Comparison of 3D Printing Rapid Prototyping Technology with Traditional Radiographs in Evaluating Acetabular Defects in Revision Hip Arthroplasty: A Prospective and Consecutive Study.

OBJECTIVE: To compare rapid prototyping technology (RP tech) in revision total hip arthroplasty (RTHA) with traditional examination methods and to see how they are different in evaluating acetabular anatomy and designing surgical procedure. METHODS: From February 2014 to March 2018, 43 RTHA patients with complex acetabulum defects were enrolled in this prospective study regardless of age or gender. Incomplete and unclear data were excluded. Three types of radiographic examination were performed on each patient before the revision surgery. Four groups of evaluations were designed: (i) X-ray; (ii) computed tomography (CT-scan); (iii) RP tech; and (iv) CT-aided RP tech. Discrepancies between preoperative radiographic analysis and intra-operative findings were separately compared by a team of surgeons. Premade surgical plans based on each evaluation method were compared with the final surgical procedure. The compliance of anatomic evaluation and surgical plan-design based on 3D RP tech and traditional radiographs were ranked manually by a of team surgeons into: (i) complete accordance; (ii) general accordance; and (iii) undetermined structure/procedure. The difference in ranks between RP tech and traditional radiographic methods were analyzed with a nonparametric Kruskal-Wallis test. P < 0.05 was considered significant. Multiple adjustments were taken for the statistical tests level according to the Bonferroni method. RESULTS: For anatomic analysis, the accordance in four groups of evaluating methods differed from each other (P < 0.05) except for the comparison of RP tech and CT-aided RP tech. RP tech displayed better anatomic evaluating accuracy than traditional methods (X-ray and CT) with the "complete accordance" rates of these groups being 88.37%, 4.65% and 27.91%, respectively. But CT-aided RP tech did not improve accuracy significantly compared with using RP tech individually, although the value seems high in the CT-aided RP group with the "complete accordance" rate of 95.35%. For surgery design, RP tech significantly showed better applicable surgical design compared with X-ray and CT (P < 0.05), and the "complete accordance" rates were 88.37%, 6.98% and 23.26%, but no significant difference was observed between RP tech and CT-aided RP tech, and the "complete accordance" rate of CT-aided RP tech group was 97.67%. RP tech showed remarkable improvement in bone defect assessment and surgical plan design. CONCLUSION: Using RP technology improved both sensibility and accuracy in acetabular defect evaluation with better locating and evaluating efficiency compared with X-ray and CT-scans. It also improved surgical schedule designing in complex acetabular defecting revision surgery. In particularly complex cases, CT aided RP tech may increase the accuracy of RP tech.

The association between the incidence risk of pneumonitis and PD-1/PD-L1 inhibitors in advanced NSCLC: A meta-analysis of randomized controlled trials.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown a significant efficacy for patients with non-small cell lung cancer (NSCLC). However, checkpoint inhibitor pneumonitis (CIP) is a rare but severe and life-threatening adverse event. Hence, we performed a systematic review and meta-analysis to evaluate the incidence and risk of CIP in patients with NSCLC. METHODS: Pubmed, Embase, Cochrane Library and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched up to December 15, 2020. Studies regarding all-grade and high-grade pneumonitis were included. The data was analyzed using meta-packages of R 3.6.0. RESULTS: A total of sixteen randomized controlled trials including 9500 patients were identified for further evaluation. The overall incidence of all-grade and high-grade CIP was 4.17% and 2.02%, respectively. Compared with conventional chemotherapy, patients treated with ICIs significantly increased risk of all-grade (RR: 4.11, p < 0.0001) and high-grade (RR: 3.16, p < 0.0001) pneumonitis. Subgroup analysis showed the ICIs combined with chemotherapy was associated with a higher incidence of CIP than monotherapy alone (6.03% vs 3.32%, p = 0.01). And the rate of death owing to CIP was higher than chemotherapy-mediated pneumonitis. CONCLUSION: There were a higher incidence and risk of pneumonitis with the application of ICIs when compared with chemotherapy. Higher mortality rate of pneumonitis was more frequent in ICIs group. Thus, early detection, proper administration and optimal management are needed for physicians prevent potentially CIP deterioration.

CT-guided percutaneous implantation of 125I particles in treatment of early lung cancer.

