Microfluidic fabrication of monodisperse microcapsules with gas cores.

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.

Concomitant double-fusion of PLEKHA7-ALK and INPP5D-ALK reveals favorable alectinib sensitivity in lung adenocarcinoma: a case report and literature review.

Anaplastic lymphoma kinase (ALK) gene fusion is a classic driver mutation in non-small cell lung cancer (NSCLC); however, ALK double-fusion variants in NSCLC have rarely been reported. In this study, we reported a case with extremely uncommon ALK double-fusion variants. A 32-year-old female diagnosed with lung adenocarcinoma, who had developed multiple intrapulmonary and brain metastases, experienced worsening of her condition despite undergoing prior chemotherapy. Subsequent testing using next-generation sequencing (NGS) detected the presence of PLEKHA7-ALK and INPP5D-ALK double-fusion. The prescription of alectinib revealed potent efficacy and resulted in an increase in the survival rate. This case presented two uncommon and concomitant ALK fusion partners in NSCLC; more importantly, the INPP5D-ALK subtype has not been reported, therefore this study broadens the spectrum of ALK double-fusion variants and provides insight into the use of ALK inhibitors for the treatment of NSCLC in patients with double ALK fusions.

Microfluidic Controllable Preparation of Iodine-131-Labeled Microspheres for Radioembolization Therapy of Liver Tumors.

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size is obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity, and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC.

Optimum fractionation of radiation to combine PD-1 blockade.

The optimum fractionation of radiation to combine with immune checkpoint blockade is controversial. This study aimed to investigate the fractionated radiation to maximize immunity during combination therapy. To evaluate the abscopal effect, C57BL/6 hPD-1 knock-in mice bearing two syngeneic contralateral MC38 murine colon cancer tumors were treated with four distinct regimens of radiotherapy. Three fractions of 8 Gy were chosen as the optimal fractionation to combine with anti-PD-1 as the optimal fractionation for maximizing immunity. Anti-PD-1 administration enhanced both local and systemic antitumor immunity in a cytotoxic T cell-dependent manner. Meanwhile, the spleen exhibited decreased myeloid-derived suppressor cells (MDSCs) under combination treatment. Furthermore, RNA-sequencing revealed significantly increased tumor necrosis factor (TNF) receptors and cytokines associated with lymphocyte infiltration in the combining group. Here we demonstrate that the hypofractionation of 8 Gy × 3f was the optimum-fractionated dosage to maximize immunity, and the combination of anti-PD-1 showed promising results in boosting abscopal effect. Underlying mechanisms may include the activation of T cells and the reduction of MDSCs, which is achieved through the action of TNF and related cytokines. This study indicates a radioimmunotherapy dosage painting method that can be developed to overcome present limitations in tumor immunosuppression.

Relationship between the Depth of Acetabuloplasty and Outcomes of Hip Arthroscopy in Patients with Global Pincer Femoroacetabular Impingement: Study with a Minimum Follow-Up Period of 2 Years.

OBJECTIVE: There has been no definite consensus on the ideal depth of acetabuloplasty, especially in cases of global pincer femoroacetabular impingement (FAI). This study aims to determine whether the depth of acetabuloplasty influences postoperative outcomes in cases of global pincer FAI. METHODS: Data were retrospectively collected from patients with global pincer FAI who underwent hip arthroscopy with a minimum follow-up period of 2 years from May 2014 to December 2018. Patients with global pincer FAI were subdivided into low or high resection depth groups based on whether the intraoperative acetabular rim was resected by more than 3 mm. Radiographic measurements; arthroscopic procedures; preoperative and postoperative PROs were recorded. Achievement of MCID and PASS was compared for the VAS, mHHS, HOS-ADL, and iHOT-12. A paired Student t-test was used to evaluate the significance of preoperative and postoperative PROs and two-tailed unpaired Student t-test was used to compare demographic data and PROs between different groups. MCID and PASS were evaluated using the chi-square test or the Fisher's exact test. RESULTS: A total of 41 hips with global pincer FAI (15 and 26 patients in low or high resection depth groups, respectively) were included in this study. Both groups showed significant postoperative improvements in the scores of all PROs (p < 0.001). Compared to the low resection depth group, the high resection depth group had a lower degree of improvement through hip arthroscopy, which manifested as lower postoperative mHHS scores (94.29 vs. 85.08, p = 0.006), higher VAS scores (0.93 vs. 2.54, p = 0.002), and lower improvements in VAS (-5.00 vs. -3.35, p = 0.028), HOS-ADL (34.99 vs. 23.90, p = 0.017) and iHOT-12 (39.89 vs. 29.27, p = 0.036). Patients in high resection depth group were less likely to achieve the MCID for the VAS score compared to low resection depth group in significant (73.3 vs. 26.9%, p = 0.004). CONCLUSIONS: For patients with global pincer, the outcomes in high resection depth group were slightly worse than the the low resection depth group. It is indicated that excessive resection of the acetabular rim during the procedure should be avoided.

