Rehabilitation exercise program after surgical treatment of patellar tendon rupture: A case report.

OBJECTIVE: This case report describes in detail a rehabilitation and exercise program following surgical treatment of patellar tendon rupture and offers postoperative therapeutic goals and recommendations, with the aim of expediting the resumption of activities of daily living and sports participation following the surgical procedure. In addition, this report analyzes the cause of the patellar tendon rupture in this case. DESIGN: Case report. PARTICIPANTS: The patient, a 25-year-old male recreational athlete (height: 184 cm; weight: 80 kg; right-hand dominant), experienced a complete rupture of the patellar tendon upon landing on the left lower extremity during an unopposed dribble turn. REHABILITATION EXERCISE PROGRAM: A well-structured rehabilitation program was implemented. Passive knee flexion range of motion (ROM) exceeded 90° at week 5 and was fully recovered at week 16. A second surgery was performed at week 19 to remove the decompression wires, and the patient progressively resumed basic physical and specialized training at 7 months post-surgery. MAIN OUTCOME MEASURES: Morphometric and functional tests were performed to measure the effectiveness of rehabilitation throughout the postoperative process. CONCLUSIONS: Early surgical repair and an immediate postoperative rehabilitation program have a positive impact on knee ROM, function, and muscle strength. The causes of the patellar tendon rupture in this patient included long-standing uncontrolled patellar tendinopathy, impaired mobility of the ankle and hip joints, poor landing technique, and muscle strength imbalances.

Heterogeneity and individualized treatment of microenvironment in glioblastoma (Review).

The heterogeneity of glioblastoma can suppress immune cell function and lead to immune evasion, which presents a challenge in developing effective molecular therapies for tumor cells. However, the study of tumor immune heterogeneity holds great potential for clinical immunotherapy. Liquid biopsy is a useful tool for accurately monitoring dynamic changes in tumor immune heterogeneity and the tumor microenvironment. This paper explores the heterogeneity of glioblastoma and the immune microenvironment, providing a therapeutic basis for individualized treatment. Using liquid biopsy technology as a new diagnostic method, innovative treatment strategies may be implemented for patients with glioblastoma to improve their outcomes.

TRIM32 promotes oral squamous cell carcinoma progression by enhancing FBP2 ubiquitination and degradation.

The aberrant expression of TRIM32, an E3 ubiquitin ligase, has been identified in multiple malignant cancer types. Nevertheless, the functional roles and detailed mechanisms of TRIM32 in oral squamous cell carcinoma (OSCC) remain to be elucidated. Here, we investigated TRIM32 expression and its functional role in OSCC. TRIM32 expression was consistently elevated in OSCC tissues, particularly in samples from patients with advanced clinical grades. Functionally, silencing TRIM32 dampened OSCC cell growth, migration and invasion. Additionally, a xenograft tumor model suggested that TRIM32 knockdown suppressed in vivo OSCC tumor growth and lung metastasis formation. Mechanistically, we discovered that TRIM32 directly bound to the FBP2 protein via mass spectrometry and co-immunoprecipitation. TRIM32 could interact with FBP2 and accelerates its degradation, eventually enhancing glycolysis in OSCC cell lines. Importantly, rescue assays demonstrated that FBP2 silencing could at least partially offset the tumor-suppressive and aerobic glycolysis inhibition effect induced by TRIM32 knockdown. Thus, our findings demonstrate that TRIM32 plays a crucial role in promoting tumor growth and enhancing glycolysis through FBP2 inhibition. Given OSCC is associated with increased glycolysis levels, our study suggests potential therapeutic targets for OSCC treatment.

Linkage of blood cell division cycle 42 with T helper cells, and their correlation with anxiety, depression, and cognitive impairment in stroke patients

