[Prevention and treatment of stroke in Chinese and African young adults].

Over the past two decades, with the improvement of living standards and the change of lifestyle, the incidence of stroke in young adults had been increasing year by year. Compared with elderly patients, young patients had a higher proportion of intracranial and subarachnoid hemorrhage. The etiologies of ischemic stroke in young patients were more diverse, with increasing risk factors such as hypertension, diabetes, smoking, alcoholism, and oral contraceptives. Due to the atypical clinical symptoms, various etiologies, the clinical inertia of the receiving physicians and the concerns about the use of statins in young stroke patients, timely diagnosis and standardized treatment are still challenging. China has been providing medical assistance to African countries for nearly 60 years. Considering the regional differences in medical level between China and Africa, in order to help Chinese medical teams to have a deep understanding of the current situation of stroke in young African adults, this paper comprehensively analyzed the epidemiology, etiology, risk factors and prevention measures of stroke in young adults, especially in Chinese and African, which could provide corresponding reference for early identification, treatment, prevention and education of stroke in young people.

[Diagnostic efficacy of metagenomic next-generation sequencing for intracranial bacterial infection pathogens after neurosurgery].

Objective: To explore the diagnostic efficacy of metagenomicnext-generation sequencing (mNGS) technique for pathogen diagnosis of intracranial infection after neurosurgery. Methods: Patients with suspected intracranial infection after neurosurgery who were treated in Beijing Tiantan Hospital of Capital Medical University from May 2017 to October 2018 were selected. Cerebrospinal fluid samples were collected for mNGS detection and bacterial culture. The sensitivity, specificity, positive predictive value and negative predictive value of these two methods were calculated, and their differences were compared. Results: A total of 80 cerebrospinal fluid samples from patient with suspected intracranial infection after neurosurgery were included, including 53 males and 27 females, with a mean age of (41±19) years old(age range: 2-80 years).After clinical review, a clinical diagnosis was made by two neurosurgery specialists through comprehensively interpretation of the patient's clinical data, laboratory tests and imaging examinations. Finally, 42 cases of intracranial infection and 38 cases of non-infection were clinically diagnosed. The sensitivity and specificity of mNGS detection were 83.33%(35/42) and 76.32%(29/38), and the positive predictive value and negative predictive value were 79.55%(35/44) and 80.56%(29/36). Meanwhile, the sensitivity and specificity of bacterial culture were 59.52%(28/42) and 68.42%(26/38), the positive predictive value and negative predictive value were 68.00% (28/40) and 60.47%(26/40). The sensitivity of mNGS detection washigher than that of bacterial culture, and the difference was statistically significant(χ2=5.83, P=0.015).Compared with bacterial culture, there was no statistically significant difference in the specificity of mNGS detection(χ2=0.59, P=0.441). Conclusion: mNGS detection technique can improve the detection rate of intracranial infection pathogens after neurosurgery, and may become a promising auxiliary diagnostic tool for pathogen detection.

[Effects of statins on mortality and neurologic outcomes in patients with traumatic brain injury: a meta-analysis].

Objective: To systematically evaluate the effects of statins on the mortality and neurologic function prognosis in patients with traumatic brain injury (TBI). Methods: The PubMed, Embase, the Cochrane Library, the Cochrane Clinical Controlled Trial Center Registry Database, Chinese Journal Full-text Database (CNKI), and WanFang database up to 2021.1 were searched to obtain clinical randomized controlled trials (RCTs) and retrospective cohort studies of statins in the treatment of TBI. Inclusion and exclusion criteria were used to screen literature and extract data. Ottawa scale and the RCT bias risk assessment tool was used for quality evaluation. Comprehensive Meta Analysis V3 statistical software for meta-analysis was applied. Results: Thirteen studies were included, with a total of 116, 500 patients, including 46, 933 patients using statins in the intervention group and 69, 567 patients in the control group. Meta-analysis results showed that compared with the control group, statins can reduce the mortality of TBI patients (OR=0.82, 95%CI: 0.74-0.92, P<0.01), significantly improve the neurologic outcomes of TBI patients (OR=0.19, 95%CI: 0.13-0.26, P<0.01), and reduce the levels of TNF-α and IL-1ß after TBI (TNF-α: OR=0.16, 95%CI: 0.07-0.34, P<0.01; IL-1ß: OR=0.08, 95%CI: 0.04-0.18, P<0.01), with statistically significant differences. Conclusion: Statins can reduce the mortality of patients with TBI and improve the neurologic outcomes. Their reduction of inflammation in the body may be the basis of potential treatment, but more high-quality RCTs are still warranted.

