[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Clinical effect of superior oblique re-tucking for recurrent or residual compensatory head position].

Objective: To evaluate the effects of re-tucking the superior oblique muscle on recurrent or residual compensatory head position. Methods: A retrospective case series study was conducted. 12 recurrent or residual compensatory head position patients (12 eyes) with congenital superior oblique palsy who underwent superior oblique re-tucking in Tianjin Eye Hospital from March 2015 to February 2021 were included. All patients had a history of superior oblique tucking procedure and showed signs of superior oblique muscle palsy without inferior oblique muscle overaction. During surgery, the Guyton forced duction test is used to evaluate the relaxation of the superior oblique muscle tendon, which affects the re-tucking length of the muscle.Their head position, vertical deviation, eye movement, fovea-disa angle, and Bielschowsky head tilt test were assessed pre-and post-surgery. Statistical analysis was performed using ttest and paired samples Wilcoxon signed rank test. Results: Out of the 12 patients, 8 were male and 4 were female, aged between 2 and 9 years. The initial surgery was done at age 6, with a superior oblique recession length of (7.17±1.03) mm. Recurrent head tilt occurred in 11 patients after (3.82±0.98) months postoperatively, and 1 patient had residual head tilt, with a followup period of six months or more. Ocular motility examination revealed underaction of the superior oblique muscle, positive Bielschowsky's head tilt test, and Guyton forced duction tese indicating relaxation of the paralyzed superior oblique muscle tendon. Scar adhesion was observed at the stop of the superior oblique muscle, as well as the previous sutures. The scar and the sutures around the stop of the superior oblique muscle were released, the mean re-tucking amount was(7.83±1.59)mm. Follow-up at 12 to 18 months postoperatively showed disappearance of compensatory head position, significant improvement in superior oblique muscle lag, normal ocular motility, and no occurrence of Brown syndrome. The results of Bielschowsky head tilt were negative in 9 cases and still positive in 3 cases after superior oblique re-tucking. The primary vertical deviation was 2.5 (2.0, 5.3) prism diopter pre-operatively and 1 (0, 1) prism diopter post-operatively, respectively. The difference was statistically significant (U=6.00, P<0.001). The total amount of FDA in both eyes was (-22.04±5.47)° and (-15.27±6.08)° pre-and post-operatively, respectively. The difference was statistically significant (t=2.87, P=0.009). All 12 patients have normal eye movement after superior oblique re-tucking procedure. All patients had no compensatory head position at last follow-up. Conclusions: Superior oblique re-tucking is suitable for patients with relaxation of the superior oblique muscle tendon and extrocular rotation as the main sign. It can effectively and safely correct the recurrent or residual compensatory head position after re-tucking the superior oblique muscle.

[Advances in high-content screening applications in toxicology research].

The toxicity data of chemicals and drugs increases rapidly, while the animal experimental-based tests method could not meet the current demand of health risk assessment. The high-throughput screening techniques based on in vitro alternative models, integrating with computational methods and information technology to establish toxicity tests strategy promises to address this problem. High-content screening (HCS) technology uses automated microscopy and quantitative image platforms to perform multi-parameter and high-throughput phenotypic analysis via a visualization and quantification manner, and to quickly and effectively assess toxicity and prioritization of chemicals, which promotes the development of in vitro toxicity tests and computational toxicology. HCS technology has been included as an important tool for Toxicity Testing in the 21st Century (Tox21) and chemical risk prioritization. Its applications have been widely utilized in the research field of toxicity tests and chemical toxicity mechanisms. In this review, we describe the development of HCS technology, technical points, toxicological applications, and the future directions and challenges of HCS, so as to provide references for the toxicity testing technology and risk assessment methodology.

[Graded vertical rectus tenotomy for small angle vertical deviation].