Outcomes in Patients with Global Pincer Versus Focal Pincer Femoroacetabular Impingement Treated with Hip Arthroscopy: A Retrospective Study with a Minimum 2-Year Follow-Up.

OBJECTIVE: Global pincer is a relatively rare form of pincer deformity and is typically associated with technical challenges during surgery. So far, controversy remains whether patients with global pincer have equivalent surgical outcomes compared to patients with focal pincer. This study compares the clinical outcomes of arthroscopic treatment between patients with global pincer femoroacetabular impingement (FAI) and focal pincer FAI in the Chinese population. METHODS: Data were retrospectively collected from patients with global and focal pincer FAI who underwent hip arthroscopy with a minimum two-year follow-up between April 2016 and December 2018. Radiographic measurements, arthroscopic procedures, preoperative and postoperative patient-reported outcomes (PROs) including modified Harris hip score (mHHS), hip outcome score-activities of daily living (HOS-ADL), international hip outcome tool-12 (iHOT-12), and visual analogue scale (VAS) scores, rates of revision surgery and conversion to total hip arthroplasty (THA) were recorded. Achievement of minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) was compared for the VAS, mHHS, HOS-ADL, and iHOT-12 scores between groups. RESULTS: The total of 33 and 167 patients were included in the global and focal group, respectively. There were no intergroup differences in age, gender, body mass index or follow-up times. Lateral center-edge angle (LCEA) was reduced in both groups postoperatively. Both groups demonstrated significant improvements in PROs compared with preoperative levels at the final follow-up. The preoperative scores showed significant differences in terms of mHHS (60.34 vs 62.90, P = 0.031) and HOS-ADL (61.45 vs 64.74, P = 0.022) scores between two groups, and the improvement of HOS-ADL score was significantly higher in global group (P = 0.027). However, the postoperative scores, including VAS, mHHS, HOS-ADL, and iHOT-12 scores, showed no significant differences between two groups. And there were no significant differences in the rate of meeting the PASS and MCID between groups. One (3.0%) in the global group and six (3.6%) patients in the focal group underwent revision arthroscopy respectively, with no significant difference (P = 0.876). There were no conversions to THA in both groups. CONCLUSIONS: Arthroscopic management of global pincer FAI can achieve excellent functional scores at minimum 2-year follow-up. The outcomes were similar to focal pincer FAI patients with a low rate of secondary procedure.

A comparison between ultrasound-guided AIIS injection and radiography in the diagnosis of subspine impingement in patients with FAI.

