[Ilizarov technique combined with center of rotation dome-shaped osteotomy for the treatment of juvenile distal femoral valgus deformity].

OBJECTIVE: To investigate the effect of Ilizarov technique combined with rotational center dome-shaped osteotomy in the treatment of juvenile distal femoral valgus deformity. METHODS: A retrospective study was conducted to analyze the clinical data of 11 patients with valgus deformity of the distal femur who had been admitted and followed up completely from January 2016 to October 2020. There were 7 males and 4 females. The 6 patients were on the right side and 5 patients were on the left side. The age ranged from 10 to 14 years old. The center of roration of angulation(CORA) was identified at the distal femur deformity, and dome-shaped osteotomy was performed with the CORA as the midpoint. The annular external fixator was installed according to the needle threading principle of Ilizarov external fixation, and the distal femur was cut off. The valgus deformity under visual inspection of the distal femur was corrected immediately, and the external fixator was fixed and maintained. The residual deformity and shortening were corrected according to the force line and length of the lower limbs suggested by the weight-bearing full-length anteroposterior and lateral X-rays of both lower limbs. RESULTS: All 11 patients were followed up for 13 to 25 months. The time of wearing external fixator was 12 to 17 weeks. In the last follow-up, both lower limbs were measured by the weight-bearing full-length anteroposterior and lateral X-rays, and the length of both lower limbs of 11 patients were equal, and the deformities were corrected. The score of hospital for special surgery (HSS) was used to evaluate the knee function, all of which were excellent. CONCLUSION: The Ilizarov technique was applied in the treatment of distal femoral valgus deformity in adolescents using a rotating central dome-shaped osteotomy. Visual femoral valgus deformity was corrected immediately during the operation. After the operation, residual deformities and shortening were dynamically adjusted and corrected according to the force line and shortening degree of lower extremities indicated by the weight-bearing anteroposterior and lateral radiographs of both lower limbs, with minimal damage and fast recovery.

ISIS 449884 Injection Add-On to Metformin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase II Clinical Study.

INTRODUCTION: ISIS 449884, a 2'-O-methoxyethyl antisense oligonucleotide that targets the glucagon receptor (GCGR), has demonstrated an ability to reduce hepatic glucose output and lower the blood glucose level. The primary objective of this study was to investigate the safety and efficacy of ISIS 449884 as an add-on to metformin in a population of Chinese patients with type 2 diabetes mellitus (T2DM). METHOD: This was a multicenter, placebo-controlled (2:1), randomized, double-blind, parallel-enrollment, multiple-dose phase II study in Chinese patients with T2DM. A total of 90 patients who were uncontrolled by stable metformin monotherapy were randomized into three cohorts. Thirty subjects were enrolled in each cohort and received injections of ISIS 449884 (50 mg or 60 mg weekly or 100 mg every other week) or a corresponding volume of placebo (0.25 mL and 0.3 mL weekly or 0.5 mL every other week) subcutaneously in a 2:1 ratio for 16 weeks. RESULTS: The primary efficacy endpoint was analyzed in 88 subjects (ISIS 449884, n = 59; placebo, n = 29). The corrected LS mean change from baseline in glycated hemoglobin (HbA1c) at week 17 in the pooled ISIS 449884 treatment group was - 1.31% (95% CI - 1.66%, - 0.96%), and that in the pooled placebo group was 0.15% (95% CI - 0.37%, 0.66%). The LS mean difference between the two groups was - 1.46% (95% CI - 1.92%, - 1.00%, P < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 53/60 subjects (88.3%) and 25/30 subjects (83.3%) in the pooled ISIS 449884 treatment group and the pooled placebo group, respectively, with similar incidences. Drug-related TEAEs occurred in 41/60 subjects (68.3%) and 9/30 subjects (30.0%), respectively. TEAEs of grade 3 or higher occurred in 5/60 (8.3%) subjects and 2/30 (6.7%) subjects, respectively, and none of them were drug related. CONCLUSIONS: The ISIS 449884 injection add-on to metformin significantly reduced HbA1c in patients with T2DM uncontrolled by stable metformin monotherapy and showed an acceptable benefit/risk profile. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn , CTR20191096.

A quinolinyl resveratrol derivative alleviates acute ischemic stroke injury by promoting mitophagy for neuroprotection via targeting CK2α'.

