Addition of Preoperative Ultrasound-Guided Suprascapular Nerve Block and Axillary Nerve Block to Parecoxib Is More Effective in Early Postoperative Pain Control After Arthroscopic Rotator Cuff Repair: A Prospective Randomized Controlled Study.

PURPOSE: To prospectively compare pain intensity and patient-reported outcomes (PROs) after arthroscopic rotator cuff repair (ARCR) between patients who received ultrasound-guided suprascapular nerve block (SSNB) and axillary nerve block (ANB) as well as preincisional parecoxib and patients who received preincisional parecoxib only. METHODS: Sixty-one patients receiving ARCR between March 2020 and March 2021 were prospectively enrolled. They were randomly assigned to the peripheral nerve block group (group N, n = 30) or control group (group C, n = 31). Two patients in group C were excluded because of miscommunication. All patients were administered 40 mg of parecoxib intravenously prior to induction of anesthesia. SSNB and ANB were performed after general anesthesia in group N, whereas no nerve block was performed in group C. Pain intensity was compared before surgery, as well as immediately, 24 hours, and 2 weeks after surgery. PROs, including the Oxford Shoulder Score, University of California-Los Angeles shoulder score, and Single Assessment Numeric Evaluation score, were compared before and 6 months after surgery. RESULTS: The numerical rating scale (NRS) score for resting pain was significantly lower in group N (4.9 ± 3.1 vs 7.6 ± 2.5, P < .001) immediately after surgery, but no difference was noted 24 hours after surgery. The resting pain NRS score 2 weeks after surgery was significantly lower in group N (1.4 ± 1.6 vs 2.7 ± 2.7, P = .03), but the scores for movement-evoked pain and night pain were similar. All PROs significantly improved 6 months after surgery in both groups, but there was no difference between the 2 groups. CONCLUSIONS: The addition of preoperative ultrasound-guided SSNB and ANB to parecoxib offered better resting pain control immediately and 2 weeks after ARCR, but there was no benefit for PROs 6 months after surgery. LEVEL OF EVIDENCE: Level II, prospective randomized controlled trial.

The increased lateral tibial slope may result in inferior long-term clinical outcome after DB-ACL reconstruction.

PURPOSE: To determine if there is a correlation between lateral tibial slope and long-term clinical results in patients who underwent double-bundle ACL reconstruction. METHODS: We retrospectively reviewed patients that received double-bundle ACL reconstruction at a single institution by a single surgeon from January 2011 to December 2014. All the magnetic resonance imaging were reviewed and lateral tibial slopes (LTS) were recorded by an experienced surgeon and rechecked by the other two authors of this study that specialized in orthopedic knee surgery. The relationship between PROMs measurement and lateral tibial slope were analyzed. The patients were then separated into two groups (LTS > 7.4° and < 7.4°) according to the previous study. RESULTS: A total of 119 patients were enrolled in this study. All enrolled patients were followed for at least 8 years. The PROMS result were negatively correlated with the lateral tibial slope (p values all < 0.001). The patients with high lateral tibial slope had significantly lower PROMS values (Lysholm 94.26 ± 5.61 vs 80.15 ± 8.28, p = 0.013; IKDC 82.99 ± 4.55 vs 70.09 ± 7.15, p = 0.003; Tegner 9.32 ± 0.95 vs 6.85 ± 1.99, p < 0.001). Finally, the LTS cutoff value between patients with "Good" and "Fair" Lysholm score in our study was 7.55 degrees. CONCLUSIONS: Patients with high lateral tibial slope may result in inferior long-term subjective outcomes. The using of double-bundle ACL reconstruction along cannot overcome the negative impact caused by steep lateral tibial slope. A lateral tibial slope of 7.55° may be used as a cut-off for a good clinical outcome. LEVEL OF EVIDENCE: III retrospective comparative prognostic trial.

Anatomic versus Low Tibial Tunnel in Double-Bundle Posterior Cruciate Ligament Reconstruction: Clinical and Radiologic Outcomes with a Minimum 2-Year Follow-Up.