Cell division cycle 42 (CDC42) regulates T helper (Th) cell differentiation and is related to psychological disorders. This study aimed to assess the correlation between blood CDC42 and Th cells, and their association with mental issues in stroke patients. Peripheral blood samples were obtained from 264 stroke patients and 50 controls. Then, serum CDC42 was measured by enzyme-linked immunosorbent assay, and Th1, Th2, and Th17 cells were detected by flow cytometry. Hospital Anxiety and Depression Scale (HADS) and Mini Mental State Examination (MMSE) were applied to patients. CDC42 was decreased (P<0.001), Th1 (P=0.013) and Th17 (P<0.001) cells were elevated, while Th2 cells (P=0.108) showed no difference in stroke patients compared to controls. In addition, CDC42 was negatively associated to Th1 (P=0.013) and Th17 (P<0.001) cells in stroke patients but were not associated with Th2 cells (P=0.223). Interestingly, CDC42 was negatively associated with HADS-anxiety (P<0.001) and HADS-depression scores (P=0.034) and positively associated with MMSE score (P<0.001) in stroke patients. Lower CDC42 was associated to lower occurrence of anxiety (P=0.002), depression (P=0.001), and cognitive impairment (P=0.036) in stroke patients. Furthermore, increased Th17 cells were positively correlated with HADS-anxiety and HADS-depression scores and inversely correlated with MMSE score, which were also associated with higher occurrence of anxiety, depression, and cognitive impairment in stroke patients (all P<0.05). Blood CDC42 and Th17 cells were correlated, and both of them were linked to the risk of anxiety, depression, and cognitive impairment. However, the findings need further large-scale validation, and the implicated mechanism needs more investigation.

Aberrant expression of long non-coding RNA PVT1 in allergic rhinitis children: Correlation with disease risk, symptoms, and Th1/Th2 imbalance.

BACKGROUND: Long non-coding RNA plasmacytoma variant translocation 1 (lnc-PVT1) exacerbates inflammation and induces T helper (Th) 1/Th2 imbalance in allergic diseases, but its clinical role in allergic rhinitis (AR) remains unclear. Hence, we conducted this study to compare lnc-PVT1 expression among AR children, disease controls (DCs), and health controls (HCs), aiming to investigate its clinical application in AR children. METHODS: Sixty AR children, 30 DCs, and 30 HCs were enrolled in the study, and then, their lnc-PVT1 expression in peripheral blood mononuclear cell was detected. Serum interferon-gamma (IFN-γ), interleukin 10 (IL-10), Th1, and Th2 cells in AR children were also analyzed. Besides, lnc-PVT1 was also detected at Week (W)4 after treatment in AR patients. RESULTS: Lnc-PVT1 was upregulated in AR children compared with DCs and HCs (both p < 0.001). Lnc-PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and total nasal symptom score (TNSS) in AR children (all p < 0.050), instead of sneezing score (p = 0.115). Lnc-PVT1 negatively associated with Th1 cells in AR children (p = 0.028) also exhibited a negative correlation trend with IFN-γ (but without statistical significance) (p = 0.065). Differently, lnc-PVT1 was positively related to Th2 cells (p = 0.012) and IL-10 (p = 0.021) in AR children. Besides, lnc-PVT1 and TNSS were reduced at W4 after treatment in AR children (both p < 0.001); notably, lnc-PVT1 expression decline was correlated with TNSS decline during treatment (p = 0.013). CONCLUSION: Lnc-PVT1 works as a biomarker, whose aberrant expression is related to disease severity, Th1/Th2 imbalance, and its decrement can reflect treatment outcome in AR children.

Glioma Stem Cells Upregulate CD39 Expression to Escape Immune Response through SOX2 Modulation.

Ectonucleotidase CD39 hydrolyzing extracellular ATP (eATP) functions as a key modulator of immune response in the tumor microenvironment, yet the role of CD39 in contributing tumor stem cells in a more immunosuppressive microenvironment remains elusive. Here we report that the upregulation of CD39 is crucial for the decrease of extracellular ATP concentration around glioma stem cells (GSCs) to maintain an immunosuppressive microenvironment. Adriamycin (ADM) is able to promote the release of ATP, which recruits dendritic cells (DCs) to phagocytose GSCs. CD39 inhibition further increased extracellular ATP concentrations following ADM treatment and DCs phagocytosis. In addition, GSCs upregulated CD39 expression by SOX2-binding CD39 promotor. In mouse tumor models, the combination of ADM and CD39 blockade increased immune cell infiltration and reduced tumor size. These findings suggest that GSCs upregulate CD39 expression by their biological characteristics to maintain an immunosuppressive microenvironment, and CD39 inhibition supplies a favorable tumor microenvironment (TME) for immunotherapeutic intervention and enhances the immune response induced by chemotherapy.

A pilot study of the ultrathin cryoprobe in the diagnosis of peripheral pulmonary ground-glass opacity lesions.

