A validated model to predict spread through air space in lung adenocarcinoma.

Background: Spread through air space (STAS) is currently considered to be a significant predictor of a poor outcome of pulmonary adenocarcinoma. Preoperative prediction of STAS is of great importance for treatment planning. The aim of the present study was to establish a nomogram based on computed tomography (CT) features for predicting STAS in lung adenocarcinoma and to assess the prognosis of the patients with STAS. Methods: A retrospective cohort study was performed in Wuhan Union Hospital from December 2015 to March 2021. The sample was divided into training and testing cohorts. Clinicopathologic and radiologic variables were recorded. The independent risk factors for STAS were determined by stepwise regression and then incorporated into the nomogram. Receiver operating characteristic (ROC) curves and calibration curves analysed by the Hosmer-Lemeshow test were used to evaluate the performance of the model. Decision curve analysis (DCA) was conducted to determine the clinical value of the nomogram. The Kaplan-Meier method was used for survival analysis and the multivariable Cox proportional hazards regression model was used to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS). Results: The sample included 244 patients who underwent surgical resection for primary lung adenocarcinoma. The training cohort included 199 patients (68 STAS-positive and 131 STAS-negative patients), and the testing cohort included 45 patients (15 STAS-positive and 30 STAS-negative patients). The preoperative CT features associated with STAS were shape, ground-glass opacity (GGO) ratio and spicules. The nomogram including these three factors had good discriminative power, and the areas under the ROC curve were 0.875 and 0.922 for the training and testing data sets, respectively, with well-fitted calibration curves. DCA showed that the nomogram was clinically useful. STAS-positive patients had significantly worse OS and RFS than STAS-negative patients (both P<0.01). OS and RFS at 5-year for STAS-positive patients were 63.1% and 59.5%, respectively. Multivariate analysis showed that age [hazard ratio (HR), 1.1; 95% confidence interval (CI): 1.035-1.169; P=0.002], diameter (HR, 1.06; 95% CI: 1.04-1.11; P=0.03) and surgical margin (HR, 32.8; 95% CI: 6.8-158.3; P<0.001) were independent risk factors for OS. Adjuvant therapy (HR, 7.345; 95% CI: 2.52-21.41; P<0.001), N stage (N2) (HR, 0.239; 95% CI: 0.069-0.828; P=0.02) and surgical margin (HR, 15.6; 95% CI: 5.9-41.1; P<0.001) were found to be independent risk factors for RFS. Conclusions: The outcome of STAS-positive patients was worse. The nomogram incorporating the identified CT features could be applied to facilitate individualized preoperative prediction of STAS and selection of rational therapy.

The effect of electromyographic feedback functional electrical stimulation on the plantar pressure in stroke patients with foot drop.

Purpose: The purpose of this study was to observe, using Footscan analysis, the effect of electromyographic feedback functional electrical stimulation (FES) on the changes in the plantar pressure of drop foot patients. Methods: This case-control study enrolled 34 stroke patients with foot drop. There were 17 cases received FES for 20 min per day, 5 days per week for 4 weeks (the FES group) and the other 17 cases only received basic rehabilitations (the control group). Before and after 4 weeks, the walking speed, spatiotemporal parameters and plantar pressure were measured. Results: After 4 weeks treatments, Both the FES and control groups had increased walking speed and single stance phase percentage, decreased step length symmetry index (SI), double stance phase percentage and start time of the heel after 4 weeks (p < 0.05). The increase in walking speed and decrease in step length SI in the FES group were more significant than the control group after 4 weeks (p < 0.05). The FES group had an increased initial contact phase, decreased SI of the maximal force (Max F) and impulse in the medial heel after 4 weeks (p < 0.05). Conclusion: The advantages of FES were: the improvement of gait speed, step length SI, and the enhancement of propulsion force were more significant. The initial contact phase was closer to the normal range, which implies that the control of ankle dorsiflexion was improved. The plantar dynamic parameters between the two sides of the foot were more balanced than the control group. FES is more effective than basic rehabilitations for stroke patients with foot drop based on current spatiotemporal parameters and plantar pressure results.

