Objective:To investigate the effect of the stress-induced protein sestrin 3(SESN3)on tumor proliferation and the sensitivity to endocrine therapy in hormone receptor-positive(HR+)breast cancer(BC)and its mechanism.Methods:The cancer genome atlas(TCGA)database was used to analyze the expression level of SESN3 in breast cancer tissue and paracancerous tissue.The clinical samples of breast cancer tissue and paracancerous tissue were collected,and immunohistochemistry(IHC)microarray was used to vali-date the expression of SESN3.Western blot was used to measure the protein expression level of SESN3 in BC cell lines with different pathological subtypes.HR+BC cell lines were used to establish the models of SESN3 overexpression and knockdown,and cell counting kit-8(CCK-8)assay and colony formation assay were used to assess the proliferative capacity of cells;Western blot was used to ana-lyze cell cycle alterations;a subcutaneous xenograft mouse model was used to validate the effect of SESN3 on proliferation in vivo.The bioinformatics analysis and Western blot were used to investigate the downstream mechanisms of SESN3 in regulating proliferation.Results:The analysis of TCGA database and clinical samples showed that the expression of the SESN3 gene in BC tissue was signifi-cantly lower than that in paracancerous tissue,and the patients with high SESN3 expression had a longer progression-free survival time.Compared with the other subtypes of BC cell lines,the HR+BC cells lines MCF-7 and T-47D had a relatively high expression level of SESN3.MCF-7 and T-47D cell lines were used to establish the cell models of knockdown(MCF-7KD and T-47DKD)and overexpres-sion(MCF-7OE and T-47DOE),and compared with the control group,MCF-7KD and T-47DKD cells showed increases in proliferative capacity and the proportion of cells arrested in the G2 and M phases.In vivo tumorigenesis experiments showed a significant increase in tumor growth in mice in the MCF-7KD group.The bioinfor-matics analyses showed a significant negative correlation between the mammalian Target of Rapamycin(mTOR)signaling pathway and SESN3 expression,and Western blot validation showed a significant increase in the expression of mTOR in MCF-7KD and T-47DKD cells,as well as reductions in the protein expression levels of autophagy-related genes.Subsequently,we further confirmed that the knockdown of MCF-7 and T-47D cells led to a decreased sensitivity to endocrine therapy.In addition,MCF-7、T-47D、MCF-7KD、and T-47DKD cell lines were treated with the mTOR inhibitor everolimus(EVE),and there was a significant reduction in proliferative capac-ity in the MCF-7KD group and the T-47DKD group;since the mTOR pathway reduced the sensitivity to endocrine therapy by reducing cell apopto-sis,there was a significant increase in the sensitivity to endocrine therapy with tamoxifen(TAM).Conclusion:The inte-grated database analysis,clinical sample validation,and in vivo/in vitro experimental models show that SESN3 inhibits the proliferation of HR+BC cells via the mTOR pathway and enhances the sensitivity to endocrine therapy.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

This study conducted in-depth interviews to analyze the use of textbooks and learning patterns among medical students from various countries and regions and then proposed loose-leaf digital textbooks as a novel pattern of textbooks. Loose-leaf digital textbooks can meet the requirements of both systematic theoretical education in domestic curricula and the self-directed learning approach in foreign education systems. Compared with traditional textbooks, such digital textbooks have the advantages of flexibility, timeliness, and strong interactivity, thereby enhancing learning efficiency and teaching effectiveness among students. The study further explored the modular design and application strategies for loose-leaf digital textbooks and suggested to achieve personalized education through the integration of digital technologies and improve the adaptability and international competitiveness of textbooks. This study provides innovative ideas for teaching reform in Sino-foreign cooperative education programs of clinical medicine.