There is currently no consensus on the optimal placement of the tibial tunnel for double-bundle posterior cruciate ligament (PCL) reconstruction. The purpose of this study was to compare the clinical and radiologic outcomes of double-bundle PCL reconstruction utilizing anatomic versus low tibial tunnels. We conducted a retrospective cohort study involving patients who underwent double-bundle PCL reconstruction between Jan 2019 and Jan 2022, with a minimum follow-up of 2 years (n = 36). Based on the tibial tunnel position on postoperative computed tomography, patients were categorized into two groups: anatomic placement (group A; n = 18) and low tunnel placement (group L; n = 18). We compared the range of motion, stability test, complications, and side-to-side differences in tibial posterior translation using kneeling stress radiography between the two groups. There were no significant differences between the groups regarding clinical outcomes or complication rates. No significant differences in the posterior drawer test and side-to-side difference on kneeling stress radiography (2.5 ± 1.2 mm in group A vs. 3.7 ± 2.0 mm in group L; p = 0.346). In conclusion, the main findings of this study indicate that both anatomic tunnel and low tibial tunnel placements in double-bundle PCL reconstruction demonstrated comparable and satisfactory clinical and radiologic outcomes, with similar overall complication rates at the 2-year follow-up.

Gemcitabine resistance in non-small cell lung cancer is mediated through activation of the PI3K/AKT/NF-κB pathway and suppression of ERK signaling by reactive oxygen species.

Lung cancer is one of the most common cancers in the world. Chemotherapy is a standard clinical treatment. However, tumor cells often develop multidrug resistance after chemotherapy, an inevitable bottleneck in cancer treatment. Therefore, this study used gemcitabine-resistant (GEM-R) CL1-0 lung cancer cells. First, we used flow cytometry and western blot analysis to examine differences in performance between resistant and parental cells. The results showed that compared with parental cells, GEM-R CL1-0 cells significantly enhanced the activation of the AKT pathway, which promoted survival and growth, and decreased the activation of the reactive oxygen species-extracellular signal-regulated kinase (ROS)-ERK pathway. Next, the AKT and ERK pathways' role in tumor growth was further explored in vivo using a xenograft model. The results showed that enhancing AKT and inhibiting ERK activation reduced GEM-induced inhibition of tumor growth. Finally, combining the above results, we found that GEM-R CL1-0 cells showed reduced sensitivity to GEM by activating the phosphatidylinositol 3-kinase/AKT/NF-kB pathway and inhibiting the ROS-ERK pathway leading to resistance against GEM. Therefore, the AKT and ERK pathways are potential targets for improving the sensitivity of cancer cells to anticancer drugs.

Early versus delayed mobilization for arthroscopic rotator cuff repair (small to large sized tear): a meta-analysis of randomized controlled trials.

BACKGROUND: The timing to start passive or active range of motion (ROM) after arthroscopic rotator cuff repair remains unclear. This systematic review and meta-analysis evaluated early versus delayed passive and active ROM protocols following arthroscopic rotator cuff repair. The aim of this study is to systematically review the literature on the outcomes of early active/passive versus delayed active/passive postoperative arthroscopic rotator cuff repair rehabilitation protocols. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) published up to April 2022 comparing early motion (EM) versus delayed motion (DM) rehabilitation protocols after arthroscopic rotator cuff repair for partial and full-thickness tear was conducted. The primary outcome was range of motion (anterior flexion, external rotation, internal rotation, abduction) and the secondary outcomes were Constant-Murley score (CMS), Simple Shoulder Test Score (SST score) and Visual Analogue Scale (VAS). RESULTS: Thirteen RCTs with 1,082 patients were included in this study (7 RCTs for early passive motion (EPM) vs. delayed passive motion (DPM) and 7 RCTs for early active motion (EAM) vs. delayed active motion (DAM). Anterior flexion (1.40, 95% confidence interval (CI), 0.55-2.25) and abduction (2.73, 95%CI, 0.74-4.71) were higher in the EPM group compared to DPM. Similarly, EAM showed superiority in anterior flexion (1.57, 95%CI, 0.62-2.52) and external rotation (1.59, 95%CI, 0.36-2.82), compared to DAM. There was no difference between EPM and DPM for external rotation, retear rate, CMS and SST scores. There was no difference between EAM and DAM for retear rate, abduction, CMS and VAS. CONCLUSION: EAM and EPM were both associated with superior ROM compared to the DAM and DPM protocols. EAM and EPM were both safe and beneficial to improve ROM after arthroscopic surgery for the patients with small to large sized tears.

Phosphorylation of Bcl-2 by JNK confers gemcitabine resistance in lung cancer cells by reducing autophagy-mediated cell death.

