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Background: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide‐binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. Methods: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high‐throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro‐computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin‐12 (IL‐6) were detected by western blot. Results: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL‐6. Conclusions: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas. [ABSTRACT FROM AUTHOR]

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p < 0.001). In patients with major thoracic injury, older age and higher injury survival scale account for higher mortality rate. Effective surgical stabilization of rib fractures shortened the ICU stay and helped achieve better performance in EIT. Thoracoscope-assisted rib fixation is suggested in severe trauma cases. [ABSTRACT FROM AUTHOR]

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p < 0.001). In patients with major thoracic injury, older age and higher injury survival scale account for higher mortality rate. Effective surgical stabilization of rib fractures shortened the ICU stay and helped achieve better performance in EIT. Thoracoscope-assisted rib fixation is suggested in severe trauma cases. [ABSTRACT FROM AUTHOR]

Aim: To compare and evaluate the efficacy of the levonorgestrel‐releasing intrauterine system (LNG‐IUD) and resectoscopy remodeling procedure for intermenstrual bleeding associated with previous cesarean delivery scar defect (PCDS). Methods: A retrospective comparative study was conducted on patients with PCDS receiving LNG‐IUD (levonorgestrel 20 μg/24 h, N = 33) or resectoscopy remodeling (N = 27). Treatment outcomes were compared over 1, 6, and 12 months. Outcomes in patients with a retroverted or large uterus size, defect size, and local vascularization also were evaluated. Results: At 12 months post‐treatment, there were no significant differences between groups in efficacy rate; however, the reduction of intermenstrual bleeding days was higher in the LNG‐IUD group than in the resectoscopy group (13.6 vs. 8.5 days, p = 0.015). Within the first year, both groups experienced a reduction in bleeding days, but the decrease was greater in the LNG‐IUD group. Individuals exhibiting increased local vascularization at the defect site experienced more favorable outcomes in the LNG‐IUD group than the resectoscopy group (p = 0.016), and who responded poorly tended to have a significantly larger uterus in the LNG‐IUD group (p = 0.019). No significant differences were observed in treatment outcomes for patients with a retroverted uterus or large defect in either group. Conclusions: Our findings support that the LNG‐IUD is as effective as resectoscopy in reducing intermenstrual bleeding days associated with PCDS and can be safely applied to patients without recent fertility aspirations. Patients with increased local vascularization observed during hysteroscopy may benefit more from LNG‐IUD intervention than resectoscopy. [ABSTRACT FROM AUTHOR]

