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 summarize and analyze the composition characteristics and problems of basic medical insurance policies for traditional Chinese medicine in various provinces of China,providing reference for optimizing and improving subsequent basic medical insurance policies for traditional Chinese medicine.Methods:Based on the perspective of policy instrument,combined with two dimensions of policy instrument types and policy development process,the content analysis method is used to quantitatively analyze the content of the basic medical insurance policies for traditional Chinese medicine released at the provincial level from 2011 to 2023.Results:The 93 included policy documents were coded and sorted,with a cumulative total of 487 codes.From the perspective of policy instrument dimensions,subcategories of policy instruments involve diverse themes,but there are differences in the level of attention paid to each policy tool.From the perspective of policy development process,each link also presents a discrete trend,indicating a dominant feature of policy planning and implementation.Conclusion:To improve the basic medical insurance policy system of traditional Chinese medicine in China,it is necessary to optimize the combination of policy instrument and construct a coordinated and balanced policy instrument framework;Overall planning of the development process of traditional Chinese medicine medical insurance policies,highlighting the unique advantages of traditional Chinese medicine;Emphasize policy synergy between dimensions and strengthen the implementation of traditional Chinese medicine medical insurance policies.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
Animals ; Rats ; Interleukin-6 ; Network Pharmacology ; Animal Experimentation ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Liver Cirrhosis/genetics* ; Medicine, Chinese Traditional ; Capsules ; Class I Phosphatidylinositol 3-Kinases ; Collagen ; Drugs, Chinese Herbal/pharmacology*

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g^-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

OBJECTIVE: To explore the clinical characteristics, treatment and prognosis of therapy-related hematological neoplasms patients secondary to malignant solid tumors. METHODS: The clinical features, treatment and prognosis of 36 hematological neoplasms patients secondary to malignant solid tumors with radiotherapy and chemotherapy in the Second Hospital of Shanxi Medical University were retrospectively analyzed. RESULTS: The 36 patients with therapy-related hematological neoplasms had a median age of 60 (47-81) years, 14 were male and 22 were female. Among them, 22 cases were acute myeloid leukemia, 5 cases were acute lymphoblastic leukemia, 4 cases were multiple myeloma, 3 cases were myelodysplastic syndrome, and 2 cases were non-hodgkin's lymphoma. The median latency of malignant tumor to hematological neoplasm was 42.5 (12-120) months. The median survival time of therapy-related hematological neoplasms was 10.5 (1-83) months, and the 3-year overall survival (OS) rate was 24.3%. The therapy-related acute myeloid leukemia patients had a very poor prognosis, with a median survival of 7 (1-83) months and a 3-year OS rate of 21.4%. CONCLUSION The prognosis of therapy-related hematological neoplasms secondary to malignant solid tumors with radiotherapy and chemotherapy is poor, and individualized treatment should be implemented according to the clinical situation of patients.
Humans ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Prognosis ; Retrospective Studies ; Hematologic Neoplasms ; Neoplasms, Second Primary ; Leukemia, Myeloid, Acute ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*