BACKGROUND: Subspine impingement (SSI) does not have effective diagnostic criteria, especially in patients who also have femoroacetabular impingement (FAI). The classification of anterior inferior iliac spine (AIIS) morphology via three-dimensional CT is controversial. PURPOSE: To propose a method for ultrasound-guided AIIS injection as a way to diagnose SSI and evaluate the accuracy of radiography methods, including 3-D CT and MRI, as well as intraoperative findings. METHODS: Patients diagnosed with FAI between September 2020 and December 2021 were evaluated in this prospective study. Those who met the criteria were included in the ultrasound-guided AIIS injection test. Whether the pain was relieved after injection was recorded in the radiology report. Patients who experienced significant relief of the anterior groin pain (more than 50%) after the AIIS injection were considered positive responders. Among these patients, radiography materials, including AIIS morphology as measured by 3-D CT as well as superior capsular oedema on MRI, were compared. The presence of congestion or bruising on the capsule side of the labrum corresponding to the AIIS during hip arthroscopy was recorded. RESULTS: A total of 73 patients with FAI underwent the ultrasound-guided AIIS injection test. Prevalence rates of 13.70% (10/73), 58.90% (43/73), 23.29% (17/73) and 4.11% (3/73) were recorded for Type I, Type IIA, Type IIB and Type III AIISs, respectively. Thirty-six patients had positive responses to injection, and 37 patients had negative responses to injection. None of the patients with Type I, 23 (53.49%) patients with Type IIA, 11 (64.71%) patients with Type IIB and 2 (66.7%) patients with Type III AIISs had positive responses to the injection. A total of 57.14% of patients with Type II or Type III AIIS had positive responses to the injection. The proportions of patients with superior capsular oedema on MRI in the Type I, Type IIA, Type IIB, and Type III AIIS groups was 0, 30.23, 29.41 and 0%, respectively. Among non-Type I AIIS patients, those who reported positive responses to the injection had a higher incidence of superior capsular oedema (38.89% vs. 14.81%, P = 0.036), but they had no significant differences in the proportion of congestion or bruising of the labrum (47.22% vs. 37.04%, P = 0.419). The results showed that no pairs of methods-ultrasound-guided injection, MRI, and intraoperative findings-achieved good consistency (κ = 0.222, κ = 0.098 and κ = - 0.116). CONCLUSIONS: Radiographic methods including 3-D CT and MRI as well as the intraoperative findings of the labrum cannot be considered an accurate and reliable basis for the diagnosis and treatment of SSI in FAI patients. It is suggested that ultrasound-guided AIIS injections be combined with radiography to better diagnose SSI. LEVEL OF EVIDENCE: IV, case series.

[Effect of unicompartmental knee arthroplasty in patients over 75 years old with knee osteoarthritis].

OBJECTIVE: To investigate the clinical effect of unicompartmental knee arthroplasty in patients with knee osteoarthritis over 75 years old. METHODS: From April 2010 to May 2015, 42 patients with knee medial compartment osteoarthritis were treated with Oxford third-generation unicompartmental knee arthroplasty. According to the single and bilateral replacement, the patients were divided into bilateral simultaneous replacement group and unilateral replacement group:11 patients in the simultaneous replacement group, 3 males and 8 females, aged (79.18±3.06) years;There were 31 cases in the unilateral replacement group, 13 males and 18 females, aged (78.16±3.48) years. The survival status of patients with knee prosthesis, the changes of hematocrit before and after operation, and the total amount of blood loss during and after operation were observed and compared;The HSS (Hospital for Special Surgery knee rating) scores of patients before and after operation were compared. RESULTS: There was significant difference in perioperative complications between two groups(P<0.05). All 42 patients were followed up for(5.7±2.3) years. One patient with a history of previous hypertension developed cerebral thrombosis in the 4th month after operation, one patient developed pad dislocation in the 4th month after operation, and two patients died of other medical diseases(1 myocardial infarction and 1 lung cancer) 3 years after operation. The total amount of postoperative blood loss in bilateral simultaneous replacement group was higher than that in unilateral replacement group(P<0.05);Four patients with bilateral simultaneous replacement received 2U blood transfusion after operation. The HSS score and total score of the two groups at 9 months after operation were higher than those before operation(P<0.05). CONCLUSION: Unicompartmental knee arthroplasty is a feasible surgical treatment for osteoarthritis patients over 75 years old with medial single compartment degeneration. For elderly patients over 75 years old with bilateral knee lesions, bilateral simultaneous unicompartmental knee arthroplasty is more traumatic than unilateral unicompartmental knee arthroplasty, which will increase the incidence of perioperative complications, affect the rapid postoperative recovery and increase the blood loss. Although the long-term effect is equivalent to that of unilateral unicompartmental knee arthroplasty, staged operation is still recommended to ensure the safety of operation.

Clinical outcomes of endoscopic synovectomy with adjuvant radiotherapy of pigmented villonodular synovitis of the hip: a case series of single center.

