Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To investigate the relationship between serum insulin-like growth factor-1 (IGF-1) levels and intracranial or extracranial atherosclerosis in patients with cerebral small vessel disease (CSVD).Methods:A total of 407 patients with CSVD admitted to Xiangya Hospital of Central South University between July 2021 and September 2023 were enrolled in the study. Carotid duplex ultrasound was used to measure the internal diameter, intima-media thickness (IMT), vascular wall thickness, plaque property score, stenosis index, and stenosis ratio of the bilateral common carotid arteries, internal carotid arteries, external carotid arteries, and vertebral arteries. Magnetic resonance angiography was used to assess the degree of stenosis in intracranial arteries. Patients were divided into 4 groups based on the serum IGF-1 levels (low level group:≤5.21 ng/ml, medium level group:>5.21 ng/ml and ≤10.73 ng/ml, high level group:>10.73 ng/ml and ≤24.26 ng/ml, extremely high level group:>24.26 ng/ml). The IMT of the common carotid artery, carotid plaques, diameters of various cervical vascular lumens, carotid artery diameter stenosis, and intracranial artery stenosis in 4 groups of the patients were compared. The relationship between IGF-1 and intracranial and extracranial atherosclerosis was analyzed by univariate Logistic regression analysis and multivariate Logistic regression analysis.Results:There were inter group differences among the 4 groups in internal carotid artery diameter [low level group 5.45 (0.50) mm vs medium level group 5.32 (0.55) mm vs high level group 5.30 (0.55) mm vs extremely high level group 5.30 (0.50) mm; H=8.210, P=0.042]. The carotid IMT [low level group 0.80 (0.05) mm vs medium level group 0.80 (0.05) mm vs high level group 0.83 (0.03) mm vs extremely high level group 0.83 (0.09) mm; H=8.107, P=0.044], the proportion of carotid artery vascular wall thickening [low level group 52.9%(54/102) vs medium level group 48.0%(49/102) vs high level group 68.3%(69/101) vs extremely high level group 60.8%(62/102); χ2=9.889, P=0.020], the carotid artery plaque property score [low level group 1 (2) vs medium level group 2 (2) vs high level group 2 (2) vs extremely high level group 2 (2); H=8.913, P=0.030] and the proportion of anterior cerebral artery stenosis [low level group 2.9%(3/102) vs medium level group 2.0%(2/102) vs high level group 4.0%(4/101) vs extremely high level group 10.8%(11/102); χ2=10.473, P=0.014] had inter group differences among the 4 groups, and the differences were statistically significant. Univariate Logistic regression analysis indicated that carotid artery vascular wall thickening ( OR=1.197, 95% CI 1.003-1.429, P=0.046), anterior cerebral artery stenosis ( OR=1.814, 95% CI 1.148-2.867, P=0.011), and basilar artery stenosis ( OR=1.530, 95% CI 1.084-2.159, P=0.015) were correlated with IGF-1 levels. Multivariate Logistic regression analysis revealed that after adjusting for age, gender, low-density lipoprotein cholesterol (LDL-C), and C-reactive protein, IGF-1 was positively correlated with the carotid artery vascular wall thickening ( OR=1.311, 95% CI 1.014-1.696, P=0.039); after adjusting for age, IGF-1 was positively correlated with the anterior cerebral artery stenosis ( OR=2.130, 95% CI 1.201-3.776, P=0.010); after adjusting for gender, low-density lipoprotein cholesterol, and cholesterol levels, IGF-1 was positively correlated with basilar artery stenosis ( OR=1.688, 95% CI 1.063-2.681, P=0.027). Conclusions:There is an association between IGF-1 levels and intracranial and extracranial atherosclerosis in patients with CSVD. IGF-1 may play a role in the development and progression of atherosclerosis in CSVD.

