Primary aldosteronism(PA)is the most common cause of secondary hypertension,yet its diagnosis remains under-recognized,with a high rate of missed diagnoses.This condition significantly impacts multiple systems,including the cardiovascular,renal,metabolic,and skeletal systems,resulting in notable complications.Patients with Klinefelter syndrome(KS)exhibit a markedly higher prevalence of metabolic disorders,which may further exacerbate cardiovascular and endocrine dysfunction.Here we report a patient who presented with refractory hypertension and an incidentally discovered adrenal mass,and was ultimately diagnosed with a left adrenal aldosterone-producing adenoma combined with KS.We provide a detailed description of the patient's clinical manifestations,biochemical indices,diagnostic process,and postoperative histopathological findings in order to enhance the understanding of PA and KS and their potential interconnections,which offers diagnostic insights to reduce misdiagnosis and missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To evaluate the role of remimazolam in lipopolysaccharide(LPS)-induced M1 microglial polarization and its relationship with Toll-like receptor 4(TLR4).Methods BV2 mi-croglia cells were randomly divided into 5 groups(n=20):control group,LPS group(1 μg/ml for 24 h),remimazolam+LPS group(remimazolam group,pretreated with 100 μg/ml remimazolam for 20 min followed by LPS),remimazolam+LPS+Neoseptin-3 group(agonist group,50 pmol Neoseptin-3 dissolved in DMSO),and remimazolam+LPS+DMSO group(agonist control group).The contents of TNF-α and IL-1β in the supernatant were detected by ELISA.The expres-sion of M1 microglia markers,inducible nitric oxide synthase(iNOS)and TLR4 at mRNA.Immu-nofluorescence staining was employed to identify the location of iNOS.Results When compared to the control group,the contents of TNF-α and IL-1β in the supernatant and the expression of iNOS[(14.757±0.986)％vs(1.561±0.08)％]and TLR4 at mRNA and protein levels were sig-nificantly higher in the other four groups(P＜0.05).Remimazolam treatment reversed the increa-ses of the TNF-α and IL-1β contents in the supernatant and mRNA and protein expression of iNOS[(3.767±0.364)％vs(14.757±0.986)％]and TLR4 induced by LPS(P＜0.05).In addi-tion,remimazolam agonist Neoseptin-3 restored the effects of LPS on above molecules[iNOS:(6.827±0.642)％vs(3.767±0.364)％,all P＜0.05].But,there were no statistical differences in above molecules between the agonist group and agonist control group(P＞0.05).Conclusion The mechanism by which remimazolam inhibits LPS-induced M1 microglial polarization is related to down-regulation of TLR4 expression.

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.

Alzheimer's disease(AD)is the most common cause of cognitive impairment in the elderly,and the formation of intracellular neurofibrillary tangles(NFT)due to the hyperphos-phorylation of Tau is one of its important pathological features.Compared to β-amyloid,the hyperphosphorylation of Tau and the resulting NFT are more closely related to the decline in cognitive ability.This review focuses on anti-AD drugs targeting Tau,em-phasizing the latest progress in inhibiting the hyperphosphoryla-tion of Tau protein,alleviating the aggregation of Tau protein,re-ducing the cytoskeletal damage caused by the hyperphosphoryla-tion of Tau protein by stabilizing microtubules,and immunothera-py,in the hope of providing new insights into drug research for AD and related cognitive disorders associated with Tau protein.

Sneddon syndrome is a rare neurocutaneous disorder that primarily affects small-and medium-sized arteries.Its clinical manifestations include livedo racemosa and recurrent cerebral ischemic events,and it may also involve multiple organs such as the heart,spleen,and kidneys.This disease can lead to early-onset stroke,making it a rare cause of stroke in young adults.This article reported a case of a young female patient who experienced two cerebral infarctions within one month.Genetic testing identified a homozygous mutation in the adenosine deaminase 2 gene,confirming the diagnosis of Sneddon syndrome.This case serves as a reference to improve clinical recognition of this disease.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To clarify the occurrence,location distribution,and risk factors of microperforations in surgical gloves used in dermatovenereology surgeries.Methods A total of 898 sterilized surgical gloves worn by right-handed medical staff during dermatovenereology surgeries in Suqian Hospital of Jiangsu Province Hospital from May 2022 to April 2024 were selected as the research objects.The occurrence and location distribution of microperforations in all sterilized surgical gloves after surgery were collected.Univariate analysis and binary Logistic regression analysis were conducted on the factors that might lead to the occurrence of microperforations.Results Among the 898 gloves selected in this study,61 gloves(6.79%)had microperforations;the incidence of microperforations in the gloves worn on the left hand was significantly higher than that in the gloves worn on the right hand(P<0.05);microperforations were prone to occur on the palmar surfaces of the index finger and thumb of the gloves.The results of univariate and binary Logistic regression analyses showed that the use of special instruments,surgery duration≥60 minutes,ingrown nails surgery,and worn by the chief surgeon were the risk factors for the occur-rence of microperforations in sterilized surgical gloves(OR>1,P<0.05),while wearing double-layer gloves was the protective factor to avoid the occurrence of microperforations(OR<1,P<0.05).Conclusion The sterilized surgical gloves are more likely to occur microperforations if involved special instruments in surgery,surgery duration≥60 minutes,and ingrown nails surgery,and worn by the chief surgeon,while wearing double-layer gloves can reduce the incidence of microperforations.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Alzheimer's disease(AD)is the most common cause of cognitive impairment in the elderly,and the formation of intracellular neurofibrillary tangles(NFT)due to the hyperphos-phorylation of Tau is one of its important pathological features.Compared to β-amyloid,the hyperphosphorylation of Tau and the resulting NFT are more closely related to the decline in cognitive ability.This review focuses on anti-AD drugs targeting Tau,em-phasizing the latest progress in inhibiting the hyperphosphoryla-tion of Tau protein,alleviating the aggregation of Tau protein,re-ducing the cytoskeletal damage caused by the hyperphosphoryla-tion of Tau protein by stabilizing microtubules,and immunothera-py,in the hope of providing new insights into drug research for AD and related cognitive disorders associated with Tau protein.