Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors

Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins.Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs. However, it was found ANGPTL3 inhibitors were also effective in reducing low-density lipoprotein cholesterol (LDL-C) and they were studied in patients with homozygous familial hypercholesterolaemia (FH). Evinacumab targets ANGPTL3 and reduced LDL-C by about 50% in patients with homozygous FH and it has been approved for that indication. The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies. ApoC3 can be inhibited by the ASO volanesorsen, which reduced triglycerides by >70% in patients with FCS and it was approved for FCS in Europe but not in the United States because of concerns about thrombocytopaenia. Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. AROAPOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies.

Analysis of conjunctival sac microflora and antibiotic susceptibility testing in adolescents after wearing orthokeratology lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the bacterial flora and antibiotic susceptibility testing of conjunctival sac in adolescents after wearing orthokeratology(OK)lens.METHODS:A total of 101 adolescents aged 8 to 14 who admitted to outpatient department of Xi'an No.1 Hospital from September 2021 to August 2022 were recruited in this cross-sectional observational study. There were 51 cases wearing OK Lens(wearing group)and 50 patients not wearing contact lens(non-lens group), the right eye of all patients was selected into the group. The culture of bacterial flora in conjunctival sac between the two groups were compared, the species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the antibiotic susceptibility testing was carried out for the positive strains cultured in the wearing group.RESULTS:The positive rate of conjunctival sac bacterial cultured in the wearing group and the non-lens group was 68.6%(35/51)and 60.0%(30/50), respectively(P>0.05). In both groups, the bacteria with the highest detection rate were staphylococcus epidermidis and staphylococcus aureus. The sensitivity rates of the strains detected in the wearing group to drugs are as follows: Levofloxacin(98%), Moxifloxacin(98%), Gatifloxacin(98%), Cefuroxime(98%), Cefathiamidine(98%), Rifampicin(98%), Chloramphenicol(96%), Cefoxitin(95%), Clindamycin(80%), Gentamicin(74%), Fusidic acid(72%), Tobramycin(64%), Compound sulfamethoxazole(26%), Mezlocillin(10%), Azithromycin(6%), of which the sensitivity rate of Gram-positive cocci was 100% sensitive to Vancomycin.CONCLUSION:Gram-positive cocci are the main bacteria isolated from conjunctival sac of adolescents after wearing OK Lens. Wearing OK Lens will not significantly increase the positive rate of conjunctival sac bacterial flora. Results of antibiotic susceptibility testing may provide guidance for empirical medication in patients wearing OK lens after eye infection.

Clinical characteristics of children with SARS-CoV-2 Omicron variant infection in Kunming / 中华儿科杂志

