Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

Effectiveness of Teriparatide for Spine Fusion in Osteoporotic Patient: A Systematic Review and Meta-Analysis of Comparative Studies.

OBJECTIVE: Our goal was to assess teriparatide's (TP) effectiveness in improving radiographic and functional outcomes after spinal fusion surgery. This meta-analysis included randomized controlled trials (RCTs) and comparative cohort studies. The findings provide valuable insights and guidance for surgeons treating osteoporotic patients undergoing spinal fusion surgery. METHODS: We conducted a systematic review to assess TP's efficacy in spinal fusion surgery for osteoporosis. Through thorough selection, data extraction, and quality assessment, we employed network meta-analysis to evaluate radiographic outcomes (fusion rate, screw loosening, vertebral fracture) and changes in bone mineral density measured by Hounsfield units. Functional outcomes were assessed using the Oswestry Disability Index scales. Our study aims to comprehensively understand TP's impact and effectiveness in spinal fusion surgery. RESULTS: A total of 868 patients were included in the analysis. All patients underwent thoracolumbar internal fixation fusion surgery and were divided into following 2 groups: the TP treatment group and the control group. The results revealed significant differences in radiological outcomes. The fusion rate showed a significant difference, as well as screw loosening, and bone mineral density measured in Hounsfield units. However, there was no significant difference in vertebral fracture. The TP group demonstrated favorable effects with statistical significance. In terms of functional outcomes, there was no significant difference in the assessment of Oswestry Disability Index scores between the 2 treatment groups. CONCLUSIONS: The meta-analysis demonstrated that the TP group exhibited significantly better outcomes, particularly in radiological measures, when compared to the control group. The use of TP in spinal fusion surgery shows promise in reducing postoperative complications and providing overall benefits.

Silencing MARCH2 Inhibits the Invasion, Migration, and EMT Transformation of Human Colorectal Cancer SW480 Cells.

Aim: This study aimed to investigate the role of MARCH2 (membrane-associated RING-CH2) in the progression, invasion, and migration of colorectal cancer (CRC). Methods: In this study, the expression levels of MARCH2 and E-cadherin in CRC tissues were detected by immunohistochemistry through retrospective study, and their correlation was analyzed. After silencing the MARCH2 gene using SiRNA MARCH2-1/-2, the invasion and migration abilities of SW480 cells were detected using Transwell and Scratch assay, respectively. Quantitative real-time PCR (qRT-PCR) and Western blotting assays were performed to detect the expression levels of epithelial-mesenchymal transition (EMT) related markers. Results: As compared to adjacent tissues, the MARCH2 expression level was significantly overexpressed in the CRC tissues, and correlated with tumor size, pathological grade, lymph node metastasis, and survival time. MARCH2 was negatively correlated with E-cadherin. MARCH2 silencing significantly restrained the invasion and migration abilities of SW480 cells in vitro. Meanwhile, the MARCH2 silencing also upregulated the mRNA and protein expression levels of E-cadherin and downregulated those of Vimentin. Conclusions: The high expression of MARCH2 was unfavorable for patients' survival. Thus, MARCH2 might be an independent predictor for CRC patients, affecting the invasion and metastasis of CRC through EMT.

Abdominopelvic Lymphatic Drainage Area Irradiation for Consolidative Radiotherapy of Advanced Ovarian Carcinoma: Analysis of Clinical Application Efficacy and Dosimetric Verification.