Cardiovascular MRI Reference Ranges for Heart, Aorta, and Pulmonary Artery in Healthy Chinese Children.

BACKGROUND: Cardiovascular magnetic resonance (cardiac MR) reference ranges in Chinese children are lacking. PURPOSE: To establish age- and sex-specific reference ranges for cardiac MR parameters in a cohort of healthy Chinese children. STUDY TYPE: Retrospective. SUBJECTS: One hundred ninety-six healthy children (mean age 9.5 ± 3.6 years, 111 boys). FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession. ASSESSMENT: Biventricular volume and ejection fractions (EF), left atrial (LA) volume, right atrial (RA) area, left ventricular (LV) mass and thickness, aortic root (AR), and main pulmonary artery (MPA) dimensions were measured. Parameters were compared between age groups and sex. The relationships between parameters and age, body mass index (BMI) and body surface area (BSA) were investigated. STATISTICAL TESTS: Independent-samples t tests; Pearson's correlation. A P value <0.05 was considered statistically significant. RESULTS: Generally, boys exhibited greater absolute measurements of LV volume (end-diastolic: 94.4 ± 29.5 vs. 81.3 ± 31.0 mL), LA volume (end-diastolic: 42.6 ± 13.4 vs. 38.0 ± 13.3 mL), RA area (end-diastolic: 11.6 ± 2.5 vs. 10.8 ± 2.6 cm2), LV thickness (base: 4.4 ± 1.1 vs. 3.8 ± 0.9 mm), AR dimensions (annuls: 16.3 ± 2.7 vs. 15.0 ± 2.8 mm), and MPA dimensions (14.3 ± 2.3 vs. 13.1 ± 2.4 mm) than girls did. However, these differences were not observed when the measurements were normalized to BSA (LV volume: 75.3 ± 11.7 vs. 71.9 ± 12.3 mL/m2, P = 0.052; LA volume: 34.8 ± 8.9 vs. 34.5 ± 7.6 mL/m2, P = 0.783; RA area: 9.7 ± 2.3 vs. 10.2 ± 2.3 cm2/m2, P = 0.107; LV thickness: 3.6 ± 0.7 vs. 3.6 ± 0.9 mm/m2, P = 0.990; AR: 13.6 ± 2.7 vs. 14.3 ± 3.4 mm/m2, P = 0.108; MPA: 11.9 ± 2.3 vs. 12.4 ± 2.4 mm/m2, P = 0.118). Boys had greater RV volume (end-diastolic: 98.7 ± 33.5 vs. 82.7 ± 33.1 mL) and LV mass (52.6 ± 20.2 vs. 41.4 ± 16.0 g) compared to girls, irrespective of whether the values were indexed or not for BSA. Additionally, there were significant associations between age, BMI, and BSA with biventricular volume, LA volume, RA area, LV mass and thickness, AR and MPA dimensions in both boys and girls. DATA CONCLUSION: This study suggests reference ranges at 1.5 T for Chinese children. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Third Harmonic Generation in Thin NbOI2 and TaOI2.

The niobium oxide dihalides have recently been identified as a new class of van der Waals materials exhibiting exceptionally large second-order nonlinear optical responses and robust in-plane ferroelectricity. In contrast to second-order nonlinear processes, third-order optical nonlinearities can arise irrespective of whether a crystal lattice is centrosymmetric. Here, we report third harmonic generation (THG) in two-dimensional (2D) transition metal oxide iodides, namely NbOI2 and TaOI2. We observe a comparable THG intensity from both materials. By benchmarking against THG from monolayer WS2, we deduce that the third-order susceptibility is approximately on the same order. THG resonances are revealed at different excitation wavelengths, likely due to enhancement by excitonic states and band edge resonances. The THG intensity increases for material thicknesses up to 30 nm, owing to weak interlayer coupling. After this threshold, it shows saturation or a decrease, due to optical interference effects. Our results establish niobium and tantalum oxide iodides as promising 2D materials for third-order nonlinear optics, with intrinsic in-plane ferroelectricity and thickness-tunable nonlinear efficiency.

