Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective:To observe any therapeutic effect of kinesio taping the orbicularis oris and cervical swallowing muscle groups on drooling among children with cerebral palsy (CP).Methods:Fifty-two children with CP salivating excessively were divided at random into a control group and an experimental group, each of 26. Both groups received routine oral and facial exercise training and sensory stimulation, but the experimental group was additionally provided with kinesio taping of the orbicularis oris muscle and related neck muscle groups. The taping was applied twice a week for 12 hours each time, continuing for 6 months. Before and after the treatment, both groups′ drooling and language use were evaluated using the teacher drooling grading method (TDS) and a language developmental delay assessment (S-S), respectively. Kendall rank correlation coefficients were computed to compare the treatment efficacy for children with the same TDS grading, cerebral palsy classification, and S-S segmentation.Results:After the treatment the average TDS scores of both groups had decreased significantly. The average TDS score of the experimental group was then significantly lower than that of the control group. The total effectiveness rate for those in the experimental group with TDS grades II or V was significantly higher than those controls with the same TDS grades, the effectiveness rate for those with spastic and mixed type or language function in stage 4-2 and stage 5-2 in the experiment group was also significantly higher than for those of the control group. According to the correlation analysis, the language function of both groups was significantly correlated with the therapeutic effect.Conclusions:Supplementing routine rehabilitation training with kinesio taping of the orbicularis oris muscle and the cervical swallowing muscle group can significantly relieve CP children′s excessive salivation. Their language use is significantly positively correlated with the effectiveness of such combined treatment.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective:To observe any therapeutic effect of kinesio taping the orbicularis oris and cervical swallowing muscle groups on drooling among children with cerebral palsy (CP).Methods:Fifty-two children with CP salivating excessively were divided at random into a control group and an experimental group, each of 26. Both groups received routine oral and facial exercise training and sensory stimulation, but the experimental group was additionally provided with kinesio taping of the orbicularis oris muscle and related neck muscle groups. The taping was applied twice a week for 12 hours each time, continuing for 6 months. Before and after the treatment, both groups′ drooling and language use were evaluated using the teacher drooling grading method (TDS) and a language developmental delay assessment (S-S), respectively. Kendall rank correlation coefficients were computed to compare the treatment efficacy for children with the same TDS grading, cerebral palsy classification, and S-S segmentation.Results:After the treatment the average TDS scores of both groups had decreased significantly. The average TDS score of the experimental group was then significantly lower than that of the control group. The total effectiveness rate for those in the experimental group with TDS grades II or V was significantly higher than those controls with the same TDS grades, the effectiveness rate for those with spastic and mixed type or language function in stage 4-2 and stage 5-2 in the experiment group was also significantly higher than for those of the control group. According to the correlation analysis, the language function of both groups was significantly correlated with the therapeutic effect.Conclusions:Supplementing routine rehabilitation training with kinesio taping of the orbicularis oris muscle and the cervical swallowing muscle group can significantly relieve CP children′s excessive salivation. Their language use is significantly positively correlated with the effectiveness of such combined treatment.

Objective To observe the neuropsychiatric behavioral performance of kainic acid(KA)-induced epilepsy rats;investigate gender differences in acute seizure and behavioral performance tasks relating to sense,motor,learning,and memory in the remission phase;and explore the potential neurobiological mechanisms of action.Methods Healthy SD rats aged 4 weeks were randomly divided into control and model groups,with 22 rats in each group(11 males and 11 females).An epileptic rat model was induced by intraperitoneal injection of KA.Seizure latency and frequency within 2 hours of KA injection were observed,seizure grade was assessed using the Racine grade standard,and a cortical electroencephalogram(EEG)was recorded.Behavioral performance was observed in a series of tasks including open field testing,balance beam walking,elevated plus maze,Y-maze,and novel object recognition.The level of GABA in the hippocampus was detected by ELISA,injury to hippocampal neurons was observed by Nissl staining,and the protein expression of synapsin-1 and synaptotagmin 1 in the hippocampus were detected by Western Blot.Results Both male and female rats presented typical epileptic behaviors after KA injection.However,compared with the effects in males,the latency of the first seizure(P=0.014)and Ⅳ～Ⅴ grading in female model rats were more pronounced(P＜0.01),and the frequency of epileptic seizures within 2 hours was significantly reduced(P=0.019).In the open field testing,KA-induced epileptic rats presented more motor but fewer hedonic behaviors,as indicated by the decrease in total movement distance in the central area,compared with the control group.Moreover,grooming frequency was significantly reduced in the female model rats compared with not only that in the control but also that in male model rats(P＜0.01).The model rats spent more time completing and had a higher score in the balance beam walking task,indicating their poorer stability and balance.In the elevated plus maze,the exploration times of male model rats in the closed arm was increased.The preference index of rats for the novel arm or object decreased in the Y-maze and novel object recognition,suggesting impairments to their learning and memory abilities.Moreover,neuronal injuries were found in the hippocampus of the model rats that were accompanied with a decline in GABA concentration and protein expression of synapsin-1 and synaptotagmin 1,with no gender differences.Conclusions Intraperitoneal injection of KA successfully induced an epilepsy rat model.However,there was a gender difference in the characters of acute seizures and performance of sensory,motor,and learning memory during epileptic remission.There was no gender differences in the hippocampal GABA concentration or expression of synaptic plasticity-related proteins,and thus no evidence was found for the mechanisms underlying the gender differences.

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Cytokines/metabolism* ; Interleukin-10 ; Interleukin-17/metabolism* ; Interleukin-6/metabolism* ; Interleukin-5/metabolism* ; Blood Coagulation Disorders ; Ferritins ; Tretinoin

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4⁺ and CD8⁺ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4⁺ and CD8⁺ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.
Humans ; Anemia, Aplastic ; CD8-Positive T-Lymphocytes ; Melatonin ; Blood Cell Count

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.
Male ; Humans ; Child, Preschool ; Nevus, Blue/pathology* ; Nevus of Ota/therapy* ; Skin/pathology* ; Face ; Skin Neoplasms/pathology*

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; &ge;80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8+T cells in A A group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4+T cells and the CD4+/CD8+ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and0.001,respectively).Furthermore,the proportion of CD4+andCD8+activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8+naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and 0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4+and CD8+TA cells,memory Tregs and CD8+TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.