Objectives: Tyrosine kinase inhibitors (TKIs) are the primary therapeutic option for patients with advanced-stage epidermal growth factor receptor-mutant (EGFR-m) lung adenocarcinoma. However, the role of EGFR-TKIs in advanced-stage lung cancer is uncertain regardless of therapeutic methods. This study investigated the outcome of the impact of epidermal growth factor receptor (EGFR)-TKI in patients with advanced lung adenocarcinoma treated with various therapeutic strategies. Methods: This retrospective analysis used cancer registry data from 1159 patients with lung cancer treated between January 2015 and December 2017 at Tri-Service General Hospital. Only patients with lung adenocarcinoma stages 3B and four were selected for the study. All lung adenocarcinoma patients with ever TKI treatment had an EGFR mutation. Results: Three-hundred sixty-two patients with advanced lung adenocarcinoma with complete medical records were enrolled. According to personalized therapeutic processes, they were divided into nine groups: only TKI treatment, only chemotherapy (CT), TKI with lung cancer salvage surgery, TKI with CT, TKI with radiotherapy (RT), CT with lung cancer salvage surgery, CT with RT, TKI with CT, and lung cancer salvage surgery. A multivariate Cox regression analysis showed TKI with lung cancer salvage surgery (HR: 4.675, p = 0.005) is the only good prognostic treatment. The poor predictors for overall survival were only CT (HR: 0.336, p = 0.048) and TKI with CT (HR: 0.359, p = 0.023). Kaplan–Meier survival analysis showed a statistical significance in an average overall survival (OS) of ever TKI treatment and never TKI treatment (33.24 vs. 17.64 months, p < 0.001). Furthermore, TKI usage duration was statistically increased in TKI with lung cancer salvage surgery (40.4 ± 20.7 vs 14.96 ± 13.13 months, p < 0.001). The survival rate (p = 0.033) and OS (p < 0.001) in lung cancer salvage surgery were statistically better than the group of TKI without surgery. Conclusion: The best therapeutic strategy for advanced lung adenocarcinoma is TKI with lung cancer salvage surgery, according to significantly longer OS and better survival. It also prolonged TKI usage. Mutated EGFR lung adenocarcinoma patients with ever TKI treatment had significantly better survival than with other treatments. Regardless of the combination of other treatments, EGFR mutation with TKI therapy is recommended as a positive prognostic factor for patients with lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether the cost-effective, pretreatment tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) can be used to predict lymph node metastasis (LNM) in endometrioid-type endometrial cancer (EC) and to develop a predictive model. Methods: This was a single-center retrospective study of patients with endometrioid-type EC who underwent complete staging surgery between January 2015 and June 2022. We identified the optimal cut-off values of CEA and CA-125 for predicting LNM using receiver operating characteristic (ROC) curves. Stepwise multivariate logistic regression analysis was used to identify independent predictors. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. Results: The optimal cut-off values of CEA and CA-125 were 1.4 ng/mL (area under the ROC curve (AUC) 0.62) and 40 U/mL (AUC 0.75), respectively. Multivariate analysis showed that CEA (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.01–3.74) and CA-125 (OR 8.75; 95% CI 4.42–17.31) were independent predictors of LNM. Our nomogram showed adequate discrimination with a concordance index of 0.78. Calibration curves for the probability of LNM showed optimal agreement between the predicted and actual probabilities. The risk of LNM for markers below the cut-offs was 3.6%. The negative predictive value and negative likelihood ratio were 96.6% and 0.26, respectively, with moderate ability to rule out the possibility of LNM. Conclusion: We report a cost-effective method of using pretreatment CEA and CA-125 levels to identify patients with endometrioid-type EC who are at a low risk for LNM, which may guide decision-making regarding aborting lymphadenectomy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the treatment effect of strabismus surgery for Graves ophthalmopathy in an ethnic Chinese population. Study design: A prospective clinical study. Methods: Thirty-one patients with Graves ophthalmopathy who had undergone strabismus surgery at National Taiwan University Hospital between 2012 and 2013 were consecutively recruited. The subjective outcome was evaluated using the Graves' Ophthalmopathy Quality-of-Life (GO-QoL) questionnaire, and the ocular deviation was measured preoperatively and postoperatively by use of a prism cover test. Results: The GO-QoL scores for visual functioning and appearance improved significantly after surgery (preoperative scores 32.6 ± 19.9 and 43.8 ± 26.4, postoperative scores 55.2 ± 24.4 and 54.1 ± 27.6, respectively; P <.05). Motor success was achieved in 61.3% of the patients, and their postoperative visual scores were higher (61.5 ± 22.5) than the scores of those who experienced motor failure (45.3 ± 26.8, P =.048). The postoperative visual function scores showed a negative correlation with the residual vertical deviation (R2 = 0.546, P =.040). A higher increase in GO-QoL visual scores and a lower residual vertical deviation in downgaze were achieved among patients without previous decompression surgery. Our surgical methods resulted in a motor success rate of 76.5% for the correction of vertical deviation. Conclusion: GO-QoL scores and ocular deviation improved significantly after strabismus surgery. Precise correction of vertical deviation was of greater importance than horizontal deviation for visual function scores. Our surgical methods were effective for the correction of vertical deviation in Graves ophthalmopathy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-related fatigue (CRF) is a common somatic discomfort in gynecological cancer patients; however, it is usually overlooked by physicians. We aimed to explore the prevalence of CRF's and the clinical characteristics of gynecological cancer patients. The results showed that 77.9% of patients had received related CRF management. A five-item predictive model was developed from the identified risk factors contributing to CRF. The risk factors included (1) diagnosis of endometrial/cervical cancer, (2) International Federation of Gynecology and Obstetrics (FIGO) stage >1, (3) Eastern Cooperative Oncology Group (ECOG) status score ≥1, (4) inadequate treatment response, and (5) having received cancer treatment in the past 1 week. The predictive model may help physicians more promptly identify high-risk patients in clinical practice. Cancer-related fatigue (CRF) is the most common somatic discomfort in patients with gynecological cancers. CRF is often overlooked; however, it can impair the patients' quality of life considerably. This cross-sectional study aimed to identify the clinical characteristics of CRF in gynecological cancer patients. Questionnaires and the International Classification of Diseases 10th Revision (ICD-10) criteria were used to identify CRF. The enrolled patients were further categorized according to the amount of fatigue-related management received. Of the enrolled 190 patients, 40.0% had endometrial cancer, 28.9% had cervical cancer, and 31.1% had ovarian cancer. On the basis of the ICD-10 diagnostic criteria, 42.6% had non-cancer-related fatigue, 10% had CRF, and 51% had BFI-T questionnaire-based fatigue. Moreover, 77.9% of the study cohort had ever received fatigue-related management. Further analysis showed that patients with endometrial/cervical cancer, International Federation of Gynecology and Obstetrics stage >1, Eastern Cooperative Oncology Group performance status score ≥1, inadequate cancer treatment response, and receiving cancer treatment in the past week had a higher probability of receiving more fatigue-related management. The five-item predictive model developed from these factors may help physicians recognize patients seeking more fatigue-related management more efficiently. This is important as they may suffer from a more profound CRF. [ABSTRACT FROM AUTHOR]