Background: The aim of the study was to evaluate the efficacy of abdominopelvic lymphatic drainage area irradiation (APLN), instead of whole abdominal radiotherapy (WART), in the consolidative radiotherapy of advanced ovarian carcinoma patients. Methods: We conducted a retrospective analysis collecting 99 patients with locally advanced ovarian cancer treated by APLN with 45 - 50 Gy/25- 28 fractions/5-7#, instead of WART. We evaluated the clinical outcome of APLN. Five patients were selected for dosimetric verifications verses WART (30 Gy/20 fractions). The normal tissue complication probability (NTCP) was calculated for the two treatment methods. Results: The mean follow-up time was 64.10 months (5.5 - 113.2 months), after APLN consolidative radiotherapy, 1-, 3-, and 5-year overall survival (OS) was 87.9%, 81.3%, and 61.5%, median disease-free survival (DFS) was 40.8 months, 5-year local recurrence free survival (LRFS) was 75.9%, and 5-year distant metastasis free survival (DMFS) was 49.2%. One patient died due to intestinal perforation. Local recurrence in the area between WART and APLN was rare (3/99 patients). The number of surgical procedures < 2 was an independent risk factor for LRFS (P = 0.023). Dosimetric comparison showed that comparing with WART, APLN significantly reduced the organ at risk (OAR) dose: 25.37 ± 3.63 Gy (25%) for liver, 8.77 ± 5.03 Gy (25%) for kidney, 8.14 ± 1.51 Gy (25%) for small intestine, etc. NTCP was reduced by 0.04-1.04% for liver, kidney, and small intestine. Conclusion: For consolidative radiotherapy in locally advanced ovarian cancer, APLN (intensity-modulated radiotherapy 45 - 50 Gy/25 - 28 fractions) could be an alternative to WART, resulting in excellent LRFS and DFS, with acceptable toxicities, comparing with previous literature reports. Dosimetric analysis also showed the benefits of APLN in NTCP.

Comparison of Neoadjuvant Chemotherapy Efficiency in Advanced Ovarian Cancer Patients Treated With Paclitaxel Plus Carboplatin and Intraperitoneal Bevacizumab vs. Paclitaxel With Carboplatin.

Objective: This study evaluated the role of neoadjuvant chemotherapy (NACT) with bevacizumab intraperitoneal perfusion in advanced ovarian cancer (AOC). Methods: In this study, 80 patients with advanced epithelial ovarian cancer (stage IIIc or IV) who received NACT at the Central Hospital of Zhuzhou between February 2019 and October 2020 were enrolled. Patients were randomized to receive paclitaxel plus carboplatin (TC) or TC plus intraperitoneal perfusion of bevacizumab (TCB). The effect of chemotherapy was assessed following two cycles of chemotherapy. Cancer antigen 125 (CA125), tumor size, ascites volume, bleeding volume, duration of operation, surgical satisfaction rate, complication rate, and residual tumor were assessed to monitor response to chemotherapy. Results: Treatment with TCB regimen significantly reduced serum levels of CA125 and ascites volume (p < 0.001). Meanwhile, the TCB group had significantly lower intraoperative blood loss and shorter operation time (p < 0.001). Most importantly, patients treated with TCB regimen had a higher surgical satisfaction rate (p < 0.01). Moreover, the incidence of postoperative wound infection, hypoproteinemia, abdominal distension, and fever was lower in the TCB group compared with the TC group. Assessment of adverse reactions during chemotherapy showed no severe complications between the two groups. Conclusions: The results demonstrated that the TCB regimen is superior to the TC regimen alone in the treatment of AOC. These findings could help improve the surgical satisfaction rate, provide more effective treatment strategies to prolong progression-free survival and reduce postoperative complications, and promote surgical recovery in AOC.

Diagnostic efficacy of FibroScan for liver inflammation in patients with chronic hepatitis B: a single-center study with 1185 liver biopsies as controls.

BACKGROUND: Noninvasive diagnostic technologies that can dynamically monitor changes in liver inflammation are highly important for the management of chronic hepatitis B (CHB) patients and thus warrant further exploration. This study assessed the diagnostic efficacy of FibroScan for liver inflammation in CHB patients. METHODS: A total of 1185 patients were selected, and ultrasound-guided liver biopsy was performed within 1 month after the FibroScan test. The liver stiffness measurement (LSM), the reliability criteria (IQR/M) of LSM, the quality of liver biopsy (complete portal area, PA), and the liver inflammation grades were the main observation items of this study. With liver biopsy as the control, the diagnostic efficacy of FibroScan for liver inflammation in CHB patients was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The grade of liver inflammation was positively correlated with the stage of fibrosis (rho = 0.829, P < 0.001). Different grades of inflammation will have significant rise in LSM values within the same fibrosis stage, and LSM values were positively correlated with liver inflammation grade and fibrosis stage, and the rho is 0.579 and 0.593 respectively (P < 0.001). Significant differences in the LSM of FibroScan were observed among different grades of liver inflammation (P < 0.0001). Liver biopsy (PA > 10) served as the control, and the cutoff point and the area under ROC curves (AUCs) of the LSMs for different inflammation grades were as follows: G2, 8.6 kPa, 0.775; G3 9.8 kPa, 0.818; and G4, 11.0 kPa; 0.832. With LSM cutoff values of 8.6 kPa, 9.8 kPa and 11.0 kPa, FibroScan showed certain diagnostic value for CHB patients with G2, G3 and G4 liver inflammation, especially those with G4 inflammation. CONCLUSIONS: The grade of liver inflammation was positively correlated with the stage of fibrosis, different grades of inflammation will have significant rise in LSM values within the same fibrosis stage. In addition to liver fibrosis, FibroScan could evaluate liver inflammation in CHB patients in a noninvasive manner.