BACKGROUND: It is very difficult to obtain samples of peripheral pulmonary ground-glass opacity lesions (GGOs) by traditional transbronchial biopsy. This study was conducted to evaluate the diagnostic efficacy and safety of transbronchial cryobiopsy (TBCB) of GGOs using a newly developed ultrathin cryoprobe with an outer diameter of 1.1 mm. METHODS: We retrospectively analyzed 20 patients with 23 GGOs who underwent TBCB using the ultrathin cryoprobe from October 2018 to November 2019 in the Shanghai Chest Hospital. The TBCB procedure was performed under the guidance of virtual bronchoscopic navigation (VBN), electromagnetic navigation bronchoscopy (ENB), endobronchial ultrasound, and fluoroscopy. We collected the baseline information of participants, reported diagnostic yield and complications, and analyzed factors may have affected the diagnostic yield. RESULTS: A total of 23 GGOs (12 pure GGOs, 11 mixed GGOs), with an average diameter of 21.58±11.88 mm, underwent TBCB, and the diagnostic yield was 82.61% (19/23). Of the 19 GGOs diagnosed by TBCB, 12 were adenocarcinomas, 5 were inflammation, 1 was occupational interstitial lung disease, and 1 was a pulmonary meningothelial-like nodule. The remaining 4 undiagnosed lesions were confirmed to be adenocarcinomas by further analysis. The diagnostic yield was unchanged by factors including size (GGOs ≥20 mm, GGOs <20 mm), navigation (VBN, ENB), fluoroscopic visibility (visible, invisible), GGO-component (pure GGOs, mixed GGOs), and guide sheath (K-201, K203). There was no presentation of pneumothorax or severe hemorrhage. CONCLUSIONS: The ultrathin cryoprobe is feasible, safe, and has a high diagnostic yield in the diagnosis of pulmonary GGOs. There is vast potential for the ultrathin cryoprobe as a tool for the diagnosis of GGOs, especially for cases suspicious of early-stage lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov. No: NCT03716284. Registered: 20 October, 2018. URL: ClinicalTrials.gov.

Identification of Mir-9 in Glioma Diagnosis and Prognosis.

BACKGROUND: Mir-9 was recognized as a potential tumor suppressor gene or oncogene in varies of diseases; however, its roles in glioma have not been investigated. Our study was to identify the mRNA expression of mir-9 gene in glioma and correlate abnormal versions of microRNAs with clinicopathological features and investigate the impact of mir-9 in glioma prognosis. METHODS: Seventy-one glioma samples, which included 22 grade II, 24 grade III, and 25 glioblastoma tumors of previously untreated patients who underwent surgical excision at Qing Hai Province People's Hospital from 2011 to 2014, were included. In addition, 2 epilepsy patients with normal brain tissue were included as a control group. The expression of mir-9 was examined by RT-PCR in formalin-fixed paraffin embedded primary tissue specimens. The clinicopathologic features, the survival rate of glioma patients were also discussed. The RNA expression of mir-9 and glioma prognosis was evaluated using a Chi-square test, Cox regression model, and GraphPad Prism survival curve analysis. RESULTS: There were 16, 20, 21 cases which showed high expression of mir-9 in grade II and III gliomas and glio-blastoma, 16/22 (72.7%), 20/24 (83.3%), 21/25 (84.0%), respectively. The expression of mir-9 was correlated with the grade of glioma. The mir-9 RNA expression in glioblastoma were higher than grade II and III gliomas (p < 0.05). The higher the grade, the higher the expression, and the difference was significant (p < 0.05), while it was not correlated with patient nationality, gender, or location (p > 0.05). Univariate analysis determined that high expression of mir-9, grade, chemotherapy, radiation therapy, and patient onset age were associated with glioma patient prognosis (p < 0.05). CONCLUSIONS: The expression of mir-9 plays a role in glioma progression, and may be used as a prognostic marker in glioma.

miR-381 Mediates the Development of Head and Neck Squamous Cell Carcinoma via Targeting STC2.