BACKGROUND: To analyze the efficacy of computed tomography (CT)-guided implantation of 125I radioactive particles in treatment of early lung cancer. METHODS: Six patients were analyzed, including 4 squamous cell carcinoma, 1 adenocarcinoma, and 1 small cell lung cancer. TPS software was used to calculate the therapeutic dose amount of particles implanted, and the spacing and distribution of seeds in the target area and adjacent tissues. Under the guidance of CT, 20-55 particles were implanted at each site, with the total number of radioactive particles being 226, the particle spacing being 0.5-1.0 cm, and the implantation being performed in accordance with the principle of uniform implantation. The patients were each followed up with repeated pulmonary CT scans at 1, 3, 6, 12, 18, 24, 30 and 36 months after the procedure. In accordance with the response evaluation criteria in solid tumors (RECIST), the following definitions for responses were used: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD). RESULTS: There were 2 CRs and 4 PRs one month after procedure; six patients were followed up 3 months after procedure, including 2 CRs and 4 PRs; one patient was lost in follow-up, and 5 patients were followed up 6 months after procedure, including 3 CRs and 2 PRs; five patients were followed up 12 months after procedure, including 3 CRs, 1 PR and 1 PD. The single PD patient was again given CT-guided implantation of 125I radioactive particles for the treatment of recurrent lesions. The pulmonary CT was repeated 6 months after procedure, and the response was evaluated as SD. Four patients were followed up 18 months after procedure, including 3 CRs and 1 PR; one patient was lost in follow-up and 3 patients were followed up 24 months after the procedure with the response being evaluated as CR for all of them; one patient was followed up 36 months after procedure, and the response was evaluated as PD. During the follow-up, no serious complications occurred in any of the patients. CONCLUSIONS: The preliminary clinical observation showed that 125I radioactive particle implantation was a safe, reliable and effective therapeutic method for early lung cancer.

Prediction of Rotator Cuff Injury Associated with Acromial Morphology: A Three-Dimensional Measurement Study.

OBJECTIVE: To analyze the relationship between the acromial morphology and the related rotator cuff injury using a three-dimensional (3D) measurement technology. METHODS: For the present study, 226 patients (113 men and 113 women) who underwent shoulder Coarthroscopy from June 2015 to December 2019 at the Department of Orthopedics at our hospital were selected retrospectively. A total of 113 shoulder joints of age-matched healthy people were selected as the control group. A 3D model coordinate system of the shoulder was established based on CT scan images. Patients were grouped according to the condition of the rotator cuff injury during surgery. The patients whose rotator cuff tear site corresponded to the 3D osseous proliferative structure of the acromion were classified into the impingement injury group (II group). The other patients were classified into the non-impingement injury group (NII group). The acromiohumeral interval (AHI), the acromial anterior protrusion (AAP), the acromial inferior protrusion (AIP), the acromioclavicular angle (AC angle), the distance from the most medial edge of the acromial anterolateral protrusion (AALP) to the most lateral point of acromion (MLPA) (a), the distance from the most posteromedial edge of the AALP to the MLPA (b), the anteroposterior diameters of the AALP (c), and the proportion of anteroposterior diameters of AALP to the anteroposterior diameters of acromion, (c/c + d) × 100(%), were measured using the 3D shoulder model. RESULTS: The results of the intraobserver (<5%) and interobserver variability (>87%) analysis found the parameters to have high intraobserver and interobserver concordance. There were no significant differences in age among the control group, the NII group, and the II group (P = 0.8416). There were significant differences in AAP among the three groups (P = 0.0374). The results were the same for men and women, respectively. The AAP in the control group and the NII group did not show a difference, while the AAP in the II group was increased by 26.9% (P = 0.015) and 25% (P = 0.023), respectively, compared with the NII group and the control group. AHI, AIP, and AC angles did not show significant differences among the three groups (P > 0.05). The (a) and (b) of the II group were significantly larger than those of the NII group; P-values were 0.0119 and 0.0003, respectively. The (a) and (b) in patients with rotator cuff injuries were larger than in the normal population (P < 0.05). The above results were the same for men and women. This suggested that the larger width of the AALP might cause the related rotator cuff injury. The (c/c + d) in the II group was significantly larger than those in the control and the NII groups, with P-values of 0.0005 and 0.0021, respectively. The risk of rotator cuff injury due to subacromial impingement was increased when the maximum width of the medial-lateral edge of the AALP exceeded 16.8 mm (17.4 mm in men, 15.1 mm in women), the maximum width of the posterior edge of the AALP exceeded 12.9 mm (13.8 mm in men,12.7 mm in women), or the anteroposterior diameters of the AALP exceeded the anteroposterior diameters of the acromion by 33.5%. CONCLUSION: We could predict the occurrence and development of the related rotator cuff injury in symptomatic patients with specific 3D changes in their acromion and intervene in the acromion of such patients as early as possible to prevent possible rotator cuff injuries in the future.

