Breast cancer is the most common malignant tumor in women worldwide.HER2-positive and HER2-low breast cancers are highly aggressive subtypes with poor prognosis.First-line combination therapies targeting HER2 have significantly improved treatment outcomes for patients with advanced and metastatic breast cancer,but resistance inevitably develops.The emergence of antibody-drug conjugates(ADCs)brings new hope for the treatment of advanced HER2-positive and HER2-low breast cancers.This article analyzes the efficacy and safety of key ADC drugs,including adotrastuzumab emtansine(T-DM1),trastuzumab deruxtecan(DS-8201,T-DXd)and other drugs in the treatment of advanced HER2-positive and HER2-low breast cancers.It also reviews mechanisms of ADC resistance and discusses corres-ponding management strategies,aiming to provide more efficient and personalized treatment options for patients with advanced HER2-pos-itive and HER2-low breast cancers.

Objective:To investigate the impact of perceived barriers to cardiac rehabilitation on adherence to cardiac rehabilitation and the mediating effect of cardiac impact denial in elderly patients after percutaneous coronary intervention (PCI) .Methods:This study was a cross-sectional survey. From August 2023 to July 2024, 336 elderly patients with PCI who were discharged from the First Affiliated Hospital of Wenzhou Medical University and needed phaseⅡ cardiac rehabilitation were selected for the study. General Information Questionnaire, Adherence of Cardiac Rehabilitation Assessment Scale in Patients with Coronary Heart Disease (ACRAS-CHD) , Cardiac Rehabilitation Barriers Scale (CRBS) , and Cardiac Denial of Impact Scale (CDIS) were used to survey the patients. Bootstrap method was used to sample 5 000 for mediating effect tests.Results:A total of 336 questionnaires were distributed and 324 valid questionnaires were recovered, with a valid recovery rate of 96.43% (324/336) . Among 324 elderly patients after PCI, ACRAS-CHD score, CRBS score, and CDIS score were (73.19±5.46) , (79.35±6.60) , and (30.57±3.66) , respectively. The direct effect of perceived barriers to cardiac rehabilitation on adherence to cardiac rehabilitation in elderly patients after PCI was -0.368, which accounted for 74.49% (-0.368/-0.494) of the total effect. The mediating effect of cardiac impact denial between perceived barriers to cardiac rehabilitation and adherence to cardiac rehabilitation in elderly patients after PCI was -0.126, which accounted for 25.51% of the total effect (-0.126/-0.494) .Conclusions:Elderly patients after PCI have poor adherence to cardiac rehabilitation. Perceived cardiac rehabilitation barriers reduce cardiac rehabilitation adherence in elderly patients after PCI, and cardiac impact denial exerts a partial mediating effect between perceived cardiac rehabilitation barriers and cardiac rehabilitation adherence.

Breast cancer is the most common malignant tumor in women worldwide.HER2-positive and HER2-low breast cancers are highly aggressive subtypes with poor prognosis.First-line combination therapies targeting HER2 have significantly improved treatment outcomes for patients with advanced and metastatic breast cancer,but resistance inevitably develops.The emergence of antibody-drug conjugates(ADCs)brings new hope for the treatment of advanced HER2-positive and HER2-low breast cancers.This article analyzes the efficacy and safety of key ADC drugs,including adotrastuzumab emtansine(T-DM1),trastuzumab deruxtecan(DS-8201,T-DXd)and other drugs in the treatment of advanced HER2-positive and HER2-low breast cancers.It also reviews mechanisms of ADC resistance and discusses corres-ponding management strategies,aiming to provide more efficient and personalized treatment options for patients with advanced HER2-pos-itive and HER2-low breast cancers.

Objective:To investigate the impact of perceived barriers to cardiac rehabilitation on adherence to cardiac rehabilitation and the mediating effect of cardiac impact denial in elderly patients after percutaneous coronary intervention (PCI) .Methods:This study was a cross-sectional survey. From August 2023 to July 2024, 336 elderly patients with PCI who were discharged from the First Affiliated Hospital of Wenzhou Medical University and needed phaseⅡ cardiac rehabilitation were selected for the study. General Information Questionnaire, Adherence of Cardiac Rehabilitation Assessment Scale in Patients with Coronary Heart Disease (ACRAS-CHD) , Cardiac Rehabilitation Barriers Scale (CRBS) , and Cardiac Denial of Impact Scale (CDIS) were used to survey the patients. Bootstrap method was used to sample 5 000 for mediating effect tests.Results:A total of 336 questionnaires were distributed and 324 valid questionnaires were recovered, with a valid recovery rate of 96.43% (324/336) . Among 324 elderly patients after PCI, ACRAS-CHD score, CRBS score, and CDIS score were (73.19±5.46) , (79.35±6.60) , and (30.57±3.66) , respectively. The direct effect of perceived barriers to cardiac rehabilitation on adherence to cardiac rehabilitation in elderly patients after PCI was -0.368, which accounted for 74.49% (-0.368/-0.494) of the total effect. The mediating effect of cardiac impact denial between perceived barriers to cardiac rehabilitation and adherence to cardiac rehabilitation in elderly patients after PCI was -0.126, which accounted for 25.51% of the total effect (-0.126/-0.494) .Conclusions:Elderly patients after PCI have poor adherence to cardiac rehabilitation. Perceived cardiac rehabilitation barriers reduce cardiac rehabilitation adherence in elderly patients after PCI, and cardiac impact denial exerts a partial mediating effect between perceived cardiac rehabilitation barriers and cardiac rehabilitation adherence.

