Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation. METHODS: The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. RESULTS: A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence. CONCLUSION: The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.

Development and validation of a novel stemness-related prognostic model for neuroblastoma using integrated machine learning and bioinformatics analyses.

Background: Neuroblastoma (NB) is a common solid tumor in children, with a dismal prognosis in high-risk cases. Despite advancements in NB treatment, the clinical need for precise prognostic models remains critical, particularly to address the heterogeneity of cancer stemness which plays a pivotal role in tumor aggressiveness and patient outcomes. By utilizing machine learning (ML) techniques, we aimed to explore the cancer stemness features in NB and identify stemness-related hub genes for future investigation and potential targeted therapy. Methods: The public dataset GSE49710 was employed as the training set for acquire gene expression data and NB sample information, including age, stage, and MYCN amplification status and survival. The messenger RNA (mRNA) expression-based stemness index (mRNAsi) was calculated and patients were grouped according to their mRNAsi value. Stemness-related hub genes were identified from the differentially expressed genes (DEGs) to construct a gene signature. This was followed by evaluating the relationship between cancer stemness and the NB immune microenvironment, and the development of a predictive nomogram. We assessed the prognostic outcomes including overall survival (OS) and event-free survival, employing machine learning methods to measure predictive accuracy through concordance indices and validation in an independent cohort E-MTAB-8248. Results: Based on mRNAsi, we categorized NB patients into two groups to explore the association between varying levels of stemness and their clinical outcomes. High mRNAsi was linked to the advanced International Neuroblastoma Staging System (INSS) stage, amplified MYCN, and elder age. High mRNAsi patients had a significantly poorer prognosis than low mRNAsi cases. According to the multivariate Cox analysis, the mRNAsi was an independent risk factor of prognosis in NB patients. After least absolute shrinkage and selection operator (LASSO) regression analysis, four key genes (ERCC6L, DUXAP10, NCAN, DIRAS3) most related to mRNAsi scores were discovered and a risk model was built. Our model demonstrated a significant prognostic capacity with hazard ratios (HR) ranging from 18.96 to 41.20, P values below 0.0001, and area under the receiver operating characteristic curve (AUC) values of 0.918 in the training set, suggesting high predictive accuracy which was further confirmed by external verification. Individuals with a low four-gene signature score had a favorable outcome and better immune responses. Finally, a nomogram for clinical practice was constructed by integrating the four-gene signature and INSS stage. Conclusions: Our findings confirm the influence of CSC features in NB prognosis. The newly developed NB stemness-related four-gene signature prognostic signature could facilitate the prognostic prediction, and the identified hub genes may serve as promising targets for individualized treatments.

[Clinical study of intercondylar fossa formation to prevent intercondylar fossa impingement after high tibia osteotomy].

OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION: Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.

Characterization and therapeutic perspectives of differentiation-inducing therapy in malignant tumors.

Cancer is a major public health issue globally and is one of the leading causes of death. Although available treatments improve the survival rate of some cases, many advanced tumors are insensitive to these treatments. Cancer cell differentiation reverts the malignant phenotype to its original state and may even induce differentiation into cell types found in other tissues. Leveraging differentiation-inducing therapy in high-grade tumor masses offers a less aggressive strategy to curb tumor progression and heightens chemotherapy sensitivity. Differentiation-inducing therapy has been demonstrated to be effective in a variety of tumor cells. For example, differentiation therapy has become the first choice for acute promyelocytic leukemia, with the cure rate of more than 90%. Although an appealing concept, the mechanism and clinical drugs used in differentiation therapy are still in their nascent stage, warranting further investigation. In this review, we examine the current differentiation-inducing therapeutic approach and discuss the clinical applications as well as the underlying biological basis of differentiation-inducing agents.

Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer.

