Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma.

Glycine N-acyltransferase (GLYAT), known to influence glycine metabolism, has been implicated in the progression of various malignant tumours. However, its clinical relevance in hepatocellular carcinoma (HCC) remains unexplored. Here, GLYAT expression levels in HCC tissues were significantly reduced compared to normal liver tissues. Similarly, GLYAT expression levels in Huh 7, HepG2, PLC and SK-HEP1 were lower than those in LO2. Receiver operating characteristic curve analysis demonstrated that GLYAT exhibited good diagnostic performance for HCC. Kaplan-Meier analyses suggested that decreased GLYAT expression was correlated with poorer progress in HCC. Low GLYAT expression was significantly associated with gender and histologic grade. Multivariate Cox regression analysis identified low GLYAT expression and T stage as independent prognostic factors. Nomograms based on GLYAT mRNA expression and T stage showed good concordance with actual survival rates at 1, 2, 3 and 5 years. Moreover, GLYAT downregulation in the Huh 7 cell line enhanced cell proliferation, invasion and migration abilities, while GLYAT overexpression in the HepG2 cell line inhibited these abilities. HCC patients with low GLYAT expression exhibited a predisposition to immune escape and poor response to immunotherapy. This research revealed that GLYAT holds promise as both a prognostic biomarker and a potential therapeutic target in HCC.

A tumour-associated macrophage-based signature for deciphering prognosis and immunotherapy response in prostate cancer.

For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour-associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy-sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC-XENA, GEO and TISCH databases were extracted for analysis. Based on both single-cell datasets and bulk transcriptome profiles, a macrophage-related score (MRS) consisting of the 10-gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial-mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high-MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E-knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.

A Single Center Exploratory Survey of Patients and Nurses on post-Surgical Oral Opioid Delivery Through Patient-Controlled Analgesia.

Background: The most common route of opioid delivery is nurse-administered pills. However, there are numerous challenges such as nursing burden, opioid diversion, medication delay, and patient dissatisfaction. In this study, we conducted two surveys, first to assess patients' and nurses' opinions on the current administration of opioids in pill form, followed by their attitudes towards an innovative concept of oral medication delivery based on a medical device currently undergoing research and development within the University, patient-controlled dispenser and deactivator (PCDD) that allows patients to self-administer liquid oral opioids on demand based on physician prescription. Methods: Questionnaires were developed, verified and deployed to assess nurse and post-surgical patient opinions on the current administration of opioids in pill form, as well as the proposed new concept of patient -controlled administration of oral liquid medication via an illustration of PCDD, from September 2022 through July 2023 at a major academic tertiary care center. Quantitative and qualitative data were collected from postoperative patients and nurses from surgical specialties including General Surgery, Surgical Oncology, Trauma Surgery, Orthopedics, and Neurosurgery. Results: Forty-three patients and 53 nurses were interviewed. Seventy percent of patients frequently called nurses for pain medication post-surgery 1-4 times daily, and 32% of patients were told each day by nurses that they could not receive medication because they were not due yet. Medication delay caused 24% of patients to worry about nursing availability for medication delivery. Likewise, nurses reported that half of patients receive delayed medication (22 minutes median delay time) and half of nursing time was spent administering pain medication. Nurses expressed moderate satisfaction with their current delivery of medication (median satisfaction score 6.5 out of 10). When being introduced to the concept of PCDD via a product illustration, 15% of patients said that they prefer liquid medication and 51% said they prefer PCDD or were interested in trying it. Conclusion: Nurse-administered pills are a common but suboptimal method for postoperative pain management. Based on patient and nurse feedback, patient controlled self-administered liquid oral opioid delivery is conceptually innovative, practically viable and potentially a preferred alternative for timely and less nurse-exhaustive pain management.

Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

SENP1 inhibits ferroptosis and promotes head and neck squamous cell carcinoma by regulating ACSL4 protein stability via SUMO1.