Sodium Tanshinone IIA Sulfonate Attenuates Tumor Oxidative Stress and Promotes Apoptosis in an Intermittent Hypoxia Mouse Model.

OBJECTIVE: Intermittent hypoxia, a significant feature of obstructive sleep apnea, has pro-tumorigenic effects. Here, we investigated the effect of sodium tanshinone IIA sulfonate on oxidative stress and apoptosis in a mouse model of Lewis lung carcinoma with intermittent hypoxia. METHODS: Mice were randomly assigned to normoxia (control), normoxia plus sodium tanshinone IIA sulfonate (control + sodium tanshinone IIA sulfonate), intermittent hypoxia, and intermittent hypoxia + sodium tanshinone IIA sulfonate groups. Intermittent hypoxia administration lasted 5 weeks in the intermittent hypoxia groups. Lewis lung carcinoma cells were injected into the right flank of each mouse after 1 week of intermittent hypoxia exposure. Sodium tanshinone IIA sulfonate was injected intraperitoneally in the control + sodium tanshinone IIA sulfonate and intermittent hypoxia + sodium tanshinone IIA sulfonate groups. Tumor oxidative stress was evaluated by detection of malondialdehyde and superoxide dismutase. The apoptosis of tumor cells was evaluated by the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay as well as by Western blot analysis of B-cell lymphoma 2-associated X protein and cleaved caspase-3 expression. Additionally, the expression of hypoxia-induced factor-1α, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B was also evaluated by Western blot. RESULTS: Compared with the control group, the intermittent hypoxia treatment significantly increased Lewis lung carcinoma tumor growth and oxidative stress (serum malondialdehyde) but decreased serum levels of SOD and pro-apoptotic markers (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, B-cell lymphoma 2-associated X protein, and cleaved caspase-3). These changes were significantly attenuated by intraperitoneal injection of sodium tanshinone IIA sulfonate. Lower nuclear factor erythroid 2-related factor 2 and higher nuclear factor kappa B levels in the intermittent hypoxia group were clearly reversed by sodium tanshinone IIA sulfonate treatment. In addition, sodium tanshinone IIA sulfonate administration decreased the high expression of hypoxia-induced factor-1α induced by intermittent hypoxia. CONCLUSION: Intermittent hypoxia treatment resulted in high oxidative stress and low apoptosis in Lewis lung carcinoma-implanted mice, which could be attenuated by sodium tanshinone IIA sulfonate administration possibly through a mechanism mediated by the nuclear factor erythroid 2-related factor 2/nuclear factor kappa B signaling pathway.

MiR-323-3p Targeting Transmembrane Protein with EGF-Like and 2 Follistatin Domain (TMEFF2) Inhibits Human Lung Cancer A549 Cell Apoptosis by Regulation of AKT and ERK Signaling Pathways.

BACKGROUND Non-small-cell lung cancer (NSCLC) is predominant and has low 5-year relative survival rate. Therefore, the mechanisms of NSCLC tumorigenesis must be comprehensively elucidated. MicroRNA-323-3p (miR-323-3p) has been widely explored and found to exert functions in tumorigenesis of several cancer types. However, the expression pattern and biological function of miR-323-3p and the molecular mechanism underlying NSCLC development and progression remain unclear. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miR-323-3p and TMEFF2 in NSCLC cell lines (A549, NCI-H3255, and H1299) and normal cell line (BEAS-2B). Methylthiazolyl tetrazolium, colony formation, and flow cytometry assays were performed to evaluate the effects of miR-323-3p and TMEFF2 on cell proliferation. Transwell assay was conducted to determine the effects of TMEFF2 on cell migration and invasion. Dual-luciferase reporter assay was used to verify whether TMEFF2 is a target of miR-323-3p. Western blot analysis was performed to analyze protein expression. RESULTS The expression of miR-323-3p increased in the 3 NSCLC cell lines (A549, NCI-H3255, and H1299). miR-323-3p regulated cellular progression by directly suppressing TMEFF2 expression and indirectly prohibited the activation of AKT and ERK pathways in NSCLC. CONCLUSIONS Overall, miR-323-3p was considered a lung cancer oncogene and could be a valuable target for NSCLC therapy.

Does mobile-bearing have better flexion and axial rotation than fixed-bearing in total knee arthroplasty? A randomised controlled study based on gait.