Dormant cancer cells account for cancer recurrence, distant metastasis and drug resistance which lead to poor prognosis in colorectal cancer (CRC). However, little is known about the molecular mechanisms regulating tumor cell dormancy and how to eliminate dormant cancer cells. Recent studies indicate autophagy affects dormant tumor cell survival. Here, we found that polo-like kinases 4 (PLK4), a central regulator of the cell cycle and proliferation, plays a crucial role in regulating CRC cells dormancy both in vitro and in vivo. Downregulation of PLK4 induced dormancy and inhibited migration and invasion in different CRC cell lines. Clinically, PLK4 expression was correlated with the dormancy markers (Ki67, p-ERK, p-p38) and late recurrence in CRC tissues. Mechanistically, downregulation of PLK4 induced autophagy contributed to restoring phenotypically aggressive tumor cells to a dormant state through the MAPK signaling pathway, and inhibition of autophagy would trigger apoptosis of dormant cells. Our findings reveal that downregulation of PLK4-induced autophagy contributes to tumor dormancy and autophagy inhibition leads to apoptosis of CRC dormant cells. Our study is the first to report that downregulation PLK4 induced autophagy is an early event in CRC dormancy and highlights autophagy inhibitor as a potential therapeutic target for dormant cell elimination.

Integrating Bulk-seq and Single-cell-seq Reveals Estrogen and MAPK Pathways Associating with Neuroblastoma Outcome.

INTRODUCTION: Neuroblastoma is the most common extracranial solid tumor in children. Patients with high-risk neuroblastoma have a 5-year survival rate less than 50% after extensive treatment. Signaling pathways control cell fate decisions that dictate the behavior of tumor cells. The deregulation of signaling pathways is etiological in cancer cells. Thus, we speculated that the pathway activity of neuroblastoma contains more prognostic information and therapeutic targets. METHODS: Using a footprint-based method, we calculated the activity of fourteen pathways in neuroblastoma. Through stepwise Cox regression analyses, we established a three-gene prognostic signature whose predictive performance was evaluated by external validation. Combining a single-cell sequencing dataset, the most active pathways in high-risk neuroblastoma were found. RESULTS: We found that several pathway activities were correlated with neuroblastoma outcomes. We built a three-gene model comprising DLK1, FLT3, and NTRK1, which exhibited superior internal and external performances. We created a nomogram that combines clinical characteristics to aid in the selection and visualization of high-risk neuroblastoma patients. Furthermore, by integrating a single-cell sequencing dataset, we found that estrogen and MAPK were the most active pathways in high-risk neuroblastoma. CONCLUSION: Our findings suggest that pathway-related therapies may hold promise for the treatment of high-risk neuroblastoma.

Tumor dormancy is closely related to prognosis prediction and tumor immunity in neuroblastoma.

Background: Neuroblastoma (NB), which is the most frequent and fatal solid tumor in early childhood, lacks an accurate approach to prevent or forecast its recurrence. Dormant NB cells are responsible for metastasis, drug resistance, and suppressive activity in the immune system. However, there is a lack of systematic research on the interaction between dormancy and NB prognosis and its potential associations with tumor immunity. Methods: We downloaded NB gene expression data and clinical information from the Gene Expression Omnibus and ArrayExpres databases. Based on consensus clustering of the expression of dormancy-associated genes, the NB samples were classified into different groups, and differentially expressed genes (DEGs) were explored in each group. Functional analyses of DEGs were performed, followed by the establishment of a predictive dormancy signature and the assessment of tumor immunity. Finally, sex, age, International Neuroblastoma Staging System (INSS) stage, and MYCN status were identified as independent overall survival-related variables, which were incorporated into the nomogram. Results: A dormancy-associated gene signature, including CDKN2A, BHLHB3, CDKN2B, MAPK14, CDKN1B, and BMP7, was established. The gene signature showed a strong correlation with NB immune infiltration and capacity to predict NB patient prognosis. A nomogram including MYCN status, INSS stage, age and gene signature risk score was established which further divided NB into high, medium and low-risk groups. This nomogram had certain guiding significance in decision-making for clinical treatment. Conclusions: Our results suggested that the 6-gene genetic signature for NB based on dormancy could predict NB survival and response to immunotherapy.

Tunable orientation of two-dimensional assembled Au octahedron superlattices in polymer films as flexible SERS substrates.

