Establishment of Reference Range for Leucine Arylamidase in Pregnant Women in China.

BACKGROUND: Leucine arylamidase (LAP) is a type of proteinase. During pregnancy, the LAP value of women will continue to rise, but there is currently no established normal range for this value. METHODS: A total of 26,208 records of LAP information from pregnant women who visited Qingdao Municipal Hospital between 2016 and 2022 were selected, including 25,582 records of healthy pregnant women. The study used the AU5800 Series Clinical Chemistry Analyzer as the detection equipment. The Wilcoxon method was appropriate for calculating confidence intervals in this study since LAP values in pregnant women have a skewed distribution. RESULTS: The reference ranges obtained were 64.00 - 70.50 U/L, 161.00 - 166.00 U/L, and 174.50 - 182.50 U/L for the first trimester, second trimester, and third trimester, respectively. CONCLUSIONS: LAP can rise significantly during pregnancy, so it is essential to establish an appropriate reference range for pregnant women. Abnormal values of LAP carry a risk of developing various pregnancy disorders.

High flow nasal cannula therapy for obstructive sleep apnea in adults.

PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by the aggravation of upper airway constriction or obstruction, and it is associated with high incidence of various metabolic diseases and high mortality. Continuous positive airway pressure (CPAP) is now recommended as the first-line therapy for OSAHS, but its application is limited by its unsatisfactory patient tolerance. Previous studies have showed that high flow nasal cannula (HFNC) may improve symptoms in some patients with OSAHS. Therefore, the aim of the present study was to evaluate the effect of HFNC on OSAHS in a larger cohort than in previous research and to study the details of its therapeutic characteristics. METHODS: Polysomnography recording with and without HFNC was performed in 56 OSAHS patients with a wide spectrum of disease severity. Subgroups were divided by different treatment response criteria to identify the effect of this device. RESULTS: Of 56 patients enrolled, 9 were of mild severity (AHI, 5 to <15 events/h), 30 were of moderate severity (AHI, 15 to <30 events/h), and 17 patients were severe (AHI ≥ 30 events/h); 34 patients were younger than 50 years old and 22 patients were older than 50 years old. AHI decreased significantly (from 26.9 ± 14.7 to 21.5 ± 17.0 events/h, p < 0.001) after HFNC treatment in general. The subjects of responder group accounted for 21%. There was a negative correlation between the difference of AI and the difference of HI in nonresponder group before and after HFNC treatment, and the negative correlation was strong (Pearson's test, r = - 0.804, p = 0.000). Of the patients with mild to moderate severity, 76% achieved any AHI reduction and 24% of patients achieved at least 50% reduction in AHI. Older patients (the age of responder group 52.6 ± 11.7 vs. nonresponder group 43.7 ± 12.1 years old, p < 0.05), especially patients older than 50 years, had a better response rate (≤ 50 years 9% vs. > 50 years 41%, p = 0.007). CONCLUSION: HFNC may be useful in treating patients with OSAHS, especially older patients and those with mild to moderate severity. HFNC may be an alternative treatment when patients are intolerant of CPAP.

A study on the causes of operative failures after microwave ablation for primary hyperparathyroidism.

