ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.

Objective To investigate the inhibitory effects of formononetin on sortase A(SrtA)of Staphylococcus epidermidis(S.epi-dermidis)and its biofilm formation.Methods Biofilm-producing S.epidermidis standard strain RP62A and biofilm-producing S.epider-midis clinical strains were collected.The minimal inhibitory concentration(MIC)of formononetin against S.epidermidis was investigated using the two-fold dilution method.The inhibitory effects of different concentrations of formononetin on the growth of S.epidermidis in vitro were studied by growth curve analysis using microplate reader.The cytotoxicity of formononetin was measured by cell culture.The biocompatibility of formononetin was studied by hemolysis assay.The inhibitory effect of formononetin on the activity of SrtA was deter-mined by fluorescence resonance energy transfer(FRET)assay.The effect of formononetin on the ability of S.epidermidis binding fi-bronectin was assessed by fibronectin binding assay.The effect of formononetin on the anchoring of serine-rich repeat proteins(SRRPs)in S.epidermidis was assessed by immunofluorescence staining.The effect of formononetin on the biofilm formation of S.epidermidis was measured by crystal violet staining.Results The MICs of formononetin against S.epidermidis were greater than 512 μg/mL.Compared with the control group,32 μg/mL of formononetin did not significantly affect the growth of S.epidermidis or reduce the viability of hu-man aortic endothelial cells.The hemolysis rate of human red blood cells was less than 5%.The inhibition rate of SrtA activity was ap-proximately 53.8%.The binding capacity of S.epidermidis to fibronectin was reduced by approximately 45.4%.Microscopic observation revealed a significant reduction in the anchoring of SRRP in S.epidermidis,and the formation of biofilm of S.epidermidis was inhibited by approximately 41.7%.Conclusion Formononetin inhibits the activity of SrtA in S.epidermidis,reduce its fibronectin-binding ca-pacity and biofilm formation,and thus represents a promising candidate for the prevention of S.epidermidis infections.

Objectives:To analyze and summarize the clinical experience of the Y-incision technique in aortic root enlargement surgery.Methods:A retrospective analysis was conducted based on the data of 53 patients who underwent aortic root enlargement using the Y-shaped incision technique by the same surgical team from January to December 2024.The primary endpoint of the study was the efficacy of the technique,as measured by the enlargement size of the valve annulus.The secondary endpoint focused on the safety of the procedure,specifically the incidence of major complications,including re-sternotomy due to bleeding,third-degree atrioventricular block,and major adverse cardiovascular events(MACE).MACE included cardiovascular death,myocardial infarction,stroke,and re-aortic valve intervention.Echocardiography was performed at 3 months after discharge.Root blood flow compliance was analyzed by computer fluid dynamics.Results:Among the 53 patients,30 were male(56.6%),with a mean age of(59.3±13.3)years(range:13-81 years).Five cases(9.4%)were reoperations.Biological valves were replaced in 36 cases(67.9%),and mechanical valves in 17 cases(32.1%).The intraoperatively measured mean native annulus diameter was(20.5±2.2)mm,the post-root enlargement implanted valve size was(25.4±2.5)mm,with a mean enlargement of(4.9±1.5)mm.The mean cardiopulmonary bypass time was(159.9±46.1)minutes,aortic cross-clamp time was(123.3±35.6)minutes,postoperative intensive care unit stay was(2.6±3.0)days,and invasive mechanical ventilation duration was(18.3±29.7)hours.One case(1.9%)required re-exploration for postoperative bleeding.One case(1.9%)developed transient postoperative elevation of cardiac troponin I,and coronary computed tomography angiography(CTA)confirmed asymptomatic compression of the coronary ostium.Follow-up at 1 month showed normal coronary blood flow.No third-degree atrioventricular block or MACE occurred in the entire cohort.Postoperative computer fluid dynamics analysis showed that the high-speed blood flow at the root disappeared after the operation,the blood flow compliance was improved,and no signs of tilt of the prosthetic valve were found.The mean follow-up was(6.2±2.7)months.The follow-up completion rate was 100%,and no death occurred during the follow-up.Both the aortic prosthetic valve and mitral valve functioned well,there was no dysfunction caused by mitral curtain injury.One case of moderate patient-prosthesis mismatch(PPM)occurred in a reoperation patient,there was no severe PPM post surgery.Compared with the preoperative values,left ventricular ejection fraction,peak transaortic valve flow velocity,and the degree of mitral regurgitation all significantly improved at 3 months after discharge(all P<0.001).Conclusions:The Y incision technique is safe and effective for aortic root enlargement,enabling the implantation of larger-diameter prosthetic valves and providing better hemodynamic outcomes.Further follow-up is required to assess its long-term efficacy.

