Association of the Inlay Structure Used in the Modified Bristow Procedure With Accelerated Bone Union: Comparing the Cuistow and Modified Bristow Procedures.

Background: The Chinese unique inlay Bristow (Cuistow) procedure is a modified Bristow surgery in which an inlay (mortise-and-tenon) structure is added to the contact surface between the coracoid tip and the glenoid. Patients who have undergone the Cuistow procedure have had satisfying clinical performance and excellent postoperative bone healing rates (96.1%). Purpose: To compare the clinical and radiographic outcomes after the arthroscopic Cuistow procedure and the arthroscopic Bristow procedure. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 91 patients who underwent either the Cuistow or Bristow procedure between January 2017 and March 2018 were selected, and 69 patients (70 shoulders; 35 in the Cuistow group and 35 in the Bristow group) were included. Clinical assessment at minimum 24 months postoperatively, including the visual analog scale for pain and instability, American Shoulder and Elbow Surgeons score, Rowe score, subjective shoulder value score, and active range of motion, was completed by independent observers and compared with values collected preoperatively. Assessment with 3-dimensional computed tomography scans was performed preoperatively; immediately after the operation; at 3, 6, and 12 months postoperatively; and at the final follow-up. Results: A total of 69 patients (70 shoulders) were included, with a mean follow-up duration of 34.41 ± 5.99 months (range, 24-50 months). Both groups saw significant improvement in visual analog scale for pain and instability, American Shoulder and Elbow Surgeons, Rowe, and subjective shoulder value scores at the final follow-up compared with the preoperative values (P < .001 for all), with no significant between-group differences on any clinical outcomes at the final follow-up. The 3-month postoperative graft union rate on computed tomography was significantly higher in the Cuistow group compared with the Bristow group (82.9% vs 51.4%, respectively, P = .003), although the graft union rate at the final follow-up was not significantly different (94.3% vs 85.7%, respectively; P = .449). Conclusion: Patients receiving the Cuistow procedure had equivalent clinical outcomes and a significantly higher bone union rate at 3 months postoperatively than those in the Bristow group. The inlay structure used in the Cuistow procedure was found to be associated with accelerated bone union.

Development and validation of a nomogram to predict cancer-specific survival of patients with large hepatocellular carcinoma accepting surgical resection: a real-world analysis based on the SEER database.

Background: Only a small percentage of patients with large hepatocellular carcinoma (HCC) can undergo surgical resection (SR) therapy while the prognosis of patients with large HCC is poor. However, innovations in surgical techniques have expanded the scope of surgical interventions accessible to patients with large HCC. Currently, most of the existing nomograms are focused on patients with large HCC, and research on patients who undergo surgery is limited. This study aimed to establish a nomogram to predict cancer-specific survival (CSS) in patients with large HCC who will undergo SR. Methods: The study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database encompassing patients with HCC between 2010 and 2015. Patients with large HCC accepting SR were eligible participants. Patients were randomly divided into the training (70%) and internal validation (30%) groups. Patients from Air Force Medical Center between 2012 and 2019 who met the inclusion and exclusion criteria were used as external datasets. Demographic information such as sex, age, race, etc. and clinical characteristics such as chemotherapy, histological grade, fibrosis score, etc. were analyzed. CSS was the primary endpoint. All-subset regression and Cox regression were used to determine the relevant variables required for constructing the nomogram. Decision curve analysis (DCA) was used to evaluate the clinical utility of the nomogram. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to validate the nomogram. The Kaplan-Meier curve was used to assess the CSS of patients with HCC in different risk groups. Results: In total, 1,209 eligible patients from SEER database and 21 eligible patients from Air Force Medical Center were included. Most patients were male and accepted surgery to lymph node. The independent prognostic factors included sex, histological grade, T stage, chemotherapy, α-fetoprotein (AFP) level, and vascular invasion. The CSS rate for training cohort at 12, 24, and 36 months were 0.726, 0.731, and 0.725 respectively. The CSS rate for internal validation cohort at 12, 24, and 36 months were 0.785, 0.752, and 0.734 respectively. The CSS rate for external validation cohort at 12, 24, and 36 months were 0.937, 0.929, and 0.913 respectively. The calibration curve demonstrated good consistency between the newly established nomogram and real-world observations. The Kaplan-Meier curve showed significantly unfavorable CSS in the high-risk group (P<0.001). DCA demonstrated favorable clinical applicability of the nomogram. Conclusions: The nomogram constructed based on sex, histological grade, T stage, chemotherapy and AFP levels can predict the CSS in patients with large HCC accepting SR, which may aid in clinical decision-making and treatment.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies.

