[Comparison of pingyangmycin fibrin glue composite and pingyangmycin dexamethasone composite in the treatment of pharyngolaryngeal venous malformation].

Objective: To analyze and compare the efficacy and safety of pingyangmycin fibrin glue composite (PFG) and pingyangmycin dexamethasone composite (PD) in the treatment of pharyngolaryngeal venous malformation (VM). Methods: The clinical data of 98 patients with pharyngolaryngeal VM who underwent sclerotherapy with pingyangmycin composite in the First Affiliated Hospital of Sun Yat-sen University from June 2013 to November 2022 were retrospectively analyzed. According to their treatment, patients were divided into PFG group (n=34) and PD group (n=64), among those patients there were 54 males and 44 females, aged 1-77(37.06±18.86)years. The lesion size, total treatment times and adverse events were recorded before and after treatment. And the efficacy was divided into three grades: recovery, effective and invalid. According to the length of VM, all patients were divided into three subgroups, to compare the differences in efficacy and treatment times between each two groups.And finally the adverse events and their treatments were analyzed. SPSS 25.0 software was used for statistical analysis. Results: The efficacy of PFG group was 94.11%(32/34), the recovery rate was 85.29%(29/34).And the efficacy of PD group was 93.75%(60/64), the recovery rate was 64.06%(41/64). No serious adverse eventst occurred in subgroup comparison, there was no statistical difference between the two groups in efficacy and the times of treatments when the length was≤3 cm (Zefficacy=1.04, ttreatment times=2.18, P>0.05); when the length was 3-5 cm, there was no significant efficacy difference between the two groups(Zefficacy=1.17, P>0.05), but the treatment times of PFG were less (ttreatment times=4.87, P<0.01); when the length≥5 cm, efficacy of PFG was significantly better than PD (Zefficacy=2.94, P<0.01), and had fewer treatments times (ttreatment times=2.16, P<0.01). There were no serious adverse events in either group during treatment and follow-up. Conclusion: Both PFG and PD are safe and effective composite sclerotherapy agent for the treatment of laryngeal VM, but PFG has a higher cure rate and fewer treatment times for massive lesions.

[Obstructive sleep apnea and metabolic syndrome: an association study based on a large sample clinical database].

Objective: To investigate the prevalence and associated risk factors of metabolic syndrome (MS) in patients with obstructive sleep apnea (OSA). Methods: From July 2007 to June 2017, a total of 8 155 adult subjects, including 6 484 males and 1 671 females, aged 18-90 (43.13±12.28), body mass index 14.61~59.56 (25.59±3.98) kg/m2,who were admitted to the Department of Otorhinolaryngology head and Neck surgery of The Sixth People's Hospital affiliated to Shanghai Jiao Tong University, were retrospectively analyzed. All patients underwent polysomnography and biochemical tests. Subjects were divided into four groups (non-OSA, mild OSA, moderate OSA, and severe OSA) according to OSA severity. The prevalence of MS was expressed as percentage, and the correlation between OSA and MS and its characteristic pathophysiological indicators was evaluated by logistic regression model after adjusting for factors such as gender, age, BMI, neck circumference, hip circumference, smoking and alcohol consumption, and was expressed by odds ratio (OR). SPSS 25.0 software was used for statistical analysis. Results: The overall prevalence of MS was 43.6%, and that of non-/mild/moderate/severe OSA group was 18.6%, 30.4%, 43.8%, 57.1%.Logistic regression showed that patients with mild/moderate/severe OSA had an increased risk of MS compared with non-OSA patients, with adjusted OR values and confidence intervals of 1.27 (1.05-1.54), 1.84 (1.53-2.22), and 2.08 (1.76-2.46), respectively (P<0.01).In addition, indicators of OSA anoxic burden [oxygen drop index(Toxygen=7.1), minimum blood oxygen(Tminimum=56.3), blood oxygen saturation below 90% cumulative time ratio (TCT90=10.6) ]were closely associated with MS disease(P<0.01), but sleep fragmentation index (arousals index) was not significantly associated with MS disease. Conclusion: The risk of MS gradually increases with the severity of OSA, and the indicators reflecting OSA hypoxia burden are closely related to MS disease.

Burden of colorectal cancer attributable to diet low in milk in China, 1990-2017: findings from the global burden of disease study 2017.

