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1.
Phys Rev Lett ; 132(17): 171001, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38728703

ABSTRACT

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

2.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 294-298, 2024 Mar 14.
Article in Chinese | MEDLINE | ID: mdl-38716603

ABSTRACT

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.


Subject(s)
Heterozygote , Pedigree , Humans , Female , Adult , Mutation , Factor XI/genetics , Male
3.
Mol Cancer Ther ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38670552

ABSTRACT

Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive and limited therapeutic options lead to poor prognosis for patients. HPN328 is a tri-specific T cell activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro concomitant with T cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T cell engagers. HPN328 exhibited linear pharmacokinetic in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3 expressing malignancies.

4.
Zhonghua Yan Ke Za Zhi ; 60(4): 343-351, 2024 Apr 11.
Article in Chinese | MEDLINE | ID: mdl-38583058

ABSTRACT

Objective: The aim of this paper is to compare the refractive correction effects of rigid gas permeable contact lenses (RGPCL) and spectacle correction in children with aphakia after congenital cataract surgery. Methods: This was a prospective non-randomized controlled trial. Children with aphakic eyes after congenital cataract surgery, who underwent vision correction in the Strabismus and Pediatric Ophthalmology Clinic of Beijing Tongren Hospital affiliated with Capital Medical University from April 2012 to November 2019, were continuously collected. Those who voluntarily chose to wear RGPCL for refractive correction were included in the experimental group. Patients with monocular disease were in trial group 1, and patients with binocular disease were in trial group 2. Patients who chose to wear frame glasses for refractive correction were included in the control group. Patients with monocular disease were in control group 1, and patients with binocular disease were in control group 2. Regional origin, medical history, and family information were collected at the first diagnosis. During the follow-up, adverse reactions occurring during the process of wearing glasses were recorded. The Teller acuity card was used for visual examination to obtain the best-corrected visual acuity and convert it into the logarithm of the minimum resolution angle. The degree of nystagmus was determined according to the amplitude and frequency of nystagmus. Treatment cost, treatment compliance, and the reasons for adopting or not adopting RGPCL were analyzed through a questionnaire completed by the parents of children with RGPCL. Results: A total of 203 children (344 eyes) who underwent congenital cataract surgery were included, including 124 males (210 eyes) and 79 females (134 eyes). The age range was 3 to 36 months. There were 28 cases in the experimental group, including 19 cases in trial group 1 and 9 cases in trial group 2. There were 175 cases in the control group, including 43 cases in control group 1 and 132 cases in control group 2. Except for 6 months of age, the visual acuity of the experimental group was better than that of the control group, and the differences were statistically significant (P<0.05). The visual acuity of children in trial group 1 was better than that of children in control group 1 at the same age. Among them, at 12 months of age [1.54 (1.27, 1.97), 1.84 (0.97, 2.12)], 18 months of age [1.27 (0.97, 1.84), 1.84 (0.97, 2.12)], 24 months of age [1.54 (1.27, 1.84), 1.84 (0.97, 2.12)], and 30 months old [0.97 (0.66, 1.27), 1.54 (0.66, 2.12)], the difference was statistically significant (P<0.001). The visual acuity of children in trial group 2 was better than that in control group 2 at the same age. Among them, at 18 months old [1.27 (0.97, 1.54), 1.27 (0.66, 2.12)], 24 months old [0.97 (0.66, 1.27), 1.27 (0.66, 2.12)], and 30 months old [1.27 (0.66, 2.12)], the difference was statistically significant (P<0.05). The remission rate of nystagmus in the experimental group was 8/9 (8 cases), the remission rate of nystagmus in the control group was 34.40% (32 cases), and the exacerbation rate was 29.03% (27 cases). The average annual cost of the experimental group was 25 125 yuan, and that of the control group was 2 511 yuan. Conclusions: RGPCL is a well-tolerated, safe, and effective treatment for infants and young children. The visual acuity and degree of nystagmus were significantly improved in children who wore RGPCL for aphakia refractive correction after congenital cataract surgery compared with spectacle correction.