The most common cancer-related death in the world is non-small cell lung cancer (NSCLC). Gemcitabine (GEM) is a common and effective first-line chemotherapeutic drug for the treatment of NSCLC. However, the long-term use of chemotherapeutic drugs in patients usually induces cancer cell drug resistance, leading to poor survival, and prognosis. In this study, to observe and explore the key targets and potential mechanisms of NSCLC resistance to GEM, we first cultured lung cancer CL1-0 cells in a GEM-containing medium to induce CL1-0 cells to develop GEM resistance. Next, we compared protein expression between the parental and GEM-R CL1-0 cell groups. We observed significantly lower expression of autophagy-related proteins in GEM-R CL1-0 cells than in parental CL1-0 cells, indicating that autophagy is associated with GEM resistance in CL1-0 cells. Furthermore, a series of autophagy experiments revealed that GEM-R CL1-0 cells had significantly reduced GEM-induced c-Jun N-terminal kinase phosphorylation, which further affected the phosphorylation of Bcl-2, thereby reducing the dissociation of Bcl-2 and Beclin-1 and ultimately reducing the generation of GEM-induced autophagy-dependent cell death. Our findings suggest that altering the expression of autophagy is a promising therapeutic option for drug-resistant lung cancer.

Outcomes of Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction According to GNRB Arthrometer Measurement.

Background and Objectives: To investigate the prognosis of combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction, we used a GNRB (Genourob, Laval, France) arthrometer to measure surgical outcomes. Materials and Methods: This retrospective study reviewed patients who underwent combined ACL and ALL reconstruction and had a minimum follow-up of 2 years. Subjective outcomes, namely the International Knee Documentation Committee (IKDC) evaluation form scale scores and Lysholm scores, were evaluated preoperatively and postoperatively. We used a GNRB arthrometer to test the side-to-side laxity under pressures of 134 and 200 N, and we calculated the differential of the slope of the curves. We also recorded complications. Results: Our study examined 18 patients (mean age: 30.56 ± 8.9 years, range: 19-53) with a mean follow-up of 27.37 ± 3.4 months (range: 24-36). Both Lysholm and IKDC scores were significantly improved following the operation. The GNRB arthrometer measured mean anteroposterior laxity side-to-side as 0.76 ± 0.78 mm and 0.82 ± 0.8 mm under pressures of 134 and 200 N, respectively. The mean side-to-side differential slope under 200 N was 3.52 ± 2.17 µm/N. These values indicated that patients displayed no graft tear or low functional knee instability. All patients had a grade 3 pivot shift preoperatively; only two patients had a grade 1 pivot shift postoperatively, with the rest having a negative pivot shift. Conclusions: Our study revealed that combined ACL and ALL reconstruction has an excellent prognosis. GNRB measurement demonstrated excellent stability, and most patients had no residual pivot shift.

Using Single Peroneal Longus Tendon Graft for Segmental Meniscus Transplantation and Revision Anterior Cruciate Ligament Combined Anterolateral Reconstruction.

This case report describes a new approach to segmental meniscal reconstruction using a peroneal longus autograft in a patient with recurrent traumatic medial meniscus tear and anterior cruciate ligament reconstruction (ACLR) failure. While allograft meniscal transplantation is the preferred method for treating meniscal deficiency, its high cost and various legal regulations have limited its widespread use. Autologous tendon grafts have been proposed as a substitute for allograft meniscus transplantation, but their initial results were poor, leading to little progress in this area. However, recent animal experiments and clinical studies have demonstrated promising results in using autologous tendon grafts for meniscal transplantation, including improvements in pain and quality of life for patients. Further research is needed to evaluate the effectiveness of segmental meniscal reconstruction using autologous tendon grafts, but it could potentially lead to more accessible and cost-effective treatment options for patients with meniscal deficiency.

Reconstruction of High-Grade Trochlea Dysplasia in a Young Female with Recurrent Patella Dislocation: A Case Report.