Obesity is a complex medical condition caused by a positive imbalance between calorie intake and calorie consumption. Brown adipose tissue (BAT), along with the newly discovered "brown-like" adipocytes (called beige cells), functions as a promising therapeutic tool to ameliorate obesity and metabolic disorders by burning out extra nutrients in the form of heat. Many studies in animal models and humans have proved the feasibility of this concept. In this review, we aim to summarize the endeavors over the last decade to achieve a higher number/activity of these heat-generating adipocytes. In particular, pharmacological compounds, especially agonists to the ß3 adrenergic receptor (ß3-AR), are reviewed in terms of their feasibility and efficacy in elevating BAT function and improving metabolic parameters in human subjects. Alternatively, allograft transplantation of BAT and the transplantation of functional brown or beige adipocytes from mesenchymal stromal cells or human induced pluripotent stem cells (hiPSCs) make it possible to increase the number of these beneficial adipocytes in patients. However, practical and ethical issues still need to be considered before the therapy can eventually be applied in the clinical setting. This review provides insights and guidance on brown- and beige-cell-based strategies for the management of obesity and its associated metabolic comorbidities.

The use of peripheral CD3+γδ+Vδ2+ T lymphocyte cells in combination with the ALBI score to predict immunotherapy response in patients with advanced hepatocellular carcinoma: a retrospective study.

BACKGROUND: Currently, there is a lack of effective indicators for predicting the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to investigate the expression and prognostic value of peripheral T lymphocyte subsets in advanced HCC. METHODS: Patients with advanced HCC who were treated with immune checkpoint inhibitors (ICIs) from December 2021 to December 2023 were included in the study. Flow cytometry was used to detect lymphocyte subsets before treatment. The patients were divided into disease control (DC) and nondisease control (nDC) groups based on treatment efficacy. Relationships between the clinical characteristics/peripheral T lymphocytes and immunotherapy efficacy were analyzed. The effectiveness of peripheral T lymphocyte subsets in predicting immunotherapy efficacy for patients with advanced HCC was analyzed using receiver operating characteristic (ROC) curves. RESULTS: A total of 40 eligible patients were included in this study. Non-DC was significantly associated with higher albumin-bilirubin (ALBI) scores. The percentages of γδ+Vδ2+PD1+ T cells and γδ+Vδ2+Tim3+ T cells were greater in the nDC group than in the DC group. Multivariable regression analysis revealed that the ALBI score and T lymphocytes expressing γδ+Vδ2+PD1+ and γδ+Vδ2+Tim3+ were founded to be independent influencing factors. The area under the ROC curve (AUC) values for these combinations was 0.944 (95% CI, 0.882 ~ 1.000). CONCLUSIONS: The calculation of the ALBI score and determination of the percentages CD3+γδ+Vδ2+PD1+ T lymphocytes and CD3+γδ+Vδ2+Tim3+ T lymphocytes in the peripheral blood of patients with advanced HCC are helpful for predicting the patients' responses to ICIs, helping to screen patients who may clinically benefit from immunotherapy. RETROSPECTIVELY REGISTERED: number: ChiCTR2400080409, date of registration: 2024-01-29.

U-Net-Based Assistive Identification of Bladder Cancer: A Promising Approach for Improved Diagnosis.