Subject(s)
Aphakia , Cataract Extraction , Cataract , Contact Lenses , Nystagmus, Pathologic , Ophthalmology , Child, Preschool , Female , Humans , Infant , Male , Cataract/therapy , Cataract/congenital , Eyeglasses , Prospective Studies
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(3): 379-384, 2024 Mar 10.
Article in Chinese | MEDLINE | ID: mdl-38582612

ABSTRACT

Objective: To understand the current status of personal protection in occupational population at high risk for brucellosis in China and provide evidence for the evaluation of implementation of National Brucellosis Prevention and Control Plan (2016-2020). Methods: Four counties in Shanxi Province and Xinjiang Uygur Autonomous Region were selected to conduct a questionnaire survey in occupational population at high risk for brucellosis from December 2019 to July 2020 by using cross-sectional survey methods. Results: A total of 2 384 persons at high risk for brucellosis were surveyed, and the standardized utilization rate of personal protective equipment (PPE) was 20.13% (480/2 384). The utilization rate of glove, mask, rubber shoe, and work cloth were 38.26% (912/2 384), 31.80% (758/2 384), 32.01% (763/2 384) and 30.87% (736/2 384),respectively. There were significant differences in the utilization rate and standardized utilization rate of the four types of PPE among populations in different age, occupation, educational level and area groups (all P<0.001). The utilization rate and standardized utilization rate of PPE were lower in people over 60 years old, women, farmers, and those with lower educational level. The results of multivariate analysis showed that occupation and area were the influencing factors for the standardized utilization of PPE, the standardized utilization rates of PPE were higher in herdsmen and veterinarians. The standardized utilization rate of PPE in Yanggao County and Huocheng County was significantly higher than that in Zuoyun County and Hunyuan County. Conclusions: The utilization rate of the four types of PPE in occupational population at high risk for brucellosis was not high in China, and the standardized utilization rate was low, lower than the requirement in National Brucellosis Prevention and Control Plan, and there were significant differences among different areas. It is urgent to distribute PPE to occupational population at high risk for brucellosis and carry out health education about PPE utilization. Meanwhile, it is necessary to strengthen information exchange or sharing among different areas.


Subject(s)
Brucellosis , Humans , Female , Middle Aged , Cross-Sectional Studies , Brucellosis/epidemiology , Brucellosis/prevention & control , Farmers , Surveys and Questionnaires , China/epidemiology
6.
medRxiv ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38496462

ABSTRACT

Mendelian randomization (MR) provides valuable assessments of the causal effect of exposure on outcome, yet the application of conventional MR methods for mapping risk genes encounters new challenges. One of the issues is the limited availability of expression quantitative trait loci (eQTLs) as instrumental variables (IVs), hampering the estimation of sparse causal effects. Additionally, the often context/tissue-specific eQTL effects challenge the MR assumption of consistent IV effects across eQTL and GWAS data. To address these challenges, we propose a multi-context multivariable integrative MR framework, mintMR, for mapping expression and molecular traits as joint exposures. It models the effects of molecular exposures across multiple tissues in each gene region, while simultaneously estimating across multiple gene regions. It uses eQTLs with consistent effects across more than one tissue type as IVs, improving IV consistency. A major innovation of mintMR involves employing multi-view learning methods to collectively model latent indicators of disease relevance across multiple tissues, molecular traits, and gene regions. The multi-view learning captures the major patterns of disease-relevance and uses these patterns to update the estimated tissue relevance probabilities. The proposed mintMR iterates between performing a multi-tissue MR for each gene region and joint learning the disease-relevant tissue probabilities across gene regions, improving the estimation of sparse effects across genes. We apply mintMR to evaluate the causal effects of gene expression and DNA methylation for 35 complex traits using multi-tissue QTLs as IVs. The proposed mintMR controls genome-wide inflation and offers new insights into disease mechanisms.