OBJECTIVE: To summarize the occurrence of operative failures after microwave ablation (MWA) in patients with primary hyperparathyroidism (pHPT), analyze the possible reasons, and explore strategies for preventing and managing these situations. METHODS: This retrospective study reviewed 91 pHPT patients who underwent MWA from April 2015 to November 2019. A cure was defined as the reestablishment of normal calcium homeostasis lasting a minimum of 6 months. An operative failure was defined as a failure to normalize serum intact parathyroid hormone (iPTH) and/or calcium levels at 6 months or longer. Patients who encountered operative failures were compared with patients who were successfully cured. RESULTS: Eighty-eight pHPT patients, consisting of 29 men and 59 women, were finally enrolled. The median follow-up duration was 15.9 months (IQR, 6.1-31.5 months). Seventy-eight patients (78/88, 88.6%) were cured. Ten (10/88, 11.4%) patients experienced operative failure, including 9 persistent pHPT (10.2%) and 1 (1.1%) recurrent pHPT. Small parathyroid nodules (maximum diameter < 0.6 cm) and incomplete ablation were the two key factors leading to operative failure. Of the 9 patients with a maximum nodule diameter less than 0.6 cm, 77.8% (7/9) of them encountered operative failure. CONCLUSION: Operative failure occurred in 11.4% of the pHPT patients who underwent MWA. The possibility of operative failure was increased when the maximum diameter of parathyroid nodule was less than 0.6 cm. Complete ablation could help avoid operative failure. KEY POINTS: • Failed to ablate the target lesion and incomplete ablation were the key factors attributed to operative failures. • When the maximum diameter of the parathyroid nodules is less than 0.6 cm, the possibility of operative failure was higher.

Linarin Protects the Kidney against Ischemia/Reperfusion Injury via the Inhibition of Bioactive ETS2/IL-12.

Ischemia/reperfusion injury (IRI), a participant in acute kidney injury (AKI), can occur as a series of pathological processes such as inflammation. Linarin (LIN) has been widely used for different diseases. To confirm the anti-inflammatory value and relevant mechanism of LIN during IRI, in vivo and vitro models were established. LIN or dissolvent was given, and histologic analysis, quantitative (q)RT-PCR, serum creatinine and blood urea nitrogen testing were used to evaluate kidney injury. Microarray analysis, protein-protein interaction (PPI) analysis and molecular docking were used to identify the target protein of LIN, and small interfering RNA (siRNA) transfection was applied to explore the crucial role of identified protein. First, we found that LIN inhibited kidney injury in an in vivo IRI model and decreased the expression of interleukin-12 (IL-12) p40 in vivo and in vitro IRI models. To explore the mechanism of LIN, we collected raw data from a public microarray database and identified E26 oncogene homolog 2 (ETS2) as a crucial protein of LIN according to microarray analysis and PPI. Meanwhile, qRT-PCR indicated that IL-12 p40 showed no significant difference between ETS2 knock down group and LIN treated ETS2 knock down group after hypoxia reoxygenation treatment. In addition, according to molecular docking the contact area is highly conserved and located on a PPI domain of ETS2 which indicates that LIN may alter the interaction with synergistic proteins in the regulation of IL-12 p40 expression. Our study demonstrated the anti-inflammatory effect of LIN during IRI-AKI, broadening the medicinal value of LIN and the therapeutic options for IRI-AKI.

Prenatal diagnosis of Meier-Gorlin syndrome 7: a case presentation.

BACKGROUND: Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were presented, and compound heterozygous mutations of CDC45 on chromosome 22 were identified by whole-exome sequencing (WES). CASE PRESENTATION: Fetal growth restriction (FGR), craniosynostosis, and brachydactyly of right thumb were found in a fetus of 28th gestational weeks. The fetus was diagnosed as MGS7 clinically. After extensive counseling, the couple opted for prenatal diagnosis by cordocentesis and termination of pregnancy. Karyotype analysis and WES were performed. Chromosomal karyotyping showed that the fetus was 46, XY. There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. Facial dysmorphism, brachydactyly of right thumb, and genitalia abnormally were proved by postpartum autopsy, and craniosynostosis was confirmed by three-dimensional computed tomography (3D-CT) reconstruction. CONCLUSIONS: It is possible to detect multiple clinical features of Meier-Gorlin syndrome in prenatal sonography. Deteriorative FGR complicated with craniosynostosis indicates MGS7. Combination of 2D and 3D ultrasonography helps to detect craniosynostosis. The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.

[Identification of metabolites of Zhali Nusi Prescription in rat plasma, bile, urine and feces after oral administration].

