Scutellaria baicalensis Induces Cell Apoptosis and Elicits Mesenchymal-Epithelial Transition to Alleviate Metastatic Hepatocellular Carcinoma via Modulating HSP90ß.

Hepatocellular carcinoma is one of the most common malignant tumors in the world and shows strong metastatic potential. Current medicine for hepatocellular carcinoma therapy is invalid, while Scutellaria baicalensis Georgi exhibits the pharmaceutical potential to treat liver diseases and liver cancer. Herein, we verified the inhibitory properties and the pivotal molecules regimented by Scutellaria baicalensis on advanced hepatocellular carcinoma. At first, the viability of SK-Hep-1 cells was significantly reduced under treatment of Scutellaria baicalensis extract in a dose-dependent manner without affecting the growth of normal hepatocyte. Scutellaria baicalensis extract application could remarkably cause apoptosis of SK-Hep-1 cells through p53/cytochrome C/poly-ADP ribose polymerase cascades and arrest the cell cycle at the G1/S phase by downregulating cyclin-dependent kinases. Meanwhile, administration of Scutellaria baicalensis extract remarkably attenuated the migration capability as well as suppressed matrix metalloproteinase activity of advanced hepatocellular carcinoma cells. The proteome profiles and network analysis particularly implied that exposure to Scutellaria baicalensis extract downregulated the expression of HSP90ß, and the clinical stage of hepatocellular carcinoma is also positively correlated with the HSP90ß level. Combined treatment of Scutellaria baicalensis extract and HSP90ß siRNAs could markedly enhance the ubiquitination activity and the degradation of vimentin to subsequently inhibit the metastatic property of SK-Hep-1 cells. Moreover, application of Scutellaria baicalensis extract and HSP90ß siRNAs depleted phosphorylation of AKT, which stimulated the expression of p53 and consecutively triggered cell apoptosis. These findings suggest that HSP90ß may be a prospective target for the effective therapy of advanced hepatocellular carcinoma via accelerating apoptosis of hepatocellular carcinoma cells and eliciting mesenchymal-epithelial transition with the administration of Scutellaria baicalensis extract.

Interpreting the Evidence of Body Mass Index in Relation to Mental Health Status in Community-Dwelling Older Adults.

INTRODUCTION: Maintaining a better physical and mental health status is an important issue for older adults in their later life. Thus, the study's purpose was to evaluate the association between body mass index (BMI) and mental health status in older adults aged 65 years old or above residing in communities of Taipei City, Taiwan. METHODS: We carried out secondary data analysis with data from a volunteer-based health examination project for older adults >65 years old residing in Taipei City from 2006 to 2010 with a retrospective study design. BMI, calculated by standardized measuring procedures for height and weight, and mental health status, evaluated by 5-item Brief Symptom Rating Scale (BSRS-5), were collected at their first visits of health examination. A BSRS-5 score ≥6 was considered an inferior mental health status for the outcome. In statistical analysis, univariable and multivariable logistic regressions were adopted to estimate the relative risk of inferior mental health status, treating BMI as the major exposure of interest. RESULTS: A total of 90,576 subjects were involved, with a mean age of 73.38 years old (SD = 6.64 years) and 49.21% females. With confounders controlled, compared to normal or overweight (23 ≤ BMI <30), an adjusted OR of 1.23 (95% CI: 1.18, 1.29) on inferior mental health status was detected for the underweight group (BMI <23) significantly. Adjusted OR for those obese (BMI ≧30) was 0.87 (95% CI: 0.79, 0.96). Significantly elevated ORs of underweight were found for both genders, but the significantly protective effect of obese was only detected for females. CONCLUSION: Keeping an appropriate weight or even being overweighted might be beneficial for older adults dwelling in the community, especially for males.