Objective:To investigate the clinical value of dynamic AI ultrasonic intelligent assisted diagnosis system for preoperative evaluation of thyroid nodules with diameter ≤1.0 cm.Methods:From Apr. 1, 2023, to Dec. 30, 2023, 742 thyroid nodules with diameter ≤1.0 cm were removed from 532 patients with thyroid nodule disease who received surgical treatment in the Department of Thyroid (hernia) of the First Medical Center of the Chinese People’s Liberation Army General Hospital. Among them, 423 were d≤0.5 cm. 319 cases (235 males and 507 females) with 0.5

Objective Investigate the clinical efficacy and application value of gasless trans-subclavian approach endoscopic surgery(GTAES)for the treatment of primary hyperparathyroidism(PHPT).Methods 55 PHPT patients who underwent unilateral parathyroid adenoma resection from January 2023 to October 2024 were absorbed.Based on surgical approaches,31 patients were divided into the traditional low-collar arc incision open surgery group(open group)and 24 patients were divided into gasless trans-subclavian approach endoscopic surgery group(endoscopic group).The perioperative data,anterior neck function recovery,and incision healing were compared between two groups.Results There were no significant differences in operation time,intraoperative blood loss,postoperative drainage volume and postoperative hospital stay between the two groups(P＞0.05).The preoperative blood calcium levels of the endoscopic group and the open group were(2.68±0.10)mmol/L and(2.63±0.16)mmol/L,respectively.The blood calcium levels on the first day after surgery were(2.39±0.12)mmol/L and(2.36±0.16)mmol/L,respectively.Preoperative parathyroid hormone(PTH)was 27.55(110.05,155.75)pg/ml in endoscopic group and 137.00(107.00,210.30)pg/ml in open group,respectively.PTH on the first day after surgery was 18.98(12.64,23.53)pg/ml and 13.85(7.36,23.23)pg/ml,respectively.Blood calcium and PTH in each group 1 day after surgery decreased compared with that before surgery,and the difference was statistically significant(P＜0.05).There were no postoperative complications such as hoarseness,bleeding and incision infection in both groups.Postoperative hand and foot numbness:5 cases(20.8％)in endoscopic group and 8 patients(25.8％)in the open group,there was no significant difference between the two groups(P=0.667).There was no significant difference in the score of neck pain 3 days after surgery between the two groups(P＞0.05).The score of swallowing tension[(1.92±1.06)points compared with(2.77±1.38)points,P=0.015]and the score of anterior neck discomfort[(1.63±0.88)points compared with(2.35±1.33)points,P=0.018]in the endoscopic group one month after surgery were better than those in the open group.There was no significant difference in the score of neck scar scale between the two groups 3 months after surgery(P＞0.05).VAS score of incision satisfaction was(9.08±0.88)in endoscopic group and(8.19±1.30)in open group,and the endoscopic group was better than the open group,the difference was statistically significant(P=0.004).Conclusion For PHPT patients caused by unilateral parathyroid adenoma confirmed through preoperative localization examination,GTAES is a safe and effective surgical approach,which offers unique advantages in intraoperative lesion identification,cosmetic outcomes of the incision,and preservation of anterior neck function,providing a new surgical option for PHPT patients.

Objective:To compare the medical costs of using standard fortified donor human milk (DHM) or preterm formula (PF) to supply very low birth weight [VLBW, defined as birth weight (BW) ≥1 000 g but <1 500 g] and extremely low birth weight (ELBW, defined as BW <1 000 g) premature infants with insufficient maternal breast milk.Methods:VLBW and ELBW preterm infants hospitalized in Peking Union Medical College Hospital from September 2017 to October 2020 were retrospectively enrolled and assigned into DHM group and PF group based on complementary feeding methods. The cost of parenteral nutrition (PN), cost of antibiotics, and total medical expenses during hospitalization were compared between the two groups.Results:A total of 89 infants were enrolled in this study, out of whom 50 was in the DHM group and 39 the PF group. The gestational age in DHM group and PF group were both (29±2) weeks. The BW of DHM group was 1 170 (919, 1 380)?g and that of PF group was 1 170 (1 010, 1 360) g. There were no significant differences in gestational age, BW, maternal age at delivery, delivery mode, gender ratio, proportion of small-for-gestational-age infants and length of hospital stay between the two groups (all P>0.05). The cost of parenteral nutrition in DHM group was significantly lower than that in PF group [3 500 (1 922, 5 704) Chinese yuan vs 7 995 (5 579, 10 788) Chinese Yuan, P<0.01]. The cost of antibiotics in DHM group was significantly lower than that in PF group [6 529 (2 265, 10 860) Chinese Yuan vs 13 676 (10 480, 18 506) Chinese Yuan, P<0.01]. The difference in total medical expense during hospitalization showed no statistical significance between two groups ( P>0.05). Amorg VLBW preterm infants, the cost of PN, cost of antibiotics, total cost of hospitalization, and daily cost of hospitalization in HDM group was significantly lower than that in PF group (all P<0.05). In ELBW preterm infants, the cost of PN and the cost of antibiotics in HDM group were significantly lower than that in PF group (both P<0.05), but the total cost of hospitalization and the daily cost of hospitalization between two groups showed no significant difference (all P>0.05). Conclusions:When mother's own milk is insufficient, using donor human milk reduces the costs of PN and antibiotics in VLBW and ELBW preterm infants compared with using PF. In VLBW preterm infants, using DHM can also reduce the total and daily cost of hospitalization.