BACKGROUND: Though radiotherapy has been widely used for knee pigmented villonodular synovitis (PVNS), there is few literatures about radiotherapy for the treatment of PVNS hip. Thus, the purpose of this study was to analyze the clinical outcomes of endoscopic synovectomy with/without radiotherapy postoperatively of PVNS hip. METHODS: We performed a retrospective study of patients who underwent endoscopy in our hospital from November 2010 to January 2021. Inclusion criteria was patients with magnetic resonance image (MRI) signs, endoscopic findings and/or histological evidence of PVNS. Exclusion criteria was patients lost follow-up. All patients underwent synovectomy endoscopically and were divided into two groups depending on receiving postoperative radiotherapy or not. The primary outcome measurements were the recurrence of PVNS, receiving revision, and/or converting to total hip arthroplasty (THA). The secondary outcome measurements were the patient-reported outcome (PRO) collected at pre- and post-operation, which consist of Hip Outcome Score Activities of Daily Living (HOS-ADL), modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (IHOT-12), Non-arthritic Hip Scale (NAHS), and visual analog scale (VAS). RESULTS: In a case series of 16 patients (8 cases of male, 50%), 4 (25%) cases were localized type and 12 (75%) cases were diffuse type. The average follow-up was 44.8 ± 38.2 months (range,3 to 110). 8 (50%) cases (6 diffuse cases and 2 localized cases) received radiotherapy postoperatively, and the rest (6 diffuse cases and 2 localized cases) received endoscopic treatment alone. At the latest follow-up, 3 (18.75%) cases (2 diffuse cases and 1 localized case) who did not receive radiotherapy converted to arthroplasty. The preoperative HOS-ADL, mHHS, IHOT-12, NAHS, VAS scores of remaining 13 patients were 63.1 ± 19.1 (range,32.0 to 98.8), 54.8 ± 20.1 (range, 10.0 to 77.0), 50.9 ± 15.4 (range, 31.0 to 76.6),51.6 ± 15.9 (range, 20.0 to 84.4), 6.0 ± 1.4 (range,4.0 to 8.0) points, respectively. The latest HOS-ADL, mHHS, IHOT-12, NAHS, VAS scores of the 13 patients were 79.7 ± 10.8 (range, 58.0 to 97.6), 78.6 ± 9.1 (range,55.0 to 87.0), 74.7 ± 9.7 (range, 55.6 to 91.0), 78.9 ± 18.7 (range,20.0 to 92.5), 3.1 ± 1.2 (range,2.0 to 6.0) points respectively. CONCLUSION: Endoscopic synovectomy can achieve satisfactory PRO in PVNS hip patients. Besides, postoperative adjuvant radiotherapy can achieve higher hip survivability than synovectomy alone in this present study.

[Application of MRI Water-Fat Separation Technology in Patients with Multiple Myeloma].

OBJECTIVE: To explore the clinical significance of magnetic resonance imaging water-fat separation (Dixon) technique in patients with multiple myeloma. METHODS: A total of 41 newly diagnosed patients with multiple myeloma who underwent Dixon in The Affiliated Hospital of Qingdao University from April 2019 to April 2021 were included in this study. Patients were divided into observation group and control group according to whether Dixon performance was normal or not. The differences of clinical data and fat fraction (FF) between the two groups were compared. The correlation between FF and clinical data, disease stages and differences before and after treatment were also compared. The receiver operator characteristic curve of patients was drawn to analyze the diagnostic value of FF combined with serum alkaline phosphatase for bone destruction in patients with multiple myeloma. RESULTS: Among the 41 patients, there were 12 cases in the control group and 29 cases in the observation group. There was no significant difference in age and sex between the two groups. In the observation group, ß2-microglobulin concentration and M protein were significantly higher than those in the control group, while serum alkaline phosphatase and FF were lower (P<0.05). In all 41 patients included in the study, there was a significant negative correlation between FF value and ß2-microglobulin concentration (r=-0.57), and a significant positive correlation between FF value and serum alkaline phosphatase (r=0.31). After treatment, FF value increased, while myeloma cell percentage, ß2-microglobulin concentration and M protein decreased in 11 patients who completed 4 cycles of chemotherapy, and the differences before and after treatment were statistically significant (P<0.05). The value of serum alkaline phosphatase combined with FF value in predicting bone destruction is higher than that of FF value or serum alkaline phosphatase alone. CONCLUSION: Dixon's different imaging manifestations can reflect the severity of the disease. FF value is correlated with clinical examination results and R-ISS staging, and there is a significant difference before and after treatment. Serum alkaline phosphatase combined with FF value is better than two indicators alone in predicting bone destruction.

The Application of Arthroscopic Techniques in the Diagnosis and Treatment of Hip-Related Conditions in China.