This study was designed to determine the metabolites of Zhali Nusi Prescription(ZLNSP) in rats. The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric(UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques were applied to analyze the metabolites of ZLNSP in rat plasma, bile, urine and feces. The biological samples were analyzed by ACQUITY UPLC BEH T_3 column(2.1 mm×100 mm,1.7 µm), with 0.1% formic acid water(A)-acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). An analytical method for biological samples of rats was established, and 8 prototype components and 36 metabolites were identified. The results showed that the metabolic pathways of the main components of ZLNSP in rats included methylation, glucuronidation, sulfation and so on. It provi-ded information for the therapeutic effect of ZLNSP in vivo.

An ac34 deletion mutant of Autographa californica nucleopolyhedrovirus exhibits delayed late gene expression and a lack of virulence in vivo.

Ac34 and its homologs are highly conserved in all sequenced alphabaculoviruses. In this paper, we show that ac34 transcripts were detected from 6 to 48 h postinfection (p.i.) in Autographa californica nucleopolyhedrovirus (AcMNPV)-infected Sf9 cells. Ac34 localized to both the cytoplasm and the nuclei of infected cells but was not a viral structural protein. To determine the function of ac34 in the viral life cycle, an ac34 knockout AcMNPV (vAc34KO) was constructed. Compared with wild-type and repair viruses, vAc34KO exhibited an approximately 100-fold reduction in infectious virus production. Further investigations showed that the ac34 deletion did not affect the replication of viral DNA, polyhedron formation, or nucleocapsid assembly but delayed the expression of late genes, such as vp39, 38k, and p6.9. Bioassays revealed that vAc34KO was unable to establish a fatal infection in Trichoplusia ni larvae via per os inoculation. Few infectious progeny viruses were detected in the hemolymph of the infected larvae, indicating that the replication of vAc34KO was attenuated. These results suggest that Ac34 is an activator protein that promotes late gene expression and is essential for the pathogenicity of AcMNPV.

Calculation of active earth pressure on external corners with equal length on both sides in excavation engineering.

Taking the external corner with equal lengths as the research object, two failure modes of the equilateral external corner are established, and the active earth pressure calculation formula of the equilateral external corner in the limit state is further deduced when the external angle is 90°. The comparison between the theoretical calculation results and Midas/GTS simulation results shows that when the ratio of the side length B to the depth H is large, the sliding wedge failure will occur at the external corner, and the active earth pressure of the external corner in the range of wedge-shaped slider will not change with the change of size B. When the ratio of the side length B to the depth H is small, the displaced soil is composed of two parts, and the earth pressure varies with the change of size B. In this paper, the magnitude and distribution law of the active earth pressure obtained by the horizontal micro-layered limit equilibrium analysis method is similar to the three-dimensional simulation value of the Midas/GTS software, which can prove the feasibility and rationality of the theoretical calculation.

Current progress of immune checkpoint inhibitors for advanced colorectal cancer: concentrating on the efficacy improvement.

Immune checkpoint inhibitors (ICIs) have paved a new pathway and revolutionized cancer treatment. Currently, ICIs have been extensively used for patients with advanced colorectal cancer (CRC), especially those harboring microsatellite instability (MSI). However, the efficacy of ICIs varies tremendously in different individuals, and some patients may not benefit from ICIs, which limits their clinical application. How to improve the efficacy of ICIs is an important issue to be solved. On the one hand, it is urgent to discover the predictive biomarkers to accurately screen the patients who gain benefit from ICIs, like microsatellite stability, tumor mutation burden (TMB), DNA polymerase ε/DNA polymerase δ1 mutations, and the expression of programmed death-ligand 1 (PD-L1). The rational use of these biomarkers will help clinicians identify suitable candidates who will benefit from ICI treatment, thereby improving therapeutic efficiency. Additionally, it is vital to design combination therapeutic strategies for optimizing the therapeutic effectiveness of ICIs. Nowadays, treatment strategies like chemotherapy, radiotherapy, targeted therapy along with ICIs, have helped improve the therapeutic effectiveness of ICIs. In this review, we have focused on the recent advancements in the predictive biomarkers and combination therapeutic strategies with ICIs for colorectal cancer.

