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.

Objective To explore the application and effect of a pulmonary rehabilitation exercise program in patients with moderate to severe COPD based on the Information-Motivation-Behavior Skill(IMB)Model.Methods The convenience sampling method was adopted to select patients with moderate to severe COPD admitted to the department of respiratory and critical care medicine in a tertiary A hospital in Yantai City from October 2021 to February 2022.They were randomly divided into an intervention group(32 cases)and a control group(31 cases).The intervention group was treated with the pulmonary rehabilitation exercise program based on the IMB model on the basis of routine nursing,while the control group was treated with routine nursing.The degree of dyspnea,exercise endurance,quality of life,pulmonary rehabilitation exercise compliance,self-management ability and lung function were compared between the 2 groups before and 6 months after the intervention.Results After intervention,the degree of dyspnea,exercise endurance,quality of life,pulmonary rehabilitation exercise compliance and self-management ability were significantly different between the 2 groups(P＜0.05).There was no statistically significant difference in lung function between the 2 groups after intervention(P＞0.05).Conclusion The pulmonary rehabilitation program based on IMB model can effectively alleviate the symptoms of dyspnea in patients with moderate to severe COPD,improve exercise endurance,improve pulmonary rehabilitation exercise compliance and self-management ability,and improve the patients'quality of life.

Objective:To investigate the clinical, neuropsychological, and neuroimage characteristics in patients with corticobasal syndrome (CBS), and to elucidate the exact diagnosis of CBS patients.Methods:Twelve CBS cases admitted to the Department of Neurology, Huashan Hosiptal,Fudan University from April 2019 to July 2021 were retrospectively enrolled in this study. Those data, including clinical features (demographic data and clinical characteristics of cortical dysfunction and movement disorder), neuropsychological assessment [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales score], brain magnetic resonance imaging (MRI) and multi-mode positron emission tomography (PET)/CT, were collected and carefully reviewed. Exact diagnosis of these patients was given according to the disease diagnosis criteria.Results:Cortical dysfunction and asymmetrical movement disorders were found in all cases, with poor response to levodopa. Patients suffered from cognitive impairment (MMSE score 16.16±9.82, MoCA score 13.44±7.35). The cranial MRI demonstrated significant asymmetric atrophy of frontal and parietal lobes, especially in the pre- and post-central gyrus. Fluorodeoxyglucose PET of 12 patients showed asymmetric frontal lobe and basal ganglia (especially caudate and putamen) hypometabolism (obviously on the contralateral side of the affected limb). Tau PET was implemented in 11 patients and displayed that abnormal tau protein deposition was positive in the cortex and/or subcortex in all patients. Of the 4 cases, who completed amyloid PET, amyloid protein deposition was positive in the cortex of 2 patients. As a result, 6 patients were diagnosed as progressive supranuclear palsy, 1 patient was diagnosed as corticobasal degeneration, and 5 patients were diagnosed as Alzheimer′s disease.Conclusions:The etiology of CBS is heterogeneous. The combination of clinical manifestation, cranial MRI and multi-mode PET/CT helps the differential diagnosis of CBS.

Objective:To investigate the pathological spectrum and variation of adult renal biopsies in People's Hospital of Xinjiang Uygur Autonomous Region from 1986 to 2020.Methods:The pathological data of 5 652 adult renal biopsies from August 1986 to December 2020 were retrospectively collected, and characteristics of pathological spectrum were analyzed. Regarding every 5 years as a research stage, the whole period was divided into 7 stages to analyze the pathological features and variation of renal biopsies. The first stage (P1) started from August 1986 to December 1990. The second stage (P2) started from January 1991 to December 1995. The third stage (P3) started from January 1996 to December 2000. The fourth stage (P4) started from January 2001 to December 2005. The fifth stage (P5) started from January 2006 to December 2010. The sixth stage (P6) started from January 2011 to December 2015. The seventh stage (P7) started from January 2016 to December 2020.Results:The age was (36.47±14.86) years old (18-83 years old) in 5 652 renal biopsies. There were 2 961 males (52.39%). There were 5 636 cases of autologous kidney biopsy and 16 cases of transplanted kidney biopsy. The descending order of incidence classified by disease types were primary glomerular disease (PGD, 4 470 cases, 79.31%), secondary glomerular disease (SGD, 994 cases, 17.64%), tubular-interstitial disease (160 cases, 2.84%), and hereditary nephropathy (12 cases, 0.21%). IgA nephropathy (IgAN, 1 573 cases, 35.19%) was the most frequent pathologic type of PGD, followed by membranous nephropathy (MN, 1 028 cases, 23.00%), mesangial proliferative glomerulonephritis (MsPGN, 878 cases, 19.64%), minimal change disease (MCD, 427 cases, 9.55%), and focal segmental glomerulosclerosis (345 cases, 7.72%). Lupus nephritis (LN, 251 cases, 25.25%) was the most common type of SGD, followed by hypertension nephropathy (193 cases, 19.42%), diabetic kidney disease (168 cases, 16.90%), purpura nephritis (138 cases, 13.88%), and ischemic nephropathy (90 cases, 9.05%). IgAN was the most common type of primary glomerulonephritis and mainly occurred in the age group of 18-59 years old. PGD was the most common glomerular disease in Han nationality (78.33%), Uygur nationality (81.72%) and other ethnic (77.15%) groups. Using Bonferroni correction method, the incidence of PGD in Uygur nationality was higher than that in Han nationality ( P<0.017). From P1 to P7, the detection rates of MN and MCD were increased in common renal pathological types, meanwhile, the ratio of MsPGN was decreased (all P<0.05). From P5 to P7, the detection rates of MN in Han nationality and Uygur nationality increased in the common pathological types of PGD, meanwhile, the ratio of MsPGN decreased (all P<0.05). LN was the most common SGD. The incidence of LN in females was higher than that in males ( P<0.001). Using Bonferroni correction method, the incidence of SGD in Uygur nationality was lower than that in Han nationality ( P<0.017). There was no significant variation in the common pathological type of SGD in Han and Uygur nationalities. Chronic rejection was the main pathological type of transplanted kidney biopsies. Conclusions:PGD is the main type of kidney disease spectrum in People's Hospital of Xinjiang Uygur Autonomous Region. IgAN is the most common PGD and mainly occurrs in the age group of 18-59 years old. As time goes by, the proportion of MN and MCD is increased, meanwhile the proportion of MsPGN is decreased significantly. LN is the most common SGD.