Ischemic stroke (IS) is a serious threat to human health. The naturally derived small molecule (E)-5-(2-(quinolin-4-yl) ethenyl) benzene-1,3-diol (RV01) is a quinolinyl analog of resveratrol with great potential in the treatment of IS. The aim of this study was to investigate the potential mechanisms and targets for the protective effect of the RV01 on IS. The mouse middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen-glucose deprivation and reperfusion (OGD/R) models were employed to evaluate the effects of RV01 on ischemic injury and neuroprotection. RV01 was found to significantly increase the survival of SH-SY5Y cells and prevent OGD/R-induced apoptosis in SH-SY5Y cells. Furthermore, RV01 reduced oxidative stress and mitochondrial damage by promoting mitophagy in OGD/R-exposed SH-SY5Y cells. Knockdown of CK2α' abolished the RV01-mediated promotion on mitophagy and alleviation on mitochondrial damage as well as neuronal injury after OGD/R. These results were further confirmed by molecular docking, drug affinity responsive target stability and cellular thermal shift assay analysis. Importantly, in vivo study showed that treatment with the CK2α' inhibitor CX-4945 abolished the RV01-mediated alleviation of cerebral infarct volume, brain edema, cerebral blood flow and neurological deficit in MCAO/R mice. These data suggest that RV01 effectively reduces damage caused by acute ischemic stroke by promoting mitophagy through its interaction with CK2α'. These findings offer valuable insights into the underlying mechanisms through which RV01 exerts its therapeutic effects on IS.

Lower psoas mass indicates worse prognosis in percutaneous vertebroplasty-treated osteoporotic vertebral compression fracture.

The correlation between lower psoas mass and the prognosis of osteoporotic vertebral compression fractures (OVCF) is still unclear. This study aims to investigate the impact of lower psoas mass on the prognosis of patients undergoing percutaneous vertebroplasty (PVP). One hundred and sixty-three elderly patients who underwent single-segment PVP from January 2018 to December 2021 were included. The psoas to L4 vertebral index (PLVI) via MRI were measured to assess psoas mass. Patients were divided into high PLVI (> 0.79) and low PLVI (≤ 0.79) groups based on the median PLVI in the cohort. The basic information (age, gender, body mass index (BMI) and bone mineral density (BMD)), surgical intervention-related elements (duration of operation, latency to ambulation, period of hospital stay, and surgical site), postoperative clinical outcomes (Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, Japanese Orthopaedic Association (JOA) scores), and incidence of secondary fractures) were compared. Patients showed no statistically significant differences in terms of age, gender, surgical sute, BMI, BMD and preoperative VAS, ODI, JOA scores (P > 0.05) between the two groups. However, there were significant differences in terms of latency to ambulation, period of hospital stay (P < 0.05). VAS, ODI, and JOA scores at 1, 6, and 12 months after surgery showed that the high PLVI group had significantly better outcomes than the low PLVI group (P < 0.05). Additionally, the low PLVI group had a significantly higher incidence of recurrent fracture (P < 0.05). Lower psoas mass can reduce the clinical effect of PVP in patients with osteoporotic vertebral compression fractures, and is a risk factor for recurrent vertebral fracture.

Parasite-derived microRNA let-7-5p detection for metacestodiasis based on rolling circular amplification-assisted CRISPR/Cas9.

