Invasive pulmonary aspergillosis among patients with severe community-acquired pneumonia and influenza in ICUs: a retrospective cohort study.

RATIONALE: The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. OBJECTIVES: To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). METHODS: We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. MEASUREMENTS AND MAIN RESULTS: Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. CONCLUSIONS: An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

Arrayed Pt Single Atoms via Phosphotungstic Acids Intercalated in Silicate Nanochannels for Efficient Hydrogen Evolution Reactions.

Single-atom catalysts, known for their high activity, have garnered significant interest. Currently, single-atom catalysts were prepared mainly on 2D substrates with random distribution. Here, we report a strategy for preparing arrayed single Pt (Pt1) atoms, which are templated through coordination with phosphotungstic acids (PTA) intercalated inside hexagonally packed silicate nanochannels for a high single Pt-atom loading of ca. 3.0 wt %. X-ray absorption spectroscopy, high-angle annular dark-field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy, in conjunction with the density-functional theory calculation, collectively indicate that the Pt single atoms are stabilized via a four-oxygen coordination on the PTA within the nanochannels' inner walls. The critical reduction in the Pt-adsorption energy to nearly the cohesive energy of Pt clustering is attributed to the interaction between PTA and the silicate substrate. Consequently, the transition from single-atom dispersion to clustering of Pt atoms can be controlled by adjusting the number density of PTA intercalated within the silicate nanochannels, specifically when the number ratio of Pt atoms to PTA changes from 3.7 to 18. The 3D organized Pt1-PTA pairs, facilitated by the arrayed silicate nanochannels, demonstrate high and stable efficiency with a hydrogen production rate of ca. 300 mmol/h/gPt─approximately twice that of the best-reported Pt efficiency in polyoxometalate-based photocatalytic systems.

Effect of oil extraction methods on walnut oil quality characteristics and the functional properties of walnut protein isolate.

Walnut oils were obtained by supercritical carbon dioxide extraction (SCB), cold-pressing (CP), hexane extraction (HE), and subcritical butane extraction (SBE), and walnut protein isolates (WPI) from the walnut cakes were performed. The results indicate that SCB has the highest oil yield for walnut oil, which was 62.72%, and the total content of trace nutrients (total tocopherols, total phytosterols, and total phenolic compounds) in SCB-walnut oil was also the highest at 2186.75 mg/kg, approximately 1.05 times higher than CP-walnut oil and 1.21 times higher than SBE-walnut oil. Meanwhile, the treatment of WPI with SCB results in a decrease in ß-Sheet and α-Helix structures and an increase in ß-Turn and Random coil structures. Thereby increasing its oil-holding capacity (OHC) and solubility by approximately 1.16 times and 1.27 times compared to CP, respectively. Interestingly, SCB as a green oil production technology, also has good prospects for retaining WPI functionality characteristics.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

A reporter gene assays for bioactivity determination of human chorinonic gonadotropin / 药学学报

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum / 药学学报

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Effect of Acupuncture on Endometrial Blood Flow in Women Undergoing in vitro Fertilization Embryo Transfer: A Single Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET).@*METHODS@#Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births.@*RESULTS@#Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05).@*CONCLUSIONS@#Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).

Polygenic Risk Score, Environmental Tobacco Smoke, and Risk of Lung Adenocarcinoma in Never-Smoking Women in Taiwan.

Importance: Estimating absolute risk of lung cancer for never-smoking individuals is important to inform lung cancer screening programs. Objectives: To integrate data on environmental tobacco smoke (ETS), a known lung cancer risk factor, with a polygenic risk score (PRS) that captures overall genetic susceptibility, to estimate the absolute risk of lung adenocarcinoma (LUAD) among never-smokers in Taiwan. Design, Setting, and Participants: The analyses were conducted in never-smoking women in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma, a case-control study. Participants were recruited between September 17, 2002, and March 30, 2011. Data analysis was performed from January 17 to July 15, 2022. Exposures: A PRS was derived using 25 genetic variants that achieved genome-wide significance (P < 5 × 10-8) in a recent genome-wide association study, and ETS was defined as never exposed, exposed at home or at work, and exposed at home and at work. Main Outcomes and Measures: The Individualized Coherent Absolute Risk Estimator software was used to estimate the lifetime absolute risk of LUAD in never-smoking women aged 40 years over a projected 40-year span among the controls by using the relative risk estimates for the PRS and ETS exposures, as well as age-specific lung cancer incidence rates for never-smokers in Taiwan. Likelihood ratio tests were conducted to assess an additive interaction between the PRS and ETS exposure. Results: Data were obtained on 1024 women with LUAD (mean [SD] age, 59.6 [11.4] years, 47.9% ever exposed to ETS at home, and 19.5% ever exposed to ETS at work) and 1024 controls (mean [SD] age, 58.9 [11.0] years, 37.0% ever exposed to ETS at home, and 14.3% ever exposed to ETS at work). The overall average lifetime 40-year absolute risk of LUAD estimated using PRS alone was 2.5% (range, 0.6%-10.3%) among women never exposed to ETS. When integrating both ETS and PRS data, the estimated absolute risk was 3.7% (range, 0.6%-14.5%) for women exposed to ETS at home or work and 5.3% (range, 1.2%-12.1%) for women exposed to ETS at home and work. A super-additive interaction between ETS and the PRS (P = 6.5 × 10-4 for interaction) was identified. Conclusions and Relevance: This study found differences in absolute risk of LUAD attributed to genetic susceptibility according to levels of ETS exposure in never-smoking women. Future studies are warranted to integrate these findings in expanded risk models for LUAD.