Objective: To observe the effectiveness of the graded vertical rectus tenotomy procedure for small-angle vertical deviation. Methods: Retrospective case series study. Twelve patients, including 8 males and 4 females, with an average age of (48±8) years were treated in Tianjin Eye Hospital from January 2017 to December 2019 for diplopia in primary gaze by strabismus surgery. The disease duration was (15±7) months. MRI/CT scan of the orbits and brain was performed to exclude the orbital and craniocerebral diseases. All patients underwent ocular movement examination, with the prism and alternate cover test to detect the deviation angle in primary gaze and the double Maddox test. Based on the results, the posterior segment of the nasal/temporal superior/inferior rectus muscle was operated. The changes of vertical and cyclotorsion deviation angle and the relationship between the vertical rectus graded tenotomy and corrected vertical deviation angle were observed at 1 day after surgery and the last follow-up. The vertical deviation angle was represented by M (Q1, Q3). Friedman test (Bonferroni correction) and linear fitting analysis were used for statistical analysis. Results: The follow-up time of all patients was (7±3) months. The vertical deviation angle in primary gaze before surgery [7.00 (5.25, 7.75) PD] was significantly different from that at 1 day after surgery [1.00 (1.00, 2.00) PD] and the last follow-up [1.50 (1.00, 2.00) PD] (P<0.001, P=0.003). There was no significant difference in postoperative cyclotorsion in all patients. Linear fitting results showed that 50% to 90% vertical rectus tenotomy corrected 5 to 8 PD vertical deviation (R2=0.72; P<0.001). Conclusion: The graded vertical rectus tenotomy procedure can effectively improve the small-angle vertical deviation in primary gaze.

[Application of indocyanine green iris angiography in the evaluation of anterior segment blood supply in different strabismus patients].

Objective: To evaluate the perfusion features of the anterior segment in patients with different types of strabismus. Methods: A cross-sectional study. Sixteen strabismus patients (16 eyes) who received the examination of iris indocyanine green angiography (ICGA) in Tianjin Eye Hospital from November 2016 to December 2021 were enrolled and divided into two groups according to whether they had a history of extraocular muscle injury/rectus muscle surgery. All patients underwent routine ophthalmic examinations. Angiographic images were obtained by the anterior segment camera, and indicators such as arm to iris circulation time, whole iris filling time, regression onset time, and complete regression time were recorded. The independent sample t test or Mann-Whitney U test was used to compare iris perfusion aspects of the two groups, and the Pearson/Spearman correlation tests was used to analyze the correlation of arm to iris circulation time and whole iris filling time with age and course of strabismus. Results: Among the 16 patients, there were 10 males and 6 females. The mean age was (49.2±13.2) years, and the course of strabismus ranged from 2 to 31 months. There were 7 patients in the group of without extraocualr muscle injury and 9 patients in the extraocular muscle injury/surgery group. There was no significant difference in age and course of strabismus between the two groups (both P>0.05). The arm to iris circulation time [M (Q1, Q3)] of the group without extraocular muscle injury and the group with extraocular muscle injury/surgery were 18 (18, 21) and 22 (20, 24) s, respectively. The average whole iris filling time was (13.86±1.95) and (12.22±3.60) s, respectively. There was no statistical significance between the two groups (both P>0.05). Correlation analysis showed that arm to iris circulation time was not correlated with age and course of strabismus (r=-0.033, -0.079; both P>0.05). And the whole iris filling time was not correlated with age and course of disease (r=0.057, -0.119; both P>0.05). The matrix scatter plots showed that in the group of extraocular muscle injury/surgery, there were three patients who were older than the average (49.2 years) and above the median of arm to iris circulation time (20 s) (two cases with the vertical muscle involved), meanwhile, there were three patients (all with the vertical muscle involved) whose course of strabismus was longer than 6 months and above the median of arm to iris circulation time, which were more than those in the group of without extraocular muscle injury (1 case, respectively). Conclusions: ICGA in patients with strabismus show that a history of injury to the extraocular muscle or surgical treatment beyond 2 months had no effect on iris perfusion. Age and course have no correlation with iris reperfusion. The vertical muscle involvement has more effects on the blood supply to the anterior segment.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆.

BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

[Screening of biomarkers in exhaled breath of mice exposed to benzene].