INTRODUCTION: Bladder cancer (BC) is a major health concern that poses a significant threat to the population, with an increasing incidence rate and a high risk of recurrence and progression. The primary clinical method for diagnosing BC is cystoscopy, but due to the limitations of traditional white light cystoscopy and inadequate clinical experience among junior physicians, its detection rate for bladder tumor, especially small and flat lesions, is relatively low. However, recent years have seen remarkable advancements in the application of artificial intelligence (AI) technology in the field of medicine. This has led to the development of numerous AI algorithms that have been successfully integrated into medical practices, providing valuable assistance to clinicians. The purpose of this study is to develop a cystoscopy algorithm that is real time, cost effective, high performing, and accurate, with the aim of enhancing the detection rate of bladder tumors during cystoscopy. MATERIALS AND METHODS: For this study, a dataset of 3,500 cystoscopic images obtained from 100 patients diagnosed with BC was collected, and a deep learning model was developed utilizing the U-Net algorithm within a convolutional neural network for training purposes. RESULTS: This study randomly divided 3,500 images from 100 BC patients into training and validation groups, and each patient's pathology result was confirmed. In the validation group, the accuracy of tumor recognition by the U-Net algorithm reached 98% compared to primary urologists, with greater accuracy and faster detection speed. CONCLUSION: This study highlights the potential of U-Net-based deep learning techniques in the detection of bladder tumors. The establishment and optimization of the U-Net model is a significant breakthrough and it provides a valuable reference for future research in the field of medical image processing.

Prevalence, distribution, accumulation, and risk of environmental corticosteroids and estrogens in biofilms from the Pearl River Delta.

Biofilms play a significant role in the biogeochemical processing of organic matter and the environmental fate of emerging pollutants. In this study, we investigated the occurrence and distribution of 32 endocrine-disrupting chemicals (EDCs), including 24 environmental corticosteroids (ECs) and 8 environmental estrogens (EEs), in natural biofilms from the Pearl River system. Their association between biofilms and water and environmental risk were assessed. The ECs and EEs ubiquitously occurred in the biofilms, ranging from <0.61-6.57 ng/g and <0.8-2535 ng/g, respectively. Temporally, there was no obvious variance in either ECs or EEs in the biofilms during the winter and summer, and their concentrations exhibited a spatial trend of upward to midstream, descending downstream, and then seaward attenuation at the estuary. For ECs and EEs, the similar levels of field-derived bioconcentration factors (BCFs) (logarithm values: 2.42-2.86 and 2.72-2.98, respectively) and biofilm organic carbon-normalized partitioning coefficients (Kboc) (3.39-3.69 and 3.35-3.95) suggest the comparable potential of accumulation and sorption by biofilms between these two classes of EDCs. In addition, higher values of BCF and Kboc for the EEs were found in winter and were correspondingly comparable to their distribution coefficients (Kd) and Koc derived from suspended particles and sediment, revealing that biofilms are a competitive environmental compartment for capturing EDCs, particularly during the mature period. A positive logKboc-logKow relationship suggests hydrophobic partitioning as a primary interaction mechanism between the biofilm and EEs. Moreover, high risks from biofilm-associated ECs and EEs might have posed to the fluvial ecosystem. This study provides original insights into the occurrence, fate, and risk of ECs in natural biofilms for the first time and demonstrates that biofilms may not only serve as reservoirs but also serve as sentinels for fluvial EDC contamination. These results contribute to the further understanding of the behavior and fate of EDCs in aquatic environments.

[Research progress in biomechanics of Bristow-Latarjet procedure for anterior shoulder dislocation].