OBJECTIVE: miR-381 is implicated in the occurrence and development of various cancers, yet its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. This study sought to research the direct target of miR-381 in HNSCC and investigate their roles in cancer progression. METHODS: miRNA and mRNA expression files of HNSCC were accessed from TCGA database and then processed for differential analysis. Bioinformatics databases were employed to predict the target mRNAs of the potential miRNA. qRT-PCR was conducted to determine the expression levels of the target miRNA and mRNA. Then, a series of in vitro experiments like CCK-8, colony formation assay, wound healing assay and transwell assay were performed to detect cell proliferation, migration and invasion. Dual-luciferase reporter gene assay was carried out for the further validation of the targeted relationship between the miRNA and mRNA. RESULTS: miR-381 was observed to be greatly down-regulated in HNSCC cells, and its overexpression could inhibit cell proliferation, migration and invasion. Besides, dual-luciferase reporter gene assay confirmed that STC2 was a direct target of miR-381, and their expression levels were reversely correlated. Moreover, rescue experiments demonstrated that overexpressing STC2 could rescue the inhibitory effect of miR-381 overexpression on cell proliferation, migration and invasion. Also, we verified that miR-381/STC2 exerted its function on HNSCC proliferation by mediating the FAK/PI3K/Akt/mTOR signaling pathway. CONCLUSION: miR-381 suppresses cell proliferation, migration and invasion in HNSCC through targeting STC2, and participates in HNSCC development probably via the FAK/PI3K/Akt/mTOR signaling pathway.

The value of navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions: A meta-analysis.

BACKGROUND: To compare the diagnostic yield of peripheral pulmonary lesions (PPLs) with and without navigation system. METHODS: Studies dating from January 1990 to October 2019 were collected from databases. Diagnostic yield of navigation bronchoscopy and non-navigation bronchoscopy was extracted from comparative studies. Subgroup analysis was adopted to test diagnostic yield variation by lesion size, lobe location of the lesion, distance from the hilum, bronchus sign and nature of the lesion. RESULTS: In total, 2131 patients from 10 studies were enrolled into the study. Diagnostic yield of navigation bronchoscopy was statistically higher than non-navigation bronchoscopy for PPLs (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.32, 2.18, P < 0.001), particularly for PPLs in the peripheral third lung (OR 2.26, 95% CI 1.48, 3.44, P < 0.001) and for bronchus sign positive PPLs (OR 2.26, 95% CI 1.21, 4.26, P = 0.011). Navigation bronchoscopy had better performance than non-navigation bronchoscopy when PPLs were ≤ 20 mm (OR 2.09, 95% CI 1.44, 3.03, P < 0.001). It also elevated diagnostic yield of malignant PPLs (OR 1.67, 95% CI 1.26, 2.22, P < 0.001) and PPLs in the bilateral upper lobes (OR 1.50, 95% CI 1.09, 2.08, P = 0.014). CONCLUSIONS: Navigation bronchoscopy enhanced diagnostic yield when compared to non-navigation bronchoscopy, particularly for PPLs in the peripheral third lung, PPLs being bronchus sign positive, PPLs ≤ 20 mm, malignant PPLs and PPLs in the bilateral upper lobes. KEY POINTS: The current study provided systematic evaluation on the diagnostic value of navigation bronchoscopy by comparing it with non-navigation bronchoscopy, and exploring the factors affecting the diagnostic yield.

Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious lung problem with advancing and diffusive pulmonary fibrosis as the pathologic basis, and with oxidative stress and inflammation as the key pathogenesis. Glycyl-L-histidyl-l-lysine (GHK) is a tripeptide participating into wound healing and regeneration. GHK-Cu complexes improve GHK bioavailability. Thus, the current study aimed to explore the therapeutic role of GHK-Cu on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. METHODS: BLM (3 mg/kg) was administered via tracheal instillation (TI) to induce a pulmonary fibrosis model in C57BL/6j mice 21 days after the challenge of BLM. GHK-Cu was injected intraperitoneally (i.p.) at different dosage of 0.2, 2 and 20 µg/g/day in 0.5 ml PBS on alternate day. The histological changes, inflammation response, the collagen deposition and epithelial-mesenchymal transition (EMT) was evaluated in the lung tissue. EMT was evaluated by ɑ-SMA and fibronectin expression in the lung tissue. NF-κB p65, Nrf2 and TGFß1/Smad2/3 signalling pathways were detected by immunoblotting analysis. RESULTS: GHK-Cu complex inhibited BLM-induced inflammatory and fibrotic pathological changes, alleviated the inflammatory response in the BALF by reducing the levels of the inflammatory cytokines, TNF-ɑ and IL-6 and the activity of MPO as well as reduced collagen deposition. In addition, the GHK-Cu treatment significantly reversed the MMP-9/TIMP-1 imbalance and partially prevented EMT via Nrf2, NF-κB and TGFß1 pathways, as well as Smad2/3 phosphorylation. CONCLUSIONS: GHK-Cu presented a protective effect in BLM-induced inflammation and oxidative stress by inhibiting EMT progression and suppressing TGFß1/Smad2/3 signalling in pulmonary fibrosis.

