Clinical and urodynamic features of secondary tethered cord syndrome: How can they be found longitudinally?

PURPOSE: Secondary tethered cord syndrome (TCS) can be diagnosed with signs of progressive deterioration in urological or neuro-orthopedic systems following primary untethering surgery. Though urological deterioration is a common secondary TCS manifestation, a paucity of diagnostic criteria makes diagnoses challenging. A detailed description of urological deterioration may help diagnose secondary TCS. Thus, the clinical and urodynamic features of the current secondary TCS cases were described. MATERIALS AND METHODS: Fifty-one patients who had undergone reuntethering for secondary TCS experienced improvement or stabilization of progressive problems. Moreover, their clinical and videourodynamic changes were longitudinally described. RESULTS: Loss of postoperative spontaneous voiding was the first urological secondary TCS sign for those who could void spontaneously. Urological problems mostly occurred during elementary school (6-12 years). Major urological presentations were recalcitrant urinary tract infection or urinary incontinence. Follow-up videourodynamic studies revealed typical changes, from acontractile bladder to overactive and low-complaint bladders. While detrusor overactivity did not always occur during the progression, detrusor sphincter dyssynergia was always present in all patients with urological deterioration. All patients postoperatively showed significant urodynamic improvement regardless of preoperative bladder dysfunction. This included four cases of restoring spontaneous voiding. Nine patients experienced newly appearing nonprogressive neuro-orthopedic complications despite their urological improvement. CONCLUSIONS: Urological deterioration should prompt secondary TCS suspicion, and changes in clinical patterns and videourodynamic studies helped diagnose it. However, reuntethering can effectively address urological problems at the cost of some neuro-orthopedic functions in some patients.

[Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In Tube in the diagnosis of pulmonary tuberculosis].

Objective: To compare the screening value of QuantiFERON-TB Gold Plus (QFT-Plus) and QuantiFERON®-TB Gold in tube (QFT-GIT) in the auxiliary diagnosis of pulmonary tuberculosis (TB). Methods: A screening test was performed. Patients who were hospitalized in Guangzhou Chest Hospital and underwent QFT-GIT testing from October to December 2020 were prospectively included as research subjects, QFT-Plus testing was added. And the basic information, clinical manifestations, laboratory test results, imaging examinations and other data of these patients were collected. A total of 207 patients were included and divided into tuberculosis group and non-tuberculosis group according to these data. There were 124 cases in the tuberculosis group (94 confirmed patients and 30 clinically diagnosed patients), including 90 males and 34 females, aged 18-93 years, with a median age of 57 (38, 67) years. The non-tuberculosis group included 83 patients (16 patients with non-tuberculous Mycobacteria and 67 patients with other lung diseases), including 49 males and 34 females, with a median age of 60 (51, 68) years. The confirmed patients were subdivided into three grades of low, medium and high Mycobacteriam tuberculosis (MTB) bacterial load, and three grades of mild, moderate and severe pulmonary tuberculosis. The results of QFT-Plus and QFT-GIT were compared, and the levels of IFN-γ in different antigen tubes were compared. Differences between different groups were compared using Mann-Whitney U test and Kruskal-Wallis H test. Results: The QFT-Plus showed a high degree of agreement with the QFT-GIT (κ=0.786, 95%CI: 0.740-0.832), while the main discordant result was QFT-GIT negative/QFT-Plus positive, accounting for 15/17. The sensitivity of QFT-GIT was 80.7%(95%CI: 0.706-0.880), the specificity was 76.3%(95%CI: 0.649-0.850), the positive predictive value was 79.8%(95%CI: 0.697-0.873), and the negative predictive value was 77.3%(95%CI: 0.659-0.859), repectively. QFT-Plus showed a sensitivity of 84.3%(95%CI: 0.743-0.910), a specificity of 78.8% (95%CI: 0.679-0.868), and a positive predictive value of 80.5%(95%CI: 0.703-0.879), the negative predictive value being 82.9%(95%CI: 0.721-0.902), slightly improved to that of the QFT-GIT. Also, this study found that there were significant differences in IFN-γ values between different MTB load or disease severity (P<0.05). Conclusions: There is a good consistency between the QFT-Plus test and the QFT-GIT test, both of which show good application value in the auxiliary diagnosis of pulmonary tuberculosis. Moreover, because of the addition of tuberculosis-specific CD8 cell antigen, the QFT-Plus test has higher sensitivity, lower uncertainty and more application value. This study also found that the bacterial load and disease severity of patients with pulmonary tuberculosis may have a certain correlation with the measured value of IFN-γ.