Hepatic Stellate Cell Modulates the Immune Microenvironment in the Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of increases in the mortality rate due to cancer that usually develops in patients with liver fibrosis and impaired hepatic immunity. Hepatic stellate cells (HSCs) may directly or indirectly crosstalk with various hepatic cells and subsequently modulate extracellular remodeling, cell invasion, macrophage conversion, and cancer deterioration. In this regard, the tumor microenvironment created by activated HSC plays a critical role in mediating pathogenesis and immune escape during HCC progression. Herein, intermediately differentiated human liver cancer cell line (J5) cells were co-cultured with HSC-conditioned medium (HSC-CM); changes in cell phenotype and cytokine profiles were analyzed to assess the impact of HSCs on the development of hepatoma. The stage of liver fibrosis correlated significantly with tumor grade, and the administration of conditioned medium secreted by activated HSC (aHSC-CM) could induce the expression of N-cadherin, cell migration, and invasive potential, as well as the activity of matrix metalloproteinases in J5 cells, implying that aHSC-CM could trigger the epithelial-mesenchymal transition (EMT). Next, the HSC-CM was further investigated and network analysis indicated that specific cytokines and soluble proteins, such as activin A, released from activated HSCs could remarkably affect the tumor-associated immune microenvironment involved in macrophage polarization, which would, in turn, diminish a host's immune surveillance and drive hepatoma cells into a more malignant phenotype. Together, our findings provide a novel insight into the integral roles of HSCs to enhance hepatocarcinogenesis through their immune-modulatory properties and suggest that HSC may serve as a potent target for the treatment of advanced HCC.

Running Training Combined With Blood Flow Restriction Increases Cardiopulmonary Function and Muscle Strength in Endurance Athletes.

ABSTRACT: Chen, Y-T, Hsieh, Y-Y, Ho, J-Y, Lin, T-Y, and Lin, J-C. Running training combined with blood flow restriction increases cardiopulmonary function and muscle strength in endurance athletes . J Strength Cond Res 36(5): 1228-1237, 2022-We investigated the effects of 8 weeks (3 d/wk) of running training (RT) combined with blood flow restriction (RT-BFR) on cardiopulmonary function and muscle strength in endurance athletes. Twenty endurance-trained male athletes (19-25 years; 177.6 ± 2.4 cm; 69.0 ± 2.2 kg) were pair matched and randomly assigned to RT-BFR and RT groups. The RT-BFR group performed running sessions (50% heart rate reserve; 3-minute × 5 sets; 1-minute rest interval) with pressure cuffs (1.3 × resting systolic blood pressure), whereas the RT group performed the same running sessions without pressure cuffs. V̇o2max, muscle mass, isokinetic muscle strength, and hormones were assessed at pre-, mid- and posttraining. Compared with the RT group, the RT-BFR group exhibited a significantly greater increase in V̇o2max (5.1 vs. -1.1%) and isokinetic knee extensor strength (16.5 vs. -5.9%). In addition, RT-BFR group presented higher leg muscle mass (10.3 vs. 9.7 kg) than that of RT group after 8 weeks of training. Furthermore, testosterone to cortisol (T:C) ratio at 24 hours after training session at pre-, mid-, and posttraining were maintained in the RT-BFR group, whereas significant decreases of T:C ratio at 24 hours after training session were observed in the RT group. These results suggested that RT combined with BFR may be a practical training strategy for promoting cardiopulmonary function and muscle strength in endurance runners.

Comparison between vertebroplasty with high or low viscosity cement augmentation or kyphoplasty in cement leakage rate for patients with vertebral compression fracture: a systematic review and network meta-analysis.

PURPOSE: This study aims to determine whether outcomes following vertebroplasty with high viscosity cement are superior to low viscosity cement and non-inferior to kyphoplasty in the setting of vertebral compression fractures. METHODS: We searched for randomized controlled trials and cohort studies assessing cement leakage rate in adult patients with VCFs who underwent vertebroplasty with high (HVCV) or low viscosity cement (LVCV) augmentation, or kyphoplasty (KP) in PubMed, Embase, Ovid, The Cochrane Library, and Web of Science from inception up to December 2019. Two authors extracted data and appraised risk of bias. We performed pairwise meta-analyses in R to compare differences between three treatments and network meta-analysis using frequentist random-effects models for indirect comparison. We used P-score to rate the overall certainty of evidence. The primary outcome was cement leakage rate. RESULTS: Five RCTs and eight cohort studies with 840 patients and a total of 1280 vertebral bodies were included in the systematic review and network meta-analysis. Compared to LVCV, the relative risk for cement leakage following HVCV and KP was 0.42 (95% CI 0.28-0.61) and 0.83 (95% CI 0.40-1.68), respectively. Our pooled results suggested that HVCV (P-score = 0.99) was better than KP (P-score = 0.36) in cement leakage rate. CONCLUSIONS: The present network meta-analysis demonstrated that HVCV may be associated with lower risk of cement leakage among patients with VCFs as compared to other augmentation techniques. Future prospective studies will validate the findings of this analysis and further elucidate the risk of symptomatic cement leakage.

Early detection and intervention for acute perforated peptic ulcer after elective spine surgeries: a review of 13 cases from 24,026 patients.