OBJECTIVE: To analyse the 6 degrees of freedom of the knee and gait data of patients with medial knee osteoarthritis before and after fixed-bearing (FB) and mobile-bearing (MB) total knee arthroplasty (TKA) â€‹and examine the influence of TKA on gait characteristics and the difference between FB and MB prosthesis. We also sought to explore the prosthesis options available for TKA in these patients. METHODS: Thirty patients who underwent TKA at the Department of Orthopedics at our hospital from June to October 2017 were included. All patients had a lower limb mechanical axis (hip-knee-ankle angle) of less than 180° which were regarded as genu varum knees and had medial knee osteoarthritis. Patients were randomised divided into the FB group â€‹and the MB group according to the knee prosthesis implanted. An infrared navigation three-dimensional portable knee motion analysis system (Opti-Knee®, Shanghai Innomotion, Inc.) was used to acquire data on the 6 degrees of freedom of both knees when walking on flat ground before and after surgery (angle of tibia relative to femur parameters: flexion-extension, internal rotation-external rotation, abduction-adduction; displacement parameters: anterior-posterior, proximal-distal, medial-lateral). Postoperative follow-up efficacy was assessed using the Oxford Knee Score system. RESULTS: There were significant differences in the maximum values of the internal/external rotation and flexion/extension angle between patients post-TKA and the healthy population, p values were 0.007 and <0.001,respectively. The postoperative maximum values of genu varum and internal rotation in both FB [(-9.49 â€‹± â€‹5.99°), (-5.77 â€‹± â€‹3.42°), respectively] and MB [(-9.64 â€‹± â€‹4.83°), (-7.54 â€‹± â€‹4.51°), respectively] groups were lower than the preoperative ones [FB (-15.13 â€‹± â€‹6.78°), (-8.28 â€‹± â€‹4.83°); MB (-13.28 â€‹± â€‹3.98°), (-9.46 â€‹± â€‹4.99°), respectively] (p â€‹≤ â€‹0.001), while the postoperative maximum values of flexion angle and anterior displacement in both FB [(46.11 â€‹± â€‹4.14°), (0.71 â€‹± â€‹0.35 â€‹cm), respectively] and MB [(49.33 â€‹± â€‹3.98°), (0.75 â€‹± â€‹0.89 â€‹cm), respectively] groups were larger than the preoperative ones [FB (43.15 â€‹± â€‹3.77°), (0.26 â€‹± â€‹0.74 â€‹cm); MB (44.62 â€‹± â€‹5.92°), (0.33 â€‹± â€‹0.79°), respectively] (p â€‹≤ â€‹0.001). The postoperative range of flexion/extension angle in both FB (40.13 â€‹± â€‹4.14°) and MB (45.82 â€‹± â€‹3.76°) groups was significantly larger than the preoperative one [FB (36.17 â€‹± â€‹6.07°), MB (37.09 â€‹± â€‹3.93°), respectively] (p â€‹≤ â€‹0.001). There were also significant increases in range of anterior-posterior displacement in the FB group (0.85 â€‹± â€‹0.32 â€‹cm) postoperatively compared with the preoperative one (0.71 â€‹± â€‹0.92 â€‹cm) (p â€‹= â€‹0.016) â€‹and significant increases in range of medial-lateral displacement (0.64 â€‹± â€‹0.73 â€‹cm) in the MB group postoperatively compared with the preoperative one (0.52 â€‹± â€‹0.91 â€‹cm) (p â€‹= â€‹0.025). The mean flexion/extension angle of the MB group was significantly greater than the FB group after surgery in both the stance phase and the swing phase (p â€‹< â€‹0.001). There were significant differences in postoperative knee axial rotation during the gait cycle between the MB and FB groups (p â€‹= â€‹0.028) â€‹and that postoperative internal rotation of the tibia relative to the femur increased in the MB group. The Oxford Knee Score at the last follow-up visit about 7.5 months after surgery was 15.6 â€‹± â€‹1.3 and 15.1 â€‹± â€‹1.1 points for FB and MB groups, respectively. This difference was not significant (p â€‹= â€‹0.428). CONCLUSIONS: TKA can make the parameters of knee gait characteristics closer to the normal population. Medial knee osteoarthritis patients who received a MB prosthesis in TKA had better joint flexion function and axial rotation than the FB one. However, there is insufficient evidence to suggest that the MB prosthesis is a better option for patients with medial knee osteoarthritis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To date, no consensus for prosthesis selection in TKA has been established. This study found significant differences in joint flexion/extension angle and internal/external rotation during gait post-TKA surgery in medial knee osteoarthritis patients who received different prostheses. This will provide some references for prosthesis selection for a large number of genu varum patients in clinical practice.

