Phyllanthus emblica Linn: A comprehensive review of botany, traditional uses, phytonutrients, health benefits, quality markers, and applications.

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.

The sources, properties, extraction, biosynthesis, pharmacology, and application of lycopene.

Lycopene is an important pigment with an alkene skeleton from Lycopersicon esculentum, which is also obtained from some red fruits and vegetables. Lycopene is used in the food field with rich functions and serves in the medical field with multiple clinical values because it has dual functions of both medicine and food. It was found that lycopene was mainly isolated by solvent extraction, ultrasonic-assisted extraction, supercritical fluid extraction, high-intensity pulsed electric field-assisted extraction, enzymatic-assisted extraction, and microwave-assisted extraction. Meanwhile, it was also obtained via 2 synthetic pathways: chemical synthesis and biosynthesis. Pharmacological studies revealed that lycopene has anti-oxidant, hypolipidemic, anti-cancer, immunity-enhancing, hepatoprotective, hypoglycemic, cardiovascular-protective, anti-inflammatory, neuroprotective, and osteoporosis-inhibiting effects. The application of lycopene mainly includes food processing, animal breeding, and medical cosmetology fields. It is hoped that this review will provide some useful information and guidance for future study and exploitation of lycopene.

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia].

OBJECTIVE: To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML). METHODS: The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed. RESULTS: Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified). CONCLUSION: D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

An estrogen response-related signature predicts response to immunotherapy in melanoma.

Background: Estrogen/estrogen receptor signaling influences the tumor microenvironment and affects the efficacy of immunotherapy in some tumors, including melanoma. This study aimed to construct an estrogen response-related gene signature for predicting response to immunotherapy in melanoma. Methods: RNA sequencing data of 4 immunotherapy-treated melanoma datasets and TCGA melanoma was obtained from open access repository. Differential expression analysis and pathway analysis were performed between immunotherapy responders and non-responders. Using dataset GSE91061 as the training group, a multivariate logistic regression model was built from estrogen response-related differential expression genes to predict the response to immunotherapy. The other 3 datasets of immunotherapy-treated melanoma were used as the validation group. The correlation was also examined between the prediction score from the model and immune cell infiltration estimated by xCell in the immunotherapy-treated and TCGA melanoma cases. Results: "Hallmark Estrogen Response Late" was significantly downregulated in immunotherapy responders. 11 estrogen response-related genes were significantly differentially expressed between immunotherapy responders and non-responders, and were included in the multivariate logistic regression model. The AUC was 0.888 in the training group and 0.654-0.720 in the validation group. A higher 11-gene signature score was significantly correlated to increased infiltration of CD8+ T cells (rho=0.32, p=0.02). TCGA melanoma with a high signature score showed a significantly higher proportion of immune-enriched/fibrotic and immune-enriched/non-fibrotic microenvironment subtypes (p<0.001)-subtypes with better response to immunotherapy-and significantly better progression-free interval (p=0.021). Conclusion: In this study, we identified and verified an 11-gene signature that could predict response to immunotherapy in melanoma and was correlated with tumor-infiltrating lymphocytes. Our study suggests targeting estrogen-related pathways may serve as a combination strategy for immunotherapy in melanoma.

Effects of glycolysis on the polarization and function of tumor­associated macrophages (Review).

Under conditions of oxygen sufficiency, tumor cells supply themselves with energy through glycolysis, which is one of the causes of their rapid proliferation, metastasis and acquisition of drug resistance. Tumor­associated macrophages (TAMs) are transformed from peripheral blood monocytes and are among the immune­related cells that constitute the tumor microenvironment (TME). Altered glycolysis levels in TAMs have an important impact on their polarization and function. The cytokines secreted by TAMs, and phagocytosis in different polarization states, affect tumorigenesis and development. Furthermore, changes in glycolysis activity of tumor cells and other immune­related cells in the TME also affect the polarization and function of TAMs. Studies on the relationship between glycolysis and TAMs have received increasing attention. The present study summarized the link between glycolysis of TAMs and their polarization and function, as well as the interaction between changes in glycolysis of tumor cells and other immune­associated cells in the TME and TAMs. The present review aimed to provide a comprehensive understanding of the effects of glycolysis on the polarization and function of TAMs.

Hippophae rhamnoides L.: A Comprehensive Review on the Botany, Traditional Uses, Phytonutrients, Health Benefits, Quality Markers, and Applications.

Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids (1-99), lignans (100-143), volatile oils (144-207), tannins (208-230), terpenoids (231-260), steroids (261-270), organic acids (271-297), and alkaloids (298-305). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure-activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.

