Anterior cruciate ligament injury should not be considered a contraindication for medial unicompartmental knee arthroplasty: Finite element analysis.

PURPOSE: The research objective of this study is to use finite element analysis to investigate the impact of anterior cruciate ligament (ACL) injury on medial unicompartmental knee arthroplasty (UKA) and explore whether patients with ACL injuries can undergo UKA. METHODS: Based on the morphology of the ACL, models of ACL with diameters ranging from 1 to 10mm are created. Finite element models of UKA include ACL absence and ACLs with different diameters. After creating a complete finite element model and validating it, four different types of loads are applied to the knee joint. Statistical analysis is conducted to assess the stress variations in the knee joint structure. RESULTS: A total of 11 finite element models of UKA were established. Regarding the stress on the ACL, as the diameter of the ACL increased, when a vertical load of 750N was applied to the femur, combined with an anterior tibial load of 105N, the stress on the ACL increased from 2.61 MPa to 4.62 MPa, representing a 77.05% increase. Regarding the equivalent stress on the polyethylene gasket, a notable high stress change was observed. The stress on the gasket remained between 12.68 MPa and 14.33 MPa in all models. the stress on the gasket demonstrated a decreasing trend. The equivalent stress in the lateral meniscus and lateral femoral cartilage decreases, reducing from the maximum stress of 4.71 MPa to 2.61 MPa, with a mean value of 3.73 MPa. This represents a reduction of 44.72%, and the statistical significance is (P < 0.05). However, under the other three loads, there was no significant statistical significance (P > 0.05). CONCLUSION: This study suggests that the integrity of the ACL plays a protective role in performing medial UKA. However, this protective effect is limited when performing medial UKA. When the knee joint only has varying degrees of ACL injury, even ACL rupture, and the remaining structures of the knee joint are intact with anterior-posterior stability in the knee joint, it should not be considered a contraindication for medial UKA.

Review on bile dynamics and microfluidic-based component detection: Advancing the understanding of bilestone pathogenesis in the biliary tract.

Bilestones are solid masses found in the gallbladder or biliary tract, which block the normal bile flow and eventually result in severe life-threatening complications. Studies have shown that bilestone formation may be related to bile flow dynamics and the concentration level of bile components. The bile flow dynamics in the biliary tract play a critical role in disclosing the mechanism of bile stasis and transportation. The concentration of bile composition is closely associated with processes such as nucleation and crystallization. Recently, microfluidic-based biosensors have been favored for multiple advantages over traditional benchtop detection assays for their less sample consumption, portability, low cost, and high sensitivity for real-time detection. Here, we reviewed the developments in bile dynamics study and microfluidics-based bile component detection methods. These studies may provide valuable insights into the bilestone formation mechanisms and better treatment, alongside our opinions on the future development of in vitro lithotriptic drug screening of bilestones and bile characterization tests.

Age and flexors as risk factors for cervical radiculopathy: A new machine learning method.

This study aimed to investigate the risk factors for cervical radiculopathy (CR) along with identifying the relationships between age, cervical flexors, and CR. This was a retrospective cohort study, including 60 patients with CR enrolled between December 2018 and June 2020. In this study, we measured C2 to C7 Cobb angle, disc degeneration, endplate degeneration, and morphology of paraspinal muscles and evaluated the value of predictive methods using receiver operating characteristic curves. Next, we established a diagnostic model for CR using Fisher discriminant model and compared different models by calculating the kappa value. Age and cervical flexor factors were used to construct clinical predictive models, which were further evaluated by C-index, receiver operating characteristic curve, calibration curve, and decision curve analysis. Multivariate analysis showed that age and cervical flexors were potential risk factors for CR, while the diagnostic model indicated that both exerted the best diagnostic effect. The obtained diagnostic equation was as follows: y1 = 0.33 × 1 + 10.302 × 2-24.139; y2 = 0.259 × 1 + 13.605 × 2-32.579. Both the C-index and AUC in the training set reached 0.939. Moreover, the C-index and AUC values in the external validation set reached 0.961. We developed 2 models for predicting CR and also confirmed their validity. Age and cervical flexors were considered potential risk factors for CR. Our noninvasive inspection method could provide clinicians with a more potential diagnostic value to detect CR accurately.

