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.

Myocardial fibrosis(MF)represents a core pathological basis for cardiovascular disease progression,strongly associated with poor prognosis.The clinical evaluation techniques were invasive,lacking specificity and unable to diagnose early MF.Targeted on activated fibroblasts,radionuclide imaging emerged as a transformative solution,leveraging molecular-level specificity for noninvasive early diagnosis,dynamicly monitoring disease progression and evaluation on treatment response of MF.The scientific foundation,evidences of early diagnostic efficacy,and potential of fibroblast-targeted radionuclide imaging applicated in cardiovascular diseases,as well as its role in risk stratification,prognostic assessment and therapeutic decision support of MF were systematically reviewed in this article.

Objective To investigate the mechanism of modified Huanglian Wendan Decoction in improving insulin resistance(IR)HepG2 cells by regulating JAK2/STAT3 signaling pathway.Methods HepG2 cells were incubated with 0.25 mmol/L palmitic acid for 24 h to induce IR model.The cells were divided into model group,drug containing serum group and metformin hydrochloride group.Blank serum,modified Huanglian Wendan Decoction drug containing serum and 2 mmol/L metformin hydrochloride intervention were administered,respectively.Normal cultured HepG2 cells were used as control group.The glucose assay kit was used to detect the glucose content in the cell supernatant,the liver glycogen assay kit was used to detect the glycogen content in the cells,the triglycerides(TG)assay kit was used to detect the TG content in the cells,PAS staining was used to observe the glycogen status of the cells,oil red O staining was used to observe the lipid droplet status of the cells,ELISA assay kit was used to detect the contents of interleukin-6(IL-6)and tumor necrosis factor(TNF)-α in cell supernatant,Western blot was used to detect the protein expressions of Janus kinase 2(JAK2),signal transduction and transcription activator 3(STAT3),LC3 and Beclin-1 in the cells.Results Compared with the control group,the glucose content in the supernatant of HepG2 cells in the model group increased(P<0.01),the intracellular glycogen content decreased(P<0.01),the TG content increased(P<0.01),the glycogen staining area decreased(P<0.01),the lipid droplet staining area increased(P<0.01),the contents of IL-6 and TNF-α in the supernatant increased(P<0.01),the expressions of JAK2 and STAT3 proteins increased(P<0.01),and the protein expression of LC3Ⅱ/LC3Ⅰ and Beclin-1 decreased(P<0.01).Compared with the model group,the glucose content decreased in the drug containing serum group and metformin hydrochloride group(P<0.01),the intracellular glycogen content increased(P<0.01),the TG content decreased(P<0.01),the glycogen staining area increased(P<0.01),the lipid droplet staining area decreased(P<0.01),the contents of IL-6 and TNF-α in cell supernatant decreased(P<0.01),the expressions of JAK2 and STAT3 proteins decreased(P<0.01),and the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins increased(P<0.05,P<0.01).The effect of modified Huanglian Wendan Decoction was better than that of metformin hydrochloride(P<0.05,P<0.01).Conclusion Modified Huanglian Wendan Decoction can possibly improve glucose and lipid metabolism and reduce inflammation in IR-HepG2 cells through intervening JAK2/STAT3 signaling pathway and mediating autophagy.