Objective: To investigate the clinical characteristics of hospitalized children infected with the Omicron variant in Kunming after the withdrawal of non-pharmaceutical interventions (NPI) and analyze the risk factors of severe cases. Methods: Clinical data was retrospectively collected from 1 145 children with SARS-CoV-2 Omicron infection who were hospitalized in six tertiary grade A hospitals in Kunming from December 10th, 2022 to January 9th, 2023. According to clinical severity, these patients were divided into the general and severe SARS-CoV-2 groups, and their clinical and laboratory data were compared. Between-group comparison was performed using t-test, chi-square test and Mann-Whitney U test. Spearman correlation test and multivariate Logistic regression analysis were used to determine the risk factors of severe illness. Results: A total of 1 145 hospitalized patients were included, of whom 677 were male and 468 female. The age of these patients at visit was 1.7 (0.5, 4.1) years. Specifically, there were 758 patients (66.2%) aged ≤3 years at visit and 387 patients (33.8%) aged >3 years. Of these children, 89 cases (7.8%) had underline diseases and the remaining 1 056 cases (92.2%) had no combined diseases. Additionally, of all the patients, 319 cases (27.9%) were vaccinated with one or two doses of SARS-CoV-2 vaccine, 748 cases (65.3%) had acute upper respiratory tract infection (AURTI), and six cases died (0.5%). A total of 1 051 cases (91.8%) were grouped into general SARS-CoV-2 group and 94 cases (8.2%) were grouped into severe SARS-CoV-2 group. Compared with the general cases, the severe cases showed a lower rate of SARS-CoV-2 vaccination and younger median age, lower lymphocyte count, as well as proportions of CD8+T lymphocyte (36 cases (38.3%) vs. 283 cases (26.9%), 0.5 (2.6, 8.0) vs. 1.6 (0.5, 3.9) years, 1.3 (1.0, 2.7) ×109 vs. 2.7 (1.3,4.4)×109/L, 0.17 (0.12, 0.24) vs. 0.21 (0.15, 0.16), respectively, χ2=4.88, Z=-2.21,-5.03,-2.53, all P<0.05). On the other hand, the length of hospital stay, proportion of underline diseases, ALT, AST, creatine kinase isoenzyme, and troponin T were higher in the severe group compared to those in the general group ((11.6±5.9) vs. (5.3±1.8) d, 41 cases (43.6%) vs. 48 cases (4.6%), 67 (26,120) vs. 20 (15, 32) U/L, 51 (33, 123) vs. 44 (34, 58) U/L、56.9 (23.0, 219.3) vs. 3.6 (1.9, 17.9) U/L, 12.0 (4.9, 56.5) vs. 3.0 (3.0, 7.0) ×10-3 pg/L,respectively, t=-20.43, χ2=183.52, Z=-9.14,-3.12,-6.38,-3.81, all P<0.05). Multivariate regression analysis indicated that increased leukocyte count (OR=1.88, 95%CI 1.18-2.97, P<0.01), CRP (OR=1.18, 95%CI 1.06-1.31, P<0.01), ferritin (OR=1.01, 95%CI 1.00-1.00, P<0.01), interleukin (IL)-6 (OR=1.05, 95%CI 1.01-1.08, P=0.012), D-dimer (OR=2.56, 95%CI 1.44-4.56, P<0.01) and decreased CD4+T lymphocyte (OR=0.84, 95%CI 0.73-0.98, P=0.030) were independently associated with the risk of severe SARS-CoV-2 in hospitalized children with Omicron infection. Conclusions: After the withdrawal of NPI, the pediatric inpatients with Omicron infection in Kunming were predominantly children younger than 3 years of age, and mainly manifested as AURTI with relatively low rate of severe SARS-CoV-2 infection and mortality. Elevated leukocyte counts, CRP, ferritin, IL-6, D-dimer, and decreased CD4+T lymphocytes are significant risk factors for developing severe SARS-CoV-2 infection.

Comparison of diagnostic criteria for acute kidney injury in critically ill children / 中华儿科杂志

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ2=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.

Role of DNMT3a in Hydroquinone-Induced Hematopoietic Stem Cell Toxicity / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity.@*METHODS@#Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively.@*RESULTS@#Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001).@*CONCLUSION@#DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.

Silencing DNMT1 Attenuates the Effect of WIF-1 Gene Promoter Methylation on the Biological Behavior of Chronic Myeloid Leukemia K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of silencing DNA methyltransferase 1(DNMT1) to the methylation of the promoter of the tumor suppressor gene wnt-1 (WIF-1) in human chronic myeloid leukemia (CML) cells.@*METHODS@#DNMT1 siRNAi plasmid was constructed and DNMT1 siRNAi was transfected into CML K562 cells. RT-PCR and Western blot were used to detect the expression of DNMT1 gene and related protein, and methylation PCR was used to detect WIF-1 gene promoter methylation level. The trypan blue exclusion and MTT assay were used to detect the cell proliferation, flow cytometry were used to detect the cell apoptosis rate, colony formation assay was used to detect cell colony formation ability. Expression of Wnt/β- catenin and its downstream signaling pathway proteins were detected by Western blot after DNMT1 gene was silenced.@*RESULTS@#The expression level of DNMT1 mRNA and its related protein in the experimental group were significantly lower than those in the control group and negative control group (P<0.05). After 72 hours of successful transfection, the WIF-1 gene in the control group and negative control group were completely methylated, while in the experimental group, the methylation level significantly decreased. The results of MSP showed that the PCR product amplified by the unmethylated WIF-1 primer in the experimental group increased significantly,while by the methylated WIF-1 primer decreased significantly. After 48 h of transfection, the OD value, viable cell number and colony formation of the cells in experimental group were significantly lower than those in the negative control group and the control group (P<0.05). The apoptosis rate of the cells in experimental group was significantly higher than those in the negative control group and control group (P<0.05). The expression levels of β- actin, myc, cyclin D1 and TCF-1 in K562 cells in the experimental group were significantly lower than those in the negative control group and control group (P<0.05).@*CONCLUSION@#Silencing DNMT1 gene can inhibit the proliferation and promote the apoptosis of K562 cells. The mechanism may be related to reverse the hypermethylation level of the WIF-1 gene promoter, thereby inhibit the activity of the Wnt/β- catenin signaling pathway.