This study conducted in-depth interviews to analyze the use of textbooks and learning patterns among medical students from various countries and regions and then proposed loose-leaf digital textbooks as a novel pattern of textbooks. Loose-leaf digital textbooks can meet the requirements of both systematic theoretical education in domestic curricula and the self-directed learning approach in foreign education systems. Compared with traditional textbooks, such digital textbooks have the advantages of flexibility, timeliness, and strong interactivity, thereby enhancing learning efficiency and teaching effectiveness among students. The study further explored the modular design and application strategies for loose-leaf digital textbooks and suggested to achieve personalized education through the integration of digital technologies and improve the adaptability and international competitiveness of textbooks. This study provides innovative ideas for teaching reform in Sino-foreign cooperative education programs of clinical medicine.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Background and Aims:The success of thyroid surgery largely depends on an accurate understanding and proper handling of cervical anatomical structures. As a key anatomical landmark,the middle cervical fascia plays a critical role in thyroid lobe resection and precise identification of the recurrent laryngeal nerve (RLN) during thyroid surgery. However,existing anatomical literature provides limited descriptions of the middle cervical fascia and surrounding spaces. This study was performed to explore the anatomical characteristics of the middle cervical fascia and its adjacent spaces in detail,providing more accurate anatomical evidence and practical guidance to improve the safety and efficacy of thyroid surgery.Methods:First,systematic anatomical studies were conducted on formalin-fixed cadaveric specimens. During the dissections,the structural features of the middle cervical fascia and its surrounding spaces were meticulously recorded,with special attention to its relationships with the thyroid gland,common carotid artery,and infrahyoid muscles. Second,real-time observations and records were made during thyroid surgery on patients with thyroid cancer. The appearance of the middle cervical fascia and changes in related anatomical structures were documented during surgery. Results:Both cadaveric dissections and intraoperative observations revealed that the middle cervical fascia is closely attached to the thyroid gland medially,while laterally it extends across the surface of the common carotid artery to the infrahyoid muscles. When the fascial plane was incised,important structures such as adipose tissue,lymph nodes,RLN,middle thyroid vein,inferior thyroid artery,and inferior thyroid vein were clearly observed. Additionally,it was found that the RLN is enveloped by a thin layer of fascia and adipose tissue. Intraoperative findings showed that RLN exposure techniques based on the middle cervical fascia significantly facilitated RLN identification and improved surgical efficacy. Conclusion:The middle cervical fascia is a key supportive structure on the thyroid surface and an independent fascial plane critical for tissue dissection and precise RLN exposure during thyroid surgery. A deeper understanding of the anatomy of the middle cervical fascia and its surrounding spaces is essential for ensuring the safety and effectiveness of thyroid surgery.

Objective To investigate the role and mechanism of acyl-CoA syntbetase long chain family member 4(ACSL4)in Sevoflurane(Sev)induced neuronal cell damage.Methods Human neuroblastoma SH-SY5Y cells were used as the research object,and control group(dimethyl sulfoxide,10 μmol/L),Sev group and Sev+iron death inhibitor Ferrostatin-1(Fer-1,10 μmol/L)group were set up.CCK-8 method was used to detect cell activity in each group.4.1%Sev exposed postoperative cognitive dysfunction model was constructed in vitro and divided into Ctrol group,Sev group,Sev+si-NC group,Sev+si-ACSL4 group,and Sev+si-ACSL4+compound C group according to the transfection category.The contents of Malonaldehyde(MDA),4-hydroxynonenal(4-HNE),Glutathione(GSH)and Fe2+in each group were detected by colorimetry.The level of reactive oxygen species was detected using a 2',7'-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe.Real time fluorescence quantitative PCR(qRT-PCR)was used to detect the mRNA expression of ACSL4,glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11).Protein immunoblotting was used to detect the expression of ACSL4,GPX4,adenosine 5'-monophosphate activated protein kinase(AMPK),phosphorylated(p)-AMPK,mammalian target of rapamycin(mTOR)and p-mTOR proteins.Results CCK-8 results showed that the cell viability of Sev group(0.41±0.11)was significantly lower than that of control group(0.98±0.07),and the cell viability of Sev+Fer-1 group(0.83±0.09)was significantly higher than that of Sev group(0.41±0.11),and the differences were statistically significant(t=7.572,5.118,all P<0.01).The levels of Fe2+,MDA,4-HNE,ROS and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev group cells,were higher than those in the Ctrol group(t=5.900,7.421,4.795,13.517,10.825,9.945,11.334),the GSH conten,p-mTOR/mTOR ratio,and mRNA and protein expression of SLC7A11 and GPX4 were lower than those in the Ctrol group(t=20.438,3.551,11.460,12.211,6.845,8.287),and the differences were statistically significant(all P<0.05)repectively.The levels of Fe2+,MDA,4-HNE,ROS,and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev+si-ACSL4 group,were lower than those in the Sev+si-NC group(t=3.818,3.164,3.054,4.465,13.088,7.918,9.737),the cell viability,GSH content,p-mTOR/mTOR ratio,and protein expression of SLC7A11 and GPX4 were higher than those in the Sev+si-NC group(t=2.912,7.248,7.574,20.092,5.915),and the differences were statistically significant(all P<0.05),respectively.The cell viability,GSH content,SLC7A11,and GPX4 protein expression in the Sev+si-ACSL4+compound C group were lower than those in the Sev+si-ACSL4 group(t=4.435,8.521,4.522,8.767),while the levels of Fe2+,MDA,4-HNE,and ROS were higher than those in the Sev+si-ACSL4 group(t=10.046,4.004,2.957,3.752),and the differences were statistically significant(all P<0.05).Conclusion Inhibiting ACSL4 expression attenuates Sev-induced iron death in SH-SY5Y cells by activating the AMPK/mTOR signaling pathway.

