Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To Investigate the efficacy of modified electroconvulsive therapy(MECT)in patients with schizophrenia across different genders.Methods From May 2018 to August 2022,481 patients with schizophrenia were recruited from three psychiatric hospitals in Luzhou,Zigong,and Yibin.According to gender grouping,both groups received adjunctive MECT treatment for two consecutive weeks for a total of six treatments.The differences in positive and negative syndrome scale(PANSS)scores before and after treatment,UKU adverse reaction rating scale(UKU),and gastrointestinal symptom rating scale(GSRS)scores were compared between the two groups.Results After quality control,463 cases were followed up for analysis including 246 males and 217 females.Compared with pre-treatment,the total PANSS score and scores on each subscale were significantly reduced in both genders after treatment(P<0.001).When comparing the reduction rates between the groups,the male patients showed a higher reduction rate in negative symptoms than the female patients(31.24%±30.24%vs.25.80%±33.96%,P<0.05).However,there were no significant differences between the two groups in the reduction rates of the total score,positive symptoms,and general psychopathology(P>0.05).The comparison of adverse reactions showed that the frequency of other types of adverse reactions was higher in female patients than in male patients(47.47%vs.37.80%,P<0.05).However,no significant differences were observed in the adverse reactions related to the mental,neurological,autonomic nervous system,and gastrointestinal systems(P>0.05).Correlation analysis revealed that the reduction rate of the PANSS total score was positively correlated with smoking history(r=0.135,P=0.034)and alcohol history(r=0.160,P=0.012)in male patients,while the reduction rate of the PANSS total score was negatively correlated with the disease duration(r=-0.210,P=0.002)and positively correlated with the age of onset(r=0.145,P=0.032)in female patients.Conclusion MECT is significantly effective for both male and female patients with schizophrenia.Compared to female patients,MECT shows a more pronounced effect on negative symptoms in male patients.Additionally,the factors related to the efficacy of MECT differ between genders,indicating that it is necessary to consider the clinical characteristics of patients comprehensively when selecting an MECT treatment plan.

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

Aim To explore the predictive value of serum free triiodothyronine(FT3)on the long-term prognosis of patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods All the subjects were from a prospective cohort study(PRACTICE study).In this study,15 250 patients with coronary heart disease after PCI in the First Affiliated Hospital of Xinjiang Medical University were selected,and the clinical data,FT3 and creatinine were collected.All the subjects were followed up regularly,and the primary follow-up endpoints were all-cause mortality and cardiogenic mortality,the secondary endpoints were major adverse cardiovascular events(MACE)and major adverse cardiovascular and cerebrovascular events(MACCE).According to the admission criteria,3 109 patients were finally in-cluded in this study.According to the baseline value of FT3,patients were divided into normal FT3 group(FT3:3.65～6.8 pmol/L,1 446 cases)and low FT3 group(FT3＜3.65 pmol/L,1 663 cases).Kaplan-Meier analysis was used for survival analysis,and Log-rank test was used for survival comparison.Multivariate Cox regression analysis was used to e-valuate the risk factors of the follow-up results of the two groups.Results Compared with the normal FT3 group,all-cause mortality and cardiogenic mortality in the low FT3 group increased significantly(P＜0.05).Kaplan-Meier analysis showed that the cumulative risk of all-cause mortality and cardiogenic mortality increased in the low FT3 group(P＜0.05).Multivariate Cox regression analysis indicated that the risk of all-cause mortality increased by 1.639 folds in the low FT3 group(HR=2.639,95％CI:1.385～5.348,P=0.007),while no statistical difference was found in cardiogenic mortality after adjusting for multiple factors(P=0.125).Conclusion The decrease in serum FT3 levels has important predictive value for all-cause mortality after PCI in patients with coronary heart disease.

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.

Aim To investigate the role and mechanism of KLHL21 gene in myocardial infarction(MI)of mice.Methods KLHL21 gene knockout(KO)mice were generated using CRISPR/Cas9 technology,and C57BL/6 wild-type mice were used as controls.Sixty KLHL21 KO mice and 60 wild-type mice were randomly divided into four groups:WT+Sham group(n=30),WT+MI group(n=30),KO+Sham group(n=30)and KO+MI group(n=30).Postoperative is-chemic and infarct areas were assessed using TTC and Evans Blue staining,myocardial injury markers were measured by ELISA,cardiac function was evaluated by ultrasound,and histological changes were examined using HE and Masson stai-ning.Western blot was used to detect proteins related to the nuclear factor-κB(NF-κB)signaling pathway.Results KLHL21 protein expression in the myocardial tissue of KO mice was significantly lower than that in WT mice.The infarct area in KO+MI mice was significantly larger than that in WT+MI group.KO+MI mice showed reduced cardiac function compared with WT+MI mice.HE staining revealed myocardial cell loss,liquefactive necrosis,nuclear fragmentation,and significant neutrophil infiltration,while Masson staining showed aggravated fibrosis in KO+MI group.Serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),creatine kinase-MB(CK-MB),and cardiac troponin Ⅰ(cTnⅠ)lev-els were significantly increased in KO+MI mice compared with WT+MI mice.Western blot analysis showed increased lev-els of phosphorylated inhibitor of nuclear factor-κB alpha(p-IKBα),P65,and P50,and decreased nuclear factor-κB al-pha(IKBα)in KO+MI mice.Conclusion KLHL21 gene plays a preventive role in myocardial infarction in mice,possibly through inhibition of NF-κB signaling pathway activation.