Navigation bronchoscopy is an emerging technique used to evaluate pulmonary lesions. Using Veran's SPiN electromagnetic navigation bronchoscopy (ENB) and Archimedes virtual bronchoscopy navigation (VBN), this study aimed to compare the accuracy and safety of these procedures for lung lesions and to identify potentially relevant knowledge for the application of artificial intelligence in interventional pulmonology in a single institute. This single-center, retrospective study compared the ENB and VBN results in patients with pulmonary lesions unsuitable for biopsy via percutaneous transthoracic needle biopsy methods. A total of 35 patients who underwent navigation bronchoscopy for pulmonary lesion diagnosis were enrolled. Nineteen patients were stratified in the ENB group, and sixteen were in the VBN group. The mean age of this cohort was 67.6 ± 9.9 years. The mean distance of the lesion from the pleural surface was 16.1 ± 11.7 mm (range: 1.0–41.0 mm), and most lesions were a solid pattern (n = 33, 94.4%). There were 32 cases (91.4%) of pulmonary lesions with an air-bronchus sign. A statistically significant difference was found between pulmonary size and transparenchymal nodule access (p = 0.049 and 0.037, respectively). The navigation success rate was significantly higher in the VBN group (93.8% vs. 78.9%). Moreover, no procedure-related complications or mortality were noted. The radiographic characteristics, such as size or solid component, can affect the selection of the biopsy procedure, either ENB or VBN. Navigation bronchoscopy-guided biopsy demonstrated acceptable accuracy and a good safety profile in evaluating pulmonary lesions when the percutaneous approach was challenging or life threatening. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to verify the importance and the timing of endobronchial ultrasound with transbronchial biopsy (EBUS TBNA) among lung adenocarcinoma patients after radical resection. Methods: We retrospectively reviewed consecutive patients with non-small cell lung cancer (NSCLC) who had ever received radical resection from January 2002 to December 2021. The patients were divided into two groups, with and without EBUS TBNA, for diagnosis or staging. Results: Of 2018 patients with NSCLC, after surgical resection of lung tumors, there were 232 with recurrences. Under multivariate Cox regression analysis, patients with recurrences who received EBUS TBNA had a statistically higher mean maximum standardized uptake value (SUVmax) (hazard ratio (HR) = 1.115, confidence interval (CI) = 1.004–1.238, p = 0.042) and better survival (HR = 5.966, CI = 1.473–24.167, p = 0.012). Although KM survival analysis showed no statistically significant difference between groups with and without EBUS TBNA (p = 0.072) of lung adenocarcinoma patients with recurrences, patients with mutated epidermal growth factor receptor (EGFR) showed significantly better survival than wild-type EGFR (p = 0.007). Conclusions: The clinical practice of EBUS TBNA is not only for diagnosis, but also for nodal staging. We found that lung adenocarcinoma patients with recurrences who received EBUS TBNA had better overall survival. Therefore, EBUS TBNA is a reliable and feasible tool that could be used in lung adenocarcinoma patients with recurrences for early diagnosis and for adequate tissue specimens for further molecular analysis. [ABSTRACT FROM AUTHOR]