Novel REST Truncation Mutations Causing Hereditary Gingival Fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare genetic disorder featured by nonsyndromic pathological overgrowth of gingiva. The excessive gingival tissues can cause dental, masticatory, and phonetic problems, which impose severe functional and esthetic burdens on affected individuals. Due to its high recurrent rate, patients with HGF have to undergo repeated surgical procedures of gingival resection, from childhood to adulthood, which significantly compromises their quality of life. Unraveling the genetic etiology and molecular pathogenesis of HGF not only gains insight into gingival physiology and homeostasis but also opens avenues for developing potential therapeutic strategies for this disorder. Recently, mutations in REST (OMIM *600571), encoding a transcription repressor, were reported to cause HGF (GINGF5; OMIM #617626) in 3 Turkish families. However, the functions of REST in gingival homeostasis and pathogenesis of REST-associated HGF remain largely unknown. In this study, we characterized 2 HGF families and identified 2 novel REST mutations, c.2449C>T (p.Arg817*) and c.2771_2793dup (p.Glu932Lysfs*3). All 5 mutations reported to date are nonsenses or frameshifts in the last exon of REST and would presumably truncate the protein. In vitro reporter gene assays demonstrated a partial or complete loss of repressor activity for these truncated RESTs. When coexpressed with the full-length protein, the truncated RESTs impaired the repressive ability of wild-type REST, suggesting a dominant negative effect. Immunofluorescent studies showed nuclear localization of overexpressed wild-type and truncated RESTs in vitro, indicating preservation of the nuclear localization signal in shortened proteins. Immunohistochemistry demonstrated a comparable pattern of ubiquitous REST expression in both epithelium and lamina propria of normal and HGF gingival tissues despite a reduced reactivity in HGF gingiva. Results of this study confirm the pathogenicity of REST truncation mutations occurring in the last exon causing HGF and suggest the pathosis is caused by an antimorphic (dominant negative) disease mechanism.

[Chromosomal aberrations detection in chronic lymphocytic leukemia by conventional cytogenetics using DSP30 and IL-2].

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion: DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Four-dimensional micro-building blocks.

Four-dimensional (4D) printing relies on multimaterial printing, reinforcement patterns, or micro/nanofibrous additives as programmable tools to achieve desired shape reconfigurations. However, existing programming approaches still follow the so-called origami design principle to generate reconfigurable structures by self-folding stacked 2D materials, particularly at small scales. Here, we propose a programmable modular design that directly constructs 3D reconfigurable microstructures capable of sophisticated 3D-to-3D shape transformations by assembling 4D micro-building blocks. 4D direct laser writing is used to print two-photon polymerizable, stimuli-responsive hydrogels to construct building blocks at micrometer scales. Denavit-Hartenberg (DH) parameters, used to define robotic arm kinematics, are introduced as guidelines for how to assemble the micro-building blocks and plan the 3D motion of assembled chain blocks. Last, a 3D-printed microscaled transformer capable of changing its shape from a race car to a humanoid robot is devised and fabricated using the DH parameters to guide the motion of various assembled compartments.

[Propensity-matched comparison of laparoscopic and open radical cystectomy for female patients with bladder cancer].