Long-term Radiological and Pulmonary Function Abnormalities at 3-year post COVID-19 Hospitalization: A Longitudinal Cohort Study.

BACKGROUND: This study aimed to evaluate the longitudinal progression of residual lung abnormalities (ground-glass opacities, reticulations, and fibrotic-like changes) and pulmonary function, three years following coronavirus disease 2019(COVID-19). METHODS: This prospective, longitudinal cohort study enrolled COVID-19 survivors who exhibited residual lung abnormalities upon discharge from two hospitals. Follow-up assessments were conducted at 6 months, 12 months, 2 years, and 3 years post-discharge, and included pulmonary function tests, 6-minute walk distance (6MWD), chest CT scans, and symptom questionnaires. Non-COVID-19 controls were retrospectively recruited for comparative analysis. RESULTS: 728 COVID-19 survivors and 792 controls were included. From 6 months to 3 years, there was a gradual improvement in reduced diffusing capacity of the lungs for carbon monoxide (DLCO＜80% predicted, 49% versus 38%, p=0.001), 6MWD (496 m versus 510 m, p=0.002) and residual lung abnormalities(46% versus 36%, p<0.001), regardless of the disease severity. Patients with residual lung abnormalities at 3 years more commonly had respiratory symptoms (32% versus 16%, p<0.001), lower 6MWD (494 m versus 510 m, p=0.003), and abnormal DLCO (57% versus 27%, p<0.001) compared to those with complete resolution. Compared to the controls, the proportion of DLCO impairment (38% versus 17%, p<0.001) and respiratory symptoms (23% versus 2.2%, p<0.001) were significantly higher in the matched COVID-19 survivors at the 3-year follow-up. CONCLUSIONS: Most patients exhibited improvement in radiological abnormalities and pulmonary function over time following COVID-19. However, more than one-third continued to have persistent lung abnormalities at the 3-year mark, which were associated with respiratory symptoms and reduced diffusion capacity.

Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy.

Left ventricular regional wall thickness (LVRWT) is an independent predictor of morbidity and mortality in cardiovascular diseases (CVDs). To identify specific genetic influences on individual LVRWT, we established a novel deep learning algorithm to calculate 12 LVRWTs accurately in 42,194 individuals from the UK Biobank with cardiac magnetic resonance (CMR) imaging. Genome-wide association studies of CMR-derived 12 LVRWTs identified 72 significant genetic loci associated with at least one LVRWT phenotype (P < 5 × 10-8), which were revealed to actively participate in heart development and contraction pathways. Significant causal relationships were observed between the LVRWT traits and hypertrophic cardiomyopathy (HCM) using genetic correlation and Mendelian randomization analyses (P < 0.01). The polygenic risk score of inferoseptal LVRWT at end systole exhibited a notable association with incident HCM, facilitating the identification of high-risk individuals. The findings yield insights into the genetic determinants of LVRWT phenotypes and shed light on the biological basis for HCM etiology.

Genetic Variants That Impact Alternative Polyadenylation in Cancer Represent Candidate Causal Risk Loci.