Photobiomodulation (800 nm Light-Emitting Diode) Treatment Promotes Bone Mesenchymal Stem Cell Proliferation Via Long Noncoding RNA MEG3-MicroRNA-217-5P Pathway.

Background: Patients with osteoporosis (OP) have a high risk of bone fracture. Abnormal bone mesenchymal stem cell (BMSC) differentiation is an essential process of OP development. In recent years, photobiomodulation has been shown to effectively promote BMSC proliferation. However, the mechanism by which photobiomodulation promotes BMSC proliferation is unclear. Long noncoding RNAs (lncRNAs) are essential mediators in multiple biological processes. The lncRNA maternally expressed gene 3 (MEG3) is a novel lncRNA gene and is related to cell proliferation. Studies have indicated that MEG3 serves as a promotor in BMSC proliferation. Objective: To investigate the effects and mechanisms of 800 nm light-emitting diode (LED) photobiomodulation in BMSC proliferation. Materials and methods: The BMSCs collected from mouse tibias and femurs were irradiated by 800 nm LED for 180 sec. CCK-8 assay was used to detect the cell viability. A dual-luciferase reporter assay was used to determine IncRNA MEG3 acted as a miR-217-5p sponge. We used reverse transcription-polymerase chain reaction (RT-PCR) and western blot to detect the mRNA and protein levels of MEG3, miR-217-5p, Notch2, Hes1, Hey2. Results: In the present study, we revealed that photobiomodulation (800 nm LED) could increase the mRNA level of MEG3, and protein levels of Notch2, Hes1, and Hey2. Moreover, we also identified that upregulated MEG3 could act as a miR-217-5p sponge to activate the Notch signaling pathway. Conclusions: The current study revealed the MEG3-related mechanism of photobiomodulation treatment in OP and identified potential gene therapies for OP.

Using ultrasound radiomics analysis to diagnose cervical lymph node metastasis in patients with nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to explore the clinical value of ultrasound radiomics analysis in the diagnosis of cervical lymph node metastasis (CLNM) in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 205 cases of NPC CLNM and 284 cases of benign lymphadenopathy with pathologic diagnosis were retrospectively included. Grayscale ultrasound (US) images of the largest section of every lymph node underwent feature extraction. Feature selection was done by maximum relevance minimum redundancy (mRMR) algorithm and multivariate logistic least absolute shrinkage and selection operator (LASSO) regression. Logistic regression models were developed based on clinical features, radiomics features, and the combination of those features. The AUCs of models were analyzed by DeLong's test. RESULTS: In the clinical model, lymph nodes in the upper neck, larger long axis, and unclear hilus were significant factors for CLNM (p < 0.001). MRMR and LASSO regression selected 7 significant features for the radiomics model from the 386 radiomics features extracted. In the validation dataset, the AUC value was 0.838 (0.776-0.901) in the clinical model, 0.810 (0.739-0.881) in the radiomics model, and 0.880 (0.826-0.933) in the combined model. There was not a significant difference between the AUCs of clinical models and radiomics models in both datasets. DeLong's test revealed a significantly larger AUC in the combined model than in the clinical model in both training (p = 0.049) and validation datasets (p = 0.027). CONCLUSION: Ultrasound radiomics analysis has potential value in screening meaningful ultrasound features and improving the diagnostic efficiency of ultrasound in CLNM of patients with NPC. KEY POINTS: • Radiomics analysis of gray-scale ultrasound images can be used to develop an effective radiomics model for the diagnosis of cervical lymph node metastasis in nasopharyngeal carcinoma patients. • Radiomics model combined with general ultrasound features performed better than the clinical model in differentiating cervical lymph node metastases from benign lymphadenopathy.

Diagnosis of hepatic inflammatory pseudotumor by fine-needle biopsy.

Hepatic inflammatory pseudotumor (IPT) is a benign lesion characterized by chronic infiltration of inflammatory cells and fibrosis that clinically, radiologically, and pathologically mimics malignancy. However, the epidemiology of IPTs remains unclear. IPTs are often misdiagnosed as malignant lesions because of the lack of characteristic features. We present the case of a 32-year-old man that was misdiagnosed as intrahepatic cholangiocarcinoma by CECT, CEMRI, and CEUS, which was finally confirmed as IPT by fine-needle liver biopsy. In this report, the key factor in the diagnosis of liver inflammatory masses was the presence of hepatic perfusion disorder.