Head and neck squamous cell carcinoma (HNSCC) is currently one of the most common malignancies with a poor prognosis worldwide. Meanwhile, small ubiquitin­like modifier (SUMO) specific peptidase 1 (SENP1) was associated with ferroptosis. However, the specific functions and underlying mechanisms of action of SENP1 in ferroptosis and tumor progression of HNSCC remain to be established. The findings of the present study implicated a novel ferroptosis pathway in the initiation and progression of HNSCC, providing new functional targets to guide future therapy. In the present study, The Cancer Genome Atlas database was employed to establish a gene model related to ferroptosis and verified SENP1 as a key gene via transcriptome sequencing. Expression of SENP1 in HNSCC tissue and CAL­27 cells was detected based on reverse transcription­quantitative PCR and western blot analysis. Proliferation and migration abilities of cells were determined using Cell Counting Kit­8, wound healing and Transwell experiments. Expression levels of iron, glutathione (GSH) and lipid peroxidation end­product malondialdehyde (MDA) under conditions of silencing of SENP1 with shRNA lentivirus were assayed. Additionally, the relationship between SENP1 and long­chain acyl­coenzyme A synthase 4 (ACSL4) was validated with the aid of immunoblotting and co­immunoprecipitation (co­IP). Finally, the influence of shSENP1 on the expression of key ferroptosis proteins, glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11, was evaluated via western blotting. It was revealed that SENP1 was significantly overexpressed in HNSCC and associated with low patient survival. Silencing of SENP1 led to significant suppression of cell proliferation, migration and invasion, increase in the contents of iron ions and MDA and decline in GSH levels in HNSCC cells, thereby enhancing ferroptosis and inhibiting disease progression. Conversely, overexpression of SENP1 suppressed ferroptosis and promoted progression of HNSCC. Co­IP and western blot analyses revealed a SUMOylation link between SENP1 and ACSL4. SENP1 reduced the stability of ACSL4 protein through deSUMOylation, leading to inhibition of ferroptosis. SENP1 silencing further inhibited the expression of the key iron death protein, GPX4, to regulate ferroptosis. Taken together, SENP1 deficiency promoted ferroptosis and inhibited tumor progression through reduction of SUMOylation of ACSL4 in HNSCC. The collective results of the present study supported the utility of SENP1 as an effective predictive biomarker for targeted treatment of HNSCC.

Metallodrugs in the battle against non-small cell lung cancer: unlocking the potential for improved therapeutic outcomes.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Platinum-based chemotherapy is standard-of-care but has limitations including toxicity and resistance. Metal complexes of gold, ruthenium, and other metals have emerged as promising alternatives. This review provides a comprehensive analysis of metallodrugs for NSCLC. Bibliometric analysis reveals growing interest in elucidating mechanisms, developing targeted therapies, and synergistic combinations. Classification of metallodrugs highlights platinum, gold, and ruthenium compounds, as well as emerging metals. Diverse mechanisms include DNA damage, redox modulation, and immunomodulation. Preclinical studies demonstrate cytotoxicity and antitumor effects in vitro and in vivo, providing proof-of-concept. Clinical trials indicate platinums have utility but resistance remains problematic. Non-platinum metallodrugs exhibit favorable safety but modest single agent efficacy to date. Drug delivery approaches like nanoparticles show potential to enhance therapeutic index. Future directions include optimization of metal-based complexes, elucidation of resistance mechanisms, biomarker development, and combination therapies to fully realize the promise of metallodrugs for NSCLC.

Association between sun-protective behaviors and hypertension: a cross-sectional study from National Health and Nutrition Examination Survey 2009 to 2014.

BACKGROUND: In previous studies, sun-protective behaviors increased cardiovascular incidence. Our present article is to further analyze the potential relationship between sun-protective behaviors (staying in the shade, wearing long-sleeved clothing, and applying sunscreen) and hypertension. METHOD: The present cross-sectional study evaluated 8,613 participants (aged 20-60 years) from the National Health and Nutrition Examination Survey (NHANES) obtained between 2009 and 2014. We performed multiple logistic regression analysis to examine the relationship between sun-protective behaviors and hypertension. Subgroup analysis was then performed. Multiple linear regression analysis was utilized to examine the relationship of sun-protective behaviors and each sun-protective behavior with systolic and diastolic blood pressure, stratified by sex and race. RESULTS: A total of 8,613 participants (weighted n = 127,909,475) were applied in our study, including 1,694 hypertensive subjects. Our study demonstrated that sun-protective behaviors of the 2-3 category were associated with increased risk of hypertension, but not with higher systolic and diastolic blood pressure. In subgroup analysis, men, Mexican American, and 25 < BMI ≤ 30 who reported sun-protective behaviors (2-3) were prone to hypertension. Multiple linear regression models showed that non-Hispanic white men with sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. The association between other-Hispanic men with frequent wearing long-sleeved clothing and diastolic blood pressure was positively correlated. CONCLUSION: Sun-protective behaviors of the 2-3 category could increase the incidence of hypertension, but not increase systolic and diastolic blood pressure. We only found that non-Hispanic white men who reported sun-protective behaviors (2-3) were positively associated with systolic and diastolic blood pressure. These findings suggested that excessive sun-protective behaviors should be avoided.