OBJECTIVE: To compare the perioperative and oncologic outcomes of female patients receiving laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC). METHODS: Retrospective review of 91 consecutive female patients with urothelial carcinoma of bladder undergoing radical cystectomy at a single academic institution from 2006 to 2017. Those female patients received open radical cystectomy were matched to the patients who underwent laparoscopic radical cystectomy by using propensity score matching in 1 ∶1 ratio. The matching factors included age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, pathologic stage and pathologic nodal stage. The perioperation and oncology characteristics were compared, and Kaplan-Meier method was used to analyze the overall survival (OS), cancer specific survival (CSS) and progression-free survival (PFS) estimates. Finally, we did a sensitive analysis by using multivariable COX regression of all the patients, adjusting for the matching factors. RESULTS: There were 65 ORC and 26 LRC patients identified in this cohort with urothelial carcinoma of bladder, the median follow-up time was 38 months (interquartile range 18-69). The age (P<0.001) and ASA scores (P=0.018) were less for LRC before being matched. There were 22 LRC and 22 ORC patients matching successfully. Before being matched, the estimate blood loss (P=0.005), transfusion rate (P<0.001) and total complications rate (P=0.015) were less for LRC, and the lymph nodes yield was greater for LRC, but there were no differences in OS (P=0.698), CSS (P=0.942) and PFS (P=0.837) between the two groups. After being matched, the estimate blood loss (P=0.009), transfusion rate (P=0.001) and total complications rate (P=0.040) were less for LRC, but there was no difference in the lymph nodes yield. Besides, there were no statistic differences in OS (P=0.432), CSS (P=0.429) and PFS (P=0.284) between the two groups. In addition, in multivariable COX regression analysis, surgical approaches (LRC/ORC) were not found to be a predictor of OS (HR 1.134, 95%CI 0.335-3.835, P=0.839), CSS (HR 1.051, 95%CI 0.234-4.719, P=0.949) and PFS (HR 0.538, 95%CI 0.138-2.095, P=0.371) of the female patients with urothelial carcinoma of bladder. CONCLUSION: It is advantageous for laparoscopic radical cystectomy in terms of estimating blood loss, transfusion rate and complication rate. But there was no evidence that laparoscopic radical cystectomy for female patients with bladder cancer had a better oncologic prognosis than open radical cystectomy from this study.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

[Clinical characteristics of the Wilson disease carrier].

Objective: To study the clinical symptoms, copper metabolism and imaging characteristics of Wilson disease (WD) carriers and to explore the treatment strategy of WD carriers. Methods: Forty WD carriers, 40 WD patients and 20 normal controls from the First Affiliated Hospital of Sun Yat-sen University from July 2007 to May 2018 were included. The modified Young scale was used for neural symptom scoring, and Child grading of liver function, mental symptoms rating scale, magnetic resonance imaging (MRI) scan, susceptibility weighted imaging (SWI) inspection, metal metabolism tests were also applied to all the included subjects. Corrected phase (CP) was measured by SWI. WD carriers were divided into symptomatic group and asymptomatic group. Symptomatic WD carriers were treated with penicillamine for 2 weeks and zinc gluconate for 3 months, then their neurological symptoms, liver function grade, metal metabolism index were rechecked. Results: Six WD carriers presented with some clinical symptoms, including 5 with neurological symptoms and 4 with liver dysfunction. The score of Hamilton anxiety (HAMA) scale of symptomatic WD carriers was higher than that of normal control group (P=0.021). 85% of carriers had ceruloplasmin level less than 0.26 g/L. 80% of carriers had serum copper between normal controls and WD patients. The free copper level of WD carriers was lower than that of WD patients (P=0.012, 0.019). Urinary copper in symptomatic WD carriers was higher than normal controls (P=0.047). The CP values of thalamus, globus pallidus and putamen in symptomatic WD carriers were lower than those in normal control group. After treatment with penicillamine in symptomatic WD carriers, urinary copper was higher than that before treatment (P=0.036). After treatment, the liver enzymes of symptomatic WD carriers returned to normal, and the score of modified Young scale was lower than before treatment (P=0.031). Conclusions: Mild copper metabolism abnormality is seen in WD carriers. A few carriers have neurological symptoms such as limb tremors, or liver symptoms such as abnormal liver enzymes. Abnormal copper metabolism is more serious in symptomatic WD carriers than in asymptomatic WD carriers. Symptomatic WD carriers can be treated with zinc gluconate.