The patellofemoral joint involves a combination of bony structures and soft tissues to maintain stability. Patella instability is a disabling condition, and the cause is multifactorial. The main risk factors include patella alta, trochlea dysplasia, excessive tibial tuberosity to trochlea grove (TT-TG) distance, and excessive lateral patella tilt. In this case report, we highlight the thinking process of diagnosis and method for selecting the optimal treatment in accordance with the guidelines by Dejour et al. when we are presented with a patient with patella instability. A 20-year-old Asian woman without underlying medical conditions, presented with recurrent (>3 episodes) right patella dislocation for 7 years. Investigations revealed a type D trochlea dysplasia, increased TT-TG distance, and excessive lateral tilt angle. She underwent trochlea sulcus deepening, sulcus lateralization and lateral facet elevation, lateral retinacular release, and medial quadriceps tendon-femoral ligament (MQTFL) reconstruction. Due to the complexity behind the anatomy and biomechanics of patella instability, an easy-to-follow treatment algorithm is essential for the treating surgeon to provide effective and efficient treatment. MQTFL reconstruction is recommended for recurrent patella dislocation due to satisfactory clinical and patient reported outcomes and a reduced risk of iatrogenic patella fracture. Controversies for surgical indication in lateral retinacular release, and whether the sulcus angle is an accurate parameter for diagnosis of trochlea dysplasia, remain, and further research is required.

Arthroscopic Lower Trapezius Tendon Transfer for a Patient with Axillary Nerve Injury and Concomitant Rotator Cuff Tear: A Case Report and Technical Notes.

Introduction: Concomitant nerve injuries with musculoskeletal injuries present a challenging problem. The goals of nerve reconstruction for the shoulder include shoulder abduction and external rotation. When patients fail to achieve acceptable shoulder external rotation and shoulder abduction, tendon transfers such as trapezius transfer offer a reliable option in the subsequent stage. Case Presentation: A 32-year-old male presented with weak external rotation in his left shoulder, after previous axillary nerve reconstruction. He received the ipsilateral lower trapezius transfer with the aim of improving the external rotation. Discussion: The lower trapezius restores a better joint reaction force in both the compressive-distractive and anterior-posterior balancing and provides a centering force through the restoration of the anterior-posterior force couple. Conclusion: We believe that the ipsilateral lower trapezius transfer to the infraspinatus is a good outcome and is effective in improving overall shoulder stability and the shoulder external rotation moment arm or at least maintaining in neutral position with the arm fully adducted in patients with post axillary nerve injuries post unsatisfactory nerve reconstruction to increase the quality of life and activities of daily living.

Clinical and functional outcomes of isolated posterior cruciate ligament reconstruction in patients over the age of 40 years.

BACKGROUND: To assess clinical and functional outcomes of patients aged 40 years or older receiving PCL reconstruction surgery. METHODS: All patients older than 40 years with isolated PCL rupture who underwent PCL reconstruction surgery were enrolled into the retrospective study. Associated meniscal injuries, osteochondral lesions, postoperative complications, and the rate of return to the preinjury level of activity were extracted. Outcomes included International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and Tegner activity score. The minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were used to evaluate the clinically relevant value of PCL reconstruction in this population. RESULTS: In total, 41 patients with a mean age of 51.7 years were included. The mean follow-up time was 32.8 months. Associated lesions included meniscal injuries (48.8%) and osteochondral lesions (97.6%). Improvement in the IKDC score (from 46.5 preoperatively to 79.0 postoperatively, p < 0.0001), Lysholm score (from 65.5 to 88.3, p < 0.0001), and Tegner activity score (from 2.3 to 4.0, p < 0.0001) was recorded. The clinically relevant value based on the MCID showed that 34 of 41 patients (82.9%) had a ΔIKDC score exceeding 16.8; all patients (100%) showed a ΔLysholm score exceeding 8.9; and 35 of 41 patients (85.4%) showed a ΔTegner activity score exceeding 0.5. Regarding the PASS, none of the patients had an IKDC score exceeding 75.9 preoperatively, whereas 27 of 41 patients (65.9%) had a score of more than 75.9 postoperatively. All patient had ≥ grade II knee instability preoperatively. Postoperatively, 36 patients (87.8%) had no significant joint translation, and 5 patients (12.2%) had grade I instability. Twenty-one patients (51.2%) returned to their preinjury level of activity. Five patients (12.2%) developed Ahlbäck grade I radiographic osteoarthritis. No rerupture or other major perioperative complications were reported. CONCLUSIONS: PCL reconstruction is a reliable surgery for middle-aged patients suffering from persistent instability even after failed conservative treatment, with significant improvement in patient-reported outcomes that exceeded MCID in the majority of patients, restoration of subjective instability, and approximately half of the patients returned to preinjury activity levels. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Functional Outcomes Are Similar After Arthroscopic Capsular Repair of Triangular Fibrocartilage Complex Tears Between Outside-In Technique and All-Inside Technique Using Pre-Tied Suture Device.