7.
Am J Hum Genet ; 111(4): 636-653, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38490207

ABSTRACT

Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle). We identified 6,350 smoking-associated CpGs in lung tissue (n = 212) and 2,735 in colon tissue (n = 210), most not reported previously. For all 7 other tissue types (sample sizes 38-153), no clear associations were observed (false discovery rate 0.05), but some tissues showed enrichment for smoking-associated CpGs reported previously. For 1,646 loci (in lung) and 22 (in colon), smoking was associated with both DNAm and local gene expression. For loci detected in both lung and colon (e.g., AHRR, CYP1B1, CYP1A1), top CpGs often differed between tissues, but similar clusters of hyper- or hypomethylated CpGs were observed, with hypomethylation at regulatory elements corresponding to increased expression. For lung tissue, 17 hallmark gene sets were enriched for smoking-associated CpGs, including xenobiotic- and cancer-related gene sets. At least four smoking-associated regions in lung were impacted by lung methylation quantitative trait loci (QTLs) that co-localize with genome-wide association study (GWAS) signals for lung function (FEV1/FVC), suggesting epigenetic alterations can mediate the effects of smoking on lung health. Our multi-tissue approach has identified smoking-associated regions in disease-relevant tissues, including effects that are shared across tissue types.


Subject(s)
Cigarette Smoking , DNA Methylation , Male , Female , Humans , DNA Methylation/genetics , Epigenesis, Genetic , Genome-Wide Association Study , Smoking/adverse effects , Smoking/genetics , Gene Expression
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(3): 339-346, 2024 Mar 10.
Article in Chinese | MEDLINE | ID: mdl-38514309

ABSTRACT

Objective: To understand the epidemiological characteristics of diarrheagenic Escherichia (E. ) coli infection in infectious diarrhea outpatients aged 15 years and older in Shanghai and provide evidence for the development of disease control strategies. Methods: Based on multistage systematic sampling, diarrhea surveillance was conducted in 22 sentinel hospitals in Shanghai, the information about cases' demographic, clinical, and epidemiological characteristics were collected. Stool samples were collected for the detection and typing of diarrheagenic E. coli by local centers for disease control and prevention. The positive rate of diarrheagenic E. coli in different populations and seasons from 2014 to 2021 were analyzed. Statistical analysis was conducted by using χ2 test. Results: In 15 185 diarrhea cases, 8.05% (1 222/15 185) were positive for diarrheagenic E. coli. The positive rate was higher in men (8.74%, 684/7 824) than in women (7.31%, 538/7 361). The positive rate was highest in age group 15-29 years (9.14%, 335/3 665) and the annual positive rate was highest in 2021 (10.21%, 83/813), the differences were all significant (P<0.05). In the 1 264 strains of diarrheagenic E. coli analyzed through PCR, enterotoxingenic E. coli was the most frequently identified pathogen (50.24%, 635/1 264), followed by enteroadhesive E. coli (27.93%, 353/1 264), and enteropathogenic E. coli (21.36%, 270/1 264). The positive rate of diarrheagenic E. coli showed obvious seasonality with peak in summer (13.92%, 774/5 562) (χ2=495.73, P<0.001). Conclusions: Diarrheagenic E. coli has become a prominent pathogen in infectious diarrhea cases in Shanghai, the disease can occur all the year round with incidence peak during summer and autumn. Predominant subtypes included enterotoxingenic E. coli, enteroadhesive E. coli and enteropathogenic E. coli. Targeted prevention and control strategies are needed for diarrheagenic E. coli-induced infectious diarrhea in different age groups, seasons and for different types of infections.