Phenomic Analysis of Chronic Granulomatous Disease Reveals More Severe Integumentary Infections in X-Linked Compared With Autosomal Recessive Chronic Granulomatous Disease.

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms. Methods: We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients. Results: XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis, and Mycobacteirum tuberculosis were the most frequent pathogens to be found. Conclusion: Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.

Invasive Mole Resulting in Uterine Rupture: A Case Report.

Uterine surgery is a common predisposing factor for uterine rupture, while an invasive mole that leads to uterine rupture is a rare clinical occurrence. Here, we report a case of a 31-year-old childless woman who underwent abortion after 53 days of pregnancy. She still experienced abdominal pain and scanty vaginal bleeding after the abortion. Her levels of human chorionic gonadotropin (HCG) were high, while ultrasound and MRI results revealed an enlarged uterus and a mass in the myometrium. During preparation for treatment, the gynecologist ruptured the uterus of the patient, leaving her shocked. Eventually the patient's uterus was removed the uterus and pathologically diagnosed as result is the an invasive mole.

Circular RNA circNRIP1 Sponges microRNA-138-5p to Maintain Hypoxia-Induced Resistance to 5-Fluorouracil Through HIF-1α-Dependent Glucose Metabolism in Gastric Carcinoma.

BACKGROUND: Hypoxia-induced chemoresistance is recognized as a major obstacle to the successful treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been proposed to implicate in resistance to chemotherapeutic drugs. However, whether circNRIP1 is involved in the development of hypoxia-induced 5-fluorouracil (5-FU) resistance remains largely unknown. METHODS: Gene expression was evaluated using quantitative real-time polymerase chain reaction and Western blot. The impact of circNRIP1 on hypoxia-induced resistance to 5-FU was investigated by determining glucose consumption, lactate production and glucose-6-phosphate (G6P) levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide assay was performed to assess cell survival. RESULTS: circNRIP1 was upregulated in GC cells. Hypoxia induced the upregulation of circNRIP1 and reduced the sensitivity of GC cells to 5-FU, as evidenced by the increase in multidrug resistance 1 gene, P-glycoprotein, hypoxia-inducible factor-1α (HIF-1α) and G6P levels, glucose consumption, lactate production, as well as cell survival. Silencing of circNRIP1 enhanced the sensitivity of GC cells to 5-FU under a hypoxic condition. microRNA (miR)-138-5p was confirmed as a downstream target gene of circNRIP1, and upregulation of miR-138-5p could reverse the effect of circNRIP1 on hypoxia-induced 5-FU resistance. Additionally, HIF-1α was a target gene of miR-138-5p. More significantly, the effect of circNRIP1 on hypoxia-induced 5-FU resistance was markedly blocked by 2-DG treatment. CONCLUSION: circNRIP1 functioned as a miR-138-5p sponge to enhance hypoxia-induced resistance to 5-FU through modulation of HIF-1α-dependent glycolysis, which provides a novel potential approach to overcome hypoxia-induced 5-FU resistance in GC.

Definition of a novel vascular invasion-associated multi-gene signature for predicting survival in patients with hepatocellular carcinoma.

