[Lung transplantation for pulmonary alveolar proteinosis: a case report and literature review].

Objective: To observe the efficacy of lung transplantation for pulmonary alveolar proteinosis (PAP) patients and to improve the understanding of the therapy. Methods: The clinical data of a patient with autoimmune PAP treated with sequential homogenous bilateral lung transplantation were described and the literatures were reviewed. Results: This 55-year-old female patient was diagnosed with autoimmune PAP and had been treated with whole lung lavage for 19 times, but only achieved short-term symptomatic relief after each operation. Inhalation of granulocyte macrophage colony stimulating factor occurred allergic reactions. Lung transplantation was performed on February 15, 2022, and a significant improvement in oxygenation and clinical symptoms were observed. The patient remained stable during follow-up. Conclusion: Treatment with lung transplantation is safe and effective for end-stage patients with PAP in the early phase, but the long-term effect remains to be observed.

[The evaluation of dietary salt and potassium intake assessed by two 24-hour urine specimens among 284 primary and secondary school students].

Objective: To estimate the dietary salt and potassium intake by two 24 hour urine salt and potassium excretion in primary and secondary school students. Methods: The boarders from Grade 5 to 6 in a rural primary school and Grade 1 to 3 in a rural middle school in Changde City, Hunan Province were recruited from October to December in 2017. Subjects who had 2 and more urinary incontinence episodes or a history of kidney disease or diarrhea and girls in menstruation were excluded. The final analysis included 284 subjects. Questionnaires on basic demographic information were collected, and height and weight were examined. Two inconsecutive 24-hour urine specimens were collected in weekdays. The differences and consistency between two 24-hour urine were tested and dietary salt and potassium intake were assessed by the average of two 24-hour urine collections. Results: A Total of 284 participants was (12.1±1.5) years old, of which 148 (52.1%) were boys and 36 (12.7%) were overweight. In the first 24-hour urine, the volume [P(50) (P(25), P(75))=670 (513, 868) ml], potassium concentration [P(50) (P(25), P(75))=29 (21, 39) mmol/L] and potassium excretion [P(50) (P(25), P(75))=0.7 (0.6, 1.0) g] were similar to those in the second 24-hour urine [P(5)0 (P(25), P(75)) values were 660 (490, 916) ml, 30 (21,40) mmol/L, and 0.8 (0.6, 1.0) g, respectively]. But the sodium and creatinine concentrations, salt excretion in the first 24-hour urine [P(50) (P(25), P(75)) values were 175 (123, 219) mmol/L, 7.20 (5.15, 10.86) mmol/L and 6.6 (5.0, 8.7) g, respectively] were lower than those in the second 24-hour urine [P(50) (P(25), P(75)) values were 188 (133, 248) mmol/L, 8.66 (5.99, 12.47) mmol/L and 7.3 (5.2, 9.2) g, respectively] (all P values<0.05). The intraclass correlation coefficients between salt and potassium excretions in the two 24-hour urine were 0.534 (95%CI: 0.412-0.631) and 0.478 (95%CI: 0.341-0.587) (P<0.001), respectively. The mean±SD of salt consumed was (7.3±2.5) g (range: 2.3 to 18.8 g) per day by all participants. Overweight children consumed more salt [(8.2±2.6) g/d] than those non-overweight [(7.2±2.4) g/d] (P<0.05). The mean±SD of potassium consumed was (1.1±0.3) g (range: 0.4 to 2.3 g) per day. Boys consumed more potassium [(1.1±0.3) g/d] than girls [(1.0±0.3) g/d] (P<0.05), and overweight children had higher potassium intake [(1.2±0.3) g/d] than those non-overweight [(1.0±0.3) g/d] (P<0.05). A total of 212 participants (74.6%) consumed more salt than the recommended level and all participants had inadequate potassium intake. Conclusion: The problem of excessive salt intake and insufficient potassium intake of rural primary and middle school students was serious.

[The association between body fat distribution and calcaneal bone mineral density in children and adolescents aged 6-16 years in Beijing].