The hip joint is the largest weight-bearing joint in the body and is surrounded by dense capsules and thick muscles. Hip arthroscopic techniques are suitable for the treatment of hip-related conditions. These minimally invasive techniques have rapidly developed in China since 2007. Moreover, they have been used in the treatment of gluteal muscle contracture, snapping hip syndrome, femoral acetabular impingement, acetabular labral injury, hip labral calcification, synovial chondroma, osteoid osteoma, synovitis, osteonecrosis of the femoral head, and developmental dysplasia of the hip. This technique has showed its advantage in the total debridement of lesions, precision treatment, and less trauma. However, we lack understanding of the overall development of arthroscopic techniques in China. This review illustrates the recent development of hip arthroscopic techniques in China and related research progress.

Novel Multifunctional Stimuli-Responsive Nanoparticles for Synergetic Chemo-Photothermal Therapy of Tumors.

In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo-photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the PNA-DOX@PDA-FA nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of PNA-DOX@PDA-FA nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo-photothermal therapy of tumors.

Cross-sectional study based on occupational aluminium exposure population.

To evaluate the different characteristics of cognitive impairment caused by occupational aluminium exposure at different ages, we surveyed 1660 workers in Shanxi Aluminium Plant, China, and assessed their cognitive function and plasma aluminium concentration. In multiple linear regression, the scores of the digit-span test (DST) and digit-span backward test (DSBT) were negatively correlated with plasma aluminium concentration when concentration reached 34.52 µg/L in younger group (＜40 years), while in the middle-aged group (≥40 years) only found when concentration reached 42.25 µg/L (ß<0, P < 0.05). In logistic regression, when plasma aluminum concentration reached 42.25µg/L, odds ratios (95 % confidence interval) were 1.695 (1.062-2.705) and 3.270 (1.615-6.620) for DST, 7.644 (3.846-15.192) and 15.308 (4.180-56.059) for DSBT in middle-aged group and younger group, respectively. These results showed that aluminium exposures were associated with cognitive impairment among aluminium-exposed workers, particularly for young workers who were more susceptible.

[Clinical efficacy and technical characteristics of percutaneous endoscopic lumbar discectomy in the treatment of upper lumbar disc herniation].

OBJECTIVE: To analyze the clinical efficacy and technical characteristics of percutaneous endoscopic lumbar discecomy in the treatment of upper lumbar disc herniation. METHODS: The clinical data of 9 patients with upper lumbar disc herniation underwent percutaneous endoscopic lumbar discecomy from January 2012 to October 2019 were retrospectively analyzed. There were 6 males and 3 females, aged 26 to 79 years, including 2 patients with L1,2 disc herniation and 7 patients with L2, 3 disc herniation. Visual analogue scale (VAS) and Japanese Orthopeadic Association (JOA) score were recorded before and after surgery. The clinical efficacy was evaluated according to the modified Macnab standard. RESULTS: All 9 patients were followedup, and the follow-up time was 1 day and 3 months after surgery. The operation time was 1.5 to 2.9 h and postoperative hospital stay was 5 to 8 d. No cerebrospinal fluid leakage or spinal cord injury occurred during the operation. Preoperative and postoperative at 1 day, 3 months, the VAS scores of 9 patients were 7 to 8 scores, 1 to 3 scores, 0 to 1 case, JOA scores were 5 to 7 scores, 15 to 24 scores, 21 to 26 scores, respectively. The improvement rate of JOA was 36.4% to 78.3% on the first day and 65.2% to 87.5% three months after operation. According to modified Macnab standard to evaluate effect, 4 cases got excellent results, 4 good, 1 fair. CONCLUSION: Percutaneous endoscopic lumbar discecomy has reliable therapeutic effect for upper lumbar disc herniation in line with the indications, and it has the characteristics of small trauma and short operation time, so it is more suitable for middle aged and elderly patients with poor physique and can replace part of transforaminal lumbar interbody fusion.

Prenatal and postnatal cadmium exposure and cellular immune responses among pre-school children.