Purpose: To report the clinical presentations and outcome of early intravitreal injection (IVI) of octafluoropropane (C3F8) for persistent macular holes (MH) after primary pars plana vitrectomy with the internal limiting membrane (ILM) peeling technique.Methods: Nineteen eyes of 18 patients with persistent MH after vitrectomy underwent intravitreal injection of C3F8 between 11 and 21 days after the initial surgery (intravitreal gas injection group). Another nine eyes with a persistent MH without additional IVI C3F8 were included (non-intravitreal gas injection group). Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) features including size and configuration of MH, and time duration between the 2 surgeries were compared between the MH closure and open groups. The closure rate of persistent MHs was compared between the intravitreal gas injection group and non-intravitreal gas injection group.Results: Twelve of 19 eyes (63%) achieved MH closure after 1 to 3 times IVI C3F8. The final BCVA after vitrectomy and IVI gas was significantly better in the MH closure group (P = .005). Nine of 12 patients (75%) in the MH closure group had a visual acuity improvement of more than 2 lines. Original MHs with smaller minimal diameter, higher macular hole index (MHI) and higher tractional hole index (THI); and persistent MHs with smaller minimal diameter, higher THI, and lower diameter hole index (DHI) showed higher MH closure rate. None of the persistent MHs closed in the non-intravitreal gas injection group (0/9 eyes).Conclusion: Early intravitreal injection of C3F8 can be a cost-effective first-line treatment for early persistent MHs after primary surgery, especially in eyes with favorable OCT features. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) using post-neoadjuvant chemoradiotherapy (nCRT) F-18-fluorodeoxyglucose (18FDG).Methods: This is a retrospective study of patients with locally advanced ESCC receiving nCRT and then esophagectomy between January 2011 and December 2018 in the Tri-Service General Hospital, Taipei, Taiwan. A total of 50 patients were enrolled in the study. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model. Univariate and multivariate analysis were used to determine the independent prognostic factors.Results: Fifty patients were enrolled in the study, and 18 had pathological complete response. Post-nCRT SUVmax ≥ 3 is a poor prognostic factor associated with overall survival (HR: 3.665, P = 0.013) and disease-free survival (HR: 3.417, P = 0.011). Poor prognosis was found in the non-pCR plus post-nCRT SUVmax ≥ 3 group compared with pCR plus post-nCRT SUVmax < 3 group.Conclusions: SUVmax ≥ 3 is a poor prognostic factor in esophageal squamous cell carcinoma after trimodality treatment, even in patients having pathological complete response. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to verify the predictors of the diagnostic accuracy of rapid on-site evaluation (ROSE) in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) among patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed consecutive patients with NSCLC who underwent EBUS-TBNA for staging or diagnosis at our hospital from June 2016 to June 2018. The patients were divided into two groups—those with a correct diagnosis and an incorrect diagnosis after ROSE. Kaplan–Meier plots and log-rank tests were used to estimate outcomes. Results: A total of 84 patients underwent EBUS-TBNA for staging and diagnosis. Sixty patients with demonstrated malignant mediastinal lymph nodes were enrolled. In the univariate analysis, lymph nodes < 1.5 cm (HR = 3.667, p = 0.031) and a SUVmax > 5 (HR = 41, p = 0.001) were statistically significant for diagnostic accuracy of ROSE. In the multivariate Cox regression analysis, only a SUVmax > 5 (HR = 20.258, p = 0.016) was statistically significant. Conclusions: A SUVmax > 5 is an independent predictor of higher diagnostic accuracy of ROSE in EBUS-TBNA in patients with NSCLC with malignant mediastinal lymph nodes. Therefore, ROSE in patients with a SUVmax < 5 might not be reliable and requires further prudent assessment (more shots or repeated biopsies at mediastinal LNs) in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Corneal biomechanics, reflecting structural vulnerabilities of the eyeball, may participate in the pathogenesis of unilateral normal-tension glaucoma. This study investigated the pathophysiology of unilateral normal-tension glaucoma using Corvis ST (OCULUS Optikgeräte GmbH) and other ocular characteristics. Methods: Eighty-three patients with normal-tension glaucoma with unilateral visual field loss and structurally unaffected fellow eyes and 111 healthy controls were included in this prospective study. Dynamic corneal response parameters, intraocular pressure measured by rebound tonometry, central corneal thickness, and axial length were assessed on the same day. Measurements were compared between affected eyes, unaffected fellow eyes, and control eyes. Risk factors for normal-tension glaucoma and unilateral involvement were the main outcome measures. Results: A shorter first applanation time (adjusted odds ratio, 0.061; 95% confidence interval, 0.018–0.215) and a larger peak distance (adjusted odds ratio, 4.935; 95% confidence interval, 1.547–15.739) were significant risk factors for normal-tension glaucoma and were associated with greater glaucoma severity (both P < 0.001). Axial length (adjusted odds ratio, 29.015; 95% confidence interval, 4.452–189.083) was the predominant risk factor for unilateral involvement in patients with normal-tension glaucoma. Conclusion: The eyes with normal-tension glaucoma were more compliant than healthy eyes. Axial elongation-associated optic nerve strain may play an important role in unilateral normal-tension glaucoma with similar corneal and scleral biomechanics in both eyes. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of levonorgestrel 52 mg intrauterine system for intermenstrual bleeding in patients with previous cesarean delivery scar defects (PCDSs). Methods: The medical records of 28 consecutive patients with previous cesarean delivery scar defect and intermenstrual bleeding who had undergone conservative treatment with levonorgestrel 52 mg intrauterine system were reviewed. The efficacy of treatment and frequency of adverse events were measured retrospectively. Results: After 1 year of treatment, 22 patients (78.6%) reported an improvement in symptoms. The mean duration of menstruation were 18 and 5 days before and after treatment, respectively. No uterine perforations or pelvic inflammatory diseases occurred during or after the insertion procedures. Eighteen (64.3%) patients did not experience any adverse events, and the patients with adverse events reported that they could be managed by adjusting their medications or observation. Conclusion: Levonorgestrel intrauterine system may have a role in the safe and effective management of intermenstrual spotting in patients with PCDSs. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of PET in predicting the prognosis of resected stage IA non-small cell lung cancer (NSCLC) and planning individualized therapeutic strategies. Methods: We retrospectively reviewed the data of patients who underwent surgical resection for lung cancer between January 2004 and December 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. Results: We evaluated 998 cases; 637 patients with pathological stage I disease were categorized as follows: stage IA1 (251 cases), stage IA2 (250 cases), and stage IA3 (136 cases). The mean follow-up period was 109 months. Significant differences were observed in sex, tumor differentiation, epidermal growth factor receptor mutation, smoking habits, lymphovascular space invasion, tumor size, maximum standard uptake value (SUVmax), and carcinoembryonic antigen level among the groups. Multivariable Cox regression revealed that ground-glass opacity ratio (hazard ratio (HR) = 0.001) and tumor SUVmax independently predicted the postoperative risk of relapse for stage IA3 NSCLC. The HR for SUVmax > 4 was 8.986 (p < 0.001). The 5-year overall survival (OS) rates were 87.2%, 92.9%, and 82.7%, and the 5-year disease-free survival (DFS) rates were 93.2%, 84.2%, and 70.51% for stage IA1, IA2, and IA3 NSCLC, respectively (both p < 0.001). OS and DFS rates were poor in stage IA3 NSCLC patients with an SUVmax uptake > 4 (OS, 71.0% and 92.2%; DFS, 50.2% and 87.3%, for SUVmax > 4 and ≤ 4, respectively; both p = 0.001). Conclusions: SUVmax was a prognostic factor for resected stage IA NSCLC. Postoperative treatment may be considered for IA3 NSCLC with SUVmax > 4. Key Points: • PET helps surgeons to assess patients with early-stage lung cancer. • This retrospective study revealed that PET plays an influential role in predicting the prognosis of resected lung cancer. • Better prognostication aids better planning of therapeutic strategies with diversification. [ABSTRACT FROM AUTHOR]

Aim: The predictive accuracy of frozen sections for borderline ovarian tumors (BOTs) is suboptimal. The aim of this study was to determine the diagnostic accuracy of BOTs and factors associated with an upgrade to a permanent pathological diagnosis of invasive carcinoma in patients diagnosed with BOTs by frozen section. Methods: We conducted a retrospective study between 2011 and 2018 at Kaohsiung Chang Gung Memorial Hospital (KCGMH). Two hundred and twenty‐five records of eligible patients with a diagnosis of BOT by frozen section or permanent diagnosis were reviewed. Positive predictive value and the diagnostic accuracy of frozen sections were calculated. Univariate and multivariate analyses were used to determine the clinicopathological factors associated with an upgrade of the diagnosis from a borderline tumor to malignancy. Results: The agreement between frozen section and permanent pathological diagnoses was 63.1%, and the positive predictive value was 72.1%. The multivariate analysis revealed that CA‐125 level > 136 U/mL (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 1.3–6.9; p = 0.012), and tumor histologic type (clear cell/endometrioid vs. mucinous; OR:32.8, 95% CI = 6.9–154.8, p < 0.001; clear cell/endometrioid vs. serous: OR 48.1, 95% CI = 8.8–261.8, p < 0.001) were independent risk factors for an upgrade of the permanent diagnosis from a BOT to ovarian carcinoma. Conclusion: An elevated CA‐125 level (over 136 U/mL) and tumor histologic type (clear cell and endometrioid subtypes) were associated with an upgrade in the diagnosis of ovarian tumor from a BOT on frozen section to a permanent diagnosis of malignancy. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC). Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O'Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival. Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (< 23 days), intermediate (23– 43 days) and late (> 43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10– 0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group. Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3– 6 weeks post-operatively. Initiating chemotherapy early (< 23 days) did not appear to benefit PFS. [ABSTRACT FROM AUTHOR]