Objective: To screen the biomarkers in the exhaled breath of mice exposed to benzene by using exhaled breath online analysis system. Methods: Thirty 8-week-old male C57BL/6 mice were randomly divided into six groups (0, 3, 32, 324, 648, and 1 296 mg/m3) and treated with benzene vapour for 28 days. At the end of the exposure, the peripheral blood cell counts and blood glutathione (GSH) were detected. The content of malondialdehyde (MDA) in HL60 cells treated by mice plasma was examined. Exhaled breath data from mice were collected by Secondary electrospray ionization source high resolution mass spectrometry (SESI-HRMS). Targeted analysis underlying benzene metabolites and oxidative stress metabolites was performed to screen the biomarkers in exhaled breath. Results: After benzene exposure, the number of peripheral blood cells was decreased in different degrees, particularly in the white blood cells (WBC) number. The WBC in 32 and 324 mg/m3 groups was declined by 27.76% and 52.87%, respectively compared to that in control group (P<0.05). Meanwhile, compared with the control group, the GSH content of peripheral blood cells from 324 mg/m3 group decreased by 13.16% (P<0.05). In addition, MDA content was increased by 18.11% in HL60 cells treated with plasma from 324 mg/m3 group mice (P<0.05). The phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in the exhaled gas of mice could be used as biomarkers for benzene exposure (R2>0.8, P<0.001). The peak intensity of five small molecular metabolites related to oxidative stress (ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA) increased with the increase of benzene concentration (P<0.05), which was negatively correlated with WBC decline (P<0.001), suggesting that these molecules mignt be used as biomarkers of benzene-induced toxicity. Conclusions: Phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in exhaled breath of mice could be used as biomarkers for benzene exposure; ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA might be used as markers of benzene-induced toxicity.

[Clinical observation of anterior tucking of the superior oblique tendon for correction of excyclotropia in adults].

Objective: To investigate the clinical effect of anterior 1/3 superior oblique tendon tucking in acquired symptomatic excyclotropia adults. Methods: Retrospective case series. Seven patients (7 eyes) with acquired symptomatic excyclotropia who underwent an anterior 1/3 superior oblique tendon tuck procedure in Tianjin Eye Hospital from January 2019 to December 2019 were included. There were 5 male patients and 2 female patients, with an average age of (49±12) years old. All the patients had a history of a closed head injury. There was torsional diplopia in primary position, and eye movement examination showed paralysis of the superior oblique muscle in the affected eye, without obvious hyperactivity of the inferior oblique muscle. The anterior 1/3 tendon of the superior oblique muscle was tucked during surgery according to the relaxation of the superior oblique tendon in the forced duction test. The paired-sample nonparametric rank sum test was used to analyze the preoperative and postoperative (at 1 day after surgery and the last follow-up) excyclotropia angle. Results: The mean tuck amount was (7.7±1.8) mm (range, 6.0 to 10.0 mm). During operation, patients complained that excyclotropia improved markedly. The excyclotropia angle with the double Maddox rod test improved significantly from preoperative 10° (8°, 15°) to 2° (0°, 3°) at 1 day (Z=-2.379; P<0.05) and 2° (2°, 5°) at the last follow-up (Z=-2.375; P<0.05). The follow-up period was (112+38) days. All patients had no complaints of excyclotropia at the last follow-up. Conclusions: The anterior 1/3 superior oblique tendon tucking can effectively improve clinical symptoms in the primary position in adults with acquired excyclotropia and diplopia. The short-term postoperative results seem to be stable, without significant regression. (Chin J Ophthalmol, 2021, 57: 685-688).

[Application of mass spectrometry combined with next generation sequencing in the diagnosis of neonatal inherited metabolic diseases].

Objective: To explore the application value of mass spectrometry (MS) combined with next generation sequencing (NGS) in diagnosing neonatal inherited metabolic diseases (IMD). Methods: The clinical information, metabolites in blood and urine, and gene sequencing results of 19 neonates with IMD coming from the Department of Neonatology of Jiangxi Provincial Children's Hospital from March 2017 to September 2019 were analyzed retrospectively. The metabolites in blood were detected by liquid chromatography tandem mass spectrometry and urine were detected by gas chromatography-mass spectrometry respectively.Meanwhile, the whole bloods were dectected by neonatal genetic disease panel based on NGS. Results: Twelve neonates had the same results between MS and NGS among the 19, 2 had different results from MS to NGS, and 4 had no disease indication by MS but were diagnosed by NGS whose clinical phenotype were partially consistent with NGS results. One of them who did not carry out MS was considered as the diagnosis of IMD because of the detection of gene, and was followed up on this basis. Conclusion: MS could diagnose IMD relatively quickly to guide clinical treatment, and while NGS could verify the results of MS detection. Combination of MS and NGS would understand the cause of disease on genetic level, so as to guide further treatment and genetic consultation.