Objective: To understand the association between body fat distribution and calcaneal bone mineral density (BMD) in children and adolescents aged 6-16 years in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method from November 2017 to January 2018. A total of 15 030 students in grade 1 to 4 of primary school, grade 1 of junior and senior middle school were enrolled after excluding subjects who were not able to participate into this study due to trauma or other uncomfortable physical conditions or with missing key values or with diabetes and kidney diseases. Questionnaire survey, body composition and calcaneus bone mineral density were conducted. The relation of fat mass percentage (FMP), trunk to total fat ratio (TrTFR), trunk to limb fat ratio (TrLFR), limb to total fat ratio (LTFR) and viscera to total fat ratio (VTFR) with calcaneus BMD were assessed using the multivariate linear regression models after adjusting for possible confounding effects. The central fat distribution types were divided into 4 groups including type 1: both trunk fat and visceral fat greater than the sex-and age-specific internal P(75); type 2: barely trunk fat greater than P(75); type 3: barely visceral fat greater than P(75); type 4: both trunk fat and visceral fat greater than P(75). The central fat distribution types were included into the model in the form of dummy variables to analyze its relationship with calcaneal BMD. The sex-and age-specific z-scores of fat distribution indicators and BMD were calculated. Results: A total of 15 030 participants aged (11.4±3.3) years (50.2% boys) were involved in the analysis. In both genders, after adjusting for age, height, lean mass index, smoking, drinking, physical activity, milk intake, vitamin D and calcium supplementation, FMP, TrTFR, TrLFR and VTFR were negatively correlated with calcaneal BMD (all P value<0.05), while LTFR was positively associated with calcaneal BMD (all P values<0.05). Compared to the central fat distribution type 1, the regression coefficients (95% CI) of type 2, 3 and 4 were -0.253 (-0.418, -0.087), -0.385 (-0.567, -0.204) and -0.428 (-0.487, -0.369) in boys, respectively; the regression coefficients (95% CI) of type 3 and 4 were -0.158 (-0.301, -0.015) and -0.226 (-0.290, -0.163), respectively. Conclusion: Body fat distribution and central fat distribution in children and adolescents were correlated with calcaneus bone mineral density.

[The association between blood lipids and calcaneus bone mineral density in children and adolescents aged 6-16 years in Beijing].

Objective: To investigate the association between blood lipid and calcaneus bone mineral density (BMD) in children and adolescents aged 6-16 years in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method from November 2017 to January 2018. A total of 14 303 students in grade 1 to 4 of primary school, grade 1 of junior and senior middle school were enrolled after excluding subjects who were not able to participate into this study due to trauma or other uncomfortable physical conditions or with missing key values or with diabetes and kidney diseases. Questionnaire survey, blood lipid and calcaneus BMD were conducted. Multivariate linear regression was applied to quantify the association between calcaneal BMD as a dependent variable and blood lipid level as an independent variable after adjusting for the potential confounding factors. Furthermore, quantile regression was used to analyze the association between blood lipid level and different percentiles (P(25), P(50) and P(75)) of ultrasonic velocity values of bone mineral density, and parallel test was conducted for regression coefficients of different percentiles. Results: A total of 14 303 participants aged (11.4±3.3) years (49.9% boys) were involved in the analysis. The mean age of 14 303 participants was (11.0±3.3) years. 7 142 boys accounted for 49.9%. The mean±SD of calcaneal BMD, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were (1 540.9±33.8) m/s, (3.90±0.76), (2.18±0.62), and (1.40±0.32) mmol/L, respectively. The P(5)0 (P(25), P(75)) of triglyceride (TG) was 0.69 (0.49-0.94) mmol/L. After the adjustment of age, height, smoking, drinking, vitamin D and calcium supplementation, dairy intake, physical activity, FMI, and MMI, a significantly inverse association (P<0.05) between TG level and calcaneus BMD was observed in both genders, which the regression coefficients (95%CI) in boys and girls were -0.064 (-0.085, -0.044) and -0.073 (-0.094, -0.053), respectively. Conclusion: The level of BMD was associated with TG in boys and girls. Therefore, it is important to prevent children from hypertriglyceridemia for the bone health promotion.

iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

[The baseline characteristics of School-based Cardiovascular and Bone Health Promotion Program in Beijing].