Alternative polyadenylation (APA) is emerging as a major mechanism of posttranscriptional regulation. APA can impact the development and progression of cancer, suggesting that the genetic determinants of APA might play an important role in regulating cancer risk. Here, we depicted a pan-cancer atlas of human APA quantitative trait loci (apaQTL), containing approximately 0.7 million apaQTLs across 32 cancer types. Systematic multiomics analyses indicated that cancer apaQTLs could contribute to APA regulation by altering poly(A) motifs, RNA-binding proteins (RBP), and chromatin regulatory elements and were preferentially enriched in genome-wide association studies (GWAS)-identified cancer susceptibility loci. Moreover, apaQTL-related genes (aGene) were broadly related to cancer signaling pathways, high mutational burden, immune infiltration, and drug response, implicating their potential as therapeutic targets. Furthermore, apaQTLs were mapped in Chinese colorectal cancer tumor tissues and then screened for functional apaQTLs associated with colorectal cancer risk in 17,789 cases and 19,951 controls using GWAS-ChIP data, with independent validation in a large-scale population consisting of 6,024 cases and 10,022 controls. A multi-ancestry-associated apaQTL variant rs1020670 with a C>G change in DNM1L was identified, and the G allele contributed to an increased risk of colorectal cancer. Mechanistically, the risk variant promoted aberrant APA and facilitated higher usage of DNM1L proximal poly(A) sites mediated by the RBP CSTF2T, which led to higher expression of DNM1L with a short 3'UTR. This stabilized DNM1L to upregulate its expression, provoking colorectal cancer cell proliferation. Collectively, these findings generate a resource for understanding APA regulation and the genetic basis of human cancers, providing insights into cancer etiology. SIGNIFICANCE: Cancer risk is mediated by alternative polyadenylation quantitative trait loci, including the rs1020670-G variant that promotes alternative polyadenylation of DNM1L and increases colorectal cancer risk.

Digital light processing 3D printing for microfluidic chips with enhanced resolution via dosing- and zoning-controlled vat photopolymerization.

Conventional manufacturing techniques to fabricate microfluidic chips, such as soft lithography and hot embossing process, have limitations that include difficulty in preparing multiple-layered structures, cost- and labor-consuming fabrication process, and low productivity. Digital light processing (DLP) technology has recently emerged as a cost-efficient microfabrication approach for the 3D printing of microfluidic chips; however, the fabrication resolution for microchannels is still limited to sub-100 microns at best. Here, we developed an innovative DLP printing strategy for high resolution and scalable microchannel fabrication by dosing- and zoning-controlled vat photopolymerization (DZC-VPP). Specifically, we proposed a modified mathematical model to precisely predict the accumulated UV irradiance for resin photopolymerization, thereby providing guidance for the fabrication of microchannels with enhanced resolution. By fine-tuning the printing parameters, including optical irradiance, exposure time, projection region, and step distance, we can precisely tailor the penetration irradiance stemming from the photopolymerization of the neighboring resin layers, thereby preventing channel blockage due to UV overexposure or compromised bonding stability owing to insufficient resin curing. Remarkably, this strategy can allow the preparation of microchannels with cross-sectional dimensions of 20 µm × 20 µm using a commercial printer with a pixel size of 10 µm × 10 µm; this is significantly higher resolution than previous reports. In addition, this method can enable the scalable and biocompatible fabrication of microfluidic drop-maker units that can be used for cell encapsulation. In general, the current DZC-VPP method can enable major advances in precise and scalable microchannel fabrication and represents a significant step forward for widespread applications of microfluidics-based techniques in biomedical fields.

Value of radiomics in differentiating synchronous double primary lung adenocarcinomas from intrapulmonary metastasis.