Deep Learning of Liver Contrast-Enhanced Ultrasound to Predict Microvascular Invasion and Prognosis in Hepatocellular Carcinoma.

Background and Aims: Microvascular invasion (MVI) is a well-known risk factor for poor prognosis in hepatocellular carcinoma (HCC). This study aimed to develop a deep convolutional neural network (DCNN) model based on contrast-enhanced ultrasound (CEUS) to predict MVI, and thus to predict prognosis in patients with HCC. Methods: A total of 436 patients with surgically resected HCC who underwent preoperative CEUS were retrospectively enrolled. Patients were divided into training (n = 301), validation (n = 102), and test (n = 33) sets. A clinical model (Clinical model), a CEUS video-based DCNN model (CEUS-DCNN model), and a fusion model based on CEUS video and clinical variables (CECL-DCNN model) were built to predict MVI. Survival analysis was used to evaluate the clinical performance of the predicted MVI. Results: Compared with the Clinical model, the CEUS-DCNN model exhibited similar sensitivity, but higher specificity (71.4% vs. 38.1%, p = 0.03) in the test group. The CECL-DCNN model showed significantly higher specificity (81.0% vs. 38.1%, p = 0.005) and accuracy (78.8% vs. 51.5%, p = 0.009) than the Clinical model, with an AUC of 0.865. The Clinical predicted MVI could not significantly distinguish OS or RFS (both p > 0.05), while the CEUS-DCNN predicted MVI could only predict the earlier recurrence (hazard ratio [HR] with 95% confidence interval [CI 2.92 [1.1-7.75], p = 0.024). However, the CECL-DCNN predicted MVI was a significant prognostic factor for both OS (HR with 95% CI: 6.03 [1.7-21.39], p = 0.009) and RFS (HR with 95% CI: 3.3 [1.23-8.91], p = 0.011) in the test group. Conclusions: The proposed CECL-DCNN model based on preoperative CEUS video can serve as a noninvasive tool to predict MVI status in HCC, thereby predicting poor prognosis.

PD-1 Checkpoint Blockade in Patients for Acute Myeloid Leukemia after HSCT Relapse Resulted in Severe GVHD and sHLH.

Treatment with immune checkpoint inhibitors (ICI) such as carrizumab leads to immune-mediated adverse effects including severe acute graft versus host disease (aGVHD) and secondary hemophagocytic syndrome (sHLH). Herein, we present two cases where aGVHD and sHLH developed after ICI administration, which was treated using methylprednisolone (MP). They developed high-grade fever complicated with liver dysfunction and diarrhea 1 day after ICI administration. Treatment with MP does not alleviate symptoms because of steroid resistance. Hyperbilirubinemia, rash with blisters, and watery diarrhea showed severe aGVHD. Hyperferritinemia, hypertriglyceridemia, and cytopenias suggested the diagnosis of HLH and met the criteria for sHLH diagnosis. They were thus administered intravenous high-dose MP, methotrexate (MTX), basiliximab, ruxolitinib, etc, which resolved these symptoms.

Hostaflavone A from Hosta plantaginea (Lam.) Asch. blocked NF-κB/iNOS/COX-2/MAPKs/Akt signaling pathways in LPS-induced RAW 264.7 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Hostaflavone A (HA) is a new flavonoid component isolated from the flower of Hosta plantaginea (Lam.) Asch., which is commonly used as a folk herbal to treat inflammatory diseases in China. Nevertheless, the anti-inflammatory effect of HA remains unknown. AIM OF THE STUDY: This work aimed to evaluate the HA with anti-inflammatory activity and mechanism in RAW 264.7 macrophages activated by lipopolysaccharide (LPS). MATERIALS AND METHODS: Anti-inflammatory effect of HA was evaluated by measuring of cell viability, nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6 levels in RAW 264.7 cells. In parallel, the HA action mechanism of nuclear factor kappa B (NF-κB) p65, inhibitor of NF-κB (IκB), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (Erk), p38, and protein kinase B (Akt) were detected by Western blot analysis. RESULTS: HA has no cytotoxicity at concentrations as high as 40 µM. Besides, HA concentration-dependently clearly suppressed the overproduction of NO, PGE2, TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS. In addition, HA remarkably reduced the upregulation of phosphorylated NF-κB p65, phosphorylated IκB, phosphorylated JNK, phosphorylated Erk and phosphorylated p38, together with iNOS and COX-2 protein expressions in a concentration-dependent manner. CONCLUSION: HA blocked the LPS activated inflammation via suppressing NF-κB, iNOS, COX-2, mitogen-activated protein kinases (MAPKs) and Akt pathways in RAW 264.7 cells, and might be a new anti-inflammatory agent.