BACKGROUND: To determine how perforated peptic ulcers be diagnosed earlier after patients undergoing an elective spine surgery. METHODS: Patients who underwent elective spine surgeries at our hospital between January 2000 and April 2018 and experienced an acute perforated peptic ulcer were included. An age-and gender-matched control group was comprised of 26 patients without a postoperative acute perforated peptic ulcer who received spine surgery during the same period. Medical records and imaging studies were thoroughly reviewed. RESULTS: Thirteen patients were enrolled in the study group, including eight females and five males. Three patients, two females and one male, died of uncontrolled peritonitis during the hospital stay. All patients in the study group experienced the sudden onset of abdominal pain, which was continuous and progressively worsening. Patients with elevated serum amylase, a peptic ulcer history and increased intraoperative blood loss had a tendency to develop a postoperative perforated peptic ulcer. CONCLUSION: Spine surgeons should be highly alert to these risk factors of postoperative perforated peptic ulcers inpatients who has history of peptic ulcer, large amount ofintraoperative blood loss and abnormal high serum amylase level after elective spine surgery. Early diagnosis and emergent surgical intervention promote better outcomes.

Miniaturized Salinity Gradient Energy Harvesting Devices.

Harvesting salinity gradient energy, also known as "osmotic energy" or "blue energy", generated from the free energy mixing of seawater and fresh river water provides a renewable and sustainable alternative for circumventing the recent upsurge in global energy consumption. The osmotic pressure resulting from mixing water streams with different salinities can be converted into electrical energy driven by a potential difference or ionic gradients. Reversed-electrodialysis (RED) has become more prominent among the conventional membrane-based separation methodologies due to its higher energy efficiency and lesser susceptibility to membrane fouling than pressure-retarded osmosis (PRO). However, the ion-exchange membranes used for RED systems often encounter limitations while adapting to a real-world system due to their limited pore sizes and internal resistance. The worldwide demand for clean energy production has reinvigorated the interest in salinity gradient energy conversion. In addition to the large energy conversion devices, the miniaturized devices used for powering a portable or wearable micro-device have attracted much attention. This review provides insights into developing miniaturized salinity gradient energy harvesting devices and recent advances in the membranes designed for optimized osmotic power extraction. Furthermore, we present various applications utilizing the salinity gradient energy conversion.

Surgical outcomes of elderly patients aged more than 80 years with distal radius fracture: comparison of external fixation and locking plate.

BACKGROUND: To compare the outcomes after surgical intervention, including external fixation (EF) with the optional addition of K-pins or open reduction and internal fixation (ORIF) with a volar locking plate (VLP), in patients with distal radius fracture aged > 80 years. METHODS: We reviewed 69 patients with a distal radius fracture aged > 80 years who treated under surgical intervention from 2011 to 2017 retrospectively. Their demographic data and complications were recorded. Preoperative, postoperative, and last follow-up plain films were analyzed. The functional outcomes of wrist range of motion were also evaluated. RESULTS: 41 patients were treated with EF with the optional addition of K-pins, while 28 patients were treated with ORIF with a VLP. The radiological parameters, including ulnar variance and radial inclination, at the last follow-up were significantly more acceptable in the VLP group (p = 0.01, p = 0.03, respectively). The forearm supination was significantly better in patients treated with VLP (p = 0.002). The overall incidence of complications was lower in the VLP group (p = 0.003). CONCLUSION: VLP provides better radiological outcomes, wrist supination and lower complication rates than EF. Therefore, although EF is still widely used because of its acceptable results and easy application, we recommend VLP as a suitable treatment option for distal radius fracture in the geriatric population aged > 80 years.

Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics.

Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.

Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice.

The purpose of this study was to investigate whether Ger-Gen-Chyn-Lian-Tang (GGCLT) suppresses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through the hypoxia-inducible factor-1α (HIF-1α)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30, 100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathology and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-1α levels, which was suppressed by 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07: 1.95 ± 0.12: 1.43 ± 0.05: 1.12 ± 0.10 fold; p < 0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-ß, α-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procollagen-III were found in BDL mice, which were attenuated with GGCLT. In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-1α-mediated pathway.

Characterization of Fibrinogen as a Key Modulator in Patients with Wilson's Diseases with Functional Proteomic Tools.