A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC), one of the highest causes of cancer-associated death, has effective treatments, especially for patients with advanced HCC. Circadian rhythm participates in several important physiological functions, and its chronic disruption results in many disordered diseases, including cancer. However, the role of circadian rhythm in the overall survival (OS) of patients with HCC remains unclear. Methods: We investigated the expression, copy number variation (CNV), and mutation profiles of core circadian clock genes in normal and tumor tissues. We developed and validated a messenger RNA signature (mRNASig) based on prognostic circadian clock genes. A set of bioinformatic tools were applied for functional annotation and tumor-associated microenvironment (TME) analysis. Results: Core circadian clock genes were disrupted in terms of the transcription and CNV of HCC samples. The mRNASig, including NPAS2, NR1D1, PER1, RORC, and TIMELESS, was constructed. We divided patients with HCC into high-risk group and low-risk group based on the median value of the risk score. The high-risk group had a poorer prognosis than the low-risk group. The high-risk group was associated with malignant processes (e.g., proliferation, oncogenic pathway, DNA repair), metabolism, and tumor mutational burden (TMB). Surprisingly, the low-risk group was associated with enriched angiogenesis and was linked to enhanced response to sorafenib. Moreover, the high-risk group showed poor infiltration of CD8 T cells and natural killer cells accompanied by higher expression of CTLA4, PDCD1, TIGIT, and TIM3. Additionally, the mRNASig was associated with TMB. Conclusions: The mRNASig based on core circadian clock genes is a potential prognostic signature and therapeutic strategy and is significantly associated with the malignant biology of HCC.

Downregulation of lncRNA SATB2­AS1 facilitates glioma cell proliferation by sponging miR­671­5p.

The antisense transcript of SATB2 protein (SATB2-AS1) is a novel long non-coding RNA (lncRNA) which is involved in the development of colorectal cancer, breast cancer and hepatocellular carcinoma. In the present study, it was aimed to investigate the consequent situation of SATB2-AS1 in tissue and cell lines of glioma. The expression of SATB2-AS1 in glioma cases was analyzed in The Cancer Genome Atlas datasets. The glycolytic metabolism was determined in glioma cells by detection of extracellular glucose level, oxygen consumption rate and extracellular acidification rate. Cell Counting Kit-8 assay and flow cytometry were used to assess cell proliferation and apoptosis in glioma cells. The interaction between SATB2-AS1 and microRNA (miR)-671-5p was verified by bioinformatic analysis, reverse transcription-quantitative PCR, dual luciferase reporter assay and RNA immunoprecipitation assay. The expression levels of the downstream targets of SATB2-AS1 were studied by western blotting. Results demonstrated that SATB2-AS1 was a downregulated lncRNA in low grade glioma and glioblastoma. Gain-of-function assay demonstrated that SATB2-AS1 inhibited cell proliferation, and glycolytic metabolism, while induced cell apoptosis in glioma cells. SATB2-AS1 sponged and suppressed the expression of an oncogenic miRNA miR-671-5p. By regulation of miR-671-5p, SATB2-AS1 upregulated cerebellar degeneration related protein 1 (CDR1) and Visinin-like 1 (VSNL1) expression in glioma cells. miR-671-5p overexpression partially reversed the antitumor effect of SATB2-AS1 in glioma. In conclusion, the current study demonstrated that there was a downregulation of SATB2-AS1 in glioma, and SATB2-AS1 regulated miR-671-5p/CDR1 axis and miR-671-5p/VSNL1 axis in glioma.

Visible-Light-Induced, Catalyst-Free Monofluoromethyl Sulfonylation of Alkenes with Iodine(III) Reagent and DABSO.

A visible-light-induced radical relay strategy to access heterocycles bearing a monofluoromethylsufonyl moiety is reported, with PhI(OCOCH2F)2 as the CH2F radical precursor and DABSO as the SO2 source. A range of oxindoles, containing a CH2FSO2CH2- group at the C3 position, were synthesized from N-arylacrylamides in up to 97% yields. The protocol features catalyst-free photochemical tandem, mild reaction conditions, broad functional group compatibility, and good to excellent yields.

Dexamethasone for delayed edema after intracerebral hemorrhage： To be or not to be?

The pathogenesis of delayed cerebral edema after intracerebral hemorrhage is still unclear. In this case report, we speculate that the formation of subdural effusion or hemorrhage is associated with delayed cerebral edema. By referring to the treatment plan of chronic subdural hematoma, adding dexamethasone to routine medication, certain therapeutic effect has been achieved. Dexamethasone may maintain the stability of blood-brain barrier by directly increasing the expression of ZO-1, and reduce the neuroinflammatory response caused by NF-κB pathway by upregulating KLF2 expression, ultimately reducing nerve injury through multiple pathways.

