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 incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To explore the predictive value of the impedance measured during leadless pacemaker Micra implantation on the trend of changes of pacing threshold post implantation. Methods: This is a retrospective cross-sectional study. Patients who received implantation of leadless pacemaker Micra at the Second Xiangya Hospital of Central South University from December 2019 to August 2020 were enrolled. The clinical data and the intraoperative electrical parameters during leadless pacemaker implantation were collected. The impedance and pacing threshold data were analyzed at three time points: immediate release, 5-10 min after release, and after traction test. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the value of the impedance at immediate release on predicting the trend of changes of pacing threshold post implantation. Results: A total of 21 patients (mean age: (72.2±12.5) years, 12 males) were included. The impedance of 21 patients was (798.1±35.3) Ω immediately after implantation, (800.9±35.6) Ω after 5-10 minutes of release, and (883.6±31.7) Ω after traction test. Impedance was similar between the three time points (P>0.05). The threshold was (0.97±0.11) V/0.24 ms immediately after implantation, (0.95±0.12) V/0.24 ms at 5-10 min after the release, and (0.59±0.06) V/0.24 ms after the traction test. The threshold was significantly lower after the traction test than that immediately after release (P=0.003) and than that at 5-10 minutes after release (P=0.008), suggesting a decreased tendency of the threshold over time. According to the analysis of the ROC curve, the immediate impedance after the release ≥680 Ω could predict the ideal pacing threshold after the traction test (AUC=0.989, 95%CI 0.702-0.964, P<0.001), the prediction sensitivity was 87%, and the specificity was 100%. The pacing threshold would be not ideal with the immediate impedance ≤ 520 Ω (95%CI 0.893-1.000, P<0.001), the sensitivity was 100%, and the specificity was 80%. Conclusions: The impedance immediately after the release has predictive value for the changing trend of threshold post leadless pacemaker Micra implantation. Impedance ≥680 Ω immediately after release is often related with ideal pacing threshold after the traction test. In contrast, the impedance ≤ 520 Ω pacing is often related with unsatisfactory threshold after the traction test, therefore, it is recommended to find a new pacing site to achieve the impedance ≥680 Ω immediately after release during leadless pacemaker Micra implantation.
Aged ; Aged, 80 and over ; Cardiac Pacing, Artificial ; Cross-Sectional Studies ; Electric Impedance ; Humans ; Male ; Middle Aged ; Pacemaker, Artificial ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D. METHODS: A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kg^-1•d^-1) for 7 days. Before and after model establishment, and after intervention, the body mass, 24 h food intake and fecal water content were observed, the visceral sensitivity was detected by abdominal withdrawal reflex (AWR); after intervention, the mental state was evaluated by elevated plus maze (EPM) test, the protein expression of NGF, TrkA and TRPV1 was detected by immunohistochemistry and Western blot in the 4 groups. RESULTS: After model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (P<0.05), first systolic latency of AWR was shortened and number of contraction wave of AWR was increased (P<0.05), and fecal water content was increased (P<0.05) in the model group, the EA group and the western medication group. After intervention, compared with the blank group, open arm residence time ratio (OT%) of EPM was decreased (P<0.05) and protein expression of NGF, TrkA, TRPV1 in colonic tissue was increased in the model group (P<0.05); compared with the model group, the body mass and 24 h food intake were increased (P<0.05), first systolic latency of AWR was lengthened and number of contraction wave of AWR was decreased (P<0.05), the fecal water content was decreased (P<0.05), OT% of EPM was increased (P<0.05), and protein expression of NGF, TrkA, TRPV1 in colonic tissue was decreased (P<0.05) in the EA group and the western medication group. CONCLUSION Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.
Male ; Rats ; Animals ; Receptor Protein-Tyrosine Kinases ; Rats, Sprague-Dawley ; Irritable Bowel Syndrome/therapy* ; Sulfonic Acids ; Nerve Growth Factors ; TRPV Cation Channels/genetics*