The aim of the present study was to identify a vascular invasion-associated gene signature for predicting prognosis in patients with hepatocellular carcinoma (HCC). Using RNA-sequencing data of 292 HCC samples from The Cancer Genome Atlas (TCGA), the present study screened differentially expressed genes (DEGs) between patients with and without vascular invasion. Feature genes were selected from the DEGs by support vector machine (SVM)-based recursive feature elimination (RFE-SVM) algorithm to build a classifier. A multi-gene signature was selected by L1 penalized (LASSO) Cox proportional hazards (PH) regression model from the feature genes selected by the RFE-SVM to develop a prognostic scoring model. TCGA set was defined as the training set and was divided by the gene signature into a high-risk group and a low-risk group. Involvement of the DEGs between the two risk groups in pathways was also investigated. The presence and absence of vascular invasion between patients of training set was 175 DEGs. A classification model of 42 genes performed well in differentiating patients with and without vascular invasion on the training set and the validation set. A 14-gene prognostic model was built that could divide the training set or the validation set into two risk groups with significantly different survival outcomes. A total of 762 DEGs in the two risk groups of the training set were revealed to be significantly associated with a number of signaling pathways. The present study provided a 42-gene classifier for predicting vascular invasion, and identified a vascular invasion-associated 14-gene signature for predicting prognosis in patients with HCC. Several genes and pathways in HCC development are characterized and may be potential therapeutic targets for this type of cancer.

Bioinformatics Analysis of Key Genes and Pathways of Cervical Cancer.

BACKGROUND AND OBJECTIVE: Globally, cervical cancer (CC) is the fourth most common cancer affecting women. Although effective screening reduces its incidence, it remains one of the most serious cancers threatening the health of women. Therefore, the purpose of this study is to find new genes that can be used as potential biomarkers for the prognosis of CC. METHODS AND RESULTS: After downloading three datasets such as GSE6791, GSE63678, and GSE63514 from the Gene Expression Omnibus (GEO), we combined the expression matrixes and analyzed them to obtain the differential expressed genes (DEGs). Next, using the STRING website, we performed the protein interaction network analysis. Subsequently, hub genes were screened using the R and Cytoscape software. Then, the expression difference and survival analyses of the hub genes were confirmed using GIPIA. Here, we established that the KNTC1 gene was correlated to the overall survival prognosis of CC. Besides, the expression of the KNTC1 gene in the GSE63514 dataset was significantly different from that of the normal cervix, cervical pre-cancerous lesions, and CC. Consequently, immunohistochemistry analysis showed that the results have a definite diagnostic value. CONCLUSION: The KNTC1 gene could be linked with the pathophysiology of CC and maybe one of the early diagnostic markers for the diagnosis of cervical pre-cancerous lesions.

17ß-Estradiol Promotes Angiogenesis of Rat Cardiac Microvascular Endothelial Cells In Vitro.

BACKGROUND The formation of new blood vessels, known as angiogenesis, is critical for recovery from ischemic heart disease, and estrogen is considered an important factor in this process. Here, we investigated the effects of 17ß-estradiol (17ß-E2) on proliferation and migration of cardiac microvascular endothelial cells (CMECs) in vitro. MATERIAL AND METHODS Rat CMECs were isolated and cultured with 17ß-E2 (0.001-1 µmol/l) in the absence or presence of the estrogen antagonist tamoxifen. Then, the expression level of estrogen receptor alpha was evaluated by using immunofluorescence assay, RT-PCR, and Western blot. Cell proliferation was detected by methyl thiazolyl tetrazolium analysis and the cell migration was verified by a scraping assay and quantified by a Transwell chamber assay. CMEC differentiation was examined using a tube formation assay. Vascular endothelial growth factor (VEGF) secretion was detected by enzyme-linked immunosorbent assay. RESULTS CMECs exhibited homogenous, polygonal, exhibited contact inhibition, and had characteristically ovoid nuclei with 1 or 2 nucleoli, and the cytoplasm exhibited red fluorescence after staining for von Willebrand factor. 17ß-E2 treatment upregulated estrogen receptor alpha expression in CMECs. 17ß-E2 treatment significantly promoted the proliferation, migration, tubular structure formation, and VEGF secretion in CMECs. The maximal proliferation occurred in the presence of 0.01 µmol/l 17ß-E2. Furthermore, estrogen and VEGF were found to synergistically stimulate angiogenesis. CONCLUSIONS Our data show that 17ß-E2 promotes angiogenesis in vitro and suggests that estrogen treatment as a novel therapeutic modality in the management of arterial insufficiency.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.