Efficacy of pericapsular nerve group block vs. fascia iliaca compartment block for Hip surgeries: A systematic review and meta-analysis.

Objective: The review aimed to compare outcomes of pericapsular nerve group block (PENG) vs. fascia iliaca compartment block (FICB) for patients undergoing hip surgeries. Methods: Randomized controlled trials (RCTs) published in the databases of PubMed, CENTRAL, Embase, and Web of Science comparing PENG vs. FICB for pain control after hip surgeries were included in the review. Results: Six RCTs were included. 133 patients received PENG block and were compared with 125 patients receiving FICB. Our analysis showed no difference in 6 h (MD: -0.19 95% CI: -1.18, 0.79 I 2 = 97% p = 0.70), 12 h (MD: 0.04 95% CI: -0.44, 0.52 I 2 = 72% p = 0.88) and 24 h (MD: 0.09 95% CI: -1.03, 1.21 I 2 = 97% p = 0.87) pain scores between PENG and FICB groups. Pooled analysis showed that mean opioid consumption in morphine equivalents was significantly less with PENG as compared to FICB (MD: -8.63 95% CI: -14.45, -2.82 I 2 = 84% p = 0.004). Meta-analysis of three RCTs showed no variation in the risk of postoperative nausea and vomiting in the two groups. The quality of evidence on GRADE was mostly moderate. Conclusion: Moderate quality of evidence suggests that PENG may result in better analgesia than FICB in patients undergoing hip surgeries. Data on motor-sparing ability and complications are scarce to draw conclusions. Further large-scale and high-quality RCTs should be conducted to supplement current findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022350342.

Reactive Oxygen Species Scavenging Functional Hydrogel Delivers Procyanidins for the Treatment of Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) is accompanied by the overload of reactive oxygen species (ROS), which can result in secondary brain injury. Although procyanidins (PCs) have a powerful free radical scavenging capability and have been widely studied in the treatment of TBI, conventional systemic drug therapy cannot make the drug reach the targeted area in the early stage of TBI and will cause systemic side effects because of the presence of the blood-brain barrier (BBB). To address this tissue, we designed and fabricated a ROS-scavenging functional hydrogel loaded PC (GelMA-PPS/PC) to deliver the drug by responding to the traumatic microenvironment. In situ injection of the GelMA-PPS/PC hydrogel effectively avoided the BBB and was directly applied to the surface of brain tissue to target the traumatic area. Hydrophobic poly(propylene sulfide)60 (PPS60), an ROS quencher and H2O2-responsive substance, was covalently bound to GelMA and exposed in response to the trauma microenvironment. At the same time, the H2O2 response of PPS60 further caused the structure of the hydrogel to degrade and release the encapsulated PC. Then PC could regulate the oxidative stress response in the cells and synergistically deplete ROS to play a neurotrophic protective role. This work suggests a novel method for the treatment of secondary brain injury by inhibiting the oxidative stress response after TBI.

Tumor-derived Exosome Promotes Metastasis via Altering its Phenotype and Inclusions.

Although tumor-derived exosomes play an important role in the process of metastasis, differences in exosomes secreted by the same cells at different stages or conditions have not been noticed by most of the relevant researchers. Here we developed a lung cancer model in nude mice, and the phenotype and inclusions of exosomes secreted by early and advanced tumors were analysed. The size distribution and surface topography of these two exosomes were not significantly different, but the expression of CD63 in early tumor exosome (E-exosome) was significantly lower than that in advanced tumor exosome (A-exosome). α-SMA expression on HELF cells treated with A-exosome was significantly higher than that treated with E-exosome. The ability of A-exosome to promote the migration of A549 cells was better than E-exosome. Furthermore, small RNA sequence showed that only 3 of the 171 detected-small RNAs were expressed simultaneously in both exosomes. These findings proved that there are significant differences in inclusions and functions between the early and late exosomes of the same tumor. The study highlights the importance of exosomes in cancer metastasis, and might suggest exosomes can be used as biomarkers and therapeutic targets for cancer metastasis.