Effects of ginsenoside Re on intestinal mucosa of mice with severe acute pancreatitis and its regulation mechanism / 解剖学报

Objective To explore the effect and mechanism of ginsenoside Re on the intestinal mucosa of severe acute pancreatitis (SAP) mice by regulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/ STAT3) pathway. Methods Totally 48 mice were divided into : control group, SAP group, SAP + ginsenoside Re group and SAP + ginsenoside Re + LY2784544 group (n = 12). The mice were intraperitoneally injected with caerulein solution (after fasting for 12 hours, 100 μg/kg, 6 times, injection interval 60 minutes) to establish SAP models. Mice in the SAP+ ginsenoside Re group were intraperitoneally injected with ginsenoside Re (4 mg/kg, 1 time a day for 7 consecutive days). Intraperitoneal injection of 12.7 mg/kg LY2784544 was used to inhibit the JAK2/STAT3 pathway. Pancreatic and intestinal mucosal injury were detected in each group. The wet to dry weight ratio of pancreas, serum amylase and inflammatory factor levels were detected in each group. The intestinal mucosal barrier function was analyzed by detecting the levels of D-lactic acid and fluorescein isothiocyanate dextran (FITC-D). The damage of pancreatic tissue and intestinal mucosa tissue was observed by HE staining. Western blotting was used to detect the levels of apoptotic proteins Bax and Bcl-2 in the intestinal mucosa. The JAK2/STAT3 pathway expression levels in pancreatic tissue and intestinal mucosa tissue were detected by Realtime PCR and Western blotting. Results The pancreatic index, serum amylase, interieukin 6 (IL-6) and tumor necrosis factor a (TNF-a), FITC-D, D-lactic acid, Bax protein levels, JAK2 and STAT3 mRNA and protein levels in the SAP group were significantly higher than those in the control group, while Bcl-2 protein was significantly lower than that in the control group (P<0.05). The Bcl-2 protein of SAP+ginsenoside Re group was significantly higher than that of SAP group, and other indexes were significantly lower than those in SAP group (P<0.05). The Bcl-2 protein of SAP+ginsenoside Re+ LY2784544 group was significantly higher than that of SAP + ginsenoside Re group, and other indexes were significantly lower than those in the SAP+ginsenoside Re group (P<0.05). Conclusion Ginsenoside Re may reduce the pancreatic injury in SAP model mice by inhibiting the JAK/STAT pathway to alleviate the inflammatory response, and may protect the small intestinal mucosal barrier by alleviating pancreatitis and inhibiting the intestinal mucosal JAK/STAT pathway to inhibit cell apoptosis.

Effect of Modified Yuquanwan Combined with Taohong Siwutang on Major Cardiovascular Risk Factors of Patients with Type 2 Diabetes / 中国实验方剂学杂志