Triphenylamine-Functionalized Coordination Cage as a Supramolecular Fluorescence Sensor for Sequential Detection of Aluminum Ions and Nitrofurantoin.

Coordination cages with a well-defined nanocavity are a class of promising supramolecular materials for molecular recognition and sensing. However, their applications in sequential sensing of multiple types of pollutants are highly desirable yet extremely limiting and challenging. Herein, we demonstrate a convenient strategy to develop a supramolecular fluorescence sensor for sequentially detecting environmental pollutants of aluminum ions and nitrofurantoin. A coordination cage (Ni-NTB), adopting an octahedral structure with triphenylamine chromophores occupying on the faces, is weakly emissive in solution due to the intramolecular rotations of the phenyl rings. Ni-NTB exhibits sensitive and selective fluorescence "off-on-off" processes during consecutive sensing of Al3+ and nitrofurantoin, an antibacterial drug. These sequential detection processes are highly interference-tolerant and visually observable with the naked eye. Mechanism studies reveal that the fluorescence switch is controllable by tuning the degree of intramolecular rotations of the phenyl rings and the pathway of intermolecular charge transfer, which is associated with the host-guest interaction. Moreover, the fabrication of Ni-NTB on test strips enabled a quick naked-eye sequential sensing of Al3+ and nitrofurantoin in seconds. Hence, this novel supramolecular fluorescence "off-on-off" sensing platform provides a new approach to developing supramolecular functional materials for monitoring environmental pollution.

Anemonin reduces hydrogen peroxide-induced oxidative stress, inflammation and extracellular matrix degradation in nucleus pulposus cells by regulating NOX4/NF-κB signaling pathway.

BACKGROUND: Excessive oxidative stress plays a critical role in the progression of various diseases, including intervertebral disk degeneration (IVDD). Recent studies have found that anemonin (ANE) possesses antioxidant and anti-inflammatory effects. However, the role of ANE in IVDD is still unclear. Therefore, this study investigated the effect and mechanism of ANE on H2O2 induced degeneration of nucleus pulposus cells (NPCs). METHODS: NPCs were pretreated with ANE, and then treated with H2O2. NOX4 was upregulated by transfection of pcDNA-NOX4 into NPCs. Cytotoxicity was detected by MTT, oxidative stress-related indicators and inflammatory factors were measured by ELISA, mRNA expression was assessed by RT-PCR, and protein expression was tested by western blot. RESULTS: ANE attenuated H2O2-induced inhibition of NPCs activity. H2O2 enhanced oxidative stress, namely, increased ROS and MDA levels and decreased SOD level. However, these were suppressed and pretreated by ANE. ANE treatment repressed the expression of inflammatory factors (IL-6, IL-1ß and TNF-α) in H2O2-induced NPCs. ANE treatment also prevented the degradation of extracellular matrix induced by H2O2, showing the downregulation of MMP-3, 13 and ADAMTS-4, 5 and the upregulation of collagen II. NOX4 is a key factor regulating oxidative stress. Our study confirmed that ANE could restrain NOX4 and p-NF-κB. In addition, overexpression of NOX4 counteracted the antioxidant and anti-inflammatory activities of ANE in H2O2-induced NPCs, and the inhibition of the degradation of extracellular matrix induced by ANE was also reversed by overexpression of NOX4. CONCLUSION: ANE repressed oxidative stress, inflammation and extracellular matrix degradation in H2O2-induced NPCs by inhibiting NOX4/NF-κB pathway. Our study indicated that ANE might be a candidate drug for the treatment of IVDD.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Information Technology-Enhanced Telehealth Consultations Reduce Preoperative Evaluation Center Visits in a Bariatric Surgery Population.