Spectral-domain optical coherence tomography (SD-OCT) has been used to observe the morphology of the palisades of Vogt (POV) with satisfactory resolutions. In this study, we used SD-OCT to examine the microstructure of the POV in ocular surface disorders with limbal involvement. We detect subclinical limbal pathologies based on five parameters, including (1) decreased epithelial thickness, (2) loss of the sharp stromal tip, (3) loss of the smooth epithelial-stromal interface, (4) dilated stromal vessels, and (5) decreased POV density. Eighteen eyes of 10 patients with advancing wavelike epitheliopathy (AWE) and 15 eyes of 9 patients with phlyctenular keratitis/ocular rosacea were recruited. SD-OCT could detect abnormal changes in the POV in 100% of the lesion sites. In presumed-healthy areas of the diseased eyes diagnosed by slit-lamp biomicroscopy, SD-OCT detected abnormal changes in the POV in 100% of the eyes in both groups. In patients with unilateral disease, abnormal changes in the POV were detected by SD-OCT in 50% and 100% of presumed-healthy eyes diagnosed by slit-lamp biomicroscopy in the AWE group and phlyctenular keratitis/ocular rosacea group, respectively. SD-OCT is powerful in detecting POV changes in ocular surface disorders and can provide useful information that cannot be provided by slit-lamp biomicroscopy. [ABSTRACT FROM AUTHOR]

Bone healing in tooth extraction sockets occurs in a complex environment containing saliva and many microorganisms and is affected by many factors. Endoplasmic reticulum (ER) stress affects bone metabolism, but the role of ER stress in bone healing after tooth extraction remains unclear. We utilized a rat tooth extraction model, in which we promoted wound healing by using salubrinal to regulate the ER stress response. Western blot analysis showed increased expression of p‐eIF2α/eIF2α, Runx2 and alkaline phosphatase (ALP) in bone tissue, and histological assays showed irregularly arranged and new bone with more collagen fibres 14 days after tooth extraction and after modulating the degree of ER stress. Micro‐CT showed that modulating ER stress to an appropriate degree increases bone filling in regards to the density in the bottom and the surrounding bone wall of the tooth extraction wounds. Transmission electron microscopy showed rough ER expansion and newly formed collagen fibrils in osteoblasts after modulating ER stress to an appropriate degree. We also used different concentrations of salubrinal to evaluate the resistance to tunicamycin‐induced ER stress in an osteogenic induction environment. Salubrinal restored the tunicamycin‐induced decrease in the viability of primary calvarial osteoblasts and increased the expression of Runx2 and ALP, and decreased p‐eIF2α/eIF2α in a dose‐dependent manner. Taken together, the results demonstrate that ER stress occurred after tooth extraction, and regulating the degree of ER stress can promote bone healing in tooth extraction sockets, providing clinical evidence for bone healing. [ABSTRACT FROM AUTHOR]