Objective:To observe the efficacy of modified Yuquanwan combined with Taohong Siwutang on major cardiovascular risk factors of type 2 diabetes and its effect on inflammatory factors and endothelial function. Method:One hundred and sixty patients were randomly divided into control group (80 cases) and observation group (80 cases) by random number table. The control group was given Tianqi Jiangtang capsule 5 tablets/time,3 times/day. Bothgroups were taken orally. aspirin enteric-coated tablets, 0.1 g/time,1 time/day, insulin for injection or oral antidiabetic, simvastatin tablets, 20 mg/time, 1 time/day, and irbesartan tablets, 150 mg/time, 1 time/day.patients in observation group were added with modified Yuquanwan combined with Taohong Siwutang for 24 weeks, 1 dose/day, and a 48-week follow-up visit were paid. Blood glucose, lipid, blood pressure, fasting plasma glucose (FPG), blood sugar 2 h after meal (2 h PG), glycosylated hemoglobin (HbA1c), systolic (SBP) and diastolic pressure (DBP) were detected for every 8 weeks, and at the 8th, 16th, and 24th week after treatment, up-to-standard HbA1c, LDL-C, SBP, DBP and all of those indexes were recorded, and levels of blood glucose, lipids and blood pressure were compared at different time points. During the treatment and within the 72-week follow-up, cardiovascular events, stroke events, peripheral vascular events and microvascular complications were recorded. And levels of tumor necrosis factor-α (TNF-α), homocysteine (Hcy), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), endothelin (ET-1) and nitric oxide (NO) were detected, and at the 8th, 16th and 24th week after treatment, body mass index (BMI) was recorded. Result:At the 24th week after treatment, the compliance rate of HbA1c in observation group was 81.16%（56/69）, which was higher than 64.71%（44/68） in control group (χ2=4.701, P<0.05), and the compliance rate of SBP was 94.2%（65/69）, which was higher than 82.36%（56/68） in control group (χ2=4.662, P<0.05). At the 16th week and 24th week after treatment, the compliance rate of LDL-C were 79.71%（55/69） and 88.41%（61/69）, which were higher than 63.24%（43/68） and 70.59%（48/68） in control group (χ2=4.5642, χ2=5.108, P<0.05). At the 16th week, the comprehensive compliance rate (blood glucose, blood pressure, blood lipid) in observation group was 59.42%（41/49）, which was higher than 41.18% （28/68） in control group (χ2=4.559, P<0.05). At the 24th week, the comprehensive compliance rate in observation group was 69.57% （48/69）, which was higher than 51.47% （36/68） in control group (χ2=4.695, P<0.05). At the 16th week, the compliance rate of BMI was 60.87% （42/69）, which was higher than 39.71% （27/68）in control group (χ2=6.136, P<0.05). At the 24th week, the compliance rate of BMI was 72.46% （50/69）, which was higher than 52.94% （36/68） in control group (χ2=5.585, P<0.05). At the 16th week after treatment, levels of 2 h PG and HbA1cin observation group were lower than those in control group (P<0.05). At the 24th week after treatment, levels of FPG, 2 hPG, HbA1c, SBP and DBP were lower than those in control group (P<0.05). Levels of TNF-α, Hcy, IL-6, hs-CRP and ET-1 were lower than those in control group (P<0.01), while level of NO was higher than that in control group (P<0.01). During 72 weeks of observation period, the rate of adverse vascular events in observation group was 13.04%(9/69), which was lower than 30.88%(21/68) in control group (χ2=5.957, P<0.05). Conclusion:In addition to the conventional western medicine therapy, modified Yuquanwan combined with Taohong Siwutang can further control the main cardiovascular risk factors of patients with T2DM, improve the endothelial function of T2DM patients, inhibit the expression of pro-inflammatory factors, and reduce the incidence of adverse vascular events.

Therapeutic effect of adjuvant treatment of acupuncture in a period of day from 7:00 am to 9:00 am on non-dipper essential hypertension / 中国针灸

OBJECTIVE@#To compare the infuences on circadian rhythm of blood pressure in the patients with non-dipper essential hypertension between the combined treatment of time acupuncture and western medication and the simple western medication.@*METHODS@#A total of 70 patients with non-dipper essential hypertension were randomized into an acupuncture plus western medication group (35 cases, 2 cases dropped out) and a western medication group (35 cases). In the western medication group, levamlodipine maleate tablets were taken orally, 2.5 mg each time, once daily. In the acupuncture plus western medication group, on the base of the treatment as the western medication group, acupuncture was applied specially in the period of the day from 7:00 am to 9:00 am. The acupoints included Fengchi (GB 20), Zhongwan (CV 12), Tianshu (ST 25), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), etc. Acupuncture was given once daily, 5 treatments a week. The duration of treatment in the two groups was 4 weeks. The clinic blood pressure before and after treatment, 24 h ambulatory blood pressure and the levels of serum melatonin (MT) and 5-serotonin (5-HT) were observed in the two groups.@*RESULTS@#The total effective rate of anti-hypertension was 75.8% (25/33) in the acupuncture plus western medication group, better than 54.3% (19/35) in the western medication group (<0.05). The 24 h average systolic blood pressure, the daytime average systolic blood pressure, the daytime average diastolic pressure, and the nighttime average systolic blood pressure were all reduced after treatment in the two groups (<0.05). The reduction effect of the aforementioned 4 indexes in the acupuncture plus western medication group was much more obvious as compared with the western medication group (<0.05). After treatment, the serum level of MT was increased and 5-HT decreased in the patients of two groups (<0.05). The serum level of MT in the acupuncture plus western medication group was higher than that in the western medication group and the level of 5-HT was lower than the western medication group (<0.05).@*CONCLUSION@#Time acupuncture therapy in the period of the day from 7:00 am to 9:00 am, combined with western medication effectively reduce blood pressure and regulate the levels of serum MT and 5-HT so as to maintain the circadian rhythm of blood pressure in patients with non-dipper essential hypertension. The therapeutic effect of this combined treatment is superior to simple western medication.