Background: Preoperative patient evaluation and optimization in a preoperative evaluation center (PEC) has been shown to improve operating room (OR) efficiency and patient care. However, performing preoperative evaluation on all patients scheduled for surgery or procedure would be time- and resource-consuming. Therefore, appropriate patient selection for evaluation at PECs is one aspect of improving PEC efficiency. In this study, we evaluate the effect of an enhanced preoperative evaluation process (PEP), utilizing a nursing triage phone call and information technology (IT) optimizations, on PEC efficiency and the quality of care in bariatric surgery patients. We hypothesized that, compared to a traditional PEP, the enhanced PEP would improve PEC efficiency without a negative impact on quality. Methods: The study was a retrospective cohort analysis of 1550 patients from January 2014 to March 2017 at a large, tertiary care academic health system. The study was a before/after comparison that compared the enhanced PEP model to the traditional PEP model. The primary outcome was the efficiency of the PEC, which was measured by the reduction of in-person patient visits at the PEC. The secondary outcome was the quality of care, which was measured by delays, cancellations, and the need for additional testing on the day of surgery (DOS). Results: The enhanced PEP improved the primary outcome of efficiency, as evident by an 80% decrease in in-person patient visits to the PEC. There was no reduction in the secondary outcome of the quality of care as measured by delays, cancellations, or the need for additional testing on the DOS. The implementation of the enhanced PEP did not result in increased costs or resource utilization. Conclusions: The enhanced PEP in a multi-disciplinary preoperative process can improve the efficiency of PEC for bariatric surgery patients without any decrease in the quality of care. The enhanced PEP process can be implemented without an increase in resource utilization and can be particularly useful during the COVID-19 pandemic.

Clinical application of spectral CT perfusion scanning in evaluating the blood supply source of portal vein tumor thrombus in hepatocellular carcinoma.

Purpose: To evaluate the characteristic of blood supply of liver portal vein tumor thrombus (PVTT) using perfusion indexes and spectral parameters. Methods: Between July 2020 and December 2022, the study enrolled 25 liver cancer patients completed with PVTT (male=20, female=5; age 41-74 years (59.48 ± 9.12)) from the Interventional Department of Jiangsu Cancer Hospital. There were 11 cases of type III PVTT, 12 of type II PVTT, and 2 of type I PVTT (Cheng's classification). All patients underwent spectral perfusion scans through dual-layer spectral detector computed tomography. The PVTTs were divided into proximal and distal groups based on the distance between the tumor thrombus and the main portal vein. The perfusion analysis was performed on the 120-kVp conventional images to generate hepatic perfusion index (HPI). The spectral based images (SBIs) during the artery and venous peak phases were extracted from the perfusion data. The iodine map and 40&100-keV virtual monoenergetic image (VMI) were generated from SBI data. HPI, iodine concentration (IC), CT value at 40 and 100-keV, and spectral slope (40-100keV) of the primary lesion, proximal and distal PVTT, and liver parenchyma were measured and compared. The correlation between the primary lesion and proximal and distal PVTT was analyzed. Results: The IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT, and distal PVTT were highly correlated (P<0.001). The differences between the IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT were statistically significant (P<0.001). The differences between the IC during venous peak phase and HPI of primary lesion, distal PVTT were statistically significant (P<0.001), and there was no statistically significant difference in arterial phase IC, arterial and venous phase spectral slopes. Conclusion: The IC, slope, and HPI of the distal and proximal PVTT were highly correlated with the primary lesion, indicating that PVTT was similar to the primary lesion in the liver that they were both mainly supplied by the hepatic artery. However, there was still significant heterogeneity between the proximal PVTT and the primary lesion, while the difference in the distal PVTT was relatively small.

MicroRNA-375 inhibits laryngeal squamous cell carcinoma progression via targeting CST1

Abstract Objective: This study aims to explore the effect and mechanism of miR-375 in Laryngeal Squamous Cell Carcinoma (LSCC) cell progression. Methods: LSCC cells (LSC-1 and TU177) were transfected with miR-375-mimic, miR-375-inhibitor or miR-375-mimic + oe-CST1. The expression of miR-375, CST1, MMP-2, and MMP-9 was measured. The effect of miR-375-mimic, miR-375-inhibitor or miR-375-mimic + oe-CST1 on cell biological functions, including cell proliferation, migration, invasion, and apoptosis, was also assessed. The potential relationship between CST1 and miR-375 was predicted by Jefferson software and validated by dual luciferase reporter gene assay. Results: Downregulated miR-375 expression was found in LSCC cells. Overexpression of miR-375 inhibited the viability and migration and promoted apoptosis of LSCC cells. Jefferson database and dual luciferase reporter gene assay confirmed that miR-375 directly targeted CST1. Over-expression of CST1 could reverse the anti-cancer effect of miR-375 overexpression in LSCC cells. Conclusion: Collected evidence showed that miR-375/CST1 axis was implicated in LSCC progression. Level of evidence: Level 3

