Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism. Conventional drugs for treating T2DM, such as metformin and glucagon-like peptide-1 receptor agonists, affect nerve repair. Even drugs for treating PD, such as levodopa, can affect insulin secretion. This review summarizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
Humans ; Parkinson Disease/drug therapy* ; Diabetes Mellitus, Type 2/pathology* ; Signal Transduction/physiology* ; Receptor, Insulin/metabolism* ; Animals ; Insulin Resistance/physiology* ; Insulin/metabolism*

Objective To investigate the clinical efficacy of Guhong Injection for the treatment of patients with coronary microvascular dysfunction(CMD)of qi stagnation and blood stasis syndrome.Methods Sixty cases of patients with CMD of qi stagnation and blood stasis syndrome who were admitted to Guangdong Provincial Hospital of Chinese Medicine from June 2021 to August 2022 were randomly divided into the control group and the trial group according to the random number table method,with 30 cases in each group.The control group was treated with conventional western medicine,and the trial group was treated with Guhong Injection on the basis of treatment for the control group.The course of treatment for the two groups covered 10 days.The changes in traditional Chinese medicine(TCM)syndrome scores,and levels of lipid indicators,serum inflammatory factors and endothelial factors in the two groups were observed before and after treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)During the trial,three cases in the control group and two cases in the trial group fell off and a total of 55 cases were finally included in the statistical analysis of efficacy,including 27 cases in the control group and 28 cases in the trial group.(2)After 10 days of treatment,the total effective rate of the trial group was 89.29%(25/28),and that of the control group was 40.74%(11/27),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group(P<0.01).(3)After treatment,the TCM syndrome scores of patients in both groups were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.01).(4)After treatment,the levels of lipid indicators triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)in the two groups of patients were decreased compared with those before treatment(P<0.05),and the level of high-density lipoprotein cholesterol(HDL-C)was increased compared with that before treatment(P<0.05).The intergroup comparison showed that the decrease of TG,TC,and LDL-C levels as well as the increase of HDL-C level in the trial group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)After treatment,the serum levels of inflammatory factors high-sensitivity C-reactive protein(hs-CRP),interleukin 6(IL-6)and tumor necrosis factor α(TNF-α)in the two groups of patients were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.01).(6)After treatment,the serum level of endothelial factor nitric oxide(NO)in the two groups of patients was increased(P<0.05)and the serum endothelin 1(ET-1)level was decreased compared with that before treatment(P<0.05),and the increase of serum NO level,as well as the decrease of serum ET-1 level in the trial group was significantly superior to that in the control group(P<0.05 or P<0.01).Conclusion Based on the conventional treatment in western medicine,the application of Guhong Injection in the treatment of patients with CMD of qi stagnation and blood stasis syndrome exerts remarkable efficacy,which can effectively alleviate the symptoms,regulate the levels of blood lipids,reduce the inflammatory response,and improve the endothelial function.

Objective To explore a new training strategy suitable for clinical education and talent cultivation in gy-necologic oncology.Methods Ninety undergraduates from each of the two grades of clinical medicine curriculum at Kunming Medical University were randomly divided into control group(n=40)and research group(n=50).The"4+3"teaching model of plan-do-check-action(PDCA)cycle integrated with TBL were adopted,whereas the control group was educated with classic methods.Two groups of students were evaluated with quantitative assessments and anonymous questionnaire surveys.Results Multidimensional questionnaire surveys indicated that the teaching model of the test group provided a better learning experience than classic teaching methods as proved by significant improvements in educational reform(58％),learning interest(64％),skill development(72％),capacity building of learning(66％)and satisfaction with the new model of training(70％)(P＜0.05,＜0.01).Further-more,the PDCA cycle can address the short-comings of the previous teaching iteration.In written exams,the class-room quiz scores,regular grades,and comprehensive scores of the research group were(18.38±5.81),(29.09±0.29),and(82.38±4.03)points respectively all higher than those of the control group(P＜0.01).Conclusions The PDCA cycle and the TBL-embedded teaching model promote the standardization of gynecologic oncology teach-ing procedures,thereby enhancing teaching quality and achieving precise alignment between student satisfaction and assessment performance.

Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

Objective:To analyze the risk factors of internalizing problems in adolescents aged 12 to 18 years,and provide supporting evidence for the scientific prevention and effective control of internalizing problems in adolescents.Methods:By systematically searching the Chinese and English databases such as CNKI,VIP,Wan-fang,PubMed,Web of Science,Psychology and Behavioral Sciences Collection,PsycInfo,PsycArticles and ERIC,literature on risk factors of internalizing problems among adolescents in the past 22 years was collected,and non-clinical literature using CBCL or YSR or TRF scales to measure related internalizing problems were included.Meta analysis was performed using CMA3.0,with r as the effect size indicator and random effects model combined with the effect size of risk factors.Results:Finally,77 and 18 risk factors literatures were included,including 7 risk fac-tors of individuals,7 risk factors of family,and 4 risk factors of school/community.The average correlation between family risk factors and internalizing problems of adolescents was the highest.Among family risk factors,parent-child attachment had the highest correlation.Conclusion:Individual risk factors,family risk factors and school/com-munity risk factors are significantly positively correlated with adolescent internalizing problems,and family risk fac-tors(especially parent-child attachment quality)have the highest correlation with adolescent internalizing problems.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.