Adaptive locomotion of artificial microswimmers.

Bacteria can exploit mechanics to display remarkable plasticity in response to locally changing physical and chemical conditions. Compliant structures play a notable role in their taxis behavior, specifically for navigation inside complex and structured environments. Bioinspired mechanisms with rationally designed architectures capable of large, nonlinear deformation present opportunities for introducing autonomy into engineered small-scale devices. This work analyzes the effect of hydrodynamic forces and rheology of local surroundings on swimming at low Reynolds number, identifies the challenges and benefits of using elastohydrodynamic coupling in locomotion, and further develops a suite of machinery for building untethered microrobots with self-regulated mobility. We demonstrate that coupling the structural and magnetic properties of artificial microswimmers with the dynamic properties of the fluid leads to adaptive locomotion in the absence of on-board sensors.

Influence of MiR-154 on myocardial apoptosis in rats with acute myocardial infarction through Wnt/ß-catenin signaling pathway.

OBJECTIVE: To explore the influence of micro ribonucleic acid (miR)-154 on myocardial apoptosis in rats with acute myocardial infarction (AMI), and to analyze whether Wnt/ß-catenin signaling pathway was involved in the regulation. MATERIALS AND METHODS: The Sprague-Dawley (SD) rat model of AMI was established via ligation of left anterior descending artery. Rats were randomly divided into model group (M group, n=12) and ICG-001 intervention group (I group, n=12). At the same time, sham operation group (S group, n=12) was established. In I group, ICG-001 (5 mg/kg) was intraperitoneally injected every day after operation. Meanwhile, an equal amount of normal saline was injected in rats of S group and M group. 21 d after operation, the cardiac function of rats in each group was detected via echocardiography. After that, the rats were immediately executed. MI area in each group was detected via 2,3,5-triphenyltetrazolium chloride (TTC) staining. Myocardial apoptosis level in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the changes of apoptotic proteins in rat myocardial cells were detected via Western blotting. Moreover, the expression level of miR-154 in myocardial cells of rats was detected via quantitative polymerase chain reaction (qPCR). Furthermore, the influence of miR-154 on Wnt/ß-catenin signaling pathway was detected via Western blotting. RESULTS: Compared with S group, left ventricular ejection fraction (LVEF, %) and left ventricular fractional shortening (LVFS, %) were significantly decreased in M group (p<0.01). However, left ventricular internal diameter at end-diastole (LVIDd) and left ventricular internal diameter at end-systole (LVIDs) were significantly increased (p<0.01). In I group, LVEF (%) and LVFS (%) were significantly higher than those of M group (p<0.05), whereas LVIDs and LVIDd were significantly lower (p<0.05). MI area in M group was remarkably larger than that of S group (p<0.01). Meanwhile, MI area in I group was significantly smaller than that of M group (p<0.01). Compared with S group, the number of apoptotic myocardial cells and the protein expression level of cleaved caspase-3 were significantly increased in M group (p<0.01). However, the expression level of B-cell lymphoma-2/Bcl-2 associated X protein (Bcl-2/Bax) was significantly decreased (p<0.01). The number of apoptotic myocardial cells and the protein expression level of cleaved caspase-3 were significantly declined in I group when compared with those of M group (p<0.01). However, the expression level of Bcl-2/Bax was significantly increased in I group (p<0.01). The expression level of miR-154 in myocardial cells of M group and I group was remarkably increased when compared with that of S group (p<0.01). Furthermore, the expression levels of ß-catenin and Cyclin D1 in myocardial cells of M group were remarkably higher than those of S group and I group (p<0.01). CONCLUSIONS: AMI significantly increases the expression level of miR-154. Moreover, miR-154 can activate Wnt/ß-catenin signaling pathway, eventually promoting myocardial apoptosis.

Application of Nonlinear Optical Microscopic Imaging Technology for Quality Assessment of Donor Kidneys.