Subject(s)
Dysentery , Enteropathogenic Escherichia coli , Escherichia coli Infections , Male , Female , Humans , Outpatients , China/epidemiology , Escherichia coli Infections/epidemiology , Diarrhea/epidemiology , Dysentery/epidemiology
9.
Nat Commun ; 15(1): 2383, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38493154

ABSTRACT

Genetic effects on functionally related 'omic' traits often co-occur in relevant cellular contexts, such as tissues. Motivated by the multi-tissue methylation quantitative trait loci (mQTLs) and expression QTLs (eQTLs) analysis, we propose X-ING (Cross-INtegrative Genomics) for cross-omics and cross-context integrative analysis. X-ING takes as input multiple matrices of association statistics, each obtained from different omics data types across multiple cellular contexts. It models the latent binary association status of each statistic, captures the major association patterns among omics data types and contexts, and outputs the posterior mean and probability for each input statistic. X-ING enables the integration of effects from different omics data with varying effect distributions. In the multi-tissue cis-association analysis, X-ING shows improved detection and replication of mQTLs by integrating eQTL maps. In the trans-association analysis, X-ING reveals an enrichment of trans-associations in many disease/trait-relevant tissues.


Subject(s)
Multifactorial Inheritance , Quantitative Trait Loci , Quantitative Trait Loci/genetics , Genomics , Phenotype , Genome-Wide Association Study , Polymorphism, Single Nucleotide
10.
Zhonghua Wai Ke Za Zhi ; 62(5): 424-431, 2024 May 01.
Article in Chinese | MEDLINE | ID: mdl-38548612

ABSTRACT

Objective: To examine the efficacy and experience of staged and segmented two hybrid surgeries for total repair of Debakey type Ⅰ aortic dissection (TIAD). Methods: This study was a retrospective case series. The clinic data of 10 patients with acute TIAD who were admitted to the Department of Cardiac Surgery, Second Hospital of Lanzhou University or the First People's Hospital of Lanzhou, between January 2016 and August 2022, were retrospectively studied. Ten patients underwent hybrid surgeries in two hospitalizations (stages), including 7 males and 3 females with an age of (60±7) years (range: 49 to 71 years). In stage 1, the first type Ⅱ hybrid arch repair was performed to treat the ascending, total arch, and descending thoracic aorta for acute TIAD without circulatory arrest. In stage 2, the second hybrid surgery including infrarenal abdominal aorta replacement, visceral arteries bypass and endovascular thoracoabdominal aortic repair was performed to treat residual thoracoabdominal aortic dissection after the first hybrid operation (segmented). Basic data, preoperative concomitant diseases, high-risk factors, surgical approaches and postoperative complications of all important organs, as well as CT imaging were analyzed. Results: There was no death in the 20 hybrid surgical procedures. In stage 1 type Ⅱ hybrid surgery, 4 cases underwent reconstruction of the aortic sinutubular junction, while Bentall and David surgery was performed for 3 cases, respectively. A patient received coronary artery bypass grafting. Then all patients were sequentially treated with arch debranching and thoracic aortic endovascular repair. Postoperative complications included renal insufficiency (4/10), hemofiltration (1/10), hypoxemia (4/10), neurologic event (1/10) and type Ⅱ endoleak (1/10). Complete false lumen thrombosis occurred in 9/10 of the patients. All complications recovered successfully at discharge and the average hospital stay was (21±4) days (range: 16 to 28 days) in the first hospitalization. At stage 2, the second hybrid surgery was successfully performed in all patients. No paraplegia, hepatic or renal insufficiency, or endoleak occurred. However, branch graft embolism of the left renal artery was found in one patient 3 days after laparotomy, as well as of superior mesenteric artery in another. Superior mesenteric artery occlusion was successfully treated by endovascular recanalization. Complete false lumen thrombosis occurred in all patients. Although all patients had different degrees of intestinal dysfunction, they were gradually relieved at discharge, and the average hospital stay was (19±2)days (range:16 to 21 days) in the second hospitalization. During follow-up, CT angiography showed aortic remodeling in all patients. Conclusion: Staged and segmented two hybrid surgeries are safe and feasible for total repair of Debakey type Ⅰ aortic dissection and are associated with acceptable early and midterm outcomes.