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by defects in the ATPase gene (ATP7B). The various clinical features result from the massive accumulation of copper in the liver, cornea and basal ganglia. Although WD can be effectively treated with proper medicine, this disease is difficult to clearly diagnose due to its indefinite symptoms. In the current study, we achieved a positive correlation between clinical symptoms and the enzymatic activity of ceruloplasmin in WD patients. Furthermore, proteome profiles of plasma as well as network analysis demonstrated that fibrinogen is a critical indicator which is significantly unregulated in WD subjects in comparison to healthy donors and closely linked to pathogenesis of WD. Here, we applied 2DE-immunoblots and immunohistochemistry to verify the protein level and localization in situ. The enhanced expression of fibrinogen in the plasma of WD subjects with respect to that of healthy controls and patients with distinct disorders was also confirmed by utilizing clinical samples. As expected, application of high dose of copper induced expression of fibrinogen, while knockdown of ceruloplasmin also resulted in upregulation of fibrinogen as well as elimination of superoxide dismutase (SOD), leading to increased oxidative stress in cells. In summary, the liver injury or oxidative stress induced by the progression of WD may account for the obvious increase of fibrinogen, which in turn triggers inflammatory responses and interferes coagulation cascades; this finding sheds light on the early detection and diagnosis of WD.

Induction of Cbl-dependent epidermal growth factor receptor degradation in Ling Zhi-8 suppressed lung cancer.

Activating mutation of epidermal growth factor receptor (EGFR) is correlated with malignant lung tumor. In our study, we demonstrated that recombinant LZ-8 (rLZ-8), a medicinal mushroom Ganoderma lucidum protein, induced cell cycle arrest and apoptosis by downregulating the expression of wild-type and mutated EGFR and inhibiting EGFR downstream effectors, AKT and ERK1/2 in lung cancer cells. We showed that rLZ-8 effectively inhibited lung cancer progression and suppressed EGFR expression of lung tumor lesions in mouse model. Functional studies revealed that rLZ-8 reduced the amount of EGFR in cell membranes by altering EGFR localization to enhance the EGF-induced degradation of EGFR. Mechanistically, we demonstrated that rLZ-8 bound to EGFR to induce EGFR autophosphorylation at tyrosine1045 and trigger ubiquitination by inducing the formation of EGFR/Cbl complexes, resulting in the degradation of EGFR; however, Cbl-shRNA abolished rLZ-8-induced EGFR degradation. We provide the first evidence showing that rLZ-8 inhibits growth and induces apoptosis of lung cancer cells by promoting EGFR degradation. The current findings therefore suggest a novel anti-cancer function of rLZ-8 that targeting EGFR overexpression or mutation as well as EGFR-dependent processes in cancer cells.

Surgical outcome of atypical subtrochanteric and femoral fracture related to bisphosphonates use in osteoporotic patients with or without teriparatide treatment.

BACKGROUND: Atypical subtrochanteric fracture and femoral fracture have been considered to be rare complications related to long-term bisphosphonates use. A reduced bone turnover rate may lead to delayed bone healing. Limited data have revealed that teriparatide treatment may reverse the effect of bisphosphonates and be effective in bone healing. METHODS: We reviewed patients with atypical subtrochanteric and femoral fracture related to bisphosphonates use between January 2008 and December 2014. Thirteen female patients were enrolled. Radiographic findings were compatible with the characteristics of atypical fracture. Surgical intervention was performed for all, and teriparatide use was advised postoperatively. Outcome measures included perioperative results, and clinical and radiographic outcome. RESULTS: Of the 13 female patients enrolled, 10 had subtrochanteric and 6 had proximal femoral fracture; 3 had bilateral fractures. The mean age of the patients at surgery was 70.15±6.36 years. Most fractures (68.8%) presented prodromal thigh pain. All patients were treated with an intramedullary fixation system without severe complications. The patients were divided into 2 groups based on whether they had received treatment with teriparatide or not. The mean time to bone union was 4.4 months in the teriparatide-treated group, and 6.2 months in the non-teriparatide-treated group (p=0.116). Six patients (75%) in the teriparatide-treated group and 4 (50%) in the non-teriparatide-treated group (p= 0.3) achieved bone union within 6 months. The means of the modified Harris Hip Score and Numerical Rating Scale were significantly better in the teriparatide-treated group at postoperative 6 months. Seven patients had the same ability to walk at the 1-year follow-up as they did before the atypical fracture. CONCLUSIONS: Teriparatide treatment in patients with atypical fracture may help in fracture healing, hip function recovery, and pain relief in this reduced bone turnover patient group.

Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes.

Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a l-fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galß1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, D-galactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent d-mannose and d-xylose, respectively), underlying the molecular basis of the FMS-induced IgM antibodies against tumor-specific glycans.