Objective:To evaluate the role of aquaporin 4 (AQP4) in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice and the relationship with protein kinase C (PKC).Methods:One hundred and fifty clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), mechanical ventilation group (group V), LY317615 group (group L), dexmedetomidine group (group D), and dexmedetomidine+ PMA group (group DP). Group C spontaneously breathed air for 6 h. The animals were mechanically ventilated for 6 h in group V. PKC inhibitor LY3176 15 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in group L. Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in D and DP groups. PKC activator PMA 15 μg/kg was intraperitoneally injected at 60 min before mechanical ventilation in group DP. Mice were anesthetized at 1 day after mechanical ventilation, then sacrificed and hippocampal tissues were taken for microscopic examination of pathological changes in the hippocampal CA1 and CA3 areas (with a light microscope). Brain tissues were also taken to measure the water content and content of Evans blue (EB) and to detect the expression of PKC and AQP4 (by Western blot). The cognitive function was evaluated using a novel object recognition task at 3 days after mechanical ventilation. Results:Compared with group C, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group V and group DP. Compared with group V, the water content and EB content of brain tissues were significantly decreased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was down-regulated, the percentage of novel object exploration and discrimination index were increased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was significantly attenuated in group D and group L. Compared with group D, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group DP. Conclusions:AQP4 is involved in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice, and the mechanism is related to inhibiting activation of PKC.

Objective: To explore the association between exposure to bedroom night light during sleep and emotional symptoms in children and provide a scientific basis for subsequent effective prevention and intervention. Methods: In December 2021, 1 926 students from grades 4 to 6 were recruited to conduct a student questionnaire survey in two primary schools in Tianchang of Chuzhou City, Anhui Province. The data, including general demographic information, use of night lights and curtains, emotional symptoms, and other information, was collected. Binary Logistic regression analysis was used to examine the correlation between night light use and children s emotional symptoms. Results: The reporting rates of depression symptoms, generalized anxiety symptoms, social phobia, and obsessive compulsive symptoms of the children were 2.5%, 2.6%, 3.4% and 2.5%, respectively. About 12.6% of children often sleep with a night light on, and 22.0% of children did not close the curtains. Binary Logistic regression analysis revealed that frequent sleep with night lights was associated with an increased risk of depression symptoms( OR=2.29, 95%CI = 1.04- 5.03), social phobia ( OR=1.93, 95%CI =1.02-3.64) and obsessivecompulsive symptoms ( OR=3.44, 95%CI =1.72-6.88) in children( P < 0.05). Conclusion There is a positive correlation between bedroom night light exposure during sleep and the detection rate of children s emotional symptoms. The attention should be paid to bedroom light environment of children during sleep to reduce the adverse effects of night light exposure on the mental health.