PURPOSE: To compare outcomes of arthroscopic triangular fibrocartilage complex capsular repair at 2-year follow-up between outside-in and all-inside techniques. METHODS: In total, 58 consecutive patients (wrists) with a Palmer 1B triangular fibrocartilage complex tear without symptomatic distal radioulnar joint instability underwent arthroscopic suture repair from 2011 to 2019 including 31 patients via the outside-in technique (group A) and 27 via the all-inside technique using a pre-tied needle device (group B). Two-year follow-up included visual analog scale (VAS) pain score, motion range, grip strength, Mayo Modified Wrist Score (MMWS), the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and complication rate. Correlation between functional result and patient satisfaction was analyzed. RESULTS: Score changes in VAS, wrist flexion-tension, supination-pronation, grip strength, MMWS, and QuickDASH at 2-year follow-up were not significantly different between group A (3.4 ± 0.8, 18.4 ± 17.5, 12.9 ± 13.3, 30.7 ± 11.2, 26.6 ± 7.9 and 19.4 ± 9.9 and group B (3.4 ± 1.0, 18.5 ± 18.3, 15.6 ± 13.7, 30.8 ± 11.4, 28.1 ± 8.6, and 7.6 ± 7.2) with P values of .400, .489, .223, .486, .240, and .223 respectively. Surgical time averaged 105 minutes (78 to 136) in group A and 94 minutes (61-126) in group B with significant difference (P = .012). Patient satisfaction averaged 1.1 (0-3.5) in group A and 1.0 (range 0-3.0) in group B. Satisfaction score was more strongly correlated with QuickDASH (coefficients: 0.863 in group A and 0.918 in group B) than with MMWS (-0.693 in group A and -0.465), grip strength (-0.619 in group A and -0.417 in group B) and VAS score (0.607 in group A and 0.222 in group B). CONCLUSIONS: Both techniques achieved comparable outcomes with shorter surgical time in all-inside repair using pre-tied needle device. Patient satisfaction was strongly correlated with QuickDASH score. LEVEL OF EVIDENCE: Level III, retrospective therapeutic comparative investigation.

Arthroscopic Pan-Capsular and Transverse Humeral Ligament Release with Biceps Tenodesis for Patients with Refractory Frozen Shoulder.

Arthroscopic capsular release allows direct visualization and release of inflamed tissues in refractory frozen shoulder. The reticular neural network in the long head of the biceps tendon (LHBT) and nerve endings of the transverse humeral ligament (THL) might be responsible for shoulder pain. We hypothesized that patients with painful refractory frozen shoulder benefited from pan-capsular release, THL release, and LHBT tenodesis. The LHBT tenodesis decreased the possibility of LHBT instability. The balance of the shoulder joint was maintained after such extensive release. From October 2013 to June 2019, patients with painful refractory frozen shoulder were enrolled consecutively at the same institute. All patients received arthroscopic pan-capsular, THL release, and suprapectoral LHBT tenodesis with a minimum of 2-year follow-up. Preoperative and postoperative shoulder range of motion (ROM), pain visual analog scale (PVAS), subjective shoulder value (SSV), constant score, LHBT score, acromio-humeral distance (AHD), and critical shoulder angle (CSA) were recorded. In total, 35 patients with an average age of 53.1 ± 9 years were enrolled. The average follow-up period was 24 ± 1.5 months. Forward elevation improved from 105.1° ± 17° to 147° ± 12° (p < 0.001), external rotation improved from 24.1° ± 13.3° to 50.9° ± 9.7° (p < 0.001), and internal rotation improved from L3 to T9 (p < 0.001), respectively, at final follow-up. PVAS improved from 7.3 ± 1.1 to 1.8 ± 0.6 (p < 0.001), constant score from 23.4 ± 11 to 80.7 ± 5.2 (p < 0.001), and SSV from 27.7 ± 10.5 to 77.4 ± 3.8, respectively, at follow-up. No differences were found in AHD and CSA after surgery (p = 0.316, and p = 0.895, respectively). Patients with painful refractory frozen shoulder benefited from pan-capsular and THL release. A radiographically balanced shoulder joint was maintained even after such extensive release.

