Objective:To investigate the relationship between the longitudinal trajectory of perioperative changes in TSH and recovery after microwave ablation of benign thyroid nodules.Methods:251 BTN patients admitted to our hospital from October 2021 to October 2024 were selected as the study subjects,and the group-based trajectory mod-eling(GBTM)model grouping principle was applied to determine the development trajectory of TSH levels.Multiple lin-ear regression was used to analyze the relationship between thyroid function and serum inflammatory factors before and after surgery in patients with different TSH level development trajectories;Cox regression was used to analyze the relationship between TSH level change trajectories and therapeutic efficacy and trend test was performed;binary log-binomial regression model was applied to calculate the relative risk(RR)of postoperative complication rates in different groups of patients.Results:In patients with BTN,four different trajectories of TSH level development were identified:low-stable(90 cases),low-growth(47 cases),medium-growth(63 cases),and high-growth(51 cases).There was a sta-tistically significant difference in surgical efficacy between the developmental trajectories of different TSH levels(P＜0.05),and the low-stable type had the highest apparent and overall efficacy rates,followed by the low-growth type.The postoperative and preoperative thyroid function indexes and serum inflammatory factors of patients with different TSH level development trajectories showed statistical differences(P＜0.05),the postoperative index levels of FT3 and FT4 were lower than preoperative,and the postoperative index levels of IL-8,hs-CRP,and TNF-α were higher than the preoperative ones,and the postoperative indexes of thyroid function(FT3,FT4)and serum inflammatory factors of the four groups of patients(IL-8,hs-CRP,TNF-α)showed statistically significant differences(P＜0.05).The results of multiple linear regression showed that TSH levels were negatively correlated(P＜0.05)with thyroid function indices(FT3,FT4)and positively correlated(P＜0.05)with serum inflammatory factors(IL-8,hs-CRP,TNF-α).The results of COX re-gression analysis showed that the difference in trend test was statistically significant(P＜0.001)among low-growth,medium-growth,and high-growth types,using low-stable type as a reference.The difference in the total postopera-tive complication rate among the four groups was statistically significant(P＜0.05),and the risk of total postoperative complications was elevated in patients with low-growth,medium-growth,and high-growth types compared with low-stable types(RR>1,P＜0.05).Conclusion:TSH levels were closely associated with recovery after microwave ablation of benign thyroid nodules,TSH levels were negatively correlated with FT3 and FT4,and positively correlated with IL-8,hs-CRP,and TNF-α.The low-stabilized type had the highest apparent and total efficiency,followed by the low-growth type.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Objective:To investigate the relationship between the longitudinal trajectory of perioperative changes in TSH and recovery after microwave ablation of benign thyroid nodules.Methods:251 BTN patients admitted to our hospital from October 2021 to October 2024 were selected as the study subjects,and the group-based trajectory mod-eling(GBTM)model grouping principle was applied to determine the development trajectory of TSH levels.Multiple lin-ear regression was used to analyze the relationship between thyroid function and serum inflammatory factors before and after surgery in patients with different TSH level development trajectories;Cox regression was used to analyze the relationship between TSH level change trajectories and therapeutic efficacy and trend test was performed;binary log-binomial regression model was applied to calculate the relative risk(RR)of postoperative complication rates in different groups of patients.Results:In patients with BTN,four different trajectories of TSH level development were identified:low-stable(90 cases),low-growth(47 cases),medium-growth(63 cases),and high-growth(51 cases).There was a sta-tistically significant difference in surgical efficacy between the developmental trajectories of different TSH levels(P＜0.05),and the low-stable type had the highest apparent and overall efficacy rates,followed by the low-growth type.The postoperative and preoperative thyroid function indexes and serum inflammatory factors of patients with different TSH level development trajectories showed statistical differences(P＜0.05),the postoperative index levels of FT3 and FT4 were lower than preoperative,and the postoperative index levels of IL-8,hs-CRP,and TNF-α were higher than the preoperative ones,and the postoperative indexes of thyroid function(FT3,FT4)and serum inflammatory factors of the four groups of patients(IL-8,hs-CRP,TNF-α)showed statistically significant differences(P＜0.05).The results of multiple linear regression showed that TSH levels were negatively correlated(P＜0.05)with thyroid function indices(FT3,FT4)and positively correlated(P＜0.05)with serum inflammatory factors(IL-8,hs-CRP,TNF-α).The results of COX re-gression analysis showed that the difference in trend test was statistically significant(P＜0.001)among low-growth,medium-growth,and high-growth types,using low-stable type as a reference.The difference in the total postopera-tive complication rate among the four groups was statistically significant(P＜0.05),and the risk of total postoperative complications was elevated in patients with low-growth,medium-growth,and high-growth types compared with low-stable types(RR>1,P＜0.05).Conclusion:TSH levels were closely associated with recovery after microwave ablation of benign thyroid nodules,TSH levels were negatively correlated with FT3 and FT4,and positively correlated with IL-8,hs-CRP,and TNF-α.The low-stabilized type had the highest apparent and total efficiency,followed by the low-growth type.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.