Demonstration and Performance Evaluation of Two Novel Algorithms for Removing Artifacts From Automated Intraoperative Temperature Data Sets: Multicenter, Observational, Retrospective Study.

BACKGROUND: The automated acquisition of intraoperative patient temperature data via temperature probes leads to the possibility of producing a number of artifacts related to probe positioning that may impact these probes' utility for observational research. OBJECTIVE: We sought to compare the performance of two de novo algorithms for filtering such artifacts. METHODS: In this observational retrospective study, the intraoperative temperature data of adults who received general anesthesia for noncardiac surgery were extracted from the Multicenter Perioperative Outcomes Group registry. Two algorithms were developed and then compared to the reference standard-anesthesiologists' manual artifact detection process. Algorithm 1 (a slope-based algorithm) was based on the linear curve fit of 3 adjacent temperature data points. Algorithm 2 (an interval-based algorithm) assessed for time gaps between contiguous temperature recordings. Sensitivity and specificity values for artifact detection were calculated for each algorithm, as were mean temperatures and areas under the curve for hypothermia (temperatures below 36 C) for each patient, after artifact removal via each methodology. RESULTS: A total of 27,683 temperature readings from 200 anesthetic records were analyzed. The overall agreement among the anesthesiologists was 92.1%. Both algorithms had high specificity but moderate sensitivity (specificity: 99.02% for algorithm 1 vs 99.54% for algorithm 2; sensitivity: 49.13% for algorithm 1 vs 37.72% for algorithm 2; F-score: 0.65 for algorithm 1 vs 0.55 for algorithm 2). The areas under the curve for time × hypothermic temperature and the mean temperatures recorded for each case after artifact removal were similar between the algorithms and the anesthesiologists. CONCLUSIONS: The tested algorithms provide an automated way to filter intraoperative temperature artifacts that closely approximates manual sorting by anesthesiologists. Our study provides evidence demonstrating the efficacy of highly generalizable artifact reduction algorithms that can be readily used by observational studies that rely on automated intraoperative data acquisition.

Characteristics and mechanisms of resorption in lumbar disc herniation.

Lumbar disc herniation (LDH) can be spontaneously absorbed without surgical treatment. However, the pathogenesis and physiological indications for predicting protrusion reabsorption are still unclear, which prevents clinicians from preferentially choosing conservative treatment options for LDH patients with reabsorption effects. The purpose of this review was to summarize previous reports on LDH reabsorption and to discuss the clinical and imaging features that favor natural absorption. We highlighted the biological mechanisms involved in the phenomenon of LDH reabsorption, including macrophage infiltration, inflammatory responses, matrix remodeling, and neovascularization. In addition, we summarized and discussed potential clinical treatments for promoting reabsorption. Current evidence suggests that macrophage regulation of inflammatory mediators, matrix metalloproteinases, and specific cytokines in intervertebral disc is essential for the spontaneous reabsorption of LDH.

MicroRNA-375 inhibits laryngeal squamous cell carcinoma progression via targeting CST1.

OBJECTIVE: This study aims to explore the effect and mechanism of miR-375 in Laryngeal Squamous Cell Carcinoma (LSCC) cell progression. METHODS: LSCC cells (LSC-1 and TU177) were transfected with miR-375-mimic, miR-375-inhibitor or miR-375-mimic+oe-CST1. The expression of miR-375, CST1, MMP-2, and MMP-9 was measured. The effect of miR-375-mimic, miR-375-inhibitor or miR-375-mimic+oe-CST1 on cell biological functions, including cell proliferation, migration, invasion, and apoptosis, was also assessed. The potential relationship between CST1 and miR-375 was predicted by Jefferson software and validated by dual luciferase reporter gene assay. RESULTS: Downregulated miR-375 expression was found in LSCC cells. Overexpression of miR-375 inhibited the viability and migration and promoted apoptosis of LSCC cells. Jefferson database and dual luciferase reporter gene assay confirmed that miR-375 directly targeted CST1. Overexpression of CST1 could reverse the anti-cancer effect of miR-375 overexpression in LSCC cells. CONCLUSION: Collected evidence showed that miR-375/CST1 axis was implicated in LSCC progression. LEVEL OF EVIDENCE: Level 3.

