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 analyze the clinical characteristics and prognosis of patients with spon-taneous coronary artery dissection(SCAD).Methods A retrospective analysis was conducted in 40 patients with acute myocardial infarction(AMI).All patients were diagnosed with SCAD during hos-pitalization through coronary angiography(CAG)or intravascular ultrasound(IVUS).The clinical characteristics,CAG or IVUS findings,and treatment regimens of the patients were analyzed,and their prognosis was assessed through follow-up.Results Among 40 SCAD patients,there were 11 males and 29 females,with a mean age of(53.04±9.15)years.Twelve patients had identified causative factors,and seven patients presented with chest pain as the initial symptom.CAG or IVUS results showed that a total of 69 SCAD lesions were detected in 40 patients,with 15 patients having a single lesion.The primary treatment approach for the patients was medical therapy.The median fol-low-up duration was 34 months(ranging 2 to 48 months),during which 5 major adverse cardiovascu-lar and cerebrovascular events(MACCE)occurred.The patients were divided into MACCE group(5 patients)and non-MACCE group(35 patients)based on occurrence of MACCE.The mean age and the incidence of regional wall motion abnormalities on echocardiography were higher in the MACCE group than in the non-MACCE group(P＜0.05).Conclusion SCAD has distinct imaging features on CAG,and IVUS can confirm the diagnosis.Most patients are treated with medical therapy and have a generally favorable prognosis.However,patients with older age or regional wall motion abnormali-ties on echocardiography have poorer prognosis.

Objective To establish a rapid detection method for Clostridium botulinum in food.Methods A rapid detection method based on RPA-CRISPR/Cas12a was developed by integrating recombinase polymerase amplification(RPA)with the CRISPR-Cas12a system.After the reaction conditions were optimized,the method's sensitivity,specificity,and usefulness were methodically confirmed.Results and Conclusion The optimized method achieved detection within 1 hour,with a limit of detection(LOD)of 1.91 copies/μL.No cross-reactivity was observed with non-target pathogens.The RPA-CRISPR/Cas12a-based detection method developed in this study exhibits high specificity,sensitivity,and operational simplicity and may provide a feasible solution for the rapid detection of foodborne pathogens.

Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.

Objective:To investigate the role of survivin in the regulation of leptin expression and its sensitivity.Methods:Survivin was overexpressed in adipocytes via lentivirus, and the RNA-sequencing(RNA-seq) was used to explore the effect of survivin on the regulation of adipocyte secretory proteins. Survivin was overexpressed in the inguinal adipose tissue(iWAT) of mice by targeted injection of adeno-associated virus(AAV). The transcription levels of leptin and adiponectin were detected by realtime quantitative PCR(RT-qPCR), and the secretion levels of leptin and adiponectin in cellular supernatants and mice serum were detected by enzyme-linked immunosorbent assay(ELISA). The protein level of phosphorylated signal transducer and activator of transcription 3(STAT3) in hypothalamus was detected by Western blotting to investigate the effect of survivin on central leptin sensitivity.Results:Survivin overexpression in both 3T3-L1 and primary white adipocyte significantly down-regulated the leptin transcriptional expression without affecting the adipocyte differentiation( P<0.01). Overexpression of survivin significantly decreased leptin level without affecting the adiponectin levels in the cellular supernatant( P<0.001). Overexpression of survivin in iWAT via AAV injection, not only specifically down-regulated leptin transcriptional level in a dose dependent manner in local adipose tissue, but also led to a decrease in serum leptin level( P<0.05). In mice fed short-term high-fat diet, STAT3 phosphorylation level in hypothalamus significantly increased, suggesting improved central leptin sensitivity. Conclusion:Survivin could downregulate leptin expression and improve leptin sensitivity in high-fat diet induced obese mice.