Objective:To investigate the relationship between serum insulin-like growth factor-1 (IGF-1) levels and intracranial or extracranial atherosclerosis in patients with cerebral small vessel disease (CSVD).Methods:A total of 407 patients with CSVD admitted to Xiangya Hospital of Central South University between July 2021 and September 2023 were enrolled in the study. Carotid duplex ultrasound was used to measure the internal diameter, intima-media thickness (IMT), vascular wall thickness, plaque property score, stenosis index, and stenosis ratio of the bilateral common carotid arteries, internal carotid arteries, external carotid arteries, and vertebral arteries. Magnetic resonance angiography was used to assess the degree of stenosis in intracranial arteries. Patients were divided into 4 groups based on the serum IGF-1 levels (low level group:≤5.21 ng/ml, medium level group:>5.21 ng/ml and ≤10.73 ng/ml, high level group:>10.73 ng/ml and ≤24.26 ng/ml, extremely high level group:>24.26 ng/ml). The IMT of the common carotid artery, carotid plaques, diameters of various cervical vascular lumens, carotid artery diameter stenosis, and intracranial artery stenosis in 4 groups of the patients were compared. The relationship between IGF-1 and intracranial and extracranial atherosclerosis was analyzed by univariate Logistic regression analysis and multivariate Logistic regression analysis.Results:There were inter group differences among the 4 groups in internal carotid artery diameter [low level group 5.45 (0.50) mm vs medium level group 5.32 (0.55) mm vs high level group 5.30 (0.55) mm vs extremely high level group 5.30 (0.50) mm; H=8.210, P=0.042]. The carotid IMT [low level group 0.80 (0.05) mm vs medium level group 0.80 (0.05) mm vs high level group 0.83 (0.03) mm vs extremely high level group 0.83 (0.09) mm; H=8.107, P=0.044], the proportion of carotid artery vascular wall thickening [low level group 52.9%(54/102) vs medium level group 48.0%(49/102) vs high level group 68.3%(69/101) vs extremely high level group 60.8%(62/102); χ2=9.889, P=0.020], the carotid artery plaque property score [low level group 1 (2) vs medium level group 2 (2) vs high level group 2 (2) vs extremely high level group 2 (2); H=8.913, P=0.030] and the proportion of anterior cerebral artery stenosis [low level group 2.9%(3/102) vs medium level group 2.0%(2/102) vs high level group 4.0%(4/101) vs extremely high level group 10.8%(11/102); χ2=10.473, P=0.014] had inter group differences among the 4 groups, and the differences were statistically significant. Univariate Logistic regression analysis indicated that carotid artery vascular wall thickening ( OR=1.197, 95% CI 1.003-1.429, P=0.046), anterior cerebral artery stenosis ( OR=1.814, 95% CI 1.148-2.867, P=0.011), and basilar artery stenosis ( OR=1.530, 95% CI 1.084-2.159, P=0.015) were correlated with IGF-1 levels. Multivariate Logistic regression analysis revealed that after adjusting for age, gender, low-density lipoprotein cholesterol (LDL-C), and C-reactive protein, IGF-1 was positively correlated with the carotid artery vascular wall thickening ( OR=1.311, 95% CI 1.014-1.696, P=0.039); after adjusting for age, IGF-1 was positively correlated with the anterior cerebral artery stenosis ( OR=2.130, 95% CI 1.201-3.776, P=0.010); after adjusting for gender, low-density lipoprotein cholesterol, and cholesterol levels, IGF-1 was positively correlated with basilar artery stenosis ( OR=1.688, 95% CI 1.063-2.681, P=0.027). Conclusions:There is an association between IGF-1 levels and intracranial and extracranial atherosclerosis in patients with CSVD. IGF-1 may play a role in the development and progression of atherosclerosis in CSVD.

Objective:To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing.Methods:Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results:Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] ( t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] ( t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] ( t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests ( t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) ( t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) ( t=3.88, P=0.005; t=3.02, P=0.017). Conclusions:The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

Objective:To compare and analyze the calcification characteristics and diagnostic efficiency of different breast lesion types using digtal breast tomosynthesis (DBT) and full-field digital mammography (FFDM).Methods:Totally 1 263 patients who underwent both DBT and FFDM at the same time from January 2015 to December 2018 in Dahua Hospital, Xuhui district, Shanghai were analyzed retrospectively. Benign and malignant calcification should be confirmed by pathology or a follow-up of 24 months or more using mammography, and the results of DBT and FFDM were taken as a gold standard. The detection rate and diagnostic efficiency of different types of benign and malignant breast calcification with the two methods were compared and analyzed. The detection rate of morphology and distribution of malignant calcification were compared among groups.Results:There were 240 cases with non-dense breast including 56 cases with benign calcification and 13 cases with malignant calcification. Meanwhile, there were 1 023 cases with dense breast, including 356 cases with benign calcification and 63 cases with malignant calcification. In the cases of non-dense breast, the detection rates of benign calcification by DBT and FFDM were 22.9% (55/240) and 21.7% (52/240), whereas the rates of malignant calcification were 5.0% (12/240) and 4.6% (11/240), all without statistically significances（χ2=0.108, 0.046, P>0.05). No significant differences were observed in the morphology and distribution of malignant calcification detection rates ( P>0.05). In the cases of dense breast, the benign calcification detection rates by DBT and FFDM were 34.2% (350/1 023) and 31.9% (326/1 023), whereas the detection rates of malignant calcification were 6.0% (61/1 023) and 4.9% (50/1 023), all without statistically significances (χ2=1.273 and 1.153, P>0.05). DBT detected more cases of amorphous and cluster distribution of malignant calcification than FFDM, with statistically significant differences (χ2=12.921 and 11.667, P<0.05). The area under ROC curve of DBT and FFDM in diagnosis of non-dense breast were 0.993 and 0.992, and 0.987 and 0.964 in dense breast, respectively, with no significant differences ( Z= 0.136 and 1.391, P>0.05). Conclusions:Compared with FFDM, DBT shows no statistical difference in the diagnostic efficiency of breast calcification. However, it has certain advantages in detecting malignant, amorphous, and clustered calcification in dense breast. DBT has a potential to improve the accuracy of BI-RADS classification of breast calcification.