Background and Objective: This study aimed to investigate the relationship between bleb formation, primary spontaneous pneumothorax (PSP) and pectus excavatum (PE). Methods: From July 2005 to December 2016, the records of 514 patients with PE who underwent the Nuss procedure were obtained from a prospectively collected database and reviewed. Clinical features, images and treatments were analyzed retrospectively. Results: The incidence rate of bleb formation was 26.5% in PE patients. The bleb group had a greater body height (174.4 cm vs. 170.4 cm, p < 0.001), a higher Haller index (HI; 4.2 vs. 3.43, p < 0.001) and a higher risk of developing PSP than the non-bleb group (risk ratio 9.8, p = 0.002). HI values larger than 3.615 had good discriminatory power for predicting bleb formation in patients with PE. With each increase in the HI, PE patients had a 2.2-fold greater odds ratio of bleb formation (odds ratio 2.221, CI 1.481–3.330, p < 0.001). Conclusion: We discovered that a high percentage of PE patients have bleb formation and a higher risk of PSP, especially those with an HI >3.615. High-resolution computed tomography of the chest may be useful for evaluating both the HI and the presence of blebs in the lungs before performing a corrective surgical procedure. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to verify the predictors of recurrence and survival in lung adenocarcinoma patients with experiences of breast cancer therapies. Methods: We retrospectively reviewed consecutive patients who were treated at our hospital for lung adenocarcinoma from 2004/01 to 2014/03. The patients were divided into groups of those with lung adenocarcinoma alone and those with lung and breast cancer. Kaplan–Meier plots and log-rank tests were used to estimate outcomes. Results: 54 patients with lung adenocarcinoma and breast cancer were compared with 457 patients with single primary lung adenocarcinomas. After propensity score matching with control of age, operation type, smoking status and pathologic stage, tumor differentiation, recurrence rate and tumor size were significantly different between two groups. The significant predictors for recurrence included undergone chemotherapy (HR = 25, p < 0.001), moderate/poor differentiation (HR = 8.125, p = 0.012), tumor size ≧ 2 cm (HR = 15, p < 0.001), LVSI (HR = 13.67, p = 0.031) and GGO ratio < 50% (HR = 14.667, p = 0.014). The significant prognostic factors for survival were accepted chemotherapy (HR = 6.182, p = 0.021), LVSI (HR = 22, p = 0.012) and GGO ratio < 50% (HR = 9.143, p = 0.045). Kaplan–Meier analysis revealed that patients with lung adenocarcinoma and breast cancer had a better 5-year disease-free survival (p = 0.009), while the Her2-negative patients obtained a better overall survival (p = 0.038). Conclusions: In patients with breast cancer and lung adenocarcinoma, independent risk factors of recurrence were undergone chemotherapy, moderate/poor differentiation, tumor size ≧ 2 cm, LVSI and GGO ratio < 50%. Only undergone chemotherapy, LVSI and GGO ratio < 50% were significant poor predictors for survival. However, patients with metachronous lung adenocarcinoma and breast cancer had better disease-free survival and less tumor recurrence than patients with lung adenocarcinoma alone. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of levonorgestrel intrauterine system (LNG‐IUS) treatment in patients with previous cesarean delivery scar defect (PCDS)‐related intermenstrual bleeding. Methods: A total of six premenopausal patients who experienced PCDS‐related intermenstrual bleeding were enrolled for conservative therapy with LNG‐IUS (levonorgestrel 20 μg/24 h) insertion. The durations of menstruation before and after LNG‐IUS insertion at 1, 6 and 12 months were recorded. A total of three missed menstrual cycles was defined as amenorrhea. Any side effects and the device expulsion rate were also recorded. Patient follow‐up was at an outpatient clinic. Any missing data were obtained by telephone. Results: At the start of the study the median duration of intermenstrual bleeding was 6.5 days (range 3–22 days). After 6 months treatment, two of the six patients had developed amenorrhea and two patients experienced cessation of vaginal spotting. One patient reported expulsion of the device. All patients except the one with device expulsion responded to the conservative treatment after 1 year. Conclusion: The findings of the current study support LNG‐IUS being effective for the treatment of PCDS‐related intermenstrual bleeding. The authors recommend LNG‐IUS as a treatment option for PCDS‐related intermenstrual bleeding. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the impact of epidermal growth factor receptor (EGFR) mutation status and tyrosine kinase inhibitors (TKIs) on the survival of brain metastases (BM) in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: We selected the patients who had developed metastatic NSCLC; analyzed the differences between brain metastases and other sites of metastases, including patient characteristics, EGFR status, and survival; and selected the patients who had BM for further investigation. We also compared the treatment effects of first-generation TKIs with those of second-/third-generation TKIs. Results: A total of 785 cases of stage I-IIIa NSCLC were reviewed. Thirty-six (4.6%) patients were identified as having BM. Among them, 14 patients had a mutated EGFR status. No association between EGFR mutation and the incidence of BM was observed (p = 0.199). Patients with mutated EGFRs had significantly longer overall survival and post-recurrence survival than patients with wild-type EGFR mutation (p = 0.001 for both). However, there was no survival difference between patients with exon 19 and exon 21 mutations (p = 0.426). Furthermore, patients who received the second- and/or third-generation EGFR-TKIs had better survival than patients who only received first-generation EGFR-TKIs (p = 0.031). A multivariate analysis indicated that the next-generation TKIs (HR, 0.007; 95% CI, 0.000 to 0.556; p = 0.026) and a longer interval before BM development (HR, 0.848; 95% CI, 0.733 to 0.980; p = 0.025) were significant factors in longer survival. Conclusions: EGFR-TKIs were effective in treating NSCLC patients with BM after curative pulmonary surgery, especially in those patients harboring EGFR mutations. Furthermore, the second-/third-generation EGFR-TKIs showed more promising results than the first-generation EGFR-TKIs in treating those particular patients, though larger studies needed to further prove the results. [ABSTRACT FROM AUTHOR]

Objectives: The beneficial application of three-dimensional (3D) printing for surgical stabilization of rib fractures (SSRF) has never been proposed in the literature before. The aim of this study was to verify patients’ surgical outcomes when utilizing preoperative three-dimensional printing for SSRF. Methods: We retrospectively reviewed the records of all consecutive patients who were treated at our hospital for SSRF from July 2015 to December 2017. The patients were divided into two groups according to whether or not 3D printing was utilized. Results: Forty-eight patients who underwent SSRF at our hospital were enrolled. Of them, three patients underwent bilateral surgeries. The patients with application of preoperative 3D printing for SSRF had statistically significant associations with shorter operation time per fixed plate (p < 0.001), and a smaller incision length (p < 0.001). Conclusions: We present an useful technique involving 3D printing for promoting SSRF significantly with shorter operation time and an appropriate incision length. [ABSTRACT FROM AUTHOR]

Evidences suggest that ERp57 and PGK-1 signaling lead to cancer cell proliferation and migration. We hypothesized that ERp57 and PGK-1 down-regulation may inactivate matrix metalloproteinase (MMP)-2, -9 expressions and inhibit hepatocellular carcinoma (HCC) migration. Antrodia cinnamomea is widely prescribed as an adjuvant to treat HCC in Taiwan. We aimed to investigate if ethanol extract of fruiting bodies of Antrodia cinnamomea (EEAC) and its active ingredients (i.e., zhankuic acid A, cordycepin, and adenosine) can modulate HCC cancer cells migration through ERp57 and PGK-1 and other molecular pathways such as PI3K/Akt and MAPK. ERp57 and PGK-1 siRNA were transfected into HCC to determine effects on MMP-2/-9 expressions and cell migration. We then examined the inhibitory effects of EEAC and its active ingredients on HCC migration and its related mechanisms including ERp57, PGK-1, PI3K/Akt, and MAPK signaling pathways. Down-regulation of ERp57 and PGK-1 by siRNA decreased MMP-2, -9 expressions and Transwell cell migration in HCC. Nontoxic EEAC markedly inhibited migration of HCC, and significantly inhibited activities and protein expressions of MMP-2 and -9, while the expression of the endogenous inhibitors (TIMP-1 and TIMP-2) of these proteins increased. Nontoxic EEAC and its active ingredients decreased ERp57, GLUD-1, GST-pi, and PGK-1 protein expressions. Finally, nontoxic EEAC inhibited the phosphorylated FAK, PI3K/Akt, and MAPK signaling. Our findings first indicate that EEAC and its ingredients effectively suppress HCC migration. Additionally, the molecular mechanisms appear to be mediated, in part, through the down-regulation of ERp57, PGK-1, MAPK, and PI3K/Akt. [ABSTRACT FROM AUTHOR]

Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC) can affect the efflux function of P-glycoprotein (P-gp) and the effect of ABCB1 genetic variants on the interaction between EEAC and P-gp. To investigate the mechanism of this interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established and the expression of P-gp was confirmed by Western blot. The results of the rhodamine 123 efflux assay demonstrated that EEAC efficiently inhibited wild-type P-gp function at an IC50 concentration of 1.51±0.08 µg/mL through non-competitive inhibition. The IC50 concentrations for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp were 5.56±0.49 µg/mL and 3.33±0.67 µg/mL, respectively. In addition, the inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant-type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase stimulator and was capable of reducing verapamil-induced ATPase levels. These results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may be required in subjects carrying variant-types P-gp. Further studies are required to translate this basic knowledge into clinical applications. [ABSTRACT FROM AUTHOR]

Glycogen synthase kinase 3β (GSK3β) is a ubiquitous serine/threonine kinase that plays a pivotal role in many biological processes. GSK3β catalyzes the transfer of γ-phosphate of ATP to the unique substrate Ser/Thr residues with the assistance of two natural activating cofactors Mg2+. Interestingly, the biological observation reveals that a non-native Ca2+ ion can inhibit the GSK3β catalytic activity. Here, the inhibitory mechanism of GSK3β by the displacement of native Mg2+ at site 1 by Ca2+ was investigated by means of 80 ns comparative molecular dynamics (MD) simulations of the GSK3β···Mg2+-2/ATP/ Mg2+-1 and GSK3β···Mg2+-2/ATP/Ca2+-1 systems. MD simulation results revealed that using the AMBER point charge model force field for Mg2+ was more appropriate in the reproduction of the active site architectural characteristics of GSK3β than using the magnesium-cationic dummy atom model force field. Compared with the native Mg2+ bound system, the misalignment of the critical triphosphate moiety of ATP, the erroneous coordination environments around the Mg2+ ion at site 2, and the rupture of the key hydrogen bond between the invariant Lys85 and the ATP Oβ2 atom in the Ca2+ substituted system were observed in the MD simulation due to the Ca2+ ion in active site in order to achieve its preferred sevenfold coordination geometry, which adequately abolish the enzymatic activity. The obtained results are valuable in understanding the possible mechanism by why Ca2+ inhibits the GSK3β activity and also provide insights into the mechanism of Ca2+ inhibition in other structurally related protein kinases. Proteins 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Trilinolein has been identified as one of the active constituents isolated from Panax notoginseng used widely in traditional Chinese medicine. Protective actions of Panax notoginseng against cerebral ischemia, beneficial effects on the cardiovascular system, and hemostatic, antioxidant, hypolipidemic, hepatoprotective, renoprotective and estrogen-like activities have been illustrated. In the present study, the effects of trilinolein on the growth of non-small cell lung carcinoma A549 were investigated. It was found that the exposure of A549 cells to trilinolein resulted in the growth inhibition and the induction of apoptosis in a dose- and time- dependent manner. Trilinolein treatment induced the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 expression, which was associated with the proteolytic activation of caspases and the concomitant degradation of poly(ADP-ribose) polymerase (PARP) protein. Intracellular reactive oxygen species seem to play a role in the trilinolein-induced apoptosis, since ROS were produced early in the trilinolein treatment. Moreover, the activity of PI3K/Akt was downregulated in trilinolein-treated cells. Our results demonstrated that the most important regulators of trilinolein-induced apoptosis are Bcl-2 family and caspase-3, which are associated with cytochrome c release and dephosphorylation on the Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Trilinolein has been identified as one of the active constituents isolated from Panax notoginseng used widely in traditional Chinese medicine. Protective actions of Panax notoginseng against cerebral ischemia, beneficial effects on the cardiovascular system, and hemostatic, antioxidant, hypolipidemic, hepatoprotective, renoprotective and estrogen-like activities have been illustrated. In the present study, the effects of trilinolein on the growth of non-small cell lung carcinoma A549 were investigated. It was found that the exposure of A549 cells to trilinolein resulted in the growth inhibition and the induction of apoptosis in a dose- and time- dependent manner. Trilinolein treatment induced the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 expression, which was associated with the proteolytic activation of caspases and the concomitant degradation of poly(ADP-ribose) polymerase (PARP) protein. Intracellular reactive oxygen species seem to play a role in the trilinolein-induced apoptosis, since ROS were produced early in the trilinolein treatment. Moreover, the activity of PI3K/Akt was downregulated in trilinolein-treated cells. Our results demonstrated that the most important regulators of trilinolein-induced apoptosis are Bcl-2 family and caspase-3, which are associated with cytochrome c release and dephosphorylation on the Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Previous studies have addressed the impact of comorbidity on short-term mortality in patients with COPD. However, the prevalence of cardiovascular disease (CVD) and the association of statins prescription with mortality for aged COPD patients remains unclear. We enrolled 296 aged, hospitalized patients who were monitored in the pay-for-performance (P-4-P) program of COPD. Factors associated with long-term mortality were identified by Cox regression analysis. The median age of the study cohort was 80 years old, and the prevalence of coronary artery disease (CAD) and statins prescriptions were 16.6% and 31.4%, respectively. The mortality rate of the median 3-year follow-up was 51.4%. Through multivariate analysis, body mass index (BMI), statin prescription, and events of respiratory failure were associated with long-term mortality. A Cox analysis showed that statins prescription was associated with lower mortality (hazard ratio (HR): 0.5, 95% Confident interval, 95% CI: 0.34–0.73, p = 0.0004) and subgroup analysis showed that rosuvastatin prescription had protective effect on long-term mortality (HR: 0.44; 95% CI: 0.20–0.97; p < 0.05). Statin prescriptions might be associated with better long-term survival in aged COPD patients, especially those who experienced an acute exacerbation of COPD (AECOPD) who require hospitalization. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00330-021-08158-4 [ABSTRACT FROM AUTHOR]