Objective To investigate the mechanism of modified Huanglian Wendan Decoction in improving insulin resistance(IR)HepG2 cells by regulating JAK2/STAT3 signaling pathway.Methods HepG2 cells were incubated with 0.25 mmol/L palmitic acid for 24 h to induce IR model.The cells were divided into model group,drug containing serum group and metformin hydrochloride group.Blank serum,modified Huanglian Wendan Decoction drug containing serum and 2 mmol/L metformin hydrochloride intervention were administered,respectively.Normal cultured HepG2 cells were used as control group.The glucose assay kit was used to detect the glucose content in the cell supernatant,the liver glycogen assay kit was used to detect the glycogen content in the cells,the triglycerides(TG)assay kit was used to detect the TG content in the cells,PAS staining was used to observe the glycogen status of the cells,oil red O staining was used to observe the lipid droplet status of the cells,ELISA assay kit was used to detect the contents of interleukin-6(IL-6)and tumor necrosis factor(TNF)-α in cell supernatant,Western blot was used to detect the protein expressions of Janus kinase 2(JAK2),signal transduction and transcription activator 3(STAT3),LC3 and Beclin-1 in the cells.Results Compared with the control group,the glucose content in the supernatant of HepG2 cells in the model group increased(P<0.01),the intracellular glycogen content decreased(P<0.01),the TG content increased(P<0.01),the glycogen staining area decreased(P<0.01),the lipid droplet staining area increased(P<0.01),the contents of IL-6 and TNF-α in the supernatant increased(P<0.01),the expressions of JAK2 and STAT3 proteins increased(P<0.01),and the protein expression of LC3Ⅱ/LC3Ⅰ and Beclin-1 decreased(P<0.01).Compared with the model group,the glucose content decreased in the drug containing serum group and metformin hydrochloride group(P<0.01),the intracellular glycogen content increased(P<0.01),the TG content decreased(P<0.01),the glycogen staining area increased(P<0.01),the lipid droplet staining area decreased(P<0.01),the contents of IL-6 and TNF-α in cell supernatant decreased(P<0.01),the expressions of JAK2 and STAT3 proteins decreased(P<0.01),and the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins increased(P<0.05,P<0.01).The effect of modified Huanglian Wendan Decoction was better than that of metformin hydrochloride(P<0.05,P<0.01).Conclusion Modified Huanglian Wendan Decoction can possibly improve glucose and lipid metabolism and reduce inflammation in IR-HepG2 cells through intervening JAK2/STAT3 signaling pathway and mediating autophagy.

Myocardial fibrosis(MF)represents a core pathological basis for cardiovascular disease progression,strongly associated with poor prognosis.The clinical evaluation techniques were invasive,lacking specificity and unable to diagnose early MF.Targeted on activated fibroblasts,radionuclide imaging emerged as a transformative solution,leveraging molecular-level specificity for noninvasive early diagnosis,dynamicly monitoring disease progression and evaluation on treatment response of MF.The scientific foundation,evidences of early diagnostic efficacy,and potential of fibroblast-targeted radionuclide imaging applicated in cardiovascular diseases,as well as its role in risk stratification,prognostic assessment and therapeutic decision support of MF were systematically reviewed in this article.

Objective:To investigate the therapeutic effectiveness and safety of "U shape" en bloc Thulium fiber laser enucleation and resection of the prostate (ThuLERP) technique.Methods:The clinical data of 105 benign prostatic hyperplasia (BPH) patients treated by a single surgeon in Peking University First Hospital from January to October 2022 were retrospectively reviewed. Among them, 50 patients underwent "U-shaped" en bloc technique prostate enucleation (UEBT), and 55 patients underwent prostate lobe removal using the lobe technique (LT). There were no significant differences between UEBT and LT groups ( P>0.05) in term of the age[(69.1±6.9)years old vs.( 68.8±9.1)years old], international prostate symptom score(IPSS)[(22.7±1.9)vs.(22.8±2.7)] and maximum flow rate(Q max ) [(9.0±3.7)ml/s vs.(9.3±4.3)ml/s]. The prostate-specific antigen(PSA) of UEBT group was higher than that of LT group[7.52(3.05, 8.76)ng/ml vs.6.78(1.61, 7.45)ng/ml], and the prostate volume of the UEBT group was larger than that of LT group [(103.49±46.19)ml vs.(75.73±30.69) ml, all P<0.05]. In the UEBT group, the apical of prostate was bluntly enucleated with pre-transection urethral mucosa at the apex of prostate technique. Secondly, glands formed grooves at 12 o'clock after vaporization, which served as anatomical marker. At last, the whole lobe which was like "U shape" were resected using laser. In the LT group, glands was divided to three lobe, the middle, the left and the right lobe was bluntly enucleated respectively. Perioperative data, postoperative complications and clinical outcomes were compared between the two groups. Correlation between enucleation efficiency and enucleation weight was analysed using linear regression. Results:There were no significant differences between the UEBT and LT group ( P>0.05) in term of morcellation time[18(9, 34)min vs.16(8, 28)min], resection rate[(0.5±0.1)g/ml vs.(0.5±0.1)g/ml], catheter indwelling duration[(3.8±1.4)d vs.(3.6±1.1)d] and hospitalization stay[(4.1±0.3)d vs.(3.9±0.8)d].The difference between the UEBT group and LT group in operation time[54(42, 100)min vs.80(60, 150)min], enucleated time[37(26, 75)min vs.47(31, 69)min], hemostasis time[4(3, 6)min vs.9(7, 15)min], enucleation efficiency[(1.8±0.5)g/min vs.(1.1±0.4)g/min] and hemoglobin decline[13(9, 22)g/L vs.17(10, 22)g/L]were statistically significant ( P<0.05). In both groups, postoperative IPSS were (6.6±1.7) and (6.2±1.4) respectively, and Q max were(18.9±3.1)ml/s and (16.8±3.8)ml/s respectively, which were significantly different from that before the operation ( P<0.05). However, there was no significant difference between the two groups ( P>0.05). The enucleation efficiency increased with the increase of prostate volume( r=0.791, 0.880 respectively, P<0.05).After 2 weeks of follow up the postoperative immediate urinary continence rate of UEBT group and LT group were 10.0%(5/50)and 27.3%(15/55), respectively, and the two groups had statistical differences ( P<0.05). But after 3 months of follow up, there was no urinary continence in the two groups, and incidence of postoperative urethral stricture were 2.0%(1/50) and 5.5%(3/55) respectively in UEBT and LT group, whose difference was not significant( P>0.05). Conclusions:ThuLERP can relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLERP with the "U-shaped" en bloc technique was statistically superior to the lobe technique in operation time, enucleation time, enucleation efficiency, hemoglobin decline and also avoided stress urinary incontinence at early stage after operation.