Objective:To systemically evaluate the characteristics of cytokine levels in intraocular fluid of neovascular glaucoma (NVG).Methods:Literature on the detection of cytokine levels in NVG published before June 2022 was searched in PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang databases, and China Science and Technology Journal Database (VIP).Two investigators independently completed the literature search, inclusion, and data extraction following the inclusion and exclusion criteria.Quantitative analyses were performed using Stata 16.0 software.Study heterogeneity was assessed using the I2 test, and effects were combined using the appropriate effect model to complete the meta-analysis. Results:A total of 24 studies were screened, including 771 NVG cases and 727 age-related cataract cases (control group).The standardized mean difference ( SMD) of the combined effect value of vascular endothelial growth factor (VEGF) mass concentration in the aqueous humor between the two groups was 8.79, with a 95% confidence interval ( CI) of 6.43 to 11.14.The SMD of interleukin-6 (IL-6) between the two groups was 12.50, with a 95% CI of 9.41 to 15.58.The VEGF and IL-6 levels in aqueous humor and vitreous humor were significantly higher in NVG group than in control group (all at P<0.05).The pigment epithelium-derived factor (PEDF) level in aqueous humor was lower in NVG group than in control group ( SMD: -3.03, 95% CI: -5.50--0.55, P<0.05).The levels of IL-8 ( SMD: 3.99, 95% CI: 1.14-6.85), erythropoietin (EPO) ( SMD: 9.62, 95% CI: 0.44-18.79), placental growth factor (PIGF) ( SMD: 2.62, 95% CI: 1.38-3.86), tumor necrosis factor-α (TNF-α) ( SMD: 3.37, 95% CI: 1.87-4.87) were all significantly higher in NVG group than in control group (all at P<0.05).There was no significant difference in IL-1β level in aqueous humor between the two groups ( P>0.05). Conclusions:In NVG patients, VEGF, IL-6, IL-8, EPO, PIGF, TNF-α levels are obviously increased and PEDF level is obviously decreased.These biomarkers can be used as potential predictors or therapeutic targets for NVG.

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Objective: To explore the relationship between isotemporal substitution of 10 min/d of vigorous physical activity (VPA), moderate physical activity (MPA), walking, sedentary behavior (SB) and sleep (SLP) and depression among vocational school students with different duration of moderate-to-vigorous physical activity (MVPA), so as to provide time allocation suggestions for reducing depression levels. Methods: The convenient cluster sampling method was adopted to conduct a questionnaire survey among 8 149 grade one to grade three students in 14 vocational schools in Shanghai and Jiangsu Province from December 2021 to January 2022. According to whether the MVPA reached 60 min/d, the vocational school students were divided into the MVPA standard group and the MVPA non-standard group, and the isotemporal substitution model was used for analysis. Results: About 19.81% of students were in the MVPA standard group. In the MVPA non-standard group, substituting MPA for all other studied behaviors and substituting SLP for walking and SB were negatively correlated with depression ( β =-0.78, -0.90, -0.88, -0.83; -0.07 , -0.05, P <0.05), and the association of MPA substitution was much greater than that of SLP substitution. In the MVPA standard group, replacing VPA, walking and SB with SLP were all negatively associated with depression ( β =-0.23, -0.12, -0.10 ), whereas replacing MPA, SB and SLP with VPA was all positively associated with depression ( β =0.15, 0.13, 0.23) ( P <0.05). Conclusion The MVPA level of vocational school students is low. The effects of isotemporal substitution for VPA and MPA are different when MVPA duration is up to standard and when MVPA duration is not up to standard. Appropriate time allocation suggestions should be provided based on the characteristics of adolescents with different MVPA durations.