[Relationship between systolic blood pressure load and sleep stability in patients with essential hypertension].

Objective: To explore the relationship between blood pressure load and sleep stability in hypertensive patients by cardiopulmonary coupling monitoring (CPC) and 24-hour ambulatory blood pressure monitoring. Methods: One hundred and fifty-five patients with essential hypertension were divided into high load group and low load group according to whether the blood pressure load was higher than 50%. The relationship between sleep stability and systolic blood pressure load was analyzed by logistic regression. Results: After adjusting for sex, age and body mass index (BMI), logistic regression analysis showed that stable sleep was the protective factor (OR=0.736,P=0.047) for the decrease of nocturnal blood pressure load, and unstable sleep was the risk factor for increasing day time blood pressure load (OR=1.336, P=0.037) in patients with hypertension. Conclusions: The effect of sleep stability on blood pressure load is different between day and night. Stable sleep is the protective factor of nocturnal systolic blood pressure load decrease, and unstable sleep is the harmful factor of daytime systolic blood pressure load increase. Increasing sleep stability helps to reduce systolic blood pressure load.

[Hazards and challenges from global e-waste pollution].

With the acceleration of global urbanization, the human health impact from growing e-waste has become increasingly serious. Several regions of China are heavily polluted by e-waste, which has led to adverse health outcomes. Critical issues need to be addressed, including how to identify adverse health effects and conduct the health risk assessment for prevention. Recently, globally governmental-based regulations and enforcement of legislation regarding the export, recycling and disposal process of e-waste have made certain achievements. In this issue, we published several articles, which summarized and analyzed the relationship between e-waste pollution and adverse health effects from various aspects such as exposure analysis, adverse health outcomes, mechanisms and risk assessment. These findings could provide basic data and guidelines for health risk assessment and disease prevention of e-waste pollution in China.

[Advances in research of synergistic divergence].

Synergistic divergence is a rare condition characterized by complete absence of adduction that is associated with simultaneous abduction of the affected eye on attempted adduction. This causes the affected eye to move further into abduction on gaze to the normal side and results in extreme divergence of both eyes. It is sometimes referred to as exotropic Duane syndrome with synergistic divergence (type 4 Duane syndrome) or congenital fibrosis syndrome with synergistic divergence. Diseases combined with synergistic divergence fall within the category of congenital cranial dysinnervation disorders (CCDDs). The ocular associations reported with synergistic divergence are uncommon and include Horner syndrome, ocular albinism, foveal hypoplasia, Goldenhar syndrome and pupillary abnormalities. MRI and electro-oculographic study suggested that this is the result of CCDDs. Various surgical techniques have been tried in individual cases including large recession of the lateral rectus muscle, lateral rectus muscle extirpation, large resection of the medial rectus (MR) muscle, weakening procedures of the oblique muscles, combination of lateral rectus orbital wall fixation with MR resection, but further investigations with large-scale samples are needed. Recent research advances in the definition, etiology, and treatment of synergistic divergence are reviewed in this article. (Chin J Ophthalmol, 2019, 55:63-67).

[A clinical retrospective study on 160 cases of multiple umbilical cord around the neck].

