Objective To assess the value of multimodal ultrasonography for diagnosing thyroid nodules—atypia of undetermined significance (AUS) of thyroid imaging reporting and data system (TI-RADS) categories 3 to 5. Methods A total of 90 AUS thyroid nodules in TI-RADS 3-5 categories from 88 patients underwent conventional ultrasonography, ultrasound elastography, superb microvascular imaging, and multimodal ultrasonography at the same time. With fine needle aspiration biopsy results as the gold standard, the methods were compared in terms of the sensitivity, specificity, accuracy, false positive rate (FPR), false negative rate (FNR), and area under the receiver operating characteristic curve (AUC) for diagnosing thyroid nodules. Results There were no significant differences between patients with benign and those with malignant thyroid nodules in terms of sex, age, and nodule locations (all P > 0.05), but the proportion of thyroid nodules ≤ 1 cm in diameter was significantly higher for malignant thyroid nodules than for benign thyroid nodules (χ²=9.610, P=0.002). Compared with benign nodules, malignant nodules were significantly more frequent to have low-level echoes or very low-level echoes, a blurred margin, a vertical diameter/horizontal diameter ratio of > 1, and microcalcifications or no calcifications (all P < 0.05). An ultrasound elastography score of ≥ 3 and type III vascularity on superb microvascular imaging indicated a higher possibility of malignant thyroid nodules (both P < 0.001). The multivariable logistic regression analysis showed that the size, echogenicity, margin, and vertical diameter/horizontal diameter ratio, and superb microvascular imaging type of thyroid nodules were not significant markers for benign or malignant thyroid nodules (all P > 0.05), while microcalcifications/no calcifications and an ultrasound elastography score of ≥ 3 were independent risk factors for malignant AUS nodules (both P < 0.05). The diagnostic sensitivity, specificity, accuracy, FPR, and FNR of conventional ultrasonography for AUS nodules were 91.30%, 71.40%, 62.70%, 28.60%, and 8.70%, respectively; the values for ultrasound elastography were 85.50%, 66.70%, 52.20%, 33.30%, and 14.50%, respectively; the values for superb microvascular imaging were 66.70%, 76.20%, 42.90%, 23.80%, and 33.30%, respectively; and the values for multimodal ultrasonography were 75.20%, 92.50%, 67.70%, 24.80%, and 7.50%, respectively. For distinguishing between benign and malignant AUS nodules, the AUC values of conventional ultrasonography, ultrasound elastography, superb microvascular imaging, and multimodal ultrasonography were 0.866, 0.745, 0.774, and 0.918, respectively. Conclusion Multimodal ultrasonography shows better diagnostic efficacy for AUS nodules of TI-RADS 3-5 compared with conventional ultrasonography, ultrasound elastography, and superb microvascular imaging, which can facilitate the malignancy risk stratification and management of AUS thyroid nodules.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective:To investigate the popularization of non-iodized salt among residents in water-borne high iodine areas and the iodine nutrition status of key populations in Shandong Province.Methods:In 2021, monitoring was conducted on a county-by-county basis in 47 counties (cities, districts, hereinafter referred to as counties) in 9 cities of Shandong Province, in accordance with the newly designated high iodine areas in the "Definition of Water Source High Iodine Areas and High Iodine Disease Areas" (GB/T 19380-2016) and historical high iodine areas. In each monitoring county, administrative villages with a median water iodine level greater than 100 μg/L were sorted by water iodine value, and a systematic sampling method was used to select 5 administrative villages as monitoring sites to investigate the water improvement situation and the iodine level of residents' drinking water. Totally 40 non boarding students aged 8 to 10 from one primary school and 20 pregnant women were selected in each village location to collect household edible salt samples and random urine samples for testing salt iodine and urine iodine levels, and the B-ultrasound method was used for thyroid examination in children.Results:A total of 364 high iodine administrative villages had been monitored, all of which had completed water improvement with a water improvement rate of 100.0%. The median iodine content in residential drinking water was 20.3 μg/L, ranging from 0.1 to 869.1 μg/L; and 11 464 edible salt samples were collected from residents' homes, with a non-iodized salt rate of 82.7% (9 481/11 464). A total of 9 197 urine samples from children and 2 335 urine samples from pregnant women were tested, with median urinary iodine levels of 219.0 and 139.0 μg/L, respectively. A total of 9 197 children were examined for thyroid, with 262 cases detected and a goiter rate of 2.8%.Conclusions:The rate of non-iodized salt in high iodine areas of Shandong Province still needs to be improved. Children's iodine nutrition is above the appropriate level, while pregnant women are at an iodine deficiency level.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