Comparison of the prognosis of neoadjuvant chemoradiotherapy treatment with surgery alone in esophageal carcinoma: a meta-analysis.

BACKGROUND: Resection remains the best treatment for carcinoma of the esophagus in terms of local control, but local recurrence and distant metastasis remain an issue after surgery. Chemo-radiotherapy (CRT) followed by surgery was associated with significantly improved survival benefit, but the effectiveness of neoadjuvant therapy in patients with resectable esophageal carcinoma remains controversial. The aim of this study was to evaluate the effects of neoadjuvant chemoradiotherapy in resectable esophageal carcinoma compared to surgery alone (SA). METHODS: A search for publications that compared the efficacy of CRT with SA in resectable esophageal carcinoma was conducted. After a rigorous review of the quality, the data were extracted from eligible trials. The major outcomes measures were odds ratios (ORs). The ORs with their corresponding 95% confidence intervals were the principal measure of effects. For the meta-analysis, Revman 5.3 software was used to analyze the combined pooled ORs using fixed- or random-effects models according to the heterogeneity. RESULTS: Our findings revealed that, compared with SA, neoadjuvant CRT was associated with improved overall survival (OS) and progression-free survival times, but the 3- and 5-year OS did not show a statistical difference (P≥0.05). The adjuvant chemotherapy group did not show significant improvement on reference rate and metastasis rate compared with the control group. CONCLUSION: CRT does significantly improve progression-free survival and OS in patients with esophageal cancer compared with SA. However, further assessment is still warranted on the role of CRT in future trials with well-selected patients.

Amphiphilic block copolymers-based mixed micelles for noninvasive drug delivery.

Amphiphilic block copolymers-based mixed micelles established as new drug-loading system showed superior characteristics in delivering drug such as improved solubility, enhanced stability, multifunctional carrier materials, targeting ability, and high bioavailability. Recently, there are increasing focuses on exploration and study of noninvasive routes, and the results present perfect feasibility, improved compliance and fewer aches and pains. The aim to apply mixed micelles to noninvasive alternative routes has driven massive pharmaceutical attention. Recently, various studies of micelles strategy for noninvasive routes have been conducted to overcome the inherent barriers for uptake across the gastrointestinal tract, mucosal membranes and other in vivo noninvasive barriers, and the result argues well. The objective of this article is to summary these studies and developments of mixed micelles used on noninvasive drug delivery and provide a reference for further research.

A Phase II Study of Concurrent Chemoradiotherapy With Paclitaxel and Cisplatin for Inoperable Esophageal Squamous Cell Carcinoma.

OBJECTIVES: A phase II study was performed to investigate the efficacy and the safety of a 3-week schedule of paclitaxel (PTX) plus cisplatin (DDP) combined with concurrent radiotherapy for esophageal squamous cell cancer. PATIENTS AND METHODS: Patients with newly diagnosed esophageal squamous cell cancer who had histologic proof of local-regional carcinoma of the esophagus, a Karnofsky performance status of 80 or greater, and normal liver, renal, and bone marrow functions were enrolled in the phase II trial. Chemotherapy consisted of DDP (25 mg/m/d) for 3 days plus PTX (175 mg/m) given for 3 hours, every 3 weeks for 4 cycles. The total dose of concurrent radiation with 68.4 Gy/44 Fx (late course-accelerated radiotherapy) or 61.2 Gy/34 Fx (conventional radiotherapy) was given at the first day of chemotherapy. RESULTS: Between July 2008 and November 2011, 76 patients were enrolled in this trial. The median age was 58 years (range, 37 to 74 y). The stages were stage II (21 patients), stage III (27 patients), and stage IV (28 patients). A total of 89.5% (68/76) and 63.2% (48/76) patients completed ≥2 cycles and all 4 cycles of chemotherapy, respectively. With the median follow-up of 36 months, the overall median survival time was 28.5 months and the progression-free survival time was 14.7 months. One- and 3-year survival rates were 75% and 41%, respectively. Neutropenia grade 3 and 4 occurred in 30.3% and 31.6% of the patients, respectively. CONCLUSIONS: Radiotherapy concurrent with a 3-week schedule of PTX and DDP resulted in an encouraging overall survival rate, but a relatively higher hematological toxicity.