Low muscle density in children with osteogenesis imperfecta using opportunistic low-dose chest CT: a case-control study.

BACKGROUND: The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. METHODS: This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. RESULTS: 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p < 0.01; 37.3 HU vs. 45.9 HU, p < 0.01). However, children with OI had lower T4 muscle size, T4 muscle density, T10 muscle size and T10 muscle density than controls measured by the Gaussian mixture model (110.9 vs. 127.2 cm2, p = 0.03; 44.6 HU vs. 51.3 HU, p < 0.01; 72.6 vs. 88.0 cm2, p = 0.01; 41.6 HU vs. 50.3 HU, p < 0.01, respectively). CONCLUSIONS: Children with OI had lower trunk muscle density indicating that OI might also impair muscle quality. Moreover, the fixed thresholds may not be suitable for segmentation of muscle in children.

Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer's disease via inhibition of ACSL4-dependent ferroptosis.

Alzheimer's disease (AD) is associated with high incidence of cardiovascular events but the mechanism remains elusive. Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase (ALDH2) activity in elderly AD patients. In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD. Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice. Cognitive function, cardiac contractile, and morphological properties were assessed. We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test, myocardial ultrastructural, geometric (cardiac atrophy, interstitial fibrosis) and functional (reduced fractional shortening and cardiomyocyte contraction) anomalies along with oxidative stress, apoptosis, and inflammation in myocardium. ALDH2 transgene significantly attenuated or mitigated these anomalies. We also noted the markedly elevated levels of lipid peroxidation, the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4), the transcriptional regulator for ACLS4 special protein 1 (SP1) and ferroptosis, evidenced by elevated NCOA4, decreased GPx4, and SLC7A11 in myocardium of APP/PS1 mutant mice; these effects were nullified by ALDH2 transgene. In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aß (20 µM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aß-induced deteriorating effects. ALDH2-induced protection against Aß-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid (TA) or the ACSL4 inhibitor triacsin C (TC), and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid (5-HETE) or the ferroptosis inducer erastin. These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis.

Design, synthesis and biological evaluation of novel benzo-α-pyrone containing piperazine derivatives as potential BRAFV600E inhibitors.

The increasingly acquired resistance to vemurafenib and side effects of known inhibitors motivate the search for new and more effective anti-melanoma drugs. In this Letter, virtual screening and scaffold growth were combined together to achieve new molecules as BRAFV600E inhibitors. Along with docking simulation, a primary screen in vitro was performed to filter the modifications for the lead compound, which was then substituted, synthesized and evaluated for their inhibitory activity against BRAFV600E and several melanoma cell lines. Out of the obtained compounds, derivative 3l was identified as a potent BRAFV600E inhibitor and exerted an anticancer effect through BRAFV600E inhibition. The following biological evaluation assays confirmed that 3l could induce cell apoptosis and marked DNA fragmentation. Furthermore, 3l could arrest the cell cycle at the G0/G1 phase in melanoma cells. The docking simulation displayed that 3l could tightly bind with the crystal structure of BRAFV600E at the active site. Overall, the biological profile of 3l suggests that this compound may be developed as a potential anticancer agent.

Discovery of Chromeno[4,3-c]pyrazol-4(2H)-one Containing Carbonyl or Oxime Derivatives as Potential, Selective Inhibitors PI3Kα.

A series of novel chromeno[4,3-c]pyrazol-4(2H)-one containing carbonyl or oxime derivatives (4a-n, 5a-n) have been synthesized and evaluated their biological activities as phosphatidyl inositol 3-kinase (PI3K) inhibitors. Out of them, compound 5l showed the most potent antiproliferative activities against HCT-116 with IC50 of 0.10 µM in vitro, and exhibited the most potent activity for PI3Kα with the value of 0.012 µM. Docking simulation of 5l into PI3Kα active site were performed to determine the probable binding model, and it indicated that compound 5l could be optimized as a potential inhibitor of PI3Kα in the further study.

Treatment of lumbar disc herniation with robot combined with unilateral biportal endoscopic technology: A case report.

BACKGROUND: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference. CASE SUMMARY: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory. CONCLUSION: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion.