Metacestodiasis is an infectious disease caused by the larval stage of cestode parasites. This disease poses a serious health hazard to wildlife, livestock, and humans, and it incurs substantial economic losses by impacting the safety of the livestock industry, the quality of meat production, and public health security. Unfortunately, there is currently no available molecular diagnostic method capable of distinguishing cysticercus- and Echinococcus-derived microRNAs (miRNAs) from other helminthes and hosts in the plasma of metacestode-infected animals. This study aims to develop a specific, sensitive, and cost-efficient molecular diagnostic method for cysticercosis and echinococcosis, particularly for early detection. The study developed a rolling circular amplification (RCA)-assisted CRISPR/Cas9 detection method based on parasite-derived miRNA let-7-5p. Using a series of dilutions of the let-7 standard, the limit of detection (LOD) of the qPCR, RCA, and RCA-assisted CRISPR/Cas9 methods was compared. The specificity of qPCR and CRISPR/Cas9 was evaluated using four artificially synthesized let-7 standards from different species. A total of 151 plasma samples were used to evaluate the diagnostic performance. Additionally, the study also assessed the correlation between plasma levels of let-7-5p, the number of Taenia pisiformis cysticerci, and the weight of Echinococcus multilocularis cysts. The results demonstrated that the RCA-assisted CRISPR/Cas9 assay could significantly distinguish let-7 from cestodes and other species, achieving a LOD of 10 aM; the diagnostic sensitivity and specificity for rabbit cysticercosis and mouse E. multilocularis were 100% and 97.67%, and 100% and 100%, respectively. Notably, let-7-5p gradually increased in the plasma of T. pisiformis-infected rabbits from 15 days post infection (dpi), peaked at 60 dpi, and persisted until 120 dpi. In E. multilocularis-infected mice, let-7-5p gradually increased from 15 dpi and persisted until 90 dpi. Furthermore, the expression of let-7-5p positively correlated with the number of cysticerci and cyst weight. These results indicated that the let-7-5p-based RCA-assisted CRISPR/Cas9 assay is a sensitive and specific detection method that can be used as a universal diagnostic method for metacestodiasis, particularly for early diagnosis (15 dpi).

2,2- dimethylbenzopyran derivatives containing pyridone structural fragments as selective dual-targeting inhibitors of HIF-1α and EZH2 for the treatment of lung cancer.

We formerly reported that EZH2 inhibitors sensitized HIF-1 inhibitor-resistant cells and inhibited HIF-1α to promote SUZ12 transcription, leading to enhanced EZH2 enzyme activity and elevated H3K27me3 levels, and conversely, inhibition of EZH2 promoted HIF-1α transcription. HIF-1α and EZH2 interacted to form a negative feedback loop that reinforced each other's activity. In this paper, a series of 2,2- dimethylbenzopyran derivatives containing pyridone structural fragments were designed and synthesized with DYB-03, a HIF-1α inhibitor previously reported by our group, and Tazemetostat, an EZH2 inhibitor approved by FDA, as lead compounds. Among these compounds, D-01 had significant inhibitory activities on HIF-1α and EZH2. In vitro experiments showed that D-01 significantly inhibited the migration of A549 cells, clone, invasion and angiogenesis. Moreover, D-01 had good pharmacokinetic profiles. All the results about compound D-01 could lay a foundation for the research and development of HIF-1α and EZH2 dual-targeting compounds.

mmu-miR-374b-5p modulated inflammatory factors via downregulation of C/EBP ß/NF-κB signaling in Kupffer cells during Echinococcus multilocularis infection.

BACKGROUND: Alveolar echinococcosis (AE) is an important infectious disease caused by the metacestode larvae of Echinococcus multilocularis, seriously threatening global public health security. Kupffer cells (KCs) play important roles in liver inflammatory response. However, their role in hepatic alveolar echinococcosis has not yet been fully elucidated. METHODS: In this study, qRT-PCR was used to detect the expression level of miR-374b-5p in KCs. The target gene of miR-374b-5p was identified through luciferase reporter assays and loss of function and gains. Critical genes involved in NFκB signaling pathway were analyzed by qRT-PCR and western blot. RESULTS: This study reported that miR-374b-5p was significantly upregulated in KCs during E. multilocularis infection and further showed that miR-374b-5p was able to bind to the 3'-UTR of the C/EBP ß gene and suppressed its expression. The expression levels of NF-κBp65, p-NF-κBp65 and pro-inflammatory factors including iNOS, TNFα and IL6 were attenuated after overexpression of miR-374b-5p while enhanced after suppression of miR-374b-5p. However, the Arg1 expression level was promoted after overexpression of miR-374b-5p while suppressed after downregulation of miR-374b-5p. Additionally, increased protein levels of NF-κBp65 and p-NF-κBp65 were found in the C/EBP ß-overexpressed KCs. CONCLUSIONS: These results demonstrated that miR-374b-5p probably regulated the expression of inflammatory factors via C/EBP ß/NF-κB signaling. This finding is helpful to explore the mechanism of inflammation regulation during E. multilocularis infection.