Differential expression of microRNAs in xenografted Lewis lung carcinomas subjected to intermittent hypoxia: a next-generation sequence analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cancer mortality, but the underlying mechanism remains poorly understood. MicroRNAs (miRNAs) are confirmed to be involved in tumorigenesis and tumor progression. However, whether miRNAs have any differential expressions in OSA population needs to be elucidated. The aim of this experimental study was to determine the alterations of various miRNAs in xenograft mice exposed to chronic intermittent hypoxia (IH) which is considered a hallmark of OSA. METHODS: Sequencing was applied to screen the miRNAs of tumor tissues in xenograft mice exposed to IH and normoxia (control, CTL), respectively. Most differentially expressed miRNAs were verified by the quantitative real-time polymerase chain reaction (qRT-PCR). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed to reveal the functional enrichment of the target genes regulated by the miRNAs. RESULTS: A total of 485 miRNAs (259 novel miRNAs and 226 known miRNAs) were differentially expressed between the IH and CTL groups. 154 miRNAs were upregulated and 331 miRNAs were downregulated among them. The top 5 differentially expressed known (miR-767, miR-466f-5p, miR-5122, miR-124-3p and miR-590-3p) and novel (miR-140, miR-130, miR-301, miR-177 and miR-90) miRNAs were validated by qRT-PCR. MiR-767, miR-124-3p, miR-590-3p and all novel miRNAs were upregulated while miR-466f-5p and miR-5122 were downregulated in IH-induced xenograft mice. In addition, GO and KEGG pathway analysis demonstrated that the predicted target genes, which were regulated by differentially expressed miRNAs were markedly enriched in related biological processes and pathways, including biological processes, cell metabolic and biosynthetic processes and molecular functions. CONCLUSIONS: Several altered miRNAs were detected in xenograft mice exposed to IH. The differentially expressed miRNAs in IH indicates that these miRNAs might involve in the molecular mechanism of tumorigenesis and tumor progression in OSA. Further studies are required to determinate the exact intermediation of certain miRNAs between IH and tumor progression.

Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities.

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea-hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea-hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3-4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.

Disruption of sleep architecture in Prevotella enterotype of patients with obstructive sleep apnea-hypopnea syndrome.

INTRODUCTION: Intermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea-hypopnea syndrome (OSAHS). Those manifestations independently affect similar brain regions and contribute to OSAHS-related comorbidities that are known to be related to the host gut alteration microbiota. We hypothesized that gut microbiota disruption may cross talk the brain function via the microbiota-gut-brain axis. Thus, we aim to survey enterotypes and polysomnographic data of patients with OSAHS. METHODS: Subjects were diagnosed by polysomnography, from whom fecal samples were obtained and analyzed for the microbiome composition by variable regions 3-4 of 16S rRNA pyrosequencing and bioinformatic analyses. We examined the fasting levels of interleukin-6 and tumor necrosis factor-alpha of all subjects. RESULTS: Three enterotypes Bacteroides, Ruminococcus, and Prevotella were identified in patients with OSAHS. Arousal-related parameters or sleep stages are significantly disrupted in apnea-hypopnea index (AHI) ≥15 patients with Prevotella enterotype; further analysis this enterotype subjects, obstructive, central, and mixed apnea indices, and mean heart rate are also significantly elevated in AHI ≥15 patients. However, blood cytokines levels of all subjects were not significantly different. CONCLUSIONS: This study indicates the possibility of pathophysiological interplay between enterotypes and sleeps structure disruption in sleep apnea through a microbiota-gut-brain axis and offers some new insight toward the pathogenesis of OSAHS.

Intermittent hypoxia enhances the tumor programmed death ligand 1 expression in a mouse model of sleep apnea.

BACKGROUND: As a hallmark of obstructive sleep apnea (OSA), intermittent hypoxia (IH) promotes tumor progress. The high expression of programmed death 1 and programmed death ligand 1 (PD-L1) in tumor leads to immune evasion and subsequently aggravates tumor progress. This study aims to determine the tumor PD-L1 expression under the IH condition. METHODS: A total of 24 C57BL/6J mice were randomly assigned to the normoxia (control, CTL) group and the IH group. Mice in the IH group were subjected to the IH condition for 5 weeks. Lung cancer cells were injected into the flank of each mouse after 1 week of IH exposure. Tumor PD-L1 expression was detected by immunohistochemistry (IHC). Correlation between tumor weight, tumor volume, and expression of PD-L1 was analyzed. RESULTS: Compared to the CTL group, mice in the IH group had a high PD-L1 expression. The IH can enhance the tumor PD-L1 expression. Tumor weight, volume, and HIF-1α levels were closely associated with the PD-L1 expression in the IH group, while dissimilar findings were observed in the CTL group. CONCLUSIONS: The IH enhances tumor PD-L1 expression in OSA mimicking mice. Additional studies are required to clarify the underlying mechanism.