A randomized, controlled multicentric study of inhaled budesonide and intravenous methylprednisolone in the treatment on acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Almost all international guidelines recommend corticosteroids for management of exacerbations of chronic obstructive pulmonary disease (COPD), because it leads to improved outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Nevertheless, due to its side effects, there are still concerns regarding the use of systemic corticosteroid (SC). Inhaled corticosteroids (IC) can be used as an alternative to SC, while reducing the risk of occurrence of side effects. PURPOSE: To measure the clinical efficacy and side effects of nebulized budesonide and systemic methylprednisolone in AECOPD. METHODS: Valid data from 410 AECOPD patients in 10 hospitals was collected. Patients were randomly divided into 2 groups; budesonide group, treated with nebulized budesonide (2 mg 3 times/day); and methylprednisolone group, treated with intravenously injected methylprednisolone (40 mg/day). COPD assessment test (CAT), arterial blood gas analysis, hospitalization days, adverse effects, fasting blood glucose, serum creatinine, alanine aminotransferase levels, and blood drug were measured and analyzed in both groups. RESULTS: Symptoms, pulmonary function and arterial blood gas analysis were significantly improved after treatment in both groups (P < 0.05), with no significant differences between them (P > 0.05), while incidence of adverse events in the budesonide group was lower (P < 0.05). No significant differences in CAT score, days of admission, blood gas analysis results and physiological and biochemical indexes were found between the two groups. Patients treated with methylprednisolone showed a higher degree of PaO2 level improvement. CONCLUSION: Results show that inhalation of budesonide (2 mg 3 times/day) and systemic methylprednisolone (40 mg/day) had similar clinical outcome in AECOPD. In conclusion, inhaled budesonide is an alternative to systemic corticosteroids in AECOPD treatment.

Remarkable regression of a lung recurrence from an undifferentiated embryonal sarcoma of the liver treated with a DC vaccine combined with immune cells: a case report.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant tumor that occurs predominantly in children and has a poor prognosis. Here, we report a novel case in which the UESL presented in the left lobe of the liver and metastasized into both lungs after surgical resection. The patient recovered after our administration of an immunotherapeutic combination of DCs (Dendritic Cells) and multi-immune cells, such as cytokine-induced killer cells (CIKs) and natural killer cells (NKs). After the third cycle of immunotherapy, a CT scan showed a remarkable regression of the lung metastases. This finding supports the conclusion that the DC-based treatment is a promising potential strategy for treating patients with relapsed UESL.

Transcriptome profiling of a multiple recurrent muscle-invasive urothelial carcinoma of the bladder by deep sequencing.

Urothelial carcinoma of the bladder (UCB) is one of the commonly diagnosed cancers in the world. The UCB has the highest rate of recurrence of any malignancy. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of UCB recurrence and is a key step to discovering biomarkers for diagnosis and therapeutic targets. Compared with microarray technology, which is commonly used to identify expression level changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing. In this study, we performed high-throughput transcriptome sequencing at ∼50× coverage on a recurrent muscle-invasive cisplatin-resistance UCB tissue and the adjacent non-tumor tissue. The results revealed cancer-specific differentially expressed genes between the tumor and non-tumor tissue enriched in the cell adhesion molecules, focal adhesion and ECM-receptor interaction pathway. Five dysregulated genes, including CDH1, VEGFA, PTPRF, CLDN7, and MMP2 were confirmed by Real time qPCR in the sequencing samples and the additional eleven samples. Our data revealed that more than three hundred genes showed differential splicing patterns between tumor tissue and non-tumor tissue. Among these genes, we filtered 24 cancer-associated alternative splicing genes with differential exon usage. The findings from RNA-Seq were validated by Real time qPCR for CD44, PDGFA, NUMB, and LPHN2. This study provides a comprehensive survey of the UCB transcriptome, which provides better insight into the complexity of regulatory changes during recurrence and metastasis.

Acquired hemophilia A in a patient associated with community-acquired pneumonia.

Acquired hemophilia A (AHA) is a rare disease induced by autoantibodies to factor VIII (FVIII) and may be correlated with pregnancy, underlying malignancies, autoimmune diseases or drug administration. An 81-year-old man who presented with cough, expectoration, hemoptysis and multiple ecchymoses was diagnosed with community-acquired pneumonia by computed tomography scan. Respiratory symptoms were ameliorated after the application of antibiotics. Despite repeated infusion of fresh frozen plasma and cryoprecipitate, his prolonged activated partial thromboplastin time (APTT) maintained in the 75-110-s range and ecchymoses were not ameliorated. Then, he was transferred to the department of hematology. Based on a prolonged APTT, decreased level of FVIII and presence of antibodies against FVIII, the patient was diagnosed with AHA. Then the patient was treated with activated prothrombin complex concentrates, prednisone and intravenous immunoglobulin, resulting in a complete remission of the bleeding, recovering the FVIII level and negativity for FVIII antibody titers. Here, we investigate this novel case retrospectively and review the relevant literature.