Background: Distinguishing synchronous double primary lung adenocarcinoma (SDPLA) from intrapulmonary metastasis (IPM) of lung cancer has significant therapeutic and prognostic values. This study aimed to develop and validate a CT-based radiomics model to differentiate SDPLA from IPM. Methods: A total of 153 patients (93 SDPLA and 60 IPM) with 306 pathologically confirmed lesions were retrospectively studied. CT morphological features were also recorded. Region of interest (ROI) segmentation was performed semiautomatically, and 1,037 radiomics features were extracted from every segmented lesion The differences of radiomics features were defined as the relative net difference in radiomics features between the two lesions on CT. Those low reliable (ICC <0.75) and redundant (r>0.9) features were excluded by intraclass correlation coefficients (ICC) and Pearson's correlation. Multivariate logistic regression (LR) algorithm was used to establish the classification model according to the selected features. The radiomics model was based on the four most contributing differences of radiomics features. Clinical-CT model and MixModel were based on selected clinical and CT features only and the combination of clinical-CT and Rad-score, respectively. Results: In both the training and testing cohorts, the area under the curves (AUCs) of the radiomics model were larger than those of the clinical-CT model (0.944 vs. 0.793 and 0.886 vs. 0.735 on training and testing cohorts, respectively), and statistically significant differences between the two models in the testing set were found (P<0.001). Meanwhile, three radiologists had sensitivities of 84.2%, 63.9%, and 68.4%, and specificities of 76.9%, 69.2%, and 76.9% in differentiating 19 SDPLA cases from 13 cases of IPM in the testing set. Compared with the performance of the three radiologists, the radiomics model showed better accuracy to the patients in both the training and testing cohorts. Among the three models, the radiomics model showed the best net benefits. Conclusions: The differences of radiomics features showed excellent diagnostic performance for preoperative differentiation between synchronous double primary lung adenocarcinoma from interpulmonary metastasis, superior to the clinical model and decisions made by radiologists.

Dual-energy CT-based radiomics for predicting invasiveness of lung adenocarcinoma appearing as ground-glass nodules.

Objectives: To explore the value of radiomics based on Dual-energy CT (DECT) for discriminating preinvasive or MIA from IA appearing as GGNs before surgery. Methods: The retrospective study included 92 patients with lung adenocarcinoma comprising 30 IA and 62 preinvasive-MIA, which were further divided into a training (n=64) and a test set (n=28). Clinical and radiographic features along with quantitative parameters were recorded. Radiomics features were derived from virtual monoenergetic images (VMI), including 50kev and 150kev images. Intraclass correlation coefficients (ICCs), Pearson's correlation analysis and least absolute shrinkage and selection operator (LASSO) penalized logistic regression were conducted to eliminate unstable and redundant features. The performance of the models was evaluated by area under the curve (AUC) and the clinical utility was assessed using decision curve analysis (DCA). Results: The DECT-based radiomics model performed well with an AUC of 0.957 and 0.865 in the training and test set. The clinical-DECT model, comprising sex, age, tumor size, density, smoking, alcohol, effective atomic number, and normalized iodine concentration, had an AUC of 0.929 in the training and 0.719 in the test set. In addition, the radiomics model revealed a higher AUC value and a greater net benefit to patients than the clinical-DECT model. Conclusion: DECT-based radiomics features were valuable in predicting the invasiveness of GGNs, yielding a better predictive performance than the clinical-DECT model.

HSPA12A was identified as a key driver in colorectal cancer GWAS loci 10q26.12 and modulated by an enhancer-promoter interaction.

Although genome-wide association studies (GWASs) have identified over 100 colorectal cancer (CRC) risk loci, an understanding of causal genes or risk variants and their biological functions in these loci remain unclear. Recently, genomic loci 10q26.12 with lead SNP rs1665650 was identified as an essential CRC risk loci of Asian populations. However, the functional mechanism of this region has not been fully clarified. Here, we applied an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk loci 10q26.12. Notably, HSPA12A had the most significant effect among the identified genes and functioned as a crucial oncogene facilitating cell proliferation. Moreover, we conducted an integrative fine-mapping analysis to identify putative casual variants and further explored their association with CRC risk in a large-scale Chinese population consisting of 4054 cases and 4054 controls and also independently validated in 5208 cases and 20,832 controls from the UK biobank cohort. We identified a risk SNP rs7093835 in the intron of HSPA12A that was significantly associated with an increased risk of CRC (OR 1.23, 95% CI 1.08-1.41, P = 1.92 × 10-3). Mechanistically, the risk variant could facilitate an enhancer-promoter interaction mediated by the transcriptional factor (TF) GRHL1 and ultimately upregulate HSPA12A expression, which provides functional evidence to support our population findings. Collectively, our study reveals the important role of HSPA12A in CRC development and illustrates a novel enhancer-promoter interaction module between HSPA12A and its regulatory elements rs7093835, providing new insights into the etiology of CRC.