Management of Persistent Air Leaks Using Endobronchial Autologous Blood Patch and Spigot Occlusion: A Multicentre Randomized Controlled Trial in China.

BACKGROUND: Optimal management of persistent air leaks (PALs) in patients with secondary spontaneous pneumothorax (SSP) remains controversial. OBJECTIVE: To evaluate the efficacy and safety of endobronchial autologous blood plus thrombin patch (ABP) and bronchial occlusion using silicone spigots (BOS) in patients with SSP accompanied by alveolar-pleural fistula (APF) and PALs. METHODS: This prospective multicentre randomized controlled trial compared chest tube-attached water-seal drainage (CTD), ABP, and BOS that were performed between February 2015 and June 2017 in one of six tertiary care hospitals in China. Patients diagnosed with APF experiencing PALs (despite 7 days of CTD) and inoperable patients were included. Outcome measures included success rate of pneumothorax resolution at the end of the observation period (further 14 days), duration of air leak stop, lung expansion, hospital stay, and complications. RESULTS: In total, 150 subjects were analysed in three groups (CTD, ABP, BOS) of 50 each. At 14 days, 60, 82, and 84% of CTD, ABP, and BOS subjects, respectively, experienced full resolution of pneumothorax (p = 0.008). All duration outcome measures were significantly better in the ABP and BOS groups than in the CTD group (p < 0.016 for all). The incidence of adverse events, including chest pain, cough, and fever, was not significantly different. All subjects in the ABP and BOS groups experienced temporary haemoptysis. Spigot displacement occurred in 8% of BOS subjects. CONCLUSION: ABP and BOS resulted in clinically meaningful outcomes, including higher success rate, duration of air leak stop, lung expansion, and hospital stay, with an acceptable safety profile.

Ameliorative effect of Ruellia tuberosa L. on hyperglycemia in type 2 diabetes mellitus and glucose uptake in mouse C2C12 myoblasts.

Ruellia tuberosa L. (RTL) exhibits a wide range of phytochemical activities, for example, on treatment of diabetes mellitus (DM), in Orient. There is, however, few study regarding the effect of RTL on glycemic-related homeostasis in type 2 DM (T2DM). We investigated the effect of RTL aqueous and ethanolic extracts on hypoglycemia in high-fat diet (HFD)-fed plus streptozotocin (STZ)-induced T2DM rats, and examined the effect of RTL on glucose uptake in tumor necrosis factor-α-induced insulin-resistant mouse C2C12 myoblasts, a mouse skeletal muscle cell line. The administration of 100 or 400 mg kg BW-1 day-1 of RTL aqueous or ethanolic extracts once a day for 4 weeks significantly ameliorated hyperglycemia, hyperinsulinemia, and the insulin resistance (IR) index in diabetic rats. RTL either aqueous or ethanolic extract at a concentration of 25-800 µg/ml significantly improved glucose uptake in insulin-resistant mouse C2C12 myoblasts, indicating inhibiting the IR in skeletal muscles. These evidences suggest that RTL ameliorates hyperglycemia in HFD/STZ-induced T2DM rats may be attributed to the alleviation of IR in skeletal muscles.

Curcumin Inhibits Lipopolysaccharide-Induced Mucin 5AC Hypersecretion and Airway Inflammation via Nuclear Factor Erythroid 2-Related Factor 2.

BACKGROUND: Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects of curcumin (CUR) on lipopolysaccharide (LPS)-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro. METHODS: For the in vitro study, human bronchial epithelial (NCI-H292) cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down with Nrf2 small interfering RNA (siRNA) to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups (n = 7 for each group): control group, LPS group, and LPS + CUR group. Mice in LPS and LPS + CUR group were injected with saline or CUR (50 mg/kg) intraperitoneally 2 h before intratracheal instillation with LPS (100 µg/ml) for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC (MUC5AC) and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid (BALF) was collected to enumerate total cells and neutrophils. Histopathological changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared. RESULTS: CUR significantly decreased the expression of MUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent (2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P < 0.05, respectively) and accompanied by increased mRNA and protein expression of Nrf2 (1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ± 0.132, t = -6.453; both P < 0.05, respectively). Furthermore, knockdown of Nrf2 with siRNA increased MUC5AC mRNA expression by 47.7%, compared with levels observed in the siRNA-negative group (6.845 ± 1.478 vs. 3.391 ± 0.517, t = -3.821, P < 0.05). Knockdown of Nrf2 with siRNA also markedly increased MUC5AC protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5AC in mouse lung (1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P < 0.05). Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells (247 ± 30 vs. 334 ± 24, t = 3.901, P < 0.05) and neutrophils (185 ± 22 vs. 246 ± 20, t = 3.566, P < 0.05) in BALF decreased in the LPS + CUR group, as well as reduced inflammatory cell infiltration in lung tissue. CONCLUSION: CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.