Objective: To compare the neonatal and maternal outcomes between the patients with umbilical cord around the neck (≥3 loops) and with (1 or 2 loops). Methods: A retrospective analysis was conducted on the clinical data of 160 cases with multiple umbilical cord around the neck (≥3 loops) in the Department of Obstetrics, Women's Hospital School of Medicine Zhejiang University between January 2014 and April 2017.For each case, two control women who gave birth at the same day with vertex position and singletons were selected.The neonatal and maternal outcomes were compared. Result: (1) The incidence of cord multiple cord around the neck (≥3 loops) in our hospital was 0.45%. (2) Comparison between groups: The rate of abnormal fetal movement or abnormal cardiotocography in case group was higher than those of the control group, (33.13%, 53/160) vs (8.13%, 26/320), with significant difference, P=0.000.The Umbilical Artery Systolic/diastolic (S/D) ratio of the case group was lower than that of the control group, 2.00(0.40) vs 2.14(0.40), with significant difference, P=0.000.The cesarean section rate of the case group was higher than that of the control group, (81.25%, 130/160) vs (7.50%, 24/320), and the difference was statistically significant, P=0.000.Birth Weight of the case group was lower than that of the control group, (3 143±367) g vs (3 323±349) g, with significant difference, P=0.000.(3) Comparison between subgroups: The rate of lateral incision or obstetrical forceps in the subgroup of virginal delivery among the case group (n=30) was higher than that in the control group (n=296), (30.00%, 9/30) vs (12.50%, 37/296), with significant difference, P=0.009.While, the Apgar score at 1 and 5 min of the virginal delivery case in the case group were lower than that in the control group, 10(1.25) vs 10(0) and 10(0) vs 10(0), there were both significant difference, P=0.000, 0.012, respectively.The rate of meconium-stained amniotic fluid, 1 min Apgar score of ≤7 and NICU admission were showed no significance, all P>0.05.(4) After Logistic regression, the four factors most closely associated with meconium-stained amniotic fluid in patients with multiple cord around the neck (≥3 loops), which were gestational age ≥39 weeks, Birth Weight >3 500 g, umbilical cord around the neck ≥4 loops, and trial of labor. Conclusion: (1) Multiple umbilical cord around the neck (≥3 loops) had a more positive treatment. Vaginal delivery led to lower APGAR score, but didn't increase the incidence of neonatal asphyxia.(2) Independent risk factors for meconium-stained amniotic fluid were gestational age ≥39 weeks, Birth Weight>3 500 g, umbilical cord around the neck ≥4 loops and trial of labor.

[Phenotype and mechanism of inducible ppp2r1a knockout mouse model].

Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a(flox/flox) mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a(flox/flox) and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes. Results: After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively (P<0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively (P<0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice (P<0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U/L and (69.40±9.55) U/L. The above results indicated that ppp2r1a knockout caused liver damage. Blood sugar level of homozygous mice was lower than in wild type mice (P<0.05), with values of (4.20±1.99) mmol/L and (8.88±0.65) mmol/L respectively. Plasma total cholesterol (TC), high density lipoprotein (HDL) and ß-hydroxybutyric acid (ß-HB) level of homozygous mice were higher than those of wild type mice (P<0.05). The values of TC, HDL and ß-HB in homozygous mice were (3.12±0.39), (1.53±0.38) and (2.49±0.89) mmol/L. The corresponding values in wild type mice were (1.69±0.92), (0.78±0.50) and (0.45±0.30) mmol/L respectively. The above results indicated that ppp2r1a loss interfered glucose and cholesterol metabolism. In addition, we also found that the white blood cell count (WBC) and lymphocyte count (LYM) of homozygous mice were lower than in wild type mice (P<0.05). The values of WBC and LYM in homozygous mice were (1.88±0.89)×10(9)/L and (0.92±0.37)×10(9)/L respectively. The corresponding values in wild type mice were (3.91±0.80)×10(9)/L and (2.74±0.52)×10(9)/L respectively. The mRNA levels of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) of homozygous were lower than wild type mice (P<0.05). The fold change of G6P and PEPCK in homozygous mice was 0.46±0.11 and 0.72±0.07 respectively. The corresponding fold change in wild type mice was 1.02±0.07 and 1.02±0.06 respectively. Conclusion: Whole body ppp2r1a is essential for the survival of adult mice, due to the important role in maintaining the metabolism of glucose and cholesterol of liver.

[Follow-up study of 116 cases of transjugular intrahepatic portosystemic shunt in the treatment of cirrhotic portal hypertension].