Saturated fatty acid intake, genetic risk and colorectal cancer incidence: A large-scale prospective cohort study.

Previous investigations mainly focused on the associations of dietary fatty acids with colorectal cancer (CRC) risk, which ignored gene-environment interaction and mechanisms interpretation. We conducted a case-control study (751 cases and 3058 controls) and a prospective cohort study (125 021 participants) to explore the associations between dietary fatty acids, genetic risks, and CRC. Results showed that high intake of saturated fatty acid (SFA) was associated with a higher risk of CRC than low SFA intake (HR =1.22, 95% CI:1.02-1.46). Participants at high genetic risk had a greater risk of CRC with the HR of 2.48 (2.11-2.91) than those at low genetic risk. A multiplicative interaction of genetic risk and SFA intake with incident CRC risk was found (PInteraction = 7.59 × 10-20 ), demonstrating that participants with high genetic risk and high SFA intake had a 3.75-fold greater risk of CRC than those with low genetic risk and low SFA intake. Furthermore, incorporating PRS and SFA into traditional clinical risk factors improved the discriminatory accuracy for CRC risk stratification (AUC from 0.706 to 0.731). Multi-omics data showed that exposure to SFA-rich high-fat dietary (HFD) can responsively induce epigenome reprogramming of some oncogenes and pathological activation of fatty acid metabolism pathway, which may contribute to CRC development through changes in gut microbiomes, metabolites, and tumor-infiltrating immune cells. These findings suggest that individuals with high genetic risk of CRC may benefit from reducing SFA intake. The incorporation of SFA intake and PRS into traditional clinical risk factors will help improve high-risk sub-populations in individualized CRC prevention.

Hyaluronic acid-based multifunctional carriers for applications in regenerative medicine: A review.

Hyaluronic acid (HA) is an important type of naturally derived carbohydrate polymer with specific polysaccharide macromolecular structures and multifaceted biological functions, including biocompatibility, low immunogenicity, biodegradability, and bioactivity. Specifically, HA hydrogels in a microscopic scale have been widely used for biomedical applications, such as drug delivery, tissue engineering, and medical cosmetology, considering their superior properties outperforming the more conventional monolithic hydrogels in network homogeneity, degradation profile, permeability, and injectability. Herein, we reviewed the recent progress in the preparation and applications of HA microgels in biomedical fields. We first summarized the fabrication of HA microgels by focusing on the different crosslinking/polymerization schemes for HA gelation and the miniaturized fabrication techniques for producing HA-based microparticles. We then highlighted the use of HA-based microgels for different applications in regenerative medicine, including cartilage repair, bioactive delivery, diagnostic imaging, modular tissue engineering. Finally, we discussed the challenges and future perspectives in bridging the translational gap in the utilization of HA-based microgels in regenerative medicine.

Large-scale single-cell encapsulation in microgels through metastable droplet-templating combined with microfluidic-integration.

Current techniques for the generation of cell-laden microgels are limited by numerous challenges, including poorly uncontrolled batch-to-batch variations, processes that are both labor- and time-consuming, the high expense of devices and reagents, and low production rates; this hampers the translation of laboratory findings to clinical applications. To address these challenges, we develop a droplet-based microfluidic strategy based on metastable droplet-templating and microchannel integration for the substantial large-scale production of single cell-laden alginate microgels. Specifically, we present a continuous processing method for microgel generation by introducing amphiphilic perfluoronated alcohols to obtain metastable emulsion droplets as sacrificial templates. In addition, to adapt to the metastable emulsion system, integrated microfluidic chips containing 80 drop-maker units are designed and optimized based on the computational fluid dynamics simulation. This strategy allows single cell encapsulation in microgels at a maximum production rate of 10 ml h-1of cell suspension while retaining cell viability and functionality. These results represent a significant advance toward using cell-laden microgels for clinical-relevant applications, including cell therapy, tissue regeneration and 3D bioprinting.