Study on the taste active compounds in Douchi using metabolomics method.

Douchi is a traditional famous seasoning in China. This study adopted electronic tongue and metabolomics to analyze the taste characteristics and taste active compounds of 12 samples from three most famous types of Douchi (Liuyang Douchi, Yangjiang Douchi, Yongchuan Douchi). Thirty-six differential metabolites mainly enriched from the arginine biosynthesis were identified among these Douchis. Umami and bitterness are considered as two taste that bring positive and negative perceptions for Douchi. The succinic acid was found to be responsible for the umami in LY, YJ and YC Douchi, with the TAVs of 2054, 643, 174, respectively, rather than the glutamic acid and aspartic acid. The leucine was identified as the main metabolite for bitterness, with the TAVs of 9, 9, 7 respectively. KEGG enrichment analysis found that the umami, sourness and saltiness might be related to alanine, aspartate and glutamate metabolism and the bitterness might be related to aminoacyl-tRNA biosynthesis pathway.

Identification of novel α-glucosidase and ACE inhibitory peptides from Douchi using peptidomics approach and molecular docking.

In this study, the effect of Douchi extract (DWE) on α-glucosidase and angiotensin-converting enzymes (ACE) were investigated, and several novel peptides with inhibitory activity against α-glucosidase and ACE were identified using peptidomics approach based on UPLC-MS/MS. The average inhibition rates of DWE on α-glucosidase and ACE were 73.75-78.10% and 4.56-27.07%, respectively. In the DWE, a total of 710 peptides were detected. Two novel peptides with potential inhibitory activity against α-glucosidase were identified using the correlation analysis, database alignment and molecular docking methods. They were DVFRAIPSEVL and DRPSINGLAGAN, with the IC50 values of 0.121 and 0.128 mg/mL, respectively. Also, four novel peptides with potential inhibitory activity against ACE were identified: PSSPFTDLWD, EEQDERQFPF, PVPVPVQQAFPF and PSSPFTDL, with IC50 values of 1.388, 0.041, 0.761 and 0.097 mg/mL, respectively. These results indicated that combining peptidomics and molecular docking is an effective alternative strategy for rapidly screening numbers of novel bioactive peptides from foods.

Risks of applying mobilising agents for remediation of arsenic-contaminated soils: Effects of dithionite-EDTA and citric acid on arsenic fractionation, leachability, oral bioavailability/bioaccessibility and speciation.

Arsenic (As) mobilisation assists in remediating As-contaminated soils but might increase ecological and health risks. In this study, risks of applying two mobilising agents were assessed, i.e. an emerging reducing-chelating composite agent [dithionite (Na2S2O4)-EDTA] and a classical low-molecular-weight organic acid (LMWOA) [citric acid (C6H8O7)]. Results showed that both agents induced sharp increase in leachability-based ecological risk of As. Interestingly, the two agents had opposite performances regarding health risks. Na2S2O4-EDTA significantly increased As relative bioavailability (RBA) to 1.83 times that in controls based on in vivo mouse model, and As bioaccessibility to 1.96, 1.65 and 1.20 times in gastric, small intestinal and colon phases based on in vitro PBET-SHIME model. Besides, it caused significant increase of highly toxic As(Ⅲ) in colon fluid. In contrast, C6H8O7 significantly reduced RBA and bioaccessibility of soil As in colon by 44.44% and 14.65%, respectively. Importantly, C6H8O7 restrained bioaccessible As(V) reduction and promoted bioaccessible As(Ⅲ) methylation, further reducing health risk. The phenomena could mainly be attributed to excessive metal components release from soil by C6H8O7 and gut microbiota metabolism of C6H8O7. In summary, C6H8O7 and similar LMWOAs are recommended. The study contributes to mobilising agent selection and development and provides a reference for managing remediation sites.