FgSKN7 and FgATF1 have overlapping functions in ascosporogenesis, pathogenesis and stress responses in Fusarium graminearum.

Fusarium head blight caused by Fusarium graminearum is one of the most destructive diseases of wheat and barley. Deoxynivalenol (DON) produced by the pathogen is an important mycotoxins and virulence factor. Because oxidative burst is a common defense response and reactive oxygen species (ROS) induces DON production, in this study, we characterized functional relationships of three stress-related transcription factor genes FgAP1, FgATF1 and FgSKN7. Although all of them played a role in tolerance to oxidative stress, deletion of FgAP1 or FgATF1 had no significant effect on DON production. In contrast, Fgskn7 mutants were reduced in DON production and defective in H2 O2 -induced TRI gene expression. The Fgap1 mutant had no detectable phenotype other than increased sensitivity to H2 O2 and Fgap1 Fgatf1 and Fgap1 Fgskn7 mutants lacked additional or more severe phenotypes than the single mutants. The Fgatf1, but not Fgskn7, mutant was significantly reduced in virulence and delayed in ascospore release. The Fgskn7 Fgatf1 double mutant had more severe defects in growth, conidiation and virulence than the Fgatf1 or Fgskn7 mutant. Instead of producing four-celled ascospores, it formed eight small, single-celled ascospores in each ascus. Therefore, FgSKN7 and FgATF1 must have overlapping functions in intracellular ROS signalling for growth, development and pathogenesis in F. graminearum.

[A cohort study on the relationship between cerebrovascular hemodynamic changing and risk of stroke].

OBJECTIVE: To study the role of cerebrovascular hemodynamic indexes (CVHI) changing in stroke and to provide reference for stroke prevention and risk factor study. METHODS: From 2003 to 2004, participants aged 40 years and above in two communities in Fengxian district were recruited by cluster sampling. Risk factors of stroke and CVHI were investigated and checked during baseline investigation. A total of 10 565 individuals completed the survey and met the inclusion criterion. After baseline investigation, the cohort was followed up for stroke occurrence. Relative risk (RR) of CVHI and common risk factors were estimated by cohort study design. RESULTS: Age of the cohort was (56.2 ± 11.4) years. 4444 (42.1%) were males and 6121 (57.9%) were females. Total follow-up duration was 67 885.7 person-years. A total of 195 stroke cases occurred and incidence density of stroke was 287.2 per 100 000 person-years. Stroke incidence in exposure groups of hypertension, heart disease and alcohol drinking was 3.47% (108/3118), 2.96% (21/710) and 2.50% (47/1882), respectively. The incidence in corresponding non-exposure group was 1.17% (87/7448), 1.77% (174/9855) and 1.70% (148/8683) respectively. There was significant difference between 2 groups (χ(2) value was 62.72, 4.56 and 4.94, respectively, P < 0.05). Stroke incidence in CVHI score < 25, 25 - 49, 50 - 74 and ≥ 75 groups was 9.12% (59/647), 5.68% (44/775), 2.52% (39/1545) and 0.72% (53/7403)(χ(2)trend = 273.57, P < 0.05), respectively. Incidence of stroke in 40 - 49, 50 - 59, 60 - 69, ≥ 70 years age group was 0.22% (8/3565), 1.28% (43/3357), 2.71% (50/1848) and 5.88% (94/1600) (χ(2)trend = 181.48, P < 0.05), respectively. Multiple Cox regression analysis indicated that RR (95%CI) value of hypertension and cigarette smoking was 1.40(1.02 - 1.92) and 1.59(1.19 - 2.12), respectively when comparing with non-exposure group. RR (95%CI) value in CVHI score < 25, 25 - 49 and 50 - 74 points group were 6.15 (4.08 - 9.26), 4.55 (2.98 - 6.96) and 2.68 (1.75 - 4.09), respectively when comparing with the score ≥ 75 points group. RR (95%CI) value in age 50 - 59, 60 - 69 and ≥ 70 years group was 4.61 (2.16 - 9.82), 7.81 (3.67 - 16.60) and 13.49(6.44 - 28.24), respectively when comparing with below 40 years group. CONCLUSION: CVHI score is the strong independent predictive factor and hypertension, cigarette smoking and age are the independent risk factors of stroke.