Thermo-responsive fluorinated surfactant for on-demand demulsification of microfluidic droplets.

Droplet microfluidics has recently emerged as a powerful platform for a variety of biomedical applications including microreactors, bioactive compound encapsulation, and single cell culture and analysis; all these applications require long-term droplet stability, which, however, makes breaking the emulsion and retrieving the loaded samples difficult. Herein, we developed a novel class of thermo-responsive fluorosurfactants to control the droplet status simply by temperature. The surfactants were synthesized by coupling perfluorinated polyethers (PFPEs) with a thermo-responsive block of poly(N-isopropylacrylamide) (pNIPAM) or poly(2-ethyl-2-oxazoline) (pEtOx) with lower critical solution temperature (LCST). These diblock surfactants can stabilize the emulsion at temperatures below LCST due to the hydrophilic head, which became hydrophobic upon increasing the ambient temperature above LCST, thereby destabilizing the droplets and realizing demulsification simply via temperature control. The diblock surfactant can be applied for templating cell encapsulation using alginate microgels, which allowed one-step and high-throughput microfluidic generation of cell-laden microgels without compromising cell viability. This non-invasive, on-demand demulsification strategy provides a high degree of freedom for microencapsulation and on-demand recovery of the samples or reaction products within the droplets, which opens a new avenue for a wide range of applications of droplet-templating microfluidics.

Comparison of walking quality variables between incomplete spinal cord injury patients and healthy subjects by using a footscan plantar pressure system.

The main goal of spinal cord rehabilitation is to restore walking ability and improve walking quality after spinal cord injury (SCI). The spatiotemporal parameters of walking and the parameters of plantar pressure can be obtained using a plantar pressure analysis system. Previous studies have reported step asymmetry in patients with bilateral SCI. However, the asymmetry of other parameters in patients with SCI has not been reported. This was a prospective, cross-sectional study, which included 23 patients with SCI, aged 48.1 ± 14.5 years, and 28 healthy subjects, aged 47.1 ± 9.8 years. All subjects underwent bare foot walking on a plantar pressure measurement device to measure walking speed and spatiotemporal parameters. Compared with healthy subjects, SCI patients had slower walking speed, longer stride time and stance time, larger stance phase percentage, and shorter stride length. The peak pressures under the metatarsal heads and toe were lower in SCI patients than in healthy subjects. In the heel, regional impulse and the contact area percentage in SCI patients were higher than those in healthy subjects. The symmetry indexes of stance time, step length, maximum force, impulse and contact area were increased in SCI patients, indicating a decline in symmetry. The results confirm that the gait quality, including spatiotemporal variables and plantar pressure parameters, and symmetry index were lower in SCI patients compared with healthy subjects. Plantar pressure parameters and symmetry index could be sensitive quantitative parameters to improve gait quality of SCI patients. The protocols were approved by the Clinical Research Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2015PS54J) on August 13, 2015. This trial was registered in the ISRCTN Registry (ISRCTN42544587) on August 22, 2018. Protocol version: 1.0.

Electroacupuncture effects in a rat model of complete Freund's adjuvant-induced inflammatory pain: antinociceptive effects enhanced and tolerance development accelerated.

We have previously shown that electroacupuncture (EA) produced antinociception through the release of endogenous opioid peptides to activate opioid receptors during acute nociception. EA produced tolerance after its prolonged application. It has reported that 100 Hz EA could reduce mechanical hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory nociception rats. The present study aims to investigate the antinociceptive effect of EA and the development of EA tolerance in chronic inflammatory nociception rats with CFA injection into the hind paw plantar. The results showed that the antinociceptive effect of 100 Hz EA was significantly enhanced in CFA-induced inflammatory nociception rats. Naloxone at 20 mg/kg could significantly block this antinociceptive effect. Chronic tolerance to EA was developed faster in CFA-induced inflammatory nociception rats than in normal rats. Therefore, 100 Hz EA could enhance antinociceptive effects and accelerate tolerance development in CFA-induced inflammatory nociception rats. The enhancement of EA antinociceptive effect in CFA-induced inflammatory nociception rats might involve the endogenous opioid peptides such as dynorphin.