[Expert consensus on early prediction and diagnosis of diabetic kidney disease].

Diabetic kidney disease (DKD) is a type of chronic kidney disease (CKD) caused by diabetes. The clinical diagnosis of DKD is usually based on the presence of increased albuminuria and/or decreased estimated glomerular filtration rate (eGFR), and exclusion of other causes of CKD. The clinical features of DKD are proteinuria, gradual decline in renal function, and severe renal failure in the later stages, which is one of the main causes of death in patients with diabetes. Any single biomarker might be insufficient to evaluate renal injury; thus, multiple methods and markers are needed. In addition, diabetic patients should be paid more attention to the kidney, and kidney damage should be evaluated with standardized assessment aimed at strengthening the early prediction and diagnosis of DKD.

[Analysis on the law of height growth spurt in adolescence of children and adolescents in Zhongshan City].

OBJECTIVE: To analyze the characteristics of the age at peak height velocity and peak height velocity of primary and middle school students in Zhongshan City, Guangdong Province, and to explore the law of the sudden increase in adolescent height in this area, and to understand the law of height growth spurt in adolescence by longitudinal tracking of the height of children and adolescents in Zhong-shan City. METHODS: Based on the physical examination database of primary and middle school students in Zhongshan City, Guangdong Province from 2005 to 2016, individuals who had been continuously tracked for more than 6 times were selected as research samples. SITAR model was used to fit the height data of the sample population, and the age at peak height velocity and peak height velocity were calcula-ted. RESULTS: A total of 49 579 subjects were included in this study, including 26 524 boys and 26 008 urban students. The median follow-up ages of boys and girls were 7.74 and 7.72 years, respectively. The boy's height spurt peak age was (12.72±0.89) years, and later than the girls at the age of (10.98±0.95) years (t=207.639, P < 0.001), the boy's height spurt peak velocity of (10.12±1.49) cm/year, higher than the girls of (8.35±1.12) cm/year (t=150.826, P < 0.001). The gender differences of height spurt peak age and height spurt peak speed in urban and rural students were consistent with the whole sample. The height surge peak age of urban male students was earlier than that of rural male students, and the height surge peak speed of urban female students was lower than that of rural female students. CONCLUSION: The peak age of the surge of girls was earlier than that of boys, but the peak rate of the surge of girls was lower than that of boys, the peak age of urban students was earlier than that of rural students, but the peak rate of urban boys was lower than that of rural boys in Guangdong Province.

Genomic profiling of the residual disease of advanced high-grade serous ovarian cancer after neoadjuvant chemotherapy.

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co-infected and HIV mono-infected patients: a retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups. METHODS: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association. RESULTS: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). CONCLUSIONS: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism.

[Analysis of comorbidity and polypharmacy in middle-aged and elderly patients].

Objective: To investigate the characteristics of comorbidities and polypharmacy in middle-aged and elderly patients and assess the potential risk of drug-drug interactions. Methods: Retrospective analysis was carried out among the outpatients aged ≥45 years in the Second Medical Center of the PLA General Hospital from January to December 2016. The patient's comorbidities and polypharmacy were collected from the electronic medical records and annual physical examination reports. The frequency and grade of drug-drug interactions (DDIs) were summarized and ranked by Lexicomp(®) Drug Interactions database. Results: A total of 1 340 patients were enrolled in the study, of which 930 patients (69.40%) used 5 or more drugs, and 660 patients (49.25%) used 10 or more drugs. Multivariate analysis showed that age and the number of comorbidities were independent factors of excessive polypharmacy. The total frequency of detecting clinically significant DDIs (C+D+X) was 857 cases, with 0.8 cases per person by Lexicomp(®) Drug Interactions database. Among them, medications for nervous system accounted for the highest proportion of X-level DDIs. Conclusions: The comorbidities and polypharmacy in middle-aged and elderly patients are very prominent. More attention should be paid to drug interactions, especially in patients with neurological medication.

[The value of left ventricular longitudinal strain in the diagnosis and differential diagnosis of myocardial amyloidosis].

