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.

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 analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

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 develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; B7-H1 Antigen/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Tomography, X-Ray Computed ; Immunotherapy