Objective: To describe the baseline characteristics of School-based Cardiovascular and Bone Health Promotion Program(SCVBH) in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method. 15 391 students in grade 1 to 4 from primary schools, grade 1 from junior and senior high schools were enrolled in the investigation with an exclusion of students who were not able to participate due to trauma or other uncomfortable physical conditions. The baseline survey including a questionnaire survey, physical examination and blood biochemical test was conducted from September 2017 to January 2018. Obesity, blood pressure, fasting blood glucose, lipid, bone density and grip were evaluated. Results: The prevalence of obesity, hypertension, hyperglycemia (impaired fasting glucose and diabetes), dyslipidemia, lower bone density were 22.3%(3 394), 14.8%(2 248), 10.4%(1 490), 20.3%(2 919) and 2.1%(316) in total respectively, and 27.2%(2 081), 16.3%(1 244), 12.8%(922), 22.2%(1 595) and 1.2%(94) for boys, 17.3%(1 313), 13.3% (1 004), 7.9%(568), 18.4%(1 324) and 2.9%(229) for girls. Boys had higher prevalence of obesity, hypertension, hyperglycemia, and dyslipidemia and lower prevalence of low bone density than girls (all P values <0.05) The mean of body mass index, systolic blood pressure, fasting plasma glucose and grip of boys were significantly higher than that of girls (all P values <0.05).The mean of body mass index, systolic blood pressure, fasting plasma glucose and grip of boys were significantly higher than that of girls (all P values <0.05), the mean of fat mass percentage, total cholesterol, triglyceride, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol of boys were significantly lower than those of girls (all P values <0.05). Conclusion: The prevalence of risk factors of chronic cardiovascular disease was high and the low bone density was appearing in children and adolescents in this study. The promotion of cardiovascular and bone health should be implemented in children and adolescents.

[Characteristics of cardiovascular health of children and adolescents aged 6-16 years in Beijing during 2017-2018].

Objective: To describe the status of cardiovascular health (CVH) of children and adolescents aged 6-16 years in Beijing during 2017-2018. Methods: The school-based Cardiovascular and Bone Health Promotion Program(SCVBH) was conducted from November 2017 to January 2018. 15 391 children and adolescents aged 6-16 years were selected from grade 1 to 4 in 8 primary schools, grade 1 in 21 middle schools and senior grade 1 in one twelve-year education school in Dongcheng, Fangshan, Miyun and Haidian Districts of Beijing by using a cluster sampling method. Seven cardiovascular health indicators, including smoking, body mass index, dietary intake, physical activity, blood pressure, blood glucose, and total cholesterol, were categorized as poor, intermediate, and ideal according to American Heart Association (AHA) criteria. The status of CVH was evaluated according to the criteria of the ideal CVH related behaviors and factors defined by AHA. Results: The proportion of children and adolescents with an ideal smoking, dietary intake and physical activity indicators reached 99.2%(4 982/15 108), 19.7%(2 921/14 805), 17.8% (2 499/14 056), respectively. The proportion of children and adolescents with 7 and 4-5 ideal cardiovascular health indicators was 1.7%(209/12 560) and 65.1%(8 176/12 560). The proportion of children and adolescents with 4-7 ideal cardiovascular health indicators, 2-4 ideal health behavior indicators and 2-3 ideal health factors was significantly higher in urban than that in rural all P values<0.001. The proportion of females with 4-7 ideal cardiovascular health indicators, 2-4 ideal health behavior indicators and 2-3 ideal health factors was significantly higher than that in males (all P values<0.001). Conclusion: The prevalence of ideal cardiovascular health of children and adolescents aged 6-16 years in Beijing during 2017-2018 was very low, particularly for healthy dietary intake and physical activity. Effective public health interventions should be implemented to improve the status of cardiovascular health of them.

[The analysis of the association of sleep with high blood pressure among children and adolescents aged 6-16 years in Beijing].

Objective: To investigate the sleep status in children and adolescents and explore the relationship between the sleep and high blood pressure in them. Methods: Data was from the Schoolbased Cardiovascular and Bone Health Promotiow Program (SCVBH) in Beijing. And 13 471 children and adolescents aged 6-16 years were selected from grades 1 to 4 in 8 primary schools, grade 1 in 21 middle schools and senior grade 1 in one twelve-year education school in Dongcheng, Fangshan, Miyun and Tongzhou Districts of Beijing during 2017-2018 by using a cluster sampling method. Self-reported questionnaires were used to collect the demographic characteristics, lifestyle habits of children and adolescents. The blood pressure was measured by electronic sphygmomanometer. Multiple logistic regression model was used to analyze the association between sleep and hypertension risk. Results: The sleep duration was (8.4±1.1) hours. The prevalence of high blood pressure was 15.0%(2 021/13 471). The incidence of mouth breathing, slobber, snoring, and suffocate was 28.4%(3 823/13 471), 23.6%(3 184/13 471) and 18.7%(2 513/13 471), 2.8%(378/13 471) respectively. After adjusting for age, gender, snoring, mouth breaking, slobber, suffocate, the time for bed and sleep duration, we found that snoring and sleep duration (5.0-6.9 h) were both associated with high blood pressure (OR=1.49, 95%CI:1.32-1.69; OR=1.53, 95%CI: 1.28-1.81). Conclusion: Snoring and sleep duration were positively associated with high blood pressure in this study. Interventions focusing on sleep status should be developed to reduce the incidence of high blood pressure in children and adolescents.

