The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To explore the diagnostic value of gradient characteristics of quantitative parameters of contrast-enhanced ultrasound (CEUS) in papillary thyroid carcinoma.Methods:A retrospective case series study was conducted. The clinical data of 120 patients with thyroid diseases who underwent pathological examination for samples collected through fine needle aspiration or surgical resection and underwent CEUS examination before surgery at Shanxi Province Cancer Hospital from January 2018 to May 2023 were collected. A total of 120 thyroid nodules were selected and divided into the benign group (37 nodules) and the malignant group (83 nodules) according to pathological results. The VueBox software was used to depict the four regions of interest in nodules of the two groups, which were the overall, central and marginal areas and surrounding normal thyroid tissues. The time-intensity curve (TIC) was drawn and the relevant parameters including peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-out rate (WoR), and time to increase (TI) were analyzed, and the gradient values (ΔPE within the nodules, ΔWiAUC within the nodules, ΔWiR within the nodules, ΔWoR within the nodules, ΔTI within the nodules) between two groups of nodules and surrounding normal tissues, as well as between the central and marginal areas of the nodules were calculated.Results:The conventional ultrasound characteristics of benign and malignant nodules showed only a statistically significant difference in aspect ratio ( χ2 = 14.76, P < 0.001). There were statistically significant differences in PE, WiAUC, WiR, and WoR between the overall malignant nodules and the surrounding normal tissues, as well as between the central and marginal areas within the nodules (all P < 0.05); there was a statistically significant difference in WiAUC between the overall benign nodules and the surrounding normal tissues (7 362.06 vs. 7 281.16, Z = -2.07, P = 0.038); there was no statistically significant difference in TI between the two groups of overall nodules and the surrounding normal tissues, as well as the central and marginal areas within the nodules (both P > 0.05); there were statistically significant differences in ΔPE, ΔWiAUC, ΔWiR, and ΔWoR in different regions of the nodules between the two groups (all P < 0.05); binary logistic analysis showed that overall ΔPE and intra nodule ΔWoR were independent predictive factors for the malignancy of thyroid nodules (both P < 0.05); receiver operating characteristic (ROC) curve analysis showed that the overall ΔPE had better diagnostic efficacy for benign and malignant thyroid nodules than the intra nodule ΔWoR, with a cut-off value of -536.23 a.u. Its combination with CEUS had the highest diagnostic efficacy for malignant thyroid nodules, with sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 81.1%, 91.1%, and 73.2%, respectively. Conclusions:The peak intensity gradient value (overall ΔPE) between thyroid nodules and surrounding normal tissues can serve as an effective indicator for distinguishing between benign and malignant thyroid nodules. The combination of overall ΔPE and CEUS has good diagnostic efficacy.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Objective:To explore the diagnostic value of quantitative analysis of contrast-enhanced ultrasound for the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) thyroid nodules 4.Methods:A retrospective case series study was conducted. A total of 87 patients with thyroid nodules from Shanxi Province Cancer Hospital between October 2018 and July 2022 were selected. All patients were diagnosed as C-TIRADS 4 thyroid nodules by routine ultrasound and had DICOM storage format ultrasound contrast dynamic data. All 96 thyroid nodules in 87 patients had clear surgical and pathological results. Based on the contrast-enhanced ultrasound features of the nodules, the nodules were reclassified by using C-TIRADS according to 3 different criteria. VueBox analysis software was used to obtain dynamic contrast-enhanced ultrasound (DCE-US) quantitative parameters, the most effective quantitative parameters for diagnosing thyroid malignant nodules were obtained by using receiver operating characteristic (ROC) curves, and their optimal cut-off values were obtained. Based on ultrasound contrast and DCE-US quantitative parameters, the nodules were reclassified by using C-TIRADS. Based on pathological results, the malignancy rates of nodules classified by C-TIRADS based on the conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters were calculated. ROC curves were drawn to compare the diagnostic efficacy of conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters for thyroid malignant nodules.Results:Among the 96 thyroid nodules, the malignancy rates of C-TIRADS 4a, 4b, and 4c nodules evaluated by conventional ultrasound were 50.0% (17/34), 72.1% (31/43) and 100.0% (19/19), respectively, which were not within the reference range provided by the C-TIRADS guideline. After reclassifying the nodules according to the contrast-enhanced ultrasound standards, the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/2), 25.0% (2/8), 31.3% (5/16), 71.9% (23/32), and 97.4% (37/38), respectively. Among them, the malignancy rate of the 4a type nodule was still relatively high, which was not within the reference range given by the C-TIRADS guideline. The area under the curve of DCE-US quantitative parameter peak intensity (PE) for diagnosing thyroid malignant nodules according to ROC curves was the largest with the optimal cut-off value of 2080.7a.u. Based on contrast-enhanced ultrasound and combined with PE, the nodules were classified again, and the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/7), 9.1% (1/11), 27.3% (3/11), 83.3% (11/13), and 98.1% (53/54), respectively, all were within the reference range provided by the C-TIRADS guideline. ROC curve analysis showed that the AUC of contrast-enhanced ultrasound combined with DCE-US quantitative parameter PE for diagnosing thyroid malignant nodules was greater than that of conventional ultrasound and contrast-enhanced ultrasound (both P < 0.05); the optimal cut-off value was type 4b, with the sensitivity of 94.0%, the specificity of 89.7%, and the accuracy of 92.7%. Conclusions:The combination of contrast-enhanced ultrasound and DCE-US quantitative parameter PE is helpful for more accurate classification of C-TIRADS 4 thyroid nodules and improves the diagnostic efficiency of thyroid malignant nodules.