Objective: To review the research progress of the biomechanical study of the Bristow-Latarjet procedure for anterior shoulder dislocation. Methods: The related biomechanical literature of Bristow-Latarjet procedure for anterior shoulder dislocation was extensively reviewed and summarized. Results: The current literature suggests that when performing Bristow-Latarjet procedure, care should be taken to fix the bone block edge flush with the glenoid in the sagittal plane in the direction where the rupture of the joint capsule occurs. If traditional screw fixation is used, a double-cortical screw fixation should be applied, while details such as screw material have less influence on the biomechanical characteristics. Cortical button fixation is slightly inferior to screws in terms of biomechanical performance. The most frequent site of postoperative bone resorption is the proximal-medial part of the bone block, and the cause of bone resorption at this site may be related to the stress shielding caused by the screw. Conclusion: There is no detailed standardized guidance for bone block fixation. The optimal clinical treatment plan for different degrees of injury, the factors influencing postoperative bone healing and remodeling, and the postoperative osteoarticular surface pressure still need to be further clarified by high-quality biomechanical studies.

Previously failed Bankart repair and the duration from first dislocation to surgery were the risk factors associated with the level of return to sports after coracoid transfer.

PURPOSE: This study aims to determine the rate of different levels of return to sports (RTS) in athletes undergoing the modified arthroscopic Bristow procedure and the factors associated with the level of RTS. METHODS: The study was performed retrospectively on patients with traumatic anterior shoulder instability who underwent the modified arthroscopic Bristow procedure with a minimum follow-up of 2 years. The RTS rate, the level of return and the timing of return were assessed. Additionally, factors such as preoperative basic information, clinical outcomes, graft position, graft healing and graft absorption were analysed to investigate their correlation with the level of RTS. Multivariate regression models were used to evaluate the factors affecting the level of RTS. RESULTS: In total, this study included 182 shoulders of 177 athletes undergoing the modified arthroscopic Bristow procedure. Of these patients, 142 (78.0%) shoulders of 137 athletes were enrolled, with a mean of 3.3-year follow-up. At the final follow-up, 134 (94.4%) shoulders were able to RTS, 123 (86.6%) shoulders were able to RTS to the pre-injury level, 52 (36.6%) shoulders could be completely "forgotten" without any psychological barrier during exercise. The multivariate logistic regression analysis identified the variable associated with RTS at the pre-injury level as previously failed arthroscopic Bankart repair (p < 0.001). As for the "forgetting" operated shoulder, the duration from first dislocation to surgery was a significant independent predictor (p = 0.034). CONCLUSION: Although a large majority of athletes were able to RTS at the pre-injury level after the modified arthroscopic Bristow procedure, about two-thirds of the athletes felt difference in shoulders on both sides and could not completely "forget" the operated shoulder during exercise. Previously failed Bankart repair and the duration from first dislocation to surgery were the risk factors associated with the level of RTS after the modified arthroscopic Bristow procedure. LEVEL OF EVIDENCE: IV.

Delayed CO2 postconditioning promotes neurological recovery after cryogenic traumatic brain injury by downregulating IRF7 expression.

AIMS: Few treatments are available in the subacute phase of traumatic brain injury (TBI) except rehabilitation training. We previously reported that transient CO2 inhalation applied within minutes after reperfusion has neuroprotective effects against cerebral ischemia/reperfusion injury. In this study, it was hypothesized that delayed CO2 postconditioning (DCPC) starting at the subacute phase may promote neurological recovery of TBI. METHODS: Using a cryogenic TBI (cTBI) model, mice received DCPC daily by inhaling 5%/10%/20% CO2 for various time-courses (one/two/three cycles of 10-min inhalation/10-min break) at Days 3-7, 3-14 or 7-18 after cTBI. Beam walking and gait tests were used to assess the effect of DCPC. Lesion size, expression of GAP-43 and synaptophysin, amoeboid microglia number and glia scar area were detected. Transcriptome and recombinant interferon regulatory factor 7 (Irf7) adeno-associated virus were applied to investigate the molecular mechanisms. RESULTS: DCPC significantly promoted recovery of motor function in a concentration and time-course dependent manner with a wide therapeutic time window of at least 7 days after cTBI. The beneficial effects of DCPC were blocked by intracerebroventricular injection of NaHCO3 . DCPC also increased puncta density of GAP-43 and synaptophysin, and reduced amoeboid microglia number and glial scar formation in the cortex surrounding the lesion. Transcriptome analysis showed many inflammation-related genes and pathways were altered by DCPC, and Irf7 was a hub gene, while overexpression of IRF7 blocked the motor function improvement of DCPC. CONCLUSIONS: We first showed that DCPC promoted functional recovery and brain tissue repair, which opens a new therapeutic time window of postconditioning for TBI. Inhibition of IRF7 is a key molecular mechanism for the beneficial effects of DCPC, and IRF7 may be a potential therapeutic target for rehabilitation after TBI.