Impact of virtual reality games on psychological well-being and upper limb performance in adults with physical disabilities: A pilot study.

INTRODUCTION: There is limited information regarding the effects of interactive virtual reality (VR) games on psychological and physical well-being among adults with physical disabilities. We aimed to examine the impact of VR games on psychological well-being, upper limb motor function and reaction time in adults with physical disabilities. METHODS: Fifteen participants completed the intervention using Wii VR games in this pilot study. Depressive, Anxiety and Stress Scales (DASS) and Capabilities of Upper Extremity (CUE) questionnaires were used to measure psychological well-being and upper limb motor function respectively. Upper limb reaction time was measured using reaction time test. RESULTS: Results showed that there was a significant difference (p<0.05) in DASS questionnaire and average reaction time score after intervention. CONCLUSION: There is a potential for using interactive VR games as an exercise tool to improve psychological wellbeing and upper limb reaction time among adults with disabilities.

Alternative fecal indicators and their empirical relationships with enteric viruses, Salmonella enterica, and Pseudomonas aeruginosa in surface waters of a tropical urban catchment.

The suitability of traditional microbial indicators (i.e., Escherichia coli and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (Bacteroides thetaiotaomicron, Methanobrevibacter smithii, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (Salmonella spp., Pseudomonas aeruginosa, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore. Salmonella and P. aeruginosa had significant positive correlations with most of the microbial indicators, especially E. coli and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e., B. thetaiotaomicron, M. smithii, and HPyVs) with E. coli and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of M. smithii and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions.

Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

SUMMARY: Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. INTRODUCTION: Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. METHODS: The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. RESULTS: A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. CONCLUSION: The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.

Self-consolidation mechanism of nanostructured Ti5Si3 compact induced by electrical discharge.

Electrical discharge using a capacitance of 450 µF at 7.0 and 8.0 kJ input energies was applied to mechanical alloyed Ti5Si3 powder without applying any external pressure. A solid bulk of nanostructured Ti5Si3 with no compositional deviation was obtained in times as short as 159 µsec by the discharge. During an electrical discharge, the heat generated is the required parameter possibly to melt the Ti5Si3 particles and the pinch force can pressurize the melted powder without allowing the formation of pores. Followed rapid cooling preserved the nanostructure of consolidated Ti5Si3 compact. Three stepped processes during an electrical discharge for the formation of nanostructured Ti5Si3 compact are proposed: (a) a physical breakdown of the surface oxide of Ti5Si3 powder particles, (b) melting and condensation of Ti5Si3 powder by the heat and pinch pressure, respectively, and (c) rapid cooling for the preservation of nanostructure. Complete conversion yielding a single phase Ti5Si3 is primarily dominated by the solid-liquid mechanism.

Predictors of bloodstream infection associated with permanently implantable venous port in solid cancer patients.

BACKGROUND: The purpose of this study is to characterize the risk factors of bloodstream infection (BSI) associated with the use of permanent implantable venous ports (Port-A) in solid cancer patients. METHODS: Solid cancer patients implanted with a Port-A were prospectively observed for the occurrence of Port-A-associated BSI (PABSI), defined as BSI without other identifiable infection foci. A PABSI risk score was developed using the Cox proportional hazards model. RESULTS: A total of 415 patients were registered; 88 PABSI episodes occurred in 58 patients (incidence1.05 per 1000 catheter-days). All but one patient had stage IV cancer. Independent predictors of PABSI occurrence included neutropenia, total parenteral nutrition (TPN), chronic steroid use, invasive procedures, postoperative antibiotics, and preoperative antibiotics. A PABSI risk score with a cut-off value of 0 (sensitivity 88.5%, specificity 64.3%) was defined for stage IV cancer patients as follows: neutropenia, +1.350; TPN, +1.256; chronic steroid use, +1.947; preoperative antibiotics, -0.970; postoperative antibiotics, +0.959; and invasive procedures, +1.098. The median PABSI-free survival was 4.47 months for patients with scores ≥ 0 but not reached for patients with scores <0 (P < 0.0001). CONCLUSION: The PABSI risk score can assist in identifying high-risk solid cancer patients and may assist in designing future preventive strategies.

Enterocin TW21, a novel bacteriocin from dochi-isolated Enterococcus faecium D081821.