【Objective】 To evaluate and analyze the impact of COVID-19 epidemic on inventory of red blood cells (RBCs)in local and municipal blood stations in China, and to provide reference for the management of public health emergencies. 【Methods】 Relevant data from 2018 to 2021 were collected, and the differences in the volume of qualified RBCs, the usage efficiency of inventory RBCs, the average daily distribution of RBCs,the blood distribution rate of RBCs prepared by 400 mL whole blood, the difference in the average storage days of RBCs at the time of distribution, the average daily inventory of RBCs and the time of the average daily inventory of RBCs to maintain the distribution in 24 local and municipal blood stations in China during the COVID-19 epidemic and non-epidemic periods were retrospectively analyzed. 【Results】 Compared with non-epidemic periods, the volume of qualified RBCs [(117 525.979 ±52 203.175)U] and the average daily distribution of RBCs [( 156. 468 ± 70. 186) U ] increased significantly, but the usage efficiency of inventory RBCs decreased(97.24%±0.51%) significantly (P<0.05).There was no significant difference in the blood distribution rate of RBCs prepared by 400 mL whole blood(73.88%±20.30%), the average storage days of RBCs distribution(13.040 ±3.486), the average daily stock quantity of RBCs[(2 280.542 ±1 446.538) U ] and the time of the average daily inventory of RBCs to maintain the distribution[(15.062 ±7.453) d] (P>0.5). 【Conclusion】 During the COVID-19 epidemic, the inventory management of RBCs operated well, the overall inventory remained relatively stable, the stock composition and storage period showed no significant change.

Objective:To investigate the predictive value of total cholesterol / high density lipoprotein cholesterol ratio (TC/HDL) for ischemic stroke in patients with coronary heart disease (CHD) .Methods:A total of 1 983 inpatients with CHD in the Affiliated Hospital of Jining Medical University from January 1, 2017 to December 31, 2017 were selected as subjects by cluster sampling method. The clinical data were collected and followed up prospectively for 2 years.Results:During the 2-year follow-up period, 36 cases of ischemic stroke occurred in patients with CHD, and the incidence rate was 1.82% (36/1 983) . There was a curvilinear relationship between TC/HDL and ischemic stroke in male patients with CHD, and the tipping point was 3.84.When TC / HDL was less than 3.84, TC / HDL was negatively correlated with the incidence of ischemic stroke. The incidence of ischemic stroke decreased by 72% for each additional unit of TC/HDL ( P=0.049) . When TC/HDL was over 3.84, there was no correlation between TC / HDL and the incidence of ischemic stroke ( P=0.267) . There was a curvilinear relationship between TC/HDL and ischemic stroke in female patients with CHD, and the tipping point was 2.81. When TC / HDL was less than 2.81, TC / HDL was negatively correlated with the incidence of ischemic stroke. The incidence of ischemic stroke decreased by 99% for each additional unit of TC/HDL ( P=0.019) . When TC/HDL was over 2.81, there was no correlation between TC / HDL and the incidence of ischemic stroke ( P=0.110) . Conclusions:TC/HDL has different thresholds in predicting ischemic stroke in CHD patients with different genders, which has a certain clinical significance in predicting the prognosis of patients with coronary heart disease.

Objective To evaluate the testing ability of iodine in the disease control and prevention institutes at all levels in Shandong,and to raise their testing ability.Methods The testing ability of salt iodine,water iodine and urinary iodine of iodine deficiency disorders laboratories at provincial,prefectural and county levels in Shandong in 2016 was evaluated.The testing results of salt iodine were evaluated by using reference value ± uncertainty.The testing results of water iodine and urinary iodine of all the participatory laboratories were evaluated by using standard Z score generated from laboratories participated in the examination.Results One provincial and 17 prefectural salt iodine,water iodine and urinary iodine laboratories and 30 county level salt iodine laboratories took part in the national examination.Both the feedback rate and qualified rate of the testing results were 100％.The 65 urinary iodine laboratories at the county level took part in the provincial examination.The feedback rate was 92.3％ (60/65),and the qualified rate was 75.4％ (49/65).Conclusions The results of the national examination have showed that the testing ability at all levels of the laboratory is maintained at a higher level;the results of the provincial examination have showed that the testing ability of most of the county level urinary iodine laboratories is relatively stable at a higher level.The testing ability of some county level urinary iodine laboratories is low.We should focus on strengthening the county level urinary iodine laboratory construction.