Denosumab treatment for progressive Enneking stage II cervical giant-cell tumor conservatively.

Cervical giant cell tumor of the bone (GCTB) is a rare, primary benign bone tumor in pediatric patients. Surgery remains the primary choice for treating resectable cervical GCTB. Additional adjuvant therapeutic options are available for patients with unresectable cervical GCTB, including the anti-RANKL monoclonal antibody, denosumab. We represented a case incidentally found in a 7-year-old female, who complained severe craniocervical pain, grade 2-3 dysphagia, dysphonia, hypesthesia, and extremity weakness. The patient showed an impressive clinical response to denosumab, both clinically and radiologically, without adverse events or recurrence. To date, this is the youngest patient ever reported to have a progressive Enneking stage II C3 GCTB treated with denosumab alone. Denosumab can be administered as a single and conservative therapy for pediatric patients with unresectable upper cervical GCTB, avoiding the risks and morbidity of surgical and radiative treatment.

Cancer-associated fibroblasts in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.

Lanostane triterpenoids from the fungus Physisporinus vitreus and their inhibitory activity against nitric oxide production.

Eight undescribed lanostane triterpenoids, physivitrins A-H, along with four known analogues, were isolated from cultures of the fungus Physisporinus vitreus. Their structures were elucidated on the basis of extensive spectroscopic methods, in which the absolute configuration of physivitrin A was elucidated using electronic circular dichroism calculation and nuclear magnetic resonance (NMR) calculation with DP4+ analysis. Physivitrins B and C showed inhibitory activities against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages with IC50 values of 7.5 and 23.5 µM, respectively. Meanwhile, proinflammatory cytokines (TNF-α, iNOS and IL-1ß) mRNA expression was also inhibited by physivitrin B significantly.

Comparative Analysis of Aristolochic Acids in Aristolochia Medicinal Herbs and Evaluation of Their Toxicities.

Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the Aristolochia genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in Aristolochia plants, except for AAs Ι and ΙΙ, still remain unclear. In this study, a total of 52 batches of three medicinal herbs belonging to the Aristolochia family were analyzed for their AA composition profiles and AA contents using the UPLC-QTOF-MS/MS approach. The studied herbs were A. mollissima Hance (AMH), A. debilis Sieb.etZucc (ADS), and A. cinnabaria C.Y.Cheng (ACY). Chemometrics methods, including PCA and OPLS-DA, were used for the evaluation of the Aristolochia medicinal herbs. Additionally, cytotoxicity and genotoxicity of the selected AAs and the extracts of AMH and ADS were evaluated in a HepG2 cell line using the MTT method and a Comet assay, respectively. A total of 44 AAs, including 23 aristolochic acids and 21 aristolactams (ALs), were detected in A. mollissima. Moreover, 41 AAs (23 AAs and 18 ALs) were identified from A. debilis Sieb, and 45 AAs (29 AAs and 16 ALs) were identified in A. cinnabaria. Chemometrics results showed that 16, 19, and 22 AAs identified in AMH, ADS, and ACY, respectively, had statistical significance for distinguishing the three medicinal herbs of different origins. In the cytotoxicity assay, compounds AL-BΙΙ, AAΙ and the extract of AMH exhibited significant cytotoxicities against the HepG2 cell line with the IC50 values of 0.2, 9.7 and 50.2 µM, respectively. The results of the Comet assay showed that AAΙ caused relatively higher damage to cellular DNA (TDNA 40-95%) at 50 µM, while AAΙΙ, AMH and ADS extracts (ranged from 10 to 131 µM) caused relatively lower damage to cellular DNA (TDNA 5-20%).