Clinical study of phacoemulsification and goniosynechialysis in the treatment of chronic angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the efficacy of phacoemulsification and intraocular lens implantation combined with goniosynechialysis in the treatment of chronic angle-closure glaucoma.<p>METHODS: Thirty-three patients(35 eyes)with primary chronic angle-closure glaucoma and cataract were enrolled in the Department of Ophthalmology, Xi'an First Hospital from May 2018 to November 2018. The best corrected visual acuity, intraocular pressure, central anterior chamber depth, angle-opening distance at 500μm from the scleral spur, trabecular iris angle, angle closure or adhesion were compared between preoperative and postoperative 6mo.<p>RESULTS: The best corrected visual acuity of 34 eyes(97%)was improved after operation. 27 eyes(77%)did not need any intraocular pressure lowering drugs after operation, and the intraocular pressure was kept below 21mmHg. The average value of anterior chamber depth, angle-opening distance at 500μm from the scleral spur and trabecular iris angle(2.04±0.31mm, 0.132±0.033μm, 15.44°±3.10°)before operation were significantly lower than the postoperative mean values(3.26±0.29mm, 0.407±0.038μm, 34.26°±3.60°). The range of angle closure or adhesion decreased after operation, and the difference was statistically significant. <p>CONCLUSION: Phacoemulsification with intraocular lens implantation and goniosynechialysis is an effective way to treat primary chronic angle-closure glaucoma.

Study on the difference of clinical manifestations of dry eye between children and adults / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the difference of dry eyes between children and adults in terms of symptoms and laboratory examinations.<p>METHODS: Patients in 2018-06/2019-02 with the subjective symptoms of dry eye, and served in Xi'an First Hospital, including 52 children clinic cases(52 eyes)and 55 adult patients cases(55 eyes), all the cases were consulted and examined by slit lamp microscope in anterior segment. Both eyes of tear meniscus height(TMH), the first tear film break-up time(BUTf), the average tear film break-up time(BUTave), lipid layer thickness(LLT)and mesangial gland loss rate were measured by a Keratograph 5M non-invasive ocular surface analyzer.<p>RESULTS: In children, patients' TMH(0.15±0.04mm), BUTf(3.22±1.24s), BUTave(4.27±1.67s), and the rate of meibomian gland loss \〖0.00%(0.00%, 5.03%)\〗 were significantly lower than those in the adult group [0.20±0.05mm, 4.36±1.93s, 5.15±1.49s, 9.90%(5.30%, 18.40%), all <i>P</i><0.01]. The LLT in the children was higher than that of the adult group, and the difference was not statistically significant(72.31±22.20nm <i>vs</i> 68.58±21.05nm, <i>P</i>>0.05). Both groups of patients had positive correlation sympathise with BUTf and BUTave, with no correlation between LLT and meibomian gland loss rate in children(<i>r</i>s=-0.23,<i>P</i>=0.10), and adult group patients with negative correlation of LLT and meibomian gland loss rate(<i>r</i>s=-0.28,<i>P</i><0.05).<p>CONCLUSION: Children's dry eyes and adult dry eyes in the symptoms, clinical manifestations and examination are different. The main symptom is the increase in the number of blinks. The inspection is mainly characterized by a short BUT. With the decrease of TMH, the rate of meibomian gland loss is relatively insignificant.