A case study on the bearing characteristics of a bottom uplift pile in a layered foundation.

The bottom uplift pile, which has been applied in practical projects, has the following advantages: the pile body is not easy to crack, good bearing characteristics, and small displacement of the pile top. Based on the bearing capacity test of foundation piles in the third stage expansion project of Lanzhou Zhongchuan International Airport, the upper part pile of the self-balancing test method was used to simulate the bottom uplift pile, and the anchor piles in the anchor pile method were regarded as normal uplift piles. The bearing characteristics of the bottom uplift pile in a layered foundation were studied by comparing these two kinds of piles. The results show that under the same displacement of the pile top, the ultimate uplift bearing capacity of the bottom uplift pile can be more than twice that of the normal uplift pile because of the fully exerted frictional resistance of the soil at the bottom of the pile, the Poisson effect of the pile body and the avoidance of the influence of pile body deformation on the pile top displacement. The maximum axial force of the bottom uplift pile appears at the bottom of the pile and gradually decreases from the bottom to the top, which is opposite to that of the normal uplift pile. The properties and thickness of the soil layers around the pile have a great influence on the distribution curves of the frictional resistance along the pile length of the two kinds of uplift piles. With changing soil layer conditions, the distribution curve may be a "parabola", a "straight line" or a "double line". The soil property plays a decisive role in the frictional resistance, which may cause softening. The influence of the pile diameter on the ultimate uplift bearing capacity is greater than that of the pile length, while the elastic modulus of the pile has little influence.

SWATH-MS-based proteomics reveals functional biomarkers of Th1/Th2 responses of tropomyosin allergy in mouse models.

Type-I food allergies are hypersensitive reactions compromising the immune organs and epithelial barriers. To investigate the organ-specific proteomic alterations of the allergy responses, the spleen and intestine of mice sensitized with high (shrimp and clam) and weak (fish) allergenic tropomyosins were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS)-based proteomics. The results showed that Th1 and Th2 tropomyosin-induced responses in the spleen are characterized by the unique upregulation of innate (cochlin) and adaptive (Ig κ chain V-III region PC 7175) immune regulators, respectively. In the intestine, tropomyosin allergy concurred with the downregulation of 35 differentiating proteins featuring the overall impairment of metabolic pathways, absorption processes and ammonium ion responses. These data provide new functional biomarkers of tropomyosin-induced immune responses as well as candidate targets for intervention.

Neutron and Photon Dose Rates in a D-T Neutron Generator Facility: MCNP Simulations and Experiments.

The deuterium-tritium neutron generator is a common neutron source for fast neutron activation analysis. The 14.1 MeV neutrons emitted from a deuterium-tritium neutron generator are difficult to shield due to their strong penetrability and the induced secondary gamma rays in the shield. A rough calculation based on attenuation factors shows that when 14.1 MeV neutrons with a yield of 1 × 10 ns penetrate the designed shielding layers, which consist of a 0.5-m-thick concrete layer and a 0.5-m-thick water layer, the neutron ambient dose equivalent rate is 2.48 µSv h. A geometric model of a neutron shielding room is constructed based on the calculation. Monte Carlo simulations indicate that the highest neutron ambient dose equivalent rate outside the neutron shielding room is 0.73 µSv h, and the neutron ambient dose equivalent rate at the detector position in the shielding room is 2.12 µSv h. The experimental results show that the highest neutron ambient dose equivalent rate outside the neutron shielding room is 1.43 µSv h, and the neutron ambient dose equivalent rate at the detector position inside the shielding corridor is 2.74 µSv h. Comparative investigations show that the experimental results are basically consistent with the results of the Monte Carlo simulations, except for some positions with large proportions of fast neutrons where it is too difficult for the neutron dose equivalent meter to provide reliable values. Moreover, the radiation dose rate outside the designed shielding room is lower than the occupational exposure dose limit, which is in line with the design expectations. Finally, the gamma spectrum at the position of the gamma detectors is measured by a high-purity germanium detector. The analyzed results show that many secondary gamma rays are generated by the interaction of neutrons with the shield materials and detector probe crystals, and some gamma rays are produced from natural background radionuclides such as K, Tl, Bi, Bi, Pb, Pb, and Ac.