Intra-tumor heterogeneity and prognostic risk signature for hepatocellular carcinoma based on single-cell analysis.

Intra-tumor heterogeneity poses a serious challenge in the treatment of cancer, including hepatocellular carcinoma (HCC). Recent developments in single-cell RNA sequencing (scRNA-seq) make it possible to examine the heterogeneity of tumor cells. The Gene Expression Omnibus (GEO) database was retrieved to obtain scRNA-seq data of 13 HCC and 8 para cancer samples, and the cells were clustered using FindNeighbors and FindClusters functions. Cell subsets were defined using the "Enricher" function of the clusterProfiler package. Monocle was used to predict cell developmental trajectory. The LIMMA package included in the R program was utilized to detect differentially expressed genes (DEGs) between HCC and paracancerous tissues. Univariate Cox analysis and Least Absolute and Selection Operator (Lasso) Cox regression analysis were conducted to establish a risk assessment model. Thirteen cell subpopulations were identified from the sequencing data of 64,634 single cells. Four cell subgroups (dendritic cells, hepatocytes, liver bud hepatic cells, and liver progenitor cells) in tumor tissues were highly enriched. Between HCC and para cancer tissues, 3024 DEGs were identified, and 641 were specific markers of four cell subgroups. To develop a prognostic risk model, 9 genes among the 641 genes were selected. In the training and validation sets, the model demonstrated a higher 5-year AUC and independently served as a prognostic marker as confirmed by multivariate and univariate Cox analyses. This study revealed the characteristics of different cell subpopulations of immune cells and tumor cells from the HCC microenvironment. We established a novel nine-gene prognostic model to determine the death risk of HCC patients. The discoveries in this research improved the current knowledge of HCC heterogeneity and may inspire future research.

Clinical and Radiographic Outcomes After Arthroscopic Inlay Bristow Surgery With Screw Versus Suture Button Fixation: A Comparative Study of 117 Patients With 3.3-Year Follow-up.

Background: Some studies have advocated the use of suture button fixation during Bristow-Latarjet surgery to reduce complications associated with screw fixation. However, data comparing these fixation methods are relatively incomplete. Purpose: To investigate the efficacy of modified arthroscopic Bristow-Latarjet surgery and compare the clinical and radiographic outcomes using screw versus suture button fixation. Study Design: Cohort study; Level of evidence, 3. Methods: We evaluated 136 patients with traumatic anterior shoulder instability who underwent the modified arthroscopic Bristow-Latarjet surgery between June 2015 and February 2018. Of these patients, 117 who met the inclusion criteria were enrolled at a mean follow-up of 3.3 ± 0.7 years. Shoulders were separated into 2 groups based on fixation technique: screw fixation (group A; n = 63) or suture button fixation (group B; n = 54). Computed tomography imaging findings and clinical results were assessed preoperatively; immediately after operation; and postoperatively at 3 months, 6 months, 1 year, and final follow-up. Results: There were no significant differences between the groups in terms of postoperative clinical scores, the level of return to sports, range of motion, graft position, or reoperation rates. Bone healing was observed in 97.4% of the cases overall (114/117), with 98.4% bone union in group A and 96.3% in group B at final follow-up. Bone absorption was more common in group A (n = 30; 47.6%) compared with group B (n = 10; 18.5%) (P = .003). There were no hardware-related complications in group B, compared with 7.9% of patients in group A (P = .034). One patient in group B had a recurrent dislocation due to an unexpected event, and there were no recurrent dislocations in group A. Conclusion: After the modified arthroscopic Bristow-Latarjet procedure, both suture button and screw fixation methods demonstrated high bony healing rates and low risk of recurrence. Less coracoid graft resorption and no hardware-related complications were seen with suture button fixation.

[Pharmacodynamic substances and therapeutic potential of Wuji Pills:based on UPLC-Q-TOF-MS/MS and network pharmacology].