Objective:To explore the effects of 5E rehabilitation nursing model on self-management behavior and fatigue symptoms of patients with chronic obstructive pulmonary disease (COPD) .Methods:Totally 110 COPD patients admitted in Yantai Yuhuangding Hospital from October 2018 to September 2019 were selected by convenient sampling, and divided into the control group ( n=53) and the experimental group ( n=57) according to the random number table. Excluding missing patients and patients with incomplete data, finally 48 patients were included in the control group and 51 patients were included in the experimental group. Patients in the control group received routine care and health guidance, while patients in the experimental group received care based on the 5E rehabilitation nursing model. The Self-Management Scale for COPD Patients and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) were used to evaluate the effects of interventions in the two groups. Results:There was no statistically significant difference in the scores of the Self-Management Scale between the two groups before intervention ( P>0.05) ; the scores of all dimensions the Self-Management Scale of the experimental group were higher than those of the control group 12 weeks after discharge, and the differences were statistically significant ( P<0.05) . There was no statistically significant difference in fatigue scores between the two groups before intervention and 12 weeks after discharge ( P>0.05) . Conclusions:The 5E rehabilitation nursing model can improve the self-management behavior of COPD patients, but it cannot ameliorate the fatigue symptoms of patients. Large-sample, multi-center, and long-term research will be further needed in the future to explore the effects of the 5E rehabilitation nursing model on patients' fatigue symptoms.

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Adrenergic Agents ; pharmacology ; Animals ; Ganglia, Spinal ; drug effects ; Hyperalgesia ; drug therapy ; physiopathology ; Hypersensitivity ; drug therapy ; Male ; Maternal Deprivation ; Neurons ; drug effects ; Patch-Clamp Techniques ; methods ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Stress, Physiological ; physiology ; Visceral Pain ; chemically induced ; metabolism

Objective:To investigate the effects of different doses and infusion methods of recombinant mouse interleukin-18(rmIL-18) on the survival time and tumor diameter of the mice with hepatocellular carcinoma,and to elucidate the rational application of rmIL-18 in vivo.Methods:A total of 60 Babl/C mice were randomly divided into 5 μg rmIL-18 intraperitoneal injection group,0.5 μg rmIL-18 intraperitoneal injection group,0.5 μg rmIL-18 tumor injection group,cytotoxic T lymphocyte(CTL) intraperitoneal injection group,CTL tumor injection group and saline control group;there were 10 mice in each group.From the 10th day of inoculation,the mice in different rmIL-18 groups were injected with the corresponding doses and methods.The mice in different CTL groups were injected with tumor-specific CTL (1×106/mouse) by intraperitoneal and intratumoral injection.The mice in saline control group were injected with an equal volume (100 μL) of saline,the injections were performed 10 times.The diameters of mice were measured weekly and the survival time was recorded.Results:Compared with 5 μg rmIL-18 intraperitoneal injection group,0.5 μg rmIL-18 intraperitoneal injection group and saline control group,the tumor growth rate of the mice in 0.5 μg rmIL-18 tumor injection group was decreased (P<0.01)and the survival rate of the mice was increased (P<0.01);compared with 0.5 μg rmIL-18 intraperitoneal injection group,the tumor growth rate and the survival rate of the mice in CTL intraperitoneal injection group were decreased (P<0.01);compared with 0.5 μg rmIL-18 tumor injection group,the tumor growth rate and the survival rate of the mice in CTL tumor injection group were decreased (P<0.01).Conclusion:The best way for rmIL-18 anti-tumor effect is tumor injection and the effect has a dose-dependent manner.

Objective: To optimize the flash extraction process of the active ingredients from Lonicera japonica by Box-Behnken design and response surface methodology.Methods: Flash extraction was used.With the concentration of ethanol,solid-liquid ratio and extraction time as the main influencing factors and the overall normalization value of the transfer rates of chorogenic acid and luteoloside as the evaluation index, Box-behnken design was performed to screen out the optimal extraction conditions.The mathematics relationship between the overall normalization value and the independent variables was established by multiple linear regression and binomial fitting, and response surface methodology was used to predict the optimal process conditions.Results: The optimal extraction conditions were determined as follows: the ethathol concentration was 66.92% ,the solid-liquid ratio was 18.82 ,the extraction duration was 1.20 min and extracted only once.Under the above conditions, the extraction rate of chloragenic acid and total luteoloside was 92.87% and 87.55% , respectively.Conclusion: The optimized technology is simple,economic and practical,which can provide new ideas for the rapid extraction and quality control of active ingredients from Lonicera japonica .