Objective To investigate the cIinicopathological features and immunohistochemical expression of gastric hyperplastic polyps(GHPs)with dysplasia/adenocarcinoma.Methods A retrospective analysis of 24 cases(44 polyps)that were diagnosed as GHPs with dysplasia/adenocarcinoma in our hospital from January 2020 to December 2024 was reviewed,and clinical,histomorphological,immunophenotypic and follow-up data were analyzed.Results There were 20 female and 4 male cases,with a mean age of(65.5±7.9)(range 56～76)years.Among 44 polyps,3 occurred in the antrum of the stomach,1 in the gastric horn,and 40 in the fundus/body.Among the polyps,32 cases were diagnosed as high-grade dysplasia,4 cases as low-grade dysplasia,4 cases as coexistence of low-grade+high-grade dysplasia,2 cases as mucinous adenocarcinoma,1 cases as poorly differentiated adenocarcinoma,and 1 cases as signet-ring cell carcinoma.The histological manifestations of 23 cases of background mucosa were autoimmune metaplastic atrophic gastritis(AMAG).the P53 of 8 polyps showed a mutant expression pattern.Through MUC5/MUC6/MUC2/CD10 joint examination,33 cases showed gastric type(25 cases of which were foveal epithelium type),4 cases were intestinal type,5 cases were mixed gastrointestinal type,and 2 cases were non-gastrointestinal type.Conclusion The neoplastic transformation of GHPs is closely related to AMAG.It is necessary for clinicians and pathologists to strengthen their evaluation of background mucosa,to achieve early detection,early diagnosis and early treatment.

Objective Investigate the clinical efficacy and application value of gasless trans-subclavian approach endoscopic surgery(GTAES)for the treatment of primary hyperparathyroidism(PHPT).Methods 55 PHPT patients who underwent unilateral parathyroid adenoma resection from January 2023 to October 2024 were absorbed.Based on surgical approaches,31 patients were divided into the traditional low-collar arc incision open surgery group(open group)and 24 patients were divided into gasless trans-subclavian approach endoscopic surgery group(endoscopic group).The perioperative data,anterior neck function recovery,and incision healing were compared between two groups.Results There were no significant differences in operation time,intraoperative blood loss,postoperative drainage volume and postoperative hospital stay between the two groups(P＞0.05).The preoperative blood calcium levels of the endoscopic group and the open group were(2.68±0.10)mmol/L and(2.63±0.16)mmol/L,respectively.The blood calcium levels on the first day after surgery were(2.39±0.12)mmol/L and(2.36±0.16)mmol/L,respectively.Preoperative parathyroid hormone(PTH)was 27.55(110.05,155.75)pg/ml in endoscopic group and 137.00(107.00,210.30)pg/ml in open group,respectively.PTH on the first day after surgery was 18.98(12.64,23.53)pg/ml and 13.85(7.36,23.23)pg/ml,respectively.Blood calcium and PTH in each group 1 day after surgery decreased compared with that before surgery,and the difference was statistically significant(P＜0.05).There were no postoperative complications such as hoarseness,bleeding and incision infection in both groups.Postoperative hand and foot numbness:5 cases(20.8％)in endoscopic group and 8 patients(25.8％)in the open group,there was no significant difference between the two groups(P=0.667).There was no significant difference in the score of neck pain 3 days after surgery between the two groups(P＞0.05).The score of swallowing tension[(1.92±1.06)points compared with(2.77±1.38)points,P=0.015]and the score of anterior neck discomfort[(1.63±0.88)points compared with(2.35±1.33)points,P=0.018]in the endoscopic group one month after surgery were better than those in the open group.There was no significant difference in the score of neck scar scale between the two groups 3 months after surgery(P＞0.05).VAS score of incision satisfaction was(9.08±0.88)in endoscopic group and(8.19±1.30)in open group,and the endoscopic group was better than the open group,the difference was statistically significant(P=0.004).Conclusion For PHPT patients caused by unilateral parathyroid adenoma confirmed through preoperative localization examination,GTAES is a safe and effective surgical approach,which offers unique advantages in intraoperative lesion identification,cosmetic outcomes of the incision,and preservation of anterior neck function,providing a new surgical option for PHPT patients.

Objective To evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.