Clinical observation on uterine and breast development in girls with Turner syndrome with the estrogen hormone replacement therapy / 中国实用儿科杂志

OBJECTIVE: To research an appropriate estrogen therapy for in the pubertal development in Turner syndrome(TS)achievedbyestradiolvalerate.METHODS: In 57 TS girls of no spontaneous puberty or puberty arrest,we retrospectively studied pubertalstageanduterinedimensionduringtheestrogenreplacementtherapy.Datafrompatientrecordswascollected,described thepubertaldevelopingprocedure,and compared in groups which grouped by estrogen dosage to detect an appropriate dosage andthatcanleadabetterbreastanduterinedevelopment.RESULTS: The median age at start of puberty induction was 15.00 years,witharangeof11.5-21.0 years.(1)Breast development:Breast development to Tanner stage B2 was achieved in 0.29(0.25-0.33)years,stage B3 in 0.75(0.46,1.08)years,stage B4 in 2.20(0.92,3.08)years and B5 in 3.67(1.71,4.44)years.(2)Uterine development:The uterine volume and length in TS girls before treatment was 0.51(0.14,0.86)ml and 1.89(1.23,2.18)cm. We groupedthepatientsofTannerstageB2 ingroupsofestrogendosage≤0.5 mg/dand>0.5 mg/d and the uterine dimension and weightshowednodifference.Whenthepatientsweregroupedasgroupsofdosage<1.0 mg/d and group of dosage≥1.0 mg/d in stageB3,the uterine indexes in lower dosage group were less than group with larger dosage. When they were grouped as groups ofdosage<1.5 mg/d and ≥1.5 mg/d,the uterine volume 6.96(3.15-11.00)ml in lower dosage group was smaller than that in group withlargerdosage.CONCLUSION: During estrogen treatment in TS girls,normal breast development can be achieved. In a clinical setting,the uterine volume and length under pubertal induction developed properly with the breast stages progressing. when the breastdevelopedtostageB2,the uterine development was more dependable on estrogen. We recommend a low daily beginning estrogendosageuntilstageB2,which can be increased gradually after B2 to speed up the uterine development.

Clinical characteristics and etiological analysis of premature pubarche:A report of 55 cases / 中国实用儿科杂志

OBJECTIVE: To analyse the clinical characteristics,aetiology distribution,and metabolic risk parameters of patients with with premature pubarche(PP). METHODS: A retrospective study was performed in 55 patients affected by PP,who received ACTH stimulation test,and the data were evaluated. Among them 17 cases were detected CYP21 A2 gene,and indicators of lipid metabolism of idiopathic premature adrenarche(IPA,15 cases)and idiopathic premature pubarche(IPP,14 cases)were analyzed. RESULTS: The sample included 55 patients with PP(53 female and 2 male),with a mean pubarche age of(7.2±0.9)years for girls and(7±0.8)years for boys. There was an accelerated bone age(BA/CA ratio>1)(1.20 ± 1.5)in girls. A total of 9 patients were classified as non-classic congenital adrenal hyperplasia(NCCAH,16.4%),15 as IPA(27.3%),14 as IPP(25.4%),16 as HPGA function launch(29.1%)and 1 with exaggerated adrenarche(EA,1.8%). There was no significant difference in the diagnostic rate of NCCAH between ACTH stimulation test and CYP21 A2 gene detection(P=0.596). The sex hormone binding protein(SHBP)of IPA was reduced(P=0.007). CONCLUSION: The etiology of premature pubarche-non-classic congenital adrenal hyperplasia(16.4%)is not uncommon. The ACTH stimulation test is useful for the diagnosis of NCCAH,but the sensitivity is not 100%.

Vitamin D status and determinants among children aged 6 to 23 months in 4 poverty-stricken ethnic minority areas of Yunnan Province / 中华疾病控制杂志

Objective To investigate the vitamin D (VD) level and determinants among young children aged 6 to 23 months in 4 poverty-stricken ethnic minority areas of Yunnan Province. Methods Multistage stratified cluster sampling method was used. 1 255 young children aged 6-23 months from 3 to 4 towns of Jianchuan County, Yiliang County, Mojiang County and Lushui County. Questionnaires on caregivers, physical and serum 25(OH)D measure were achieved. VD level and influencing factors were described and analyzed. Results Overall VD level was 20.6(16.3,25.4) ng/ml. The proportion of VD deficiency, VD insufficiency and VD sufficiency were 7.1%, 39.2% and 53.7% respectively. The risk of VD insufficiency elevated with children’age increasing or no VD supplement (P<0.05). Hani minority can decrease the risk of VD deficiency and insufficiency (all P<0.05). Thus, the risk of VD deficiency and insufficiency in children of female, Lisu or Bai minority, or in children who had no nutritional package supplement would increase (all P<0.05). Conclusions The VD level of children aged 6-23 months in poverty-stricken ethnic minority areas of Yunnan Province was low. VD insufficiency was dominating. The intervention of VD deficiency and insufficiency may focus on the children of female, Lisu minority, Bai minority or older than 18 months. This study highlight that enhancing caregivers’ knowledge of VD nutrition, adding VD and nutritional package supplement actively are beneficial to improve VD nutrition of young children in minority poverty areas of Yunnan.