Objective:To evaluate the role of transient receptor potential vanillic acid 4 (TRPV4) in dexmedetomidine-induced improvement in cognitive function in mice with mechanical ventilator-caused brain injury.Methods:Ninety clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=18 each) using a random number table method: control group (group C), mechanical ventilation group (group V), HC-067047 group (group H), dexmedetomidine group (group D), and dexmedetomidine+ GSK1016790A group (group DG). In group C, the animals breathed air spontaneously for 6 h without mechanical ventilation. In group V, the animals were mechanically ventilated for 6 h. In group H, TRPV4 blocker HC-067047 10 mmol was injected into the cerebral ventricle at 3 and 6 h of mechanical ventilation. In D and DG groups, dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation. In group DG, TRPV4 agonist GSK1016790A 5 μmol was injected into the cerebral ventricle at 60 min before mechanical ventilation. Morris water maze test was performed on 6 mice in each group at 1 day before mechanical ventilation and 3 and 7 days after mechanical ventilation. Six mice in each group were randomly selected and sacrificed at 1 day after mechanical ventilation, and the brain tissue was taken for determination of the neuronal apoptosis in hippocampal CA1 area by TUNEL method, and the apoptosis index was calculated. Six mice in each group were randomly selected and sacrificed at 1 day after mechanical ventilation, and the hippocampal tissues were taken for determination of the expression of TRPV4, serine-threonine protein kinase (Akt), phosphorylated Akt (p-Akt), Bcl-2, Bax and caspase-3 by Western blot. Results:Compared with group C, the escape latency was significantly prolonged and the number of crossing the original platform was reduced at 3 and 7 days after mechanical ventilation, the expression of TRPV4 and caspase-3 was up-regulated, the ratio of Bcl-2/Bax was decreased, and the apoptosis index of neurons was increased in group V and group DG ( P<0.05). Compared with group V, the escape latency was significantly shortened and the number of crossing the original platform was increased at 3 and 7 days after mechanical ventilation, the expression of TRPV4 and caspase-3 was down-regulated, the expression of p-Akt was up-regulated, the ratio of Bcl-2/Bax was increased, and the apoptosis index of neurons was decreased in group D and group H ( P<0.05). Compared with group D, the escape latency was significantly prolonged at 3 and 7 days after mechanical ventilation, the number of crossing the original platform was reduced, the expression of TRPV4 and caspase-3 was up-regulated, the expression of p-Akt was down-regulated, the ratio of Bcl-2/Bax was decreased, and the apoptosis index of neurons was increased in group DG ( P<0.05). Conclusions:TRPV 4 is involved in dexmedetomidine-induced improvement in cognitive function, which is related to up-regulation of p-Akt expression and inhibition of apoptosis in hippocampal neurons in mice with mechanical ventilation-caused brain injury.

Objective:To evaluate the clinical efficacy of Jianpi Bushen Zhixie Recipe combined with conventional western medicine therapy in the treatment of diabetic diarrhea patients with spleen and kidney yang-deficiency syndrome.Methods:According to the random number table method, 62 patients with diabetic diarrhea with spleen and kidney yang-deficiency syndrome from June 2019 to June 2021 in Shunyi Hospital of Beijing Traditional Chinese Medicine Hospital, who met the inclusion criteria, were divided into two groups, with 31 in each group. The control group was treated with standardized hypoglycemic and mecobalamin treatment, while the treatment group was treated with Jianpi Bushen Zhixie Recipe on the basis of the control group. Both groups were treated for 2 weeks and followed up for 2 weeks. Before and after treatment, TCM syndrome scores and Bristol Stool Form Scale (BSFS) scores were performed before and after treatment. The Health Related Quality of Life Scale (SF-36) was used to evaluate the quality of life of patients. The number of bowel movements and adverse reactions during treatment were recorded before and after treatment, and followed up for 2 weeks to observe the disease recurrence rate.Results:The total effective rate was 93.55% (29/31) in the treatment group and 74.19% (23/31) in the control group, with a statistically significant difference between both groups ( χ2=5.44, P=0.020). After treatment, the number of bowel movements in the treatment group [(1.02±0.23) times/d vs. (2.35±0.45) times/d, t=14.65] was significantly lower than that of the control group ( P<0.01); the BSFS scores (1.93±0.43 vs. 3.23±0.43, t=11.87) and TCM syndrome score (0.93±0.25 vs. 1.95±0.36, t=12.96) in the treatment group were significantly lower than those in the control group ( P<0.01); the SF-36 score (92.32±2.99 vs. 86.23±3.12, t=7.85) in the treatment group was significantly higher than that of the control group ( P<0.01). No gastrointestinal adverse events were found in both groups during treatment. During the follow-up period, there were 4 cases (4/23) of recurrence in the control group after treatment, and no recurrence in the treatment group. There was a statistically significant difference in the recurrence rate between the two groups ( χ2=4.28, P=0.039). Conclusion:The Jianpi Bushen Zhixie Recipe combined with conventional western medicine can improve symptoms and quality of life of patients with diabetic diarrhea with spleen and kidney yang-deficiency syndrome, reduce adverse reactions and recurrence rate.

Objective:To summarize the hotspots and developmental status of non-suicidal self-injury research by clustering and co-occurrence to the literature on non-suicidal self-injury on the basis of Cite Space, and in order to provide references for future research and intervention.Methods:Non-suicidal self-injury literature included in the Web of science core collection from January 1975 to August 2020 was searched, and the included literature was visualized and analyzed using Cite Space 5.5.R2 knowledge mapping software.Results:A total of 974 articles were retrieved, and the number of articles published showed an increasing trend year by year, mostly in developed countries. The country with the highest cumulative number of articles was the United States, with a total of 412 articles, and the first organization was Katholieke Univ Leuven, with a total of 42 articles. Key words co-occurrence and clustering showed that the current research focus was on adolescents, suicidal behavior, dialectical behavior therapy, and borderline personality disorder. The most cited literature was by Muehlenkamp.Conclusions:Non-suicidal self-injury research has developed rapidly in recent years. At present, non-suicidal self-injury population, related intervention measures, screening and evaluation tools, Meta-analysis and risk factor analysis are its research frontiers and hot spots.