The mode of community home-based care with combination of medical care and elderly care is im-portant for promoting healthy aging. But now the services contents provided by community health service agencies were not clear, related system of policies and regulations were imperfect, human resources were insufficient and net-work of service resource was not perfect. All of these factors caused the service cannot met old people medical de-mands and the use for community health services is inadequate. So we should proposesupply-side reform on communi-ty health service to meet the medical demands for old people and even to stimulate new demand.

Objective To develop a diagnosis model for active pulmonary tuberculosis. Methods The proteomic fingerprinting of 264 sera from active tuberculosis patients and controls were analyzed using the surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and protein-chip technology. The peaks were detected and filtrated by Ciphergen PrnteinChip(R) Software (version 3.1.1). Using the Biomarker Pattern 5.0 software, a diagnostic model was developed for diagnosis of active tuberculosis. Re-sults Fifty protein peaks were significantly different between the patients with active pulmonary tuberculosis and the controls with overlapping clinical features (P<0.01). Five protein peaks at 4360, 3311, 8160, 5723, 15173 m/z were chosen for the system classifier and the development of diagnosis model 1. The model differenti-ated the patients with active pulmonary tuberculosis from the controls with a sensitivity of 83.0%, and a speci-ficity of 89.6%. The diagnostic accuracy was up to 86.4%. Three protein peaks at 5643, 4486, 4360 m/z were chosen for the system classifier and the development of diagnosis model 2. The model differentiated the pa-tients with active pulmonary tuberculosis from the controls with a sensitivity of 96.9%, and a specificity of 97.8%. The diagnostic accuracy was up to 97.3%. Conclusion It might be a new diagnostic test for the de-tection of sera from the patients with active pulmonary tuberculosis using SELDI-TOF-MS and protein chip.

BACKGROUND: High molecular materials have been proved to enhance the mechanical properties of calcium phosphate bone cement, as well as attenuate the injectability of composite materials. It thereby influences the clinical application of composite materials.OBJECTIVE: To observe the compressive strength and injectability of silk fihroin compound calcium phosphate bone cement, to evaluate the effect of silk fibroin on calcium phosphate, and to investigate the feasibility of applying silk fibroin as an injectable hone substitute to repair hone defects.DESIGN, TIME AND SETTING: Controlled study was performed in the central laboratory of Analysis and Testing Center, Soochow University from September to December in 2007.MATERIALS: Calcium phosphate cement was purchased from Shanghai Rebone Biomaterials Co., Ltd; silk fibroin was offered by Institute of Material & Engineering, Soochow University.METHODS: Six groups were set with different mass fractions (0.5%, 1%, 1.5%, 2%, 2.5%, 3%) of silk fibroin, which were mixed with bone cement at a certain liquid/solid ratio of 0.4 mL/g to prepare the calcium phosphate composite. The calcium phosphate cement without silk fibroin was served as control group.MAIN OUTCOME MEASURES: The compressive strength and injectability were determined. The characteristic microstructure was observed using scanning electron microscope.RESULTS: The compressive strength increased firstly and then decreased with the addition of silk fibroin. The compressive strength of the experimental groups was remarkably higher than the control group when the silk fibroin content was 1%-2.5% (P<0.05). The injectability of the paste diminished with the addition of silk fibroin, which was statistically different when the silk fibroin content was 1.5%-3% (P<0.05). Scanning electron microscope result revealed that the silk fihroin penetrated throughout calcium phosphate crystals, which were tightly connected.CONCLUSION: Silk fibroin can improve the compressive strength of silk fibroin/calcium phosphate cement composites without significant influence of manipulation, and can widen the application field of calcium phosphate bone substitute.