A retrospective comparative study of robot-assisted unilateral biportal endoscopic lumbar decompression and fusion surgery versus percutaneous endoscopic lumbar decompression and fusion surgery.

The objective of this study is to illustrate the advantages of robot-assisted unilateral biportal endoscopy in lumbar decompression fusion and internal fixation surgery. According to the different surgical methods, we divided the 26 patients into 2 groups, robot-assisted unilateral biportal endoscopy for lumbar interbody fusion (R-ULIF) group and percutaneous endoscopic lumbar decompression and interbody fusion (Endo-LIF) group, with a 1:1 ratio. Gender, disease course, lesion site, fluoroscopy times, operative time, blood loss, postoperative hospital stay, screw placement success rate, fusion rate, complications rate, postoperative pain visual analog scale (VAS) (The VAS score is used only to evaluate pain in the lower back and legs.) Oswestry Disability Index (ODI) (The ODI score can serve as a reference indicator for evaluating the effectiveness of treatment for patients with low back pain, and has good responsiveness in assessing patients with chronic low back pain), and MacNab (The MacNab standard is divided into 4 levels: excellent, good, fair, and poor, which can be used to evaluate the therapeutic efficacy of certain spinal surgeries) standard efficacy evaluation were analyzed and compared between the 2 groups. All patients successfully completed the surgery. Compared with the Endo-LIF group, the R-ULIF group had fewer fluoroscopy procedures, less intraoperative blood loss, and shorter postoperative hospital stay (P < .05). The VAS scores and ODI scores of both groups significantly decreased at all-time points (P < .05). The ODI scores of the R-ULIF group were better than the Endo-LIF group at 1 month and 3 months after surgery (P = .017/P = .047), but there was no statistically significant difference between the groups before surgery and 1 week after surgery (P > .05). The efficacy was evaluated using the MacNab criteria at 6 months after surgery. The R-ULIF group has an excellent and good rate of 84.6%, while the Endo-LIF group has an excellent and good rate of 76.9% (P = 1.000). Robot-assisted unilateral biportal endoscopy for lumbar interbody and fusion surgery has shown short-term clinical efficacy in the treatment of lumbar disc herniation combined with lumbar instability, surpassing endoscopic lumbar interbody fusion surgery. Robot-assisted unilateral biportal endoscopy for lumbar interbody and fusion surgery has demonstrated high success rate in screw placement, minimal radiation exposure, less intraoperative blood loss, shorter hospital stay, and thus deserves further clinical promotion.

Reference Values for Paravertebral Muscle Size and Myosteatosis in Chinese Adults, a Nationwide Multicenter Study.

RATIONALE AND OBJECTIVES: The paravertebral muscles, characterized by their susceptibility to severe size loss and fat infiltration in old age, lack established reference values for age-related variations in muscle parameters. This study aims to fill this gap by establishing reference values for paravertebral muscles in a Chinese adult population. MATERIALS AND METHODS: This cross-sectional study utilized the baseline data from the prospective cohort China Action on Spine and Hip (CASH). A total of 4305 community-dwelling participants aged 21-80 years in China were recruited between 2013 and 2017. Pregnant women, individuals with metal implants, limited mobility or diseases/conditions (spinal tumor, infection, etc.) affecting lumbar vertebra were excluded from the study. Psoas and paraspinal muscles were measured in quantitative computed tomography (QCT) images at the L3 and L5 levels using Osirix software. Age-related reference values for muscle area, density, and fat fraction were constructed as percentile charts using the lambda-mu-sigma (LMS) method. RESULTS: The paravertebral muscles exhibited an age-related decline in muscle area and density, coupled with an increase in muscle fat fraction. Between the ages of 25 and 75, the reductions in psoas and paraspinal muscle cross-sectional area at the L3 level were - 0.47%/yr and - 0.53%/yr in men, and - 0.19%/yr and - 0.23%/yr in women, respectively. Notably, accelerated muscle loss was observed during menopause and postmenopause in women (45-75 years) and intermittently during middle and old age in men (35-55 and 60-75 years). Besides, the age-related decreases in PSMA, PMA, and PSMD and the increases in PSMFF were more pronounced in L5 than in L3 CONCLUSION: This study shows distinct patterns of accelerated muscle loss were identified in menopausal and postmenopausal women and in middle-aged and old men. The findings contribute valuable information for future investigations on paravertebral muscle loss and myosteatosis.