AIMS: Purification and characterization of a novel bacteriocin produced by strain Enterococcus faecium D081821. METHODS AND RESULTS: Enterococcus faecium D081821, isolated from the traditional Taiwanese fermented food dochi (fermented black beans), was previously found to produce a bacteriocin against Listeria monocytogenes and some Gram-positive bacteria. This bacteriocin, termed enterocin TW21, was purified from culture supernatant by ammonium sulfate precipitation, Sep-Pak C18 cartridge, ion-exchange and gel filtration chromatography. Mass spectrometry analysis showed the mass of the peptide to be approximately 5300·6 Da. The N-terminal amino acid sequencing yielded a partial sequence NH2 -ATYYGNGVYxNTQK by Edman degradation, and it contains the consensus class IIa bacteriocin motif YGNGV in the N-terminal region. The open reading frame (ORF) encoding the bacteriocin was identified from the draft genome sequence of Enterococcus faecium D081821, and sequence analysis of this peptide indicated that enterocin TW21 is a novel bacteriocin. CONCLUSIONS: Enterococcus faecium D081821 produced a bacteriocin named enterocin TW21, the molecular weight and amino acid sequence both revealed it to be a novel bacteriocin. SIGNIFICANT AND IMPACT OF STUDY: A new member of class IIa bacteriocin was identified. This bacteriocin shows great inhibitory ability against L. monocytogenes and could be applied as a natural food preservative.

Pattern of esophageal eosinophilic infiltration in patients with achalasia and response to Heller myotomy and Dor fundoplication.

Eosinophilic esophagitis (EoE) is now recognized as a common cause of dysphagia. Eosinophilic infiltration of the esophagus has also been associated with other conditions, such as gastroesophageal reflux disease (GERD); however, the incidence, pattern, and clinical significance of eosinophilic infiltration in achalasia are poorly documented. We sought to characterize this histological finding in patients undergoing Heller myotomy (HM) for achalasia. Ninety-six patients undergoing laparoscopic HM for primary achalasia between 1999 and 2008 were identified from a prospective database. Serial mid and distal per-endoscopic esophageal biopsies taken from patients before and after surgery were assessed for the presence of elevated intraepithelial eosinophils (EIEs). Slides from patients with reports suggestive of EIE were reviewed independently by two pathologists, and the highest eosinophil count/high-power field (eos/hpf) was recorded. Dysphagia scores (0 = none to 5 = severe dysphagia), GERD health-related quality of life scores (0 = best to 45 = worst), and 24-hour pH results were compared before and 3 months after surgery. We related the highest eos to the symptoms and response to HM. Data are presented as median (range). Paired t-test and Wilcoxon signed-rank test determined significance, *P < 0.05. Of 96 patients with achalasia, 50 had undergone pre-HM biopsies revealing EIE in 17/50 (34%), with a median of 3 eos/hpf (1-21). Two patients were found to have superimposed esophageal candidiasis. One patient met the pathologic criteria for EoE. Twenty-five of 50 (50%) postoperative biopsies demonstrated a median of 5 eos/hpf (1-62) for a total of 28/50 patients (56%) with EIE in either the preoperative or postoperative period. Four patients (8%) met the pathologic criteria for EoE, and two demonstrated persistent esophageal candidiasis. A decrease in eosinophils was found in 6/28 patients (21%) from 3/hpf (1-21) to 0.5/hpf (0-4). Increase in eosinophils was found in 22/28 patients (79%) from 0.5/hpf (0-8) to 5/hpf (1-62). Preoperative and postoperative dysphagia scores were available in 23 patients. Dysphagia scores improved in 22/23 patients. (3 [0-5] to 0 [0-2])*. Preoperative and postoperative GERD scores were available in 21 patients. GERD scores improved in 20/21 patients (10 [3-38] to 2 [2-14])*. Four of 13 patients (30.7%) demonstrated significant reflux in the postoperative period. No difference in clinical response to HM was detected between patients with preoperative EIE compared with patients with no EIE. No correlation between postoperative esophageal pH and eos was observed. A significant number of patients with achalasia demonstrate esophageal eosinophilic infiltration even at numbers demonstrable in patients with EoE (8% 4/50). While the interaction between achalasia and esophageal eosinophilic infiltration needs further investigation, this does not represent a distinct clinical entity. Thus, the presence of esophageal eosinophils in patients presenting with dysphagia should not preclude further work-up for other etiologies, including achalasia.

Transcript imaging of the development of human T helper cells using oligonucleotide arrays.

Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.

Skeletal muscle-secreted myokine interleukin-6 induces white adipose tissue conversion into beige adipose tissue in myostatin gene knockout pigs.

Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN-/-) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN-/- pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN-/- pigs.

Founding mutations and Alu-mediated recombination in hereditary colon cancer.

By screening members of Finnish families displaying hereditary nonpolyposis colorectal cancer (HNPCC) for predisposing germline mutations in MSH2 and MLH1, we show that two mutations in MLH1 together account for 63% (19/30) of kindreds meeting international diagnostic criteria. Mutation 1, originally detected as a 165-base pair deletion in MLH1 cDNA comprising exon 16, was shown to consist of a 3.5-kilobase genomic deletion most likely resulting from Alu-mediated recombination. Mutation 2 destroys the splice acceptor site of exon 6. A simple diagnostic test based on polymerase chain reaction was designed for both mutations. Our results show that these two ancestral founding mutations account for a majority of Finnish HNPCC kindreds and represent the first report of Alu-mediated recombination causing a prevalent, dominantly inherited predisposition to cancer.

The assessment of efficacy of Diascorea alata for menopausal symptom treatment in Taiwanese women.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of Diascorea alata for treatment of menopausal symptoms. MATERIALS AND METHODS: Two-center, randomized, double-blind, placebo-controlled clinical investigation on 50 menopausal women randomly assigned to two groups, treated for 12 months with either placebo or two sachets daily of Diascorea extracts containing 12 mg/sachet. Primary outcome measures were changes in the Greene Climacteric Scale caused by Diascorea compared with placebo; secondary outcomes were changes in plasma hormone profiles. One-way ANCOVA test was performed to investigate the significance. RESULTS: At 6 months and at the end of treatment, those women who received Diascorea showed general improvement in almost all the clinical symptoms investigated. A significant reduction was noted in the total Greene scores in the Diascorea group assessed at the end of 12 months' treatment (p < 0.01). This phenomenon was more significant for the psychological parameters of anxiety than for other parameters. Apparent improvements were noted in the parameters 'feeling tense or nervous' (p = 0.007), 'insomnia' (p = 0.004), 'excitable' (p = 0.047) and 'musculoskeletal pain' (p = 0.019) among those receiving Diascorea. Diascorea consumption also resulted in positive effects on blood hormone profiles. CONCLUSIONS: Compared with placebo, Diascorea alata improves symptoms, particularly the psychological parameters in menopausal women. Safety monitoring indicated that standardized extracts of Diascorea alata were safe during daily administration over a period of 12 months.

[Immunogenicity and safety of a boost dose of measles, mumps, and rubella combined vaccine for 4-6 years old children].

Objective: To investigate the immunogenicity and safety of a boost dose of measles, mumps, and rubella combined vaccine (MMR) for children 4 to 6 years old. Methods: Children, aged 4 to 6 years old, had vaccinated with 1 dose of measles and rubella combined vaccine(MR) at the age of 8 months and 1 dose of MMR vaccine at 18-months, were recruited in Shanxi, Inner Mongolia, and Beijing, respectively. All children were assigned into 4, 5 and 6-year-old group. The children who met inclusion and exclusion criteria were vaccinated with 1 dose MMR vaccine, and were collected blood samples before vaccination and 35 to 42 d after the vaccination. During the study period, adverse events were collected at 30 min, 1 d, 2 d, 3 d, 4-12 d, and 13 to 42 days after vaccination. Serum was tested for IgG antibodies against measles, mumps and rubella. Geometric mean concentrations (GMC) of measles, mumps, and rubella antibodies were compared among groups by analysis of variance or non-parametric test. Seropositive rates and adverse event rates were compared among groups by Chi-square test or Fisher exact test. Results: A total of 500 children were included in immunogenicity analysis and 535 children were included in safety analysis. The overall adverse event rate was 20.37%, the most of severity for adverse events was mild. The rates of local and systemic adverse events were 0.37% and 20.00%, respectively. Symptoms of local adverse events were redness. The main systemic adverse events were fever, followed by cough, rash and runny nose. Received a dose of MMR vaccine for booster immunization, the seropositive rates of measles antibody, mumps antibody and rubella antibody were above 99% for all 3 age groups, and there was no significant difference between groups. There were significant differences in mumps antibody GMC among groups (P=0.042), but no significant differences in measles and rubella antibodies GMC. Conclusion: The immunogenicity and safety of a boosted MMR vaccintion in children aged 4, 5 and 6 years were all similar good.