Objective:To investigate the effect of baicalin on cognitive function of mice with brain injury induced by mechanical ventilation and its mechanism.Methods:Seventy two C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were randomly divided into control group (group C), mechanical ventilation group (group V), baicalin group (group B), baicalin+ Akt inhibitor MK-2206 group (group BM) according to random number table method, with 18 in each group.Mice in group C did not have mechanical ventilation and breathed air independently for 6 hours.Mice in group V received mechanical ventilation for 6 hours.Mice in group B and group BM were intraperitoneally injected with baicalin 100 mg/kg 30 minutes before mechanical ventilation, and mice in group BM were injected intraventricular with Akt inhibitor MK-2206 300 μg/kg 60 minutes before mechanical ventilation.Six mice in each group were randomly selected to test their learning and memory abilities by Morris water maze test 1st day before mechanical ventilation and 3rd day and 7th day after mechanical ventilation.One day after mechanical ventilation, six mice in each group were killed, and the brain tissue was taken.TUNEL method was used to detect the neuronal apoptosis in hippocampal CA1 area, and the apoptosis index was calculated.One day after mechanical ventilation, six mice in each group were killed, and the hippocampus was taken, Western blot was used to detect the protein expressions of caspase-3, caspase-9, Akt, p-Akt, GSK-3β and p-GSK-3β.SPSS 22.0 software was used for statistical analysis of data, repeated measure ANOVA and one-way ANOVA were used for comparison between multiple groups.LSD- t test was used for further pairwise comparison. Results:The results of water maze test showed that the time and group interaction of the four groups were not significant ( F=1.14, P>0.05), the main effect of time and group were both significant ( F=47.36, 59.65, both P<0.05). At 3rd day and 7th day after mechanical ventilation, the escape latencies of mice in group V were higher than those in group C (both P<0.05), and the numbers of platform crossing were lower than those in group C (both P<0.05). And 3 days and 7 days after mechanical ventilation, the escape latencies of mice in group B were lower than those in group V (both P<0.05) and the numbers of platform crossing were higher than those in group V (both P<0.05). The escape latenies of mice in BM group on the 3rd and 7th day were higher than those in group B (both P<0.05), and the numbers of platform crossing were lower than those in group B on the 3rd day and 7th day after mechanical ventilation(both P<0.05). TUNEL and Western blot results showed that apoptosis index of hippocampal neurons and expression levels of apoptosis-related proteins caspase-3 and caspase-9 were significant different in the four groups ( F=51.42, 41.21, 40.19, all P<0.05). The apoptosis index of hippocampal neurons ((40.6±3.9)%), the expression levels of caspase-3 (4.93±0.92) and caspase-9 (4.81±0.88) in the hippocampus of mice in group V were higher than those in group C ((13.7±1.4)%, (1.87±0.27), (1.71±0.25), all P<0.05), the apoptosis index of hippocampal neurons ((15.6±1.6)%), the expression levels of caspase-3 (1.95±0.30) and caspase-9 (1.76±0.28) in group B were lower than those in group V ((40.6±3.9)%, (4.93±0.92), (4.81±0.88), all P<0.05), the apoptosis index of hippocampal neurons ((27.8±2.7)%), the expression levels of caspase-3 (3.58±0.61) and caspase-9 (3.49±0.57) in BM group were higher than those in group B ((15.6±1.6)%, (1.95±0.30), (1.76±0.28), all P<0.05). Expression level of p-Akt, p-GSK-3β in hippocampal tissues of the four group of mice were significantly different ( F=37.54, 43.23, both P<0.05). The expression level of p-Akt (0.51±0.06) and p-GSK-3β (0.47±0.05) of hippocampal tissues of mice in group V were lower than those of group C ((1.07±0.10), (1.11±0.12), both P<0.05), the expression level of p-Akt (0.99±0.10) and p-GSK-3β (1.08±0.09) of hippocampal tissues of mice in group B were higher than those of group V (both P<0.05), the expression level of p-Akt (0.83±0.08) and p-GSK-3β (0.81±0.07) of hippocampal tissues of mice in group BM were lower than those in group B (both P<0.05). Conclusion:Baicalin can improve the cognitive function of mice with brain injury induced by mechanical ventilation, which is related with activation of Akt/GSK-3β signaling pathway and inhibition of hippocampal neuron apoptosis.