BACKGROUND: Nonlinear optical microscopic (NLOM) imaging technique shows its high resolution imaging features in histocytology. The purpose of this study was to investigate NLOM imaging technique as a useful tool for a donor kidney quality assessment. MATERIALS AND METHODS: Eighty-three pretransplant kidney biopsies from adult donors were analyzed retrospectively. Each specimen was paraffin-embedded and sectioned into 2 consecutive 5-µm thick sections. One section was stained with Masson trichrome, and the other was left unstained for NLOM imaging using second harmonic generation combined with two-photon excited fluorescence (SHG/TPEF). The pretransplant kidney quality was assessed by an experienced pathologist using the Remuzzi scoring system, which characterizes renal tissue morphology into 4 aspects: tubular atrophy, interstitial fibrosis, glomerulosclerosis, and vascular injury. The K coefficient was used to measure the consistency of the Remuzzi scores between conventional Masson trichrome stained images and SHG/TPEF images. RESULTS: NLOM imaging technology can capture high-resolution tissue images from unstained renal tissue, is easy to operate, and shortens time-consuming histological processing procedures. No significant differences (P > .05) were found between the Remuzzi scores of the SHG/TPEF images and the Masson trichrome stained images. The high κ coefficients (0.804-0.895) showed a good consistency between these 2 techniques. CONCLUSION: The NLOM technique is suitable for renal tissue imaging and could potentially be used for routine pretransplant kidney evaluation in clinical settings.

[An experimental study of CD4 targeted chimeric antigen receptor modified T cell with anti-lymphoma activity].

Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay. Results: ①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8+ T cell acquired dim expression of CD4 membrane protein after activation. CD4+T cell and CD8+CD4dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01). Conclusions: CD4 targeted CAR-T has an immunophenotype of CD8+CD4-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4+T cell and CD4+T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4dim target cell.

Clinicopathological features and course of cutaneous protothecosis.

BACKGROUND: Protothecosis is an uncommon infection caused by the achlorophyllic algae found more commonly in tropical areas. Only a limited number of cases have been reported. OBJECTIVE: We aimed to evaluate the clinicopathological features and treatment outcomes of cutaneous protothecosis. METHODS: We retrospectively identified 20 pathology-confirmed cases of cutaneous protothecosis based on skin biopsies in two tertiary medical centres in Taiwan from 1997 to 2015. RESULTS: The age of the patients at the time of diagnosis ranged from 48 to 85 years (mean age of 74 years). All lesions developed on the limbs. Twelve (60%) patients had adrenal insufficiency, but no patients had active malignancy at diagnosis. Interestingly, four (20%) patients had concurrent scabies infestation. Clinically, most lesions were erythematous plaques studded with punctate ulcers. Microscopically, the most common finding was granulomatous inflammation. Nineteen (95%) cases were successfully treated with itraconazole for 14-148 days with only one case of recurrence. Concomitant scabies should be suspected if pruritus is recalcitrant despite itraconazole treatment. CONCLUSION: Despite its rarity, cutaneous protothecosis has become more significant due to an increased prevalence of immunocompromised individuals. Steroid overuse or iatrogenic adrenal insufficiency predisposes individuals to high-risk infections. Neglecting the disease leads to a chronic and incurable state. Protothecosis should be suspected in chronic eczematous and ulcerative plaques on the limbs refractory to conventional antibacterial and antiviral treatments, especially in patients with adrenal insufficiency. Clinical suspicion should be confirmed by skin biopsies, and confirmed cases can be successfully treated with itraconazole.

Upregulation of LncRNA PANDAR predicts poor prognosis and promotes cell proliferation in cervical cancer.