The Integrated Prediction of Clinical and Pathological Factors on the Prognosis of Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The primary objective was to construct a high-performing prognostic risk model to accurately forecast the prognosis of patients diagnosed with intrahepatic cholangiocarcinoma (iCCA). METHODS: We retrospectively collected clinical data from the MSK database on 125 patients diagnosed with iCCA. Random sampling was utilized to divide patients into a training set and a validation set, maintaining a ratio of 7:3. Univariate and multivariate Cox proportional hazards regression models were utilized to identify independent prognostic factors influencing OS. Based on these independent factors, a model nomogram was established. The performance of the prognostic prediction models was assessed through calibration curves and C-index calculations. The Kaplan-Meier method was used to plot survival curves. Time-dependent ROC curve was used to evaluate the accuracy of the model. RESULTS: A nomogram was developed, incorporating hepatitis C, CA19, tumor extent, tumor size, LVI, positive lymph nodes, and TMB as predictive factors. The C-index for the training set was .78 and the validation set was .68. Using the riskscore derived from the nomogram, patients were stratified into high- and low-risk groups. The high-risk group exhibited considerably lower OS and RFS compared to the low-risk group in the training set (P < .05). However, no significant difference was detected in RFS among different risk groups in the validation set (P > .05). The AUC for 1-year, 3-year, and 5-year survival was .89, .69, and .69, respectively. CONCLUSION: We successfully developed and validated a prognostic nomogram for iCCA, demonstrating its excellent accuracy in predicting patient outcomes and providing clinicians with a potential prognostic tool.

What are exposure biomarkers of rare earth elements for the ionic rare earth occupational population?

Rare earth elements (REEs) are widely utilized in industries. However, The specific exposure features of REEs and potential biomarkers of exposure in occupational populations remain unclear. In this study, we evaluated the external and internal REEs exposure levels among the participants working in the ionic rare earth smelting plant. For the external exposure, the concentrations of 14 REEs and total rare earth elements (ΣREEs) in airborne particles were significantly elevated in the REEs-exposed versus non-exposed group (P < 0.05). Meanwhile, the levels of Yttrium (Y), Gadolinium (Gd), Terbium (Tb), Dysprosium (Dy), Holmium (Ho), Thulium (Tm), Ytterbium (Yb), and ΣREEs in urine were higher in the REEs-exposed group compared to the non-exposed group (P < 0.05). Notably, a significant positive correlation was observed between Y in both the airborne particles and urine samples as well as Gd, and the Spearman correlation coefficient was 0.53 and 0.39 respectively, both P < 0.05. Conversely, no statistically significant differences were found in the levels of 15 REEs or ΣREEs in the blood samples between the REEs-exposed group and non-exposed group. Moreover, the concentrations of ΣREEs and 9 REEs in nail samples of the exposed group were significantly higher than those of the non-exposed group (P < 0.05), and the composition ratios of REEs in the nail samples closely resembled those found in individual airborne particles. Therefore, nail and urine samples were proposed to reflect long-term and short-term exposure to ionic rare earth respectively. Exposure biomarkers confirmed by external and internal exposure characteristics accurately provide the situation of human exposure to REEs environment, and have profound significance for monitoring and evaluating the level of REEs pollution in human body. It also provides a vital basis to find out the effect biomarkers, susceptible biomarkers and the health effects of rare earth environment for the future research.

EZH2/G9a interact to mediate drug resistance in non-small-cell lung cancer by regulating the SMAD4/ERK/c-Myc signaling axis.

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.

MRI-based central sarcopenia negatively impacts the therapeutic effectiveness of single-segment lumbar fusion surgery in the elderly.

Central sarcopenia is associated with the prognosis of various orthopedic surgeries in the elderly. This study aims to investigate its impact on the outcomes of single-segment lumbar fusion surgery in elderly patients. Retrospective analysis was conducted on 314 patients aged 60 to 80 who underwent single-segment posterior lumbar fusion surgery due to degenerative lumbar diseases. Patients were categorized into high psoas and L4 vertebral index (PLVI) and low PLVI groups according to the MRI-measured PLVI for central sarcopenia. Basic patient data, surgery-related parameters, functional assessments at preoperative and postoperative 3, 6, and 12 months, and X-ray-based fusion status were compared. The basic data of the two groups showed no significant differences. Parameters including the operative segment, preoperative hemoglobin levels, surgical duration, and intraoperative blood loss exhibited no significant variances. However, notable differences were observed in postoperative initial hemoglobin levels, transfusion requirements, and length of hospital stay between the two groups. During the postoperative follow-ups at 3, 6, and 12 months, the VAS scores for lower back pain and ODI scores in the lower PLVI group were significantly higher compared to the high PLVI group. Additionally, the EuroQoL 5D scores were notably lower in the low PLVI group. There were no significant differences between the groups in terms of leg pain VAS scores at each time point and the fusion status at 12 months postoperatively. MRI-based central sarcopenia has a negative impact on the therapeutic effectiveness following single-segment lumbar fusion surgery in elderly patients.

Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes.

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

Predictive value of intraoperative contrast-enhanced ultrasound in functional recovery of non-traumatic cervical spinal cord injury.

OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: • Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. • The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. • Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.

Arthroscopy-assisted reduction and simultaneous robotic-assisted screw placement in the treatment of fractures of the posterior talar process.

PURPOSE: A fracture of the posterior talar process is easily missed because of its hidden position. Inappropriate treatment is likely to result in complications, such as nonunion of the fracture and traumatic arthritis. This study evaluated the outcomes of arthroscopy-assisted reduction combined with robotic-assisted screw placement in the treatment of fractures of the posterior talar process. METHODS: The clinical data for nine patients who underwent surgical treatment of a fracture of the posterior talar process at our institution between September 2017 and January 2021 were retrospectively reviewed. Arthroscopy-assisted reduction of the fracture was performed, and a cannulated screw was placed using three-dimensional orthopedic robotic-assisted navigation. RESULTS: The patients (seven men, two women) had a mean age of 36.33 ± 9.77 years and were followed up for 21 ± 5.43 months. The operation time was 106.67 ± 24.5 min with blood loss of 47.78 ± 9.05 ml. Primary healing was obtained in all cases, and no patient sustained a nerve or tendon injury, had fracture nonunion, or developed talar osteonecrosis. One patient developed subtalar arthritis, for which subtalar joint fusion was performed; pain was markedly less severe after cleaning. CONCLUSION: Arthroscopy-assisted reduction and robotic-assisted screw placement have the advantages of visualization of fracture reduction, minimal injury, and precise screw placement in the treatment of fractures of the posterior talar process.

An innovative approach to assess spinal canal expansion following French-door cervical laminoplasty by intraoperative ultrasonography.

OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and Bland‒Altman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: • Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. • Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. • Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.

The Interplay Between HIF-1α and EZH2 in Lung Cancer and Dual-Targeted Drug Therapy.

Interactions between oncogenic proteins contribute to the phenotype and drug resistance. Here, EZH2 (enhancer of zest homolog 2) is identified as a crucial factor that mediates HIF-1 (hypoxia-inducible factor) inhibitor resistance. Mechanistically, targeting HIF-1 enhanced the activity of EZH2 through transcription activation of SUZ12 (suppressor of zest 12 protein homolog). Conversely, inhibiting EZH2 increased HIF-1α transcription, but not the transcription of other HIF family members. Additionally, the negative feedback regulation between EZH2 and HIF-1α is confirmed in lung cancer patient tissues and a database of cell lines. Moreover, molecular prediction showed that a newly screened dual-target compound, DYB-03, forms multiple hydrogen bonds with HIF-1α and EZH2 to effectively inhibit the activity of both targets. Subsequent studies revealed that DYB-03 could better inhibit migration, invasion, and angiogenesis of lung cancer cells and HUVECs in vitro and in vivo compared to single agent. DYB-03 showed promising antitumor activity in a xenograft tumor model by promoting apoptosis and inhibiting angiogenesis, which could be almost abolished by the deletion of HIF-1α and EZH2. Notably, DYB-03 could reverse 2-ME2 and GSK126-resistance in lung cancer. These findings clarified the molecular mechanism of cross-regulation of HIF-1α and EZH2, and the potential of DYB-03 for clinical combination target therapy.

Giant complex hepatic cyst causing pseudocystitis: A case report.