BACKGROUND: Experimental studies have demonstrated that cadmium exposure induces alterations on immune function, but epidemiological evidence is lacking. OBJECTIVE: To examine the associations between prenatal and postnatal cadmium exposure and cellular immune responses among pre-school children. METHODS: Pre-school aged children (n = 407) were followed from a prospective birth cohort study in Wuhan, China. Maternal urinary and children's plasma cadmium concentrations were measured as biomarkers of prenatal and postnatal cadmium exposure, respectively. Children's cellular immune responses were assessed by peripheral blood T lymphocyte subsets and plasma cytokines. Multivariable adjusted models were applied to estimate the associations of prenatal and postnatal cadmium exposure with T lymphocyte subsets and cytokines, and the effect modification by child gender were also examined. RESULTS: Maternal urinary cadmium was associated with reduced absolute counts of CD3+CD4+ cells (-12.45%; 95% CI: -23.74%, 0.40% for the highest vs. lowest quartile; p for trend = 0.045). Inverse associations of maternal urinary cadmium with %CD3+CD4+ cells and CD4+/CD8+ ratio were only observed among females (both p-interaction < 0.050); whereas an inverse association with absolute counts of CD3+CD8+ cells was only observed among males (p-interaction = 0.057). Positive associations of maternal urinary cadmium with %CD3+CD4+ cells, interleukin-4 (IL-4), and IL-6 were only observed among females, although there were no significant interactions. We observed no clear associations of children's plasma cadmium with T lymphocyte subsets and cytokines. CONCLUSION: Prenatal but not postnatal cadmium exposure was associated with sex-specific alterations on children's cellular immune responses.

Expression of SUMO1P3 Compared with SUMO1 is an Independent Predictor of Patient Outcome in Lung Adenocarcinoma.

BACKGROUND The small ubiquitin-like modifier 1 (SUMO1) and small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) are long noncoding RNAs (lncRNAs). The prognostic significance of SUMO1 and SUMO1P3 expression in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to use clinical, genetic, and survival data from the Cancer Genome Atlas (TCGA), to analyze the prognostic significance of SUMO1 and SUMO1P3 expression in the two main subtypes of NSCLC, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MATERIAL AND METHODS Data were acquired from TCGA and in silico survival analysis was performed. SUMO1 and SUMO1P3 expression were compared between patients with LUAD and LUSC. Patient outcome was assessed as complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). Recurrence-free survival (RFS) was defined as the survival time from primary surgery to the time of locoregional or distant recurrence of lung cancer. RESULTS SUMO1P3 was significantly increased in LUSC and LUAD tissues compared with adjacent normal lung tissue and was significantly co-expressed with SUMO1. SUMO1P3 expression was significantly increased in patients with LUAD but not LUSC with reduced RFS after primary or follow-up treatment. Although patients with LUAD who had high SUMO1 or SUMO1P3 expression had reduced RFS compared with low expression groups, univariate and multivariate analysis showed that only SUMO1P3 expression was independently associated reduced RFS (HR, 1.418; 95% CI, 1.041-1.930; p=0.027). CONCLUSIONS SUMO1P3 expression was an independent indicator of reduced RFS in patients with LUAD.

Heterotopic ossification after arthroscopy for hip impingement syndrome.

BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome. METHODS: A retrospective study was conducted on 242 patients (140 men and 102 women, mean age: 36.2 ±â€Š9.5 years) who underwent hip arthroscopy for femoroacetabular impingement (FAI) between January 2016 and January 2018. The average follow-up period was 22.88 ±â€Š11.74 months (range: 11-34 months). Thirteen (5.37%) cases of HO (six men and seven women, five left hips and eight right hips; mean age: 37.5 ±â€Š4.7 years) were observed. Among them, four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO. Monthly follow-up was conducted. Visual analog scale (VAS), modified Harris Hip Score (mHHS), and non-Arthritis Hip Score (NAHS) were evaluated and compared between HO and non-HO patients. Independent sample t test, Mann-Whitney U test and the Chi-square test were used for inter-group comparisons. HO degree was evaluated using Brooker classification. Symptoms and function were evaluated before and after revision. RESULTS: A total of 242 patients were involved in this study. Thirteen cases (5.4%) had imaging evidence of HO. Nine (9/13) were classified as Brooker stage I, three (3/13) Brooker stage II, and one (1/13) Brooker stage III. HO was detected by ultrasonography as early as 3 weeks after operation. After primary surgery, the mHHS of the HO group and non-HO group increased by 13.00 (8.50, 25.50) and 24.00 (14.00, 34.50) points (Z = -1.80, P = 0.08), NAHS increased by 18.00 (9.50, 31.50) and 26.00 (13.50, 36.00) points (Z = -1.34, P = 0.18), and VAS decreased by 3.00 (2.00, 4.00) and 4.00 (3.00, 4.50) points (Z = -1.55, P = 0.12). Average follow-up time after revision was 9.00 ±â€Š2.94 months; mHHS increased by 34.75 points (t = -55.23, P < 0.01) and NAHS by 28.75 points (t = -6.03, P < 0.01), and VAS decreased by 4 points (t = 9.80, P < 0.01). HO and non-HO patients were similar for demographic and surgical data, and clinical and functional scores. CONCLUSION: HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies. Most HO have no effect on clinical symptoms. Patients who undergo revision HO resection show improvement in pain and joint function.