Recurrent Shoulder Instability after Arthroscopic Bankart Repair in an Elite Baseball Pitcher-A Case Report.

A 16-year-old right-handed male pitcher had a first-time right anterior shoulder dislocation during a baseball game. X-ray and MRI revealed no apparent glenoid bone loss or Hill-Sachs lesion, but an anterior labroligamentous periosteal sleeve avulsion (ALPSA) lesion with mild posterolateral decompression of the humerus head. His instability severity index score (ISIS score) was 5 with an on-track lesion. He had an arthroscopic Bankart repair using two all-suture anchors and returned to pitching 6 months after the index surgery. However, he had an unstable sensation after 50 pitches during a game one year postoperatively. This time, he presented with a significant Hill-Sachs lesion and a recurrent APLSA lesion. His ISIS score was 6 with an on-tract lesion. During the arthroscopic examination, the previous suture was stable, while anterior capsuloligament tissues were dislodged from sutures, and a Hill-Sachs lesion was observed. This time, a revision arthroscopic Bankart repair and Remplissage procedure were done on him with four double-loaded soft tissue anchors. Pitchers often develop more external rotation in their throwing arm because of a repetitive stretch of the anterior shoulder capsule and ligaments during pitching. The decrease in external rotation after surgery may limit the pitching speed of the pitcher, making a return to play (RTP) more difficult. There is still a paucity of best evidence to revise a failed arthroscopic Bankart repair in the dominant arm of a pitcher. Arthroscopic Bankart repair and Remplissage procedure have gained increasing popularity because they can provide a stable shoulder without harvesting the coracoid. The Latarjet procedure provides a high RTP rate; however, we did not perform it in the revision surgery and decided to revise the Bankart lesion again on its own with a Remplissage procedure, even with his ISIS score being 6 before the revision surgery. A salvage Latarjet procedure is left as a bailout procedure.

Pneumothorax, an Uncommon but Devastating Complication following Shoulder Arthroscopy: Case Reports.

Shoulder arthroscopy is a mature and widely used treatment to deal with various shoulder disorders. It enables faster recovery and decreases postoperative complications. However, some complications related to shoulder arthroscopy cannot be neglected because they could be life threatening. We presented three cases of various clinical manifestations of pneumothorax after shoulder arthroscopy. The first case was a 65-year-old female who underwent arthroscopic rotator cuff repair under general anesthesia and interscalene nerve block in the beach-chair position. The second case was a 58-year-old male undergoing arthroscopic rotator cuff repair and reduction in glenoid fracture under general anesthesia in the lateral decubitus position. The third case was a 62-year-old man receiving arthroscopic rotator cuff repair under general anesthesia in the lateral decubitus position. Each case's operation time was 90, 240, and 270 min. The pressure of the irrigation pumping system was 30, 50, and 70 mmHg, respectively. The second and third cases did not undergo interscalene nerve block. Although the incidence of pneumothorax following shoulder surgery and interscalene nerve block was only 0.2%, it is one of the most life-threatening complications following shoulder arthroscopy. In these cases, multifactorial factors, including patient positioning, interscalene nerve block, long surgical time, size of rotator cuff tears, and the pressure of the irrigation and suction system, can be attributed to the occurrence of pneumothorax. It is crucial to fully comprehend the diagnosis and management of pneumothorax to reduce the risk for patients receiving shoulder arthroscopy.

Signal transducer and activator of transcription 3 mediates apoptosis inhibition through reducing mitochondrial ROS and activating Bcl-2 in gemcitabine-resistant lung cancer A549 cells.

Lung cancer is a leading cause of cancer-related death worldwide. In this study, we used lung adenocarcinoma cells as a model, as lung adenocarcinoma has the highest mortality rate among all lung cancers. For the past few years, medical treatments or lung cancer have been limited because of chemotherapy resistance. Therefore, understanding the pathogenesis of the development of drug resistance in lung cancer is urgent. Gemcitabine is widely prescribed in the chemotherapeutic treatment of lung cancers. In this study, we developed gemcitabine-resistant lung adenocarcinoma cells (A549-GR) from the A549 cell line. The results showed that apoptotic protein expression and reactive oxygen species (ROS) generation were reduced in A549-GR cells compared to A549 cells. Interestingly, we found that signal transducer and activator of transcription 3 (STAT3) translocated to the nucleus and mitochondria to affect the apoptotic pathway and ROS generation, respectively. Furthermore, treatment with STAT3 small interfering RNA diminished the increase in ROS production, proliferation and antiapoptotic proteins in A549-GR cells. Taken together, the study demonstrated that STAT3 acts as an essential regulator and moderates apoptosis through two major mechanisms to induce gemcitabine resistance in cells; and these findings provide a potential target for the treatment of gemcitabine-resistant lung cancer.