BACKGROUND: Colorectal cancer (CRC) has emerged as a major public health concern. However, little is known about the burden attributable to specific risk factors. The present study aimed to estimate the temporal trends and geographical variation of CRC burden attributable to a diet low in milk in China. METHODS: Following the general analytic strategy used in the 2017 Global Burden of Disease study, we assessed the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of CRC caused by a diet low in milk in China from 1990 to 2017. RESULTS: In 2017, a diet low in milk contributed 32 032 [95% uncertainty interval (UI) = 11 350-53 806] deaths and 726 710 (95% UI = 256 651-1 218 153) DALYs for CRC with a population attributable fraction of 17.1%. The age-standardised mortality and DALY rates per 100 000 were 1.7 (95% UI = 0.6-2.9) and 36.8 (95% UI = 13.0-61.7), respectively. An upward trend with age in rates of mortality and DALYs was observed. Males had higher age-standardised rates than females. The number of deaths and DALYs increased significantly from 1990 to 2017, whereas the corresponding age-standardised rates showed relatively stable trends. In 2017, Hunan and Liaoning were ranked as the top two provinces in terms of disease burden. Socio-demographic index had a weak correlation with the age-standardised mortality (r = 0.348, P = 0.047). CONCLUSIONS: The present study shows a substantial increase in the CRC burden attributable to a diet low in milk over the past three decades. Greater priority in CRC prevention should be given to males and the elderly population throughout China, particularly in less-developed provinces.

Expressions of miR-525-3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia.

BACKGROUND: Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that the SEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear. OBJECTIVES: To study the molecular mechanism of high expression of SEMG1 gene and its potential roles in AZS. MATERIALS AND METHODS: Western blot and real-time PCR were used to detect the expression levels of SEMG1 protein and mRNA in the ejaculated spermatozoa from normozoospermic males and AZS patients. Bioinformatics analysis was used to predict miRNAs targeting for SEMG1 3'-untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa in AZS patients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind to SEMG1. Correlation of miR-525-3p and SEMG1 mRNA expression with clinical sperm parameters were also analyzed. Finally, we conducted a follow-up study of reproductive history about all the subjects. RESULTS: SEMG1 mRNA and protein level were significantly higher in AZS patients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA-525-3p (miR-525-3p) which was predicted as a candidate regulator of SEMG1 was found lower expressed in ejaculatory spermatozoa in AZS patients (p = 0.0074). Luciferase experiment revealed that microRNA-525-3p could directly target SEMG1 3'-untranslated region and suppress its expression. Importantly, our retrospective follow-up study showed that both low miR-525-3p expression and high SEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility. DISCUSSION AND CONCLUSION: The elevated expression of SEMG1 and reduced expression of miR-525-3p are associated with AZS and male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy.

Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.

Comprehensive proteomics analysis of exosomes derived from human seminal plasma.

Exosomes are membranous nanovesicles of endocytic origin that carry and transfer regulatory bioactive molecules and mediate intercellular communication between cells and tissues. Although seminal exosomes have been identified in human seminal plasma, their exact composition and possible physiologic function remain unknown. The objective of this study was to perform a comprehensive proteomics analysis of exosomes derived from human seminal plasma. Seminal exosomes were isolated and purified from 12 healthy donors using a 30% sucrose cushion-based exosome-isolation protocol, followed by characterization by western blot, transmission electron microscopy, and nanoparticle tracking analysis before performing extensive liquid chromatography tandem mass spectrometry proteomics analysis. The identified proteins were analyzed by bioinformatics analysis, and seminal exosomes-associated proteins were selectively validated by western blot. A total of 1474 proteins were identified in all seminal exosomes samples, with Gene Ontology analysis demonstrating that these identified seminal exosomes-associated proteins were mostly linked to 'exosomes,' 'cytoplasm,' and 'cytosol.' Bioinformatics analysis indicated that these proteins were mainly involved in biologic processes, including metabolism, energy pathways, protein metabolism, cell growth and maintenance, and transport. Of these identified proteins, PHGDH, LGALS3BP, SEMG1, ACTB, GAPDH, and the exosomal-marker protein ALIX were validated by western blot. This study provided a more comprehensive description of the seminal exosomes proteome and could also be a resource for further screening of biomarkers and comparative proteomics studies, including those associated with male infertility and prostate cancer.

Expression patterns of two heat-shock cognate 70 genes during immune responses and larval development of the Chinese mitten crab Eriocheir sinensis.