Anisotropic nanoparticles have been widely used as building blocks for preparing surface-enhanced Raman spectroscopy (SERS) substrates. However, tailoring the SERS activity at the self-assembly level through the anisotropic nanoparticle orientation is a big challenge, mainly due to the lack of simple assembly methods. In the present work, we report an air-water interface mediated co-assembly (AWIMCoA) strategy to prepare flexible 2D superlattices of Au octahedra with tunable orientations. We have demonstrated that Au octahedra can self-assemble into face-up, edge-up and vertex-up orientations on changing the surface wettability of Au octahedra, which determines the interparticle anisotropic interactions and the interaction between Au octahedra and the poly(styrene-ethylene-butylene-styrene) (SEBS) nanomembrane. The effect of assembly orientation on the SERS performance of 2D superlattices has been studied through correlated SEM characterization and SERS mapping. Among all the orientational modes, flexible 2D superlattices with the vertex-up orientation show the highest enhancement performance and uniformity, which is further demonstrated by theoretical simulation. Partially embedded 2D superlattices in the SEBS nanomembrane are robust to remove the surface ligands without breaking the whole nanostructure. This post-treatment process boosts the SERS performance of the 2D superlattice with the edge-up orientation by forming fused nanostructures among neighboring Au octahedra. We expect that the co-assembly method will be widely applied in the preparation of reusable and high-performance SERS substrates for broad application.

Advanced plasmonic technologies for multi-scale biomedical imaging.

The use of imaging technologies has been critical in deciphering biological phenomena, structures, and mechanisms across a wide range of spatial scales. The spatial resolution of traditional imaging modalities cannot meet the needs of high-precision research and diagnosis in biomedical fields. Plasmon resonance is the light-matter interaction that allows localizing far-field radiation in the near field with an intense electromagnetic field, enhancing the nanometric ablation, elastic/inelastic scattering of the adsorbate, and photoluminescence of the fluorophore nearby. Further, plasmon resonance scattering of nanoparticles can sensitively indicate the local environmental changes. This is accomplished by combining the spatially resolved capability with molecular spectrometry techniques such as Raman, infrared, fluorescence, etc., leading to a series of excellent imaging techniques to interrogate diverse biological processes from the tissue to subcellular level. In this tutorial review, we first provide the fundamental aspects of plasmonics. Then we give a systematic discussion of the working principle of these plasmon-based imaging techniques with an emphasis on the achievable spatial resolutions: surface-enhanced Raman spectroscopy (micrometre to nanometre), tip-enhanced ablation and ionization mass spectrometry (submicrometre), scattering-type scanning near-field optical microscopy (nanometre), tip-enhanced Raman spectroscopy (nanometre), tip-enhanced fluorescence spectroscopy (nanometre), and plasmon/molecular ruler microscopy (nanometre to angstrom). We also review the recent developments of the bioimaging applications of these techniques and expect that the plasmon-based techniques will not only pave a new way to decipher mysteries in life sciences but also hold great potential to be extended from fundamental research studies to real-life biomedical applications.

Treatment of primary tracheal schwannoma with endoscopic resection: A case report.

BACKGROUND: Schwannoma is a benign tumor originating from the peripheral nerve sheath. The clinical symptoms of tracheal schwannoma depend on the location of the tumor, and the most common clinical symptoms are cough and hemoptysis. The most effective treatment for benign tumors is complete resection of the primary lesion at an early stage. Our experience has demonstrated that primary tracheal schwannoma can be safely excised with a high-frequency electric knife in a minimally invasive manner. CASE SUMMARY: We report a 61-year-old asymptomatic woman who underwent chest computed tomography (CT), which accidentally found an intraluminal tracheal mass without enlarged lymph nodes. Then, the patient underwent bronchoscopy, which found that the tracheal mass originated from the left wall of the upper trachea, was less than 1.5 cm in size, immovable, smooth and 4 cm away from the vocal cord, resulting in partial upper respiratory tract obstruction. Treatment was performed using an endoscopic resection for en bloc removal of the tracheal mass. The diagnosis was primary tracheal schwannoma. A follow-up was performed after endoscopic surgery, and bronchoscopy and thoracic CT were used to monitor whether there was a recurrence. At present, there is no evidence of recurrence, and the patient had a good quality of life. Endoscopic resection may be effective and safe in the treatment of primary tracheal schwannoma. CONCLUSION: Primary tracheal schwannoma is a very rare benign tumor. In this case, we cured it by complete endoscopic resection.

Medial compartment cartilage repair and lower extremity biomechanical changes after single-plane high tibial osteotomy of distal tibial tuberosity.