Amsacrine, an anticancer drug first synthesised in 1970 by Professor Cain and colleagues, showed excellent preclinical activity and underwent clinical trial in 1978 under the auspices of the US National Cancer Institute, showing activity against acute lymphoblastic leukaemia. In 1984, the enzyme DNA topoisomerase II was identified as a molecular target for amsacrine, acting to poison this enzyme and to induce DNA double-strand breaks. One of the main challenges in the 1980s was to determine whether amsacrine analogues could be developed with activity against solid tumours. A multidisciplinary team was assembled in Auckland, and Professor Denny played a leading role in this approach. Among a large number of drugs developed in the programme, N-[2-(dimethylamino)-ethyl]-acridine-4-carboxamide (DACA), first synthesised by Professor Denny, showed excellent activity against a mouse lung adenocarcinoma. It underwent clinical trial, but dose escalation was prevented by ion channel toxicity. Subsequent work led to the DACA derivative SN 28049, which had increased potency and reduced ion channel toxicity. Mode of action studies suggested that both amsacrine and DACA target the enzyme DNA topoisomerase II but with a different balance of cellular consequences. As primarily a topoisomerase II poison, amsacrine acts to turn the enzyme into a DNA-damaging agent. As primarily topoisomerase II catalytic inhibitors, DACA and SN 28049 act to inhibit the segregation of daughter chromatids during anaphase. The balance between these two actions, one cell cycle phase specific and the other nonspecific, together with pharmacokinetic, cytokinetic and immunogenic considerations, provides links between the actions of acridine derivatives and anthracyclines such as doxorubicin. They also provide insights into the action of cytotoxic DNA-binding drugs. [ABSTRACT FROM AUTHOR]

Demethoxycurcumin (DMC), through a self-assembled amphiphilic carbomethyl-hexanoyl chitosan (CHC) nanomatrix has been successfully developed and used as a therapeutic approach to inhibit cisplatin-induced drug resistance by suppressing excision repair cross-complementary 1 (ERCC1) in non-small cell lung carcinoma cells (NSCLC). Previously, DMC significantly inhibited on-target cisplatin resistance protein, ERCC1, via PI3K-Akt-snail pathways in NSCLC. However, low water solubility and bioavailability of DMC causes systemic elimination and prevents its clinical application. To increase its bioavailability and targeting capacity toward cancer cells, a DMC-polyvinylpyrrolidone core phase was prepared, followed by encapsulating in a CHC shell to form a DMC-loaded core-shell hydrogel nanoparticles (DMC-CHC NPs). We aimed to understand whether DMC-CHC NPs efficiently potentiate cisplatin-induced apoptosis through downregulation of ERCC1 in NSCLC. DMC-CHC NPs displayed good cellular uptake efficiency. Dissolved in water, DMC-CHC NPs showed comparable cytotoxic potency with free DMC (dissolved in DMSO). A sulforhodamine B (SRB) assay indicated that DMC-CHC NPs significantly increased cisplatin-induced cytotoxicity by highly efficient intracellular delivery of the encapsulated DMC. A combination of DMC-CHC NPs and cisplatin significantly inhibited on-target cisplatin resistance protein, ERCC1, via the PI3K-Akt pathway. Also, this combination treatment markedly increased the post-target cisplatin resistance pathway including bax, and cytochrome c expressions. Thymidine phosphorylase (TP), a main role of the pyrimidine salvage pathway, was also highly inhibited by the combination treatment. The results suggested that enhancement of the cytotoxicity to cisplatin via administration of DMC-CHC NPs was mediated by down-regulation of the expression of TP, and ERCC1, regulated via the PI3K-Akt pathway. [ABSTRACT FROM AUTHOR]

Background: This study hopes to establish the timeframe for a safe return to driving under different speed conditions for patients after minimally invasive total knee arthroplasty and further explores how well various kinds of functional tests on knee performance can predict the patients' braking ability.Methods: 14 patients with right knee osteoarthritis were included in the present study and instructed to perform three simulated driving tasks at preoperative, 2 weeks postoperative and 4 weeks postoperative.Results: The results showed that the total braking time at 4 week postoperative has attained the preoperative level at the driving speed 50 and 70 km/hr but not at the driving speed 90 km/hr. It had significantly improving in knee reaction time and maximum isometric force at 4 weeks postoperative. Besides, there was a moderate to high correlation between the scores of the step counts and the total braking time.Conclusions: Summary, it is recommended that driving may be resumed 4 weeks after a right knee replacement but had to drive at low or moderate speed and the best predictor of safety driving is step counts. [ABSTRACT FROM AUTHOR]