Objective: To investigate the characteristics of left ventricular longitudinal strain (LS) in myocardial amyloidosis (CA), hypertrophic cardiomyopathy (HCM) and Fabry disease (FD), as well as the correlation between left ventricular LS and these diseases. Methods: A total of 14 CA patients, 28 HCM patients and 5 FD patients who visited the Department of Cardiology of the First Affiliated Hospital of Suzhou University from June 2017 to November 2019 were retrospectively included. EchoPAC software was used to analyze left ventricular LS, and univariate logistic regression analysis was used to analyze the correlation between echocardiographic LS indexes and various myocardial hypertrophy diseases. The receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of echocardiograph LS indexes in the diagnosis of various myocardial hypertrophy diseases. Results: There were significant differences in LS of left ventricular basal segment, inferior wall, posterior wall, lateral wall and posterior septum among the three groups (P<0.05). The absolute value of LS in the left ventricular basal segment decreased in the CA group; the absolute value of LS in left ventricular posterior wall and lateral wall decreased significantly in the FD group (P<0.05); the absolute values of LS in left ventricular basal segment, inferior wall, posterior septum, lateral wall and posterior wall increased significantly in the HCM group (P<0.05). The absolute value of LS < 7.9% in the left ventricular basal segment, or > 13.2% in the inferior wall and > 9.2% in the basal segment, or < 8.3% in the lateral wall and < 7.9% in the posterior wall were the indicators of high sensitivity and specificity in the diagnosis of CA, HCM and FD, respectively. Conclusions: Left ventricular LS was an important index to differentiate myocardial hypertrophy. Combined with their respective clinical characteristics, it could provide certain reference value for clinical practice.

[Expression of GTF2IP23 in breast cancer and it mediated regulation of GTF2I].

Objective: To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 (GTF2IP23), in breast cancer and its effect on the host gene general transcription factor Ⅱi (GTF2I). Methods: The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results: The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues (P=0.007). The expression of GTF2IP23 was negatively correlated with GTF2I (r=-0.335, P=0.025). The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells (P<0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P<0.01). Overexpression of GTF2IP23 in ZR-75-30 cells significantly reduced the expression of GTF2I (P=0.034) and enhanced cell proliferation (P=0.017) and migration (P=0.026) capacity. Conclusions: GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.

[Study on the application of oral magnesium sulfate solution in split doses as bowel preparation for colonoscopy in elderly patients].

Objective: To evaluate the efficacy and safety of oral magnesium sulfate solution in split doses as bowel preparation in elderly patients undergoing colonoscopy. Methods: A total of 368 elderly patients undergoing colonoscopy were enrolled at PLA General Hospital. The patients were randomly divided into magnesium sulfate solution orally in split doses group (group A, n=178) and single dose group (group B, n=190). Parameters including general information, defecation frequency, Boston bowel preparation score (BBPS), detection rate of lesions and adverse reactions. Results: The frequency of defecations in group A was (7.6±1.4), more than that in group B (6.6±1.5) with statistical significance (P<0.05). The duration of bowel preparation in group A was (128.6±25.3) min, shorter than that of group B (165.4±29.7) min (P<0.05). The BBPS in group A was (8.09±0.67), better than that of group B (7.34±0.58) (P<0.05). The detection rates of intestinal polyps and micropolyps (diameter<0.5 cm) in group A were 73/178 (41.0%) and 51/178 (28.7%) respectively, compared with 58/190 (30.5%) and 37/190 (19.5%) in group B (both P<0.05). In group A, 8 patients reported adverse reactions as abdominal distension and discomfort. One patient had ST-T abnormality of electrocardiogram (ECG). No nausea or vomiting occurred, yet 2 cases needed enema for inadequate bowel preparation. Twenty-one cases in group B reported adverse events including 7 with nausea and vomiting. There were 13 patients treated with enema. Abnormal ECG was found in 4 patients in group B. The satisfaction rate of group A was 97.8%, higher than that of group B (91.6%) (P<0.05). Conclusions: The effect of bowel preparation of elderly patients with magnesium sulfate solution in split dose has a better tolerance, good cleaning effect and low incidence of adverse reactions. It is an ideal choice for the elderly to prepare colonoscopy.

[Cross-sectional study on clinic behavior and therapeutic status of patients with psoriatic arthritis in multi-center].