Subject(s)
Aortic Dissection , Blood Vessel Prosthesis Implantation , Humans , Male , Middle Aged , Female , Aortic Dissection/surgery , Retrospective Studies , Aged , Blood Vessel Prosthesis Implantation/methods , Treatment Outcome , Aortic Aneurysm, Thoracic/surgery , Aorta, Thoracic/surgery , Stents
11.
Int J Tuberc Lung Dis ; 28(2): 73-80, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38303039

ABSTRACT

BACKGROUND: The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS: A retrospective multi-centre observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD.RESULTS: Of the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1???49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66???17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73???1.00) demonstrated negative association.CONCLUSIONS: In the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.


Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , Humans , Anti-Bacterial Agents/therapeutic use , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/microbiology , Lung Diseases/drug therapy , Lung Diseases/microbiology , Prospective Studies , Retrospective Studies
12.
Rev. esp. anestesiol. reanim ; 71(1): 54-57, Ene. 2024. ilus
Article in Spanish | IBECS | ID: ibc-230175

ABSTRACT

El síndrome de Jarcho-Levin es un epónimo usado para describir un espectro de displasias esqueléticas de tórax pequeño con el compromiso variable de vertebras y costillas. Inicialmente considerado letal, actualmente es compatible con la vida en sus presentaciones más leves. Las alteraciones óseas que conllevan un patrón respiratorio restrictivo, las infecciones respiratorias de repetición y el fenotipo particular pueden dificultar el manejo anestésico perioperatorio. Es de especial interés la adecuada valoración de la vía aérea por presentar predictores de vía aérea difícil, así como la prevención, el diagnóstico precoz y el tratamiento adecuado de la insuficiencia respiratoria. Presentamos el caso de un paciente con síndrome de Jarcho-Levin intervenido de distracción vertebral, con sus implicaciones más destacables en el manejo anestésico.(AU)


Jarcho-Levin syndrome is an eponym used to describe a spectrum of small thoracic skeletal dysplasias with variable involvement of vertebrae and ribs. Initially considered lethal, it is currently compatible with life in its mildest forms. Bone alterations that lead to a restrictive respiratory pattern, recurrent respiratory infections and particular phenotype can make perioperative anesthetic management difficult. The proper assessment of the airway is of special interest because it presents predictors of a difficult airway, as well as the prevention, early diagnosis and adequate treatment of respiratory failure. We present the case of a patient with Jarcho-Levin syndrome who underwent vertebral distraction surgery, with its most notable implications in anesthetic management.(AU)


Subject(s)
Humans , Female , Child , Respiratory Insufficiency , Thorax/abnormalities , Radiography, Thoracic , Congenital Abnormalities , Anesthesia/methods , Perioperative Period , Anesthesiology , Inpatients , Physical Examination
13.
Eur Rev Med Pharmacol Sci ; 28(1): 126-135, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38235864

ABSTRACT

OBJECTIVE: This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia. PATIENTS AND METHODS: The study was separated into two parts. In the first part, patients were to determine the median effective dose (ED50) and the 95% effective dose (ED95) of alfentanil in combination with 2.5 mg·kg-1 propofol to inhibit body movements during the abortion using the Dixon up-and-down sequential allocation method. In the second part, 170 patients were randomly divided into group C (2.0 mg·kg-1 propofol with alfentanil 12.16 µg·kg-1) and group E (2.5 mg·kg-1 propofol with its ED95) to compare the anesthetic effect. The primary outcome was the sedation level during general anesthesia. The secondary outcomes were circulation, respiratory complications, and postoperative recovery quality. RESULTS: The ED50 and the ED95 values of alfentanil were 3.37 µg·kg-1 (95% CI: 2.58-3.97 µg·kg-1) and 4.68 µg·kg-1 (95% CI: 4.04-9.32 µg·kg-1). The frequency of deep sedation in group E was significantly higher than in group C (76.5% vs. 60%). Patients in group C showed more wakefulness even during the surgery (14.3% vs. 4.4%). The results of our exploratory analyses did not reveal differences in respiratory depression, circulatory depression, postoperative side effects, or recovery outcomes. CONCLUSIONS: The combination of 2.5 mg·kg-1 propofol and 4.68 µg·kg-1 alfentanil produces a better sedative effect than the combination of 2.0 mg·kg-1 propofol and 12.16 µg·kg-1 alfentanil without increasing additional risks associated with anesthesia.