Post-traumatic cauda equina nerve calcification: A case report.

BACKGROUND: Post-traumatic cauda equina nerve calcification is extremely rare in clinical practice, and its etiology, pathogenesis, treatment and prognosis are unclear. There are few studies and reports on Post-traumatic cauda equina nerve calcification, and this review reports a case of Post-traumatic cauda equina nerve calcification for reference. CASE SUMMARY: A 52-year-old patient presented to our hospital with a history of lumbar spinal stenosis and a lumbar vertebral fracture caused by trauma. The patient's right lower limb had weakness in hip flexion, knee extension and plantarflexion with muscle strength grade 3, right ankle dorsiflexion and thumb dorsiflexion with muscle strength grade 0. The patient's skin sensation below the right knee plane disappeared. The patient's Computed tomography (CT) data showed signs of cauda equina nerve calcification and the terminal filaments in the plane of the third to fifth lumbar vertebrae. After treatment the patient's symptoms were slightly relieved. CONCLUSION: We provide an extremely rare case of Post-traumatic cauda equina nerve calcification and offer a conservative treatment plan. However, the etiology, mechanism and treatment of Post-traumatic cauda equina nerve calcification are still unclear. This requires scholars to conduct more research and exploration in this area.

Muscle fat infiltration but not muscle cross-sectional area is independently associated with bone mineral density at the lumbar spine.

OBJECTIVE: Although sarcopenia and osteoporosis are inter-related conditions that are common with advancing age, few studies have explored relationships between muscle quality and bone mineral density (BMD). We investigated age- and sex-specific paraspinal muscle fat infiltration (MFI), muscle cross-sectional area (CSA), and spine volumetric BMD (vBMD) in healthy Chinese adults. METHODS: 605 healthy adults aged 20-59 years (340 women, mean age 39.2 years; 265 men, mean age 38.8 years) had axial T2WI MRI imaging of the lumbar spine and CSA (cm2) and MFI (%) were measured in the psoas and multifidus and erector spinae (MF-ES) muscles (L3-L4). MFI measurements were calibrated against a region of interest in an adjacent area of subcutaneous pure fat. L2-L4 vBMD was measured by quantitative CT. Age- and sex-specific subgroups were compared using the Mann-Whitney test. Multiple regression was used to test independent associations of MFI and CSA with vBMD. RESULTS: Females had lower CSA and higher MFI than males in both the psoas and MF-ES muscles (p < 0.001). In females and males, MF-ES MFI increased with age (p < 0.001) and in females age-related increases were observed for the psoas muscles (p < 0.05). Greater fat infiltration of the MS-ES muscle unit was associated with lower vBMD in both sexes (p < 0.001) but not with CSA. Following adjustment for demographic variables and CSA, MS-ES MFI remained predictive of vBMD (ß = -0.408 to -0.157, p < 0.001). CONCLUSION: We have demonstrated that, independent of CSA and demographic variables, MFI of the MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes. ADVANCES IN KNOWLEDGE: This is the first study to demonstrate that, independent of muscle size and demographic variables, MFI of the paraspinal MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes.

Short-Term Efficacy of Different First-Line Chemotherapy Regimens for Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis.