TTK predicts triple positive breast cancer prognosis and regulates tumor proliferation and invasion.

This study was conducted to investigate the expression of the spindle assembly checkpoint kinase tyrosine/threonine kinase (TTK) in triple positive breast cancer (TPBC) and its effect on TPBC cells. We analyzed the status of TTK in 69 TPBC samples using immunohistochemistry. The correlation between TTK and clinicopathological parameters was analyzed using a chi-squared test. The prognostic value of TTK was evaluated using Kaplan-Meier survival curves. We analyzed the role of TTK in the invasion and proliferation of TPBC cells in vitro and in vivo. The mean age of the 69 patients with TPBC enrolled in this study was 53 years (range: 29-86 years). TTK expression was positively correlated with tumor size (p=0.034), p53 status (p=0.023), TNM stage ([p=0.023), and Ki-67 index (p<0.001). The Kaplan-Meier curves revealed that TTK expression was correlated with poor disease-free survival (p=0.001) and overall survival (p=0.050). Multivariate proportional hazard regression analyses showed that TTK and TNM staging were significant independent predictors of disease-free survival (p=0.007 and p=0.034, respectively). Additionally, TTK knockdown inhibited the invasion and proliferation of the BT474 TPBC cell line. The findings of this study indicate that TTK overexpression is associated with cancer progression and prognosis in patients with TPBC, whereas TTK knockdown inhibits the invasion and proliferation of TPBC cells. Thus, TTK might serve as a prognostic marker for TPBC.

Validation of American College of Radiology Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US): Analysis on 1054 adnexal masses.

OBJECTIVE: To assess the diagnostic performance and inter-observer agreement of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US). METHODS: From January 2016 to December 2018 a total of 1054 adnexal lesions in 1035 patients with pathologic results from two hospitals were retrospectively included. Each lesion was assigned to an O-RADS US category according to the criteria. Kappa (κ) statistics were applied to assess inter-observer agreement between a less experienced and an expert radiologist. RESULTS: Of the 1054 adnexal lesions, 750 were benign and 304 were malignant. The malignancy rates of O-RADS 5, O-RADS 4, O-RADS 3, and O-RADS 2 lesions were 89.57%, 34.46%, 1.10%, and 0.45% respectively. Area under the receiver operating characteristic curve was 0.960 (95% CI, 0.947-0.971). The optimal cutoff value for predicting malignancy was >O-RADS 3 with a sensitivity and specificity of 98.7% (95% CI, 0.964-0.996) and 83.2% (95% CI, 0.802-0.858) respectively. When sub-classifying multilocular cysts and smooth solid lesions in O-RADS 4 lesions as O-RADS 4a lesions and the rest cystic lesions with solid components as O-RADS 4b lesions, the malignancy rate were 17.02% and 42.57% respectively, which showed better risk stratification (P < 0.001). The inter-observer agreement between a less-experienced and an expert radiologist of O-RADS categorization was good (κ = 0.714). CONCLUSIONS: The ACR O-RADS US provides effective malignancy risk stratification for adnexal lesions with high reliability for radiologists with different experience. Sub-grouping of O-RADS 4 lesions into two groups facilitated better stratification of the intermediate risk.

Giant schwannoma of thoracic vertebra: A case report.

BACKGROUND: It is relatively rare for schwannomas to invade bone, but it is very rare for a large mass to form concurrently in the paravertebral region. Surgical resection is the only effective treatment. Because of the extensive tumor involvement and the many important surrounding structures, the tumor needs to be fully exposed. Most of the tumors are completely removed by posterior combined open-heart surgery to relieve spinal cord compression, restore the stability of the spine and maximize the recovery of nerve and spinal cord function. The main objective of this article is to present a schwannoma that had invaded the T5 and T6 vertebral bodies and formed a large paravertebral mass with simultaneous invasion of the spinal canal and compression of the spinal cord. CASE SUMMARY: A 40-year-old female suffered from intermittent chest and back pain for 8 years. Computed tomography and magnetic resonance imaging scans showed a paravertebral tumor of approximately 86 mm × 109 mm × 116 mm, where the adjacent T5 and T6 vertebral bodies were invaded by the tumor, the right intervertebral foramen was enlarged, and the tumor had invaded the spinal canal to compress the thoracic medulla. The preoperative puncture biopsy diagnosed a benign schwannoma. Complete resection of the tumor was achieved by a two-step operation. In the first step, the thoracic surgeon adopted a lateral approach to separate the thoracic tumor from the lung. In the second step, a spine surgeon performed a posterior midline approach to dissect the tumor from the vertebral junction through removal of the tumor from the posterior side and further resection of the entire T5 and T6 vertebral bodies. The large bone defect was reconstructed with titanium mesh, and the posterior root arch was nail-fixed. Due to the large amount of intraoperative bleeding, we performed tumor angioembolization before surgery to reduce and avoid large intraoperative bleeding. The postoperative diagnosis of benign schwannoma was confirmed by histochemical examination. There was no sign of tumor recurrence or spinal instability during the 2-year follow-up. CONCLUSION: Giant schwannoma is uncommon. In this case, a complete surgical resection of a giant thoracic nerve sheath tumor that invaded part of the vertebral body and compressed the spinal cord was safe and effective.