OBJECTIVE: To investigate and analyse the features of treatment behavior and standardized therapeutic status of patients with psoriatic arthritis (PsA). METHODS: Out patients diagnosed with PsA in People's Hospital of Peking University, Haidian Hospital, People's Hospital of Jianyang City, Central Hospital of Xinxiang City, Integrated Traditional Chinese and Western Medicine Hospital of Cangzhou City, The Third Hospital of Hebei Medical University from February to June 2018 were enrolled in this investigation. The data including gender, age of onset, course of disease, site of first consulting department, time of the first visit and definite diagnosis, follow-up interval, and use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and biological DMARDs (BioDMARDs) were collected and analyzed. RESULTS: In the cross-sectional study, 133 PsA patients were investigated. The mean age of onset was (47±11) years, the male to female ratio was 1.3:1, and mean disease duration was (16±8) years. Rheumatology department was the most common site of first hospital visit (37.6%, 50/133). Orthopedics department and dermatological department were visited by 24.1% (32/133) and 23.3% (31/133), respectively. Ratio of definite diagnosis was the highest in rheumatology department which was 78% (39/50). The ratio of definite diagnosis of dermatological department was the second highest, which was 19.4% (6/31). The mean definite diagnosed time was 7.6 months since the first visit of PsA patients, and diagnosed time was the shortest in rheumatology department, which had statistical significance. 37% PsA patients were treated appropriately in 3 months, 17.3% PsA patients were treated in 3-6 months and 40.2% patients with PsA visited their doctor more than once a year. 48.8% patients hadn't received standardized treatment before visit, and one third patients never received the therapy of DMARDs. Methotrexate was the most commonly used cDMARDs (58.3%), followed by leflunomide (20.5%) and BioDMARDs (19.7%), and biologicals were tumor necrosis factor antagonists. CONCLUSION: In this multi-center study, the first visit department of PsA patients was widely distributed, and most patients were definitely diagnosed in Rheumatology Department. The time of their first visit and definite diagnosis were delayed due to multi factors. Nearly half of the patients did not receive standardized treatment.

[Analysis of the influential factors of late diagnosis among newly identified HIV/AIDS cases in Anhui Province, 2011-2015].

Objective: To analyze the base situation and influential factors of late diagnosis among newly identified HIV/AIDS cases in Anhui Province from 2011 to 2015. Methods: Database information of the newly identified HIV/AIDS cases in Anhui Province from 2011 to 2015 were downloaded from the National HIV/AIDS Comprehensive Information System of China's disease prevention and control information system. To analyze the data including basic information, sample source, route of HIV transmission, population mobility, venereal disease, death and first CD4 count; and the number of 7 073 cases were classified according to late diagnosis and non-late diagnosis criteria. The Chi-square test and logistic regression analysis were used to analyze the influential factors of HIV late diagnosis. Results: A total of 7 073 newly identified HIV/AIDS cases were analyzed, and the mean age was (38.5±15.0) years. The proportion of late diagnosis in all counted cases was 41.7% (2 949/7 073); from 2011 to 2015, the proportions of late diagnosis were 59.7% (485/812), 46.5% (531/1 141), 42.7% (587/1 376), 36.1% (609/1 686), and 35.8% (737/2 058), respectively. Compared with the 0 to 19 years group, the 40 to 59 years group and over 60 years old group have higher risk of late diagnosis (OR=2.68, 95%CI: 1.94-3.71; OR=2.18, 95%CI: 1.53-3.10, respectively). Compared with the high education group, the illiterate and primary school education group have higher risk of late diagnosis (OR=1.74, 95%CI: 1.36-2.22; OR=1.64, 95%CI: 1.34-2.01, respectively). Compared with other sample sources, medical institutions have higher risk of late diagnosis (OR=2.64, 95%CI: 2.28-3.05). Compared with migrant population, the resident population have higher risk of late diagnosis (OR=1.80, 95%CI: 1.53-2.11). Conclusion: The proportion of late diagnosis among newly identified HIV/AIDS cases in Anhui province was relatively high from 2011 to 2015. The main risk factors of late diagnosis included cases reported by medical institutions, resident population, over 40 years old age group and low education level.

Prothionamide susceptibility testing of Mycobacterium tuberculosis using the resazurin microtitre assay and the BACTECMGIT 960 system.