Use of endo-bronchial end-tidal CO2 test for location of the pleural air leakage in patients with intractable pneumothorax.

BACKGROUND: Location of the affected bronchus of pleural air leaks is the most important step of trans-bronchoscopic bronchial occlusion for the treatment of intractable pneumothorax. The balloon occlusion test is the most commonly used technique, but has failed in some cases. The aim of the present study was: (1) to determine if endo-bronchial end-tidal CO2 (EtCO2) measurement can identify the affected bronchus that is the source of a persistent pleural air leak; and (2) to establish a methodology for endo-bronchial EtCO2 testing in locating affected bronchus in intractable pneumothorax. METHODS: A total of 28 patients with intractable pneumothorax underwent bronchoscopy with (1) the balloon occlusion test for the identification of the affected bronchus; and (2) endo-bronchial EtCO2 measurement (EtCO2 test) at the orifices of the bronchus of the affected lung. The effectiveness of these two methods of affected bronchus identification were compared. The threshold EtCO2 (T-EtCO2) was determined. RESULTS: The positive rates of locating the affected bronchus by the endo-bronchial EtCO2 test, balloon occlusion test, and combination of the two techniques were 60.7% (17/28), 64.3% (18/28) and 96.4% (27/28), respectively. The average differences in EtCO2 between the affected bronchus and the main carina, main bronchus, and non-affected bronchus were (in mmHg) 4.41 ± 1.99 (95% confidence interval: 3.5, 5.3), 4.73 ± 2.10 (3.80, 5.66 ) and 5.57 ± 2.53 (4.45, 6.69), respectively. CONCLUSIONS: (1) The endo-bronchial EtCO2 test is complementary to the balloon occlusion test of the leading bronchus. (2) A threshold (T-EtCO2) value of >5 mmHg is optimal for this technique.

ß-Elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/ß-catenin pathway.

Benign airway stenosis is a clinical challenge because of recurrent granulation tissues. Our previous study proved that a Chinese drug, ß-elemene, could effectively inhibit the growth of fibroblasts cultured from hyperplastic human airway granulation tissues, which could slow down the progression of this disease. The purpose of the present study is to find out the mechanism for this effect. We cultured fibroblasts from normal human airway tissues and human airway granulation tissues. These cells were cultured with 160 µg/ml normal saline (NS), different doses of ß-elemene, or 10 ng/ml canonical Wnt/ß-catenin pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the expression of six molecules involved in canonical Wnt/ß-catenin pathway, Wnt3a, glycogen synthase kinase-3ß (GSK-3ß), ß-catenin, α-smooth muscle actin (α-SMA), transforming growth factor-ß (TGF-ß), and Collagen I (Col-I), were measured. At last, we used canonical Wnt/ß-catenin pathway activator (LiCl) to further ascertain the mechanism of ß-elemene. Canonical Wnt/ß-catenin pathway is activated in human airway granulation fibroblasts. ß-Elemene didn't affect normal human airway fibroblasts; however, it had a dose-responsive inhibitive effect on the proliferation and expression of Wnt3a, non-active GSK-3ß, ß-catenin, α-SMA, TGF-ß, and Col-I of human airway granulation fibroblasts. More importantly, it had the same effect on the expression and nuclear translocation of active ß-catenin. All these effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl. Thus, ß-elemene inhibits the proliferation of primary human airway granulation fibroblasts by down-regulating canonical Wnt/ß-catenin pathway. This pathway is possibly a promising target to treat benign tracheobronchial stenosis.

Effect of Femoral Component Flexion Implantation on the Mediolateral Bone-prosthetic Fit in Total Knee Arthroplasty.