Objective:To explore the diagnostic value of gradient characteristics of quantitative parameters of contrast-enhanced ultrasound (CEUS) in papillary thyroid carcinoma.Methods:A retrospective case series study was conducted. The clinical data of 120 patients with thyroid diseases who underwent pathological examination for samples collected through fine needle aspiration or surgical resection and underwent CEUS examination before surgery at Shanxi Province Cancer Hospital from January 2018 to May 2023 were collected. A total of 120 thyroid nodules were selected and divided into the benign group (37 nodules) and the malignant group (83 nodules) according to pathological results. The VueBox software was used to depict the four regions of interest in nodules of the two groups, which were the overall, central and marginal areas and surrounding normal thyroid tissues. The time-intensity curve (TIC) was drawn and the relevant parameters including peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-out rate (WoR), and time to increase (TI) were analyzed, and the gradient values (ΔPE within the nodules, ΔWiAUC within the nodules, ΔWiR within the nodules, ΔWoR within the nodules, ΔTI within the nodules) between two groups of nodules and surrounding normal tissues, as well as between the central and marginal areas of the nodules were calculated.Results:The conventional ultrasound characteristics of benign and malignant nodules showed only a statistically significant difference in aspect ratio ( χ2 = 14.76, P < 0.001). There were statistically significant differences in PE, WiAUC, WiR, and WoR between the overall malignant nodules and the surrounding normal tissues, as well as between the central and marginal areas within the nodules (all P < 0.05); there was a statistically significant difference in WiAUC between the overall benign nodules and the surrounding normal tissues (7 362.06 vs. 7 281.16, Z = -2.07, P = 0.038); there was no statistically significant difference in TI between the two groups of overall nodules and the surrounding normal tissues, as well as the central and marginal areas within the nodules (both P > 0.05); there were statistically significant differences in ΔPE, ΔWiAUC, ΔWiR, and ΔWoR in different regions of the nodules between the two groups (all P < 0.05); binary logistic analysis showed that overall ΔPE and intra nodule ΔWoR were independent predictive factors for the malignancy of thyroid nodules (both P < 0.05); receiver operating characteristic (ROC) curve analysis showed that the overall ΔPE had better diagnostic efficacy for benign and malignant thyroid nodules than the intra nodule ΔWoR, with a cut-off value of -536.23 a.u. Its combination with CEUS had the highest diagnostic efficacy for malignant thyroid nodules, with sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 81.1%, 91.1%, and 73.2%, respectively. Conclusions:The peak intensity gradient value (overall ΔPE) between thyroid nodules and surrounding normal tissues can serve as an effective indicator for distinguishing between benign and malignant thyroid nodules. The combination of overall ΔPE and CEUS has good diagnostic efficacy.

Objective:To explore the diagnostic value of quantitative analysis of contrast-enhanced ultrasound for the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) thyroid nodules 4.Methods:A retrospective case series study was conducted. A total of 87 patients with thyroid nodules from Shanxi Province Cancer Hospital between October 2018 and July 2022 were selected. All patients were diagnosed as C-TIRADS 4 thyroid nodules by routine ultrasound and had DICOM storage format ultrasound contrast dynamic data. All 96 thyroid nodules in 87 patients had clear surgical and pathological results. Based on the contrast-enhanced ultrasound features of the nodules, the nodules were reclassified by using C-TIRADS according to 3 different criteria. VueBox analysis software was used to obtain dynamic contrast-enhanced ultrasound (DCE-US) quantitative parameters, the most effective quantitative parameters for diagnosing thyroid malignant nodules were obtained by using receiver operating characteristic (ROC) curves, and their optimal cut-off values were obtained. Based on ultrasound contrast and DCE-US quantitative parameters, the nodules were reclassified by using C-TIRADS. Based on pathological results, the malignancy rates of nodules classified by C-TIRADS based on the conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters were calculated. ROC curves were drawn to compare the diagnostic efficacy of conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters for thyroid malignant nodules.Results:Among the 96 thyroid nodules, the malignancy rates of C-TIRADS 4a, 4b, and 4c nodules evaluated by conventional ultrasound were 50.0% (17/34), 72.1% (31/43) and 100.0% (19/19), respectively, which were not within the reference range provided by the C-TIRADS guideline. After reclassifying the nodules according to the contrast-enhanced ultrasound standards, the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/2), 25.0% (2/8), 31.3% (5/16), 71.9% (23/32), and 97.4% (37/38), respectively. Among them, the malignancy rate of the 4a type nodule was still relatively high, which was not within the reference range given by the C-TIRADS guideline. The area under the curve of DCE-US quantitative parameter peak intensity (PE) for diagnosing thyroid malignant nodules according to ROC curves was the largest with the optimal cut-off value of 2080.7a.u. Based on contrast-enhanced ultrasound and combined with PE, the nodules were classified again, and the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/7), 9.1% (1/11), 27.3% (3/11), 83.3% (11/13), and 98.1% (53/54), respectively, all were within the reference range provided by the C-TIRADS guideline. ROC curve analysis showed that the AUC of contrast-enhanced ultrasound combined with DCE-US quantitative parameter PE for diagnosing thyroid malignant nodules was greater than that of conventional ultrasound and contrast-enhanced ultrasound (both P < 0.05); the optimal cut-off value was type 4b, with the sensitivity of 94.0%, the specificity of 89.7%, and the accuracy of 92.7%. Conclusions:The combination of contrast-enhanced ultrasound and DCE-US quantitative parameter PE is helpful for more accurate classification of C-TIRADS 4 thyroid nodules and improves the diagnostic efficiency of thyroid malignant nodules.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.