Retrospective cohort study on radial head arthroplasty comparing long-term outcomes between valgus type injury and fracture dislocation.

BACKGROUND: Radial head arthroplasty (RHA) has been commonly adopted for irreparable radial head fractures while little information is addressed on valgus type injury. The purpose of this study is to report long-term outcomes and radiographic analysis in RHA for valgus type injury with comparison to fracture dislocation injury. METHODS: A retrospective cohort study was conducted in patients receiving unilateral RHA with loose-fit, modular metal prosthesis for irreparable radial head fractures between 2004 and 2012. Totally, 33 patients with a mean follow up of 9 years (range, 7 to 15 years) were enrolled and divided into two groups including 14 valgus injuries and 19 fracture-dislocations. Demographics of the patients, injury details, clinical and radiographic outcomes, and correlation analysis were investigated and compared between two groups. RESULTS: In patient demographics, significant difference was noted in sex distribution (p = 0.001), lateral collateral ligament involvement (p = 0.000) and time from injury to RHA (p = 0.031) between two groups. No patient underwent subsequent removal or revision of prosthesis. Good to excellent results according to Mayo Elbow Performance Score (MEPS) was achieved in 13 and 14 patients in group A and B respectively. Final motion range and Disabilities of the Arm, Shoulder, and Hand score was significantly better in valgus injury group. Radiographic analysis demonstrated fewer patients in valgus injury group presented periprosthetic osteolysis with weak to moderate negative correlation between radiolucency score and MEPS. CONCLUSIONS: With an average of 9 years follow-up, RHA using loose-fit, modular metal prosthesis achieves encouraging outcomes for both valgus injury and fracture dislocation. In valgus type injury, better motion range, lower disability score and lower incidence of periprosthetic osteolysis is noted while correlation analysis of radiolucency score suggests extended, long-term investigation.

Clinical and Functional Outcomes of Anterior Cruciate Ligament Reconstruction With Autologous Hamstring Tendon in Patients Aged 50 Years or Older.

PURPOSE: To assess the clinical and functional outcomes, including the return to sports and the progression of arthritis, in patients aged 50 years or older after anterior cruciate ligament (ACL) reconstruction. METHODS: A retrospective series of patients aged 50 years or older with ACL rupture who received ACL reconstruction surgery with autologous hamstring tendon was examined. Preoperative and postoperative functional outcomes were evaluated with the International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and Tegner activity score. Associated injuries, postoperative complications, and the rate of return to preinjury sports were documented. A paired t test and the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were used for statistical evaluation. RESULTS: A total of 67 patients with a mean age of 56.6 years were enrolled. The mean follow-up time was 30.2 months. Clinical improvement in the IKDC score (from 41.4 preoperatively to 88.9 postoperatively), Lysholm score (from 49.8 to 86.1), and Tegner activity score (from 2.7 to 4.4) was noted. Regarding clinically relevant values of the MCID, all patients (100%) showed a ΔLysholm score exceeding 8.9; 66 of 67 patients (98.5%) revealed a ΔIKDC score exceeding 16.7; and 47 of 67 patients (70.1%) showed a ΔTegner activity score of more than 1. For the PASS, none of the patients had an IKDC score over 75.9 preoperatively whereas 60 patients (89.5%) had a score exceeding 75.9 postoperatively. Associated lesions included meniscal injuries (73.1%) and osteochondral lesions (89.6%). Of the patients, 36 (53.7%) returned to preinjury sports and 18 (22.9%) returned to sports with less intensity. No major complication, rerupture, or deterioration of arthritis was noted. CONCLUSIONS: Patients aged 50 years or older receiving ACL reconstruction achieved significant improvements in IKDC, Lysholm, and Tegner scores. All patients reached the MCID for the ΔLysholm score; 98.5%, for the ΔIKDC score; and 70.1%, for the ΔTegner activity score. None of the patients reached the PASS for the preoperative IKDC value, whereas 89.5% reached the PASS postoperatively. Among patients aged 50 years or older, 53.7% returned to preinjury sports and 26.9% returned to sports with lower intensity. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Pyramiding Bacterial Blight Resistance Genes in Tainung82 for Broad-Spectrum Resistance Using Marker-Assisted Selection.