OBJECTIVE: To investigate the expression level of long non-coding RNA promoter of CDKN1A antisense DNA damage activated RNA (lncRNA PANDAR) in cervical cancer and to analyze the effects of PANDAR on biological behaviors of cervical cancer and the clinical significance of PANDAR. PATIENTS AND METHODS: A total of 68 pairs of cervical cancer and paired cancer-adjacent tissue specimens were collected. The relative expression of PANDAR in tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) so as to analyze the relationship between PANDAR and clinicopathological factors of cervical cancer and evaluate its clinical significance. qRT-PCR was used to detect the relative expression of PANDAR in cervical cancer cells. Interference in PANDAR was conducted. Cell counting kit-8 (CCK-8) assay was used to detect the changes in cell proliferation capacity. RESULTS: The results of qRT-PCR showed that the expression level of PANDAR was significantly up-regulated in cervical cancer tissues compared with that in cancer-adjacent tissues. Statistical analysis showed that PANDAR expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) staging, tumor size and tumor invasion degree. Kaplan-Meier survival analysis showed that the survival time of patients with highly expressed PANDAR was shorter than that of patients with lowly expressed PANDAR. Cox multivariate regression analysis showed that PANDAR could be used as an independent prognostic factor for patients with cervical cancer. CCK-8 results showed that interference in PANDAR significantly inhibited tumor cell proliferation. CONCLUSIONS: The expression level of PANDAR is up-regulated in cervical cancer tissues and cells, and PANDAR promotes tumor growth. PANDAR may be a biomarker for the early diagnosis of cervical cancer and a potential therapeutic target for reversing the malignant phenotype of tumors.

Reactive oxygen species downregulate ARID1A expression via its promoter methylation during the pathogenesis of endometriosis.

OBJECTIVE: Oxidative stress caused by reactive oxygen species (ROS) plays an important role in the pathogenesis of endometriosis. The gene AT-rich interactive domain 1A (ARID1A), is frequently down regulated and inactivated in endometriosis. This report is focused on the molecular mechanism of the correlation between oxidative stress and ARID1A gene expression in endometrial cell oxidative damage model. PATIENTS AND METHODS: In this study, the ARID1A gene expression level and its promoter methylation level were detected in 30 endometriosis and normal tissues. The primary endometrial cell was co-cultured with H2O2. Then, MDA and Gpx level were used to test the ROS level, RT-PCR was employed to detect the expression level of ARID1A. At last, the ARID1A gene promoter methylation level was detected by methylation-specific PCR (MSP). Finally, the expression level of DNMT1 was detected by both RT-PCR and Western blot. RESULTS: The expression level of ARID1A gene was down regulated in endometriosis compared with normal tissues. The low expression level of ARID1A gene was associated with its promoter hyper-methylation. In H2O2 simulated endometrial cells, ARID1A gene expression level was decreased. Finally, ROS regulated ARID1A gene expression by changing the methylation level of ARID1A gene promoter. Finally, both the mRNA level and protein level of DNMT1 increased in H2O2 simulated endometrial cells. CONCLUSIONS: In endometriosis, the down-regulated ofARID1A gene was highly correlated with its promoter hyper-methylation. ROS decreased the expression level of ARID1A gene via regulating methylation of its promoter which contributing to the understanding of the pathogenesis of endometriosis. The possible mechanism of ARID1A gene promoter hyper-methylation is ROS up-regulated DNMT1gene expression.

[Difference in imaging and metal metabolism between hepatic and cerebral type Wilson disease].

Objective: To evaluate the difference of metal metabolism, damage to structure and functional activity in brains between hepatic and cerebral type Wilson disease (WD). Methods: Forty patients with WD, including 20 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls in the First Affiliated Hospital, Sun Yat-sen University between Jul 2013 and May 2016 were enrolled.All study subjects underwent diffusion tensor imaging (DTI), resting state functional MRI (rs-fMRI) and susceptibility weighted imaging (SWI) of the brain.Six regions of interest (ROIs) were chosen.The values of fractional anisotropy (FA), λ in ROIs were determined on DTI, FA and fiber volumes between ROIs were also determined on DTI.The values of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (REHO) in ROIs were determined on rs-fMRI.The values of corrected phase (CP) were calculated on SWI.The copper and iron content were measured.The difference of imaging and metal metrics between cerebral type and hepatic type WD were evaluated. Results: DTI metrics differed between patients with the cerebral and hepatic types of WD.ALFF values in the caudate nucleus, and thalamus were lower (P=0.037, 0.040), and REHO values in the caudate nucleus were lower (P=0.029), in patients of cerebral type than in hepatic type patients.CP values of the right caudate nucleus and left putamen in cerebral type WD patients were lower than in hepatic type patients (P=0.020, 0.23). The serum iron content of hepatic type WD patients was higher than the normal (P=0.013), and the urine copper content was higher than the cerebral type patients (P=0.021). Conclusions: Metal deposition and damage to the structure and functional activity in the brain may occur in hepatic type WD patients.The structural and functional activity damage of the brain in hepatic type is less severe than that in cerebral type patients, while the metal deposition is not significant different between hepatic and cerebral type.