Vancomycin associated acute kidney injury in patients with infectious endocarditis: a large retrospective cohort study.

Background: Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Methods: Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. Results: In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. Conclusion: The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.

Low-Dose Computed Tomography Screening in Relatives With a Family History of Lung Cancer.

INTRODUCTION: The role of a family history of lung cancer (LCFH) in screening using low-dose computed tomography (LDCT) has not been prospectively investigated with long-term follow-up. METHODS: A multicenter prospective study with up to three rounds of annual LDCT screening was conducted to determine the detection rate of lung cancer (LC) in asymptomatic first- or second-degree relatives of LCFH. RESULTS: From 2007 to 2011, there were 1102 participants enrolled, including 805 and 297 from simplex and multiplex families (MFs), respectively (54.2% women and 70.0% never-smokers). The last follow-up date was May 5, 2021. The overall LC detection rate was 4.5% (50 of 1102). The detection rate in MF was 9.4% (19 of 202) and 4.4% (4 of 91) in never-smokers and in those who smoked, respectively. The corresponding rates for simplex families were 3.7% (21 of 569) and 2.7% (6 of 223), respectively. Of these, 68.0% and 22.0% of cases with stage I and IV diseases, respectively. LC diagnoses within a 3-year interval from the initial screening tend to be younger, have a higher detection rate, and have stage I disease; thereafter, more stage III-IV disease and 66.7% (16 of 24) with negative or semipositive nodules in initial computed tomography scans. Within the 6-year interval, only maternal (modified rate ratio = 4.46, 95% confidence interval: 2.32-8.56) or maternal relative history of LC (modified rate ratio = 5.41, 95% confidence interval: 2.84-10.30) increased the risk of LC. CONCLUSIONS: LCFH is a risk factor for LC and is increased with MF history, among never-smokers, younger adults, and those with maternal relatives with LC. Randomized controlled trials are needed to confirm the mortality benefit of LDCT screening in those with LCFH.

Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study.

BACKGROUND: Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. MATERIAL AND METHODS: New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. RESULTS: Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50-3092.00] mL/day vs. 1069.00 [722.00-1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS: In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.

Appraisal of lung cancer survival in patients with end-stage renal disease.

Introduction: The survival outcome of lung cancer patients with end-stage renal disease has been poorly studied in the literature. In this study, we evaluated the effect of end-stage renal disease on lung cancer survival. Material and methods: A retrospective, multicenter, matched-cohort study of lung cancer patients with end-stage renal disease under renal replacement therapy (WITH-ESRD) and without end-stage renal disease (WITHOUT-ESRD) was performed. One WITH-ESRD patient was matched to four WITHOUT-ESRD patients. Results: Baseline clinical characteristics did not differ statistically significantly after matching between the WITH-ESRD and WITHOUT-ESRD groups. WITH-ESRD included 133 patients and WITHOUT-ESRD included 532 patients. Kaplan-Meier survival analysis demonstrated no significant difference in median overall survival between WITH-ESRD patients and WITHOUT-ESRD patients (7.36 months versus 12.25 months, respectively, p = 0.133). Lung cancer WITH-ESRD patients receiving medical treatment had a median overall survival of 5.98 months (95% CI: 4.34-11.76) compared to 14.13 months (95% CI: 11.30-16.43) for WITHOUT-ESRD patients, p = 0.019. Although patients receiving surgical treatment compared to those receiving medical treatment had an improvement of survival by 46% (HR = 0.54, 95% CI: 0.19-1.53, p = 0.243), the difference did not reach statistical significance. Cox regression analysis revealed that male gender and stage IIIA-IV were independent factors associated with poor outcome for WITH-ESRD patients. Conclusions: In our limited experience, the survival for lung cancer with ESRD is not inferior to lung cancer patients without ESRD. The reasons for poor survival for the WITH-ESRD medical treatment group and late diagnosis despite frequent medical visits merit further investigation.

The neuroprotective effect of salidroside prophylactic administration on MCAO model rats / 中国药理学通报

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

Pharmacokinetics and blood-brain barrier penetration of a novel salidroside derivative pOBz in rats / 中国药理学通报

Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry ( UPLC-MS/MS ) method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue, and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz. Methods SD rats were administered pOBz at a dose of 50 mg • kg

Research progress on effects of radiation exposure during pregnancy on offspring health / 中国辐射卫生

With social development and technology progress, there is an increasing use of daily electronic products and radioactive medical devices, which increases the risk of exposure to radiation in medical practices, daily life activities, and work. Notably, the effects of radiation exposure on pregnant women and their offspring have attracted increasing attention. Comprehensive and accurate assessment and intervention of the effects of radiation exposure on pregnant women and their offspring are of great significance to reduce birth defects and achieve eugenics. This article reviews the effects of radiation exposure during pregnancy on offspring health based on animal experiments and clinical studies, and describes the possible mechanisms, so as to provide the basis for further studies.