Objective To explore the clinical effect of reconstructing distal radioulnar ligament with al-lograft tendon under wrist arthroscopy in the treatment of chronic PalmerⅠD type triangular fibrocarti-lage complex injury complicated with distal radioulnar joint instability.Methods Clinical data of 15 pa-tients with chronic PalmerⅠD type triangular fibrocartilage complex injury and admitted to our hospital between January 2017 to January 2020 were retrospectively analyzed.All of them were treated with wrist arthroscopic allograft tendon reconstruction of distal radioulnar ligament.During the postoperative follow-up,the wrist range of motion and grip strength were evaluated,while the wrist pain and wrist function were assessed using the visual analogue scale(VAS)and modified Mayo score.Results All pa-tients were followed up twelve to twenty-four months,with an average of(18.15±2.20)months.The postoperative VAS score was(2.56±0.69),significantly better than the preoperative one(6.78±1.24)(P<0.05).Moreover,the postoperative ratio of grip strength between the affected and the healthy hand was(76.18±9.72)%,significantly better than that of(50.18±6.79)%(P<0.05),with increased grip strength.Meanwhile,the postoperative rotational motion of wrist joint[(151.09±12.38)°]improved significantly compared with that before operation[(142.87±10.19)°](P<0.05).According to the modi-fied Mayo score,8 cases were excellent,6 cases were good,and 1 case was fair,reaching an excel-lent and good rate of 93.33%.Conclusion Wrist arthroscopic reconstruction of distal radioulnar liga-ment with allograft tendon is effective in the treatment of chronic PalmerⅠD type triangular fibrocarti-lage complex injury with lower radioulnar joint instability,relieving pain and promoting grip strength and rotational motion.