Induction of Au-methotrexate conjugates by sugar molecules: production, assembly mechanism, and bioassay studies.

Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm. Moreover, in vitro bioassays showed that cancer cell viabilities upon incubation with free MTX, Au-MTX conjugates doped with glucose, dextran and sucrose for 48 h were 74.6%, 55.0%, 62.0%, and 63.1%, respectively. Glucose-doped Au-MTX conjugates exhibited a higher anticancer activity than those doped with dextran and sucrose, therefore potentially presenting a promising treatment platform for anticancer therapy. Based on the present study, this work may provide the first example of using biocompatible sugars as regulating agents to effectively guide the shape and assembly behavior of Au-MTX conjugates. Potentially, the synergistic strategy of drug molecules and sugar molecules may offer the possibility to create more gold-based nanocarriers with new shapes and beneficial features for advanced anticancer therapy.

Novel morphologies of poly(allyamine hydrochloride)-methotrexate nanoassemblies for methotrexate delivery.

Poly(allylamine hydrochloride)-methotrexate (PAH-MTX) nanoassemblies with novel morphologies (i.e. nanostrips, nanorolls, nanosheets, and nanospheres) were achieved for the first time via supramolecular self-assembly directed by the synergistic action of various non-covalent interactions between PAH and MTX molecules in aqueous solution. Herein, MTX acted in a versatile manner as both a morphology-regulating agent and a small molecular hydrophobic anticancer drug. Moreover, different morphologies presented diverse drug release profiles, which may be caused by the distinctive interactions between PAH and MTX molecules. Synergistically non-covalent interactions, including electrostatic interactions, van der Waals forces, and hydrogen bonding, favored easier matrix corrosion and more rapid drug release of non-spherical structures (i.e. nanostrips, nanorolls, and nanosheets) through the ligand exchange process. On the other hand, the highly sealed encapsulation mode for hydrophobic MTX molecules made the nanospheres exhibit slower and better controlled release. In addition, in vitro bioassay tests showed that nanostrips displayed the most obvious suppression on the viability of cancer cells among other morphologies, especially after a longer duration. The strategy of using small molecular anticancer drugs not as passively delivered cargoes but as effective molecular building blocks, opens up a new way to develop self-delivering drugs for anticancer therapy.

K+ -Responsive Block Copolymer Micelles for Targeted Intracellular Drug Delivery.

In this work, a novel type of block copolymer micelles with K+ -responsive characteristics for targeted intracellular drug delivery is developed. The proposed smart micelles are prepared by self-assembly of poly(ethylene glycol)-b-poly(N-isopropylacry-lamide-co-benzo-18-crown-6-acrylamide) (PEG-b-P(NIPAM-co-B18C6Am)) block copolymers. Prednisolone acetate (PA) is successfully loaded into the micelles as the model drug, with loading content of 4.7 wt%. The PA-loaded micelles display a significantly boosted drug release in simulated intracellular fluid with a high K+ concentration of 150 × 10-3 m, as compared with that in simulated extracellular fluid. Moreover, the in vitro cell experiments indicate that the fluorescent molecules encapsulated in the micelles can be delivered and specifically released inside the HSC-T6 and HepG2 cells responding to the increase of K+ concentration in intracellular compartments, which confirms the successful endocytosis and efficient K+ -induced intracellular release. Such K+ -responsive block copolymer micelles are highly potential as new-generation of smart nanocarriers for targeted intracellular delivery of drugs.