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation ( RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid ( CONCLUSIONS For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
Birth Weight ; Cesarean Section ; China ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pregnancy ; Retrospective Studies

OBJECTIVE: To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery. METHODS: Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora. RESULTS: Compared with the control group, the GMDI of rats in the model group was increased (<0.01), the gastric mucosal pathological changes were significant, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all decreased (<0.05), the diversity index Simpson was increased (<0.05). Compared with the model group, the GMDI of rats in the acupuncture group and medication group was reduced (<0.01, <0.05), the gastric mucosal damage degree was reduced, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all increased (<0.05) and the diversity index Simpson decreased (<0.05). Compared with the medication group, the GMDI of rats in the acupuncture group was reduced (<0.01), the recovery of gastric mucosal injury was better than that of the medication group. CONCLUSION Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Gastrointestinal Microbiome ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; microbiology ; therapy

Objective To understand the prevalence and risk factors of metabolic syndrome (MS) among different ethnic groups. Methods A multicenter cross-sectional survey was conducted. Subjects were selected by multistage stratified random sampling. Physical examination and laboratory testing were performed to collect MS related indicators, and the prevalence was standardized by the 6th general survey data. Further multivariate and logarithmic linear model methods were applied to analyze the risk factors and interaction. Results The overall prevalence of MS was 19.58%. The highest prevalence of MS was in Korean, followed by Han, while the lowest was in Kazakh. The rates of MS, overweight and obesity were higher in men than those in women, and increased along with age. Multivariate analysis result showed that the odds ratio (OR) of female to male was 0.556, and aging increased the risk of MS. The OR of central obesity was 2.765, and would reach to 4.259 when the waist-to-body ratio was over 0.52. The logarithmic linear model showed that the overweight/obesity, hyperglycemia, hypertension and dyslipidemia had independent effects on the risk of MS. Also, there were interactions in the four indicators. Conclusions The incidence of MS is high and the positive interaction between the overweight/obesity, hyperglycemia, hypertension and dyslipidemia is observed, making MS a common crisis to clinical and public health. In order to prevent and control MS, and to reduce the risk of cardiovascular and cerebrovascular diseases and diabetes, early screening of MS should be strengthened and lifestyle intervention should be carried out.

In order to determine the quality evaluation method for standard decoction of Coptidis Rhizoma,15 batches of standard decoction of Coptidis Rhizoma were prepared by using standardized process. Parameters such as traits,p H value,indicative component content,fingerprint similarity,composition transfer rate and dry extract rate were selected as the indexes for quality evaluation. Similarity evaluation and cluster analysis were performed for HPLC fingerprint of standard decoction,and mathematical model was used to study the correlation between dry extract rate,berberine content,berberine transfer rate in standard decoction and berberine content in decoction pieces. The results showed that the similarity of fingerprints was greater than 0. 99 for these 15 batches of standard decoctions of Coptidis Rhizoma. In cluster analysis,the standard decoctions of Coptidis Rhizoma from 4 producing areas were classified into 3 categories,consistent with the content determination results,indicating that there were quality differences among different producing areas.R2 in three linear regression mathematical models established was all greater than 0. 9,with significant difference. The validation of three batches of data showed that the models had good accuracy. Therefore,this model can be used to predict the quality of standard decoction prepared from different Coptidis Rhizoma pieces. In the standard decoction process established in this study,the integrity of the traditional process was greatly preserved,and the established quality evaluation method could be used to comprehensively examine the quality of the standard decoction,which can provide a demonstration for the related research of water extraction preparation containing Coptidis Rhizoma pieces.
Berberine/analysis* ; Chromatography, High Pressure Liquid ; Coptis/chemistry* ; Coptis chinensis ; Drugs, Chinese Herbal/analysis* ; Linear Models ; Quality Control ; Rhizome/chemistry*

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.