[Comparison of allogeneic or autologous hematopoietic stem cell transplant for high-risk peripheral T cell lymphomas].

Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (12-58) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 angioimmunoblastic T-cell lymphoma (AITL). Twenty-one patients (21/60) received allo-HSCT, and thirty-nine (39/60) auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients partial remission (PR) and 18/60 patients not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients auto-HSCT, respectively. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients auto-HSCT, respectively. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS by auto-HSCT and allo-HSCT were 61% and 60% (P=0.724) , respectively. The 5-year OS by auto-HSCT and allo-HSCT were 62% and 61% (P=0.724) , respectively. There were no statistically significant differences between auto-HSCT and allo-HSCT. And the cumulative TRM of auto-HSCT and allo-HSCT were 22.7% and 41.8% (P=0.250) , respectively within 5-years after transplantation. At the end of the last follow-up, 7 and 2 patients relapsed in auto-HSCT and allo-HSCT groups respectively, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively. Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. Outcome by allo-HSCT may be better for NR patients.

[Efficacy of surgery and rituximab in primary gastric diffuse large B-cell lymphoma].

OBJECTIVE: To evaluate the outcome of surgical resection and rituximab for treatment of primary gastric diffuse large B cell lymphoma (PGDLBCL). METHODS: Data of 83 patients with primary gastric diffuse large B cell lymphoma were reviewed retrospectively. 40 patients received surgical resection followed by chemotherapy, and the other 43 patients chemotherapy alone. The two groups were further divided into four sub- groups according to chemotherapy regimens (CHOP or R- CHOP). Overall survival (OS) and progression free survival (PFS) as two prognostic indexes were analyzed. RESULTS: The median age of these 83 cases at diagnosis was 52 years (range, 20-76 years) with a male-to-female ratio of 43 to 40. And the follow-up duration ranged from 4-59 months (mean 36 months). The 5-year PFS for the patients received surgery and chemotherapy was 66.7%. PFS for the patients received chemotherapy alone was 82.6%. And 5-year OS for these two groups was 68.4% and 85.9%,respectively. OS and PFS of chemotherapy alone group were better than the other one without statistically significance. In the combined group, the 5- year OS were 73.6% for patients received R- CHOP and 64.2% for patients received CHOP; the 5- year- PFS were 71.2% and 62.5%, respectively. Meanwhile, the 5- year OS for patients received R-CHOP and CHOP were 85.7% and 83.5%; the 5-year-PFS were 83.4% and 81.8%, respectively. The OS and PFS did not differ significantly (P>0.05) between two chemotherapy regimens. According to the Lugano stage, those who received chemotherapy alone for the patients with advanced stage (Ⅱ2, ⅡE or Ⅳ) had better OS compared with received surgery and chemotherapy. A significant difference was found between the two groups (P<0.05). However for the patients with early stage (Ⅰ or Ⅱ 2), there was no statistically significance between the two groups (P>0.05). Univariate analysis showed that age, ECOG, Lugano stage, level of LDH and IPI score (P<0.05) were factors of survival in patients with PGDLBCL. And multivariate analysis showed that IPI score was an independent prognostic factor for OS. CONCLUSION: The survival of the patients received combined surgery and chemotherapy was not superior to those received chemotherapy alone. There was no statistically significance between two different regimens for prognosis of PGDLBCL. Because of poor quality of life caused by surgery, surgery shouldn't now been recommended for the patients with PGDLBCL without operative indication. Rituximab had no positive influence on OS and PFS in most patients with PGDLBCL, but this result should be confirmed by further large sample and multi-center study.