Tainung82 (TNG82) is one of the most popular japonica varieties in Taiwan due to its relatively high yield and grain quality, however, TNG82 is susceptible to bacterial blight (BB) disease. The most economical and eco-friendly way to control BB disease in japonica is through the utilization of varieties that are resistant to the disease. In order to improve TNG82's resistance to BB disease, five bacterial blight resistance genes (Xa4, xa5, Xa7, xa13 and Xa21) were derived from a donor parent, IRBB66 and transferred into TNG82 via marker-assisted backcrossing breeding. Five BB-resistant gene-linked markers were integrated into the backcross breeding program in order to identify individuals possessing the five identified BB-resistant genes (Xa4, xa5, Xa7, xa13 and Xa21). The polymorphic markers between the donor and recurrent parent were used for background selection. Plants having maximum contribution from the recurrent parent genome were selected in each generation and crossed with the recipient parent. Selected BC3F1 plants were selfed in order to generate homozygous BC3F2 plants. Nine pyramided plants, possessing all five BB-resistant genes, were obtained. These individuals displayed a high level of resistance against the BB strain, XF89-b. Different BB gene pyramiding lines were also inoculated against the BB pathogen, resulting in more than three gene pyramided lines that exhibited high levels of resistance. The five identified BB gene pyramided lines exhibited yield levels and other desirable agronomic traits, including grain quality and palatability, consistent with TNG82. Bacterial blight-resistant lines possessing the five identified BB genes exhibited not only higher levels of resistance to the disease, but also greater yield levels and grain quality. Pyramiding multiple genes with potential characteristics into a single genotype through marker-assisted selection can improve the efficiency of generating new crop varieties exhibiting disease resistance, as well as other desirable traits.

Real-time detection of antibiotics cytotoxicity in rabbit periosteal cells using microfluidic devices with comparison to conventional culture assays.

BACKGROUND: Local antibiotic application has been widely used in orthopedic surgery. The dose-related toxicity of antibiotics towards periosteal tissues and resulting effects on osteogenic expression are yet to be studied. METHODS: Periosteal cells harvested from the medial tibia of New Zealand White rabbits were used. A seeding density of 5 × 103 cells/cm2 was determined to be optimal for testing in the pilot study; the cells were cultured in xCELLigence 96-well plates. Microfluidic impedance analyzers were used to monitor cellular proliferation in microfluidic culture systems with exposure to three different concentrations (10 µg/mL, 100 µg/mL, and 1000 µg/mL) of cefazolin, ciprofloxacin, and vancomycin, respectively. The correlation of cell index at day 7 with optical density values from WST-1 assays using conventional cultures was evaluated by calculating the Pearson's coefficient. RNA analysis was performed to investigate the expression of osteogenic markers in the cultured cells, including core-binding factor alpha 1 (Cbfa1), osteopontin (OPN), and osteopontin promoter (OPNp), relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the endogenous control. RESULTS: A significant dose-related inhibition of cell index was found for all the 3 antibiotics, whereas the WST-1 assays showed a significant dose-related inhibition of cellular proliferation only at a high dose of cefazolin (1000 µg/mL) and medium-to-high dose of ciprofloxacin (100 µg/mL and 1000 µg/mL). Pearson's coefficient analysis indicated a high correlation between the cell index and optical density values of WST-1 assays only for medium and high doses of ciprofloxacin (100 µg/mL and 1000 µg/mL); a moderate correlation was seen for cefazolin, and a low dose of ciprofloxacin (10 µg/mL). RNA analysis confirmed significant dose-related inhibition of cfba1, OPN, and OPNp expression by all three antibiotics. CONCLUSION: With optimal seeding amounts, rabbit periosteal cells can be dynamically monitored in the xCELLigence microfluidic system. Dose-related inhibition of cellular proliferation and osteogenic expression was found after exposure to cefazolin and ciprofloxacin. By providing real-time detection and exhibiting comparable correlation, microfluidic impedance-based analyzer is a feasible alternative to the conventional WST-1 assays.