Subject(s)
Propofol , Pregnancy , Female , Humans , Alfentanil/adverse effects , Outpatients , Prospective Studies , Double-Blind Method
14.
bioRxiv ; 2024 Feb 11.
Article in English | MEDLINE | ID: mdl-37398030

ABSTRACT

Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson's disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with a neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO modulated pathways to slow symptom onset and limit pathology in PD patients.

15.
Ultrasound Obstet Gynecol ; 63(2): 222-229, 2024 02.
Article in English | MEDLINE | ID: mdl-37519188

ABSTRACT

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Ultrasonography, Prenatal , Uterine Artery , Pregnancy , Infant, Newborn , Female , Humans , Infant , Male , Pregnancy Trimester, Third , Uterine Artery/diagnostic imaging , Retrospective Studies , Prospective Studies , Infant, Small for Gestational Age , Fetal Growth Retardation/diagnostic imaging , Gestational Age , Ultrasonography, Doppler , Pulsatile Flow
16.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(1): 54-57, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37678455

ABSTRACT

Jarcho-Levin syndrome is an eponym used to describe a spectrum of small thoracic skeletal dysplasias with variable involvement of vertebrae and ribs. Initially considered lethal, it is currently compatible with life in its mildest forms. Bone alterations that lead to a restrictive respiratory pattern, recurrent respiratory infections and particular phenotype, can make perioperative anesthetic management difficult. The proper assessment of the airway is of special interest because it presents predictors of a difficult airway, as well as the prevention, early diagnosis and adequate treatment of respiratory failure. We present the case of a patient with Jarcho-Levin Syndrome who underwent vertebral distraction surgery, with its most notable implications in anesthetic management.


Subject(s)
Abnormalities, Multiple , Anesthetics , Hernia, Diaphragmatic , Humans , Hernia, Diaphragmatic/surgery , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/surgery , Spine
17.
J Dent Res ; 103(1): 101-110, 2024 01.
Article in English | MEDLINE | ID: mdl-38058134

ABSTRACT

Adding dental pulp stem cells (DPSCs) to vascular endothelial cell-formed vessel-like structures can increase the longevity of these vessel networks. DPSCs display pericyte-like cell functions and closely assemble endothelial cells (ECs). However, the mechanisms of DPSC-derived pericyte-like cells in stabilizing the vessel networks are not fully understood. In this study, we investigated the functions of E-DPSCs, which were DPSCs isolated from the direct coculture of human umbilical vein endothelial cells (HUVECs) and DPSCs, and T-DPSCs, which were DPSCs treated by transforming growth factor beta 1 (TGF-ß1), in stabilizing blood vessels in vitro and in vivo. A 3-dimensional coculture spheroid sprouting assay was conducted to compare the functions of E-DPSCs and T-DPSCs in vitro. Dental pulp angiogenesis in the severe combined immunodeficiency (SCID) mouse model was used to explore the roles of E-DPSCs and T-DPSCs in vascularization in vivo. The results demonstrated that both E-DPSCs and T-DPSCs possess smooth muscle cell-like cell properties, exhibiting higher expression of the mural cell-specific markers and the suppression of HUVEC sprouting. E-DPSCs and T-DPSCs inhibited HUVEC sprouting by activating TEK tyrosine kinase (Tie2) signaling, upregulating vascular endothelial (VE)-cadherin, and downregulating vascular endothelial growth factor receptor 2 (VEGFR2). In vivo study revealed more perfused and total blood vessels in the HUVEC + E-DPSC group, HUVEC + T-DPSC group, angiopoietin 1 (Ang1) pretreated group, and vascular endothelial protein tyrosine phosphatase (VE-PTP) inhibitor pretreated group, compared to HUVEC + DPSC group. In conclusion, these data indicated that E-DPSCs and T-DPSCs could stabilize the newly formed blood vessels and accelerate their perfusion. The critical regulating pathways are Ang1/Tie2/VE-cadherin and VEGF/VEGFR2 signaling.