Objective: To investigate the incidence rate of transjugular intrahepatic portosystemic shunt (TIPS) complications in the treatment of cirrhotic portal hypertension, and analyze the cause of complication to management methods. Methods: Data of 116 patients obtained from Zhongnan Hospital of Wuhan University were retrospectively analyzed. Portal venous pressure, routine blood test, coagulation test, liver and kidney function test, ammonia blood test, imaging and endoscopy reports were collected before and after procedure. The incidence rate of hepatic encephalopathy, gastrointestinal bleeding, ascites and shunt dysfunctions were observed. Data were expressed as mean ± Standard deviation and analyzed by t-test. A chi-squared test was used for comparison between categorical variables. Results: The success rate of TIPS operation was 97.41% (113/116). Two patients underwent prompt TIPS procedure due to active bleeding. Bleeding was successfully stopped. Portal venous pressure of 113 patients decreased from (42.73 ± 7.64) cmH(2)O to (24.92 ± 7.60) cmH(2)O, and the difference was statistically significant (P < 0.01). Twenty cases were of hepatic encephalopathy. Preoperative level of Child-pugh class C patients was more susceptible to hepatic encephalopathy within 3 months after procedure than class A and B. After TIPS procedure, there were 22 cases of gastrointestinal bleeding, 18 cases of shunt dysfunctions and 26 cases of disease related death. Conclusion: Rational patient selection strategies can effectively reduce portal venous pressure, incidence of hepatic encephalopathy, improve mid-and long-term therapeutic effects, and provide opportunities for liver transplantation.

[A prospective control study of Saccharomyces boulardii in prevention of antibiotic-associated diarrhea in the older inpatients].

Objective: To study the value of Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in older inpatients. Methods: A total of 163 older patients who were treated with wide-spectrum antibiotics at least three days during January 2014 to December 2015 were randomly divided into control and study group. In study group, 81 patients were administrated with oral Saccharomyces boulardii 500 mg twice a day for 21 days. The control group was of no intervention. Morbidity rate of antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea, frequency and duration of diarrhea were recorded. Results: The incidence of antibiotic-associated diarrhea in study group was significantly lower than that in control group [14.8%(12/81) vs 28.0%(23/82), P<0.05], whereas no difference was seen in the incidence of Clostridium difficile-associated diarrhea [3.7%(3/81) vs 4.9%(4/82), P>0.05] in two groups. The frequency and duration of diarrhea in the study group were significantly lower and shorter than those in control group[(4.3±1.7) times/day vs (6.9±2.0) times/day; (3.0±1.1) days vs (5.7±1.8) days, both P<0.01]. Conclusion:Saccharomyces boulardii may reduce the incidence of antibiotic-associated diarrhea therefore improving the symptom of diarrhea in older inpatients.

[The relationship between histone H3Ser10 phosphorylation and DNA damage in periphery blood lymphocytes of polycyclic aromatic hydrocarbons exposed workers].

Objective: To investigate the effect of polycyclic aromatic hydrocarbons (PAHs) exposure on the level of histone H3Ser10 phosphorylation (p-H3S10) and DNA damage degree in peripheral blood lymphocyte (PBLCs). Method: 75 coke oven workers from Benxi steel plant in Liaoning Province of China (PAHs-exposed group) and local 50 hot rolling workers (control group) were recruited in this study with age, working years, labor intensity and high temperature for matching factors using cluster sampling method in 2014. HPLC-fluorescence was performed to determine the level of urinary 1-hydroxypyrene (1-OHP), DNA damage and specific histone modification were measured in PBLCs of the subjects through comet assay and ELISA assay, respectively. Linear regression model analysis was used to analyze the differences among PAHs exposure, DNA damage and p-H3S10 level in two groups. The Mediation analysis was used to analyze the regulated relationships between urinary 1-OHP, DNA damage and histone modification through the bootstrap method. Results: Age of the control and the exposed group were (45.32±8.32) and (43.87±5.67) years old (P=0.284). The concentration of urinary 1-OHP, OTM value, Tail DNA% and p-H3S10 level in exposure group were higher than that in control group, while the M (P(5)-P(95)) of p-H3S10 levels in control and exposed group were 2.21 (0.68-4.71), 4.54 (1.85-23.91) (P<0.001). The degree p-H3S10 level was increased after the subgroups which were (2.59±1.19)%, (3.24±2.81)%, (5.55±3.25)%, (8.77±7.84)%, respectively, divided by quantitated 1-OHP concentration as P(0)-P(25), P(26)-P(50), P(51)-P(75) and P(76)-P(100) (P<0.001). We also found the correlations between urinary 1-OHP and p-H3S10 level or OTM value or Tail DNA%, ß (95%CI) were 0.264 (0.167-0.360), 0.500 (0.299-0.702), and 0.510 (0.384-0.671), respectively (P<0.001). Similar result was also observed between p-H3S10 level and OTM value or Tail DNA%, ß (95%CI) were 0.149 (0.073-0.226) and 0.220 (0.132-0.308) (P<0.001). Moreover, the mediation effect value of DNA damage on PAHs induced p-H3S10 alteration was 0.054(P=0.040). Conclusion: The results suggested that PAHs exposure could induce DNA damage and an increase in histone H3Ser10 phosphorylation in PBLCs. Particularly, the alteration of H3S10 phosphorylation may play an important role in regulating cell DNA damage repair.