OBJECTIVE: To observe the cartilage repair of the medial compartment and the biomechanical changes of the lower extremities after single-plane high tibial osteotomy of distal tibial tuberosity (DTT-HTO). METHODS: A total of 30 patients, including 11 males and 19 females, who underwent DTT-HTO with arthroscopic operation in our hospital from January 2020 to January 2021 and underwent arthroscopic exploration again during the second operation for internal fixation were enrolled. There were 32 knees, including 13 left knees and 19 right knees. Age ranged from 50 to 78, with an average of 63.20 ± 6.61 years old. All patients completed two surgeries and were followed up, and no adverse events occurred during the period. International Cartilage Repair Society (ICRS) was used to assess the cartilage condition of the medial compartment of the knee during the two surgeries. In this paper, the weight-bearing line ratio (WBLR), the medial proximal tibia angle (MPTA), the femoral tibial angle (FTA) and the posterior tibial slope (PTS) were used to evaluate the changes of the mechanical state of the lower limbs. The visual analogue scale (VAS) score and the Western Ontario and McMaster University Osteoarthritis (WOMAC) Index score were used to evaluate the improvement in knee pain and function. RESULTS: All patients completed two operations without adverse events and serious complications. The medial compartment cartilage of all patients had different degrees of repair during the second operation, and the difference was statistically significant compared with the first operation (P < 0.05). During the second operation, the WBLR was corrected from (17.69 ± 2.16)% to (60.90 ± 1.97)%, the MPTA was corrected from (80.72 ± 1.61)° to (89.91 ± 2.58)°, the FTA was corrected from (182.31 ± 3.03)° to (171.81 ± 2.24)°, the difference was statistically significant (P < 0.05). There was no statistical difference in PTS between the two surgeries (P > 0.05). At the second operation, the VAS score decreased from 7.50 ± 1.34 to 0.34 ± 0.85, the WOMAC score decreased from 119.50 ± 10.43 to 46.25 ± 4.13, and the difference was statistically significant (P < 0.05). CONCLUSION: DTT-HTO can significantly correct the weight-bearing line, restore the biomechanical parameters of the lower limb to the normal range, significantly relieve pain and improve knee function, and the medial compartment cartilage repair and regeneration phenomenon will occur after the correction of the weight-bearing line.

Self-Calibration 3D Hybrid SERS Substrate and Its Application in Quantitative Analysis.

Surface-enhanced Raman spectroscopy (SERS) has been widely applied in many fields as a sensitive vibrational fingerprint technique. However, SERS faces challenges in quantitative analysis due to the heterogeneity of hot spots. An internal standard (IS) strategy has been employed for correcting the variation of hot spots. However, the method suffers from limitations due to the competitive adsorption between the IS and the target analyte. In this work, we combined the IS strategy with the 3D hybrid nanostructures to develop a bifunctional SERS substrate. The substrate had two functional units. The bottom self-assembly layer consisted of Au@IS@SiO2 nanoparticles, which provided a stable reference signal and functioned as the calibration unit. The top one consisted of appropriate-sized Au octahedrons for the detection of target analytes, which was the detection unit. Within the 3D hybrid nanostructure, the calibration unit improved the SERS performance of the detection unit, which was demonstrated by the 6-fold increase of SERS intensity when compared with the 2D substrate. Meanwhile, the reproducibility of the detection was greatly improved by correcting the hot spot changes through the calibration unit. Two biomedical molecules of cotinine and creatinine in ultrapure water and artificial urine, respectively, were sensitively determined by the 3D hybrid substrate. We expect that the developed bifunctional 3D substrate will open up new ways to advance the applications of SERS.

On the Effect of Electroacupuncture in Promoting Healing after High Tibial Osteotomy.