BACKGROUND: Hepatic cysts are common benign liver tumors that are typically asymptomatic. However, larger cysts, particularly giant liver cysts, can potentially induce symptoms. If the diameter of the cyst exceeds 10 cm, it can exert pressure on adjacent organs, leading to manifestations of corresponding symptoms. Here, we report the case of a complex giant hepatic cyst that caused pseudocystitis. CASE SUMMARY: A 16-year-old girl was admitted to our hospital with frequent and urgent urination. Ultrasonography revealed no obvious uterine adnexal abnormalities but showed a hypoechoic, cystic mass (173 mm × 84 mm × 138 mm) with clear boundaries, and an unclear blood flow signal in the abdominal cavity (extending from the lower edge of the left lobe of liver to the upper edge of the bladder). Abdominal contrast-enhanced computed tomography revealed a giant cystic mass in the abdominal and pelvic cavities, possibly originating from the liver, and a small amount of free fluid in the pelvic cavity, which subsequent magnetic resonance imaging confirmed. The imaging characteristics were consistent with a benign lesion. The patient underwent laparoscopic resection of the giant liver cyst with partial liver resection. Post-surgery her symptoms urinary symptoms were relieved completely and she was discharged on the sixth postoperative day. CONCLUSION: Our patient presented with symptoms suggestive of pseudocystitis, stressing the need for considering possibilities of other etiologies and differential diagnoses.

[Microbial remediation of cadmium-contaminated soils and its mechanisms: a review].

Excessive levels of cadmium (Cd) in soil exert serious negative impacts on soil ecosystems. Microorganisms are a common component of soil and show great potential for mitigating soil Cd. This review summarizes the application and remediation mechanisms of microorganisms, microbial-plants, and microbial-biochar in Cd-contaminated soil. Microorganisms such as Bacillus, Acinetobacter, Pseudomonas, and arbuscular mycorrhizal fungi (AMF) can change the biological validity of Cd through adsorption, mineralization, precipitation and dissolution. Different factors such as pH, temperature, biomass, concentration, and duration have significant effects on Cd bioavailability by microorganisms. Pseudomonas, Burkholderia, and Flavobacterium can promote the uptake of Cd2+ by hyperaccumulator through promotion and activation. Biochar, a soil amendment, possesses unique physicochemical properties and could act as a shelter for microorganisms in agriculture. The use of combined microbial-biochar can further stabilize Cd compared to using biochar alone.

Cysticercus pisiformis-derived novel-miR1 targets TLR2 to inhibit the immune response in rabbits.

Cysticercosis pisiformis, a highly prevalent parasitic disease worldwide, causes significant economic losses in the rabbit breeding industry. Previous investigations have identified a novel microRNA, designated as novel-miR1, within the serum of rabbit infected with Cysticercus pisiformis. In the present study, we found that C. pisiformis-derived novel-miR1 was released into the rabbit serum via exosomes. Through computational analysis using TargetScan, miRanda, and PITA, a total of 634 target genes of novel-miR1 were predicted. To elucidate the functional role of novel-miR1, a dual-luciferase reporter assay was utilized and demonstrated that novel-miR1 targets rabbit Toll-like receptor 2 (TLR2). Rabbit peripheral blood lymphocytes (PBLCs) were transfected with novel-miR1 mimic and mimic NC, and the in vitro experiments confirmed that novel-miR1 suppressed the expression of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 through the nuclear factor kappa B (NF-κB) pathway. In vivo experiments demonstrated that novel-miR1 was significantly upregulated during the 1-3 months following infection with C. pisiformis in rabbits. Notably, this upregulation coincided with a downregulation of TLR2, P65, pP65, TNF-α, IL-1ß, and IL-6 in PBLCs. Collectively, these results indicate that the novel-miR1 derived from C. pisiformis inhibited the rabbits' immune response by suppressing the NF-κB-mediated immune response. This immune modulation facilitates parasite invasion, survival, and establishment of a persistent infection.

DNA Methyltransferase 3A: a Significant Target for the Discovery of Inhibitors as Potent Anticancer Drugs.

DNA methyltransferase (DNMT) is a conserved family of Cytosine methylases, which plays a crucial role in the regulation of Epigenetics. They have been considered promising therapeutic targets for cancer. Among the DNMT family, mutations in the DNMT3A subtype are particularly important in hematologic malignancies. The development of specific DNMT3A subtype inhibitors to validate the therapeutic potential of DNMT3A in certain diseases is a significant task. In this review, we summarized the small molecule inhibitors of DNMT3A discovered in recent years and their inhibitory activities, and classified them based on their inhibitory mechanisms.