Objective To demonstrate the feasibility of high-resolution computed tomography(HRCT)reconstructed with a model-based iterative reconstruction (MBIR)for evaluating early peripheral lung cancer (≤3 cm),by comparing image quality obtained from MBIR,filtered back proj ection reconstruction(FBP)and state of the art adaptive statistical iterative reconstruction(ASIR)algorithm respectively.Methods A total of 30 patients confirmed with lung cancer by postoperative pathology were enrolled in the study.A chest phantom was also used to evaluate image noise,spatial resolution and density resolution.Both patients and chest phantom were received HRCT,and the images were reconstructed using FBP,ASIR(40% ASIR and FBP mix)and MBIR.The objective CT value, standard deviation(SD)and signal noise ratio(SNR)were measured.Two radiologists used a semi-quantitative to rate subjective image quality of lung nodules.Results There was no significant difference in CT value between the three reconstruction algorithms (P>0.05).But significant improvements in objective image noise were observed in MBIR compared with FBP and ASIR (P<0.05):including the SD value in back muscle [(12.63±1.70)with MBIR vs (31.58±5.21)with FBP and (24.55±4.14)with ASIR],and in subcutaneous fat [(12.77±2.53)vs (24.39±5.08)and (19.20±4.11)].Subjective image noise of the three group were also significantly difference:FBP with lowest subjective noise score;and MBIR with highest subjective noise score.The sharpness of small vessels and bronchi and diagnostic acceptability with MBIR were significantly better than with FBP and ASIR (P< 0.05).Conclusion Lung HRCT reconstructed with MBIR provides diagnostically more acceptable images for the detailed analyses of peripheral lung cancer compared with FBP and ASIR.

Objective: To validate a nomogram model based on prostate health index (PHI) for predicting prostate cancer (PCa). Methods: The pre-operation serum and clinical data were collected for suspected PCa patients (aged 34 to 90 years), who visited Peking University First Hospital from August 2015 to May 2017 and received transrectal ultrasound-guided prostate biopsy. A total of 391 suspected PCa with total prostate-specific antigen (tPSA)>4 ng/ml were selected into this study, including 235 cases with tPSA level of 4-10 ng/ml and 156 cases with tPSA>10 ng/ml. The p2PSA was tested in all cases and then PHI was calculated. The biopsy results were considered as the gold standard to diagnose PCa. The nomogram model established in Shanghai based on PHI, age and prostate volume was validated in all cases enrolled in this study. Receiver operator curves (ROC) were used to assess the ability of nomogram model to predict PCa. Results: Of 391 male patients included in this study, 175(44.8%)were finally diagnosed as PCa. ROC curves indicated that, the area under the curve (AUC) of the nomogram model for predicting PCa among 391 cases was higher than that of the traditional indicator tPSA (AUC: 0.786 vs 0.578, P<0.000 1). And f/t(AUC: 0.786 vs 0.672, P=0.000 2). For those people with tPSA level of 4-10 ng/ml, the AUC of the nomogram model was also higher than that of tPSA (AUC: 0.720 vs 0.513, P=0.000 3) and f/t(AUC: 0.720 vs 0.626, P=0.042 5). Conclusion The nomogram model based prostate health index (PHI) was validated to have a good auxiliary diagnostic value for PCa in our center.(Chin J Lab Med, 2018, 41: 536-540)