Subject(s)
Stem Cells , Vascular Endothelial Growth Factor A , Animals , Mice , Humans , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Stem Cells/physiology , Angiopoietin-1/pharmacology , Angiopoietin-1/metabolism , Dental Pulp , Human Umbilical Vein Endothelial Cells , Cadherins/metabolism , Cells, Cultured
18.
Phys Rev Lett ; 131(23): 236003, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38134800

ABSTRACT

Spin-triplet superconductors play central roles in Majorana physics and quantum computing but are difficult to identify. We show the methods of kink-point upper critical field and flux quantization in superconducting rings can unequivocally identify spin-singlet, spin-triplet in centrosymmetric superconductors, and singlet-triplet admixture in noncentrosymmetric superconductors, as realized in γ-BiPd, ß-Bi_{2}Pd, and α-BiPd, respectively. Our findings are essential for identifying triplet superconductors and exploring their quantum properties.

19.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 35(5): 464-475, 2023 Nov 30.
Article in Chinese | MEDLINE | ID: mdl-38148535

ABSTRACT

OBJECTIVE: To measure the burden of hepatitis B-associated diseases in China from 1990 to 2019, and to predict its changes from 2020 to 2030. METHODS: The age-standardized prevalence, incidence, mortality and disability-adjusted life years (DALY) rate of hepatitis B-associated diseases in China from 1990 to 2019 were extracted from the Global Burden of Disease 2019 (GBD 2019) data resources, and the trends in burdens of hepatitis B-associated diseases were evaluated from 1990 to 2019 using estimated annual percentage change (EAPC) and annual percent change (APC). In addition, the changes in the burden of hepatitis B-associated diseases were predicted in China from 2020 to 2023 using the Bayesian model. RESULTS: The overall incidence of hepatitis B-associated diseases reduced from 2 725.98/105 in 1990 to 1 397.31/105 in 2019 in China [estimated annual percentage change (EAPC) = -2.35%, 95% confidential interval (CI): (-2.58%, -2.13%)], with a reduction in the prevalence from 12 239.53/105 in 1990 to 6 566.12/105 in 2019 [EAPC = -2.34%, 95% CI: (-2.54%, -2.14%)], a reduction in the mortality from 24.67/105 in 1990 to 8.07/105 in 2019 [EAPC = -4.92%, 95% CI: (-5.37%, -4.47%)], and a reduction in the DALY rate from 793.38/105 in 1990 to 247.71/105 in 2019 [(EAPC = -5.15%, 95% CI: (-5.64%, -4.66%)]. The DALY rate of hepatitis B-associated diseases were mainly attributed to liver cancer, and the DALY rate of hepatitis B-associated diseases appeared a tendency towards a rise in China from 2012 to 2019 [APC = 1.30%, 95% CI: (0.16%, 2.45%)]. The overall burden of hepatitis Bassociated diseases was higher in males than in females, and the DALY rate of hepatitis B-associated diseases increased with age, with the greatest DALY rate seen among patients at ages of 50 to 69 years. The overall incidence of hepatitis B-associated diseases was projected to be 866.79/105 in China in 2030, with the greatest incidence seen in acute hepatitis B (854.87/105), and the burden of hepatitis B-associated diseases was predicted to decline in China from 2020 to 2030; however, the burden of liver disease was projected to appear a tendency towards a rise. CONCLUSIONS: The burden of hepatitis B-associated diseases appears an overall tendency towards a decline in China from 1990 to 2030; however, the burden of liver cancer appears a tendency towards aggravation. Early diagnosis and treatment of liver cancer should be given a high priority.