Purpose: To explore the clinical effect of electroacupuncture in promoting the healing of the osteotomy area after high tibial osteotomy. Methods: 50 patients with knee osteoarthritis who underwent open wedge high tibial osteotomy (OWHTO) were selected and randomly divided into the observation group and control group. The control group got the common postoperative treatment, and the observation group was added electroacupuncture from the 3rd day after the operation on the basis of the control group. The electroacupuncture acupoints were selected SP10, ST34, ST32, EX-LE2, ST40,KI6, KI3, SP6, and ST41, once a day, and 14 days were a course of treatment. And then we contrasted the index of the Lane-Sandhu X-ray score, the skin incision healing time, the swelling subsided time, Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index Score (WOMAC), and Lysholm in different time. Results: The Lane-Sandhu X-ray score of the observation group was better than that of the control group at all time points (P < 0.05), and the time to achieve bone healing was about 2 weeks earlier than that of the control group. The skin healing and swelling were the subsided time in the osteotomy area. Both were better than the control group, and the difference was statistically significant (P < 0.05). The VAS score, WOMAC score, and Lysholm score of the two groups were significantly improved compared with preoperatively, and the difference was statistically significant (P < 0.05). The improvement of the observation group's VAS score, WOMAC score, and Lysholm score at 1 week, 4 weeks, and 8 weeks after the end of the treatment course was better than that of the control group, and the difference was statistically significant (P < 0.05). Conclusion: Electroacupuncture can quicken the healing of bone tissue and surrounding soft tissues in the osteotomy area after high tibial osteotomy, and at the same time, it can help the relief of knee joint pain and improve knee joint function.

Patellar Height after High Tibial Osteotomy of the Distal Tibial Tuberosity: A Retrospective Study of Age Stratification.

OBJECTIVE: To explore the effect of age stratification on patellar height after single-plane high tibial osteotomy of the distal tibial tuberosity (DTT-HTO). METHODS: A retrospective analysis was performed on 110 knee joints undergoing DTT-HTO. Patients were divided into three groups according to age: under 60 years old, 28 cases; 60 to 70 years old, 61 cases; and over 70 years old, 21 cases. All patients were followed up for no less than 12 months, and at each follow-up, short-leg radiographs and whole-leg radiographs were taken. The values of the Caton-Deschamps index (CDI) and Blackburne-Peel index (BPI) of single-short-leg radiographs and the femoral-tibial angle (FTA) and weight-bearing line ratio (WBLR) of whole-leg radiographs were measured before and at the last follow-up. The Lysholm score before and at the last follow-up and the visual analogue scale (VAS) score before and 3 days after surgery and at the last follow-up were calculated. The frequency of classification of the normal-height patella, patella alta, and patella baja before and after surgery was recorded. RESULTS: There were no significant differences in CDI and BPI preoperatively or postoperatively among the three groups (P > 0.05), and there were no statistically significant differences in FTA and WBLR. There were no significant differences in CDI, BPI, FTA, or WBLR between the three groups before and after the operation (P > 0.05). The Lysholm score increased from 48.84 ± 10.10 before surgery to 91.96 ± 3.082 after surgery (P < 0.05); the VAS score decreased from 8.23 ± 0.99 before surgery to 1.93 ± 0.953 at 3 days after surgery and 1.07 ± 0.53 at the last follow-up (P < 0.01). No significant difference was observed in the incidence of each patellar height classification between the three groups preoperatively and postoperatively. CONCLUSION: Patellar height is not influenced by DTT-HTO. The age of patients is not a limiting factor for the selection of this surgical procedure. Without affecting the height of the patella, DTT-HTO can effectively reduce pain in the knee joint, restore the function of the knee joint, and delay the progression of patellar arthritis.

Three-dimensional surgical planning and clinical evaluation of the efficacy of distal tibial tuberosity high tibial osteotomy in obese patients with varus knee osteoarthritis.