STARD-rapid screening for the 6 most common G6PD gene mutations in the Chinese population using the amplification refractory mutation system combined with melting curve analysis.

Dot-blot hybridization and high-resolution melting curve methods are used to detect G6PD gene mutations; however, the performance and throughput limitations of these methods hinder their use for screening large populations. For simple screening, we developed a novel approach called "Amplification Refractory Mutation System combined with Melting Curve Analysis (ARMS-MC)," which enables rapid and batch-based detection of the 6 most common G6PD mutations.In this method, we established 4 PCR reaction systems that can be used to detect the 6 most common G6PD mutations (c.95A>G, c.392G>T, c.871G>A, c.1024C>T, c.1376G>T, and c.1388G>A) in the Chinese population.The ARMS-MC method was evaluated with 174 cases of clinical G6PD-deficient samples, and the results were verified by direct sequencing at G6PD gene exons. The results showed that 170 samples had ≥1 of the 6 mutations, which accounted for 97.70% of all mutations. These results were consistent with the results of direct sequencing with 100% accuracy and specificity. Sequencing validation revealed other mutations in the 4 samples in which no mutation was detected by the ARMS-MC method.ARMS-MC provides a rapid, simple, inexpensive, and accurate screening method for detecting the most common G6PD mutations in Chinese people.

The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus.

Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. However, the role of cGas-Sting pathway in response to ECTV is not clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication.

Managing a grossly comminuted and infected mandibular fracture using a maxillary extra-oral distractor as stabilizing agent: A clinical case report.

Facial fracture management dates as early as Hippocratic era. Comminuted mandibular fractures are one of the challenging clinical condition requiring high surgical expertise to achieve a good functional and esthetic outcome. In presence of infection and other facial fractures managing comminuted mandibular fracture becomes more challenging. Here we present a case of grossly comminuted and infected mandibular fracture with delayed presentation managed by using maxillary distractor as stabilizing agent. Using a maxillary distractor for managing a fractured mandible has been seldom reported in literature. Current case report gives idea to practicing clinician about the possibility of treatment beyond the established principles.

Generating a host range-expanded recombinant baculovirus.

As baculoviruses usually have a narrow insecticidal spectrum, knowing the mechanisms by which they control the host-range is prerequisite for improvement of their applications as pesticides. In this study, from supernatant of culture cells transfected with DNAs of an Autographa californica multiple nucleopolyhedrovirus (AcMNPV) mutant lacking the antiapoptotic gene p35 (vAc(∆P35)) and a cosmid representing a fragment of Spodoptera exigua nucleopolyhedrovirus (SeMNPV), a viral strain was plaque-purified and named vAcRev. vAcRev had a broader host range than either vAc(∆P35) or SeMNPV parental virus, being able to infect not only the permissive hosts of its parental viruses but also a nonpermissive host (Spodoptera litura). Genome sequencing indicated that vAcRev comprises a mixture of two viruses with different circular dsDNA genomes. One virus contains a genome similar to vAc(∆P35), while in the other viral genome, a 24.4 kbp-fragment containing 10 essential genesis replaced with a 4 kbp-fragment containing three SeMNPV genes including a truncated Se-iap3 gene. RNA interference and ectopic expression assays found that Se-iap3 is responsible for the host range expansion of vAcRev, suggesting that Se-iap3 inhibits the progression of apoptosis initiated by viral infection and promotes viral propagation in hosts both permissive and non-permissive for AcMNPV and SeMNPV.