Chinese patient with cerebrotendinous xanthomatosis confirmed by genetic testing: A case report and literature review.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a treatable autosomal recessive inherited metabolic disorder. It results from a deficiency of sterol 27-hydroxylase (CYP27A1), which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis. Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain, eyes, tendons, and vessels, resulting in juvenile cataracts, tendon xanthoma, chronic diarrhea, cognitive impairment, ataxia, spastic paraplegia, and peripheral neuropathy. CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports. CASE SUMMARY: A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy. CONCLUSION: CYP27A1 genetic analysis should be the definitive method for CTX diagnosis. This case suggests that urinary system diseases may be neglected in CTX patients. The clinical, biological, radiological, and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.

[Expression and Clinical Significance of Long Non-coding RNA AC002454.1 in Children with Acute Leukemia].

OBJECTIVE: To study the difference of long non coding RNA (lncRNA) expression profile in bone marrow specimens of children with acute leukemia (AL) and other hematological disease children with normal bone marrows as controls, to screen the lncRNA related with childhood hematological diseases, and to explore the expression of lncRNA AC002454.1 and its clinical significance in AL children. METHODS: The microarray gene chip technology was used to statistically analyze the lncRNA in bone marrow cells of newly diagnose AL children and control children. Ninty-seren differentially expressed lncRNAs were selected. The bone marrow specimens of ALL children (21 cases), AML children (22 cases) and control children (21 cases) were verified and compared by using qRT-PCR; then the lncRNA with maximum differential expression-lncRNA AC002454.1 was selected and used to analyze the relation of relative expression level with clinical indicators. RESULTS: The microarray gene chip detection showed that 1 884 differentially expressed lncRNA were found in ALL children, and 4 289 differentically expressed lncRNA were found in AML children. The results confirming these differentically expressed lncRNA by qRT-PCR showed that 9 lncRNA expression were significantly up-regulated in ALL children, and 12 lncRNA expression were significantly up-regulated in AML children. Among these up-regulated lncRNA, the difference of AC002454.1 expression was most significant in ALL and AML children (P＜0.05, P＜0.01). The detection showed that there was a significant difference, in AC002454.1 relative expression level of newly diagnosed T-ALL and B-ALL children (P＜0.01), moreover, this difference also was found in ALL and AML children (P＜0.05). The detection analysis showed that there was no statistical difference in AC002454.1 relative expression level among the different sex, age, WBC count at initial diagnosis, chromosome, fusion gene, and risk stratification (P＞0.05 for all). CONCLUSION: The lncRNA expression profile of AL children has been gained by using the lncRNA microarray gene chip technicology. AC002454.1 the significantly high expression exist in AL children, which relates with immunotyping and prognosis of AL children in a certain degree.

Efficacy of mesenchymal stem cells in the treatment of gastrointestinal malignancies.

Mesenchymal stem cells (MSCs), which are a kind of stem cell, possess an immune privileged nature, tumour homing features, and multi-lineage differentiation ability. MSCs have been studied in many fields, such as tissue engineering, nervous system diseases, and cancer treatment. In recent years, an increasing number of researchers have focused on the effects of MSCs on various kinds of tumours. However, the concrete anticancer efficacy of MSCs is still controversial. Gastrointestinal (GI) malignancies are the major causes of cancer-related death worldwide. The interactions of MSCs and GI cancer cells in specific conditions have attracted increasing attention. In this review, we introduce the characteristics of MSCs and analyse the effects of MSCs on GI malignancies, including gastric cancer, hepatoma, pancreatic cancer, and colorectal cancer. In addition, we also provide our perspectives on why MSCs may play different roles in GI malignancies and further research directions to increase the treatment efficacy of MSCs on GI malignancies.