Resazurin microtitre assay (RMA) has been successfully used to detect minimal inhibitory concentrations (MICs) of both first-line and several second-line drugs in drug susceptibility testing (DST) of Mycobacterium tuberculosis (MTB). In this study, we firstly compared prothionamide (PTH) susceptibility testing of Mycobacterium tuberculosis (MTB) using resazurin microtitre assay (RMA) and MGIT. Overall, the sensitivity and specificity of RMA for detecting PTH susceptibility was 96.5% [95% confidence interval (CI): 91.7-100.0] and 93.2% (95% CI: 89.6-96.8) respectively. In addition, the median time to positivity was significantly shorter for RMA than for the automated MGIT 960 (RMA, 8 days [range: 8-8 days] vs MGIT, 10.1 days, [range: 5.0-13.0]; P < 0.01). Concordance rate for MICs between RMA and MGIT for PTH-resistant group was 64.3% (95% CI: 46.5-82.0), which was significantly lower than that of PTH-susceptible group (85.9%, 95% CI: 78.8-93.0; P= 0.01). In conclusion, our data demonstrated that RMA can be used as an acceptable alternative for determination of PTH susceptibility with shorter turn-around time. When compared with MGIT 960, RMA method was prone to produce higher MICs for PTH-resistant MTB strains.

A genome-wide association study of heat stress-associated SNPs in catfish.

Heat tolerance is a complex and economically important trait for catfish genetic breeding programs. With global climate change, it is becoming an increasingly important trait. To better understand the molecular basis of heat stress, a genome-wide association study (GWAS) was carried out using the 250 K catfish SNP array with interspecific backcross progenies, which derived from crossing female channel catfish with male F1 hybrid catfish (female channel catfish × male blue catfish). Three significant associated SNPs were detected by performing an EMMAX approach for GWAS. The SNP located on linkage group 14 explained 12.1% of phenotypical variation. The other two SNPs, located on linkage group 16, explained 11.3 and 11.5% of phenotypical variation respectively. A total of 14 genes with heat stress related functions were detected within the significant associated regions. Among them, five genes-TRAF2, FBXW5, ANAPC2, UBR1 and KLHL29- have known functions in the protein degradation process through the ubiquitination pathway. Other genes related to heat stress include genes involved in protein biosynthesis (PRPF4 and SYNCRIP), protein folding (DNAJC25), molecule and iron transport (SLC25A46 and CLIC5), cytoskeletal reorganization (COL12A1) and energy metabolism (COX7A2, PLCB1 and PLCB4) processes. The results provide fundamental information about genes and pathways that is useful for further investigation into the molecular mechanisms of heat stress. The associated SNPs could be promising candidates for selecting heat-tolerant catfish lines after validating their effects on larger and various catfish populations.

[Clinical characteristics of glucocorticoid-induced eye adverse reactions in children with primary nephrotic syndrome].

OBJECTIVE: To investigate the clinical features and side effects, with regard to glucocorticoid-induced ocular hypertension, glaucoma or cataract in children with primary nephrotic syndrome. METHODS: Clinical data were collected and analyzed from 71 cases of primary nephrotic syndrome with glucocorticoid-induced ocular hypertension, glaucoma or cataract from Jun. 2014 to Jun. 2016. These children were hospitalized in Peking University First Hospital. RESULTS: Totally 1 580 children with primary nephrotic syndrome were collected, glucocorticoid-induced complications in eyes were found in 71 cases, and the incidence was 4.5%. There were 66 cases with ocular hypertension, 2 cases with glucocorticoid glaucoma, 2 cases with glucocorticoid glaucoma combined with cataract, 1 case with high intraocular pressure combined with cataract. There were 41 boys and 30 girls with eye-related side effects caused by glucocorticoid. The average age of onset of glucocorticoid-induced eye adverse reactions in children with primary nephrotic syndrome in our research were 8 (2, 16) years. The average duration or interval time from glucocorticoid medication use to eye adverse effects was 157 (6, 420) days. No statistical significance was found in intraocular pressure between different genders, types of glucocorticoid, different route of glucocorticoid and whether methylprednisolone pulse treatment (P>0.05). There was no significant correlation between age, body mass index, blood pressure, cumulative dosage, duration time of glucocorticoid, mean daily dosage and glucocorticoid-induced ocular hypertension (P>0.05). The ocular hypertension was controlled after treatment. CONCLUSION: Children with nephrotic syndrome after treatment of glucocorticoid are susceptible to ocular complications, and the occurrence of ocular hypertension is closely related to glucocorticoid susceptibility of the nephrotic children. Regular eye monitor is indispensable for the children suffering from primary nephrotic syndrome.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

BACKGROUND AND OBJECTIVES: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. MATERIALS AND METHODS: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. RESULTS: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. CONCLUSIONS: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting.