Two heat-shock protein (HSP) 70 family transcripts, heat-shock protein 70 cognate 5 and heat-shock protein 70 cognate 3 (designated as EsHSC70-5 and EsHSC70-3, respectively), were isolated from the Chinese mitten crab Eriocheir sinensis and their expression profiles were evaluated for their responsiveness to larval development and immune challenge in adult crabs. The HSPs exhibited 45-89% identity with other heat-shock proteins, and they shared similar structural features. EsHSC70 mRNA expression was detected not only during infection but also during the developmental larval stages. The EsHSC70s were enriched, and their expression fluctuated during early development. EsHSC70 mRNA expression was significantly induced by Vibrio parahaemolyticus challenge in all of the tissues studied (P < 0.05). Expression of EsHSC70 mRNA in the hepatopancreas and at the early zoeal stages was particularly pronounced, and the two EsHSC70s exhibited differential expression patterns both chronologically and spatially. The EsHSC70-5 mRNA level was significantly downregulated in the intestine and gills compared to that in controls at nearly all time points, and was expressed at a lower level after the bacterial challenge, indicating that EsHSC70-5 and EsHSC70-3 respond to immune challenges. The stage-specific enrichment of EsHSC70 transcripts in crabs suggests that these stress proteins play an essential role during brachyurization events.

Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.

Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day-1 metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P<0.0001); and 25.3% of patients in the metformin group had LDL-C ≥3.37 mmol l-1, which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.

Interleukin-10 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.

It has been reported that interleukin-10 (IL-10) promoter genes (1082 A/G, 819 T/C, 592 A/C) are associated with nasopharyngeal carcinoma (NPC). However, the results remain controversial and ambiguous. To resolve inconsistencies in published data, we performed a meta-analysis to ascertain the association between IL-10 polymorphisms and NPC risk. Two case-control studies and two cohort studies were quantitatively analyzed to evaluate IL-10 promoter gene polymorphisms and NPC risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each genetic model and allelic comparison. A random-effect model or a fixed-effect model was used to calculate the overall combined risk estimates. Overall, the variant genotypes (AA and AG) of the IL-10-1082 A/G polymorphism were associated with elevated risk of NPC compared with the GG homozygote (AG vs GG: OR = 1.77; 95%CI = 1.39-2.26; AG + GG vs AA: OR = 1.78; 95%CI = 1.42-2.22); no significant associations were observed in allelic contrast and the recessive model. Strong positive association was seen in the cohort studies but not in the case-control studies. No statistically significant association was detected between IL-10-819 T/C and IL-10-592 A/C polymorphisms and NPC. Additionally, publication bias was not found. Based on the current evidence, this meta-analysis suggests that IL-1082 A/G polymorphism may increase the risk of NPC, but IL-10-819 T/C and IL-10-592 A/C polymorphisms do not. Further multicenter studies that are better controlled are required to confirm these findings.

Interleukin-1ß +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: a meta-analysis.

The purpose of this meta-analysis was to determine whether genetic variants of the interleukin-1ß[+3954 C>T (rs1143634)] (IL-1ß +3954 C>T) gene polymorphisms were associated with orthodontic external apical root resorption (EARR). A meta-analysis was carried out using data entered into the PubMed and Embase electronic databases before October 5, 2012. A total of 7 studies were identified for meta-analysis. The strength of the relationship between IL-1ß +3954 C>T polymorphism and the risk of EARR was assessed using odds ratio (OR). The studies provided overall OR estimates for EARR. Overall, the variant genotypes (CC and CT) of the IL-1ß +3954 C>T polymorphism were unassociated with EARR risk compared with the TT homozygote [CC vs TT, OR = 1.28, 95% confidence interval (95%CI) = 0.27-6.08; CT vs TT, OR = 0.74, 95%CI = 0.11-5.02]. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 1.08, 95%CI = 0.24-4.86; recessive model, OR = 1.85, 95%CI = 0.87-3.93). No publication bias was found, and no association was apparent between the IL-1ß +3954 C>T polymorphism and risk of EARR in orthodontic treatment patients. Further multicenter and better-controlled studies are required to confirm these findings.

[Studies on chemical constituents of Phyllanthus urinaria L].

OBJECTIVE: To investigate the chemical constituents of Phyllanthus urinaria. METHOD: Various chromatographic techniques were employed for isolation and purification of the constituents. The structures were elucidated by chemical and spectral analyses. RESULT AND CONCLUSION: Fourteen compounds were isolated and seven of them were identified as corilagin(I), rutin(II), brevifolincarboxylic acid(VI), isostrictiniin(IX), geraniin (X), gallic acid(XI) and ellagic acid (XII). Compound VI was found from P. urinaria for the first time and compound IX was found from genus Phyllanthus for the first time.