Background and Aims:The success of thyroid surgery largely depends on an accurate understanding and proper handling of cervical anatomical structures. As a key anatomical landmark,the middle cervical fascia plays a critical role in thyroid lobe resection and precise identification of the recurrent laryngeal nerve (RLN) during thyroid surgery. However,existing anatomical literature provides limited descriptions of the middle cervical fascia and surrounding spaces. This study was performed to explore the anatomical characteristics of the middle cervical fascia and its adjacent spaces in detail,providing more accurate anatomical evidence and practical guidance to improve the safety and efficacy of thyroid surgery.Methods:First,systematic anatomical studies were conducted on formalin-fixed cadaveric specimens. During the dissections,the structural features of the middle cervical fascia and its surrounding spaces were meticulously recorded,with special attention to its relationships with the thyroid gland,common carotid artery,and infrahyoid muscles. Second,real-time observations and records were made during thyroid surgery on patients with thyroid cancer. The appearance of the middle cervical fascia and changes in related anatomical structures were documented during surgery. Results:Both cadaveric dissections and intraoperative observations revealed that the middle cervical fascia is closely attached to the thyroid gland medially,while laterally it extends across the surface of the common carotid artery to the infrahyoid muscles. When the fascial plane was incised,important structures such as adipose tissue,lymph nodes,RLN,middle thyroid vein,inferior thyroid artery,and inferior thyroid vein were clearly observed. Additionally,it was found that the RLN is enveloped by a thin layer of fascia and adipose tissue. Intraoperative findings showed that RLN exposure techniques based on the middle cervical fascia significantly facilitated RLN identification and improved surgical efficacy. Conclusion:The middle cervical fascia is a key supportive structure on the thyroid surface and an independent fascial plane critical for tissue dissection and precise RLN exposure during thyroid surgery. A deeper understanding of the anatomy of the middle cervical fascia and its surrounding spaces is essential for ensuring the safety and effectiveness of thyroid surgery.

Purpose: Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. Methods: A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. Results: Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup.According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. Conclusion High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients.These results are potentially considered beneficial in establishing treatment decisions.

Objective To summarize the outcomes and experience of arterial switch operation (ASO) in the past 10 years in our center.Methods From September 2008 to July 2017,238 patients underwent ASO at Guangzhou Women and Children Medical Center for repair of transposition of the great arteries and Taussig-Bing anomaly.There were 193 male and 45 female.Median age at operation was 2 months (2 days to 10 years) and mean body weight was(4.2 ± 1.7) kg (1.8-20.6 kg).There were TGA and VSD 91 cases,TGA/IVS 110 cases,and Taussig-Bing anomaly 37 cases.Among them 24 patients had an aortic arch anomaly.Intramural coronary artery was found in 8 patients.Results All patients successfully completed the operation,one-stage ASO was perfonned in 232 patients.Two-stage ASO was performed in 6 patients.The mortality was 14.2％.The follow-up duration was 1-10 years (median time,46 mouths).There were 3 died.Two suffered sudden death,and another one arrhythmia.10-year survival rate was 92.8％.Conclusion The outcomes of ASO were satisfactory.The long-term reoperation rate was rare.