Research progress and literature review of animal models of osteoporosis / 中国组织工程研究

BACKGROUND: Osteoporosis, known as "a quiet epidemic disease", is an "invisible killer" that impairs the health of the elderly. Fracture as the most dangerous complication of osteoporosis is not only a medical problem, but also a serious social problem. OBJECTIVE: To summarize the selection, establishment methods, characters and evaluation of the animal model of osteoporosis. METHODS: A computed-based search of CBM, WanFang, VIP, CNKI and PubMed databases was conducted for the relevant articles published from January 1986 to December 2016 using the keywords of "osteoporosis, animal models" in English and Chinese, respectively. Finally 39 articles were included for result analysis after reading the title and abstract. RESULTS AND CONCLUSION: Animal experiments play an important role in the studies of osteoporosis, so a desirable animal model should hold similarity, reliability, repeatability, applicability, controllability, efficacy and economy. Osteoporosis is a progressive and long-lasting disease that has different characteristics at different stages. But an animal model only simulates one etiology, one stage, major symptoms and pathophysiological changes, and cannot exhibit the whole pathological changes. The current study suggests that animal species and modeling methods can affect the characters of models, and there is a lack of standards for animal age, feeding methods, modeling time and assessment.

Application of immunoassay techniques in glyphosate residue detection / 中国免疫学杂志

Glyphosate is widely used in agricultural production as an efficient herbicide.At the same time,the residual problems of glyphosate and its potential harm are gradually attracting people′s close attention.In recent years,glyphosate residue detection method has become a research hotspot,fluorescence immunoassay,enzyme-linked immunosorbent assay and immunosensor are developed rapidly by sensitive,specific and fast characteristics.This paper reviews the immunoassay techniques of glyphosate residue and provides a reference for the rapid detection of glyphosate residue.

Effect of Letrozole on the Reproductive Function and Linear Growth in the Early and Mid Puberty Boys / 中山大学学报(医学科学版)

[Objective] To investigate the effect of letrozole on the reproductive function and linear growth in the early and mid pubertal boys.[Methods] 43 early and middle pubertal boy with seriously damaged predict adult height,treated with letrozole 1.5 mg/m2/d Po ((＞)2.5mg/d) were enrolled as treatment group.48 cases of healthy pubertal boys were enrolled as control.Growth parameters,sex hormone profiles,IGF-1,AMH and Inhibin B (INHB) were elevated at the beginning and after letrozole treatment.[Results] At baseline,no significant differences appeared in age,bone age,observation time,height for chronological age,height for bone age,midparental target height,BMI,or testis volume between two groups.After intervention,treatment group of bone age delayed,predict adult height increased,testicular volume increased and BMI increased compared with the control group (P=0.001,0.018,0.002,and 0.027,respectively).The serum FSH,△FSH,LH,△LH,LH/FSH,T,and △T in the treatment groups were much higher (all P＜0.001),while the serum E2 and △ E2 levels were obviously lower than the control group (P=0.043 and P=0.033,respectively).17 cases of control group and 13 cases of treatment group had serum AMH,INHB level tested before and after letrozole treatment.Serum AMH level in the control group appeared with a decreasing trend with the progress of puberty,while the treatment group showed the opposite tendency.And the △ AMH was significant difference between control group and treatment group (P＜0.001).The serum INHB in the two groups increased in varying degrees after the intervention,the INHB level in control group increased more than the treatment group,but the difference was not statistically significant (P=0.517).[Conclusion] Letrozole treatment can elevated levels of serum T with E2 reduce,bone age delay,predict adult height improved,and can obviously promote the secondary sex characters development in adolescent boys.And the longer letrozole treatment time,the more obvious growth effect.As to the reproductive function,letrozole may have inhibitory effect on testis maturity and cannot deny testis sertoli cells function affected with letrozole exposure.

