Objective To investigate low density lipoprotein receptor (LDLR)gene mutation in familial hypercholesterolemia (FH) patients. Methods The proband was given clinical diagnosis of homozygous FH based on marked features and blood lipid tests results. After apoB100R3500Q mutation was excluded, the promoter region and all of the 18 exons of LDLR gene were amplified by touch-downpolymerase chain reaction (PCR). The PCR products were analyzed by single-strand conformationalpolymorphism (SSCP). The PCR products with abnormal single strands were sequenced directly. Thesecondary structures of the mutational and wild type proteins were analyzed and compared byANTHEPROT5.0, and then the tertiary structures of the mutant and wild type LDLR were predicted atSWISS MODEL homepage online. Results A homozygous mutation A606T at exon 13 of the patients wasfound by SSCP and confirmed by DNA sequencing. GOR Ⅰ method in ANTHEPROT5.0 indicates that therandom coils and turns would replace some helixes at the mutation site. The online prediction from theSWISS MODEL homepage indicates the backbone structure of the mutant LDLR has no difference from thewild type one. Conclusion The results suggest the A606T mutation of LDLR gene is the cause of the FH inthis pedigree.

Objective To detect and analyse CRP level in rat chronic periodontitis and atherosclerosis compound model.Methods Sixty rats were randomly divided into four groups,15 in each group: Group A:control group;Group B:periodontitis group;Group C:atherosclerosis group;Group D:periodontitis and atherosclerosis group.Every group accepted the corresponding treatment.Pathological changes in periodontal tissue of experimental teeth and arterial vessels were observed.CRP level in serum was assayed by ELISA.Results Histopathological observation of periodontal tissue revealed: Obvious inflammation of periodontal tissue was observed in group B,D.Attachment loss levels in group B and D were higher than that of A,C groups(P

OBJECTIVE: Cisplatin is a widely used chemotherapeutic agent in the treatment of cancers in clinic; but it often induces adverse effects on ovarian functions such as reduced fertility and premature menopause. Mesna could attenuate the cisplatin-induced ovarian damages; however, the underlying mechanism is still unknown. This study aimed to figure out the underlying mechanism of the protection of mesna for ovaries against cisplatin therapy in cancers. METHODS: We performed female adult Sprague-Dawley rats into normal saline control (NS), low-dose cisplatin (CL), high-dose cisplatin (CH), CL plus mesna (CL+M), and CH plus mesna (CH+M) groups and detected anti-Mullerian hormone (AMH)-positive follicle, oxidative stress status and anti-oxidative capability in ovaries. RESULTS: AMH-positive follicles were significantly decreased after cisplatin administration, which was significantly reversed when mesna was co-administered with cisplatin. The end product of lipid peroxidation, malondialdehyde (MDA), was significantly increased, but the anti-oxidative enzymatic activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly decreased in cisplatin groups when compared with NS group. In contrast, after co-administration of cisplatin with mesna, MDA was significantly decreased whereas the activity of SOD and the concentration of GSH were increased. Moreover, mesna did not decrease the anti-tumor property of cisplatin in HePG2 cell lines. CONCLUSION: Cisplatin damages the granulosa cells by oxidative stress to deplete the ovarian reserve and mesna could protect ovarian reserve through anti-oxidation. These results might highlight the mechanism of the protection of mesna for ovarian reserve and open an avenue for the application of mesna as a protective additive in cisplatin chemotherapy in clinical practise.
Adult ; Animals ; Anti-Mullerian Hormone ; Cisplatin ; Female ; Fertility ; Glutathione ; Granulosa Cells ; Hep G2 Cells ; Humans ; Lipid Peroxidation ; Malondialdehyde ; Menopause, Premature ; Mesna ; Ovary ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase

Objective:The matria-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS) and sequencing methods were performed to assess the methodology (biochemistry methods) for identifying the Pandoraea sputorum and provide the more preferred approach to identify Pandoraea species. Methods:This paper is a study on performance evaluation of identification method. Ten lines of Pandoraea sputorum were isolated from blood cultures of inpatients were collected at Zhongnan Hospital of Wuhan University from July to October 2018 and were confirmed by the cultural characteristics, colonial morphology and Gram′s stain. Further identification was carried out by using the manual biochemical method (API 20NE), automatic biochemistry systems(BioMerieuxVITEK 2 Compact, BD Phoenix-100andThemo ARIS 2X), MALDI-TOF MS (BioMerieuxVITEK MS and Bruker MALDI Biotyper) and the sequencing methods of the 16S rRNA to identify the Pandoraea sputorum. Results:Pandoraea sputorum was non-fermented gram-negative bacteria that are non-motile, oxidase positive, and catalase positive. Ten lines of Pandoraea sputorum were identified as Achromobacter denitrificans, Alcaligenes faecalis or Cupriavidus pauculus and the accuracy rate of genus and species identification was 0 by API 20NE. Among all the samples, six lines were identified as the Pandoraea spp. with the accuracy rate of genus identification was 6/10 by VITEK 2 Compact; whereas the other four lines were identified as the Burkholderia cepacia, Sphingomonas paucimobilis, Ralstonia pickettii, or "Low Discrim" . All of these were identified as "No Identification" by Phoenix-100, which the accuracy rate of genus and species identification was 0. Seven isolates were identified by ARIS 2X as Stenotrophomonas maltophilia, Acinetobacter lwoffii, Sphingomonas paucimobilis, Pseudomonas luteola, Acinetobacter baumannii/Acinetobacter haemolyticus; whereas the other three lines were identified as rare species, thus, the accuracy rate of genus and species identification was 0. Both VITEK MS and MALDI Biotyper indicated all the isolates were Pandoraea sputorum with the accuracy rate of genus and species identification was 10/10. 16S rRNA sequencing for the 10 isolates showed they have 100% of similarity to Pandoraea sputorum by blasting with Genebank. Conclusions:Methods based on biochemical reactions often failed to accurately identify the Pandoraea sputorum to species level. MALDL-TOF MS and 16S rRNA sequencing technology identify Pandoraea sputorum efficiently and precisely enough.

OBJECTIVES: This population-based, prospective cohort study investigated the association between glaucoma and mortality in older adults. METHODS: Participants aged 45 years or older at baseline (47.9% male) were enrolled in 2011 for the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was observed during 7 years of follow-up. The baseline data were collected in the 2011 CHARLS, and participants were followed up for 7 years (until 2018). The risk of all-cause mortality was investigated using Cox proportional-hazards regression with age as the time scale, adjusting for significant risk factors and comorbid conditions. RESULTS: Among the 14,803 participants included, the risk of all-cause death was significantly higher among people with glaucoma than among those without glaucoma, after adjustment for other confounders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04 to 2.03). In a subgroup analysis based on the mean age of death, among those who were 75 years and older (n=1,231), the risk of all-cause death was significantly higher in patients with glaucoma than in those without glaucoma (HR, 1.89; 95% CI, 1.24 to 1.89). CONCLUSIONS Participants with glaucoma had a higher risk of all-cause mortality, especially those aged 75 years and above. Our findings revealed potential mechanisms underlying an association between glaucoma and all-cause mortality. They also highlighted the importance of glaucoma management to prevent premature death in middle-aged and older adults.

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

OBJECTIVETo investigate the related factors of renal functions in hypertensive patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).

METHODSA total of 438 hypertensive patients with complain of snoring at night were enrolled in the study from the First teaching Hospital of Xinjiang Medical University during March 2011 and March 2014. The diagnosis of OSAHS was confirmed with polysomnography examination, and the patients were divided into 4 groups according to the apnea hypoventilation index (AHI): hypertensive group (AHI<10/h, n=102), mild OSAHS group (AHI 10-<15/h, n=97), moderate OSAHS group (AHI 15-<30/h, n=149), and severe OSAHS group (AHI≥30/h, n=90). The blood urea, creatinine, eGFR, 24h-urinary total protein (24h UTP), 24h-urinary microalbumin, cystatin C (Cyst C) were measured and compared among groups, and the influencing factors of renal function were analyzed.

RESULTSThere were no significant differences in age, gender, body mass index(BMI), 24-hour systolic blood pressure (24hSBP), fasting blood-glucose, high-density lipoprotein cholesterol (HDL-C) among the groups (P<0.05). 24h-UTP and 24h-urinary microalbumin in the severe OSAHS group were higher than those in other groups (P<0.05); and all patients with OSAHS had higher Cyst C levels than those without OSAHS (all P<0.05). Logistic regression analysis showed that BMI (OR=1.486, 95% CI 1.022-2.160) and severe OSAHS (OR=7.138, 95% CI 1.835-27.769) were influencing factors of 24h-UTP; blood pressure (OR=2.368, 95% CI 1.324-4.234) and BMI (OR=1.678, 95% CI 1.263-2.230) were influencing factors of 24h-urinary microalbumin; age (OR=1.998, 95% CI 1.325-3.013), blood pressure (OR=3.202, 95% CI 1.319-7.773) and severe OSAHS (OR=5.462, 95% CI 1.103-27.041) were influencing factors of Cyst C.

CONCLUSIONOSAHS is a risk factor for early renal damage in patients with hypertension. Age, BMI, blood pressure and severe OSAHS may be influencing factors for renal function in hypertensive patients with OSAHS.