OBJECTIVE: Femoral component overhang in total knee arthroplasty (TKA) has been reported in previous studies. The purpose of this study was to evaluate the effect of femoral component flexion implantation on mediolateral bone-prosthetic fit in TKA. METHODS: Virtual prosthesis implantations were performed on computed tomographic models of 10 Chinese knees with femoral prostheses of the Advance Medial-Pivot knee system (MicroPort Orthopedics, Arlington, TN, USA), with the femoral component positioned at 0°, 3°, or 6° of flexion in the sagittal plane. For each degree of flexion implantation, the differences between the knee and femoral component models on the lateral and medial sides at trochlea (zone 1), anterior-distal condyle (zone 2), posterior-distal condyle (zone 3), and posterior condyle (zone 4) were measured. Positive difference values indicate component overhang, and negative difference values indicate component underhang. The values of component overhang (underhang) in each zone were statistically analyzed across the 3° of flexion implantation. RESULTS: With a greater degree of flexion implantation, overhang was reduced and even changed to underhang. With 0° of flexion implantation, an overhang exceeding 3 mm existed mainly on the medial side of zone 1 (5.81 mm) and the lateral side of zone 2 (3.39 mm). With 3° of flexion, overhang exceeding 3 mm was observed only on the medial side of zone 1 (3.10 mm), and underhang was observed only on the medial side of zone 4 (-0.32 mm). No overhang exceeding 3 mm was observed for 6° of flexion, while underhang was observed except on the lateral sides of zone 2 (1.32 mm) and zone 4 (1.10 mm) and on the medial side of zone 1 (1.54 mm). A significant difference in overhang values on the lateral and medial sides of zone 1 was observed between 0 and 6° of flexion (P < 0.05). CONCLUSION: The present study demonstrated that femoral component flexion implantation by 3° can reduce excessive overhang, although 3.10 mm of overhang remained at the medial side of zone 1. Conversely, 6° of flexion implantation can avoid 3 mm of overhang for any zone, but increases the risk of underhang. Slight flexion implantation may be an effective alternative technique to prevent excessive component overhang, especially in the trochlea and anterior region of the distal condyle, in Chinese patients with standard TKA prostheses.

Erythropoietin levels in patients with sleep apnea: a meta-analysis.

Currently available data regarding the blood levels of erythropoietin (EPO) in sleep apnea (SA) patients are contradictory. The aim of the present meta-analysis was to evaluate the EPO levels in SA patients via quantitative analysis. A systematic search of Pubmed, Embase, and Web of Science were performed. EPO levels in SA group and control group were extracted from each eligible study. Weight mean difference (WMD) or Standard mean difference (SMD) with 95% confidence interval (CI) was calculated by using fixed-effects or random effect model analysis according to the degree of heterogeneity between studies. A total of 9 studies involving 407 participants were enrolled. The results indicated that EPO levels in SA group were significantly higher than that in control group (SMD 0.61, 95% CI 0.11-1.11, p = 0.016). Significantly higher EPO levels were found in patients with body mass index <30 kg/m2, and cardiovascular complications in the subsequent subgroup analysis (both p < 0.05). High blood EPO levels were found in SA patients in the present meta-analysis.

4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4.

The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expression level was downregulated by siRNA. The POLD4 protein levels in the A549 cells decreased following treatment with 4NQO; however, MG132 could reverse this phenotype. Downregulation of the POLD4 expression by siRNA enhanced A549 cell sensitivity to 4NQO, but not to Taxol. In conclusion, 4NQO affects human lung adenocarcinoma A549 cells by regulating the expression of POLD4.

Effects of sex and lower extremity alignment on orientation of the knee joint line in knee surgery.

BACKGROUND: Determination of the proper orientation of the knee articular surface is required both for correction of knee malalignment by osteotomy and for correct component alignment in knee arthroplasty. We sought to determine whether the patients' sex and lower extremity alignment (hip-knee-ankle angle) affects proper knee realignment in osteotomy or component alignment in total knee arthroplasty. METHODS: We examined 199 healthy adult knees with malalignment of < 5° to determine the mechanical medial distal femoral angle, mechanical medial proximal tibial angle, surgical transepicondylar axis angle, and discrepancies between bone-cut orientations of osteotomy or total knee arthroplasty and the joint line of the distal femoral condyles, posterior femoral condyles and proximal tibial plateaus, using a three-dimensional computed tomography model. RESULTS: The mean mechanical medial distal femoral angle and mean mechanical medial proximal tibial angle were (94.4 ± 1.9)° and (87.6 ± 1.8)° respectively for women and (93.8 ± 2.0)° and (87.1 ± 1.4)° respectively for men. The surgical transepicondylar axis angle was (2.9 ± 1.6)° for women and (3.2 ± 1.7)° for men. Independent of sex, the hip-knee-ankle angle was closely related to the mechanical medial distal femoral angle and mechanical medial proximal tibial angle, but not to the surgical transepicondylar axis angle. A slightly more valgus alignment of the knee and a more valgus angulation of the distal femoral joint line were found in women, whereas a more varus angulation of the proximal tibial joint line was found in men. Sex had the greatest effect on knee joint line orientation when the lower extremity was valgus in alignment. CONCLUSIONS: A more valgus femoral joint line can be expected in women and in persons with valgus lower extremity alignment; a more varus tibial joint line can be found in men and in persons with varus lower extremity alignment.