[Isolation and identification of a noval polyphenolic compound from Phyllanthus urinaria L].

OBJECTIVE: To investigate the chemical constituents of Phyllanthus urinaria. METHOD: Various chromatographic techniques were employed for isolation and purification. The structures were elucidated by spectral analyses. RESULT AND CONCLUSION: A novel polyphenolic compound was isolated and named phyllanthusin F.

[Studies on the simultaneous measurement of several cephalosporins by RP-HPLC (I)].

This paper reported the research on the simultaneous separation and determination of six cephalosporins by RP-HPLC. Six cephalosporins are cefalcor, cefalexin, cefradine, cefadroxil, cefominox and cefoxitin. The analytical conditions for this method were as follows: a Hypersil ODS C18(200 mm x 4.6 mm i.d., 5 microns), detection wavelength: 254 nm; a mobile phase solution of 50 mmol/L monopotassium phosphate (pH 3.4)-acetonitrile (87.5:12.5) and DAD detector. The flow rate was 1.0 mL/min. The calibration curves of the six compounds were linear, the correlation coefficients were 0.9951 for cefominox, 0.9999 for the others, the range were 164 ng-16.4 micrograms for cefominox, 99 ng-9.934 micrograms for cefadroxil, 104 ng-10.358 micrograms for cefalcor, 122 ng-12.224 micrograms for cefalexin, 107 ng-10.702 micrograms for cefradine and 115 ng-11.506 micrograms for cefoxitin. The recovery rates were 103.5% for cefominox, 99.3% for cefadroxil, 101.4% for cefalcor, 101.5% for cefalexin, 98.7% for cefradine and 97.6% for cefoxitin. Six cephalosporins were all stable in 50 mmol/L monopotassium phosphate (pH 3.4-4.6). When preparations of these cephalosporins were determined, it is indicated there were no difference between the results by using this method and the pharmacopoeia methods. The total separation time of these cephalosporins was within fifteen minutes. This method is simple, sensitive, rapid and accurate.

Bicarbonate-activated adenylyl cyclase in fluid-transporting tissues.

A bicarbonate-stimulated adenylyl cyclase (AC) activity was found in ocular ciliary processes, which secrete the aqueous humor of the eye. Other fluid-transporting tissues also showed HCO3(-)-stimulated AC activity. Relative to basal, the response to 10 mM NaHCO3 was greatest in the particulate fraction of bovine ciliary processes, followed by bovine corneal endothelium, bovine choroid plexus, and rat kidney (medulla and cortex). However, no activity was detectable in bovine retina, cerebral cortex, or cerebellum. The activity in ciliary processes was present only in the particulate fraction, was supported by Mg2+ or Mn2+, was independent of GTP, and was additive to the stimulatory G protein-dependent AC response (via beta-adrenergic receptor stimulation). The activation of AC was dose dependent up to 100 mM bicarbonate with a 50% effective concentration of 2-3 mM. The HCO3- response was unaffected by 1 mM methazolamide, a carbonic anhydrase inhibitor, but HSO3- was a partially selective inhibitor compared with its effect on forskolin-stimulated AC activities. The presence of membrane-bound bicarbonate-sensitive AC in fluid-transporting tissues suggests an autoregulatory mechanism for intracellular HCO3- concentration acting via adenosine 3',5'-cyclic monophosphate in the control of membrane ion transporters.

Interaction of vanadate and iodate oxyanions with adenylyl cyclase of ciliary processes.

Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated response of FSK in the presence of VO3- was due to an increase in Vmax without a change in the apparent affinity of FSK or VO3-, and therefore differs from the potentiated response of activated G-protein (Gs) and FSK, where the affinity of FSK was increased by 1-2 orders of magnitude. Potentiation occurred at low Mg2+ and was not observed at free [Mg2+] > 3 mM. Iodate (IO3-) inhibited the FSK, ISO, and VO3- activations of AC in ciliary process membranes (IC50, 0.3 mM). In vivo topical treatment of the rabbit eye with 50 microL of 5% NaIO3 had no effect alone but completely blocked the intraocular pressure response to a 50-microL topical dose of 1% FSK and partially blocked the response to a 50-microL dose of 0.001% ISO. These findings indicate that some AC enzymes may have a binding site for oxyanions which can directly regulate enzyme activity.