Feminizing/demasculinizing effects of polychlorinated biphenyls on the secondary sexual development of Xenopus laevis.

We have previously demonstrated that polychlorinated biphenyls (PCBs) have caused phenotypic feminization/demasculinization of gonadal development in Xenopus laevis. Whether PCBs affect secondary sexual development has remained unknown. In this study, X. laevis tadpoles were exposed to Aroclor1254 and PCB(3) from stage 46/47 (system of Nieuwkoop and Faber) for up to 1 month postmetamorphosis. After 24 months postmetamorphosis, the degree of secondary sexual development was examined. Male oviducts were observed in some of the PCB-exposed male frogs, but not in control males. These male oviducts had not completely developed in histological structure when compared with mature female oviducts. Larynx weight and width of PCB-exposed males were significantly less than those of control males. Laryngeal histology showed that PCBs inhibited cartilaginous and muscular development of male frogs, i.e. elastic cartilages had not completely developed and laryngeal muscle fibers were smaller. In a further study on adult male frogs, a decrease in serum testosterone level was found in PCB-exposed frogs compared with controls, but serum estradiol level was not significantly affected. Our study suggests that PCBs can cause phenotypic feminization/demasculinization of male genital ducts and larynges, and these effects may, in part, result from the decrease in serum testosterone level in X. laevis.

CCK(B) receptor antagonist L365,260 potentiates the efficacy to and reverses chronic tolerance to electroacupuncture-induced analgesia in mice.

Cholecystokinin octapeptide (CCK-8) is a physiological antagonist of endogenous opioids in the central nervous system (CNS). Our previous work has shown that CCK-8 plays an important role in the development of tolerance to morphine analgesia and electroacupuncture (EA) analgesia in the rat. The present studies were designed to examine whether the CCK(B) receptor is involved in the modulation of EA analgesia and the development of EA tolerance in mice. The latency to flick the tail in the radiant heat was used as index to assess the efficacy of EA analgesia. Subcutaneous (s.c.) injection of the CCK(B) receptor antagonist L365,260 produced a dose-dependent (0.125-2.0 mg/kg) potentiation of the analgesia induced by 100 Hz EA, with a maximal effect occurred at 0.5 mg/kg. In addition, L365,260 (0.5 mg/kg) significantly reversed chronic tolerance to 100 Hz EA in mice. These results suggest that the CCK(B) receptor might play a role in the tonic inhibition of 100 Hz EA-induced analgesia and in the mediation of chronic tolerance to 100 Hz EA in mice. The results opened a way for further investigation of the function of CCK-8 in pain modulation using inbred strains of mice.

Ketamine potentiates the effect of electroacupuncture on mechanical allodynia in a rat model of neuropathic pain.

Mu-opioid agonists and N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to attenuate mechanical allodynia in neuropathic pain models. We have previously reported that 2Hz electroacupuncture (EA) produced analgesia via releasing endogenous opioid peptides (i.e. beta-endorphin and endomorphin) and the activated micro-opioid receptors. The present study aimed to examine whether ketamine, an NMDA receptor antagonist, can enhance the anti-allodynic effects induced by 2Hz EA in a rat model of neuropathic pain following spinal nerve ligation (SNL). The results are as follows: (1) EA itself or i.p. injection of ketamine reduced mechanical allodynia (i.e. increase in withdrawal threshold). (2) Although injection of ketamine at a low dose (1.0mg/kg) alone did not influence mechanical withdrawal threshold, combination of ketamine at this dose with EA produced more potent anti-allodynic effect than that induced by EA alone. (3) The anti-allodynic effect of EA combined with ketamine could be reversed by i.p. injection of naloxone (2.0 mg/kg). These results suggested that ketamine potentiate the anti-allodynic of EA in rats with spinal nerve ligation, and endogenous opioid system is likely to be involved in this process.