Postoperative meningitis after spinal surgery: a review of 21 cases from 20,178 patients.

BACKGROUND: Postoperative bacterial meningitis is a rare complication of spinal surgery and is considered to be a complication related to intraoperative incidental durotomy. A high index of suspicion for meningitis is essential in patients who have the clinical triad of fever, neck stiffness and consciousness disturbance during the postoperative period. A delay in diagnosis or treatment can lead to morbidity and mortality. Due to the low incidence of postoperative meningitis, very few studies have reported this complication. The purpose of this study was to report the clinical features, laboratory evaluations, treatment course and prognosis of 21 patients with post spinal surgery meningitis. METHODS: We retrospectively reviewed 21 patients (13 male, 8 female) with the diagnosis of postoperative meningitis after lumbar spinal surgery between January 2001 and Aug 2011. The median age of the patients was 67 years old (range 27 to 82 years) at the time of surgery. We recorded the preoperative diagnosis, operative methods, amount of drainage, clinical manifestations, laboratory evaluations, cerebrospinal fluid study, and infectious organisms. All patients diagnosed with postoperative meningitis received at least two weeks of antibiotic treatment. Clinical outcomes were assessed after at least two years of follow-up. RESULTS: From January 2001 to August 2011, 20,178 spinal operations were performed in our institution, and 21 patients (0.10%) were diagnosed with postoperative meningitis. Eighteen patients (85.7%) had fever, 19 (90.5%) had neck stiffness, and 16 (76.2%) had consciousness disturbance. All patients had at least two of the classic triad. In addition, 9 patients (42.9%) had headache, 3 (14.3%) had focal neurological deficits, and 2 (9.5%) had seizure attacks. There was no mortality in this series. Postoperative meningitis showed no adverse effect on the results of spinal surgery after follow-up for at least two years. CONCLUSIONS: Postoperative meningitis is a rare complication after spinal lumbar surgery. A high index of suspicion for meningitis should be maintained in patients with the clinical triad of fever, neck stiffness, and consciousness disturbance after spinal surgery. Intraoperative incidental durotomy is the most important predictor. An early diagnosis and appropriate antibiotic treatment can lead to a good outcome.

The effects of anterior vacuum disc on surgical outcomes of degenerative versus spondylolytic spondylolisthesis: at a minimum two-year follow-up.

BACKGROUND: The vacuum phenomenon within the intervertebral disc usually represents disc degeneration. There are no reports in the English literature that focus on the effect of an anterior vacuum disc on surgical outcome of same-segment spondylolisthesis. METHODS: Patients with degenerative spondylolisthesis (DS) or isthmic spondylolisthesis (IS) who underwent a spinal surgery between January 2005 and December 2006 were reviewed. Patients who met certain criteria, including (1) only mono-segment spondylolisthesis, (2) gas air within the disc space of the spondylolisthesis segment on preoperative radiographs, (3) having received posterior decompression, posterior pedicle screw fixation, and posterolateral fusion, and (4) at least 12 months of follow-up radiographs available to define the posterolateral fusion rate, were enrolled into the study. Four radiographic parameters (disc height, translation, intradiscal angle, segmental angle) were assessed. Two-year postoperative radiographs were used to determine whether the posterolateral segment was fused or not. Clinical outcome and complications during the follow-up period were documented. RESULTS: Incidence of the disc vacuum phenomenon was significantly higher in the IS group than in the DS group (p < 0.001). The IS group had more listhesis and a narrower disc height on preoperative static radiographs; however, the DS group had a more prominent angle and listhesis change in preoperative dynamic variables. The posterolateral fusion rate was significantly higher in the IS group (p = 0.019). The preoperative Oswestry Disability Index (ODI) score, the final ODI, and the ODI difference were similar between groups. More excellent and good results were seen in the IS group. Besides, better final ODI and results were seen in the bilateral fusion group than in the nonfusion group. CONCLUSION: The disc vacuum phenomenon is not equal to anterior instability absolutely. Determination of stability or instability in a vacuum disc should be considered by a combination of dynamic radiographs. In the present study, vacuum discs in the DS group showed more instability and a higher posterolateral pseudoarthrosis rate.

Comparison of two-stage open versus percutaneous pedicle screw fixation in treating pyogenic spondylodiscitis.