PURPOSE: High tibial osteotomy (HTO) is an effective surgical treatment for varus knee osteoarthritis. However, obese patients require reinforced internal fixation materials to prevent internal fixation fractures and hardware failure after osteotomy. Therefore, the purpose of our study is to evaluate the clinical efficacy of distal tibial tuberosity high tibial osteotomy (DTT-HTO) using the new patented π-shaped plate in obese patients with varus knee osteoarthritis. METHOD: Thirty-four obese patients (39 knees) with varus knee osteoarthritis who underwent DTT-HTO with the π-shaped plate and second-look arthroscopy when implant removal occurred from September 2017 to June 2020 were retrospectively reviewed. Three-dimensional surgical planning using DTT-HTO on the knees is performed. There were 9 males and 25 females, with body mass index (BMI) values ranging from 30.3 to 38.5 kg/m2 and ages ranging from 50 to 75 years old. The radiological assessment was performed with the femora tibial angle (FTA) and the weight-bearing line ratio (WBLR). The clinical outcomes were evaluated by the Hospital for Special Surgery (HSS) knee score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The status of the cartilage was evaluated by the International Cartilage Repair Society (ICRS) grading system. RESULTS: All patients were followed up for 18-30 months. The FTA significantly changed from 181.68±1.68.preoperatively to171.29±1.51.at the last follow-up (P<0.001). The WBLR significantly increased from 16.85±2.20 to 55.41±2.46% from before surgery to the last follow-up after surgery (P<0.001). The HSS score significantly improved from 56.65±5.27 preoperatively to 68.79±2.61, 77.82±2.15, and 86.12±2.78 at the 6-month, 12-month, and last follow-up after surgery (P<0.001). The WOMAC score significantly decreased from 105.47±3.89 preoperatively to 80.50±4.20, 71.44±4.65, and 52.44±3.14 at the 6-month, 12-month, and last follow-up after surgery (P<0.001). During implant removal, no internal fixation fractures occurred in any patient. The articular cartilage grade in the medial compartment of the knee were significantly higher in the second arthroscopy than in the first arthroscopy, according to the ICRS grading system (P<0.001). The articular cartilage grade in the lateral compartment of the knee showed no statistical differences from the first- to the second-look arthroscopy (P>0.05). CONCLUSION: There are no correlation between BMI and postoperative outcomes. DTT-HTO shows yield excellent clinical results in obese patients with varus knee osteoarthritis. It can be recommended to be used for the heavy patients.

The impact of decreased expression of SVEP1 on abnormal neovascularization and poor prognosis in patients with intrahepatic cholangiocarcinoma.

Introduction: Intrahepatic cholangiocarcinoma (ICC) is one of the most highly heterogeneous malignant solid tumors; it is generally insensitive to clinical treatment and has a poor prognosis. Evidence suggests that abnormal neovascularization in the tumor microenvironment is an important cause of treatment resistance as well as recurrence and metastasis, but the key regulatory molecules are still largely unknown and should be identified. Method: We assessed the novel extracellular matrix protein (ECM) Sushi, von Willebrand factor type A, EGF and pentraxin containing 1 (SVEP1) expression pattern in the ICC by using immunohistochemistry. Multiplex immunofluorescence and Kaplan-Meier analysis were applied to explore the correlation between the low expression of SVEP1 and abnormal blood vessels and the clinical prognosis of ICC. Results: Our study showed that the expression of SVEP1 in most ICC samples was relatively lower than in the adjacent tissues. Statistical analysis suggested that patients with decreased SVEP1 expression always had shorter overall survival (OS) and disease-free survival (DFS). Moreover, the expression of SVEP1 was negatively correlated with the proportion of abnormal neovascularization in the tumor microenvironment of the ICC. Consistently, the key molecule of promoting vascular normalization, Ang-1, is positively correlated with the SVEP1 expression and prognosis in the ICC. In addition, the proportion of high Ki-67 expression was higher in the ICC samples with low SVEP1 expression, suggesting that the SVEP1 low expressed sample is in a malignant phenotype with high proliferation. Conclusion: This study reveals that SVEP1 is a promising prognostic biomarker for ICC and provides fresh insight into the role and potential new mechanism of abnormal neovascularization in ICC progression.

Identification of a Five-Gene Signature Derived From MYCN Amplification and Establishment of a Nomogram for Predicting the Prognosis of Neuroblastoma.

Background: Neuroblastoma (NB), the most common solid tumor in children, exhibits vastly different genomic abnormalities and clinical behaviors. While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments. Materials and Methods: Six data sets of gene expression and related clinical data were downloaded from the Gene Expression Omnibus (GEO) database, ArrayExpress database, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to the presence or absence of MYCN amplification, patients were divided into two groups. Differentially expressed genes (DEGs) were identified between the two groups. Enrichment analyses of these DEGs were performed to dig further into the molecular mechanism of NB. Stepwise Cox regression analyses were used to establish a five-gene prognostic signature whose predictive performance was further evaluated by external validation. Multivariate Cox regression analyses were used to explore independent prognostic factors for NB. The relevance of immunity was evaluated by using algorithms, and a nomogram was constructed. Results: A five-gene signature comprising CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 was established. The five-gene signature had good performance in predicting survival and was demonstrated to be superior to International Neuroblastoma Staging System (INSS) staging and the MYCN amplification status. Finally, a nomogram based on the five-gene signature was established, and its clinical efficacy was demonstrated. Conclusion: Collectively, our study developed a novel five-gene signature and successfully built a prognostic nomogram that accurately predicted survival in NB. The findings presented here could help to stratify patients into subgroups and determine the optimal individualized therapy.

PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway.

Some studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.

[High tibial osteotomy combined with lateral retinacular release for the treatment of knee varus osteoarthritis with lateral patellar compression syndrome].

OBJECTIVE: To investigate the clinical effect of high tibial osteotomy combined with arthroscopic lateral retinacular release in the treatment of knee varus osteoarthritis. METHODS: From October 2017 to April 2019, a retrospective analysis was performed on 43 patients with knee varus osteoarthritis and lateral patellar compression syndrome treated by high tibial osteotomy combined with arthroscopic lateral retinacular release. There were 15 males and 28 females, aged 53 to 72(62.05±5.17) years. The visual analogue scale(VAS), Lysholm, and the knee range of motion were used to evaluate knee pain and functional recovery before operation, 2 weeks, 3 months and 12 months after operation. And the congruence angle (CA), patellar tilt angle (PTA), and femala-tibial angle (FTA) were measured respectively before and 12 months after operation to evaluate the congruence of patellar joint, and the improvement of line of gravity of lower limb. RESULTS: All 43 patients were followed up for more than 12 months, with a follow-up time of 14 to 28 (19.60±4.50) months. The VAS scores decreased from 6.65±0.65 before operation to 2.16±0.95, 0.51±0.77 and 0.33±0.64 at 2 weeks, 3 months and 12 months after operation, and the difference was statistically significant (P<0.001). Lysholm score increased from 43.02±8.54 before operation to 46.84±2.81, 72.42±5.30, and 93.40±5.44 at 2 weeks, 3 months and 12 months after operation, and the difference was statistically significant (P<0.001). The knee range of motion increased from (86.97±5.02)° before operation to (99.38±3.27)°, (110.13±4.13)°, and (113.03±4.85)° at 2 weeks, 3 months and 12 months after operation, the difference was statistically significant (P<0.001). The CA decreased from (7.81±1.21)° before operation to (5.82±4.10)° at 12 months after operation, the PTA decreased from (15.87±2.89)° before operation to (13.79±4.26)° at 12 months after operation, and the FTA decreased from(182.61±2.07)° before operation to(170.89±0.89)° at 12 months after operation, and the differences were statistically significant (P<0.05). One case received proper braking and anticoagulation after operation, and was improved after 1 week. The swelling was observed in 14 patients after operation, and subsided about 2 weeks later. CONCLUSION: High tibial osteotomy combined with arthroscopic lateral retinacular release can relieve weight-bearing pain in frontal axis and improve the function of knee in sagittal axis.

Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma.

BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are highly sensitive for diagnosing and staging lung cancer. In recent years, targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma (NSCLC). Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach. AIM: To evaluate the feasibility and accuracy of tissue samples obtained using EUS-FNA and EBUS-TBNA for molecular diagnosis of NSCLC. METHODS: A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019. All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture. We detected abnormal expression of EGFR, KRAS, MET, HER2, ROS1 and anaplastic lymphoma kinase protein. Two patients failed to complete molecular testing due to insufficient tumor tissue. The clinical features, puncture records, molecular testing results and targeted treatment in the remaining 81 patients were summarized. RESULTS: In a total of 99 tissue samples obtained from 83 patients, molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9% (93/99). Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue. In the remaining 81 patients, 62 cases (76.5%) were found to have adenocarcinoma, 11 cases (13.6%) had squamous cell carcinoma, 3 cases (3.7%) had adenosquamous carcinoma and 5 cases (6.2%) had NSCLC-not otherwise specified. The results of molecular testing showed EGFR mutations in 21 cases (25.9%), KRAS mutations in 9 cases (11.1%), ROS-1 rearrangement in 1 case (1.2%) and anaplastic lymphoma kinase-positive in 5 cases (6.2%). Twenty-four patients with positive results received targeted therapy. The total effectiveness rate of targeted therapy was 66.7% (16/24), and the disease control rate was 83.3% (20/24). CONCLUSION: Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.