Objective To evaluate the combination score of albumin-bilirubin index(ALBI)and alkaline phosphatase(ALP)in predicting the prognosis of patients with cirrhosis complicated by portal hypertension after receiving transjugular intrahepatic portosystemic shunt(TIPS).Methods A total of 61 patients with cirrhosis complicated by portal hypertension,who received TIPS treatment at the Lishui Municipal Central Hospital of China from January 2016 to June 2024,were retrospectively collected.According to the Youden index of ALBI and ALP,the optimal cut-off values were calculated,and the patients were divided into low ALBI-low ALP group(0-point group),high ALBI-high ALP group(2-point group),and high ALBI-low ALP or low ALBI-high ALP group(one-point group).The efficacy of ALBI-ALP score in predicting the prognosis of patients was evaluated,and the survival rate and median survival time were compared between each other among the three groups.The independent risk factors affecting the survival time of patients were analyzed.Results The maximum Youden indexes of ALBI and ALP were 0.31 and 0.34 respectively,and the optimal cut-off values were-1.56 and 108.50 respectively.There were statistically significant differences in MELD score,Child-Pugh classification,and alanine aminotransferase level between each other among the three groups(all P＜0.05).The area under the ROC curve(AUC)of ALBI-ALP score was 0.77(95％ CI:0.66-0.89,P=0.000 2),which was better than 0.52 of the MELD score(95％ CI:0.37-0.67,P=0.77)as well as better than 0.57 of the Child-Pugh classification(95％ CI:0.43-0.72,P=0.34).The total mortality of patients was 49.18％.The mortality in the 0-point group was 11.11％(2/18),which was significantly lower than 59.46％(22/37)in the one-point group as well as than 100％(6/6)in the 2-point group,and the differences were statistically significant(x2=18.20,P＜0.001).In the 0-point group,as a large number of patients were still alive at the end of the study,the median survival time was unable to be calculated.The median survival time in the one-point group was 38.00 months(95％ CI:23.01-52.99 months),which in the 2-point group was only 1.00 month(95％ CI=0.00-2.60 months),the difference was statistically significant(x2=33.08,P＜0.000 1).In the 0-point group,one-point group and 2-point group,the one-year survival rates were 100％,66％ and 17％respectively,the 2-year survival rates were 100％,64％ and 17％ respectively,and the 3-year survival rates were 90％,53％ and 0％ respectively.Cox multivariate regression analysis showed that the combination score of ALBI and ALP(HR=7.11,95％ CI:2.95-17.15)was an independent risk factor for the survival time of patients with cirrhosis complicated by portal hypertension after receiving TIPS.Conclusion The combination score of ALBI and ALP can effectively predict the prognosis of patients with cirrhosis complicated by portal hypertension after receiving TIPS,and this score is an independent risk factor affecting the survival time of patients.

The structure and potential antigenic epitopes of FliCEcN were analysed using bioinformat-ics technology.With the help of ClonExpress? homologous recombination technology,primers were designed to deletion of different structural domains in the highly variable region of FliCEcN and cloned into pET-28a(+)expression vector for expression.The expressed flagellin variants were identified by SDS-PAGE and Western blot.Endotoxin residues in the flagellin variants were detected by horseshoe crab reagent chromatography,and Caco-2 cells were stimulated with differ-ent concentrations of flagellin variants.The biological activity of each flagellin variant was assessed by detecting the secretion level of IL-8.Bioinformatic analysis showed that most of the structural domains in the highly variable region of FliCEcN were predicted to contain potential antigenic epitopes.PC R results showed that fliC△820-1 518,fliC△736-963,fliC△985-1 200,fliC △748-828,fliC△1 114-1 191,andfliC△1 225-1311 were approximately 1 095,1 566,1 578,1 713,1 716 and 1 707 bp,respectively.SDS-PAGE results showed that the sizes of the flagellin variants treated with nickel column purifi-cation and dialysis replication were about 41.36,57.06,57.50,61.97,61.95 and 61.56 kDa,respec-tively.Western blot results showed that all six flagellin variants reacted specifically with anti-His monoclonal antibody and E.coli H7 antigen diagnostic serum.The results of TLR5 activity assay showed that the flagellin variants missing different structural domains retained their TLR5 agonist function.In this study,six flagellin variants with different structural domains of FliCEcN deletion hypervariable region were successfully constructed,and all of them retained their TLR5 agonist function and showed good biological properties.This provides a reference for further research on the adjuvant effect of flagellin after deletion of different structural domains and the effect of flagel-lin antibody titer on its adjuvant effect.

Parathyromegaly refers to chronic enlargement of the parathyroid glands caused by multiple etiological factors. Pathological conditions, such as hyperparathyroidism, parathyroid hyperfunction, parathyroid adenoma, parathyroid cysts, and parathyroid carcinoma may all lead to parathyromegaly. Notably, calcium intake insufficiency and/or vitamin D insufficiency (CVI), which is the predominant etiology of parathyromegaly, now has been recognized as a global public health challenge. Chronic CVI induces negative calcium balance and relative low serum calcium level, stimulating compensatory parathyroid hyperplasia and enlargement. This progression triggers parathyroid hyperfunction and secondary hyperparathyroidism, resulting in bone mass loss, height reduction, kyphosis, osteoporosis, pathological fractures, metastatic vascular calcification and systemic abnormal calcium migration and calcinosis (such as urolithiasis). During the early stages of parathyromegaly, the condition remains preventable and treatable; However, delayed intervention may lead to irreversible tertiary hyperparathyroidism. CVI-associated parathyromegaly exhibits high prevalence and heterogeneous clinical manifestations, representing a critically underrecognized clinical entity. This article will systematically discuss the etiology, pathological characteristics, clinical consequences, and prevention and control strategies for CVI-related parathyromegaly.

