Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

OBJECTIVE: To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD). METHODS: A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups. RESULTS: Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05). CONCLUSION Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.
Humans ; Acupuncture Therapy ; Sleep ; Acupuncture Points ; Down-Regulation ; Sleep Duration

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Mitochondria is involved in many important physiological activities such as energy supply, signal transduction, cell differentiation, etc., and plays an significant role in the occurrence and development of diseases. Using mitochondria as a target is a new strategy for cancer treatment. The use of nanotechnology to construct a mitochondrial targeted nano-drug delivery system can improve the solubility of traditional drugs, prolong the half-life of drugs in the body, increase the bioavailability and concentration of drugs at the tumor site, and reduce the toxic and side effects of drugs. It is expected to solve the resistance in the process of tumor treatment. This review focuses on the field of cancer treatment. Firstly, it introduces the mechanism of mitochondrial targeted nano-drug delivery system for cancer treatment. Secondly, it outlines the design ideas, classification and application research of mitochondrial targeted nano-drug delivery systems in the past five years. Finally, it expands the analysis of other studies that target mitochondria, such as bionic vectors, and presents its advantages and disadvantages, which provide a basis for in-depth research on drug delivery systems in the future.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

Objective:To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference.Results:1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients ( P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS ( P<0.05). Conclusions:EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Objective:To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference.Results:1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients ( P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS ( P<0.05). Conclusions:EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.

Adult ; Cesarean Section/statistics & numerical data* ; China/epidemiology* ; Female ; Humans ; Pregnancy ; Pregnancy Outcome/epidemiology* ; Risk Factors ; Trial of Labor ; Young Adult

OBJECTIVE: To study the effect of bronchopulmonary dysplasia (BPD) on neurobehavioral development within one year after birth in preterm infants. METHODS: A retrospective analysis was performed for the preterm infants with a gestational age of <34 weeks who were born from September 2017 to December 2019 and completed the follow-up assessments of neurobehavioral development at the corrected gestational ages of 40 weeks and 3, 6, and 12 months. According to their diagnosis, they were divided into a BPD group with 23 infants and a non-BPD group with 27 infants. The outcome of neurobehavioral development was compared between the two groups at different time points. RESULTS: There was no significant difference in the neonatal behavioral neurological assessment score between the BPD and non-BPD groups at the corrected gestational age of 40 weeks (P>0.05). Based on the Gesell Developmental Scale, compared with the non-BPD group, the BPD group had significantly lower global developmental quotient (DQ) and DQs of fine motor, adaptive behavior, and personal-social behavior at the corrected gestational ages of 3, 6, and 12 months (P<0.05). For both groups, the DQ of language at the corrected gestational age of 6 months was significantly higher than that at the corrected gestational age of 12 months (P<0.017), the DQ of personal-social behavior at the corrected gestational age of 6 months was significantly higher than that at the corrected gestational age of 3 months (P<0.017), and the DQ of adaptive behavior at the corrected gestational age of 12 months was significantly higher than that at the corrected gestational ages of 3 and 6 months (P<0.017). Based on the BSID-II scale, there were no significant differences in mental development index and psychomotor development index at each time point between the two groups (P>0.05). The mental development index at the corrected gestational age of 3 months was significantly higher than that at the corrected gestational ages of 6 and 12 months in both groups (P<0.001). CONCLUSIONS Preterm infants with BPD have delayed neurodevelopment within one year after birth compared with those without BPD, which should be taken seriously in clinical practice.
Bronchopulmonary Dysplasia ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Neonatal Screening ; Retrospective Studies