[Comparison of bone marrow biopsy and smear efficacy in patients with multiple myeloma].

This study was aimed to explore the significance of the bone marrow biopsy for the diagnosis of multiple myeloma. Bone marrow smears and bone marrow biopsy originated from 279 cases of multiple myeloma were detected and compared in term of bone marrow hyperplasia, bone marrow plasma cell infiltration, proliferation mode, pathological changes in the bone marrow stroma and myelofibrosis. The results indicated that the levels of proliferation in bone marrow biopsy was significantly higher than that in bone marrow smears. Plasma cell proliferation mode in bone marrow biopsy was not completely consistent with the proportion of plasma cells in bone marrow smears. The myelofibrosis level displayed influence on the consistency of the proliferation between bone marrow smears and biopsies. It is concluded that as compared with bone marrow smears the bone marrow biopsy can more accurately reflect the levels of bone marrow hyperplasia and bone marrow plasma cell infiltration, proliferation mode and so on. Bone marrow biopsy is valuable for multiple myeloma diagnosis.

Effective treatment of advanced cholangiocarcinoma by hepatic arterial infusion chemotherapy combination with sorafenib: one case report from China.

BACKGROUND/AIMS: Cholangiocarcinoma, especially intrahepatic type, is difficult to be found early and diagnosed at early stages. Although it was reported as rare to happen, it is a well-known devastating malignancy with little treatment effects. As a result, most of the patients suffer from poor prognosis. On the other hand, the incidence of intrahepatic cholangiocarcinoma arises worldwide. Radical surgical resection was regarded as the most effective treatment, in spite of recurrence. Unfortunately, only 30 percent of patients qualify for this at the time of diagnosis. Hence, for advanced cholangiocarcinoma, chemotherapy is the only modality left to be chosen. Recently LaRocca and Kudoh reported about effective chemotherapy for cholangiocarcinoma. Even so, because of no randomized study, no standard chemotherapy for cholangiocarcinoma has been accepted, and most of the projects were based on 5-Fu. Sorafenib, a multikinase inhibitor, which can competitively inhibit RAF/MEK/ERK pathway, human vascular endothelial growth factor receptors (VEGFR2, VEGFR3) platelet-derived growth factor receptor beta (PDGFR), Flt3, and C-kit receptors, has been successfully applied for solid tumors such as renal cancer and hepatocellular carcinoma. Sorafenib used alone or in combinations, can induce growth-inhibition and apoptosis in vitro experiments. Application of sorafenib alone for cholangiocarcinoma has also been published. The role of combination with other chemotherapy drugs in advanced cholangiocarcinoma still needs to be defined. METHODOLOGY: A patient admitted for exploratory operation was demonstrated to be suffering from unresectable, biopsy-proven intrahepatic cholangiocarcinoma. A pump was placed inside hepatic artery, for the purpose of infusion chemotherapy. Program of chemotherapy was scheduled and hepatic arterial infusion of 5-Fu/LV +oxaliplatin +hydroxycamptothecine was performed. Three months later, no effect was discovered, so sorafenib was suggested to combine with infusion chemotherapy. For the first time we applied sorafenib combination to hepatic arterial infusion chemotherapy RESULT: After lower dosage of sorafenib was used as a combination with hepatic arterial infusion chemotherapy, size of hepatic lesions and level CA19-9 of peripheral blood count were decreased, without any damage to the hepatic function, except for temporary skin hyperkeratosis as well as vomit. Efficacy of treatment was demonstrated by computed tomography (CT) scan. CONCLUSION: So far as in our patient, the application of sorafenib combination with other agents through hepatic arterial infusion chemotherapy may be an effective way for cholangiocarcinoma, but the definite mechanism has to be confirmed by methods of molecular biology.