Objective To evaluate the effect of quorum sensing luxS gene on biofilm formation through construction of a luxS overexpression strain by Streptococcus mutans(Sm).Methods In order to construct pIB-luxS plasmid,the luxS gene fragment amplified by PCR was inserted into the shuttle plasmid pIB169 by corresponding double digests.The pIB-luxS plasmid was linearized electro-transformed into Sm cell and the overexpression strain was selected on chloramphenicol plate and testified by electrophoresis and western blot.The growth rate of both Sm wild type strain and its luxS overexpression strain were observed.Methyl thiazolyl tetrazolium(MTT) assay method was used to compare the biofilm formation quantificationally by both strains at different time points and containing different sucrose.The structures of the biofilms were observed by using confocal laser scanning microscopy,and biofilm-related gene expressions were investigated by real-time PCR.All experiments were performed in triplicate.Results The luxS overexpression strain was successfully constructed and confirmed by electrophoresis and Western blotting.The planktonic growth mode of the wild-type and luxS overexpression strain showed no difference,but biofilm formed by Sm overexpression strain was 0.400 ±0.009 and 0.609±0.041 at 14 and 24 h,higher than the wild type strain biofilm at the same time point(0.352 ±0.028 and 0.533 ±0.014,respectively,P＜ 0.05).After adding 0.125％ sucrose,biofilm formed by Sm overexpression strain raised to 1.041 ±0.038,higher than that by the wild type strain(0.831 ±0.020,P＜0.05).The biofilm formed by both strains were also increased with the sucrose concentration increase,but there was no difference between them.The overexpression strain aggregated into distinct clusters on structure,genes expression including gtfB,ftf,gbpB,relA,brpA,smu630,comDE,vicR were increased(6.10±0.12,3.34±0.07,8.75±0.13,2.96±0.04,5.20± 0.19,2.20±0.06,2.32±0.07 and 10.67±0.57 fold) compared to the wild-type strain(P＜0.05).Conclusions Quorum sensing luxS gene can promote the biofilm formation of Sm.

Objective To investigate the predominant contribution of methyl-metabolism pathway to the regulation of LuxS of Strecptococcus mutans.Methods The differences in biofilm formation and aciduricity of Strecptococcus mutans among the methyl-metabolism-complementation strain(KO-S),the parental wide-type strain(WT) and the luxS null strain(KO) were observed by real-time PCR for monitoring the transcriptional level of genes related to biofilm formation(smu.238,gtfD) and aciduricity(smu.44,smu.46) of the studied strains,methyl thiazolyl tetrazolium(MTT) for quantifying the biofilm of the exhibited strains and confocal laser scanning microscopy for estimating the structure of the biofilm.Results The transcriptional level of smu.44,smu.46,smu.238,gtfD in WT were 1.289±0.051,1.694±0.140,1.565±0.107,1.667±0.196 respectively; in KO were 1.001 ±0.045,1.007±0.151,1.000±0.021,1.012±0.196 respectively,downregulated compared with WT(P＜0.05); in KO-S were 4.662 ± 0.091,5.019 ± 0.258,3.462 ± 0.029,3.071 ±0.136 respectively,upregulated compared both with KO and with WT(P＜0.05).The quantity of biofilms formed by the studied strains were WT(1.592± 0.213),KO(0.939± 0.029),KO-S(2.177 ± 0.226),KO-P(1.020±0.093),respectively,representing a less quantity by KO and KO-P than WT(P＜0.05) and a more quantity by KO-S than other three stains(P＜0.05).According to the observation of biofilms texture by confocal laser scanning microscopy,the WT biofilm was condensed and even.In contrast,fissures and gaps were found scattered in biofilms of KO,KO-P while lessened in that of KO-S,in which high-density bacterial aggregates were observed.The acid assay indicated a smaller biofilm decrease by WT and KO-S than that by KO and KO-P(P＜0.05).Conclusions The methyl-metabolism pathway contributes to LuxS regulation on biofilm formation and auiduricity of Strecptococcus mutans.

Objective To develop a short Chinese version of the center for epidemiological studies depression scale(CES-D).Method A stratified random nationwide sample with 30801 normal people and a mentally ill sample with 415 patients were tested.Items in the short version were chosen according to both the result of independent t-test in current study and the result of reliance and validity.Cut-off scores were offered to check up depressions.Result The internal consistency reliability of the 9-item Chinese version CES-D ranged from 0.85 to 0.88.The test-retest reliability was 0.49(P＜0.001).All item-total correlations were higher than 0.5.The correlation between sumscores of the original scale and sunscores of the Chinese short version ranged from 0.94 to 0.96 (P＜ 0.001) in all the samples.The sum scores of initial diagnosis depression sample were significantly higher than that of treated depression sample and common sample.A two-dimension structure was testified.The cut-off scores of the short version were 10 and 17.Conclusion The 9-item Chinese version of CES-D can be used in various samples with reliable and valid effect.