Dyslipidemia and Its Related Factors in Chinese Children and Adolescents with Turner Syndrome / 中山大学学报(医学科学版)

[Objective] To analyze blood lipid and its related factors in Chinese children and adolescents with Turner syndrome.[Methods] The untreated TS patients were divided into two groups according to age (＜11 years old and 11～15 years old) and enrolled two groups of age-matched control girls,blood lipid and the incidence of dyslipidemia were compared between the four groups,the related factors of blood lipid were also analyzed.Moreover,TS patients were divided into two groups according to karyotype,including 45,XO karyotype (55 cases) and other karyotypes (53 cases),blood lipid and the incidence of dyslipidemia in two groups were compared.[Result] Compared to age-matched control girls,TS patients of age 11～15 years group had higher TG levels and higher incidence of hypertriglyceridemia and borderline-hypertriglyceridemia (P＜0.05) and the incidence of borderline-hypercholesterolemia was also significantly higher (P＜0.01).But there were no differences in blood lipid level,incidence of dyslipidemia and the incidence of borerline-dyslipidemia between TS patients who were less than 11 years old and age-matched control girls.Total cholesterol of TS patients was negatively related to bone age (P＜0.05).Triglyceride of TS patients was positively related to waist circumference (P＜0.01).TS patients of 45,XO karyotype had lower TG levels,higher HDL levels and lower incidence of low HDL,borderline-high non-HDL and borderline-hypertriglyceridemia compared with those of other karyotypes (P＜0.05).[Conclusions] Triglyceride in TS patients of age 11-15 years were higher than the control subjects,which may be related to estrogen deficiency and chromosome karyotype.

Effects of Huoxue Huayu Decoction combined with musculus pterygoideus lateralis closure on patients with temporomandibular joint dysfunction syndrome due to wind-cold stasis / 中成药

AIM To investigate the clinical effects of Huoxue Huayu Decoction (Angelicae sinensis Radix,Saposhnikoviae Radix,Schizonepetae Herba,etc.) combined with musculus pterygoideus lateralis closure in managing patients with temporomandibular joint dysfunction syndrome (TMJ) due to wind-cold stasis.METHODS From January 2015 to December 2015,68 cases of patients with TMJ due to wind-cold stasis identified and recruited by the department of stomatology of Hebei Provincial Hospital of Traditional Chinese Medicine were randomly assigned to treatment group and control group,each with 34 cases and given the musculus pterygoideus lateralis closure.But the treatment group was administered with an extra two-week adjuvant therapy of Huoxue Huayu Decoction,and generally one week such medication was taken as a therapeutic course.RESULTS After the intervention,the treatment group presented an overall better performance than the control group in terms of the open limit,NRS score,and the differences were statistically significant (P ＜ 0.05);and the values of CMI,PI,DI (P ＜0.05),in contrast to the not significantly varied values between the groups before the intervention (P ＞ 0.05).The treatment group also displayed its advantage if evaluated by TCM criteria,extent of the mandibular movementabnormalities,facial pain,temporomandibular joint sound or noise,irritability,sleeping difficulty,dark purple lips,tongue scores and wind-cold stasis scores (P ＜ 0.05).And generally a remarkably higher total effective rate was observed in the treatment group,and its difference to the control group was statistically significant (P ＜0.05).CONCLUSION Huoxue Huayu Decoction combined with conventional western medicinal approach in the management of TMJ due to wind-cold stasis can achieve a better therapeutic efficacy.

The Effect of PCDH15 Gene Variations on the Risk of Noise-induced Hearing Loss in a Chinese Population / 生物医学与环境科学（英文）

Noise-induced hearing loss (NIHL) is a complex disease caused by interactions between environmental and genetic factors. This study investigated whether genetic variability in protocadherin related 15 (PCDH15) underlies an increased susceptibility to the development of NIHL in a Chinese population. The results showed that compared with the TT genotype of rs11004085, CT/CC genotypes were associated with an increased risk of NIHL [adjusted odds ratio (OR) = 2.64; 95% confidence interval (CI): 1.14-6.11, P = 0.024]. Additionally, significant interactions between the rs11004085 and rs978842 genetic variations and noise exposure were observed in the high-level exposure groups (P < 0.05). Furthermore, the risk haplotype TAGCC was observed when combined with higher levels of noise exposure (P < 0.05). Thus, our study confirms that genetic variations in PCDH15 modify the susceptibility to NIHL development in humans.