Patients with initially diagnosed breast cancer and uncontrolled hyperthyroidism are at high risk of perioperative thyroid crisis. This article reports two cases of early-stage breast cancer initially diagnosed concurrently with uncontrolled primary hyperthyroidism. In Case 1, the patient received neoadjuvant chemotherapy to control breast cancer progression while concurrently taking antithyroid drugs to manage hyperthyroidism. Hyperthyroidism was controlled during chemotherapy, and the patient successfully underwent surgery after neoadjuvant chemotherapy. Case 2 involved recurrent primary hyperthyroidism with leukopenia after antithyroid drug therapy. Since leukopenia is a relative contraindication for antithyroid drugs, the patient underwent radioactive iodine therapy (iodine-131) and endocrine therapy for one month before proceeding with breast cancer surgery. Through a literature review, this article analyzes preoperative management strategies for uncontrolled hyperthyroidism in initially diagnosed breast cancer patients, emphasizing the importance of normalizing thyroid function to prevent thyroid crisis and reduce perioperative risks.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.

Parathyromegaly refers to chronic enlargement of the parathyroid glands caused by multiple etiological factors. Pathological conditions, such as hyperparathyroidism, parathyroid hyperfunction, parathyroid adenoma, parathyroid cysts, and parathyroid carcinoma may all lead to parathyromegaly. Notably, calcium intake insufficiency and/or vitamin D insufficiency (CVI), which is the predominant etiology of parathyromegaly, now has been recognized as a global public health challenge. Chronic CVI induces negative calcium balance and relative low serum calcium level, stimulating compensatory parathyroid hyperplasia and enlargement. This progression triggers parathyroid hyperfunction and secondary hyperparathyroidism, resulting in bone mass loss, height reduction, kyphosis, osteoporosis, pathological fractures, metastatic vascular calcification and systemic abnormal calcium migration and calcinosis (such as urolithiasis). During the early stages of parathyromegaly, the condition remains preventable and treatable; However, delayed intervention may lead to irreversible tertiary hyperparathyroidism. CVI-associated parathyromegaly exhibits high prevalence and heterogeneous clinical manifestations, representing a critically underrecognized clinical entity. This article will systematically discuss the etiology, pathological characteristics, clinical consequences, and prevention and control strategies for CVI-related parathyromegaly.

Patients with initially diagnosed breast cancer and uncontrolled hyperthyroidism are at high risk of perioperative thyroid crisis. This article reports two cases of early-stage breast cancer initially diagnosed concurrently with uncontrolled primary hyperthyroidism. In Case 1, the patient received neoadjuvant chemotherapy to control breast cancer progression while concurrently taking antithyroid drugs to manage hyperthyroidism. Hyperthyroidism was controlled during chemotherapy, and the patient successfully underwent surgery after neoadjuvant chemotherapy. Case 2 involved recurrent primary hyperthyroidism with leukopenia after antithyroid drug therapy. Since leukopenia is a relative contraindication for antithyroid drugs, the patient underwent radioactive iodine therapy (iodine-131) and endocrine therapy for one month before proceeding with breast cancer surgery. Through a literature review, this article analyzes preoperative management strategies for uncontrolled hyperthyroidism in initially diagnosed breast cancer patients, emphasizing the importance of normalizing thyroid function to prevent thyroid crisis and reduce perioperative risks.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.

The structure and potential antigenic epitopes of FliCEcN were analysed using bioinformat-ics technology.With the help of ClonExpress? homologous recombination technology,primers were designed to deletion of different structural domains in the highly variable region of FliCEcN and cloned into pET-28a(+)expression vector for expression.The expressed flagellin variants were identified by SDS-PAGE and Western blot.Endotoxin residues in the flagellin variants were detected by horseshoe crab reagent chromatography,and Caco-2 cells were stimulated with differ-ent concentrations of flagellin variants.The biological activity of each flagellin variant was assessed by detecting the secretion level of IL-8.Bioinformatic analysis showed that most of the structural domains in the highly variable region of FliCEcN were predicted to contain potential antigenic epitopes.PC R results showed that fliC△820-1 518,fliC△736-963,fliC△985-1 200,fliC △748-828,fliC△1 114-1 191,andfliC△1 225-1311 were approximately 1 095,1 566,1 578,1 713,1 716 and 1 707 bp,respectively.SDS-PAGE results showed that the sizes of the flagellin variants treated with nickel column purifi-cation and dialysis replication were about 41.36,57.06,57.50,61.97,61.95 and 61.56 kDa,respec-tively.Western blot results showed that all six flagellin variants reacted specifically with anti-His monoclonal antibody and E.coli H7 antigen diagnostic serum.The results of TLR5 activity assay showed that the flagellin variants missing different structural domains retained their TLR5 agonist function.In this study,six flagellin variants with different structural domains of FliCEcN deletion hypervariable region were successfully constructed,and all of them retained their TLR5 agonist function and showed good biological properties.This provides a reference for further research on the adjuvant effect of flagellin after deletion of different structural domains and the effect of flagel-lin antibody titer on its adjuvant effect.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.