BACKGROUND: Percutaneous pedicle screw instrumentation is a minimally invasive surgical technique; however, the effects of using percutaneous pedicle screw fixation in treating patients with spinal infections have not yet been well demonstrated. The aim of this study, therefore, was to determine whether percutaneous posterior pedicle screw instrumentation is superior to the traditional open approach in treating pyogenic spondylodiscitis. METHODS: We retrospectively reviewed data for 45 patients treated for pyogenic spondylodiscitis with anterior debridement and interbody fusion followed by a second-stage procedure involving either traditional open posterior pedicle screw fixation or percutaneous posterior pedicle screw fixation. Twenty patients underwent percutaneous fixation and 25 patients underwent open fixation. Demographic, operative, and perioperative data were collected and analyzed. RESULTS: The average operative time for the percutaneous procedure was 102.5 minutes, while the average time for the open procedure was 129 minutes. The average blood loss for the percutaneous patients was 89 ml versus a 344.8 ml average for the patients in the open group. Patients who underwent the minimally invasive surgery had lower visual analogue scale scores and required significantly less analgesia afterwards. After two years of follow-up, neither recurrent infection nor intraoperative complications, such as wound infection or screw loosening, were found in the percutaneous group. Moreover, there was no significant difference in outcome between the two groups in terms of Oswestry Disability Index scores. CONCLUSIONS: Anterior debridement and interbody fusion with bone grafting followed by minimally invasive percutaneous posterior instrumentation is an alternative treatment for pyogenic spondylodiscitis which can result in less intraoperative blood loss, shorter operative time, and reduced postoperative pain with no adverse effect on infection control.

Ganoderma microsporum immunomodulatory protein combined with KRASG12C inhibitor impedes intracellular AKT/ERK network to suppress lung cancer cells with KRAS mutation.

KRAS mutations are tightly associated with lung cancer progression. Despite the unprecedented clinical success of KRASG12C inhibitors, recurrent mechanisms of resistance and other KRAS mutations require further therapeutic approaches. GMI, a protein from the medicinal mushroom Ganoderma microsporum, possesses antitumor activity; whereas, the biological function of GMI on regulating KRAS mutant lung cancer cells remains unknown. Herein, RNA-sequencing and bioinformatics showed that GMI may regulate KRAS-modulated MAPK and PI3K-AKT pathways in A549 (KRASG12S) cells. Further experiments demonstrated that GMI inhibited KRAS activation and suppressed ERK1/2 and AKT signaling in A549 cells. Intriguingly, GMI inhibited AKT signaling but increased phosphorylation of ERK in H358 (KRASG12C) cells. GMI significantly suppressed tumor growth in LLC1 cells-allograft and H358 cells-xenograft mice. GMI showed a synergistic effect with KRASG12C inhibitors in inhibiting cell growth, KRAS activation and KRAS-mediated downstream signaling, leading to apoptosis in H358 cells. Combination of GMI and KRASG12C inhibitor, AMG 510, resulted in more durable inhibition of tumor growth and KRAS activity in H358 cells-xenograft mice. This study highlights the potential of GMI, a dietary fungal protein, as a viable therapeutic avenue for KRAS-mutant lung cancer in combination with KRASG12C inhibitors.

Targeting TGFß receptor-mediated snail and twist: WSG, a polysaccharide from Ganoderma lucidum, and it-based dissolvable microneedle patch suppress melanoma cells.

Cutaneous melanoma is a lethal skin cancer variant with pronounced aggressiveness and metastatic potential. However, few targeted medications inhibit the progression of melanoma. Ganoderma lucidum, which is a type of mushroom, is widely used as a non-toxic alternative adjunct therapy for cancer patients. This study determines the effect of WSG, which is a water-soluble glucan that is derived from G. lucidum, on melanoma cells. The results show that WSG inhibits cell viability and the mobility of melanoma cells. WSG induces changes in the expression of epithelial-to-mesenchymal transition (EMT)-related markers. WSG also downregulates EMT-related transcription factors, Snail and Twist. Signal transduction assays show that WSG reduces the protein levels in transforming growth factor ß receptors (TGFßRs) and consequently inhibits the phosphorylation of intracellular signaling molecules, such as FAK, ERK1/2 and Smad2. An In vivo study shows that WSG suppresses melanoma growth in B16F10-bearing mice. To enhance transdermal drug delivery and prevent oxidation, two highly biocompatible compounds, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), are used to synthesize a dissolvable microneedle patch that is loaded with WSG (MN-WSG). A functional assay shows that MN-WSG has an effect that is comparable to that of WSG alone. These results show that WSG has significant potential as a therapeutic agent for melanoma treatment. MN-WSG may allow groundbreaking therapeutic approaches and offers a novel method for delivering this potent compound effectively.