This study intends to compare short-term efficacy of 12 chemotherapy regimens in treatment of advanced non-small cell lung cancer (NSCLC) by a network meta-analysis (NMA). PubMed, Cochrane Library, and Embase were searched from the inception of each database to June 2018. Randomized controlled trials (RCTs) of the 12 chemotherapy regimens for advanced NSCLC were included. Direct and indirect evidence were combined by NMA to evaluate the odds ratio and the surface under the cumulative ranking curves (SUCRA) of the 12 chemotherapy regimens. Nineteen RCTs that met our inclusion criteria were collected in this study. For partial response (PR), gemcitabine exhibited relatively poor efficacy compared with cisplatin + gemcitabine, carboplatin + gemcitabine, carboplatin + paclitaxel, paclitaxel + gemcitabine, and cisplatin + gemcitabine + vinorelbine. For overall response rate (ORR), gemcitabine had poorer efficacy than cisplatin + gemcitabine and paclitaxel + gemcitabine. For disease control rate (DCR), compared with carboplatin + gemcitabine and gemcitabine, paclitaxel + gemcitabine had a better efficacy. Gemcitabine had the lowest SUCRA values in terms of complete response, PR, ORR, stable disease, and DCR; whereas paclitaxel + gemcitabine ranked the highest in ORR, progressive disease, and DCR. The cluster analysis revealed that cisplatin + gemcitabine, paclitaxel + gemcitabine, and cisplatin + gemcitabine + vinorelbine had better short-term efficacy for advanced NSCLC. Collectively, short-term efficacy of multidrug combination chemotherapy regimens was superior to that of single-drug chemotherapy regimens for advanced NSCLC. Cisplatin + gemcitabine, paclitaxel + gemcitabine, and cisplatin + gemcitabine + vinorelbine may have particularly prominent short-term efficacy for advanced NSCLC.

Pulmonary Langerhans cell histiocytosis in adults: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease of unknown aetiology. While it may affect any organ of the body, few cases of solitary lung involvement are published in the literature. Here, we report a rare case of pulmonary LCH (PLCH) in an adult. CASE SUMMARY: A 52-year-old male presented to hospital in July 2018 with complaints of progressively worsening cough with sputum, breathlessness, easy fatigability, and loss of appetite since 2016, and a 32-year history of heavy cigarette smoking (average 30 cigarettes/d). Physical examination showed only weakened breathing sounds and wheezing during lung auscultation. Chest computed tomography (CT) showed irregular micronodules and multiple thin-walled small holes. Respiratory function tests showed a slight decrease. Ultrasonic cardiogram showed mild tricuspid regurgitation and no pulmonary hypertension. Fibreoptic bronchoscopy was performed with transbronchial biopsies from the basal segment of right lower lobe. LCH was confirmed by immunohistochemistry. The final diagnosis was PLCH without extra-pulmonary involvement. We suggested smoking cessation treatment. A 3-mo follow-up chest CT scan showed clear absorption of the nodule and thin-walled small holes. The symptoms of cough and phlegm had improved markedly and appetite had improved. There was no obvious dyspnoea. CONCLUSION: Imaging manifestations of nodules, cavitating nodules, and thick-walled or thin-walled cysts prompted suspicion of PLCH and lung biopsy for diagnosis.

[Determination of magnetic mitomycin C-polybutylcyanoacrylate nanoparticles in mouse plasma].

OBJECTIVE: To establish a method by high-performance liquid chromatography (HPLC) for determining the concentration of magnetic mitomycin C-polybutylcyanoacrylate nanoparticles in mouse plasma. METHODS: Chromatography was performed on a LiChroCART C18 (250 mm x 4 mm, 5 microm) column with the mobile phase consisting of acetonitrile-NaAC (15:85), the flow rate of 1.0 ml/min, and the detection wavelength of 365 nm. Sample extraction was carried out with ethylacetate. RESULTS: The linear range of mouse plasma mitomycin C concentration was 0.04-1.00 microg/ml, and the linear equation of Y=16 388X-17.17 (r=0.999 8) was derived. CONCLUSION: This method is very easy to operate and suits the need of perclinical pharmacokinetic studies of mitomycin-magnetic nanoparticles and yields accurate and precise results.

Ursolic acid promotes apoptosis of SGC-7901 gastric cancer cells through ROCK/PTEN mediated mitochondrial translocation of cofilin-1.

Ursolic acid, extracted from the traditional Chinese medicine bearberry, can induce apoptosis of gastric cancer cells. However, its pro-apoptotic mechanism still needs further investigation. More and more evidence demonstrates that mitochondrial translocation of cofilin-1 appears necessary for the regulation of apoptosis. Here, we report that ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis. These findings imply that induction of apoptosis by ursolic acid stems primarily from the activation of ROCK1 and PTEN, resulting in the translocation of cofilin-1 from cytoplasm to mitochondria, release of cytochrome c, activation of caspase-3 and caspase-9, and finally inducing apoptosis of gastric cancer SGC-7901 cells.