Association of propofol induction dose and severe pre-incision hypotension among surgical patients over age 65.

STUDY OBJECTIVE: We aimed to study the association between propofol induction dose (mg/kg) and pre-incision severe hypotension (Mean Arterial Pressure (MAP) ≤ 55 mmHg) among patients ≥65 years of age. DESIGN: Retrospective Observational. SETTING: 40 centers participating in the Multicenter Perioperative Outcomes Group consortium. PATIENTS: Patients ≥65 years of age undergoing non-cardiac, non-vascular surgery who received propofol for general anesthetic induction prior to endotracheal intubation between January 2014 and December 2018. INTERVENTIONS: None. MEASUREMENTS: The primary exposure was total propofol induction dose in mg/kg, and the primary outcome was occurrence of severe hypotension (MAP≤55 mmHg) prior to surgical incision, stratified by non-invasive vs. invasive blood pressure monitoring type. MAIN RESULTS: Among 320,585 total patients, 22.6% experienced the outcome of pre-incision severe hypotension (MAP≤55 mmHg). When stratified by blood pressure monitoring type, 20.7% with non-invasive blood pressure measurements, and 35.0% with invasive blood pressure measurements had the outcome. After controlling for a variety of patient and procedural factors, there was a significant independent association between propofol induction dose and pre-incision hypotension (Non-invasive blood pressure cohort odds ratio (OR) 1.10; 95% confidence interval (CI) 1.07 to 1.13; p < 0.001; and Invasive blood pressure cohort OR 1.15; 95%CI 1.10 to 1.21; adjusted p < 0.001). The association was robust to alternative definitions of the outcome, including less severe hypotension (MAP≤65 mmHg) and blood pressure drop from baseline as a continuous measure. Although no threshold safe induction dose was identified at which hypotension was avoided, an analysis of propofol dose greater or less than 1.5 mg/kg (i.e. the maximum FDA-defined typical induction dose) demonstrated that doses in excess of the FDAs threshold were positively associated with odds of severe hypotension (Non-invasive cohort: OR 1.05; 95% CI 1.02 to 1.08; p < 0.001; Invasive cohort: OR 1.11; 95%CI 1.05 to 1.17; adjusted p < 0.001). CONCLUSIONS: In a multicenter cohort of geriatric surgical patients receiving propofol for general anesthetic induction and endotracheal intubation, severe pre-incision hypotension (MAP ≤55 mmHg) that has previously been associated with postoperative morbidity was common. The dose of propofol used was significantly associated with increased odds of this outcome after controlling for a number of clinically relevant factors. Future studies that are designed to test different approaches to anesthesia induction for reducing severe post induction pre-incision hypotension are warranted.

Clinical Features and CT Imaging Analysis of Hepatic Sinuscase-Syndrome and Budd-Chiari Syndrome.

Objective: This study aimed to analyze the clinical features and computed tomography (CT) manifestations of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum, a Chinese herbal medicine, so as to improve the clinical understanding and diagnosis of the disease. Methods: Relevant clinical and laboratory parameters and CT imaging data of 20 patients with HSOS confirmed by liver biopsy were retrospectively analyzed and compared with 16 patients with Budd-Chiari syndrome (BCS). Results: Levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and glutamyl transpeptidase increased significantly (p < 0.05) in HSOS patients compared to the BCS patients, while the albumin level and prothrombin time, which are indicators of liver synthesis function, decreased and prolonged significantly, respectively. All 20 patients with HSOS had manifestations of ascites and heterogeneous hypoattenuation on CT, including 18 cases (90%) with heterogeneous enhancement (characteristic map-like enhancement), 17 (85%) with hepatomegaly, 18 (90%) with gallbladder wall oedema, and 16 (80%) with stenosis of main hepatic veins and characteristic "clover-like" enhancement at the second porta hepatis. Conclusion: Both HSOS and BCS are post-sinusoidal portal hypertension, but have different etiologies and durations. Although they both cause liver congestion, the clinical manifestation of HSOS is acute liver injury. The CT manifestations are characterized by ascites, map-like enhancement and heterogeneous hypoattenuation of the liver parenchyma, and stenosis of the main hepatic veins. BCS is often found in the stage of decompensated liver cirrhosis, resulting in liver shrinkage, splenomegaly, and ascites.

