Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective To investigate the related factors of early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels. Methods Clinical materials of 480 elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels were retrospectively analyzed. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function of patients within 72 hours after thrombectomy, and the patients were divided into deterioration group and non-deterioration group. The baseline materials were compared between the two groups, the factors of early neurological deterioration were analyzed, and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of risk. Results Among 480 elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels, 92 cases (19.17%) had early neurological deterioration; the blood glucose level, white blood cell count, incidence of dysphagia, and incidence of coma in the deterioration group were significantly higher than those in the non-deterioration group (P < 0.05); the Logistic regression analysis showed that high level of blood glucose (95%CI, 1.203 to 1.478), high level of white blood cell count (95%CI, 1.159 to 1.408), dysphagia (95%CI, 7.049 to 31.475), and coma (95%CI, 8.375 to 43.195) were risk factors for early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels (OR>1, P < 0.05). ROC curve results showed that blood glucose, white blood cell count, dysphagia, and coma had certain predictive value for early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels[the area under the curve (AUC) was 0.733, 0.708, 0.707 and 0.701]; the ROC curve showed AUC was 0.934, indicating that the model was reliable and stable. Conclusion Early neurological deterioration in elderly patients with thrombolysis for acute occlusive stroke of large intracranial vessels may be related to factors such as blood glucose, white blood cell count, dysphagia, and coma. Early risk assessment and relevant intervention measures can be taken clinically to improve prognosis.

The biological characteristics and pathogenicity of Klebsiella oxytoca isolated from sick carrier pigeons in Gansu province were explored by morphological observations,biochemical testing,16S rRNA PCR analysis,and RNA sequencing.The drug resistance and pathogenicity of the isolated strains were studied by histopathological observation,drug susceptibility testing,and pathogenicity analysis.The livers,lungs,hearts,and other organs of the sick pigeons were bleeding.In addition,the livers were yellow and brittle,and the lungs were purulent.A Gram-negative,short,rod-shaped bacterium was successfully isolated from the sick pigeon.Pink,smooth,moist,and round colonies grew on MacConkey's agar.The result of the indigo matrix test was positive.The homology between the amplified 16S rRNA sequence and MN330093.1 was 100.00％,indicating that the sick pigeon was infected with K.oxytoca.The strain was named GS-BY-GG.K.Oxytoca GS-BY-GG was resistant to 10 drugs,including penicillin,ampicillin,and furazolidone,and sensitive to 5 others,which included florfenicol,meropenem,and gentamicin.Histopathological observation showed bleeding in multiple organs.The liver cells were irregu-larly arranged with brown-yellow pigmentation.Extensive cell necrosis and exfoliation were observed in the trachea and mucosal epithelium,with inflammatory cell infiltration in the mucosal layer.The isolates were highly pathogenic in specific pathogen-free chickens.These findings provide support for the clinical diagnosis and control of K.oxytoca GS-BY-GG.

Chlamydia psittaci is a worldwide distributed zoonotic pathogen that infects a variety of birds.In order to char-acterization of the duck originated C.psittaci strains,lung samples were collected from suspected infection ducks and was de-tected by real-time PCR.The positive samples were homogenized in phosphate buffered saline with kanamycin and streptomy-cin,and then inoculated onto L929 cells monolayer.After several sets of passages,chlamydial inclusions of the isolate in cul-tured cells were observed after Giemsa staining or by electron microscope.For species identification,16S rRNA,16-23S IGS gene fragments were sequenced and analyzed.Genotyping of the isolate was performed by comparative analysis of the obtained ompA gene sequence with that of different genotype of C.psittaci strains.A C.psittaci strain was successfully isolated from the lung sample of duck by cell culture and was identified as genotype A.This study expanded our understanding of the host range of genotype A C.psittaci strain,and provided basis for further research on the pathogenicity,transmission,and public health risk of this pathogen.

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Background: and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). Methods: We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. Results: IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity.However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. Conclusions Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.
Humans ; Central Venous Pressure ; Respiration ; ROC Curve

Objective    To study the relationship between preoperative heart rate variability (HRV) and postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Methods    A retrospective analysis was performed on the clinical data of 290 patients who were admitted to the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command from May to September 2020 and received OPCAB. There were 217 males and 73 females aged 36-80 years. According to the incidence of POAF, the patients were divided into two groups: a non-atrial fibrillation group (208 patients) and an atrial fibrillation group (82 patients). The time domain and frequency domain factors of mean HRV 7 days before operation were calculated: standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences, percentage difference between adjacent normal-to-normal intervals that were greater than 50 ms, low frequency power (LF), high frequency power (HF), LF/HF. Results    The HRV value of patients without POAF was significantly lower than that of patients with POAF (P<0.05). The median SDNN of the two groups were 78.90 ms and 91.55 ms, respectively. Age (OR=3.630, 95%CI 2.015-6.542, P<0.001), left atrial diameter (OR=1.074, 95%CI 1.000-1.155, P=0.046), and SDNN (OR=1.017, 95%CI 1.002-1.032, P=0.024) were independently associated with the risk of POPAF after OPCAB. Conclusion     SDNN may be an independent predictor of POAF after OPCAB.

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Life Style ; Risk Factors ; Smoking/epidemiology* ; Aged

Aim To observe the effect of betulinic acid (BA) on the migration and invasion of human gastric cancer MKN-45 cells induced by transforming growth factor-pi (TGF-β1), and to explore the effect of BA on epithelial-mesenchymal transition (EMT) and the potential mechanism. Methods The MKN-45 cells were cultivated in vitro, and the effects of different concentrations of BA on the proliferation of MKN-45 cells at 24, 48 and 72 h were detected using CCK-8 method. The effects of BA (5, 10, 20 jjunol • L) and TGF-01 inhibitor LY2109761 (10 ^mol • L"