Advances in gene editing and natural product synthesis of Rhodotorula toruloides / 生物工程学报

Rhodotorula toruloides is a non-conventional red yeast that can synthesize various carotenoids and lipids. It can utilize a variety of cost-effective raw materials, tolerate and assimilate toxic inhibitors in lignocellulosic hydrolysate. At present, it is widely investigated for the production of microbial lipids, terpenes, high-value enzymes, sugar alcohols and polyketides. Given its broad industrial application prospects, researchers have carried out multi-dimensional theoretical and technological exploration, including research on genomics, transcriptomics, proteomics and genetic operation platform. Here we review the recent progress in metabolic engineering and natural product synthesis of R. toruloides, and prospect the challenges and possible solutions in the construction of R. toruloides cell factory.

Screening of specific DNA barcode, identification of germplasm resources, and analysis of genetic diversity of Atractylodes chinenesis / 药学学报

italic>Atractylodes chinensis has important medicinal and economic values. In this study, the chloroplast genome sequences of four A. chinensis samples from different producing areas were sequenced using the Illumina platform. The specific DNA barcodes were screened and the germplasm resources of A. chinensis samples from different producing areas and the genetic diversity of the population were analyzed basing on the specific barcodes. The whole chloroplast genomes of the four A. chinensis samples had a typical cyclic tetrad structure, with 112 genes annotated. The comparative genomics results indicated that ccsA and trnC-GCA_petN were potential specific DNA barcodes for intraspecific identification of A. chinensis. Polymerase chain reaction (PCR) analysis of ccsA and trnC-GCA_petN was performed on 256 samples from 14 areas in 9 provinces, and the amplification efficiency was 100%. Sequence analysis showed that ccsA and trnC-GCA_petN had 11 and 22 variant positions, which could identify 16 and 22 haplotypes, respectively. The combined sequence analysis identified 39 haplotypes, named Hap1-Hap39, of which the most abundant and widely distributed genotype was Hap9. Haplotype diversity (Hd) = 0.896 and nucleotide diversity (Pi) = 0.002 22 indicated high genetic diversity at the species level in A. chinensis. The genetic distances of the haplotypes were 0.000 00-0.004 88, indicating that there were small genetic differences among the haplotypes. The results of phylogenetic tree analysis showed that 39 haplotypes had very close genetic relationship, and formed two obvious branches with other groups of the same genus except Atractylodes macrocephala. This study plays an important role in the identification of the origin of A. chinensis and the protection and breeding of germplasm resources.

The Etiological Study of Three Hunter Syndrome Families in Southern China / 中山大学学报(医学科学版)

ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.

Analysis of a child with Very early onset inflammatory bowel disease due to compound heterozygous variants of IL10RA and DUOX2 genes / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a child with Very early onset inflammatory bowel disease (VEOIBD).@*METHODS@#A female child who had presented at the Children's Hospital of Fudan University on May 23, 2018 due to occurrence of diarrhea and fever 6 days after birth was selected as the study subject. Clinical data of the child was collected. Family-based whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and PCR of the patient and her parents.@*RESULTS@#The child had developed the symptoms 6 days after birth, with main manifestations including diarrhea, fever, failure to thrive, rectovestibular fistula and hypothyroidism. An enterostomy was performed at the age of 3.5 months due to severe intestinal adhesion and obstruction. Based on her clinical manifestations, colonoscopic finding, and results of biopsies, she was diagnosed with VEOIBD in conjunct with congenital hypothyroidism. Replacement treatment of levothyroxine was given since one month of age. Family-based WES revealed that the child has harbored compound heterozygous variants of the DUOX2 gene, namely c.2654G>T (p.R885L) and c.505C>T (p.R169W), in addition with a heterozygous c.301C>T (p.R101W) variant of the IL10RA gene. Re-analysis of the WES data revealed that the patient also had a 333 bp deletion spanning exon 1 of the IL10RA gene (Chr11: 117857034_117857366).@*CONCLUSION@#For patients with VEOIBD, genetic testing is recommended. Presence of additional DUOX2 gene variants might have exacerbated the clinical symptoms in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for this family, and raised clinicians' awareness of this rare disease.

Acupuncture for Patients with Chronic Spontaneous Urticaria: A Randomized, Sham-Controlled Pilot Trial / 中国结合医学杂志

OBJECTIVE@#To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU).@*METHODS@#A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA).@*RESULTS@#A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was -8.63 (95%CI, -11.78 to -5.49) and -6.21 (95%CI, -9.43 to -2.98) in the sham acupuncture group for a between-group difference of -2.42 (95% CI, -6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant.@*CONCLUSIONS@#Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776).