Bone Marrow Mesenchymal Stem Cells Overexpressing HIF-1α Prevented the Progression of Glucocorticoid-Induced Avascular Osteonecrosis of Femoral Heads in Mice.

Glucocorticoid (GC)-induced avascular osteonecrosis of femoral head (AOFH) is a devastating complication, and no cures are currently available for it. Previous studies have demonstrated that implantation of bone marrow mesenchymal stem cells (BMMSCs) may prevent the progression of pre-collapse AOFH. Based on previous observations, we hypothesized that GCs induce AOFH via the COX-2 (cyclooxygenase-2)-PGE-2 (prostaglandin E2)-HIF-1α (hypoxia-inducible factor-1α) axis, and that modification of BMMSCs may improve the efficacy of their implantation. BMMSCs isolated from wild-type (WT) mice were treated with dexamethasone (Dex) and the results showed that Dex repressed the expression of COX-2. Femoral head samples harvested from both WT and COX-2 knock-out (COX-2-/-) mice were subjected to micro-computed tomography and histological examinations. Compared with their WT littermates, COX-2-/- mice had larger trabecular separations, diminished microvasculature, and reduced HIF-1α expression in their femoral heads. In vitro angiogenesis assays with tube formation and fetal metatarsal sprouting demonstrated that Dex repressed angiogenesis and PGE-2 antagonized its effects. An AOFH model was successfully established in C57BL/6J mice. In vitro experiment showed that BMMSCs infected with Lentivirus encoding HIF-1α (Lenti-HIF-1α) resulted in a robust increase in the production of HIF-1α protein. Implantation of BMMSCs overexpressing HIF-1α into femoral heads of AOFH mice significantly reduced osteonecrotic areas and enhanced bone repair, thus largely preserving the structural integrity of femoral heads. Our studies provide strong rationales for early intervention with core decompression and implantation of modified BMMSCs for GC-induced AOFH, which may spare patients from expensive and difficult surgical procedures.

[Vestibular rehabilitation in patients with vestibular peripheral vertigo].

Objective:To evaluate the efficacy of vestibular rehabilitation in patients with anterior peripheral vertigo and analyze its influencing factors. Methods:From January 2018 to June 2021, 153 cases with peripheral vertigo diseases（including 47 cases of benign positional paroxysmal vertigo, 38 cases of Meniere's disease, 26 cases of sudden deafness with vertigo, 23 cases of vestibular migraine and 19 cases of vestibular neuritis） were enrolled. One hundred and three cases were treated with vestibular rehabilitation combined with drugs, and 50 cases only treated with drugs were used as controls. Self-rating scale and vertigo disorder scale were evaluated at the beginning of treatment, 4 weeks and 8 weeks, respectively. The curative effects of the two groups were tested by t-test, and the independent risk factors affecting the curative effects were analyzed by multiple linear regression. Results:There was no difference in clinical data, self-assessment scale and vertigo disorder scale between the two groups（P>0.05）. At 4 and 8 weeks, the scores of self-assessment scale and vertigo disorder scale in the experimental group were better than those in the control group（all P<0.01）, and the curative effect at 8 weeks was better than that at 4 weeks, especially the decrease of emotional score during walking and the proportion of severe vertigo disability（all P<0.01）. The scores of self-rating scale and vertigo disorder scale of the cases with benign positional paroxysmal vertigo and vestibular neuritis were better than Meniere's disease, vestibular migraine and sudden deafness with vertigo（P<0.05）. Headache（P<0.05） and severe vertigo disorder before intervention（P<0.01） were independent risk factors affecting the efficacy of vestibular rehabilitation. Conclusion:Vestibular rehabilitation combined with anti-vertigo drugs in the treatment of vestibular peripheral vertigo is better than that of only using drugs, especially in improving the degree of emotional disorder and vertigo disability. It is more suitable for benign positional paroxysmal vertigo and vestibular neuritis, while the effect of combined headache or severe vertigo is relatively poor.