Objective:To assess the clinical result of repeated combined detrusor-trigone botulinum toxin A(BTX-A)injection and intermittent catheterization(IC) for male adults with neurogenic detrusor overactivity (NDO) and urinary incontinence(UI) secondary to spinal cord injury(SCI).Methods:From January to August 2021, the data of 43 adult male patients with NDO and UI secondary to SCI who received repeated trigone-including intradetrusor BTX-A injection in Guangdong Provincial Work Injury Rehabilitation Hospital were retrospectively analyzed. The mean age of the patients was (29.1±10.7) years. The mean incontinence specific quality of life (I-QOL) was (39±4.8). The UI episodes was (11.9±2.6), mean voiding volume was (170.7±20.1)ml, mean maximum detrusor pressure at first NDO was (81.4±19.6) cmH 2O and mean volume at first NDO was (169.1±40.0)ml.All patients received trigone-including intradetrusor BTX-A (300 U, 30 sites) injection for four times and IC. Clinical data including I-QOL, bladder diary, video-urodynamic test and adverse events were recorded at baseline and 12 weeks after each injection. Results:Mean interval between four injections were (220.6±27.4), (222.8±24.1) and (224.4±39.0) d ( P=0.13). Compared with baseline data before first injection, mean I-QOL after the first, second, third and fourth injection increased to (54.9±9.1), (56.1±7.9), (61.7±9.1) and (68.8±8.9) (all P<0.001). The number of urinary incontinence cases decreased to 36, 35, 35 and 33 (all P<0.05). The mean urinary incontinence episodes per day decreased to (4.4±0.6), (3.8±0.4), (2.2±0.5) and (2.1±0.3)(all P<0.001). Mean voiding volume increased to (288.3±40.2), (300.0±38.6), (316.9±46.8) and (319.5±36.7) ml (all P<0.001). Mean maximum detrusor pressure at first NDO decreased to (29.4± 11.0), (26.1±8.7), (20.3±5.9) and (18.5±6.0) cmH 2O (all P<0.001) and mean volume at first NDO increased to (270.0±48.7), (284.9±51.3), (287.7±47.9) and (303.0±46.2) ml (all P<0.001), respectively. Compared with four injections, no difference in response was found in the mean I-QOL, the number of urinary incontinence cases, mean urinary incontinence episodes mean voiding volume, mean maximum detrusor pressure at first NDO and mean volume at first NDO (all P>0.05). No de novo VUR occurred and 2 cases of grade Ⅱ VUR at baseline had resolved after the first injection. 9 patients experienced serious gross hematuria within first week after injection, but the urine returned to clear by prolonging the catheter indwelling time or bladder irrigation. 12 patients with active urinary tract infection were treated with indwelling catheter and sensitive antibiotics. Patients continued IC when the symptoms, signs and laboratory examination were normal. Conclusions:Combined detrusor-trigone BTX-A injection and IC could help decrease detrusor pressure, restore some of the lower urinary tract function and improve the quality of life for male patients with NDO and UI secondary to SCI. Repeated injection is as effective and safe as the first injection.

Objective: To analyze under 5 years old mortality rate during 2016-2021 in Xicheng District, Beijing, and to provide scientific basis for further reducing infant mortality rate and under 5 years old mortality rate. Methods: A descriptive statistical analysis was conducted on the mortality surveillance data of children under 5 years old reported by Preventive Health Department of Xicheng District Community Health Service Center during 2016-2021. Results: During 2016-2021, under 5 mortality, infants and newborn mortality in Xicheng District decreased from 2.31‰, 1.85‰ and 1.12‰ to 1.55‰, 1.07‰ and 0.48‰ respectively. There was no significant difference in mortality rate between 2016 and 2021( P >0.05). The leading cause of death among children under 5 years of age included other congenital abnormalities(except congenital heart disease and down s syndrome)(18.79%), preterm birth/low birth weight (16.36%) and birth asphyxia(7.88%). Infant deaths accounted for 69.23%- 80.00 % of deaths of children under 5 years of age, and neonatal mortality accounted for 44.44%-71.43% of infant mortality. Conclusion It is necessary to carry out relevant preventive intervention and quality management based on the main causes of death, and to further improve the management of critically ill neonates and reduce neonatal mortality.