[Value of DNA content in comet tail in predicting changes in blood cell counts in workers exposed to benzene].

Objective: To investigate the value of DNA content in comet tail (TailDNA) in predicting the changes in peripheral blood cell counts in workers exposed to benzene. Methods: In 2011, cluster sampling was used to select 150 male workers exposed to benzene in a petrochemical factory. Cubital venous blood and urine samples were collected for routine blood rest, comet assay, and measurement of s-phenylmercapturic acid (SPMA) and urine creatinine. The population was divided into groups according to urinary SPMA or TailDNA, and routine blood test results within 3 years were collected to analyze the changes in blood cell counts. Results: The low-SPMA group had significantly higher white blood cell and neutrophilcounts in all years than the high-SPMA group (P<0.05) . The low-Tail DNA group had a significant increase in platelet count from 2012 to 2014 (P<0.05) , while the high-Tail DNA group had no significant change (P>0.05) . During the 4-year period, the high-TailDNA group had a significantly lower red blood cell count than the low-TailDNA group (P<0.05) . The high-TailDNA group showed a gradual reduction in white blood cell count over time (ß=-0.113, P<0.05) , and the low-TailDNA group showed no trend of the reduction in white blood cell count (P>0.05) . Conclusion: TailDNA can be used to predict the changes in blood cell counts in workers exposed to benzene.

Desmoglein 4 diversity and correlation analysis with coat color in goat.

Desmoglein 4 (DSG4) has an important role in the development of wool traits in domestic animals. The full-length DSG4 gene, which contains 3918 bp, a complete open-reading-frame, and encodes a 1040-amino acid protein, was amplified from Liaoning cashmere goat. The sequence was compared with that of DSG4 from other animals and the results show that the DSG4 coding region is consistent with interspecies conservation. Thirteen single-nucleotide polymorphisms (SNPs) were identified in a highly variable region of DSG4, and one SNP (M-1, G>T) was significantly correlated with white and black coat color in goat. Haplotype distribution of the highly variable region of DSG4 was assessed in 179 individuals from seven goat breeds to investigate its association with coat color and its differentiation among populations. However, the lack of a signature result indicates DGS4 haplotypes related with the color of goat coat.

[Electrophysiological subtypes and long term prognosis of Guillain-Barré syndrome].

OBJECTIVE: To assess the electrophysiological subtypes of Guillain-Barré syndrome (GBS) acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), and long-term prognosis in northeastern China. METHODS: One hundred and eighteen patients with GBS were recruited between 2010 and 2012 and retrospectively reviewed. RESULTS: According to electrodiagnostic criteria, patients were classified as AMAN (49, 46.7%) or AIDP (39, 37.1%), or were unclassified (17, 16.2%). Between the AMAN and AIDP groups, age, sex, and clinical disability did not differ significantly, but the AMAN patients more frequently had preceding gastroenteritis. By 4 weeks after onset, 24.5% of the AMAN patients (12) and 33.3% of the AIDP patients (13) had regained the ability to walk; by 1 year, 77.6% of the AMAN patients (38) and 79.5% of the AIDP patients (31) could walk. Recovery was generally favorable in both subtypes. Immunotherapy was effective in patients with either AIDP or AMAN, and glucocorticoids and immunoglobulin treatment could achieve similar effect. CONCLUSIONS: AMAN and AIDP are the main subtypes of GBS in northeastern China. The prognosis of patients with AMAN is similar to that of patients with AIDP. Different immunotherapies have similar effect on long term prognosis.