Subject(s)
Hepatitis B , Liver Neoplasms , Male , Female , Humans , Middle Aged , Aged , Bayes Theorem , Quality-Adjusted Life Years , Hepatitis B/epidemiology , Liver Neoplasms/complications , Liver Neoplasms/epidemiology , China/epidemiology , Incidence
20.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 35(5): 476-485, 2023 Dec 06.
Article in Chinese | MEDLINE | ID: mdl-38148536

ABSTRACT

OBJECTIVE: To measure the burden of hepatitis C-associated diseases in China from 1990 to 2019, and to predict its changes from 2020 to 2044, so as to provide insights into formulation of the targeted hepatitis C control strategy. METHODS: The total burden due to hepatitis C-associated diseases in China from 1990 to 2019 were extracted from the Global Burden of Disease 2019 (GBD 2019) data resources, and the trends in age-standardized prevalence, incidence, mortality and disability-adjusted life years (DALYs) rate of hepatitis C-associated acute hepatitis C (AHC), chronic liver diseases (CLD) and liver cancer in China from 1990 to 2019 were evaluated in China from 1990 to 2019 using estimated annual percentage change (EAPC). In addition, the changes in the burden of hepatitis C-associated diseases were predicted in China from 2020 to 2044 using a Bayesian model. RESULTS: The prevalence, incidence, mortality and DALY rate of hepatitis C-associated diseases all appeared an overall tendency towards a decline in China from 1990 to 2019 (EAPC = -2.64%, -2.24%, -3.81% and -3.90%, respectively); however, there was a minor rise in the incidence and prevalence of hepatitis C-associated diseases from 2015 to 2019. The overall prevalence of hepatitis C-associated diseases reduced from 2 152.7/105 in 1990 to 1 254.1/105 in 2019 in China, with a reduction of 41.7%. The overall incidence reduced from 87.9/105 in 1990 to 55.0/105 in 2019 in China, with a reduction of 37.4%, and the highest incidence was seen for AHC, followed by CLD and liver cancer. The overall mortality and DALY rate of hepatitis C-associated diseases was 4.0/105 and 100.8/105 in China from 1990 to 2019, with CLD showing the largest contributions to the gross mortality and DALY. The mortality and DALY rate of hepatitis C-associated diseases were 5.5/105 and 142.4/105 among men in China in 2019, which were both much higher than among women (2.8/105 and 60.3/105, respectively), and the overall prevalence (1 604.9/105), mortality (30.2/105) and DALYs (437.1/105) of hepatitis C-associated diseases were all highest among patients at ages of 70 years and older, and the highest incidence was seen among patients at ages of 0 to 9 years (167.3/105). The incidence of hepatitis C-associated diseases was predicted to rise in China from 2020 to 2044; however, the DALY rate was projected to appear a tendency towards a decline. CONCLUSIONS: Although the burden of hepatitis C-associated diseases showed a tendency towards a decline in China from 1990 to 2019, the burden remained high, and was predicted to slightly rise from 2020 to 2044. High attention should be paid to screening of hepatitis C among infants and treatment among adults.


Subject(s)
Hepatitis C , Liver Neoplasms , Male , Adult , Infant , Humans , Female , Bayes Theorem , Quality-Adjusted Life Years , Hepatitis C/epidemiology , Liver Neoplasms/epidemiology , China/epidemiology , Incidence
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