The differentiation deficiencies of osteoclast precursors (pre-OCs) may contribute to osteoporosis. Research on osteoporosis has recently focused on microRNAs (miRNAs) that play crucial roles in pre-OC differentiation. In the current study, we aimed to analyze the expression and function of the glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation. We found that dexamethasone induced osteoclast differentiation and inhibited miR-338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor cells attenuated GC-induced osteoclast formation and bone resorption, whereas inhibition of miR-338-3p reversed these effects. The expression of the nuclear factor κB ligand RANKL, a potential target gene of miR-338-3p, was inversely correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone resorption. Taken together, these findings demonstrate that miR-338-3p may play a significant role in GC-induced osteoclast differentiation and function by targeting RANKL in osteoclasts.

[Expression of FAS-AS1 in breast cancer and its effect on the host gene sFas].

OBJECTIVE: To investigate the expression level of antisense transcript of FAS (FAS-antisense 1, FAS-AS1) in breast cancer, and its effect on the host gene soluble Fas receptor (sFas). METHODS: The expression of FAS-AS1 and sFas gene was detected in 20 cases of breast cancer tumors and breast cancer cells and their normal counterparts by using real-time quantitative polymerase chain reaction(RT-qPCR). The effects of FAS-AS1 on the expression of sFas gene in breast cancer cells were analyzed by overexpressing FAS-AS1 in breast cancer cells. RESULTS: FAS-AS1 expression in breast cancer tissue and cell lines was significantly lower than that of adjacent breast tissue (P=0.000) and normal breast cells (P<0.01). However, sFasexpression in the breast cancer tissue and cell lines was significantly higher than that of adjacent breast tissue (P=0.001) and normal breast cells (P<0.01). The expression of FAS-AS1 was negatively correlated with the expression of sFas(r=-0.751, P=0.020). FAS-AS1 expression was observed to be closely correlated with tumor size (r(2)=0.351, P=0.025) and lymph node metastasis (r(2)=0.265, P=0.043). Expression of sFas and cell proliferation was significantly reduced in FAS-AS1-overexpressing MCF-7 cells (P<0.05). CONCLUSION: FAS-AS1 is distinctly downexpressed in breast cancer, and it has certain effects on the expression of host gene sFas and breast cancer development.

Prevention of hepatitis C virus infection by adoptive allogeneic immunotherapy using suicide gene-modified lymphocytes: an in vitro proof-of-concept.

Hepatitis C virus (HCV)-induced, end-stage liver disease is a major indication for liver transplantation, but systematic graft reinfection accelerates liver disease recurrence. Transplantation recipients may be ineligible for direct-acting antivirals, owing to toxicity, resistance or advanced liver disease. Adoptive immunotherapy with liver graft-derived, ex vivo-activated lymphocytes was previously shown to prevent HCV-induced graft reinfections. Alternatively, the applicability and therapeutic efficacy of adoptive immunotherapy may be enhanced by 'ready for use' suicide gene-modified lymphocytes from healthy blood donors; moreover, conditional, prodrug-induced cell suicide may prevent potential side effects. Here, we demonstrate that allogeneic suicide gene-modified lymphocytes (SGMLs) could potently, dose- and time-dependently, inhibit viral replication. The effect occurs at effector:target cell ratios that exhibits no concomitant cytotoxicity toward virus-infected target cells. The effect, mediated mostly by CD56+ lymphocytes, is interleukin-2-dependent, IFN-γ-mediated and, importantly, resistant to calcineurin inhibitors. Thus, post-transplant immunosuppression may not interfere with this adoptive cell immunotherapy approach. Furthermore, these cells are indeed amenable to conditional cell suicide; in particular, the inducible caspase 9 suicide gene is superior to the herpes simplex virus thymidine kinase suicide gene. Our data provide in vitro proof-of-concept that allogeneic, third-party, SGMLs may prevent HCV-induced liver graft reinfection.