knee flexed deeply for protected weight bearing in the injured leg which may have exacerbated the posterior instability and reduced the possibility of PCL healing. The end result of knee function was poor even though PCL reconstruction was done later. In case 2, the female patient with diagnosed posterior cruciate ligament injury on the day of injury, her knee was immobilized in brace with full extension, which improved PCL healing. In addition, she received rehabilitation of quadriceps strengthening, and hamstring muscle contraction was avoided in her daily activity. After rehabilitation, the female patient did not complain of severe subjective instability even with an obvious posterior translation on posterior drawer test.We need to perform a careful physical examination of ipsilateral knee in cases of leg fractures, and MRI of knee before surgery if any doubt exists. However, a further research is needed to conclude on the best operation and rehabilitation program in patients with combined tibial shaft fracture and PCL injury.

Mid-shaft clavicle fractures have traditionally been treated conservatively, although this has been associated with non-union and unsatisfactory shoulder function. The preferred approach is plate fixation, with a reconstruction plate for open reduction and internal fixation. Infection is a potential complication after such surgery, with rates of 0.4-7.8% reported in the literature. In our cases, an infection rate of 4.9% (7 of 142 patients) was noted; five of the seven patients suffered from acute postoperative infection within 1 month of surgery. The average time to presentation with an infection was 28 (23-32) days, with signs and symptoms of wound dehiscence in one patient and sinus discharge in four patients. Two patients suffered from subacute infections, with durations of 72 and 103 days, presenting with local heat and radiographic findings of screw loosening. Six of the cases healed with primary bony union after intensive debridement and early removal of the implants.

Snapping knee syndrome describes the sudden movement of a soft-tissue structure across a bony prominence around the knee with a popping sound at some specific activity. Symptomatic snapping knee syndrome may result from an intra-articular tumor, but this situation is rare. To the best of our knowledge, an intra-articular ganglion cyst leading to snapping knee has not been reported previously. A 20 year old female with painful snapping knee was successfully treated by open en-bloc excision of the ganglion cyst sized 4.5 x 1.5 x 1 cm on the ligamentum mucosum. Snapping and pain were completely relieved after surgery. Although the snapping knee is not common over the antero-lateral portion of the knee joint, a ganglion cyst from the ligamentum mucosum is a possible cause.

Anterior subtalar dislocations are extremely rare. To our knowledge, six cases have been reported in detail in the literature, but for only two of these was an anteroposterior view radiograph used to confirm the diagnosis. We report a case of anterior subtalar dislocation in which the posterior tibialis tendon was incarcerated in the talonavicular joint and that required an open reduction. We discuss the diagnosis, mechanism, and treatment.