As a classic prescription, Wuji Pills is composed of Coptidis Rhizoma, Euodiae Fructus Preparata, and stir-fried Paeo-niae Radix Alba at the ratio of 6∶1∶6. The practical application of it is limited compared with other famous Chinese medicine prescriptions. Only one company produces Wuji Pills in China. In this study, ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to analyze and identify 26 identical compounds from Wuji Pills and drug-containing plasma of rats. Based on these components, 46 potential targets were screened out with network pharmacology methods, followed by the component-target network construction, Gene Ontology(GO) term enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and disease prediction. It was concluded that Wuji Pills acted on core targets such as PTGS2, PTSG1, NCOA2, HSP9 OAD1, and RXRA through magnoflorine, hydroxyevodiamine, daucosterol, and berberine and exerted pharmacodynamic effects through various pathways such as calcium ion signaling pathway, phosphatidylinositol-3-kinase-protein kinase B(PI3 K-Akt) signaling pathway, and vascular endothelial growth factor(VEGF) signaling pathway. Thus, Wuji Pills has therapeutic potential for Alzheimer's disease, diabetes mellitus, myocardial ischemia, and other diseases in addition to the conventional disease(irritable bowel syndrome, IBS). The above research results can provide a reference for the comprehensive interpretation of the pharmacodynamic basis of Wuji Pills and the expansion of clinical application. At the same time, a lot of components in serum and the in vivo transformed and metabolized components of Wuji Pills have similar structure and relative molecular weight. In theory, these components may show additive effects and the competitive/antagonistic effects on the same target. According to the hypothesis of "additive effect of multiple components for a single target" in traditional Chinese medicine, multiple similar components may exert the additive effects on local targets. This study can partly prove the scientificity of this hypothesis and provide laboratory evidence.

Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination

hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice.

BACKGROUND: Spinal cord injury (SCI) is a common disease that results in motor and sensory disorders and even lifelong paralysis. The transplantation of stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), or subsequently generated stem/progenitor cells, is predicted to be a promising treatment for SCI. In this study, we aimed to investigate effect of human iPSC-derived neural stem cells (hiPSC-NSCs) and umbilical cord-derived MSCs (huMSCs) in a mouse model of acute SCI. METHODS: Acute SCI mice model were established and were randomly treated as phosphate-buffered saline (PBS) (control group), repaired with 1 × 105 hiPSC-NSCs (NSC group), and 1 × 105 huMSCs (MSC group), respectively, in a total of 54 mice (n = 18 each). Hind limb motor function was evaluated in open-field tests using the Basso Mouse Scale (BMS) at days post-operation (dpo) 1, 3, 5, and 7 after spinal cord injury, and weekly thereafter. Spinal cord and serum samples were harvested at dpo 7, 14, and 21. Haematoxylin-eosin (H&E) staining and Masson staining were used to evaluate the morphological changes and fibrosis area. The differentiation of the transplanted cells in vivo was evaluated with immunohistochemical staining. RESULTS: The hiPSC-NSC-treated group presented a significantly smaller glial fibrillary acidic protein (GFAP) positive area than MSC-treated mice at all time points. Additionally, MSC-transplanted mice had a similar GFAP+ area to mice receiving PBS. At dpo 14, the immunostained hiPSC-NSCs were positive for SRY-related high-mobility-group (HMG)-box protein-2 (SOX2). Furthermore, the transplanted hiPSC-NSCs differentiated into GFAP-positive astrocytes and beta-III tubulin-positive neurons, whereas the transplanted huMSCs differentiated into GFAP-positive astrocytes. In addition, hiPSC-NSC transplantation reduced fibrosis formation and the inflammation level. Compared with the control or huMSC transplanted group, the group with transplantation of hiPSC-NSCs exhibited significantly improved behaviours, particularly limb coordination. CONCLUSIONS: HiPSC-NSCs promote functional recovery in mice with acute SCI by replacing missing neurons and attenuating fibrosis, glial scar formation, and inflammation.