Field effect transistor(FET)biochemical sensors show great potential in the fields of environmental monitoring,food safety,disease diagnosis and clinical treatment due to their low noise,low power consumption,label-free,easy integration and miniaturization characteristics.Two-dimensional(2D)materials,as a new generation of channel materials for FET biochemical sensors,have atomic-level thickness,high carrier mobility,high specific surface area and tunable bandgap,which can further improve the performance of FET biochemical sensors,extend their application areas,and promote the rapid development of FET biochemical sensors.This review focused on the development and latest progress of 2D material-based FET biochemical sensors,along with the challenges and prospects of 2D material-based FET biochemical sensors,which aimed to provide new device design conceptions and promote the further development of biochemical sensing technology.

Objective:To explore the expression of connexin 43 (Cx43) in hippocampus of post-stroke depression (PSD) model rats and its effect on cell apoptosis and depressive-like behavior.Methods:Sixty SPF-grade male SD rats aged 6-8 weeks were randomly divided into five groups (12 rats in each group): normal group, stroke group, depression group, PSD group and carbenoxolone(CBX) group. The stroke model was established by injection of endothelin-1.Chronic unpredictable mild stress (CUMS) combined with solitary rearing was used to establish a depression model. Rats in PSD group were given CUMS and raised alone on the seventh day of stroke modeling.Rats in CBX group were given intraperitoneal injection of CBX(20 mg/kg) on 14th day after PSD modeling. The depressive-like behavior of rats was evaluated by sugar water preference test and open field test. The expression of Cx43 mRNA in hippocampus of rats was detected by RT-PCR, the expression levels of Cx43, caspase-3, Bax and Bcl-2 were detected by Western blot, and the changes of apoptosis rate were detected by TUNEL staining. SPSS 23.0 software was used for statistical analysis, the behavioral data were analyzed by repeated measurement ANOVA, the remaining data were analyzed by one-way ANOVA, and the LSD- t test was used for further pairwise comparison. Results:(1)As for the preference rate of sugar water and the times of crossing the grid, the interaction effects between time and group were significant among the 5 groups( Finteraction=35.57, 111.43, both P<0.05). On the 28th day after operation, the preference rate of sugar water and the times of crossing grid in depression group and PSD group were lower than those in stroke group (all P<0.05), while the preference rate of sugar water and the times of crossing grid in CBX group were both lower than those in PSD group (both P<0.05). (2) The levels of Cx43 mRNA and Cx43 protein in the five groups were significantly different ( F=273.57, 64.56, both P<0.05). The levels of Cx43 mRNA and Cx43 protein in depression group ((0.59±0.05), (0.69±0.08)) and PSD group ((0.61±0.07), (0.63±0.12)) were lower than those in stroke group ((1.01±0.03), (1.05±0.08)) (all P<0.05). The levels of Cx43 mRNA and Cx43 protein in CBX group ((0.30±0.01), (0.37±0.09)) were lower than those in PSD group (both P<0.05). (3) The protein levels of caspase-3, Bax, Bcl-2 and Bcl-2/Bax and the apoptosis rate of the five groups were significantly different ( F=102.40, 90.27, 47.42, 159.99, 115.21, all P<0.05). The levels of caspase-3, Bax protein, apoptosis rate in stroke group ((0.44±0.06), (0.54±0.07), (29.16±5.03)) and depression group ((0.45±0.07), (0.59±0.09), (27.00±4.93)) were higher than those in normal group ((0.21±0.08), (0.33±0.07), (4.83±3.18)) (all P<0.05), the levels of Bcl-2 protein and Bcl-2/Bax in stroke group ((0.80±0.04), (1.51±0.20)) and depression group ((0.60±0.09), (1.03±0.09)) were lower than those in normal group ((1.04±0.13), (3.14±0.38)) (all P<0.05).The levels of caspase-3, Bax protein and apoptosis rate in PSD group ((0.76±0.05), (0.84±0.02), (44.50±3.83)) were all higher than those in stroke group and depression group (all P<0.05), and the levels of Bcl-2 protein and Bcl-2/Bax in PSD group ((0.50±0.14), (0.59±0.17)) were lower than those in stroke group and depression group (both P<0.05). The levels of caspase-3 and Bax protein and the apoptosis rate in CBX group ((1.03±0.10), (1.02±0.05), (56.00±4.81)) were higher than those in PSD group (all P<0.05).The levels of Bcl-2 protein and Bcl-2/Bax in CBX group((0.26±0.08), (0.25±0.08)) were lower than those in PSD group (both P<0.05). Conclusion:The expression level of Cx43 in the hippocampus of PSD model rats is downregulated, which can promote cell apoptosis and exacerbate depressive behavior.

Background: and Purpose This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). Methods: We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. Results: In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). Conclusion An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.