Objective: To understand current situation epidemiology and associated factors of suicidal ideation among high school students in Yixing, so as to provide basis for targeted intervention. Methods: From March to May 2019, a questionnaire survey was conducted on 12 799 students from 3 junior high schools and 4 senior high schools in Yixing City, Jiangsu Province, using a stratified cluster random sampling method. Latent profile analysis was used to classify suicidal ideation among high school students, the chi square test was used to compare the differences in suicidal ideation among different characteristics of students, multiple Logistic regression was used to analyze influencing factors, a risk predictive nomogram model was constructed and then verified. Results: Three latent classes of suicidal ideation among high school students was divided into three categories were observed: none or mild, moderate, and severe. Among them, 3 034 (23.7%) had moderate suicidal ideation and 753 (5.9%) had severe suicidal ideation. The Logistic regression results showed that gender was female, academic performance was lower midrange, smoking, drinking, popularity with classmates(less popular and unpopularity), family member relationships(general/occasional contradictions/contradictions), trust in others(more trusted/less trusted/less trusted at all), past or current relationships, physical bullying, relationship bullying, verbal bullying, and sexual bullying were the influencing factors for severe suicidal ideation among students ( OR =3.27； 2.18 ；1.63；1.72；2.66, 6.05；3.00,3.29, 6.38；1.71, 6.04, 12.48； 2.50； 1.59； 2.16； 1.45； 1.63, P <0.05). The nomogram prediction model had good discrimination. Conclusions Suicide ideation is influenced by multiple factors. Family and peer situations, as well as being bullied, are all related to the degree the severity of suicidal ideation. Efforts can be made to improve students family and interpersonal relationships, control bullying, then reduce their suicidal ideation which might help prevent suicide ideation among students.

Objective To investigate the expression and clinical significance of mismatch repair (MMR) protein,human epidermal growth factor receptor (HER)2 and Ki-67 in colorectal cancer.Methods The clini-cal data of 559 patients with colorectal cancer who underwent surgical treatment in the hospital from October 2017 to May 2022 were retrospectively analyzed.The expressions of MMR protein (MLH1,MSH2,PMS2, MSH6),HER2 and Ki-67 in colorectal cancer were detected by immunohistochemistry,and the relationship between them and the clinicopathological features of colorectal cancer was analyzed.Results Among the 559 patients with colorectal cancer,43 cases (7.7％) were deficient mismatch repair (dMMR),8 cases(1.4％) were HER2 +++,and 251 cases (44.9％) were Ki-67 +++.The expression rate of dMMR in the colorec-tal cancer patients with different age,tumor location,tumor maximum diameter,gross type,histological grade,lymph node metastasis and TNM stage was significantly different (P<0.05).The expression rate of HER2 ++/+++ in the patients with different gross types of colorectal cancer was statistically significant (P<0.05).The expression rate of Ki-67 +++ in the colorectal cancer patients with different histological types,histological grades,lymph node metastasis,distant metastasis and TNM staging was statistically signifi-cant (P<0.05).There was no correlation between MMR protein and the expression of HER2 and Ki-67 (P>0.05).Conclusion The expression of MMR proteins in colorectal cancer is closely related to its clinicopatho-logical features.

Objective:To investigate the distribution of potential suitable habitats for Ixodes persulcatus in Heilongjiang Province during different climatic periods. Methods:The geographical location data of Ixodes persulcatus in Heilongjiang Province from 1980 to 2023 were collected through literature search and field ecological investigation. The environmental factor variables were downloaded from the WorldClim website and the Resource and Environmental Science and Data Platform. A combination of SDMtune, ENMTools packages, and the maximum entropy (MaxEnt) model were used to predict the potential habitats of Ixodes persulcatus in Heilongjiang Province during different climatic periods and determine its dominant environmental factors. Among them, the time range of historical climatic period data was 1970 - 2000. The future climatic period data (2021 - 2040, 2041 - 2060) were selected as the low forcing scenario (SSP126 scenario) of the shared socioeconomic pathways (SSP) in the Beijing Climate Center - Climate System Model version 2-Medium Resolution, to simulate the impact of global warming on the distribution of potential habitats for Ixodes persulcatus in Heilongjiang Province. Results:A total of 83 geographical distribution sites of Ixodes persulcatus in Heilongjiang Province were obtained. After screening, 10 environmental factors were included in the MaxEnt model. Among them, the cumulative contribution percentage of annual precipitation, average annual temperature, and vegetation type was 67.3%. Compared with historical climatic period, the total potential habitats of Ixodes persulcatus in Heilongjiang Province increased from 29.81 × 10 4 km 2 to 32.24 × 10 4 km 2 in 2041 - 2060. The center of potential habitats moved to 47.75° N, and 128.66° E, with a northwest offset of 126.07° and a migration distance of 45.83 km. Conclusion:With global climate warming, the total potential habitats of Ixodes persulcatus in Heilongjiang Province has increased, showing an overall trend of migration to the northwest.